19 Episode results for "Myeloid Leukemia"

090 - Curis Shows Positive Data in AML with First in Class IRAK4 Inhibitor

Breaking Biotech

52:08 min | Last month

090 - Curis Shows Positive Data in AML with First in Class IRAK4 Inhibitor

"Hey everybody welcome breaking biotech. Thanks for being with me here today. My name is matt. If you like the show you can help out. By clicking the light or subscribe button you can also donate using the patient. Lincoln the description below. So i'm excited to be back and i've got a great show for everybody today. The company we're going to focus on for the most part of the show is called curious inc and i've been asked to cover this company for quite a while now and i finally saw a nice update in data from their abstract submitted to e i saw they run up in the stock that i totally missed out on. So i figured why not dive into the stock. Now so that's gonna be our main story for today. And before i jump into that we're going to talk about two other companies that gave some updates. One is a novus that has a drug looking at helping alzheimer's disease or parkinson's and then also gonna talk about seo gene therapies that also shared some updates. So i want to thank everybody for all your support appreciate all responses and the engagement you can send me an email at matthew apart agena dot com or follow me on twitter at matthew apart so with that. Let's get read into it. And the first company. I want to touch on is called. Novus ticker symbol a n v s. They're trading at a one hundred sixty five million dollar market cap and they presented at the benzinga global small-cap conference and what it was pitched as originally is that they were gonna share some parkinson's disease biomarker data from their compound in how it affects parkinson's patients because they showed a bit of efficacy data earlier and this was supposed to be a follow on but we ended up seeing that the ceo only really presented their corporate presentation. They showed the same effect that there was in parkinson's which was nice but we would have liked to see an update in that data sharing some biomarkers that potentially there molecule had so. That was kind of a letdown. The stocks sold off on that news but has since recovered and i'm recording. This on may seventeenth twenty twenty one so things might change from now until then but i'm still holding a position. They are supposed to be releasing some data in two to three weeks. So i'm going to hold in expectations of a data released coming there. The ceo maria. She seems very sweet and seems to know what she's doing. But there is a bit of miscommunication on the timelines. And i think some people are getting frustrated with how that is playing out and myself included but i think we need to give her the benefit of the doubt for now until this continues to happen so all that is to say that i'm gonna keep holding and hopefully in the next two to three weeks. We will see an update in alzheimer's data. Which i would expect the stock to increase. If it was positive data the next company. I want to touch on is called. Sia gene therapies. the ticker symbol is ex. They are trading at around one hundred and twenty five million dollar market cap and they were supposed to give a presentation on a number of their programs at this gene therapy conference. They released a press release for their. Gm one ganglia side programs specifically and they totally ignored the other presentations that they were giving. Which i think is what led to the decrease in stock because what a lot of the value for seo. X is is in their parkinson's disease trial even though there are multiple hangups with that side of their business right now that a lot of people are expecting some resolution for myself included. So what they did announce in the press release was that they saw csf reductions in gm one ganglia side from clinical trial of aso. A the gm one gene therapy and what they showed. Is that at six months. Following gene transfer serum bagel acta aside as enzyme activity approximately doubled and was restored to between twenty three and fifty seven percent of the lower limit of the normal reference range in the low dose covert. They showed that eighteen to forty nine percent reductions from baseline in accumulated substrate. Gm one ganglia side were observed in csf of four out of five children. In in the low dose cohort six months so this is for their rare disease. Gm one ganglia side and they're trying to cheat treat it with an ab vector that would restore the expression of vaguely that would then lead to a reduction in this in this molecule gm. One ganglia side so what it looks like is there is efficacy in the four out of five of the children which is really good to see at six months now the issue though is i think that this company there was an expectation that this company was going to release some update on their parkinson's disease trial and we didn't get a press release on this so i think people assume that it was just old data. They're presenting again so we're left in kind of a tough spot again with this company. There's gonna be some thin cabalists in the next little while and the updates are going to be from their programs besides the parkinson's disease trial so what we're going to see. Is that in the second half of this year. We're going to get an update in twelve months. Data from the low dose cohort of this trial. The gm ganglia side in one of two thousand twenty. Two we're gonna see twelve months. Update from the high dose cohort. And then what they said. Is that in q four. Twenty twenty one. They're going to be able to certify or they're hoping to get certification of their new parkinson's disease gene therapy product so they're pregnancies product is in collaboration with another company in the uk. And there's been some issues with getting material and getting approval and getting enough material to do these trials. So i'm still holding onto the company and it's tough because i'm playing kind of a resolution of this parkinson's disease product as well. I think there is some upside from their rare disease programs. The gm wanting jim to ganglia sides. But it's definitely difficult. So i'm still holding on to do a lot of cash but if they continue to push this out and are unable to restart their parkinson's disease trial or they don't present any parkinson's disease updates because they do have patients that were treated before and it would be nice to see an update on that. I think we're gonna see these lows on the company so i'm still holding. It is definitely a difficult company to hold onto. But i do see them potentially having significant upside if they can resolve some of these issues. So i'm gonna hold on but it has been difficult so i understand that and with that. Let's get to our main story for today and that is talking about curious. inc ticker symbol cri s. They traded on. Monday may seventeenth at fifteen bucks a share a market cap of one point. Four ish billion dollars their q one. Two twenty one net loss was nine point nine million and they're sitting at hugh on twenty twenty one current assets of hundred and sixty two million dollars with q one twenty twenty one abilities at seven million dollars and what the company is doing is trying to develop novel cancer therapeutics and they had two main programs. The first one is focusing on inhibiting protein called is four and the other one is focused on antagonizing. Another protein called vista there iraq. Four inhibitor is called c. A four nine. Four eight and hear the looking for indications in acute myeloid leukemia as well as milo plastic syndrome. They're also looking at indications in non hodgkin's lymphoma. Ci eight nine three refers to the vista antagonists. That they're clinically developing and here the looking at indications in solid tumors and. That's pretty broad. But i'm gonna talk about that program in a little more detail later. So before i get into the data. I i wanted to talk about targeted cancer treatments in general because they do act as kind of their own sub-sector and there's a few reasons for this but when i talk about targeted cancer therapy they're different from legacy treatments in that they're going to bind to a specific eissa form or a specific protein in a pathway. That's in a certain cell type and this is different from a legacy cancer treatment because those will often target just proliferating cells broadly and whether it's radiation or chemotherapy. Here i mentioned a couple clara mbusa or cyclophosphamide. And there's many but these treatments preferentially target just proliferating cells and as we know high proliferation isn't just a feature of cancer cells and it's an important feature cancer cells but there's a number of different cell types that also rapidly proliferate that would also be affected by chemotherapy or radiation. So what we want to do with the targeted cancer therapy is potentially target a specific or specific mutation that avoids the negative side effects associated with a classic chemotherapy or radiation treatment. That will target normal cells lead to higher side effects so here at targeted cancer therapy potentially has a better side effect profile and also potentially has greater efficacy because if the targeted therapy is it good enough in that it. Preferentially binds to its target. Well enough they'll be able to go sit at much higher levels than a treatment. That could be more. Broadly applied because the on target effects will only affect that single mutation. That single molecule. And i'm talking in broad terms because there's different molecules that could be referred to as a targeted therapy or not but if we look for example morad treatment for this is a good example. Because they're molecule will preferentially bind to a specific mutant. And what this means is that it will avoid the normal grass protein that is found in every single cell in our body and what this means is that we can potentially dose moralities treatment higher levels. Because it won't bind to those normal rasp proteins and only bind the mutant care ass. Now we do see some side effects of moretti's treatment but they're much better than if it was just a general rasool inhibitor which wouldn't be viable in the clinic because so many of ourselves express rats and need it to function properly. So in this way you can think of a number of different genes that are mutated in different cancers that could be potential targets for biotech companies to generate compounds against. And if they're able to see success here there's a lot of potential in different avenues. So that's the theory behind why the treatment could be so powerful in different types of cancers now other things related to cancer treatments is that these companies are highly sought after by large pharma for acquisition. Now listed. Couple of here from a cyclic was acquired by abbvie. Rq by merck and lock owes acquired by lily's so despite the fact that we haven't seen much emon activity. Recently oncology candidates are big potential acquisition targets for large pharma. So for that reason it is. It is a reason why we should pay attention to them. Another benefit here is that on college. Candidates generally have a lower bar of success from a clinical and a regulatory standpoint. Comparing the oncology space to the cns space is very much a night and day. The bar for cns. Drugs is extremely high. Whereas oncology companies can easily show single armed data that has a beneficial effect compared to previous single earned data and other compounds. And if it's good enough the fda will approve it so the bar is definitely lower for oncology companies and for that reason we should be focusing on them in general lastly i wanted to mention that these drugs have a major market potential. Improve akiva in banana. Clocks are examples of drugs that target specific proteins and they have seen significant revenue numbers from their respective companies. So it's for these reasons that targeted cancer treatments are very interesting and we should be looking at them as a primary part of biotech portfolio. Now before i get into curious i wanted to talk about acute myeloid leukemia. And the reason for this is focused before a non hodgkin lymphoma quite a bit and am l. is a big cancer indication. That is another hematological malignancy but it focuses on a different sector of the blood said to put that in more detail when we're talking about non hodgkin lymphoma and i'm looking here at a the different blood cells that are found in the body when we're talking about non hodgkin lymphoma we're talking about cancers that arise from the lymphoid progenitor cells not directly but cells that are associated with that side of the humana poetic pathway. So t lymphocytes b lymphocytes plasma cells and small lymphocytes. These are cells that are involved to some extent in the non hodgkin lymphoma side of hematological malignancies. When we're talking about acute myeloid leukemia. Though we're talking about cells. That derive from the maya lloyd progenitor pathway so these are cells that are eventually going to become as officials. Neutral fills lia cinefils monocytes macrophages re through sites and so forth. So what happens. Is that immature myeloid cells in the bone marrow. Get some kind of mutation and it's unclear exactly why a male will happen in one patient or another patient but enough. Mutations will happen such that they'll be an overgrowth of immature myeloid cells in the bone. Marrow this will spill into the regular blood compartment and eventually overtake the blood compartment leading to a number of negative effects. The primary thing that happens is blood counts become abnormal. So patients up with really low platelets red blood cells and white blood cells so they become susceptible to infection and then what they also get an increase in what they call. It's so this primarily occurs in the bone marrow but then it does end up happening in the regular blood compartment so when we're looking for resolution what we're hoping to see is that in the bone marrow blast reduce down to below five percent and blast can be upwards of above fifty percents sometimes which can be very dangerous for patients. In general progresses quite rapidly and it can absolutely be fatal if it's not treated so things to look for here are the baseline blasts and what happens. After treatment occurs in terms of blasts were also going to be talking about is whether or not the haematological profile returns to normal and specifically red blood cells platelets and white blood cells. We want those to all come back to normal in a treatment. In terms of the total addressable market there are twenty thousand cases per year of am l. in the usa. These are projected numbers for twenty twenty one and general leukemia. Sit around sixty one thousand cases per year now to talk about the treatment of am l. In general would is traditionally used as what's called a seven-plus three regimen and this of site tarabin and an anthracite clean and what they do. Is they seven days of satire being and then three days of and recycling and there's a number of different anthr- cycling drugs that doctors could choose from but though cycle through this and what this is referred to is induction therapies. This is the first thing that an am l. patient will see in order to remove the blasts from the blood and the bone marrow. And what happens here is up to seventy percent of patients will achieve remission on this therapy. Not all patients will be suitable candidates from this type of regimen. What's called unfit aml patients. And in particular patients that are above a certain age and so these elderly patients will seek a different kind of therapy. Sled it's not so hard on their body because this combination of chemotherapies can be pretty difficult for these patients. And i mentioned here that this is a target for trillium. Their targeting patients that are in this unfit Category unfortunately even though seventy percent of patients achieve remission there is a need for something called consolidation therapy because it's not enough for remission to occur. This doesn't necessarily mean that there's going to be a cure because there might be a couple of cells that remain that had this mutation that allows them to repopulate the bone marrow and eventually the blood compartment of the body and then there is a relapse so there is a need in this market for treatments. That can better remove all of those blasts. All of the minimal residual disease of the mutated blasts from the blood so that patients can seek a cure and no longer need to worry about recurrences. So recurrences are pretty common in this and for that reason there. Is this need for better therapies. Now what's been discovered lately. Are these certain mutations that are currently included in what's called international routes stratification schema and four different genes here f lt three n. p. m. one. Cpa and see kit. These are genes that if they're mutated can lead to potentially greater risk of a recurrence and the reason is complicated. There's these proteins have different functions within the cell but what's been discovered so far is that especially nfl t three if you treat patients with a seven plus three regimen as well as an f lt three inhibitor. You tend to see a greater improvement in outcomes in patients. So there's a real opportunity here for biotech companies to develop targeted therapies that target these genes or other genes that are in am l. patients to potentially lead to better outcomes and this is what curious is doing. I'm putting here. The percent of population different disease driver jeans and iraq for the long version is shown here the top with apparently above fifty percents incidents in the al population. Here that has this mutation. It makes sense to reason that if we could inhibit iraq for we'd be able to help anna patients that have this mutation in particular. You'll notice here. That f lt three is found in about twenty five to thirty percent of patients. And i'm also going to talk about inhibitors of two that are found in around nine to thirteen percent of patients now given the fifty percent or greater potential patient population in am l. Works out to about a ten thousand patients per year. Total addressable market for curious in md s. The incidents of md s in general is seventeen thousand and forty three thousand per year. So we take half of that. It's around eight point. Five thousand and bs patients per year as a total addressable market those two markets in general i would say are the primary market. Curious is gonna provable in. They're also looking at non hodgkin lymphoma but right. Now it's looking like it's just a basket of different non hodgkin lymphomas so it's difficult for us to say exactly what a good total addressable market is for these patient populations so i put here up to seventy five thousand and h. l. patients per year. This is very generous. And i don't think it's fair for us to include it into our model just yet because they're going to specify into something like deal or something else now. They also have a molecule that they're looking at indications in solid tumors. There are many many patients in different solid tumors so the upside is potentially infinite. Given that and for that reason. I'm not gonna include that in the valuation here. The other thing. I wanted to mention is that there might be potential for this molecule in non iraq for mutated cancers. And i'm gonna touch on this a little bit later. Because the data that they showed seemed to implicate that there might be effect in cancers that are not primarily driven by a mutation in iraq. For that's all i'll say for now and we'll touch on that a little bit later so if we add up to ten thousand patients for am l. and eight point five thousand patients for md s. It's around eighteen. Point five thousand patients per year. That could be part of curious. Total addressable market. If we assume the costs of this drug is going to be something in the neighborhood of one hundred and fifty thousand dollars per year. We assume they can get about half of those patients as a potential peak. We're looking at around a one point. Five billion dollar total revenue per year. If everything goes well and i think that's a reasonable jumping off point for evaluation assuming everything continues to go well for them in. Am our md s. Now this is not including anything for non hodgkin lymphoma and not including anything for solid tumor so rate now sitting at a one point four billion dollar valuation at say. It seems reasonable to say that it's fairly ish valued but let's look at some competing molecules and not direct competitors but specifically. I want to look at f lt. Three inhibitors in an hitter. So f lt. Three inhibitors is a few of them on the market. One is called ministering or ride at and it was approved by the fda combination therapy with the seven plus three regimen in two thousand seventeen specifically for f. l. t. three mutant aml patients and it was approved based off of an overall survival. Readout in one of their big trials that they did and the hazard ratio was point. Seven seven four compared to placebo which is very nice improvement. It's at novartis drug. That garnered a three hundred million dollar revenue in twenty twenty and it's projected to hit one billion dollars eventually as like their peak revenue so as a twenty twenty one though and it took her three years for them to get this. They're able to hit three hundred million dollars in revenue. Guiltier or zo. Spotta is another f lt three inhibitor. And it was approved by the fda in twenty eighteen for f lt. Three mutant am l. patients. The reason why it was approved was due to a trial versus a chemotherapy regimen. The complete response rate was fourteen point two percent of patients with the duration of response. That was very impactful. Fourteen point eight months and then the overall survival compared to chemo was a hazard ratio of point. Six which is very nice as well be drug is made by a company called steps pharma and they garnered a revenue of two hundred and seventeen million. Us dollars in twenty twenty so again only a couple years on the market and they've seen two hundred seventeen million dollars of revenue and this is for nfl t three which as i mentioned potentially has twenty five to thirty percent of am l. patients for another category of targeted therapy. Too is another potential driver of a pilot. Kenia and so a company developed something called anisette and it specifically targets patients with an idea to mutation and this is what they say is up to nineteen percent of ammo. Patients was approved by the fda in twenty seventeen and it was approved on only single armed data showing a nineteen percent complete response with a median duration of eight point two months in these patients. The company that owns the rights is bristol. Myers and in their twenty twenty report. I was looking for the revenue numbers but they were not shared there so we don't really know how well it's doing just yet but i assume once it does make a larger impact will start to see those numbers but so the early numbers that we're looking at here in general is around three hundred million year and if curious can reach a larger patient population we could see garner a larger revenue number. So with that. Let's talk about the efficacy of see a four nine four eight in am l. And this is a trial in phase. One and two. And i wanna i talk about the data. They showed before the update in the last week. And the reason for this is. I think really need to see. Are the changes in data from early to say now. So the data cutoff that i'm showing right here is from november. Twenty twenty one and this is a cohort of patients. That are heavily pre-treated. They each received on average around three prior therapies. And we're looking at only six patients right now. It's an oral dosing. Regimen of twenty eight day cycles and how the trial design is three plus three escalation starting at two hundred milligrams twice a day then going to three hundred four hundred and five hundred milligrams twice a day and so the data they shared here are two bone marrow complete responders out of six just very nice thirty three percent and what qualifies mero complete response is that the patients blast count must be elevated above five percent at baseline and then to achieve that complete response it has to decrease by fifty percent or greater to below five percent into that normal range in the bone marrow so the two that received this mero complete response originally had eleven percent and twenty three percent respectively in the bone marrow blast counts and those dropped all the way down to two percent and one percent respectively so the changes over fifty percent the baseline was about five and then they went to below five percent if we see here on each individual patient. It looks like there's going to be nice efficacy. In every one of these patients we have some patients that have blast in the forty percent range. Here some in the twenty percent range and they do drop pretty substantially one patient who had md s had a blast baseline and then it went down to two percent so this is a pretty big impact on a percentage basis but because it wasn't above five percent they couldn't call it a complete response so they're being fair here in the being pretty transparent with the data so this is obviously encouraging to see now what we saw in the update last week was abstracts and a press release that showed an update in data that they're going to present in the european hematology association conference happening in early june of twenty twenty one now. This data update is a cutoff now from february. Twenty twenty one so it's adding about four months worth of data here. These are again in heavily pre treated patients but they've increased the end from six to fifteen and this includes eight mdis patients and seven am l. patients. And what they tell us here. Is that bone marrow. Blast reductions were observed tested doses in eight of the nine invaluable patients. So there's fifteen patients that have been dosed now but only nine of them or valuable and of those evaluate patients. Only one of them did not see a bone marrow blasts reduction so it's pretty nice data so far then what they go on to say. Is that the objective responses that were observed are one patient experiencing a full hematological recovery. Complete response one incomplete response with negative minimal residual disease and then to bone marrow complete responders. Now i am not a hematologist by training and all of the research. That i've been doing on this showed some mixed information on what these two other categories of complete responders are. Maybe somebody can tell me what i missing here. But what we really want. Are these bone marrow. Complete responders what this is suggesting. Is that the bone marrow. Blast percentage is going down into that normal healthy range. And i believe that the haematological profile is coming back to normal. Now what they say here. Is that one patient experiencing a full hematological recovery. Complete response to me suggests that the hematology isn't quite yet in the normal range but they're getting their starting to show that the playland numbers the red blood cells are getting into that normal range but they can't call it a complete response yet because it's not there. The incomplete response and here is a similar thing in my opinion in that the hematology isn't completely back to normal but they have seen negative minimal residual z's so what that means to me is that they're not seeing any leukemia cells there and the bone marrow is on its way back to getting to normal percentage of glass but the hematology might not be totally there yet. Now all of this is still very positive. So i don't wanna take anything away from the press release but maybe my lack of understanding hematology just doesn't make me quite get it but the two bone marrow. Cr's here are probably the ones from before that we that they showed here and then they're also starting to see these. Other patients come in with an improvement in their bone marrow and their hematology what they also mentioned here. Is that three patients that had a sf three be one or a youtube af. One spices mutation achieved marrow. Cr or what this means is that they're sharing with us that patients that had mutations that would lead to an iraq for long version potentially driving the disease are the ones that achieve the complete responses. This is validating to everybody that the drug that targets iraq foreign particular is able to have an effect preferentially in patients that have mutations that would lead to iraq for long version now it seems like other patients are also getting improvements in their percentage of blass irrespective of whether or not they have these spices. Oh mutations to me what this says is that there could be potential for ca four nine four eight patients that don't necessarily have a iraq for long version but it could be an other subset of patients that could benefit from this drug. So it's a little bit curious here. And i think the expansion cohorts that the company is looking at and blowing it up. Here is a response to this. So they're going to be looking at four monotherapy cohorts. The looking at md s that are relapsed or refractory to a hypo methylated agent. Those that have a spices on mutation. And those that don't have as places or mutation they're also gonna look at relapsed or refractory am l. patients. That have been f lt. Three mutation or those that are epilepsy. Not three wild type so they also think that potentially it makes sense to Partition patients based off of their nfl. Lt three status. And i'm not sure exactly what they're thinking. Here if they're relapsed or refractory to f lt three inhibitor. Potentially that potentially the cells that are escaping the cure. The treatment are those that might be responded to iraq for inhibitor. So i'm just speculating here. I'm not sure exactly what they're thinking but to me. It just seems like iraq for could be a target that could work in patients outside of those that have spices. oh mutation so in combination. They're going to be looking at two different cohorts. One is c. Four nine for eight with as acidity looking at am l. or end s. In hypo methylated agent naive patients. They're also going to be looking at ca four nine four eight with fanatic lacks in md patients in veneta naive patients. So they're really expanding their reach with what they're hoping to see in different types of am l. md mdis patients. And it's really exciting to see. I hope that the data that come from these are going to be able to shed some into who would be the best patient to receive four nine four eight. 'cause here what it's looking like is a lot of patients could benefit from it. They're seeing effects in eight out of nine of the patients and that includes patients. That don't have places. Oh mutations so the other thing that they say is that all patients with objective responses also saw signs of hematological recovery. So they're not normal hematology just yet but they're seeing that recovery some capacity so the presentation can present so this data was all from a press release as well as a abstract that was submitted to be european hematology association but actual or presentation on friday june eleventh at three am eastern time. So some of the questions. That i had here about what it means to be a patient experiencing full hematological recovery complete response. They're gonna shed more insight into that for us to really know what they're talking about when they say the stuff the bone marrow. Cr's we've got a pretty clear definition from the prior data. But i'm going to be curious to see what they mean by these other things and also to see what these patients had a baseline like. I'm curious to see which patients had the forty percent blasts in their bone marrow. And whether or not they were able to get those patients all the way down to incomplete response or something like that. So i'm excited to see what they're going to show on june eleven. The next thing. I wanted to talk about is the safety data because they didn't just present efficacy. They also shared some insights into safety and a lot of people were negative on this. And i'm gonna share. Why don't think there are reasons to be concerned. And i'm quoting here. Jerry's updated that the five hundred milligrams twice a day. Dosing regimen in the am l. md. Study has exceeded the maximum tolerated dose. According to protocol guidelines to patients in the cohort were observed have dose limiting toxic cities. One of whom had agreed three rhabdomyolosis and the other experience agreed three. Sing cope i think. That's how you say. Both adverse events resolved after discontinuation of dosing current enrollment is exploring lower dose levels to determine the appropriate recommended phase. Two dose. So what the company is saying here is that they've reached a maximum tolerated dose according to the three plus three trial design. And for those. Who aren't familiar with this. Three plus three trial design. I've outlined it here. i'm not gonna read it. I'll just explain that. How it works is that they treat three patients in their lowest dose. If no patient has a dose limiting toxicity. They moved to the higher dose with three patients. If no patients have a dose limiting toxicity there they moved to the next higher dose and so forth now if they get one dose limiting toxicity. They'll treat another three patients at that. Same dose level and if two or more dose limiting toxicities occur in that expansion to another three patients the prior does will be known as the maximum tolerated dose and the company should move ahead with that dose will say so. What we're left with here is trying to question whether or not be patients that were responders are in that five hundred milligram dose group because if the five hundred milligram dose group includes all the patients ahead a response. You can obviously see how it's gonna be a problem because they saw these serious grade three adverse events so what we want is that four hundred or below to be the dose where they did see some effects of their drought and. I don't think that these responders are in the five hundred milligram dose and the reason for that is in fifteen patients that were valuable. It looks like six of them are probably in that five hundred milligrams twice a day dosing regimen. The reason for this is we can count. Three patients were in the two hundred three patients in the three hundred three patients. In the four hundred that totals nine patients then. They did six patients in the five hundred milligram dose. Because they probably saw three patients one of them. Had a dose limiting toxicity. They did another three. And got another dose limiting toxicity. That's why they're saying that they're probably going to move ahead with the four hundred milligram twice a day dosing. But the reason why. I don't think the responders were necessarily in the five hundred milligram. Dosing regimen is that they saw to mero complete responses in only six patients with which probably only went up to three hundred milligram. Dosing regimen is my sumptious the additional patients that they saw are probably either in the four hundred or the five hundred milligrams dosing regimen potentially but because of the way the patients are a valuable here. They're only evaluating nine patients. And i'm assuming that those are doses up to the four hundred milligram dosing regimen. Because they haven't quite gotten yet to the fifteen patient total here. They're only showing data from nine patients. So for that reason why. I'm pretty confident that of the nine patients. None of them are in that five hundred milligram dosing regimen. But i'm just speculating here. And we're really. We're going to see more of that data coming up in their june eleventh presentation. So it's for these reasons that i don't think that this update in safety is anything to be worried about if they're gonna move ahead with a three hundred or four hundred milligrams dosing regimen. So that's kind of a convoluted answer i would say. I think that we don't have to worry too much about this safety. So i wanna quickly move onto the non-hodgkin's lymphoma trials because they are looking at a basket of different non hodgkin lymphoma cancers and so what they've done here. In phase one is they done two different dosing regimens at once a day or twice a day in the traditional three plus three design. They're looking at a variety of different doses in heavily pre treated patients who've used up to four median prior lines of therapy so highly pre-treated and what they've shown here is the potential recommended face to dose of three hundred milligrams twice a day. They saw effects in six out of seven of those patients. So the balloons here are those that were on three hundred milligrams twice a day and one two three four five six able to see some positive response as opposed to a progression of the cancer. Now these patients here that only saw best response of maybe negative five negative ten. They might be considered as stable disease partial responses so. We don't quite know yet how they're going to be officially categorized but they're going to be updating this data in the second half of this year and i think it's gonna be exciting to see whether or not there will to improve this or maintain this in a follow on in terms of safety for non hodgkin's lymphoma most of those treatment related adverse events occurred in the four hundred milligrams twice a day group. Now they didn't really mention great. Three or four t ease in the am l. Study and the patients are different. So it's potential that non hodgkin lymphoma patients are more susceptible to treatment related adverse events. I'm not too sure but it is something to note that in the four hundred milligrams group here. They are seeing more human related adverse events now having said that with non hodgkin lymphoma. They're thinking of moving with just the three hundred milligram dose group so anything that occurs in the four hundred milligram. Group might not be anything we need to worry about. They do mention that rabdah. My office occurred in two patients in that. Four hundred milligram dose group and they did this based on muscle soreness and Elevations so what happens in rubbed in my office is a big danger for the kidney and what they can look at is cryonics or cbk elevations in the urine and if it gets too high there is a risk of renal failure so it could very well be a very serious side effect that the company has to worry about what they say here is that there was no renal dysfunction observed and both cases were observed in cycle one dosing and then they had early monitoring ck so they could see whether or not there was going to be a problem long term or not they said these patients had additional risk factors associated with vigorous exercise dehydration or co medications such as lipid lowering standards so other factors could have been involved in leading to this rubbed my office. I do think that it is something we should be mindful of once. We see the full data set but here. Because it's in the four hundred milligram dose cohort. I don't think it's something that we need to worry about too much. What might be more concerning. Are these two treatment. Discontinuations due to treatment. Emergent adverse. Events at the low doses. So this is something to watch out for. I think in the updated data in the second half of the year. If it becomes a trend that there are treatment discontinuations due to t ease. That could be a bigger problem than significant events. That occur at higher doses. Since they're not going to be used so like i mentioned the company is moving ahead with reporting initial data in the second half of this year in an ongoing phase one two in combination of c four nine. Four eight plus a brute native in patients with relapsed or refractory non hodgkin lymphoma. We don't really know what they're going to do with the monotherapy. So i do think it's interesting that they're shifting a little bit to a combination therapy with a bruton hip which potentially could have a synergetic effect. Air remains to be seen. But i do think that this catalyst in the second half of this year could be a pretty big mover for the stock depending on what we see the last thing. I want to talk about with regards to curious. Is there molecule in solid tumors called. See i eight nine nine. Three and this molecule was originally developed by janssen. It was known as this janssen molecule that was licensed from a company called immunex in two thousand twelve and they initiated a phase one study in two thousand sixteen toll patients were enrolled and they started a dose level of point zero zero five milligrams per keg what they discovered though. Is that low grade. Transient cytokine release syndrome was occurring at zero point. One five mix per gig and above. What happened is that. Jj halted the study after one dose limiting toxicity at sub therapeutic dose levels. The only patient treated at point three mix per king experienced agreed three sierra s associated with encephalopathy after thirty six hours of treatment. The patient was treated with antibiotics and symptoms result after this treatment. With toss eliza mab what cured says here is that the target range for expected. Anticancer activity is that doses of zero point five to two mix per kick and that. Jj was never able to this before they just canceled the treatment. So i'm showing here's some pre clinical data suggesting that treatment with anti vista is able to improve a melanoma preclinical model. So what the company is doing. Is they got the right. So this molecule. And they're moving ahead in a basket of solid tumors. For a phase one study. They're targeting patients in advanced refractory solid tumors including mesothelioma melanoma non small cell lung cancer in triple negative breast cancer. So all of these indications combine are a huge total addressable market upwards of one hundred thousand patients per year and what curious says is that their design of their phase one incorporates key learnings from the janssen phase one study. They also say here. That said it can release. Syndrome is likely an on target toxicity indicating that the drug is hitting the target and inducing inflammatory responses but that now that the ecology community is so used to dealing with cytokine release syndrome their now familiar with a treatment regimen. That is able to manage it. And so they mentioned that the nc c. n. guidelines were issued in two thousand eighteen. But when i looked at these guidelines said that the recommendations archery matassa lizzy mab and or corticosteroid. So it's not like. Jj did something different than what would be normally recommended with. These newly issued guidelines from two thousand eighteen cure says though is that the fda cleared the study which outlined their plan for managing sierras and enabled escalation to therapeutic dose levels. And then i'm just going to blow this up here. What they say is their plan for dose escalation. So i think there's definitely potential here but it's one of those things where it's going to be a high risk trial where the likelihood of success is very low fact that jj saw a lot of sierra s in the sub therapeutic dose levels suggests to me that they're gonna see a similar thing when curious as a phase one trial. Now one opportunity that. I see here though is that jane. J. halted the study. Only after one patient was dose and this could have been a fluke. Only one patient getting a grade three sierras. While it's not a good thing. Obviously it does leave opportunity to suggest that if they dozed more patients it might just be a minority of patients that see this great s. And if it's a great one sierras in most patients may be can be manageable by this new regiment now. This is the unlikely scenario. I think that if one patient sogari through sarah the likelihood is that more patients are going to see it and it's going to be a lot higher burden than what may be curious as letting on here. But i took a look at some carty therapies. That were approved specifically. Because i knew that grade three sierra was problem for them and escada and katie x nineteen in different non hodgkin lymphomas had around thirteen percent of grade three sierras so if curious can show that their treatment of patients of eight nine three can be effective and also have a limited amount of sierra's down to around thirteen percent. There could be a path to approval here. So it really is gonna take seeing the data and right now. We just be speculating. But it's going to be one of those things that if they are seeing good data the stock will move hugely on the news. But more likely than not. They're going to see safety issues that preclude them from moving forward so to talk about some upcoming catalyst. The main one obviously is this oral presentation at the european hematology association conference. This is going to happen on june eleven at three. Am eastern times obviously a european conference. So it's going to be presenting hats kind of an inconvenient time for those of us. In the usa companies. Also gonna do a qa session on june sixteenth and that's going to be happening at eleven am eastern time. The company also has a poster presentation but this is just preclinical data. So i don't see this being big mover for the stock. Another callous is going to be coming in the second. Half of this year of their phase one and two combination study of ca four nine four eight plus abreu in patients with relapsed or refractory non hodgkin lymphoma and then in the second. Half of this year they're going to be sharing data from that. See i eight nine nine three study and the treatment of relapse refractory solid tumors. So overall my take though is that four nine four eight. It's going to be first in class. Potentially iraq four inhibitor. And it seems to have a significant improvement in hematological malignancies. Now being a first in class molecule has tremendous advantages. Obviously this company is probably starting to get the attention of a lot of larger pharma companies. That might be looking to break into a molecule that could be first in class in. Am l. t. g. Therapeutics has a competing molecule. But they're still in preclinical development. So we to see clarity on that timeline before we can think about seeing tgt axes being a competitor to them. Just yet i think that in terms of countless the added data in june is not likely to surprise us. But like i mentioned before with how they presented the press release. They're gonna give us more granularity on the baseline of these patients as well as what does they were treated with and all of this stuff is going to be very helpful. I think in helping us analyze whether or not we can be really excited about the data. I do think the data is super positive. But more granularity. Here i think is going to be. Well received the combination data release in non hodgkin lymphoma in the second half of this year. I think it's going to be a big challenge for the company. I would see a potential upside of only around two billion dollars and downside of around seven hundred million on the callous. If it didn't go their way so you know. Is it worth it to play this. It's up to you to decide if the company is able to garner a buyout. I would say that it's fair to say they could potentially do five to ten billion dollars buyout but that's like a long shot. I don't think we should be planning. Our trades based off of potential emanate activity. Which lately there hasn't been much of so. I think that we can get excited about being first in class. Getting a lot of attention from big pharma but we need to temper expectations. Because we just don't know if it's on the table or not the solid tumor data could potentially see a huge upside if they are able to see an effect but like i mentioned. I think that there's a lower chance of success. But depending on what. The company is trading at in the second half of this year you wanna throw a few shares on it and see whether or not they are able to get that positive data. It could be worth it for you. The upside is gonna be weighed. Greater than the downside. I think for that. So i might look into playing Cabinets or maybe the non hodgkin lymphoma catalyst but for me. I'm gonna kinda sit on the sidelines. Watch the companies. Go through this run up in the stock and we're sitting now. I don't see ton of upside necessarily unless the update in june is particularly amazing. I think we've seen most of the details there. If the company does see some selling off. I might take a position in the second. Half in hopes of a positive readout in hodgkin lymphoma. Or maybe the solid tumor indication which could be a pretty big mover to the two comparisons. That i think are valid for. This company is one which i've touched on before which is the company forty. Seven mcgrillen was a pretty much first mover in the cd. Forty seven face to show efficacy in. Am l. as well and they were bought out by gilead for four point. Nine billion dollars then veneta climax and that's the trade name here which has been collects sta was the first in class. B c o two inhibitor. And now they have indications in cielo. Sol unfit aml so. It's not quite a valid comparison to curious but their revenue in twenty twenty one point three billion dollars so there's definitely a huge market that is available here depending on what they can end up showing so so all this to say. I think the company has a lot of potential and it's really gonna take us reaching those added milestones to see whether or not they can deliver but it's very exciting for patients that have am l. are unable to get a response with the legacy treatments that exist today. So that's curious. Let me know what you think in the comments. Am i off base. Tell me what i'm missing about. The complete responders in terms of upcoming catalysts. Already touched on a notice and gene therapies. Were still waiting for a cheek data but we did hear from their year end or the q one wrap up that there were no dose limiting toxicities observed yet. I see that as a very positive outlook even though the stock has sold out quite a bit in the last little while had the on. We're still waiting for dating you to on terminal updates yet. But they're gonna present something lasko. Alex oncology we're still waiting for mid twenty twenty one updates and then four d molecular therapies. The lockup is firing in june. Early june so i would not hold the company into that number shares that are going to be thrown onto the market are going to be substantial so definitely watch out for that in terms of portfolio. Wrap up the last couple of weeks than rough. I'm not gonna lie. I'm sitting at around negative seventeen percent on the year quite nicely with archie to be honest and i don't even hold names like beam or crisper so very frustrating but it is what it is. We expect these kind of big swings in the b. I the iv and xp are also downturn quite a bit and. I think it's really going to take some big changes in rhetoric from the government or some surprise news in emini or something like that before. We can really see a turnaround here. So we'll see. I'm still holding onto names that i do have conviction in but like i mentioned before i'm very heavily invested so i think in the next month or two i'm going to look to reduce all my position so i can have some cash on hand. So that's that. I did want to mention that. I added more novus here. So i fifty shares now looking to exit after the alzheimer's disease data read out but with that. I'm going to wrap it up. I want to thank everybody for tuning in appreciate all support. Click that link button and share this with a friend if you think that they might appreciate this kind of content. So with that thanks again. Everybody and we'll see you next time.

parkinson's disease hodgkin lymphoma cancers gm iraq alzheimer's disease myeloid leukemia fda curious inc european hematology associatio
Tia Stokes and Choosing Happy: Finding the Good Through Cancer, Covid, and Grief

Mint Arrow Messages

42:34 min | 4 months ago

Tia Stokes and Choosing Happy: Finding the Good Through Cancer, Covid, and Grief

"Tears stokes is a thirty five year old mother of five kids who was diagnosed on april twenty fourth. Two thousand twenty with acute myeloid leukemia. And she's been documenting her journey everyday sense of fighting cancer. She has fiercely loyal following of supporters. Who dance cheer her on and are inspired daily by her positive attitude and dedication to her family and faith and looking for the good and everything is a dancer choreographer and owner of two dance studios and former backup dancer to celebrity singer. Beyond say novick deal. Tia has share the raw and real ups and downs of having cancer getting covert an ammonia needing a liver transplant and also losing her mother after her. First round of chemo. This interview was one of the most inspiring stories. I've ever heard and if you need some positive motivation to just keep going no matter what trial you're facing in life this episode is just for you. I have a new friend with me today. And her name is tia. Stokes and i have just admired and loved her so much from afar for quite a while now and the so excited to have the chance to talk to her today and share her love. Enjoy with so many of us not say hi and tell us a little bit about you who you are and what you do in all of those things as hello hello. I'm kia stokes. Five major legend maze. Tasman rose i am married to the handsome andrew stokes. I'm thirty five years old. Just trying thirty five years old just barely and two hundred and seventy three days ago. I was diagnosed with acute myeloid leukemia. And so i have been sharing my journey and documenting my experiences Because i know that one day we'll beat this in ring. That bell and i will be able to see the fight that was and how hard i actually fought so i love documenting the good days as well as the bad and the hard ugly days that give me strength and helped me july on my savior and my heavenly father and I'm grateful to be here. I tried to choose happiness every day. No matter the circumstances that i'm going through. I know that happiness is a choice. And that's something that's free agency that we've been given and all i. I hope that my story and my experiences can be able to shed light and love to all those around me. So that's a little bit about me. Amazing absolutely amazing. Your story is so inspiring. And i can't wait to get into it. I want to ask you what you were doing before your diagnosis. Like what life looked like for you what you were up to and what your husband does and kind of get a little bit of background there. Yeah while i'm a very busy mom. I own two dance studios will as you know. I have five kids. And i was actually pregnant before my diagnosis was my fifth baby. Which is our only girl. We have four boys and one little girl and i was teaching dance classes. I just opened up a studio up in orem utah. I have one in saint george. I've had for thirteen years and we just opened one in orem. Our studios are dedicated service and dancing for a cause. So they're not like competition bay studios they. We actually choose a family within the community. That's going through a real life calamities such as cancer or meeting a transplant. Or something of that nature. Something that life is you know given us a challenge and we dedicate and dance for those families in need and we donate one hundred percent of our concert. Fees are concerts and um fundraisers to those families so i was super active and busy busy choreographing performing teaching. I was teaching all the time. I at nighttime and early orange. I was waking up at four. Am for practices Because our dance team are company practices in the morning at four. Because obviously we're all moms and we all have jobs and things like that so and it's a service based dance group so it was a good time for us to do it so getting away of family and i was teaching fitness classes for women I was being obviously running a uber to my kids for their practices classes and things of that nature But life was my husband's a head football coach at you high school. He is teacher as well and so football. It keeps in our family. Obviously you know anything about football coach position. It's a family thing Oh we were all involved and really busy with that as well and so. I'm just a really active busy family and we're always together with our kids our kids either. We'll go to dance. You know if. I could take him to dance class with me if i needed to. And andy take him to football. We were just always go going and Together as a family so a lot different than now. Yeah so you also had a pretty amazing dance career before. I don't know if it was completely before kids or a little bit mixed in but tell us just a little bit too about your dance background because it's pretty amazing yeah I started when i was ten. And i always wanted to be a professional dancer. That's all i wanted to do. And i obviously rehearsed ad group in a studio My sister was trainer And as a. I started auditioning when i was a senior in high school. And i got my first like dance gag as a backup dancer. Fiancee knowles no big deal. Yeah it was pretty awesome. Cool experience that i was able to have and and able to do that with her at the billboard music awards and i did a little bit of things with jennifer love hewitt and the back and the two k. movies and things like that before i started to get into having a family and wanting to settle down and change my dance grew to dancing costs so incredible. Yeah so cool and just fun to hear your background and the things that you were driven to. Do you know in an earlier stage of life so tell me what you remember about getting this diagnosis and kind of how that all came about While i was sick. After i had rose my baby. I was sick for about five months leading up to my diagnosis. And so when i got diagnosed in april i was just like so ready to be done being sick because i had been teaching classes. Still and my children remember. I could not breathe for the life of me. Like i'd be teaching a class and or trying to dance rehearsals and i could barely finish a routine and i just end up on the ground just and i thought and i get thinking. Oh it's i'm outta shave. I just had a baby. You know i'm post partner online kushner off to that. Like i was just a ma i just had a baby and so But little did. I know i was just super anemic. I had no red blood cells in king so i. That's the reason why i couldn't breathe. When i got diagnosed it was like it was a relief. It was obviously a shock. Because you never want to hear the words cancer you know and you never. You never think it's going to happen to you right but a part of me had a feeling i just had a feeling that it was more than just like being sick you know and i think that was the tender mercy for my heavenly father. Just letting me be prepared and let me have those feelings of. I knew that it was more than what it why. What what we thought and my husband i think she was more shocked because he didn't want to believe he's more. He's super positive but also doesn't you know we try to not think of bad things happening like that you know and When i got diagnosed Actually it was right before right before. We got the final diagnosis I went to my doctors and they had me go back for more blood work. They had told me that they had. They thought it was leukemia. But they wanted me to go get more blood work done. I and so as i was coming back from Getting more blood work. We had stopped at the grocery store. 'cause we were gonna make s'mores that night and my husband ran into the grocery store and i was sitting in my car waiting for him and i just had this. My dad passed away seven years ago. And i just had this feeling like i could hear his voice so loud in my head and he just said let's go like let's go. We got this and that's kind of where the we got. This thing came from on all my posts Because it was my dad loud and clear in my head because my dad training for marathons when i used to run marathons and i could just hear him in his marathon boys. Let's go office now. You know that. Just that stern dad like what's to work we're gonna we're gonna get this you know we're gonna to this and i just had an overwhelming feeling of like okay like right. I'm not scared and we're gonna do this like we got this. Let's go to work all my. That's like all my feelings. Were like let's work. let's get this done. And that was just such gender mercy from you know from. It's they're closer than you think you know yeah Such a strong just strong tender mercy that i was able to fill my dad in the crazy thing is throughout this journey had been able to fill him and my mom in so many different ways and so when we got the final diagnosis right after that. That was an hour later my doctor. He's the family friend. He came over to my house and told us that he was crying. Tears in his eyes and he just said. I'm so sorry like your blood smear doesn't look good and they they it looks like leukaemia and they want you to go to the hospital right away. You have to be admitted right away. And that was obviously obviously during cova covid and he andy asked am able to be with her and he said no you have to just drop her off at the front. You can't even go in you know. You can't user so that was hard. Because it was. I was that was a month. You know he basically from the day. I was diagnosed right then. An hour later he dropped me off at the hospital and to battle for the next thirty one days. Oh my gosh and you have five kids. And i have five kids. Yeah the heck. So what did you do with your kids on your husband. Who is a teacher and a coach. And how did you guys even so next. We have so many good people. You know when things like this happen. That's the beautiful thing about life. Calamities is that so many people come together and serve and that is the ultimate. That's the ultimate gift. That's what we're supposed to learn here on. This earth is service and being able to help one another and because we're all brothers and sisters and that's the beautiful thing about these kind of situations that bring so many people out so many strangers strangers church members to school scold members to next door neighbors you know som- many old dot com. So that might. My cousin came and picked up our kids. We didn't tell our kids right away that i had cancer Because we were we were trying to take it in ourselves right. I don't want. I didn't want to leave them and have them be crying. I'd rather them be happy. You know that they get to go their cousin's house so my my cousin nani came and picked them up and she took them for The night andy was able to drop me off but after that i mean and his job is really good about helping all the black tender mercy about the blessing about it was it was during covid so school was actually not in at the time anyway. Okay so that was actually a blessing. Because andy didn't have to go to work he wasn't working anyways. You know right. Oh he didn't have to take time off. He was doing everything online. And then Yeah and we had in laws are laws came and helped out with the kids and took them for a little bit but yeah. You just can't plan for that kind of stuff you know and uh crazy just depend on others and hopefully you know it all works out so yeah so so you said thirty one days was your first stretch so tell me what that was like so thirty one days. That's your first chemo induction. And they have you stay. I hadn't stayed in the hospital for that thirty one days because of it. Was my first chemo induction. So they try to monitor everything. They monitor your. How your how you react to everything. And if you're what they need to adjust and how you're 'cause you've never had chemo for obviously so they have to make sure that everything's going to work out the way it's supposed to and so it was. It was how it's lonely moments obviously out. Because i couldn't have any visitors. There is no visitors allowed but my nurses made it super awesome. Might nurse the nurses there at the cancer. Cancer unit are just super amazing and just genuine and heartfelt and they love their patients and they made it super just easy to be there and but thank goodness for you know. Social media was a great outlet for me. Because you're never alone you know. We're long physically. But honestly there's so many positives to social media and to that there's so many people that were reaching out and looking out for me and talking to me that i never actually felt really alone. you know. Yeah that's amazing okay. So that thirty one days and then you were able to go home and tell me what happened next So that was thirty one days so made twenty four hours. I went home and that same day. i that morning he actually so will the thirty days that i was there We would zoom with my family. My brothers and i have seven brothers and sisters and my mom and we would zoom every single night together too because my mom. She couldn't be there with me physically and so she wants. She wanted so bad baby on the baby of the family security so badly wanted to be with me. They all live in saint george and so that was kind of our way that we would all catch up and they wanted to know what was going on and you know and every update everybody let everyone know mike ganley what was going on so we would zoom every single night and the last night I was there is zoomed with my mom and it just so happened that i was the only one that got on me and my brother. My brother gotten on for a little bit. My sister go on for a little bit. Everyone else was busy. Doing they're working on my house. And so i was able to talk to my mom that night and the next morning i called my mom for my scripture because every morning i would call her and she'd give me a scripture a special scripture and i called her that morning and she didn't answer in so i just thought okay. Well she'll call me back. And i went and got in the shower and got ready. My husband came to pick me up and right when he came and picked me up. I got the news that she had passed away that morning. So she That was that was really really hard. I was probably the harder diagnosis. Obviously because i just didn't wanna believe it. I i remember. I was in the hospital room. Just like crying and screaming and yelling. No this isn't happening. No like this isn't this is real and I just remember that morning. Though i was able to fill hurt like i said i got in the shower and after i got in the shower i could fill this overwhelming love like happiness and joy and love around me that i just started bawling and i thought i thought i was crying because i was going home and i thought that's the feeling was but now i know now. I know that that was her. You know now. I know that that was her spirit. That was her comfort me telling me that she finally gets to be with me after all this time and so that day she went back to my dad and i went back to with my husband after that. So wow here. I just can't even imagine with going through the current trial you were going through with fighting cancer to then find out that your mom had passed away and i just think this is one of the many things that have brought like just drawn so many people to you because you've been really real about how difficult that was also really determined to stay positive to look for the good to you know so so. Walk me through. I guess the next little while and what that felt like and what some of the things that you did to to deal with everything that was going on in your life. Yeah so. I'm still dealing with it. Yeah definitely i still. I feel like it's still. I like it's i you now. It was so everything happens so fast like she passed away and we had a funeral. Right away you know and covid during covid and that was like my break in between chemo treatments and then right. After the funeral i came back to. I had to go back to the hospital for more chemo. And when. I do my chemo for a week. At a time i have to it and so And after that. Round of chemo. I i had a lot of neurological like damage. They call it neurotoxicity. Where the chemo. Basically damages like your nerves and your brain function to your nerves in your muscles and so there was a time after that. Second round of chemo. For like a month. I had to go back to. I was back in the hospital for about a month. Because i had to learn how to walk and talk. And and e n and use my fine motor skills again. And i couldn't even there was. It was so scary. Like there was a point where i couldn't even lift up my legs By myself because there were there was no like no coordination muscle in that you know like no. Yeah an o Which i understand now. Like i know it's funny because you know as sad as i am about losing my mom you know and her not physically being here i get it why she had to go like an. I get that she can do more for us. You know on the other side. Then she can do here in person you know and she actually be with me spiritually in these in these hard times so in that moment of like me learning how to walk again and i was using the walker and i couldn't even dance and i mean there were so many so many curve balls and then cova i mean after that i went home for a little bit and then i got kovin and i had zero. Immune system like it was literally zero point zero and I was in the hospital for another thirty two days. And i just remember feeling my mom and dad so strongly with me at so many different moments and like another time was when my dad i i was laying in the bed when i had covid and this was probably like four days. I'd been there already and they just. They weren't really treating me with anything yet. Because i was a pre transplant and so they didn't want to ruin my transplant process. They don't wanna ruin anything right and they didn't know how to treat me and so i i felt my dad and he just said it's it's going to get worse and like another. You know just like that. Tough love dat like. That's very tough law of like very stern but very like he loved you so much that he would teach you these things and so i just remember him saying it's going to get worse and little little. Did i know like an hour later. The doctor came in and told me. I had acute kidney failure and pneumonia and i was just just cried because mike. Thanks dad like i dunno. It's kind of like comforting. It's like a comforter. You know like when your dad tells you these things before it actually have to. yeah oh. I had kobe kobe for that month. And that was really hard and i. I had pneumonia for awhile after that But it's just been it's been an up and down experience and lots of lots of opportunities along the way of just cancer you know so Now i'm home. I had my transplant. And i'm home But i feel like now that i'm home in. This is the longest. I've been home on the last nine months the longest. I've been home. I'm just trying to now. Hit like face this phase of my life. You know of being a mom a wise. Like i'm still recovering from my so. I'm not fully one hundred percent yet. and and i'm greeting still in howdy chance to grieve her and it's been well and just i mean you said just cancer but this is seriously one of the most gnarly stories. I have ever heard as someone having to go through trial after trial after trial. I remember so many times to like watching your stories in the hospital where you're like now. I have pneumonia now. I have kobe. Now have now. I need a transplant. Now you know like it just is like one thing after another kind of seemed like wow. Let's just kick her while she's down. Why don't we universe you know. But i want to know what one thing that has been incredibly inspiring to me as the connection that you seem to have like with your faith and with your heavenly father like you were saying before and i loved what you were sharing about scripture so i wanna know what what part of your faith has. What part has played in. All of this that you've been going through in are still currently going through. Oh i would say all of it you know there. I don't know how how would get through these. I mean we didn't have faith in have the knowledge of you know of the plan and just knowing that you know all these things are for the greater good and you know my brother was saying something the other day and and he said if we died this is you know faith and all this stuff all liden. What what harm to actually. Do you know why didn't do any harm at all. Like help us to have more faith that helped us to be. You know better moms a betters. A better person a better sister a better wife a better you know. What harm did it actually do to help us to be a better human for our brothers and sisters and i would say like i'm just. I'm grateful for that knowledge. I'm grateful for my parents and for the foundation that they set for me and my brothers and sisters you know. Prayer is the greatest wireless connection that we have like. Oh you know. There's no feeling there's no wires there's not nothing but it's and it's free and he's given that us that gift and i think that it's so important to use it and no matter what religion you are we can all fray and without a doubt that my like i would not be the same person if it wasn't for my faith and for believing in him and having the knowledge that i have you know and i know my strength and my my choosing to be positive and choosing to have a better outlook in choosing like those are all choices for agency that we've been given and I know that i wouldn't be choosing as i didn't have that. You know. Talk to me about choosing positively on some of these really hard day's talk to me about what that is and what it isn't and why you. Why such a huge thing for you that you teach people in that you live by Because it's what. I want to be remembered by. You know if you think about like if you think about our legacy we're leaving a legacy behind and what do you want to be remembered How do you want people to remember you. you know. And how do you want when you that. I always think like that. And i always think i want. I want people to remember me as a happy smiling positive. Yes i'm real. And i share real moments in life but at the end of the day i'm choosing to be too shy and bill bush. Choose to be a positive person. And i want people to remember me like that. I love you seeds or not. You know i want to be someone. That was uplifting and and that you felt good that you're around that and that they made you want to be better and i hope i know there's so many people in my life that have done that for me and i hope i just hope to give that back. That's something that. I want to be able to give that back to all of those around me. Will you are truly such a light and and so inspiring to so many people myself included. I will sometimes think. I'm having a bad day. And then i see your stories. And i see or i see a live of yours and unlike not having not having too bad of a day and it reminds me to just put things into check. What actually matters what i feel like for me at least in some of these really trying times helps ground me right back to what actually matters like. There's so many things that distract us and take our attention away from the things that truly matter and so that's always so inspiring and refreshing to me to hear these messages from you. But i wanna know really like give me what you actually the tactical things that you do when you wake up and you're like today sucks unless i choose something like what. How do you change your mind. How do you what do you do. What do you do to really make that choice to be positive. What do i do well. I i have this like thing like before. I wake up right out of bed. I talked myself myself. And i asked my like asked my i have kids. You know. I have to keep living for. And i have a husband that i had my days in this week is especially hard week and emotionally immensely and i think that I you know you just keep moving forward. It's minute by minute. It's hour by hour day by day. You know and you just have to keep moving forward and for me. I have a conversation with myself. I tell myself i want. I wanna be a happy person. I want to be positive. And i wanna shine light on that and want to give that way and i think that it's important to have that time with yourself and i have a grateful journal that i do obviously is like a lotta people do work or i. I've seen huge benefits in my life from having a grateful journal. We'll do that. It's such an awesome thing is awesome it really does change your mindset like i write down three things that i'm grateful for every day i try to use my social media platforms as more of like a grateful journalists. Well as well as documenting everything. Because i want to i want to show i i need that reminder. You know. I'm not perfect on it. And i want that reminder to switch my mindset to being more grateful and thinking about the things i do have instead of the things that don't have and when i'm thinking about all the positive things in my life i i have helped me to continue to work outs me to continue to keep moving forward else me too shy. Remember that i've so many good things in my life. Seen heavenly father's blessing me with so many good things and this cancer journey has not been a bad thing. It's been something to help me to strengthen my testimony. It's helped me to build new relationships. I've been able to build More friends and that at the end of the day. That's all we get to take with us is. Our relationship has not dried yet. Fake relationships totally young and so how awesome is that you know and so a lot of people ask me like. Oh my gosh cancer. That's yes that's also really awesome like there. Is that days at a really hard. But at the end in the grand scheme of things it is. It's been it's been a beautiful experience. So i feel like you showing gratitude and a writing down actually writing down those things which are grateful for every single day three things every single day. Super easy doesn't take a lot of time it will help you change your mindset. Helped you change the way you think. Help you change your mind. You more grateful mindset. Rather than what i don't have you know. Yeah it and it actually is like scientifically proven. We do change that you know. There's a chemical release in you. That change that helps you to change. So it's really super awesome. What gratitude can do. I love that. I love that suggestion that that. It's like an actionable takeaway that you're feeling like overwhelmed or things aren't going well for you that you can write down three things day and it will totally change your mindset. I love that. I want to ask you what people in your life have done whether they are people you know you know personally in real life or people you've connected with online our social media. What have people done that have really helped and supported you through this time. Because i feel like more and more we know of people who are going through cancer. Who are grieving or who you know are just going through a really hard time. So what has been the most helpful to you. What has been the most helpful to me has been So many people have reached out have have messaged. obviously i get so many dams and let others I think the most like what's been the most helpful just being there. I think i that i get asked that question. What can we do for someone. That's going through cancer or going through. You know hard life situation. And i think just being there for someone no matter what even if you think they have loads of love and they have so much love around them and oh they have so many followers they have so many people and i think just continue to be there for them you know. Continue to write those messages continued to. Dm continue to write those letters. You know knowing. You never have enough love and i think that's been the greatest thing that i've been able to experience. This experience is all the lawn from so many different people. Is there something that you can think of that. Like it at particular experience or something you received that maybe on like a really hard day picked you up or help you out. Yeah actually during kovin. I got so when it was probably a week after i had cova that was in the kobe unit. Obviously and i couldn't dance and tiktok. So i love to doc i and it's fun for me. It's a fun app But i've met a lot of good friends on talking. I had a really good friend. Jd warn him and his wife they actually started t a day so they had ever and this is like a total shock. Me like i didn't know what was going on. I had no idea that this was happening but until the day it happened and he put out a big message video message to everybody on talk saying this day is going to be dedicated to wear red for ti. Because i gave her collar type food. If you have time to. Because i love Dance to holy justin bieber or danced any song or do anything to dedicate to tia and it was so that outpouring love. I saw from that day from the rest. I mean the love was spreading for days and days and days but it was so cool to see tiktok. This app just filled with like every every for you page. Every page i was going to was read for chia day and it was so beautiful and such i at a time where i was facing cove and and i was facing cancer and i was facing pneumonia and acute kidney failure like i was in dallas of the downs and this like literally brought my spirits up and help to fight and when you know the cool thing about community like that it's like when you know there's so many other people fighting for you you know that are dancing for you. They're they're wearing red for you. They're doing using their talents for you like it just helps you boost you up to fight even harder and so that's why That day was so special to me and such a cool experience in just such a cool labor of love. you know. that's so awesome. I remember that day too. I remember the i don't. I don't even get on tic tac. And i thought i was seeing people post post on instagram and it was spreading on instagram. To even though. I'm not tiktok user and i was like this is so awesome that you have so many people willing to just show up for you and down for you and wear red for you. And that was super. Yeah it was just a really cool thing to see so many people coming together to create a positive effect and it's cool to hear to really lifted your spirits and helped you feel like you had a little more fight left. It was awesome. That is so girl. What do you feel like you wish people would understand more like i guess if you could go back because sometimes when i go through hard things and i look back and i'm like oh i didn't understand this before and now i know better or now i understand better. What do you like. is there something that you're like. This would help people if people would understand this a little bit more about anything that you've been through like your cancer junior your grief for having cova dirt or being away from your family or anything like what are some of those lessons that you've learned that you issue maybe would have known before or the have been really impactful that you would hope for other people to learn i would say A big one is enjoyed today. Today's gift yesterday was history. Tomorrow is a mystery today as a gift. And that's why they call the president. And i think that is just so that is it's so true and you know we're so busy going through life and we're so busy doing things that we need to do that. We forget to just enjoy the moment and we forget to just play and find joy and beauty in everything around us that we just you know. Sometimes we get caught up in the hustle. And i think that just to remember to enjoy enjoy life in life was meant to be enjoyed not endured and we're supposed to joy the beautiful gift that we've been given we're supposed to enjoy air families enjoy the time time is so you know time is a gift and it's priceless and it's something that we don't get back like we do not get time back and if we were to really you know. Put that in our minds like we don't get this moment back so cherish it like cuddle all your babies as long as you possibly. Can you know they're gonna grow up in. They're gonna leave us one day and you know we're not going to get that moment back so i would say you know enjoy today. Today's guest time is priceless. And that's you know that's ultimately the best that you can give anybody what is your what. What do you have ahead of you as far as getting to that. Finish line of ringing the bell. How much more do you have ahead of you that that we can know that we can keep cheering you on and keep watching for you. Know what you're going through So right now i'm facing. I'm having a graph hosts disease symptoms. So they've been treating me for that with the steroid and with medicines. And so. I'm actually going to be having like a colonoscopy and andom something oscar and yeah in the next week and a half and so just to see where it's at and to see what they need to treat it with I have like fifty days in one. Hundred days is up to see my where my in grandma is with my cells And then i think. I have another bone marrow biopsy after that to see about see if my cancer cells are dead and all that stuff so it's still a little bit of the process but Were one day at a time. And then as far as like you're damn studios and Things that you're doing to still like where i i just saw yesterday. You were talking about how you're able to virtually connect with your audience so tell me about that as far as like your dance. Yes so i can't. Obviously i can't teach in studio yet with. I can't be around like groups of people right and Teaching virtual hip hop class. I teach at on tuesday's at five o'clock mountain standard time. And i teach it to people all over the world so anybody all ages. I have monster that the class at grandma's azam. I'd have kids jake class so i only do it once a week. I only do one One class a week just to kind of slowly. Get me into things you know. It's such a great at such a great way for me to start dancing slowly getting back into things again and teaching So it's so fun and it's yeah it's a blast. It's been so much fun being to be able to do that. So cool will definitely linked to those resources to the show notes I wanna know too when you ring that bell and when you when you know cova does over and your cancer journey is a little more completed. What are you looking forward to like. Are there things that you are hoping to do or that you are like. Is there something that you're kind of like okay. This is this keeps me motivated. Or i'm looking forward to or excited about this. Yes i want to take my family to disneyland. Yeah want to take them to hawaii. I wanna take my kids to hawaii. They've never been me. Andy been one time for a couple of days and we. I was loved. I'm looking forward just like doing little bit of travelling after has recently with cancer cove. Ed the eds not a thing. I'm just excited to spend time and make memories with my family. So cool okay. I have one last question for you. Tia in this interview has been absolutely amazing seriously. One of my favorites. And i'm just feeling so uplifted. And so grateful for your energy and your spirit and everything that you've taught me over social media and then even just in our interview today. My last question is if there's one message that you want people to remember from this podcast episode. What do you want that one message to be prayers work and are heavily. Father is always there for us. I know that when we choose him. Our lives are so much more simple and easier. It takes the stress off the win. I'm gonna challenge my young out there to make that decision to choose him to choose him and two when we choose him that he will always take care of. He's bound to keep his promises. And i know that. And i truly truly believe that i know that he loves us user opportunities. That are having me father's even us tell us to to be able to learn from and to be better and to become more like our savior. Jesus christ so. I would say if you're in if you're in a phase of your life where you're just not sure i promise you if you choose him and you pray and you use that rate wireless connection that you'll always be there for you and i say these things named jesus christ human here to fall. Amen thank you so much tia zinc such a gift for me to hear and to be inspired by your testimony and your experiences and your faith today. So where can people find you if they wanna keep following along and become part of your community and keep cheering you on where can thank you. Yes you can find you on instagram. At the t. abuse stopes at the tm. Stokes or on tiktok on at the abi stopes I have youtube channel. Tb stokes there Be as in buzzing me. And but yeah. I loved family members as those fun yet. We will link to all of those resources in the show notes and thanks again for spending your time with me today. Thank you so much. Thank you for having me. Thanks so much for listening to mint aero messages. Follow us on instagram. At mit arrow. Subscribe to our apple podcasts. And rate and review us. If you like us and to get show notes go to meant arrow dot com slash podcast and you can even sign up to get shown outs emailed right to your inbox and will you every time. There's a new episode.

cancer acute myeloid leukemia andy football orem kia stokes andrew stokes Fiancee knowles pneumonia cova covid mike ganley novick saint george Tia cova kobe kobe stokes Stokes kushner
Keeping Hope and Faith During Childhood Cancer

Focus On the Family Daily Broadcast

28:23 min | 2 months ago

Keeping Hope and Faith During Childhood Cancer

"The four years of hospitals and treatments three relapses to faith filled parents. One brave brave boy and one. God our god does With world says is impossible. That's the story that you're going to hear today. The story of brennan simpkins. His parents are here. Turner and tara and your host for this focus on the family broadcast. Is jim daly a jump. Perseverance is referenced. Several times in the new testament and hebrew. Christians are told that we need endurance in philippians. Paul mentions pressing on to the heavenly prize. Through christ jesus in james Being jim i like that book. We're told that the crown of life is waiting for those who persevere under trial and as an orphan. And i know when life feels like you're trudging uphill in four feet of snow and it doesn't seem to be getting easier in that context. Perseverance can be hard It can be so difficult to find the courage to take even one more step forward. But what i think is really interesting. Is that the verb perseverance as it was originally written in the greek didn't simply mean to patiently stay in a difficult situation but it implies action on our part in other words. It's christians. Were not called the simply keep going were called to be active participants in the stories. God has called us to be a part of trusting him with the results and our guest. Today are very inspiring couple and their son as well. I would agree jim. Turner and terrorist simpkins our co founders of the press on fund which is a nonprofit established to identify groundbreaking alternative therapies for children with cancer. And they have three teenage boys turner and tara. Welcome to focus on the fan. Thank you for having us thank you. Let's jump right in From the time you're middle son brennan was a baby. You had a feeling. And i thought this is interesting in the book but you said you had a feeling that god had something special in mind for him. Describe that feeling. And what was your reaction to. It is difficult to articulate. I mean from the first moment that held him there was something about he. Just a glow or an energy you can just tell and then from the point that he could interact with us. He was always reaching out. I mean he was always wanted to hug. He was always happy and he was always. He was sort of the glue between wants his little brother. Christopher came along between the the three of them and then he had had these prodigious hand eye coordination and just about everything he did. And i it was just a feeling out. Really something something about the kids. You actually had a friend that also said something to you about him every now and then you remember a conversation that was relatively. It was late later in the evenings. I'm glad i recall. You know when someone says that he was looking at him and photo of him and having seen him early in the day. I remember my. It was his godfather. Frank and he said there's something about this kid. I think he's going to do something special. Wow that's that's amazing that the lord of give you that because that i'm sure became a strength for you as you begin to unfold. What happens and we're going to get to that at the. Tell us about brennan as a child understand. He was Showing major promise in his golf game. Dad was proud of that. I'm sure we all are appealing. People were talking about him five years old. I mean he's even entering the junior events and live with augusta. Georgia area gets play golf relatively young. You're not competitive. They do everywhere. But yeah i mean he could chip and putt in which is very difficult for most of the younger kids out there and he and he had a beautiful swing and i remember looking at the video of tiger woods when he was about that age on the johnny carson show and and say well brennan can do that to dad. You know it was. Yeah and of course you know. Terry you had a little kid. I mean you saw a lot of that as well. Very special little mom's insight there so he gets to his seventh birthday are almost to his seventh birthday and he suddenly started showing some signs of illness. Tell us about the night that he was diagnosed in. What were the two of us. Mom and dad feeling and thinking and this is where people that are going through hard stuff right now with their own children diagnosis. That somebody may have just gotten for their child. This is where we're all going to lean into the story so tell us about that day. What was unique about it. What caught your attention. And why did you take him to the doctor. Well he had started as turner said he was very active kid and his brother was in the third grade and he was in the first and he was so fatigued over the christmas holiday. And we thought that it was just. He's trying to get stay. Stay up with his brother brother and all the third graders complaining about his lane planning about leg pain and the grandmothers had said he was pale so when he was complaining about his leg pain took him to an orthopedic pediatric orthopedic surgeon. Who of ours. And he did x-rays and all of this and he said he's absolutely fine but the next time you go to your pediatrician. You might want to ask for some blood work. So i just kind of put that in the back of my brain and we take an all of the kids up to the mountains to cease to know and all the kids were out there. Playing brennan was just too tired and then all three children. The kids are making snowman snowball fights and he's in the bed really in so that we had a walk with terraced sister that day and we had this heaviness just we sorta knew then and we didn't ominous i mean there was And then we then they'll a fever so we cut the trip short and we went to our pediatrician. The two boys had ear infections and burn did not and thankfully a had. The doctor's instruction in the back of my brain and i said would you mind doing some blood work and he said no problem so i went to go to my law office. We the kids went with the babysitter tournament to work. And i kept waiting for that phone to ring and launch went by and no no phone call and after about three o'clock i knew my this is a phone call a doctor's gonna make and at five o'clock i got the call from jackson nurse will make that call. Yes right nothing doctor calls. It's new it's not a good sign and so they said there's something suspicious in the blood work go get brennan. Come back to the hospital and we were. I remember thinking driving to go pick him up to meet. Turner like leukemia. It just was on my part. I thought it and i even called. His mother said it but remember. We had to go to the fifth floor of the children's hospital and that's down college. Okay take off the elevator and there was this really sweet kid Who we became close with who actually It's a whole nother story. But that's when you knew. I mean you saw the kid with no hair on the bag of blood all these other things hanging off and avi police devastation. And he listed a wedding i mean. What did they say to you the doctors when you've got the news what was said. Your child has cancer. Your child has leukemia a little while. It took him several days to pinpoint exactly what it was i. I thought he had a l. Which is more common form of childhood leukemia. Young dumb and then they thought it was a plastic anemia which is another terminal blood disease and then finally ammo and am l. Is acute myeloid leukemia. And he had a weird subtype of it it was a chromosome deficiency seven cute to leave. That's a very aggressive cancer at. Yeah as one of the most difficult of the childhood cancers To cure and in fortune we had our head in. The sand is a little bit that time. You know so. We didn't take on the fear that we would have had you know. In retrospect so that point we're thinking okay we can do this positive and were And but you know that was short-lived. Obviously that was short-lived. But i want to. I want to hear your heart's on. That says mom and dad talked to me as mom and dad when doctors say that people listening they may have heard it or they're going to hear it and i want you to connect with them because that's a moment where you can go a lot of different directions in your faith in your anger. Yeah it's happened to you guys. It's almost like a cyclone of emotions thoughts at that point. I think that to answer your question. There's a process that just human nature. Right you start to i. You approach this as a business problem or something that you know we can handle this right. We can handle it and i remember. I had a friend who was a pediatric oncology nurse and she says it takes family seven times to hear. Your child has cancer before the full effect of that actually falls on him. And i remember that night. We were so naive. We taken him to the hospital and we are you know. It's like nine o'clock at night. we go. We've got two other kids at home. We gotta get down to bad light operation. There's a cut for yourself. You're not going anywhere tonight stay. You're not going anywhere like things. It takes a while to sink in our remember the next day when the oncologist walked into the room. Who was on. Call that day and she happened to be an acquaintance and she hugged me and she saw and she said i am so sorry and at that moment i thought oh my gosh we have this is. This is a big deal. What the depth of this is. And then i remember. You're caught between two worlds right. You're trying to go through. He still have all the daily duties he gets the other kids to school. Their lunches prepared there. That point would even know what we were. Do our jobs or any of that stuff. I mean again. Are you in a fog. Are you trying to say okay. What are we gonna do today. Hyperfocused in a sense that did like i think military When you're we're on a mission there's the fear that focuses you that allows you to focus on things also distracts you from the depth of what's going on with your heart but i remember that as the days went by the fear that understanding grew that what we were getting ready to go through and turner sitting there reading. We were in the hospital room. We were able to stay there as a family and sleep and so he's going through the protocol with all the side effects and it's terrifying. And then i just hear this voice in it says in the midst of fear fall deeper into love in the midst of fear fall deeper into love. And i knew that we were being told to trust to trust in something gives me chills. Trusted something bigger. I will hold you through this right. You will be held through this. You will not go through this alone. And so that is Phenomen courage moment and that had begun speaking to you right. And if you're tracking along with any aspect of this story please know that we have caring christian counselors that you can talk to here calling Schedule a consultation with them. We have resources and our phone. Number is eight hundred. The letter a. in the word family. So brennan goes through his first bone marrow transplant. The doctor sits you down and says what well he had sailed through transplant. So we almost a little too easy. Ca- your thought things. We great little. We were also told that you know post transplant. There needs to be some signs of friction. Fevers rashes. Certain things to show that this new immune system is effectively taking over and we'll hopefully see the cancer is something bad and foreign is fighting something and none of that happened that you know that day is the one where you're the cyclone really kicks in taranaki. Actually got physically lost driving home in the car on a road that we traveled also took an exit. Not because my mind was just okay. Well he said there's no curative option. Yeah they gave him two months. He said call hospice guetta jesty world use. It was very just black and white when he was sympathetic. I mean this is a tough thing for due in part of that kindnesses directness right right but but the difference was not react in a way. That said okay. I guess this is over at lord. You have our son. Thank you for the time we had a little kick in the pants in that regard about that one of our close friends who i went to college with an actually from augusta. His son had neuroblastoma and his son. Patrick had relapsed. Which is a non a good spot to be that's a very difficult disease to survive at relapse. They were in philadelphia at children's philadelphia. We're driving home. We call stephen tell him what's going on and we're talking about this gloomy shirt and he said you know screw that i mean they just forget because man no in show we kind of looked at each other and it was kind of what we needed. And it's like the football coach. Then get back in the game guys you know and we knew that we were certainly behind but we came home and we got everybody that we knew had a connection. We rounded up the troops in. We started making phone calls. Yeah mama bear thing right you were like kick it into gear. Let's go right defiance. I think what does that sound like in your mind. What i mean. Some people will say. Okay it's over that part. Yes you're right and that's what worries me. I think that one of the places of grace that we had was we weren't alone right. We knew we were not alone. We knew we'd been promised that we would be walked through this not by ourselves. Our friends were so important. The that we had a community and other family he was going through it but we saw all kinds of families single moms but children that never were able to come to the hospital and there was always. What is it that we can do. How can we serve. How can we be of use. What is a better question that we can ask instead of. why us. how might i be used. How might i be of service so as we work through this though i mean we have about ten minutes and i want to make sure we grab all of this It's a long story. You no but it paints an incredible picture. The second transplant didn't take the third translate. Did take and you know. There's a difference in the transplant. Took but then. The cancer came back in each those right so i mean. We defied all the odds of. He's in the second one. He survived the third. One is apparently a donor to think about that as a half a match. You know the child is half terry. I mean he's half me and the third one that donor for the third one and it took and then things went haywire and we He was given last rites and we brought his brotherston to tell him goodbye. He was on a ventilator in you. Hear about it but you could feel it. I mean it was a physical energy of peace knowing that you have peeled off the things that done everything you could and it was. I mean it's hard to describe it so emotionally you're saying goodbye to brin. Yes point three. We had we had never done inside. Yeah i mean because we had almost all of the doctors and nurses and your child life specialists all were in the room. They're all weeping. Think and their member dr philadelphia saying i try to transfer second transplant on a kid in less than a year and he died a pretty gruesome death on a ventilator. And so i've never left my mind right. And so here's this kid and trains plant and he's on a ventilator and And then the decision to try for with any came back you know and then Yeah tyranny you still have. That sense of. We can get through this. I always had the sense that we could get through this without being hopeful of what the outcome could be but without having to need the outcome to serve and to define that we were held right. There's discredit of his. This such a difference that we didn't have to say god you're gonna prove it to us by saving our son right like we're gonna have faith and we need this outcome to happen. It was this you know in the midst of fearful deeper into love was. We always had this moment and the question was how can we feel love and be channels for that love in this moment and allow it to be enough and that was our human struggle which i do think turner does such a beautiful job in the book. 'cause the science is one thing but we're talking about a daily living in the practice of some hopeful expectancy and trust and believe and some kind of mixture. All of all of that with some type of confidence in the i remember during this time at the root of confidence is confident. Oh right walk in. Fay so we knew that this was all of that and at the point. Turner describes as the ultimate letting. Go that piece that passes all understanding that we read about right. That's the ultimate letting go it doesn't mean that we didn't have any of those feelings that we didn't have any of that doubt that we didn't struggle but that became an active part of that. Lock what she's talking about is really. You know the one thing that we were taught through that because you're in this cocoon submarine. I mean whatever you wanna call it the rest of the world's going on outside it and i realize if i'm afraid of the outcome or worried about the outcome or angry about why we're here. I'm gonna lose this moment. That i have with this kid with me right now. While in his brothers in in in that moment may not be here fifteen minutes from now in in his case because it has all the fine. i mean. when you're going through the mundane things alive. I mean it's easy to kind of have that smart it up a little bit and so this situation peeled off all that mundanity in when you're in an environment when she gets to saint jude's horace hospital. These are a lot of these kids. Don't come out right there. In lots of reaction she divorce was streaming high rate of divorce in pediatric cancer. Well that's part of it You guys were able to hold together. I mean even through this very stressful time and the good news is brennan. Received that fourth transplant in. It did work and he's now doing gray seventeen. He's no longer that seven old year old fighting for life in the way he had to. He's doing much better right as remarkable. Yes he seventeen. He has a lot of side effects from his treatment. But again we're just so grateful and if we can remember. Stay in that place of gratefulness that this is what we prayed for. Even the days. I want to strangle high praise for this is good. We did this. But when talking about that specialness of brennan. And i do. I think for parents who go out there. That child never doubted that he was loved. He was a fighter. He never felt abandoned. We saw never felt abandoned by god. He never felt a ben. I mean we. I had people write letters that said this child is paying for the sin of you and your ancestors and blah blah blah and i would just like oh my gosh or that we were being frank cast any in some way and making this kid endure things that he felt do and we knew where he he was seven mayoress. We were trying to cocoon them. Will once you're out of transplant relapse. Your kids start dying. I mean the gigs. Yeah hands out of the bag right so in our kids would go to funerals of other children. I mean that's not something when you could do that. On a semi routine basis at the age of seven on that's had an impact on them. But you know what was what was good. This is the quote out of the book. That really got hold of me. You said the interim nature of childhood itself should be sufficient to hold every one of our kids tight for every possible second. We should not need cancer for this. And that is powerful. I mean you guys went through a traumatic experience where your son almost died. Not once not twice not three times but almost many times and that fourth bone marrow transplant. And if you don't know anyone who's done a bone marrow transplant. I have a good friend. Chuck ball to who just went through that and it is horrific brutal brutal. It takes about a year to recover if everything goes one well. And i've just been watching that from a distance and here when your son went through four of those in a short period of time it caught my attention. It was like this is not. This isn't even normal for someone who's going through that the other aspect of it is your attitude to fight and just so appreciate that you didn't give up after the first situation where it didn't it didn't work and You didn't give up his parents. That's a good lesson for all of us. When it comes to medical issues that we may encounter at some point. I hope the people listening will take that as declarin way forward if they're given a a poor diagnosed not going to hurt anybody's feelings. If you try and opinion i mean you may be on the right track but you need to. You need to make sure that you got all the cards on the table. And i so appreciate that the last question which is really perhaps the most difficult and my own brother and his wife went through this cancer with their son and he was doing well but then it got him again and he didn't make it at a young age and so i think the question is a tough one but it's for those families that did fight the good fight but they lost their loved one. They lost their child their son or daughter. What word would you have for them. I i have enough. This understanding that every human's life is enough. That whatever it is. They were meant to be to love who ever they were. They were born to touch they. Did they touched them. And that it was enough and to find some peace in that right to find something in that we can spend aren't higher rest of our lives. What if being second guessing and if we're doing that we aren't living the lives that we've been called to. Do you really saying contentment has to be your goal that you can't control these outcomes in that you have. Everything has a consequence every little seed in the ground every little pebble in the pond and we may be a long ways off before that matures and we may never know what it is but it's something and each of those children who've been in the hospital of touch someone. They've touched another family. They've touched another doctor and There is meaning there. It may not be the one that you know was written up in the handbook. The child was born. it's certainly I do think that we we know in there. You know that if we push the doubt aside then faith is there and then you can but that doesn't mean you don't have the anger have all of these human emotions to process. Process them learn from them get held bottle. It up like law ought to talk about it with your friends. Those are also with other families. You guys. I'm so grateful for you to be able to share your pain points with the audience and to be able to hear your wrestling through this and the fact that you know thus far brennan's in a good place maybe not a perfect place but he's in a much better place than he was ten years ago and god has been faithful slightly and the point is he's faithful. Always no matter. The circumstances circumstances are in john as you said before I can only imagine some of the pain in the people who are listening and things that they're encountering and focuses here for you. That's the whole point. We have so many generous donors who equip us to have Counselors in place to hear where your heart is to help you to give you some idea and direction to give you biblical wisdom on what you can do to stay in the fight. The human fight of Doing better in this life and leaning into him and we've got lots of resources to help you do them. we do. Were a phone call away. And that number is eight hundred. The letter a. and the word family and online can find help and we'll have the links in the episode show notes and perhaps you'd like to pass this encouraging message along to someone who's going through a tough time similar to this. We'd love to send you a cd of this broadcast so you can do that. That'll be yours for gift of amount to help us. Continue giving families hope. And you'll find details at our website along with information about turner's book possibilities perseverance. Grace and the story of one. Family's life with leukemia at turner and tara. What an amazing story. Bless you guys. You continue this journey of family life. Thank you for this. We're really grateful. We really grateful for all the families out there when you when you come back from something like this. You don't understand that there's still a lot of fight ahead of you like family so you know us here. The military members that are coming back. And trying to reintegrate please. I just urge all of your listeners. To use the resources that you have available for them and used that you're your cry. Which is hug your kid tonight. Hukou tonight to yeah well. I'll be half of gym daily and the entire team here at focus on the family. Thanks so much for joining us today. For focus on the family. I'm john fuller inviting back next time as we once again help you and your family thrive in christ find fun for your kids. Just a click away now adventures in odyssey the adventures in odyssey club. Where your eight to twelve year old can find trusted faith-building building entertainment in a safe online club. It features almost every episode. Ever plus special monthly club only episodes in content and a focus on the family clubhouse magazine subscription sign up today. Just go to a i o club dot org slash radio.

brennan cancer Turner turner leukemia brennan simpkins jim daly press on fund tara avi police jim augusta simpkins Fevers rashes guetta jesty golf johnny carson philippians myeloid leukemia
NEJM This Week  December 24, 2020

NEJM This Week - Audio Summaries

27:25 min | 6 months ago

NEJM This Week December 24, 2020

"Welcome this is the new england journal of medicine. I'm dr lisa johnson this week december. Twenty four th twenty twenty. We feature articles on ultrasound sub talamante for parkinson's disease antenatal decks a method zone for early preterm birth orel as society maintenance therapy for a m l. paclitaxel coated devices in peripheral artery disease and seizure frequency during pregnancy. A review article on estrogen receptor positive breast cancer. A case report of a man with headache and covid nineteen and perspective articles on the gift on new order new hope on resilience in the face of covid nineteen and on holding up randomized trial of focused ultrasound. Sub kalamata me for parkinson's disease by role martinez fernandez from cu some pablo university ma. Stoli's spain the subtitle hamic nucleus is the preferred neuro-surgical target for deep brain stimulation to treat cardinal motor features of parkinson's disease focused. Ultrasound is an imaging guided method that allows for the ablation of deep brain structures including the sub telemetry nucleus without craniotomy and electrode penetration in this study forty patients with markedly asymmetric parkinson's disease. Who had motor signs. Not fully controlled by medication or who were ineligible. For deep brain stimulation. Surgery were randomly assigned in a two to one ratio to undergo focused ultrasound sub talamante on the side opposite their main motor signs or a sham procedure the main score on the movement disorder society unified parkinson's disease rating scale for the more affected side decreased from nineteen point nine at baseline to nine point nine at four months in the active treatment group and from eighteen point seven to seventeen point one in the control group. The between group difference was eight point. One points adverse events in the active treatment group included speech and gait disturbances weakness on the treated side and discount nesia focused ultrasound sub talamante me in one hemisphere improved motor features of parkinson's disease in selected patients with asymmetric signs in an editorial joel pearl mutter from the washington university school of medicine. Saint louis writes that the development of alternative procedures to deep brain stimulation is important to the field of parkinson's disease treatment. The current trial begins the past to that goal and improvements in bargaining may improve the risk benefit ratio and permit the use of lesions in both hemispheres. Which would widen the population of eligible patients limiting the treatment to one side of the brain by ultrasound produced lesion inning constrains the application since most patients with parkinson's disease have progression of symptoms on both sides of the body as was shown in a trial of radio frequency sub talamante in one hemisphere the potential advantages and limitations of focused ultrasound produced lesion ing should be discussed with patients. The editorialists hope that improved technique will reduce the associated risks and increase the applicability of this provocative procedure anti-nato decks methadone for early preterm birth in low resource countries by the. Who action trials collaborators. Preterm birth is the leading cause of death in infants and children younger than five years of age. Globally the safety and efficacy of antenatal glucocorticoid 's in women in low resource countries. Who are at risk for preterm. Birth are uncertain. The who action one randomized. Trial was conducted in twenty nine secondary and tertiary level hospitals across bangladesh india kenya nigeria and pakistan And involved two thousand eight hundred fifty two pregnant women and their three thousand seventy fetuses who were at risk for preterm birth. The participants were assigned to intramuscular dexamethasone or identical placebo. The trial was stopped for benefit. At the second interim analysis neonatal deaths occurred in nineteen point six percent of infants in the decks of methadone group and in twenty three point five percent of infants in the placebo group stillbirth or neonatal. Death occurred in twenty five point seven percent of fetuses and infants in the deck som episode group and in twenty nine point two percent in the placebo group. The incidents of possible. Maternal bacterial infection was four point. Eight percent and six point three percent respectively. There was no significant between group difference in the incidence of adverse events among women in low resource countries. Who are at risk for early. Preterm birth the use of decks. Methadone resulted in significantly. Lower risks of neonatal death alone and still birth or neonatal death than placebo without an increase in the incidence of possible. Maternal bacterial infection. Dwight rouse from the warren alpert medical school of brown university. Providence rhode island writes in an editorial that the who action one trial makes clear that there are many areas in low and middle income countries. Were antenatal glucocorticoid can be prescribed safely and effectively facilities that meet the clinical standards of the trial sites or to which resources could be provided to meet these standards should use them with a number needed to treat of twenty five to prevent one neonatal. Death the who action. One trial confirms the tremendous benefit of antenatal glucocorticoid for the right patient at the right time and in the right setting the minimum level of obstetrical in neo natal care necessary for glucocorticoid to achieve. Their promise remains uncertain. Since a plurality of birth in low and middle income countries occur in the nebulous space between good and demonstrably inadequate. Peri natal care. This is a question of urgency oral as cited in maintenance therapy for acute myeloid leukemia in first remission by andrew 'way from alfred hospital melbourne victoria australia although induction chemotherapy results in remission in many older patients with acute myeloid leukemia. Am l. relapses. Common and overall survival is poor in this phase. Three trial the oral formulation of as aside editing. Cc for eighty six a hypo methylated. Agent was evaluated as maintenance therapy in four hundred seventy two patients fifty five years of age or older with am l. Who were in remission. After intensive chemotherapy with or without consolidation therapy and not candidates for her madda poetic stem cell transplantation at trial entry median overall survival from the time of random association was significantly longer with c. c. Four eighty six than with placebo. Twenty four point seven months and fourteen point eight months respectively median relapse. Free survival was also significantly longer with c. c. four eighty six ten point two months and four point eight months respectively benefits of c. c. Four eighty six with respect to overall and relapse free survival were shown in most subgroups defined according to baseline characteristics side effects with cece four eighty six maintenance therapy were mainly gastrointestinal symptoms and neutra. Pierre quality of life measures were maintained throughout treatment. Cc for eighty. Six maintenance. Therapy was associated with significantly longer overall and relapse free survival than placebo among older patients with am l. Who are in remission. After chemotherapy mortality with paclitaxel coated devices in peripheral artery disease baio akeem. norden stieg from gothenburg university. Sweden the results of a recent meta analysis aroused concern about an increased risk of death associated with the use of paclitaxel coated angioplasty balloons and stents in lower limb endovascular interventions for symptomatic peripheral artery disease these investigators conducted an unplanned interim analysis of data from a clinical trial in which two thousand two hundred eighty nine patients with peripheral artery disease received treatment with paclitaxel coated or uncoated endovascular devices during a mean. Follow up of two point four nine years. Five hundred seventy four patients died including two hundred ninety. Three patients twenty five point five percent in the drug coated device group and two hundred eighty one patients. Twenty four point six percent in the uncoated device group at one year all cause mortality was ten point two percent in the drug code device group and nine point nine percent in the uncoated device group during the entire follow up period. There was no significant difference. In the incidents of death between the treatment groups among patients with chronic limb threatening ischemia thirty three point four percent of patients in the drug coated device group and thirty three point one percent in the uncoated device group or among those with intermittent codification ten point nine percent and nine point four percent of patients respectively the results of this unplanned interim analysis of all cause mortality in patients with peripheral artery. Disease did not show a difference between the drug coated device group and the uncoated device group in the incidents of death during one to four years of follow-up changes in seizure frequency and anti-epileptic therapy during pregnancy before page personnel from brigham and women's hospital. Boston this prospective study involving women with epilepsy compared the frequency of seizures during pregnancy through the perry pardon period the first six weeks after birth epoch. One with the frequency during the postpartum period the following seven point five months after pregnancy epic to non pregnant women with epilepsy were enrolled as controls during the same time period the investigators also compared changes in the doses of anti epileptic drugs. That were administered in the two groups during the first nine months of epoch. One among the two hundred ninety nine pregnant women and ninety three controls who had a history of seizures that impaired awareness and who had available data for the two epochs seizure frequency was higher during epoch. One then during epic to in twenty three percent of pregnant women and in twenty five percent of controls during pregnancy. The dose of an anti epileptic drug was changed at least once in seventy four percent of pregnant women and in thirty one percent of controls among women with jesse the percentage who had a higher incidence of seizures during pregnancy then during the postpartum period was similar to that in women who are not pregnant during the corresponding epochs changes in doses of epileptic drugs occurred more frequently in pregnant women then in non pregnant women during similar time periods. Systemic therapy for estrogen receptor positive. Her two negative breast cancer. A review article by harold burstein from the dana farber cancer institute boston breast cancers that are positive for estrogen receptor e. r. and negative for human epidermal growth factor receptor to her to are the most common subset of breast cancers accounting for sixty five percent of cases of breast cancer among women less than fifty years of age and seventy five percent of cases among older women. Er positive breast cancer is heterogeneous tumors vary with respect to quantitative levels of er progesterone receptor pr expression which is er driven history. Logic grade degree of proliferation as much by k. I sixty seven labeling or other indexes patterns of gene expression and the type and frequency of genomic alterations these features are highly interrelated with important clinical implications estrogen production and e r signaling our drivers of breast cancer tumor genesis growth or proliferation and metastasis and are the focus of drugs that are effective in the treatment of early stage breast cancer novel targeted treatments in combination with endocrine therapy can improve outcomes in advanced breast cancer and inhibit the activity of key pathways in cell growth proliferation and metastasis anti estrogen. Therapy is the cornerstone of systemic therapy and its efficacy depends on such factors as grade k. I sixty seven labeling and progesterone receptor expression a twenty four year old man with headache and covid nineteen a case record of the massachusetts general hospital. By howard heller and colleagues a twenty four year old man was admitted to the hospital with a three week history of headache and a positive test for sars covy two are in a three weeks earlier. Fatigue generalized weakness and headache developed two weeks later headache and weakness persisted and new shortness of breath pluralistic pain and anorexia developed sars covy to aren a was detected in a nasal swab four days later. The headache worsened and he sought evaluation at the emergency department. On arrival multiple episodes of vomiting occurred he appeared fatigued. Diet heraldic and lethargic results physical examination were consistent with signs of meningioma inflation. Ninety minutes later the patient was found on the ground next to the stretcher on his hands and knees incontinent of urine. Mri showed multiple small hyper intense pho. Sai in the caught eight nuclei amputate jonah. Several pho sai appeared to be cystic on lumbar puncture. The opening pressure was higher than fifty five centimeters of water. The white cell count was one. Oh eight per micro leader the patient's history. Mri findings and lumbar puncture results suggested. Mingo encephalitis due to a viral or fungal infection. The condition that is most commonly associated with cystic grape. Like appearance in the brain especially in the basal ganglia and typically causes a very high. Intra cranial pressure is cryptococcal says it most commonly occurs in immunosuppressed patients especially in the presence of advanced. Hiv infection the gift a perspective by rafael rush from toronto grace health centre canada. The patients swollen knee stood out in a body sculpted by illness. His limbs were pale and tapered his belly tented by the end stage. Cirrhosis that he knew could soon take his life more hopeful than expectant. dr rush. Who was a resident at the time explained that the patients knee would need to be drained that dr rush had done this before that the fluid should come out easily. Will it hurt. The patient asked. Yes dr rush said but you'll feel a lot better word. at least you're honest. The patient said a mesh of wrinkles dipped into his hollow temples and sunken cheeks as he signed the hospitals brief consent form in spidery script but the fluid did not come out easily. The joint aspiration hurt more than expected. His breathing came in shallow. Waves as dr rush withdrew and reinserted the needle hitting bone and hunting. Dr rush reiterated the risks. Each time he swapped the needle for a larger gauge one from the pile of supplies. He assembled on his meal tray. Repositioned ref- rose and tried again. He suggested having someone more experienced takeover but instead of acceding to that suggestion. The patient urged dr rush to continue dr rush new. Why he kept going out of the hope that these experiences which shape him into the therapeutic instrument he longed to be so he didn't press the matter much further right then finally. A flash of golden fluid filled the syringe. Dr rush withdrew and sank into the chair by the patient's bed. The patient lay back recovering. The patient had known what doctor rushes sweat and repositioning implied and what his repeated offers to stop had meant. Dr rush had spent the afternoon exposing his inexperience until it couldn't be clearer in response the patient had offered himself the new order new hope a perspective by andrew tambi raja from the royal infirmary of edinburgh in the simpler times before covid nineteen. Dr tambi raja used to play a game with medical students who joined him in the operating room. There's a giant flood coming that will devastate the earth and its inhabitants. You've got a big boat in which to preserve human civilization. There's room for one hundred citizens of the world and five doctors witch doctors. Do you want to take on the boat. The students start considering the most valued members of the medical establishment doctors who can be entrusted to secure the future of the human race not once has a vascular surgeon like dr tambi. Raja got near the boat and rightly so in his specialty. Young doctors are seduced by the excitement of major hemorrhage the potential for limb or life salvage and the peculiar instant gratification afforded by meticulous anastomosis on a delicate blood vessel yet. Here we are in what is considered the greatest global health care crisis of our generation. The perfect opportunity for us to measure and reflect on our utility and value hospitals around the world have had to rapidly redraw critical incident plans. The headline actors of this rewrite are now the front line emergency. Physicians intensive ists and pulmonologist. Surgical staff have suffered an undignified fall from favour. They have been stripped of their surgical arenas and forsaken by their anesthetic. Wingmen for a better. 'cause as non urgent surgery has become largely obsolete but the sudden loss of purpose has left him and his surgical colleagues in an unfamiliar state akin to grief sewing masks resilience in the face of covid a perspective by eva rosenburgh from brigham and women's hospital. Boston the phone calls from that night. In march linger in dr written burg's thoughts at nine thirty pm. A woman wept in pain saying her. Knee were swollen and excruciating. Dr written. Didn't want her to go to the emergency department. But she also didn't know whether the patient could bear it at home then at ten pm. I don't feel so good. A patient murmured my head hurts whenever i get up. My nose is stuffy. Dr ridden berg thought cove it. Dr ridden berg. The risks decided to advise both patients to treat themselves with tylenol and see if they improved enough to avoid the emergency department. Two months earlier she would have said otherwise at five. Am a caller pleaded. My mother is having trouble breathing. She was diagnosed with covid last week. Her fever hasn't gone away. The mother tried to speak managed to words before gasping for air. You need to go to the hospital. Dr written berg said now. The following morning sunlight from the uncertain outside world fell through the window. Dr ridden berg knelt next to a plastic been filled with fabrics that her mother had gathered over the decades. She pulled out her sewing machine and chose the blue dotted cotton. Another mask as we make it through months. After months of this pandemic we are starting to consider what recovery will look like. How can we mitigate the trauma of covid nineteen and its treatment for our patients. Plotting the way forward feels like finding the right materials. Tracing out a pattern carefully pressing down the pedal on the sewing machine holding up a perspective by polly maitre from brigham and women's hospital. Boston how are you holding up. This question has become dr matrix. Pandemic refrain the way she begins all her virtual visits these days. At present the world is especially heavy as a primary care doctor. Seeing patients with a range of lived experiences. Dr maitre cannot know until she asks the burdens they carry. When how are you feels untenable. She asks how are you holding up the question. Anticipates intensity challenge or recent experience of pain. It assumes to that care transpires in continuity holding reflects life as an ongoing blur of time rather than distinct moments neatly punctuated by medical visits the phone call or visit ends but patients stories linger each one shiny pebble in a vast quarry but collectively wadey in bengali. When the load is lessened they say how far low i feel lighter so when she steps unwittingly into the minefield another's grief and occurrence that has become far more common these days. Dr maitre envisions her task. As one of holding up. It is her privilege and burden as a physician to carry stories but she is not alone. Her patience tenacity their tenderness. Buddha's her up between visits her colleagues grit and grace under pressure inspire her to persist her family is her refuge. The container for both her tears and her laughter in the devastation wrought by covid nineteen. We all hold up or fall apart together that the practice of medicine is accompaniment. Bearing others sorrow walking the bumpy path alongside them feels true or now than ever are images in clinical medicine features a sixty year old man with sickle cell disease who presented with fatigue and shortness of breath. He was found to have anemia and bone marrow. Biopsy revealed huma phagocytes hostess of sickle cells. Hema phagocytes hosts in sickle. Cell disease is a rare but recognized entity that is associated with viral infections. Selective him oh phagocytes hosts of sickle cells with peripheral disappearance of hemoglobin as a cause of severe. Anemia is highly unusual in another image sixty five year old. Man who had undergone total replacement of both hips was subsequently hospitalized to repair dislocated right hip adopter device that was used to assess the pulses in his feet picked up music in addition to the pulse. See the video at any j. m. dot. Org it was thought that the doppler may have picked up a radio signal being received by one or both of the patients prosthetic hips although other equipment in the room such as the hospital bed could have received the signal. This concludes our summary. Let us know what you think about our audio summaries. Any comments or suggestions may be sent to audio at any. Am dot org. Thank you for listening.

parkinson's disease peripheral artery disease dr rush headache breast cancer dr lisa johnson estrogen receptor positive bre martinez fernandez pablo university Dr rush brigham and women's hospital myeloid leukemia joel pearl mutter parkinson's disease treatment
Who Is Your Hero? He Was Mine

THE BRENDON SHOW

08:05 min | 2 years ago

Who Is Your Hero? He Was Mine

"It's Brennan Bouchard. And welcome to another episode of the Brendan show. Hey on behind the scenes and event right now. And I was asked to talk about who my hero is in my life. And I get asked this a lot. I realize I've actually never shot video on this. So love to tell that story. Limit my hero is my dad and many guys were with me as I built my brand my business in my life when my dad passed away so dad passed away in two thousand nine to acute myeloid leukemia. He was healthy and good. And and literally like on mother's day. He wakes up he's walking down the hallway, and he kind of felt a little off, and he grabbed his side. And my mom's said what's wrong with this? I just feel funny sat down his his back inside was hurting throughout breakfasts. He was feeling funny. I'm said, well, let's figure out what's going on. So we went to hospital and within two hours. They let them know. Hey, done some tests here, and your spleen is enlarged wanted a few more tests. We think you you might have you know, who came in. And of course, he's had no context of this. And literally the doctors gave him seven days to live. Hadn't been sick or anything. And if you know about leukemia, there's two kinds and AM L Q one it mealy just takes over your body and very few people live, let alone months dad who was a marine and spent twenty years in the marines did three tours and Vietnam cannery sergeant he made it fifty nine days and. During that time. I got to be with the most of the time. And I remember just. Just so fearful of losing him because he'd been such a hero in my life. And I asked him if I could interview him, and I was having to be literally traveling when I found out that they said his third round of chemo didn't work, and they were suggesting he go home and enter hospice and pass away. And so I called him. I didn't know if I was going to get there on time. I was so terrified just having a trip, and I said Chi interview over the phone, and I recorded and showed that with you because if your parents or here or your caregiver your loved one, your grandma somebody really care about the it'd be a beautiful thing for you sit down and interim I just interviewing with falling recorded it. And I asked him like thirty questions about life has asked that, you know, about how he grew up, and what he learned from his parents where he hope, you know, what do you hope for life? What do you love what made him successful or struggle with? How do you my mom? You know, what he wanted? Each of us kids to know about life. And what message you wanna leave us these things and he shared something with me in that area. That was so amazing because he's actually always said it throughout our lives in different ways. And I never really realized it, and they was just I didn't realize how intentionally been because when asked what something you know, what some advice you wanna give all of us. And he basically said seven things that I realize said them he'd been teaching us that all our life, and what he said to us. You know, be yourself. Be honest. Take care of your family. Treat people with respect. Be a good citizen. Follow your dreams. Do your best. You know, he was always saying these things to us. And just even as I say them. I it's weird to be hearing. So it's hard to talk to you guys little about, but it's like. It really was one of the greatest blessings I gave myself as recording in because now every year on on the day that he passed and every year on his birthday. I try to listen to the audio. I mean, sometimes I can't because it's hard to hear his voice, and I miss him so much, but I also am grateful. I have that. So encourage you to record interview, the people you love, but also because you know, so cooled as they started my career many guys were with me the very beginning. When I wrote my first book called life's golden ticket. And my dad got to see that published and I decided I wanted to bring life school and ticket like to life. So if you ever read life's going tickets, it's a parable as the story about a man who experiences some transformational magic at the circus. And he's like kind of opens up and changing the search. I don't want to little story. But so I decided bring the book to life, and I literally rented like the Mexican national circus had like their tents and. All of their performers, and we took over the city in Long Beach and had all these people come to attend this event, which was like a personal development seminar in a tent revival. Right. But my dad got to come and see and being the old gunnery sergeant he was up five AM in the morning carrying boxes helping us put together. You know, just doing everything to help out the staff and the team and motivating them, and he was so proud to see his son do his thing. And even though the thing was kinda fallen apart. Oldham? I didn't know what I was doing. I never done that kind of seminar had no money. I was constantly stressed and everything else. He got to see his son do his thing. And I just tell you know, what the greatest gift that you could ever give in your life isn't about how much money you make what you succeed at the people around. You get to see you do your thing. And that would be my dad's last summer with me he would come out at the end and after volunteering look so hard, and he came out and his hand are moms hand and raise it up in dad was just so happy, and I know not not everybody gets that blessing with their parents or with their loved ones or with their caregivers or the people admire, but it's one of the great moments in my life. Because my dad was my hero growing up because he told me those things and I became who. I am because he told me those things and I still work and try to connect with him. Motioning spiritually all the time. Because I'm always remember what he taught me what I wanted to live life. So he's proud. And I'm I'm honored. He got to see his son tried to live his dream. No matter what level at the cheap. I mean, one of the greatest gift you can give is live your dream like chase the things that inspire you. Because other people seeing that it reads a magic into the world. So I hope maybe this episode makes you guys think about someone you admire who you love and the messages they taught you and that you try to carry it on in some way and your life to. If you're ready to take your life to a whole new level. Make sure you grab my book high performance habits. How extraordinary people become that way. It's available on Amazon right now. And when you order your copy, you really supporting my channel and the message, and you're also getting a book that will reveal to you twenty years of my research into what is it that helps people go to a new level of success in their life. What is it really take? What habits are proven to help you reach long term success in your career, your health your personal life. Your relationships is called high performance habits. How extraordinary people become that way. It's available on Amazon right now.

Amazon Brendan Brennan Bouchard Vietnam cannery leukemia chemo Long Beach marines Chi Oldham twenty years fifty nine days seven days two hours
Episode 16: Controversies In Hematology

Novel Targets

46:13 min | 4 years ago

Episode 16: Controversies In Hematology

"Uh-huh. This is novel talk it's bringing to life the science around innovative, new drugs, gene and self Therapy's. I'm happy new year and welcome to the season two. Finale. This episode comes from the two thousand and sixteen annual meeting the American society of hematology, commonly known as ash we've called it controversies in hematology because each of the expert show here officer, very personal view. The not everyone is going to agree with leading them fomer specialist tells us what he really thinks about Carty. So I I'm not ready to go to my desert island with only a cartesian L agent to treat whatever patient, I might encounter and have the right targets being chosen for pioneering trial in acute myeloid leukemia. AM, oh, you're over sixty the survival rates. No more than about two percent at ten years. We have to do something better in ceelo, chronic lymphocytic. Leukemia will hear what it liberal expert for it was exciting at the me too. So it's sort of tastes great less filling version of brew. Linden. Now is it really better in his own little trial. It seems to be better. Finally, one of the prominent topics at fishes ash meeting was sickle cell disease, while we're excited about novel therapies, a lot of ad is actually controlling the disease, but what about cure? We'll hear more about the potential for gene editing and gene therapy later immature. This so despondent punch and Intech over the past two years. They sponsored fifteen episodes would grateful for their support and just to be clear if we do mention any products we made an independent Detroit decision to do. So our sponsors have no control of the topics. We cover who we interview of questions we asked. So let's start with a mentioned for the leukemia and lymphoma society at Ashby out to major new initiative called beat AML, this postering and adaptive clinical trial that will investigate multiple targets with multiple drugs from different companies. This approach has never been done before AML. Will it be a game changer? I spoke to one of lead investigators. I'm Brian Drucker director of the Oregon Health and science university night, Ken through toot in Portland, Oregon beat AML really is groundbreaking. We're going to be able to assign patients over sixty two treatment based on their genetic makeup of leukemia within seven days of diagnosis and our goals to try to have a treatment for every single patient who enrolls, and that's truly remarkable when you look at the treatment of AM L over the past four decades, we just haven't moved much at all. It's the same drugs I trained with when I was in my fellowship many many years ago. And it's still gonna rubel center either roofs in an era. See our outcomes are still quite poor. If you're over sixty the survival rates, no more than about two percent at ten years. We have to do something better the plan for AML's use a very similar to what we used for C L, and that's to match the right patient with the right drug. Now, the difference is see Mel is one disease homogeneous. It's one molecular driver, and it's one drug with AM L, it's dozens of their drivers and they associate with one another in many different combinations. Ultimately, this heterogeneity is part of the problem. That's why a one-size-fits-all approach isn't going to work for AM L. But our hope is that we can identify certain signaling pathways. It'll be amenable to target their Ps, but we might also identify some broad categories a cell surface marker, they could work broadly. And then use that in combination with a target of their be. So we can actually. Instead of thinking about this hundreds of different types, we might get down to ten or twelve and then treat them accordingly. But the beauty of this trial is we can be pretty nimble if we bring a drug in and it doesn't work at all. We can stop that treatment. If it's working, really. Well, that's what we hope we see a big effect. We can move this very very quickly to FDA approval is like a jigsaw puzzle. Making move things in and out very quickly to get to the right answer launching this trial that a lot of people didn't think could happen is starting to generate even more enthusiasm because the reality is our were open. We'll be open at twenty centers by the end of twenty seventeen and people now want to be a part of something successful. And that's that's really exciting. Because now we can take success and get even more success and really finally make an impact against AM L. So as we start the trial. We have four different drugs from four different companies from cell, gene, we have their ideas to inhibitor AG to twenty one from Barringer Ingelheim, we have their CD thirty three antibody, which has a b I am a number from Alexi on we have their CD two hundred targeted antibody and from Gilead. We have they're sick inhibitor. The companies are absolutely actively involved both with the planning of the trial the end points of the trial. They're excited about the fact that this could be a quick path. Jeff registration. If all goes, well, we might actually see something next year. Dash that would be amazing to see that such a show period of time. We're trying to celebrate progress are patients needs something. They're waiting for us and they're behind us. So we're trying to do something for them. If people want to know more information about his trial wish video simple, they should go to the leukemia. Lymphoma society, website LS. Dot org. We've put a link of us on the novel talk. It's website. Now, let's move onto CLL the ash. Twenty fifteen episode of Nova targets we heard about Veneto class and some of the challenges associated with its use by the way, if you wanna HIV episode any of us, go to our website, novel talk. It's don't come. So what was exciting CLL a vicious ash meeting. I'm Bruce Chessen professor of medicine at Georgetown University hospital, the Lombardi Comprehensive Cancer Center in Washington DC. Well, obviously what's catching everybody's attention in CLL as the possibility for non chemotherapy regimens for patients that not only results in greater efficacy, but reduced toxicity. And we've heard a lot of this over the last few years there have been a number of new drugs that have been approved for ceelo or in clinical trials. There are the BT K inhibitors such as Everton and calibrates in ebb and what we. Heard at ash this year that impressed me was the long term follow up with brute. We saw Susan O'Brien. Make a presentation of five year follow up of patients in the relapse refractory setting and almost as long and patients in the frontline setting. And what was absolutely astounding was that more than ninety percent of patients are free of progression out at three four five years in the frontline setting and a significant proportion in the relapse setting. But that varies a bit with their cited genetic abnormalities, particularly seventeen p deletion, but even those patients are doing better than ever they had with any chemotherapy regimens, but it would be nice if we could tell who was going to recur, and when it was going to happen and towards this Jennifer Y-ish from the Ohio State University, presented a very interesting. It's Hearns out that patients on a brute nab, it's a Vela p- resistance with what's called the BT K C four eight one mutation and this can be quantified in the laboratory. And what she demonstrated was. If you follow these patients serially and monitor them for this mutation and for another downstream, you tation of that you can predict which patients are going to relapse and when they're going to relapse before there is any clinical evidence of recurrence. So what this gives you is the opportunity to intervene. You get the mutation. And you could do a clinical trial which results in putting in a new drug at that point in time versus watching and see what happens and see if you can really improve the outcome of those patients. Now, I've talked a lot about a Bruton it, but there are toxins with Putin and not everybody responds and patients become resistant to brute nib, so there has been interest in developing the newer and better Bruton two point. And there are a couple of these out there, the one that seems to be the most promising is a calibrate nip this is the second generation version of Bruton. And in preliminary studies, thus far a caliber appears to have less toxicity in particular less. Diarrhea less cardiac talk city and particularly less bleeding. It also in the early publish data, and what we've seen this far since then appears to be at least as active as prudent so it's sort of tastes great less. Filling version of Bruton now is it really better in his own little trial. It seems to be better. But what we need is a head to head comparison, and this trial is ongoing in high risk relapse refractory seal, which would be eleven Q and seventeen pizza leader patients. Head to head a Calabrian verses Abreu nip the smackdown cage match, the two drugs, and we'll see whether what seem. Seems to be a safer drug and seems to be one which may be at least if not more effective manifests those characteristics in a head to head comparison. You mentioned the use of targeted therapy. I Bruton instead of chemotherapy in the first line setting one of the challenges, perhaps is with younger patients. Do we want to give targeted therapy and keep giving that for a long period of time is that something is a concern to you? That's the question occupies. Most of my time in clinic with my patients. I have a lot of patients in their thirties. Forties. Fifties some younger, but particularly the forties and fifties because they're very educated. They're very scared. And they asked the question I've heard about these capsules I've heard about these pills, and I really don't want chemotherapy once has that seems to be important is determining where they're seventeen Peter leader or not if they are then chemo immunotherapy is totally off the table in my. Because Bruton and vanita clocks and calibrate nib are much more effective than chemo immunotherapy in those patients. So you have the discussion you say, okay. And even older patients, you say, look we have chemo. Immunotherapy whether it be FC are in the mutated or be are in the mutated patients here. Six and done. You get six cycles, you're over you have a substantial proportion of patients who can complete remission in may last for years, and then you can get your target therapy down the line or you can just take three capsules a day of new and just fine and dandy. But what you have to remember is just because it's argued therapy doesn't mean that it doesn't have its adverse effects and outlined some of these previously. The other issue is and this is the biggest problem that the drug is taking indefinitely and. You run issues of expense. You run into issues of compliance and some patients just get really tired of some low grade chronic toxicity. Whether it's the diarrhea, whether it's the arth rally, although most of those dissipate over a period of few weeks when you talk to patients who've been on the drug for years, they say, yeah, I've got these are thrashes, but I'm just on capsules from leukemia, and I've learned to put up with it. So it's a decision that the patient has to have a very active role in do. I want to be six and done. But it is chemotherapy it is intravenous. You don't lose your hair, but there is associated nausea and vomiting with CR, you may lose your hair, but not much be. Are you don't or I want these capsules which are probably better tolerated? But it's indefinite. The second major issue is how do we limit the duration of therapy? It's expensive. It's a nuisance and patients. Just don't want to do it. So we need to find a way there are patients who can come off it Bruton tube for tolerability who may last for a year or two without progressing, but those who come off for progression do very poorly. So what we need to do is to find a combination of drugs such as our kindness inhibitor into to ever which may be expensive in the short term. But you may be able to stop therapy. Let's say six months or twelve months or eighteen months rather than going on for years and years. So a number of clinical trials are approaching that issue. What should we be looking forward to it? It's on the horizon where I think that would be exciting is a novel combination of targeted therapies that is not only tolerable but results in cure seal. And I think that as possible, and I think that will be accomplished in the next five to ten years. One of my thought processes is that one way to approach these diseases CLL or foam, the insulin be selling and sees it's the think of them as a three compartment model you've got the outside of the cell, which we attack with monoclonal antibodies. You've got the innards of the cell the signaling pathways which you get with the BT Cain hitters, the PI three K and Evers the second hitters what have you and the two in hippies, and then you've got the micro environment. And I think we need to really focus more on the micro environment. There are drugs that target the micro environment. There is lenna litt- might which has actively and ceelo. There were two what I think are somewhat disappointing. Studies presented at at this year. Lentil, a mine maintenance with a whopping progression free survival benefit following various forms of therapy. But with no. Survival benefit which is always a disappointment. But we also have the checkpoint inhibitors the PD one and PD one targeting drugs, and they are now approved for a variety of solid tumors as well as Hodgkin lymphoma and are being studied in CLL as well as other be, and perhaps even T cell lymphomas as was shown at one of the sessions today, so one can envision a combination of an antibody such as. To a checkpoint inhibitor and vanita clocks and put those together and g you'd have a whopping Lee expensive regimen. But if you could cure patients with a finite ration- of therapy, then it would be worth it. You're listening to the novel targets podcast. We will need to be sure that the benefit of three drug combination of the comes financial city associated with it. Does more of my interview with Chechen biotech strategy block? It's a subscription publication, but provides country and analysis on construct development. It's time for a message from us sponsor as regular listeners know instead of reading coporate message would doing many interviews on vignettes with company. Scientists on researches name is Michael winger. I work at genetic in south San Francisco in clinical development due to German accent. You totally did. Yes. I worked nine years out of Basel, and I'm originally German trained in Germany, and I did a brief spell in the United States, but not enough to get rid of my germ, Nixon trading US, scientist or hematologist both. I'm a hematologist oncologist MD PHD in Matilde. I'm told everybody has to be smart at Genentech. It helps having a few smart people around you because if that happens, I get a lot of good ideas from them, and that can help them developing though, said here's what do you do? I'm overseeing the development of three drugs. One is called platoon Fedotova, which is an antibody drug country. Antibody drug conjugates are really cool molecules we can develop pre clinically super of medicines. But they just happen to be a little bit too toxic to be given to patients so the country itself. This problem by attaching a tiny amount of the toxin to the antibody by means of Lincoln drug and that contact the body plus Lincou, plus the toxin Senan jetted to the patient and travels to the cancer cell, the antibody ducks to sell the whole complex gets internalized and only then the toxin gets released, and then the talks starts killing the cell, but only the cancer cell, and that gets rid of a lot of the toxicity we would need to fear otherwise. So this is like a small bump, but goes to. Specific target amendments to reach target releases its payload and kills cancer. That's absolutely, correct. And yes, they could be called smart bombs still chemotherapy. So it's not necessarily something that is very different from conventional chemotherapy other than it's delivered just to the cancer cell. So tell me about him. What does that target pilot? Does that deliver them Fedotova in targets an antigen called CD seventy nine b which is part of the receptor, and that is also essential for this molecule to work because the only want to kill licnen B cells and CD seven nine beats only expressed on b cells. So that's important because otherwise we would have that same problem that we have was the stem chemotherapy that a lot of the good cells in the body would be affected Pulitzer is this antibody against CD ninety than linka cold VC and toxin called M E, which is essentially a about a thousand times more potent version of alkaloid, Kristen or Vinson and. Inserted in patients with lung cancers. It's able to pretty effectively on its own destroy blood Kansas, but we have learned in the development. That's probably best used in combination. And that's the data was showing at this meeting. We have three posters in one or a presentation and in all of these we show data together with either retire or twos a map or with the Mustang or chop chemotherapy. So tell me about the strategy behind targeting some of these aggressive lymphomas, we're not just targeting aggressive lymph Olmos well to targeting indolent lymphomas data and both of these here at the meeting specifically on film, which is the most common of the indolent lymphomas and diffuse large film, which is the most common of the aggressive lymph illness. The strategy is relatively simple in that. We think the single agent activity of these molecules is impressive, but probably not enough to really make a huge difference for patients, and that's what we really are here for two to make a difference for patients. So what? We think right now is we want to replace part of a standard chemotherapy in the chop regimen. That's when Kristen and want to replace it with politics of adult in increasing the efficacy, but not necessarily having any additional safety issues, which is a tall order to do. But the initial data was showing here the poster by every Tilly on thirty three patients with DB L treated frontline with a regimen called R chop minus Kristen's referred to. This is our CHP are chip plus politics methadone open show, an eighty five percent overall response. Wade with a seventy percents rate. We quite convinced that this is better than what we would see with our chil- alone. We've just finished another trial with our chip that we compared with another drug called open to to them up and chop, and we have a database to compare this to our patients who are sicker than the average patients and achieving this eighty five percent overall response rate is super encouraging. So if we can maintain these sponsors, and we have another twelve patients that we're waiting to see results from this. Well, we might will pursue this further faith real we'll look forward to see where for face retrial is full coming reasonably hopeful that this will be the case we put a graphic of how politics advocating worse Nova talk. It's website. So what else was interesting in foam? I'm John Leonard. I may lymphoma specialist and researcher at Weill Cornell medicine, New York Presbyterian hospital in New York, so on Twitter, you've shed hash list. What is about him? What gave you idea kind of woke up when they basically and said, maybe I'll countdown some interesting abstracts and put them out there and see if colleagues and others will react to them. So is some significance to not really I don't really intend to save the best for last David Letterman's top ten list always had kind of a weird cadence to it. And that the funniest one was not always the last one. So it's just kinda mix it up a little bit. So in the spirit of Letterman number one on Leonard list, Nevada MAB with respect to lymphoma has a great deal of activity and importance in Hodgkin lymphoma. We're kind of sorting out where it's going to be used the other lymphoma subtypes, you know, in the range of twenty to forty percent response rate that for most of them foams settings is modestly interesting, but not off the charts. Unlike in Hodgkin lymphoma, where the checkpoint inhibitors too much better. This was a study small number of patients with central nervous system. Foment testicle film had a meaningful number of responses. I don't think that the numbers are at a point where we can say what a response rate is. But I thought this was exciting just to bring the checkpoint inhibitors into a very specific subtype where they may very well make some impact. But obviously need further study. Number two is a studied the alliance for clinical trials on college, which I'm very involved with has led that goes back to two thousand three. This has been a long study that compared our chop versus R E pock chemotherapy with retired som in both arms and the difference between our chopping. Our epoch is really the addition of Tope aside, the top line summary is that they're not big differences between the regimens as far as efficacy. Our epoch a little more toxic and a little more complicated. Number three. It strikes me how many Fulham foam patients are getting a brunette. And I think that impart reflects just in general practice off label use it Bruton Btk inhibitor that is active predominantly in chronic lymphocytic leukemia where it's approved mantle cell lymphoma where it's approved. This study reports data in recurrent flick Ulum foam patient, showing overall response rate of about twenty percent and progression free survival of between four and five months, which for full kilolam foam is not particularly exciting. I would say I don't want to say, it's a negative trial. But I think it's important to the clinical community to know that Britney you can't just say, well, it's foam give it Bruton. If you have to know the sub type. The subtleties of this. I think it's important that people in practice need to get after rather than just kind of lumping all these together. Number four is a study of Bren tux Avedon in cutaneous T cell lymphomas and T cell lymphomas often express CD thirty the antibody drug conjugate printouts from a randomized trial had a dramatically improved progression free survival in particular compared to some standard therapies now. Admittedly, one could have thought of more robust comparison perhaps. But nonetheless, I think this shows that this is an active drug for CD thirty positive patients and probably does give some validation to its use particularly given that its face trial. Number five. There are interesting Carlot's with vitamin d levels vitamin d insufficiency and outcomes in lymph Oma, and this is a large trial, basically observational trial showing that vitamin d insufficiency carlights with outcome with respect to early clinical failure in patients with fully kilolam foam, and this has been seen in other lymphoma subtypes as well as certainly other malignancies and other diseases. So the big question is, obviously. This fixing vitamin d levels result in a better outcome is this just a car elation and an association for less favorable disease or less favorable characteristics. Versus the concept that the vitamin d deficiency itself could be treated and therefore improve outcomes, and we're working on how to pursue this a little bit further. Number six, say chemotherapy based trial that comes out of group in China. And it's a poster so you know, I try to pick some things out of the posters that people also might not see or might not get as much attention. But the reason I picked it is that purple T cell foam is an unfavorable infamous sub-type chop is one of these standard therapies, although we often Atty Tope aside and the net of this trial. Was it was a randomized trial of GDP t basically Jim side being Dexsa method zone platinum combination along with the little Meyde, which was an interesting addition to this regiment, and one could either be interested in or question. But nonetheless, there was a significant difference with respect to overall survival in this study now, admittedly, it's a study that is relatively small. I would be interested in, you know, seeing if this could be explored, and perhaps followed up in large numbers of patients houseware. Number seven refers to the plenary presentation by Robert Marcus that looks at a population of patients with untreated flick. You'll and foam who are getting chemotherapy, either bennema Steen chop or CV VP, and it's a randomized trial of chemotherapy plus for tux, both as induction and maintenance versus the novel anti-seizure twenty two MAB also as induction and maintenance, and so obviously made the plenary session. It's a positive trial with respect to progression free survival. I think that you know, there may be many people that lead to using bene- twos. Basically for all patients in this sort of scenario. The question might be does the chemotherapy matter are more nuance to this many my patients, I don't give maintenance too because maintenance has a progression free, but not overall survival benefit. And so I think the question may be also for patient ops. Not to have maintenance. These results may not entirely apply. And so what would one do? So I think it'll be an interesting time in the use of bene- twos. Abba up front full akilah MoMA. Number eight is a European study that basically reports on an overall survival benefit of maintenance for touch some AB after stem cell transplant in mantle cell lymphoma. The use of maintenance and mantle cell has kind of been up and down. There are some positive overall survival trials and some less convincing data, particularly with bend, the Mustang that were recently reported Lasko. This is I think from the abstract at least well conducted trial over three hundred patients most of them went into remission with induction treatment went onto get auto transplant and then randomize in those patients to maintenance Tacoma versus survey Shen showing not only progression free survival benefit, but an overall survival benefit in the range of as I recall seven to ten percent. So when you see an overall survival benefit, I think you have to pay attention to prospective study suggesting that if you're choosing transplant which is a whole nother question mantle cell. But if you're choosing a transplant you. You probably should get maintenance for because of this overall survival benefit. Number nine Zeh study led by Matt m-? Our and the mayo clinic group among others. It's also a poster, and it's an observation that we noted as we were looking at prospective studies of celery in directed therapies in large cell lymphoma in a randomized trial fashion that require a step to select the patient meaning that you have to buy the patient sample. The patients ended off have some sort of central process that takes some time and then enroll the subject onto the study of let's say arch op versus arch shop, plus the targeted drug the nature of that process, which makes a lot of scientific cents results in the fact that a subset of patients. Can't wait for that process. They end up one way or another intentionally or unintentionally dropping out of the study or not going on the study the net is that the patient population ends up being more favorable doing better and potentially. Dicing the design of the trial in that the control group does much better than expected. And so what mad and his colleagues did which I think is great as they looked at the mayo database. They looked at the patients who had a longer or shorter time from diagnosis to treatment with lard Selam foam, and I think they used about a two week cut off. And they basically showed that for whatever reason retrospectively if you went longer than two weeks from your diagnosis to treatment, you tended to have better prognostic features and attended to do better have better outcomes. And so that I think is very consistent with the first point in that if we're going to be selecting patients for trials we have to have a way to do it very very quickly because the perceived or actual time involve is going to result in different patient populations. And potentially more favorable patient populations and less therapeutic effect. And finally number ten didn't think we could go without cartesian abstract. And there's a kite cartesian study single arm trial and recurrent large cell lymphoma. Patients predominantly being presented in the late breaking abstract session. And you know, I think that there's a lot of patient interest in cartesian. Clearly, there's a lot of interest in number of quarters with the recent data issues with toxic and risk issues with efficacy. And so I think that's certainly an area everyone's paying attention to. I think that the inherent issues in cartesian self. Studies are going to be in part selection biases because patients have to wait in some cases over a month before they can get treated not necessarily in this trial. I don't know the details of this one. But in some cases, at least, it's a it's a long time that the patients waiting again results in that selection of more favorable patients. And then at the end of the day, how do you interpret the results recognizing that the process inherently? Elected out, some patients in a single arm trial that issue plus in my mind. The key other things are gonna be obviously, the toxicity how toxic is therapy, which might be acceptable. If it cures patients might be acceptable. If they live a long time because of the therapy. But if they only live a little longer have a short term response is not going to be so balancing out the efficacy and tolerability is really going to be a key factor as at and in my mind, the success of these single on trials such as they are is going to be very very contingent upon durability and the nature of the patient population. So out of top ten as you had to only select one of these trials to take desert island, which would be to my desert island to treat a limb foam patient or my desert island to be interested in excited about something. You can take one of each I think certainly trials have overall survival benefits and bad diseases. You'd wanna take with you. So, you know, I think probably well, it's a little less sexy because it's tucked som. The mantle cell transplant trial with an overall survival benefit suggests that there will be something there. I'm not ready to go to my desert island with only a cartesian L agent to treat whatever patient, I might encounter. And I think I'd probably need an ICU on my desert island to do that in some cases. So I think perhaps one of the checkpoint inhibitor studies would be something else that would get my attention as being quite exciting. I hope you don't mind me having some fun with sound effects. And if you wondered whether does I learned question came from do search BBC radio for for desert island discs. Immature level targets. Don't come. You can find links to Lovie upstream of made for hash than it list. What also caught my attention of the Ateneo meaty, and San Diego was the prominence given to curing sickle cell disease. I spoke with an expert at the full front of research. I'm Alexis Thompson. I'm the hematology section head at Lurie children's hospital in Chicago. I also happen to be vice president. So this is particularly exciting meeting for me. What does that mean to be advice? President one is elected vice president and in the subsequent years you become president elect, and then I'll be president of ash in twenty eighteen. Wow. So you're really going to be senior in the organization. So you're gonna catch me while I can this year. Okay. Not that there won't be excited things to talk about next year and the year after but I think they've got me pretty busy. What we wish you ever says him that? So what is the sickle cell disease initiative? This is actually the culmination of many years of work. We recognize that this is fundamentally a blood disorder that really needs. More attention. We are really really focused on research, and what the research priorities for sickle cell disease are. But we also recognize it always comes back to the patient and the questions is Huckabee we improve outcomes for people globally. It means something slightly different in the US and in high resource countries. But you know, we want to also be impactful in those parts of the world where resources are scarce, and unfortunately, where lots of sickle cell patients live one of the challenges. I hear is of the country's wherever sickle cell disease is going to be challenging to get access to innovative new medicines from the western world. How are we going to become those challenges? I think we have to take a few steps back. The vast majority of people in these countries don't have any idea that they have sickle cell disease. So when I talk about diagnosis there are three hundred thousand babies born every year with sickle cell disease worldwide. Eighty percent of them in sub Saharan Africa. Newborn. Screening hasn't arrived in most of the continent of Africa. And so certainly we want to begin with that. There are simple things like penicillin prophylaxis immunizations early treatment of malaria that could begin to be so impactful right now in Africa where fifty to ninety percent of these children will not see their fifth birthday that is so different than what we see in the US and the UK so at some point on looking forward to talking about novel therapies in Africa. I really just want to see us get started and to be impactful from the ground up there doing a great job of raising awareness of this meeting even to stent of having a sense cope chair in one of the main meeting areas, which focused on curing sickle cell disease. It's just fabulous. I think everyone thinks that it's just so much fun, especially you're here in San Diego. It's the dentist winner. Can. I just say I left Chicago there snow on the ground during the football game yesterday. The sun is shining here with palm trees everywhere. So having a sand sculpture couldn't be a more fun way. But really it's showing the pillars of our program access to care education clinical trials and global as part of this sculpture. And so I it's reminding people of the things that we really wanna focus on it Ashish, certainly lots of potential we'll put a picture novel targets website. So people can go to if they haven't seen it already moving onto some of the data at the meeting you introduce some data yesterday on pain in sickle cell disease in the plenary session while he's paying important pain is the seminal symptom of sickle cell disease. It's not the only one, but it is the one that certainly patients, obviously, appreciate most is their biggest fear, and it is often their biggest sibility. It's also the one that we have the most challenges with treating and so to the extent that we can fundamentally improve that symptom think that is probably the the symptom that if we can make agress with that we can really feel like we're making progress with controlling this disease. But they said yesterday is that progress it absolutely is. I think that what's fascinating is that this is a red cell disorder yet over time we've learned about all of these other components of sickle cell disease that are beyond the red cell and this research that was presented yesterday. As an example of that, we know that there are interactions between the red blood cells and sickle cell disease with white blood cells, and with the Thelia more the lining blood vessels, all of which contribute to the complications of this disease. And so this particular study was looking at an and he's your molecule fest typically expressed on endothelial cells and white blood cells and looked at the ability to inhibit the Houston of white blood cells to the Indo feely amend to ask the question, if you can block that can you actually see a clinical phenotype change, the exciting thing for this was this was a three armed placebo controlled randomized clinical trial, which showed a significant reduction in the frequency of return visits. The length of time from that. I. Visit to the second. Visit was also significantly reduced in those who received active drug complex, placebo. This is just a once a month injection. So imagine these folks have to come by your office once a month get their shot on their way, and they can look forward to going back to work staying in school really finding themselves being far more productive and less disabled by their disease. So is this data changing? This is actually a key step. I think the next step is moving this drug to being FDA approved. We're really hoping that when we see these scientific breakthroughs that we get assistance from the FDA to get these approved as quickly as possible. But in terms of pain, how does it manifest itself you see their faces and it's really a true shooting to watch. And I dare say can't imagine how it feels. But for many of them, they are able to do much of anything when they're in this severe amount of pain. Many of them will have medications that are a little bit stronger at home ultimately some of the need to be house. Penalized for fairly strong narcotics. Sometimes for weeks at a time before they're to get back on their feet and get back to life. So sounds like it's disability. Absolutely is not only is debilitating. You know, frankly, it's expensive in the United spates. We spend one point one billion dollars annually taking care of sickle cell patients. A lot of that is managing inpatients for pain while we're excited about novel therapies, a lot of ad is actually controlling the disease. But what about cure, and I think at this meeting. They'll be a presentation later today on gene therapy in sickle cell disease. The gene therapy trouser currently focused on adding a normal beta-globin. Shame because the cycle gene is still there. But we're adding in copies of a normal beta-globin, gene that can make normal adult hemoglobin A the expectations are that. These patients may still make some sickle. But if I could convert a patient with sickle cell disease to having sickle cell trait by making partially mclovin that outweighs the amount of hemoglobin s people with sickle cell trade are remarkably well, these are not individuals who have any symptoms, and so that could really be a breakthrough gene editing is also something that I think we're terribly excited about it is still in the preclinical phases. But this is actually even more advanced science that's going to allow us to go in and correct. If not the sickle gene than other genes that are genetic modifiers of sickle cell disease. And if one can say. Increase the amount of fetal hemoglobin that would normally be gone by six months of aid. If we can find ways to actually increase that in adults. This also could be way of ameliorating the pain and all the other complications of sickle cell. So this is really terribly exciting time not just for disease management, but also potentially cure. What's the difference between gene therapy, and gene editing for both of those the patient is owner one of the challenges with stem cell transplants. Is you have to have a brother or sister who happens to be a perfect tissue type match. And most of us are simply just not fortunate enough to have that situation. So in both of those cases, the patient is their own donor their own stem cells are taken out of their bone marrow. They grow more so you can do without a few of them and then in a laboratory setting theirselves manipulated. So in the case of gene therapy, a lengthy viral vector in those seem to be the most popular and safest vehicle right now is used to actually insert a new gene into their cells. And then once that we've. Confirmed that the transducer or the the modified cells are healthy and safe. They are returned to the patient there. Rian fused into the patient for gene editing. The manipulation is also done in the laboratory the difference. There is that there is not new viral genetic material that continues into the patient. Instead, the manipulations are made in the patient's ability to transcribe new are a as a quantum Quance making new pro team, but still wants a modifications were made the hope is these are modifications that are permanent. And so when those selves return to the body that you would continue to produce whatever the modification is in most cases, it would seem it will be an elevation in one of the genes that controls field him globe in. And so whether it's species eleven A or any of the other genes to the extent that we can permanently modify those enhanced production of fetal hemoglobin, we hope that pheno typically these are individ-. Nls again that will begin to have sickle him global circulating. But certainly exciting prospect as a pediatric hematologist the idea of picking children up early and getting a deficiencies before I have transfusion related side effects complications of lifetime transfusions that must be exciting prospect absolutely is. So there's a part of me, I'm a hematologist, but I'm a pediatrician at heart and the average family who's bringing baby home from the hospital. Just think of all the hopes and dreams that we all tie to our infant children yet, you get this letter two weeks later that says your baby's not perfect and many of them. I will tell you that that first that first meeting with them is tough. That's a really hard thing. But to be able to in that same conversation, give them very hopeful perspective. I mean, certainly the United States we know that ninety eight percent of these children will live to their eighteenth birthday with our current therapy. We could also tell them about new drug development and the possibility of curative therapy with real. Possibilities that their child will be eligible to receive these things. And so they do need to focus on that. College fund. The news focus on on doing well in school. They needed to focus on all the other hope that they had for their children because we really are looking at them being that only survivors, but thrives we look forward to her motive allotments from you. And wish you every future presidency of Ashish. Thank you so much. Nova talk is dot com. You complain to linked to New England Journal of medicine paper by to take colleagues use of Chris listen mob to prevent pain crises in sickle cell disease. This also to the RAV LA sense cope show, we talked about. Immunotherapy is like a large wave that surface already writing think of gene editing a wave foaming on the horizon. Say hope is a belief in the plausibility of the possible. I definitely think it's possible that we may be able to cure sickle cell disease, fruit, gene editing. The end of this extended episode from sixteen like do hope the full coming year innovative signs these exciting new break. I. This is noble targets bring to life the science around innovative new drugs, gene. And so for peace its production of blue is publishing. Executive producer Sally church. I'm put thanks for listening.

United States CLL Bruton leukemia cure Leukemia Hodgkin lymphoma AML large cell lymphoma FDA Oregon Health and science univ sickle cell trait lymphoma Nova Chicago diarrhea American society of hematology Kristen
Why Were Treating Cancer Wrong, And How We Can Get It Right

Diane Rehm: On My Mind

35:53 min | 1 year ago

Why Were Treating Cancer Wrong, And How We Can Get It Right

"Ringo's now on dish city from WMU out doesn't immigration cuisine distinguish itself in DC. Listen wherever you get your podcasts case a de as pad Thai and Sushi why are so many scenes mashed together at local restaurants I think it was mainly for they. This except for those where targeted therapies have worked mostly we are relying still on Chemo radiation so many exciting announcement there's been talk about precision medicine talk about immunotherapy assessment of just how little progress we actually made in the so-called war on cancer tell us why B.'s and surgery what surprises me about what you've just said is that throughout the years we have heard nations while and my fundamental question Diane is that why are we still using the Siem Slash poison husband is he was dying of leukemia she became convinced that modern medicine is getting it wrong excitement about new breakthroughs I have been treating in studying cancer for now thirty five years at least I have ending billions of dollars in trying to develop better treatments all we have managed to do except of course few cancers Rolling Chemotherapy radiation therapy and surgery by basically what it does to the patients and despite country's war on cancer noting medical breakthroughs also watched as the price tag continued to grow Raza cared for those suffering from a disease non colleges at Columbia University she's closely tracked as well as the suffering of her patients and their families after being both doctor and wife for her our Phil and sobering I have ever read you offer a very downcast a crisper techniques and other advances but apparently as you point out in the first sale job done well with other treatments two obvious examples are chronic myeloid leukemia and acute promyelocytic leukemia and a few other learn approach to treat cancer after fifty years slash poison burn explain what you mean that is a way of book was exactly what you have summarized and the sentence that our current cancer paradigm is simply not good enough it is and the last doctor Rhonda I'm US tell you that this book is one of the most why you believe no one is winning that war Diane I want to begin by saying that the whole purpose of writing ailing our patients anyone who has advanced disease really the outlook is not very much different than it was fifty years ago for those Oh not much help for most cancer patients then why has there been all is say that right in the beginning when I started treating and studying acute myeloid leukemia particularly deadly form of cancer I was full of open excitement I'm an immigrant I had just come to America as a young person wanting to find a cure for cancer and acute myeloid this disease will not be cured and so I turned my attention towards trying to prevent this disease from occurring and stuff cumia was one of the deadliest and often treating patients for about six seven years it was clear to me that in my lifetime talking about too is now out with a new book it's titled that I sell Hatton the human costs of pursuing cancer acute myeloid leukemia also just around the corner why because animal models have shown improvement or cures so uh-huh and a third of them can develop into acute myeloid leukemia but since one thousand nine hundred seventy seven Diane I have been regularly hearing about cures for whereas one of my colleagues is very fond of saying Azra there are a lot of healthy mice running around with acute myeloid leukemia but unfortunately gene patients who present with a kind of a pre-leukemic state these patients suffer from a group of syndrome scarred Milo dysplasia syndrome in animals yes and I would like to specifically clarify something here because I'm so concerned them as tools to study biology but once we start thinking that we can give a drug to an animal seats effecting the animal and then immediately as seven and three because we give seventies of one three days the other the same seven and three since nineteen seventy seven to two thousand nineteen wonderful podcast also that what I'm criticizing is one aspect of animal studies animals are wonderful model as long as we use not the for the patients and this is the killer then I'm still using the same combination of two drugs popularly you say in the book that animal studies including those mice are not only misleading extrapolate the results into humans. That's where my problem is I don't think animal models are good for drug development but they are very good for her arguing is that researchers doctors must go back and look at what is displayed but it I will be misunderstood when I criticize animal models I have said it over and over in the book and I would like to clarify here on your IOS or any animal model and we just don't even bring it to the bedside and they'd have been instances I have quoted in the book my as well misleading and they are harmful actually to what happens in humans I stand by that statement why are they harmful win for treason's that if we find something has worked in animals we try it and bring it to the bedside and it doesn't work and the patient suffered all the side effects linked to kill every single cell but water reusing it's like somebody said using a baseball bat to hit the dog with it to try and one of the reasons for me to write the book is that we as oncologists who are charged with protecting our patients and treatment is failing our patients at so many levels but you know there is that apocryphal kind of story about the frog if that some of the drugs could work in humans but didn't work anonymous Doctor Rhonda what you seem to be arguing is that tissue and normal cells and individual and those are my serious concerns that the current paradigm of Cancer Research and Richard of its fleas so if you have that kind of draconian measures to kill minimal residual disease than you end up hurting a lot of normal Indian diagnose but illnesses the holistic effect of that disease on the patient that so many fundamental level doc is that we need to bring back that paradigm where we treat illness differently from disease diseases something Dr St other at the first cell how in the world can doctors do actually I'm saying a couple of things one of them is what you often talk societies of the treatment we are giving them but none of the benefits and on the other hand the Converse is true as well that if a drug fields in mouse model without jumping out I feel like that's even though scientific lien correct the story has been quoted many times and proved wrong scientifically but it eighty and that takes its toll on humans but before I get into the first and last selden I'd like to also emphasize the you said that all of our efforts right now are directed at trying to eliminate every last cancer cell from the study so I'm not criticizing everything else and we must continue studying animals or those kinds of purposes but yes they are too many researchers are looking at the cancer once it has already shown itself what you are during the past two decades seventy percent of them were at best useless sadly yes that doing is experimenting on patients with whom they really are not talking about the fact practice today because we are treating disease and illness as if they are synonymous they are not one reason which compelled me to write this book being but they're actually harmful for cancer patients because that is he can't be accurately reproduced mix the point that we have become desensitized because of accepting you little absurdities one at a time it's really a shocking fact and it makes me wonder whether in fact what doctors are through a frog into boiling water it will jump out but if you put it in cold water and slowly start heating the water doesn't realize and will die we disagree with you I hope you won't mind but honestly in my thirty five years in America I have yet to meet in consent forms to sign which has everything in black and white but on the other hand the given the frailties of human nature and our desperation when cancer trying to prevent they're suffering from the time of diagnosis until they're dead seemed to have somehow become a little muddled in our to this obscene point in our practice where forty two percent Americans lose every penny for example can you imagine how much drugs are costing these days I am reading about that day and how have we come lifesaving. After two years of diagnosis of cancer forty two percent and you point out that up the cancer drugs approved a single oncologist who didn't deeply care for the patients are styles may be different but believe me I have never met anyone who would harm me sound like jargon but everyone tries to convey and as I said patients are given consent forms and the have Google too oh it may not work but we tell the truth to every patient that it may not work for you in fact we give all the statistics in fact there knowingly anybody or experiment on patients the whole thing is that all oncologists are desperate to do something for their patients even though because without them knowing they noy I mean ninety percent of the time stark through to the patients then percent we may use language that young man that has been coming in and out of my house since fifteen years of age my daughter's traveled with him all over Europe four best us and this is why it becomes very important about the kind of human cost of Jesus after the last cancer cell how do I get myself even in the mirror because I had nothing to offer this poor young man nor Saudi suffering from one of the most aggressive malevolent kanses known to man globe last moment for me and it was a nine I'm studying hard partying hard whatever kids do these days one fine day he develops a weakness and pain in his arm and for shunt chemotherapy radiation therapy mutated feed more chemotherapy more radiation more immune his whole mouth strikes I mean think of twenty two year old boy who story I recount and ruined the book yes his mother would tell me all the time if there's one in finally pushed me to write this book because Andrew is a twenty two year old boy my daughter's best friend this beautiful that these drugs could be useless and could indeed cause more harm than good I'm sorry they're completely a million chances are we want to take it so it's not fair to say that we are experimenting on patients or offering them what nothing in the sixteen months it took this boy to I what did we do to him. Multiple surgeries placement very rapidly gets to the point where he's rushed to the emergency room and within ours he's quadriplegic and neurosurgeons find he has sources he turned to his mother lay nine he simply said mom don't worry at all just call Ezra she's on the cutting edge she'll find the cure for me all back on these days so they really become well informed and yet they go in trying to take whatever is available with the hope that there's a slim chance because I couldn't talk about my late husband who died I took care of him for five years but it took me eighteen years and Andrew to shake soclean's for them to respond tell us what happened to hit Andrew Tell us his story actually Andrew is the reason that basically friends Rebecca Charles Sheldon Andrew going to Amsterdam to Montreal to Paris and London vocations you know all the time replete chick and his mother and his sister have to stand in his father and his grandmother have to watch this happen every day me he told them to go away not signing they left that evening his father game to relieve Elena his mother and Carrie and how many Andrews will it take to change this is the question I asked myself and this is why I wrote this book won't be pushed to really try and change the paradigm imagine he's now turn Justin twenty-three couple of weeks before dying label is Zero Point Zero Zero but you know what happens Diane is he as soon as he opened his eyes from that surgery and was told his dad Hi Diane on my mind cancer for decades Dr Nine now I couldn't do it because in front of my mother insisted they wouldn't be able to handle it even this twenty three centimeter tumor which could not be completely removed so now from the get go we know that this young man's John's of Sir brought him a form to sign which is a dnr do not resuscitate Foale twenty-three-year-old how is he to say don't Russ's resuscitate thinness off against one raw open wound the whole time he couldn't swallow at the end he couldn't move anything is called ordered is being protective in the end of his mother in his sister why are we feeling Andrew the last thing I'll tell you about him his sword soaping full but I want to sit because suffering is what I see on a daily basis suffering is what I write about in the first cell because until and unless we go into the granularity of this suffering be Desisto who had been with him all day as soon as his mother insisted left Andrew Goal back the tending who had brought the form and said I'll lean-to writing about even harvey when he came back more from Dr Arabica after a short break twenty more about the eighteen day cruise aboard the ship Silver Muse is at Diane Ream Dot Org we need to do things differently at least we have to accept that the current strategies of not successful and the hope for cure in new and different way as you watched over your husband daughter was four years old barely and I'd when she was eight but it was Andrew and Omar the younger people and all of my patients that I'm using now on a weekly basis who finally have pushed me into accepting that that must have been so difficult for you as a doctor to try to care for your own husband yes that is something I don't wish on anybody did that mean that you saw kanter and treatment did I from the outside the lymphoma marched on it seamless mono maniacal journey to resolution with a motiveless unbearably painful disease could be that's what I lived through with Harvey for five years when he was diagnosed he don't see travel writers going there and Lake Waxing poetic about the amazing Pusa they had a local fender on dish here's the reds did my conversation with Dr Oz Route Raza she's an oncologist at Columbia University elsewhere without warning fresh lesions began with a tingling burning sensation becoming bright red and sizzling hot with dinars no matter clem former selves meandered autonomously rudderless. They wondered the body with studied carelessness entering and leaving organs at will as successful as we'd want them to be and that a change in strategies gold for now I'm not saying that instead of chasing after the last cell return to early detection this is an easy solution or that it will be the ultimate solution no but we assed Harby was your husband and as you said you took care of him for five years Alec Nettie Cancer is what I had been treating for two decades yet until I shared a bed with cancer patient I had no idea stacey and the author of a new book titled the First Cell and the human costs of pursuing cancer to the last the book please Harvey was suffering so much from this lymphoma swelling subsided in one joint bobbed up at grunted edgy exploring possible niches in various organs rejecting some settling in others this we watched the drama unfold Harvey from inside adventurously watched him die I don't think it changed me as an oncologist and as Dr who takes care of patients it can papa gain more respect for Salvadoran food in DC that's under city WMU listen wherever you get your podcast not changed my perception of the whole world completely taking care of Hobby I'll review just two sentences from the Frolo in his good and taking care of cancer Lee's good it's not cancer that kills it's the d'alene treating that kills point is why would someone who's eliminate abnormal cells did Andrew have any signs before his huge all understand that prevention is the best cure anyone who has cancer you will hear them say oh no but it was quarterly so it's taken care of so we normally detect twenty two at Andrews Age would be even screened for having cancer since no one is immune since children get cancer the on addicts what we need to do is continuously look for and try and identified addict and sitters that we need to have a constant monitoring of the human body as a machine instead of having sporadic and periodic annual exams and you had no idea that cancer is growing inside him and so this is where I feel that we have to turn ought attention towards studying humans towards trying to identify this disease as early as possible and for this purpose adore until just two or three weeks before when he started developing pain how many people do you hit off right now my I mean pre leukemia and acute myeloid leukemia which has been collected by a single physician I have no more than sixteen thousand samples from thousands of patients the whole country's morning for what is happening with Alex Trebek's he didn't realize stage four pancreatic cancer he looks fantastic he looks beautiful us can indicate to you who it is who might develop a blood cancer later in life grown up in this country wants my mind was made up to study pre leukemia and UPI would have developed or try to develop an animal model for it but end unbearable symptoms appeared this is why the human bodies such a complex thing Diane we think we know what he's not following my patients as the develop up medium and the one good thing that game out of my being an immigrant and a foreign is that I was too naive had I have been committed to early detection since one thousand nine hundred ninety four when I began to turn my attention and focus on pre leukemia and of leukemia that could appear later in life is present at birth birth so now we can go to do banks of public do means that contain DNA sequencing information on hundreds of thing about the cancer can spread to stage four and attack practically ninety percent of an organ and we won't know Andrew had no sympathy gum from Pakistan. It helped me to be naive and I said if I'm willing to study patients I better save their samples and so in one thousand nine hundred eighty four I started to see blood and bone marrow samples on my patients and today this is the largest shooter Balza Tree in the country the dedicated to patients with Geez we go in interrogate these samples properly and trace are we back Diane weaken figured out what germline which means what kind of Dini they were born with that made them susceptible to develop this kind of disease in later life thousands of held individuals identify those with this kind of polymorphism follow them and see is there any evidence of early pre leukemia in those people's I'm saying it is very possible people have actually shown that many breast cancer starting you true so yes L. D. volunteers through germline DNA but there are other technologies that are becoming available that can constantly monitor the human body. Oh I think there's a very good possibility not all cases but I do think that one possibilities to detect early in give you one simple example as soon as cancer starts attest to attract nutrition to itself because it divides faster by multiple technologies available genomics proteome extrance Crypto mixmaster below makes Banamex all kinds of Technology Lucy okay those individuals who developed let's say Myelodysplasia Syndrome affecting chromosome five had a polymorphism in this gene as and BS CS and colonoscopies in fact thirty six percent of these common cancers reduction in mortality by thirty six emigrants had they not proven effective very effective Diane in fact that is a twenty six percent decline do we go from acute leukemia to pre-leukemic to healthy volunteers we have all the samples in the shooter positively ready to be studying but where are the resources where is the Will Dr Browser are you saying to me that an indication so that we'd be able to trace back acute leukemia to pre-leukemic and then looking at germline DNA of patients with pre Lewke me than normal sales nutritionist provided by blood vessels so it starts making new blood vessels area becomes hot. Why can't we pick up this me others have been developed in twenty years and I have seen longitudinal samples on these patients now if we go back and look at thousands of these patients if this is exactly what I'm saying Diane because I have followed these patients from a some patients took a year to develop a cute the oil in the head of the pancreas there is a hot spot that's appeared what about the current cancer screenings the colonoscopy eased and not one single cell has been contributed by another doctor so what you're saying is that this collection of sample screening measures if you would explain the debate over the primeval caught have cast within incorrect number of chromosomes? You sound like a scientist and I am quoting that's not really very helpful but I'm saying we should use the latest cutting edge technologies to actually supplement what we are doing with the current nine and mortality in the last several decades and most office or do early detection by mammograms and fats mute signs of changes that you want to see happen in our understanding and treatment of cancer in your book is I think it's very clear to everyone that no matter what the cause rounded whether it's the environment of the salvage every time it divides the cell has to double its DNA enduring the doubling it can make copying errors in the DNA a coughing editor that percents is off to these techniques but then these are they have their limitations they can sometimes detect cancers very early that may never the end result is that the functioning of the cell becomes abnormal and because the function of the cell is controlled by g media that is hard to many of our imaging devices that can be worn like the telephone or a bed sheet that can scan you overnight the individual in their lifetime if detected prostate cancer in eighteen year old that's going to take thirty to grow into a truly malignant killer then Gina or too much message or too little it is shut off for or reasons and so in the final was is golden mutation so each time against cell divides it picks up new mutations in other words it can become a new cancer now this jeans which and their expression so either there is a mutation in a gene or a gene is dysfunctional it is producing too much her whether it actually begins as to genetic mutation of a cell or as a cell did you bullet type drugs or treatments have been developed but the vast majority of cancers are either to a new ploy D. or too much damage in the Mike aw give the patient will kill yes I think that is just unacceptable so the point I'm making is we should at least that are caused by single genetic abnormalities most of them have already been identified and for them targeted and Johnston selection pressures this constant evolution. It's a moving target how optimistic are you doctor that the stalks on whether it is the an actual damage to the cell it self directly but seed or soil in other words crow environment of the cell as well as the cell is a very complicated issue and the single most complicating is that once a cancer cell forms assist ultimately it always has to be a genetic component to things there is a debate whether it's whole chromosomes approach needs to occur and occurs soon thank you again thank you Diane it's been an honor being with you educational and I'm sure many people fully agree that something new zander damaged or just small jeans what in the end it's just the functioning and my own bias is that it did a very rare cancers that the PUSA is one of the most recognizable dishes in El Salvador and one of the most delicious street foods and the world and yet ends Dr Browser thank you so much for joining us this was so helpful I feel very optimistic in one area which is that this is a capitalist country once we set a goal and we financially incentivize it everyone acknowledge that the current cancer better name is feeling and if that is failing water their strategy can be used the only strategy that has win rush

Diane leukemia breast cancer WMU Ringo DC Google Europe edge technologies Andrew coughing scientist El Salvador Banamex Gina editor Johnston Dini
#552 The First Cell

Science for the People

54:20 min | 1 year ago

#552 The First Cell

"Welcome to science for the people. I'm Rochelle Saunders with me is Dr Azra Raza. She is the chance soon professor of medicine and Director of the MD Center at Columbia University. She is an oncologist. Seeing thirty to forty cancer patients every week and directs a cutting edge basic cancer research lab with hundreds of original publications in high profile journals. She's the author of two books. The first Gallup epistemology of elegance and the second which is here to talk to us about today the first cell and the human cost of pursuing cancer to the last Azra. Welcome to science for the people. It is lovely to have you thank you. Shallan honor to be on your researcher and a doctor. Can you give our audience? A really quick summary on your focuses in your research and your patient work. Yeah I have a third bit of credential which could be important by an oncologist to cease thirty to forty patients. As you said I also direct basic research lab and I'm also a cancer widow yet that I have had the chance to see cancer from both sides of the bed as the caregiver and the wife of a world class cancer researcher. My husband who got very easy this trying to kill so I came to this country. America in nineteen seventy seven completely dedicated already to do research and to treat patients with acute myeloid leukemia. A form of bone marrow cancer which I began to study and treat by nineteen eighty. Four it was apparent to me that given the complexity of the disease in my lifetime. It's unlikely that it would be cute. But many of my patients were giving history of having had low. Blood counts or anemia. Six months to a year or sometimes even longer before they actually were diagnosed with. Up Mia and these states the pre-leukemic syndromes called Milo plastics and drums and so back in nineteen eighty. Four a shell. I made the decision that we have to catch the disease at its earliest stage so that it's not as complicated and the molecular genetic lesions are not that fought it bonds that we cannot do anything about them So I stood my attention toward simultaneously studying the pre-leukemic Syndrome which are called myelodysplasia syndrome. So Milo dysplasia syndromes is a malignant disease. Which can kill by itself but a third of the patients get develop acute myeloid leukemia. This is what I have been doing. Since Nineteen eighty-four I'm entirely focused on and obsessively focused. I should say on studying in treating patients with them. Ds following them to the natural history of the disease and Studying them see really and sequentially is the disease goes through It's progression your book is an intense mixture of information on the current state of cancer research and visceral experience of what late stage cancer is like for the patient for their friends and family and for their doctor Some people would have just an emotional book on the experience and others would have written a kind of hyper factual and emotionally detached book focusing on the current state of the research. Why did you decide to combine them? I think the subtitle of my book is equally important as the tight. The subtitle is the human cost of pursuing answer to the last in other words. I wanted to look at everything we are doing. And cancer cruel the prism of human anguish. It is not an indifferent sign here. We are dealing with individuals who are facing very challenging disease in fact it was a stigma to have catnip for the longest time because is just so difficult to treat. It seemed to bring seems to bring a death sentence. The only good thing you can say about cancer is old but it was quarterly so street to everyone knows that so my question after forty three years of being in this country and studying and treating the same disease with the same tool drugs that I was using in one thousand nine hundred seventy seven. I'm using in two thousand nine to treat acute myeloid leukemia. The drugs popularly known as separate and three because we give seven days of one in three days of another now think about my mental state having to repeat the same conversation over and over for forty three years and despite my steph trying so hard to improve outcome of patients with the same dreadful herself this is what has made me very sober about where we are going and made me examine nor just a sign spot. Look to see why. The science has drifted so far away from the human part one thing. I found both major book. More compelling and also at times harder to read was how you are in describing the lived experience of late stage cat cancer patients both from their cancer and from their treatments. I think even though cancer is something that touches a lot of people. The actual impact isn't well understood. I mean we know it's bad and we know. Chemotherapy is bad but your book was a huge eye. Opener for me on the realities and the experience of cancer. Thank you Shit because this is what I have felt do things that really have felt all along. Is that one year not appreciating in honor of its granularity green and suffering that. Go with the diagnosis of cancer. Uh scores for the patient but also for the families and the second is that somehow the language that we have used the manner in which we announce the discoveries in cancer. The kind of small can mirror approach. We have been using. Leeann giving the public a general impression that things are hunky-dory things are improving. Great advances are being made in cancer treatment. I had met that they were greeted. But and one of the best reasons to celebrate is we are now killing sixty eight percent of the cancers diagnosed today pure north just that There is a one percent decline in mortality from cancer for the last thirty years. That means that Pity percent decrease in mortality from cancer. That sound wonderful but if you look closely one percent decline in mortality from cancer every Why has that happened? Thirty percent decline talk overall. Not because we have found some brand new drug store matching bullets to treat this disease but only for mainly for two reasons. One the anti-smoking campaigns for started fifty years ago began to show dividends and benefits and do because early detection. We're finding cancers earlier and earlier treating and doing that. Sixty eight percent are being cured but using what using the same slash poisoned burn approach and the thirty two percent were diagnosed with advanced disease today. The Shell Dan. Outcome is basically no better than it was fifty years ago. So when my oncology colleagues stand in national meetings and pump their chests with dried that they have accomplished so much. I tend to be sad about that. Because what have we really achieved? Fierstein using the Baillio Elliptic stone-age treatments. We were using fifty years ago. It's chemotherapy does not distinguish a cell which is cancerous from normal cell. It's like a sledgehammer. It's like taking a baseball bat to a dog to get rid of lease. Yearbooks primary argument is that the way we approach cancer research now is expensive for us all and isn't working I want to unpack some of the context there in particular for our audience. Who has science savvy and knows? Broadly how and why science research has done the way. It is because your arguments. I think will challenge some closely held ideals around our research should be done in particular for our audience. So can you give us an overview of the way cancer research is generally done today? I just kind of a high level of of what cancer research looks like. Generally in nineteen seventy one President Nixon declared war on cancer in the United States and billions of dollars since then have gone into support cancerous odd and the standing of the molecular and genetic underpinnings of cancer. Odd dramatically improve. We can justifiably agnostic on the back with the great achievements in this area. The problem is that not much has been translated into improved treatments. So let's start with seventies when the money started pouring in we discovered oncogenes very rapidly. It was found that there are a lot of oncogenes present which means that cancer causing genes which are present in the human body. But that did not materialize into giving us a better Dog for treatment. Then we were interested in studying for example in the nineteen nineties Choking off blood supply to the Kansas and that was felt to be a very important area. it cured a lot of mice but it didn't do very much when the these drugs that target. The blood supply were brought to the bedside next week. Dr Hopes on the Human Genome Project and it would say and we kept thinking. When that happens we will have better targets. Unfortunately it's now twenty years later and the targeted therapies have been developed have been the tried distant and sadly most of them help only a fraction of patients for a limited amount of. None of them are curious. There's a lot being talked about regarding cellular therapies using the board Bob body's own immune system immune cells to find. Then kill the cancer cells this area for example One type of therapy. This particular areas very popular and highly talked about and Was the basis of the Nobel Prize justifiably and a very correctly given to Dr James Allison and the his counterpart in Japan for development of This type of immune therapy and it has produced some great responses but in a very small number of patients that reason is that even this magical therapy which I have to say again and again is one of the grand accomplishments of humanity to be able to engineer the body's own diesels which are a form of immune cells In such a way that they are activated and they are Seis Lee made to attack a certain kind of cell which is expressing receptor that it recognizes but nowhere do researchers. Were talking about this kind of self therapy nowhere. Do they mention that? Even this fantastic approach to treatment. Getting more differentiate between normal and cancer cells. So it goes and kills the whole lore for example. The only thing we could use it for the last eight nine years since it's being used is bee's and which are also a form of immune cells in the body. B. Cell cancers that they are Informa- acute lymphocytic leukemia. Why because B. Cells can all be killed in the body whether they are normal or cancer and then we can replace the B. Cell function by giving immunoglobulins for the rest of their life to the patients. But if you use the same approach to kill the whole liver because the liver cancer it would kill every liver cancer sale but also every normal liver cell than Uganda. Replace that liberal. You can't replace the Kidney. You can't replace For example the Gi Track so all of the signs that has gone in. You asked me what is history will The history is that we focus on one area. Most of the scientists are working in that area so it was oncogenes or then it was Angiogenesis followed by sequencing of the human genome. And now the immune therapies are being talked about all the time and there have been advances in all of these areas. I know where in the book do. I say that there are no influences. They are incremental. They're not enough. They're not curative. They still don't distinguish between the two. So where do we go from here? That's the question that Muskie if we continue the same old same old than keep insisting that no this is the right way to go then where will be being fifty years from now or ten years from now one of the themes in your book is that we are focusing too much on the late stages of cancer and that definitely comes out Quite strongly As I was reading. So why is there so much research that is focusing on late? Stage treatment options and there seems to be comparatively last that is focusing on preventative treatment or early treatment. I wouldn't say that The thing I'm talking about when I say late stages is the price we pay by going after the late stages and actually we are focusing on early. Cancer is my idea is not original idea and the sixty percent cancers we are curing today at all because of early stage cancer but using the same old treatments. Why are we still giving chemotherapy? Why we cutting off women's British. So why are we radiating and causing so much damage why haven't we developed techniques to diagnose cancer even at an earlier stage where we don't need these draconian measures that are required in this and then end stage monstrosity that is presented by thirty two percent of the patients? Most of our resources go in research towards trying to find some solution for those individuals. Now I absolutely admit that we have cancer patients today. We need to worry about them. We need to keep investing in developing better therapies for them. And if you asked me to sheriff I have acute myeloid leukemia. What would I do today but I take the chemotherapy? I have been giving since nineteen seventy seven or not. My answer is yes I will take it also because there is a twenty four percent chance that I will be alive in five years with chemotherapy. The question is why is that the only thing being offered? Why is that the only choice I would have? And why is that terrible choice being repeatedly given and how to do better going forward so yes? I think that there has been Concentration on early detection but North Enough. We need more resources. We need now. That more technology has become available. We need to have a completely different approach. Are there some ideas out there? About what type of approaches we should be focusing more on than we are now when to begin with we have to get away from reductionist approach that has been always used in the beginning. We felt that they be one gene producing abner abnormal protein. That can be targeted with one magic bullet and we'd find a cure and LO and behold. It turned out to be correct because Right after this approach was started we did discover that didn't very potentially lethal and aggressive kind of. Up Mia that evolves from Something called Chronic myeloid leukemia which getting become acute and we'll the universally. Fatal illness was found that this particular type of U. P. Chronic myeloid leukemia or C. L. is caused by one genetic do defect and the Drug Matt and that was developed to target that cure. It so it's basically curing it now at this was a great success but then it also has put her feedback by twenty years because basically everyone zoomed then that each answer would have the same one problem one treatment Kind of issue and all we have to do is find the gene that has malfunctioned in pancreatic cancer or lung cancer and targeted. It turned out that there is a soon Nami of genetic mutations that most of the cancer that they are not caused by one and if you think about chronic myeloid leukemia the same drug matinee which is curing chronic myeloid leukemia patients. Today is useless when the disease it bounces to even accelerated phase or an acute phase so in other words you're catching that you earliest form in the chronic phase and treating it right there. That's what I was hoping to do with. Md and treated the MD stage and not not let it develop into acute myeloid leukemia. Unfortunately turned out for me that more. Mda's by itself is very can be a very malignant and very complex disease and there is no single genetic abnormality that can be targeted like in chronic myeloid leukemia. So that has been really the issue that we are. We have used a kind of reductionist approach so what should be the next. The next step is let's get away from trying to find cancers by using ancient technology in this day and age of imaging and scanning techniques that are so efficient and so we have to be able to develop Better ways of finding early cancer. And what I'm saying is instead of using reductionist approach trying to find one gene that school for pluralist stick approach which means stubby whole cells that are cancerous there are innate the DNA their protein their metabolites that they are producing studied them repeatedly studied them in all kinds of secretions blood. Sweat tears urine stool everywhere. Essentially treat the human body as Dr Sam Gambhir from the Canary Cancer Center at Stanford says treat the human body as if it is a machine and Gone Stanley monitored for appearance of the footprints of cancer. This is what we need to have a really Pluralistic approach using not one test to diagnose cancer early like a mammogram article or no Skopje or a PSA but rather using all the latest sophisticated things even if it means two hundred points of information needs to be generated. That's what we have to generate. And that's how we will find cancer before it becomes clinically step wished. I remember reading through the book. And it's I sort of knew this already but I felt like I didn't really appreciate it in the same way I do now Which is your analogy of seed in soil with cancer and also the idea that cancer is so complex and so different from person to person that one of the biggest challenges for treatments especially he wants cancer gets into its later stages is that it different treatments work for different people are mostly. Don't work for different people and we aren't actually doing a great job in tracking what treatments might be better for what types of people with the quote unquote same cancers and that. I found really surprising that we're not trying to figure out which treatments that may be. Have a twenty percent. Efficacy rate are more likely to work. For which twenty percent of people if that makes sense? I found that really surprising that we're not doing a better job of of tracking and trying to at least target some of those treatments better completely. Unconscionable imagine that we are doing clinical trials today more than ninety percents. Unical trials that are done today for cancer or done in the same exact way that they were done in nineteen seventy seven just given to everybody see the thirty percent responded and get the drug approved without making any attempt to try and understand what these thirty percent responded and why and why aren't they institutions. Were supposed to protect us. Not doing anything to demand that sponsors of those trials make some attempt when the stand because imagine when you give the drug to a hundred patients. Seventy not respond. Which means they're getting the drugs for no reason at all. They're going to be physically and financially suffering all the talk society that comes along with no benefit at all for the sake of the thirty percent who will benefit for a short time basically month so I know experimental. Trials are a very. It's how a lot of medicine is done An in particular with cancer at feels like a lot of people are more willing to jump into experimental trials of all types. Because a like you say. There's this mixture of hope and despair. You you'll try just about anything because you want to. You want to keep living. But they're they're often challenges there because patients who are selected for experimental. Trials aren't necessarily representative of the types of patients who are more likely to get these kinds of cancers and so you end up with kind of sometimes skewed results in these trials that when you take those treatments that even appear to have maybe a thirty percent efficacy which isn't great but I guess at something and then move them into a general population. You find even like smaller numbers because you. It's just the trial groups just aren't reflective of the actual population who who's experiencing these these diseases absolutely right and let's not forget that ninety five percents ninety five percents of canceled experimental. Trials failed today the five percent. That succeed in my opinion should have fairy because they're only prolonging survival by a few months for a fraction of patients and causing financial ruin completely in forty two percent patients diagnosed in America with cancer today by two plus years are have lost every penny of their life savings. For what do you think the? Us system of kind of hyper focusing on treatment in later stages of cancer. When it's paid by insurance I mean I I have. I'm not personally a an American or live in the US. But I do have some friends in the US who I know forego preventive medicine or visiting a doctor until until they absolutely have to because of the way the health care system is in the US. I'm curious how much you think. This is a potential artifact of the expensive insurance system in the US and the way that's been set up and if that if that has any any influence on why we still kind of hyper focus in a bit on treating late stage or going to a doctor so late. I don't think so to Schilling. You have to be very honest. I think that the American system is still the very best system in the world and we are the leaders in the field and most areas in cancer research also and The reason that we can treat End Stage patients because we are affluent enough and can't afford it but not for long That's what I'm saying. So it is still the best system and the whole world looks to America for leadership. Where is our leadership? Now if we are going to develop therapies like car T. therapy that costs million dollars per patient. Which is good for a few thousand patients. Compared to one point seven million diagnosed in a year then the whole healthcare system will become Bankrupt and is on the verge of COLLAPSE HAVING TO SUPPORT FUEL. These expensive therapies. So right now. That's what's happening. I'm asking for a padded. I'm shift at least for the future. Let us imagine an invasion of better future. You know a lot of my colleagues will point. this thing to me and say ass be are all looking at the same thing but we are looking at the glass half full and you're looking at the class of fifty. I don't agree with that or shell because I'm looking at the whole loss. I want to see all of cancer treatment. I am not denying all advances. I'm not denying that we have cured. Sixteen puts in Beijing. I'm asking how can we do better? That's all very simple. Not JUST FOR THE THIRTY. Two percent were dying terrible debts but also the sixty eight percent were being cured. How can we do better by them? Also won in two minutes. One in three women will get cancer and in today's statistics. Why do we have to either receive slash boys and burn to live or die? A terrible death with with useless therapies. Can you talk a little bit about your MD s and am l. tissue repository and some of the challenges? You've had around getting funding to pursue research with this repository. That is a question that is really close to my heart. So back in Nineteen eighty-four When I decided to study really Yukimi online or dysplasia syndrome being an immigrant has helped me because had I gone to school in this country. My next step would have been to make a mouse model for studying mildest plastic syndrome but coming from Pakistan I depended on in instinct rather than on custom and tradition and my instinct. Mean that if I want to study this disease I should have sense from the patients I started. Banking sends back in nineteen eighty four today the tissue repository that. I have Houses over sixteen thousand samples from thousands of patients with MD as we have progressed in their disease and either gone and died of MDA's or are still living or have evolved into acute myeloid leukemia. B-samples are extremely precious. Because they trace the natural history of participants from pre-leukemic staged Wikipedia or pre-leukemic stage to a stage where it becomes viciously Malignant and kills the patient. We have cereal samples on them on the other hand. We have all the technology that has evolved whether we want to look for rare cells by using technologies of off Liquid biopsies by looking at a whole tube of blood and finding one abnormal malignant cell through. We're working with the pasture institute. Professor Patrizia Petrolini To find this kind of circulating tumor cell then we can also look at Oddity Dini proteins. We can look at metabolites biomarkers. We have all kinds of samples stored so that technology has beaten aboard. The tissue is available. Resources are what is needed. Resources to apply all the latest technology to so many compartments and to study them at all simultaneously in a few thousand patients and then subject the data to machine learning and artificial intelligence for analysis. And come up with the biomarkers the signatures. The combinations of tests that are needed to find the earliest footprint of cancer. It's all there. This can be accomplished fatty rapidly within a period of a couple of two to five years if we put our resources in this area and the idea That I began with is. Is the idea still have bitches once? We know the earliest markers of preview P me and then we can ask the question. Why did some healthy individuals get spree? Kimia? Even what made them susceptible. There's some genetic inheritance they had or was there some exposure or some Abnormal protein or micro environment that was abnormal in their bone marrow. Once we have that I that recognize which is which is going to definitely emerge from these kinds of studies. Then we can identify healthy individuals. Tired of getting really. And then you see me. And that's how we work our way back to really start focusing on targeted monitoring of individuals high-risk the way we do for example smokers for lung cancer. We can do Brca Mutations for breast and ovarian cancer in women the same way for every cancer we can develop it so the shooter poetry that I have now. a moss together with It's backed with a computerized clinical pattern logic. Genetic Data Bank. It's very unique in that. Every single cell has come from patients that I have personally taken care of. Nortre sellers contributed by another physician. It's the largest tissue bank in the world and the oldest belonging to Md SEM and going back to nineteen hundred four. I am so I have certain published hundreds of papers as you said earlier in my introduction in high profile journals looking at one gene one signaling pathway a set of thing but what we need is a focus study in a few realistic manner. A all the markers that I mentioned earlier the proteome genomics the metabolic transcript. Don't mix all studied simultaneously sequentially and then subjected to machine learning This is what has to be done. So why hasn't it been done yet? I said Piecemeal I've been doing it and I would be a mission papers all over in whether it's nature or cell or Molecular Sandler New England Journal of Medicine sure we make these discoveries but a serious commitment is needed and it may sound like a lot of money but it actually isn't what we need something like Hundred million dollars which is nothing if you think about the dividends that it's going to The idea that I have is either. You can raise this kind of money from philanthropists somebody who is emotionally involved and has the bandwidth to support this kind of work people. Ask Me Doctors. Why should we give you money? And not the American Cancer Society. My onset is where is the issue with the American Cancer Society? I'm the only one who has been not only Obtain the tissue but I spend a million dollars a year just maintaining this tissue bank. No-one supports me. No one funds for it. There are no grants available to do this. I do it because my patients help me. My benefactors had been asked me. What can we do to help you? I supported to shoot a poetry that soy I or fundraisers To do it. And that's how I've been supporting tissue repository. So why should you support me and North American Cancer Society because I have all the tissue available ready to school we can do it immediately and one ways as I said is to go to one single or a couple of ten individuals we each give ten million dollars. The other is And I don't want to scare anybody Rachelle. But the truth is that one in five cancers which are diagnosed new appeared in people who are who have survived previous. Can't like my husband. Harvey had one cancer thirty four years of age and survived that but then got a completely different type of cancer at fifty seven and died of it. Why because whatever was there to make people susceptible to one cancer usually still be and if they no longer live long enough they get a second cancer so one in five new cancer diagnosed in cancer survivors. Today there's something like seventeen million cancer survivors. In America. They will be twenty million in a couple of years. Even if one million cancer survivors give just ten dollars a month for one year. That's it that's one hundred and twenty million dollars that can help me study this entire to shoot of three. I'm so Frustrated and anxious about it all the time because I feel like we have the answer dipper fingers. Now how do we raise the resources to do the work? Why have you I I guess Some people will immediately ask why there haven't been kind of grants Out there to help Work through some of this because it sounds like an excellent idea to go through and take tissue repository and minute and try and look at. What are the patterns that come out when you look at all of these patients who you've collected tissue from over these long durations? As their disease changes over time. So why have you found that? You've been struggling to get people to donate or to take the goals of your tissue repository and that research more seriously. I'm not sure one reason obviously is that people don't know about it. This is the reason for me to write the book. My goal in writing the book is that I should make it obsolete as quickly as possible because I should do the work. But I'm supposed to be doing. I'm not at right. I'm not north. I'm a scientist in on colleges. I want to do the work I'm supposed to do. The book is just my latest assault in my battle for finding resources to try to do the real work. Why haven't I been able to do it because these kinds of drums just aren't available because these kinds of tissue has not been available? I keep writing to the heads of all kinds of institutes. The National Cancer Institute the National Institute of Health the Leukemia Lymphoma Society. Everybody right to I get very polite. Responses please apply to this grant or that grant and what is the ground going to give two hundred and fifty thousand dollars a year for three years. I can hear the frustration in your voice because this is clearly Your Life's work and reading the book. You can tell your life's work in so many different ways both as someone researching cancer but also someone who is very much still a clinician and spends a lot of your time with people who will ultimately die of cancer and That frustration definitely comes out and it it it transferred some of it transferred over to me. As I was reading the books I felt myself also getting frustrated as I read. Oh thank you so much. Because the human stories are are stories they have to affect all of us. One of the quotes. That stuck with me in your book Was a cancer is what I'd been treating for two decades yet until I shared a bed with a cancer patient. I had no idea how unbearable unbearably painful a disease. It could be and that really really stuck with me. Because as I was reading through the book I was thinking a lot about my grandfather who died a few years back about seven or eight years now from cancer and while I was reading your book I was thinking about him and his experiences but also how shocked. I was by what I was reading about late. Stage cancer experiences. I kept thinking like why. Don't I know this? Is this what my grandfather experience like? Why didn't somebody tell me? Why didn't I know and it felt like a kind of terrible awakening that there was clearly a part of that experience that I had been sheltered from or protected from or maybe that had been hidden from me that I really should know. Yeah I mean some some things are unspeakable ratios and it is. It is now eighteen years since my husband died. I have never spoken about before but when I began to write the book and I started writing about my other patients in such gene about the suffering. The pain went through about the emotional crises and the families then I felt dishonest and insincere by holding back by old story. I'm felt that if I'm writing about others in such detail than I have to tell my own story about Harvey as well and when I began to tell that story then he harvey story became like a red line running through a book because at every level I have experienced indignities and the pain that cancer inflicts on its victims and their families and so it even my own family. Racial were shocked by reading the book. Because my siblings who? I'm very close to did not realize how much we had suffered. And what I had gone undergone. My daughter was only four is or when he was diagnosed and so it was a very difficult period and It's impossible to talk about some of these. Things as one is living through the dizzying disorienting. Experience this is why I feel like a very important part of my book is going back to. The families of missions live written about and asking them to cost a backward glance. Someday expedience and see that with this luxury of Heinz hindsight scan. They think about decisions people would have altered steps they would have taken in a different direction and patients families have. Britain many movingly about About holiday feeding now with this Elapsed time in between and unfortunately the onto the come up with most of the time. Is that the only onset is that it is the ones that are trying to Bring some methods some logic to completely random sequence that of disease and illness and horrible pain and suffering. But there is. This is completely random. Why did they get it? Why did they suffer so much An idea that of writing about all of this is not because I want to rebel in the pain. The idea is to liberate ourselves from the pain to see the human cost and to try to do better in the future. That's the whole idea. And that is why I had to write about Harvey and it's true that even I think you picked on the right sentence that even though I'm kidding for so many patients Delight shared a bed with Hoffy. I didn't know this diseases lately. It's amazing to me that something that is so widespread can feel so hidden at the same time. What do you mean by that hidden as in sort of what we both just articulated in that we kind of all know factually that people suffer because suffering tends to be profoundly private only those one or two people really closest to the person who suffering really get a true window into what that means. I think because it's it's so personal and so private yes and speaking about cancer Keeping its secrets you know. I was working at George Washington University in the eighties and In that period I started having often lunch with Dr a Youtube Maya Pakistan in neuro surgeon. Who invented the reservoir for delivering drugs into the brain and he was obsessed with everything to do with the brain so once. I asked him over lunch what he thought would be. The final level of reductionism needed to site to root of consciousness. Meaning would it be like a physical molecule that is crossing some settled membrane or would it be a electric signal? That pretentious Something in the cell. Where did he think we would find consciousness and you know his own civil suit telling share he said to me that? Asra if you took the dodge but held apart brick by brick to discover the source of its beauty. All you'll find is rubble. It's the same that the brain the emergent complexity from simple individual parts. Actually what accounts for its essential mystery and this made a dramatic impression upon me back in the nineteen eighties because I realize that this is the reason by cancer will not yield it. Secrecy Secrets through a reductionist approach. Because think of it one can't cancer starts always in one sense that has gone through but this is now going to divide more rapidly than normal counterpart so if a normal cell divides in one week becomes to sell this cell. Cancer cells will become to sell in twenty four hours. So it's str- it's Traversing journey so rapidly beans that it has to double its DNA at such speed that it's going to make more and more copying errors in the DNA and each editor is what's called the mutation so when one cancer cell divides into two doors to sales now have picked up new mutations. Those store divided into more and the next four cells have new mutations this is why treating cancer as one disease is like treating. Africa's one country cancer is not the same in one place from one day to the next because sales have now acquired. You actress six. Which means that they're still dividing and they're still cancerous but they metabolize drugs. We give them differently now. Because you passenger mutations they have picked up this is why even something that looks the same so obvious. A big tumor. That humid inside itself contains infinite of Kansas thousands and thousands of potential new. Kensuke and this is why to sort of impossible to keep ahead of the curve ahead of the Kansas City and try to develop Techniques to target one because by the time we take out the tumor and study eat and develop a precise treatment for it. Cancer is moved on and has become a different disease because of all the new mutations and so this is the kind of reductionist dualistic approach that I'm talking about. We should just be able to become realistic. Realize that cancer is too complicated for us on this fan. It's like artificial intelligence. Basically we don't even know what are the parameters that he is recognizing distinguish between two things. We don't know it. We just know that machine learning will eventually be able to do it but we don't understand how all we can do is write algorithms to start that process of machine learning. This is what I'm saying. We don't have to understand every single signaling partway in cancer cell in order to cure it. We have to just find the earliest possible algorithm. And try to get rid of it. Then I think we need to take the blinders off our is. We need to see reality for what it is. We need to stop over. Spur exaggerating and using hyperbolic language to describe to the public which who is starved for good news and cancer and try to Basically delude them into thinking that. Oh great treatment has been discovered and forget to say in mice You know we have to stop using hyperbolic language to wall drugs that are improving survival by two months as game changes. We have to stop mollycoddling public. As if they are too vulnerable and should not be told the reality and the truth. Why on the On colleges when they talk about immune therapies using Gardez. Why don't they ever mention the fact that he can not distinguish between normal and cancer cells? It kills all the sales and resulting toxicities so bad that all industries auditor rising to try and control the side effects of Cardi therapies. It's just not right to do I. I'm not saying therapies. Shouldn't be followed. All I'm saying is that may be using the same party therapies and earliest stages of the disease when we don't have kilograms of tumors to kill and maybe making them war specific finding the right Zip Code and address for the cancer cells. An arming that. He sells with them. That's the kind of thing we need to do. We know what we have to. We have to just stop this me to meet to kind of approach and keep doing the same old same old. It's been interesting the last couple of years as I speak to. A wide variety of science researchers authors investigators and journalists about different areas of science from medicine to environmental science to climate science. And it feels like we are coming out or slowly starting to come out of a stage of a wider stage in science. Where we we've kind of feel like we've squeezed. Every last bit you can get out of a reductionist worldview and it has been good for us. In many places we've learned a lot by by that worldview but we're starting to find its limitations and it's been interesting to hear other areas of science who are very much looking to zoom out and looking at a more complex view of something that they have mostly been looking at an a reductionist way for a lot of time and it seems like perhaps we need to do the same in medicine and cancer research. I'm very optimistic and About the future of cancer research because Mark My words. Rochelle no matter what people try to do. The what's coming in all of healthcare not just cancer is a preventive approach. We don't have to treat disease. We have to identify and prevent disease as my friend. Lee Hood says instead of the elderly. We should have the wilder individuals. The well elderly who live To the maximum life span that Humanity can Experience and then die Without the crippling horrible chronic diseases that are affecting us now walk how we do that is by then defying the footprints the networks that are perturbed before diseases become apparent. And we have to start doing that. Work now do identify those so that twenty is from now we can at least have implantable devices that can be put under the skin of infants born and that can start the surveillance that is needed for the For the targeting and Detection of the earliest signs of any disease not just cancer. Alzheimer's disease urologic diseases mental illnesses. Everything should be detected early so just as we end if there are people listening who are interested in supporting Cancer Research. Closer to type. That's close to your heart. A cancer research that is focusing on a more complex overview research. That is looking at a more preventative. more preventative measures. You have some places or some shoutouts that you WANNA do for research at UC. That should be supported more. I would Give a shout out the tissue depositry. I think it would help me. A lot of people. Just give ten dollars a month. Even just for a yeah. That would be amazing or whatever amount you can give My website is available. As Roma's DOT COM. You can go on. There's a donate button apart from that. I think that healthy living is very important. Preventive measures and lifestyle changes that guarantee A good sense of wellbeing. I think mentally speaking. Psychologically socially every way we should try and optimize Factors that help us Liberal healthy life. I think those are all important issues that we should be looking into other. Thank you much for your time today. It's been really good talking with you. And I have very much enjoyed reading the book I found it very impactful and I will remember it. Thank you so much for this genre. Share you ave good questions and I hope that your support of this idea of finding against Early will be reflected in your audience responses. Well thank you learn by coaching. Something for you okay From Emily Dickenson. She says a word is dead when it is said some say icee just begins to live that day. That's an excellent quote. Thank you and if you want to learn. More about Azure Raza her research or her book the First Cell and the human cost of pursuing cancer. To the last as always you can find all those links to click on our website for the show notes in this episode science for the People Dot C. Science for the people is listener supported. You can find some patron on where you can support us with monthly donations in any amount. Your support keeps US afloat and able to keep making great new episodes. And we thank you for it. The show was produced by Shel Saunders and edited by Ryan Bromsgrove. We get help with special projects from Kale Myers. Our theme song was written and recorded by facto pattern and its title is binary consequence the show was hosted by Bethany Brookshire. And he has rea- Marian Kill Gaur and me Michelle Saunders.

cancer Cancer Research American Cancer Society lung cancer United States America North American Cancer Society Md researcher professor of medicine and Dire National Cancer Institute Canary Cancer Center Kansas Rochelle Saunders baseball scientist myelodysplasia syndrome Mda leukemia
Learn about leukemia, advancing care for leukemia patients

Mayo Clinic Q&A

24:24 min | 5 months ago

Learn about leukemia, advancing care for leukemia patients

"Welcome to clinic. I'm not sange caca. Leukemia is a cancer of the blood forming tissues including the bone. Marrow and the lymphatic system. There are many types of leukemia. Some affecting children while other forms most a current adults indeed approximately one and a half percent of men and women will be diagnosed with leukemia at some point during their lifetime. Joining us to discuss. Today is dr james foreign chair of the acute leukemia. Myeloid neoplasms disease group at the american cancer center. Welcome to the program to foreign. Thanks very much good morning. Thank you for speaking with me so you know. We hear about leukemia. and sort of cancer. the blood-forming tissues. Can you actually explain what happens. Yeah simplistically we break. Key down into acute leukemia and chronic virginia and in acute leukemia. It's it. I'm glad you use the word cancer. That can be confusing for people. It is a blood cancer. And it's the early bone marrow cells that are growing throughout your life. Other than my lloyd ones that we call acute myeloid leukemia or the lymphoid one that typically would turn into antibody producing cells or t. cells Some cases that for some reason become just regulated and behave as a cancer. Overgrowth the bone marrow. Still into the blood and doesn't really behaved like other cancers. It's not something where there's a stage necessarily you have it or you don't have it and increasingly common as a matter of fact the The chronic leukemia is our little bit different They're more process of accumulation of cells. That should be turning over dying. Normally they begin to accumulate lymphoid. Ones that we call. Cll or my loved ones. We call cml and the chronic ones take a different path. A usually Developer years as opposed to the ones that developed over months or sometimes shorter. So you mentioned About leukemia. Being a blood cancer when we think of cancer we think of growth and lumps and bumps does. Leukemia presented a similar way. No it's typically. Nab normal blood count If you think about your blood being red cells and white cells and platelets you see a disruption in the normal numbers or An increase in the white cells typically And so that you end up with nonspecific symptoms at first fatigue bruising sometimes fever the white cell count is dropped because of leukemia And so that you don't typically end with lumps or bumps now the exception to that is. Cll you can get lymph node involvement. You may notice lymph nodes in your neck or in your shoulder But most commonly somebody comes in other words picked up just on a regular blood count. They can have another normal. White cell count for the chronic came is or they come in with nonspecific symptoms over a few weeks of feeling fatigued out of breath and having fever and somebody notices and not normal blood count. There are situations where you could have leukemia with a skin rash or came here form a lump but that's that's exceptional. I see and you talk about the different forms of leukemia. What actually causes it a great question. We've been studying that question You know We don't know here's the short answer we know there's certain risk factors In adults the most common leukemia is called acute myeloid leukemia or am l. We know that if somebody's a smoker. They're a little more likely to get leukemia or Obesity associated with increased risk of leukemia. We used to say that acute leukemia did not run in the family. There are some rare situations with what might be true. We're learning although also exceptional and we haven't found a specific cause that we can attribute an individual almost ever. There's one exception to that if someone's been treated for another cancer let's say. They were treated for breast cancer or lung cancer and they got radiation treatment or chemotherapy. Less than one percent chance that you can develop a leukemia from that. Just from the stress on your blood having been treated with chemotherapy or radiation therapy. And so very rarely. We'll see somebody who's been treated for another cancer and we can say. The leukemia came from. That mostly happens when we don't know why they were. Actively studying for the chronic. Leukemia is especially the l. l. com chronic lymphocytic leukemia. About ten percents possibly more than can run in the family. That was something we didn't. We didn't think in the nineteen nineties nearly two thousands So there may be some familial risk to that But even that is not something you can control not something you can screen before and we're still learning about what the risk factors are for people in which gets the yellow. When that happens. I say okay. And so we talked about the The signs symptoms and then in terms of diagnosis. You mentioned it could be up on a on. A blood test is that. Is that the main way. That chemo is diagnosed. It is leukemia. You know is an old greek word for white blood is what it really means and classically somebody would have a very high white cell counts and their blood would take on a whitish tinge Back in the eighteen hundreds early nineteen late. Eighteen hundreds early nineteen hundreds was recognized so we think of it as a disease. The high white cell count and that's typically the case in children young adults even into middle age older adults. It presents a little differently with a bug counts can draw because the leukemia. We'll overthrow the bone marrow where your blood is produced and she can. Paradoxically have a low blood count and need to have a evaluation of bill with a bone marrow biopsy to find it but in all cases there's virtually all cases. There's an abnormal blood count. It is the clue and so. That's the tricky part is that you often don't know until you have some symptoms that you put up with for a while. You're feeling rundown have fevers. Or somebody knows his blood count then they have to actually go and chase it and make make the correct diagnosis. But that's a point that you mentioned. I mean we're in the winter season now now thankfully hasn't been a tremendous amount of flu because of of masking but some of these symptoms to me so to suggest a it could be like flu like symptoms. How would you ferenci eight if you experience the these types of symptoms know. Ironically somebody will come in with the flu or chest infection or cold feeling more rundown than they thought they should and then find that had blood count and realize in retrospect they've been feeling rundown for longer. There were some studies. Oh gosh almost twenty years ago. That suggested leukemia was more likely to be diagnosed than follow winter. And there was a seasonal variation to it and Not that that's definitive That happens but i think it's more that's the time of year when we get other things like cough or cold or flu and we then seek medical care and somebody realizes the blood cancer and then you think back then yes i guess i really been unwell longer than i thought i was There are situations where somebody has a routine blood count especially the chronic leukemia's and find the white so count is very high. Didn't know they had something. And then they go down the path of seeing the hematologist and finding they had chronically team. Here that happens sometimes. Also when you talk about dookie you mentioned about white cells. Can you just explain to us you. You've mentioned red cells white cells. What are the difference. Yeah your blood is red. Because it's predominant red cells and a red cells carry hemoglobin carry oxygen gives you strength We call reduction in your red cell and nimia and And so if the red cell count is low you're typically tired or fatigued You haven't anemia and their multiple causes leukemia. Rare cause of that you tired deficiency or something else white cells are your immune system The fight bacteria fungus viruses. They're different types of white cells. The type of leukemia have if somebody has lee came. Yeah is labeled by the type of white cell that cell would have been a mine would sell like sell the fights. Bacteria void sell. We would call that lymphoblastic leukemia or tv. So your white cells are your immune system and the different components of it and then you're played this. Stop you from bleeding. They clump together. When you injure yourself or tight yourself and the plate account can can drop if came as active when people can bruiser bleed more easily so this is the three major components of one. Thank you for explaining that and then we talked about the different types of leukemia of for example. I think you mentioned acute lymphocytic leukemia in children. How does that affect the treatments. Well it's one of great successes really the last forty fifty years in in In cancers the treatment of childhood leukemia so you're absolutely right acute lymphoblastic leukemia. We call it. All is actually the most common cancer of children. And it's not a common thing but it's it's well known to happening. Children presenting with high white cell counts. And we've learned through a series of studies over decades that we can cure the large majority of children in some cases seventy percent eighty percent or higher with intensive chemotherapy treatments And so that's been a success story. It's not easy. It's a hard road hard for the person heart for their family but a But a remarkable thing that we can we can do that. In children and adults even adults get acute lymphoblastic leukemia which is less common over. The age of twenty think seem to get a different strain of it the genetics. So they're looking a little different. They're not as sensitive to. Chemotherapy was progress there as well. We have better treatments and better strategies but not quite as effective was in children and even well the average age of getting acute leukemia around seventy so we think of it as a childhood disease but really it happens in older adults and so that makes it a little bit tricky. When they're maybe not as strong not as fits. Have they started more difficult with advocate. Leukemia it's uncommon and what we call the adolescent or young adult population. We call it in hawaii population But still it happens and that's a group of we can actually Do very well as long as we can keep somebody coming for treatments and keep them on protocol and and get them through all the therapies. They need chemotherapy the mainstay of treatment fully kimia or the other treatments that you use as well. Yeah it is my my hope in my career that we stop giving chemotherapy one day and But it's still essential for leukemia especially in younger dogs. Chronic leukemia is almost completely moved away from therapy. We learned a little over twenty years ago. That for chronic myeloid leukemia. Cml that there's a targeted therapy we can use all patients with c. m. l. We'll have an abnormal chromosome. Did they acquire. They're not born with it. We call it the philadelphia chromosome because it was discovered in philadelphia. And there's a their medications pills that can actually specifically target that philadelphia chromosome to put people into long term remissions and we've learned for cml in the nineteen nineties. The average person lived for years in two thousand and twenty. Somebody was c. L. has the same long term survival as another person their age. Who doesn't have stand now as long as they're under therapy and under observation so that's been also remarkable success story for c. l. l. which is a little more common than adults. We used to give chemotherapy. We learned in some random studies published in the last two three years one of which was published by one of our colleagues teach. Nfl when he was at mayo clinic. The targeted oral therapies which are much easier to take are more effective than chemotherapy. Give better long term survival. So in the chronic leukemia is it's less and less common for us to talk about human therapy and acute leukemia. We still rely on chemotherapy to get remissions. We're looking at antibody. Based treatments we're looking at immune based treatments. We have some solid leads there and we can do bone marrow. Transplants in certain situations Secure them. But we're looking for more targeted treatments. And i hope that they will come in my career. When i don't have to use the word of chemotherapy just extend that thought for one second. I'm sorry to jump in. Lee's i'd say the problem with that works and so it's a scary concept and people have a notion of mental notion from tv movies or from somebody in their family from you know ten or twenty years ago. How difficult it is. But we're better giving it we get people through it. Were very good at the side effects. Now and the only reason to do it because it works and when the day comes we have something better. Will you know we. We will rush to move to that but but right now they work and so we use them so given the different forms of treatment that either currently available on the horizon. What does mayo clinic doing. In terms of clinical trials. That patients may be able to access. No i think that's really critical question. You know to to to get better treatments. We need clinical trials and we are believers. And then we're innovators and at the front of the field and yeah My colleague mark lasalle. Who's acute leukemia. Dr rochester leaves one of the national study groups and killed leukemia We've had leadership in. Chronic leukemia is as well We are looking at multiple avenues for patients who are newly diagnosed and also for those who've been through treatment and didn't go into remission or relapse for that where we're using innovative sometimes chemotherapy but more likely innovative targeted treatments or innovative. Immune treatments so we have a series of clinical trials depending on the exact situation That we're looking to try to get better outcomes for patients trying to get more emissions second time around or even upfront and your people more often and so. That's that's really a critical Avenue for us one of the great innovations in acute leukemia so far applied only children but being developed in adults or children in adolescence. I'll say is the use of something called kartini therapy. And i'm not sure if you've heard of that but it stands for america. Antigen receptor t. cell and that's an immune treatment where you take a person's own t. cells You collect their their immune cells from their blood genetically modify them to target them to fight that leukemia. And you give them back to the person to really unleash their immune system to fight the leukemia. Now that's been approved in All in children and adolescents. Were studying that. All in adults. We're looking for ways to do that. And other routine news as well and We are now At the front of the field mayo clinic and doing that but that's really been a massive innovation and It's complicated and expensive and takes resources but we're really putting a lot of pieces resources into that to the field forward foreign as you mentioned you know. One of the distinguishing features at mayo clinic is the innovation and so it patients who aren't at mayo clinic. But they hear about these things or they want to get a second opinion to see if they may be eligible to try these new treatments. How should they go about doing that. Yeah i mean That's important to us. We want to extend this to more people. we and democ has actually been useful in one way it's showed us that we can reach more patients electronically through virtual concerts and virtual visits than we appreciate it in the past and we are making an active effort to reach out to patients. Who aren't necessarily in jacksonville. Florida or phoenix. Arizona rochester minnesota. Excuse me to make sure they can access us even virtually for or second opinions and so we've active pathway and go into the mayo central appointments office we've actually expedited and acute leukemia. Pathway so patients can get more rapid appointments so that we can reach out to them even if they're not in our media area Advise them on what their options are and in some cases maybe have them come to mayo clinic it. There's something we have that they can't get where they live. Which is often the case. Yeah as you said. The health care is critical. And you know we're here at mayo clinic. We're trying to address health disparities. Have you seen that in terms of Patients with leukemia and how various disparities can affect access to calf. Yeah that's a real issue and it's a national issue. And i think we've we've always kind of known it but really i've come to appreciate it in the last few years that we need to extend to get better outcomes for people. We really have to extend therapies those. Who can't who in the past could not easily get them. So you're absolutely right. There are some recent Studies that show for instance In the african american population that they're worse outcomes with the leukemia. We think some of that might be because of the way that People access care We're committed to trying to address those disparities. We think that are built to reach people. Virtually true a virtual concept or consult on zoom for instance may help give advice in that situation and we're looking for ways to impact on that We haven't appreciated any true disparities and who gets what type of leukemia Cll chronic lymphocytic leukemia. And maybe more common in a caucasian populations in an african american population but there aren't really major disparities otherwise in terms of who gets it but who gets care for it they're definitely disparities and that's something that we really are committed to try to address into to reaching out to more patients now. That's wonderful thank you for that in your your teams hot work at f. So we talked about the different treatments. What's the what's the prognosis like When patients get treatment now It's variable and on the person and the actual strain of leukemia. They have as i said already. If somebody has chronic myeloid leukemia We can do a lot. We can We think get them on. Track to live alone jetty there would have had otherwise for. Cll we have taken a disease. We're in the past. Somebody might have only lived nine or ten years and we've about double that and sometimes much more for. All in children we know See that about ninety percent of children are in some studies over ninety percent in adults they allow. Were about half of that. We've made some impacts. We've improved that by ten or fifteen percents in the last decade. We have some new avenues with immune based treatments to try to augment that and so it's not as high as we'd like it to be but it's still real number and we're now pushing to a point where about half the people Half of adults with acute leukemia can be cured under the age of sixty or sixty leukemia's leukemia. Little more difficult and sometimes people who have what we call a co morbid disease. They may have Advanced diabetes or they may have heart disease or something else that makes it hard to go through treatment and then you have to individualize the goals and individualized that there be. We've learned from some studies done over ten years ago that it's better to treat the not treat even if you can't cure somebody you can help them feel better. You can help them live longer. You can improve their quality of life and so the first goal is to get somebody better in the second goal is to see is there. Is there an opportunity to ensure that person when the time is right and so we can impact on the disease for all patients but the prognosis is still variable and depends on the person the actual strain of you when you look at the the covid nineteen pandemic and how that's affected healthcare in general acid. Would you say your practice in treating patients with leukemia. It's been hard it's It's been really hard for my patients. I had four clinic patients tests positive for covid last week on wednesday and almost every other day. Somebody's gonna testing positive for covid. Nineteen where you are in the country. There are different rates different times and florida's been a little more active lately. I know arizona were Mayo clinic has a hospital as a lot of patients. And minnesota's been up and down and It's hard to go through chemotherapy treatments and it's hard to go through immune treatments when somebody has covered infection. And so that's been very complicated. We have gotten many patients. Through cove into the damone. Yeah we've had to halt therapies or Change therapies Sometimes it's been a little harder for people but not always We know that it's riskier. Somebody has leukemia and had covid infection. So we really are asking our patients to To follow cdc guidelines and maintain social distancing. We're very hopeful that vaccine efforts roll out into the population that will impact on it. But i know that's months away so i think it's been a difficult and the problem is leukemia does need treatment. Have it and so that we've had to balance the risks of the treatment with the risks of the pandemic and work on that person by person to achieve those goals. You touched upon the vaccine and as you said You know that that is coming. Howie how you seeing getting a vaccination and if patients currently having treatment about balancing that. It's a really hard one in cancer in general and specifically in a blood cancer when you need your immune system to generate a response to a vaccine and yet we're sometimes giving treatments that impair your ability to do that. If we're giving extreme the lowers your immune system you can imagine you may not get as much benefit from a vaccine and The problem is we don't have much day to go on. We know in well people. What the effectiveness of vaccines are we. Don't know when people who are going through treatment for chronic disease or for a cancer our guidance at the moment is for the vaccines that are currently approved in the united states. We believe that they're safe. We don't know if they're as effective. We do want to do that. But not in the middle of chemotherapy treatments when they're at least likely to work and so As the vaccines come we're going to have to learn how to stage that my real hope that we can get more of the population vaccinated. Because i think it's more of a help to my our patients If the family members and those in their community are vaccinated that the individual with leukemia is not at risk and getting covid. That's going to be my real hope. But that's not the way. I think about foreign anything else. You'd like to discuss that. We haven't touched upon no leukemia's a shock when you hear the word. It's a shocking word and There's sometimes they rush to once again onto a treatment or start something immediately. But i think actually if you if you or somebody in your family were diagnosed with leukemia. We'd want you to stop and catch your breath. Look to of the resources to make sure your as educators you can be in the first few days to know. What do you need to do There are some excellent resources for patients. Mayoclinic dot org is excellent. Leukemia would keep me lymphoma society l. l. s. dot org Mayo clinics part of the national comprehensive cancer network which has great Patient virtual websites for latronic learning nc n. dot org. And so you have a chance to learn about it and not get overwhelmed by it. We've built a pathway where people can access us an expedited fashion. Even if they're not able to come to mayo clinic so that we can help them from a distance and help guide them and their and their physicians locally and so we'd like to help and so my message would be to stop and catch your breath and get the best advice. You can Because we can do something for everybody who has leukemia with. Cure it or not we can. We can on that positive note. We've been discussing the diagnosis and treatment. Leukemia mayo clinic. Oncologists to james foreign chair of the acute leukemia disease group but mayoclinic cancercenter anchor being with us today. Thank you very much mayoclinic q. And a. is a production of the mayo clinic news network and is available wherever you get and subscribe to your favorite podcasts. To see a list of all male clinic podcasts. Visit news network dot mayoclinic dot. Org then click on podcasts. Thanks for listening and be well.

leukemia blood cancer cancer Leukemia mayo clinic lymphoblastic leukemia flu acute leukemia Chronic leukemia dr james Myeloid neoplasms disease american cancer center lymphocytic leukemia fatigue bruising sometimes fev chest infection philadelphia
NEJM This Week  December 12, 2019

NEJM This Week - Audio Summaries

24:13 min | 1 year ago

NEJM This Week December 12, 2019

"Welcome this is the New England Journal of Medicine. I'm Dr Michael Beer this week. December Twelfth Two Thousand Nineteen we feature articles on a randomized controlled trial of Ebola treatments MMA topalov in COPD assimilative in chronic myeloid leukemia and therapeutic therapeutic hypothermia for cardiac arrest with non shock. -Able Rhythm a review article on penicillin allergy a case report of a man with Disney. I and abnormalities on chest imaging and perspective articles on machine learning and the cancer diagnosis problem on kicking the can down the road. Food and on Azure a randomized controlled trial of Ebola Virus Disease Therapeutics by Sabu Mulago from attitude. Nacional I'll do a sheriff's Biomedical Democratic Republic of Congo in this trial of four promising experimental treatments. For a Bulla virus disease eve six hundred eighty one patients of any age who had a positive result for Ebola virus AREN A on. Rt Pr Essay received Standard Care and were randomly assigned to intravenous administration of the triple monoclonal. Antibodies Z.. Map The control group. The antiviral agent Ramdas severe the single monoclonal antibody Mab one one four or the triple monoclonal antibody Red Jen Ibi. Three patients were enrolled from November. Two thousand in eighteen to August two thousand nineteen at which time the data and Safety Monitoring Board recommended that patients be assigned only to the MAB one one four and regine agenda Ebay three groups for the remainder of the trial. The recommendation was based on the results of an interim analysis that showed superiority of these groups to Z CMAP and Rim Desa Vir with respect to mortality. At Twenty eight days. Death had occurred in thirty five point one percent of patients in the MAB. One one four four group as compared with forty nine point seven percent in the Z map group and in thirty three point five percent in the regin e B three group as compared with fifty fifty one point three percent in the Z map subgroup a shorter duration of symptoms before admission and lower baseline values for viral load and for serum creating and aminotransferase levels each correlated with improved survival for serious adverse events. Were judged to be potentially related related to the trial drugs both Mab one one four and read Gen three were superior to Zima in reducing mortality polity from EDD scientifically and ethically sound. Clinical research can be conducted during disease outbreaks and can help inform the outbreak rake response Myron Levin from the University of Maryland. School of Medicine. Baltimore writes in an editorial that regin e B three and Mab one one four showed significantly superior efficacy in preventing death from the therapeutic effects of these two monoclonal antibody products were sufficiently only promising that it is worth exploring the cost the number of doses that can be manufactured and the possible target populations for us the product act that would be more suitable for large scale economically viable production and the storage requirements and stability over time are unclear. A single single monoclonal antibody based product offers some advantages it would be desirable to have stockpiles of both products if licensure is obtained for for them the efficacy of these two agents in reducing the case fatality rate was greater among patients who sought treatment early after symptom onset who had low viral loads and who had lower baseline creating or Allen aminotransferase levels. That is these products were more effective in patients who were less severely. Ill and who are ill for shorter durations. Social engagement with the community can encourage patients chance to seek care early but early care of patients also requires the availability of rapid diagnostics and ease of travel to treatment centers. These issues must be addressed in future Ebola outbreaks to enhance the therapeutic effect of the monoclonal antibody products that we hope hope we'll be available motto for the Prevention of Acute exacerbations of COPD by Mark Transfield from the university diversity of Alabama at Birmingham observational. Studies suggest that Betablockers may reduce the risk of exacerbations and death in patients with moderate or severe chronic obstructive pulmonary disease. COPD but these findings have not been confirmed in randomized trials in this this randomized trial. Five hundred thirty two patients between the ages of forty and eighty five years who had copd were assigned to receive either a Beta blocker her extended release motto parallel or Placebo. The trial was stopped early. Because of futility with respect to the primary endpoint of the time until until the first exacerbation of COPD and safety concerns there was no significant between group difference in the median time until the first exacerbation which was two hundred two days in the Matteo Paul Group and two hundred twenty two days in the Placebo Group. veto-proof was associated with a higher risk of exacerbation leading into hospitalization the frequency of side effects. That were possibly related to Mottola was similar. In the two groups. As was the overall rate of non respiratory serious series adverse events during the treatment period there were eleven deaths in the Topalov group and five in the placebo group among patients with moderate or severe. COPD who did not have an established indication for Beta blocker use the time until the first COPD exacerbation was similar in the Motto Parallel Group Group and the Placebo Group hospitalization for exacerbating was more common among the patients treated with NATO. Paul William mcney from the University of Edinburgh. Medical School writes in an editorial that cardiovascular disease which is common in patients with COPD has a profound found effect on morbidity and mortality yet. The condition is often unrecognized and as a result is under treated current. COPD management strategies energies indicate that Betablockers should be prescribed in patients with COPD who have cardiovascular indications even in those with severe COPD COPD. So what do the results of this trial by Transfield mean for the use of Betablockers in COPD in answering this question it is important to understand the clinical composition of the trial population patients with COPD. Who did not have overt cardiovascular disease and thus did not have an indication for treatment with a Beta blocker this population contrast with the patients in most observational studies that have shown positive effects of Beta blockers as in patients with COPD who had an indication for treatment with a Beta blocker thus the results of this trial are applicable to patients? Who did not have a therapeutic indication for treatment with a Beta blocker and who have severe? COPD with a high risk of severe exacerbations. The trial does not provide any support for the use of Beta Ada blockers in such patients for the prevention of an exacerbating of COPD. There is little evidence that Beta blockers are currently prescribed for for this indication on the contrary there is good evidence that physicians are still reluctant to prescribe betablockers even in patients with COPD who have proven cardiac indications the results of this trial should not deter the use of Beta blockers in patients with COPD who have cardiovascular indications with the caveat that the risk benefit ratio should be considered carefully in patients with very severe COPD at high risk for severe exacerbation assimilative in chronic myeloid leukemia after able kinase inhibitor. Failure here by Timothy Hughes from the South Australian Health and Medical Research Institute Adelaide South Australia assimilative is a potent specific orally orally bioavailable BBC are able one inhibitor. That has a mechanism that is distinct from approved able one kind inhibitors. assimilative targets both native eighty and mutated VCR able one including the gatekeeper T.. Three one five. I mutant this phase. One dose escalation study enrolled one hundred hundred forty one heavily pre treated patients with chronic myeloid leukemia. CML WHO had resistance to or unacceptable side effects from at least two ooh previous ATP competitive tyrosine kinase inhibitors tk is the maximum tolerated. Dose of assimilative was not reached among patients with chronic phase. CML WITHOUT A T. Three one five. I mutation the incidences of complete cytogenetics response and major molecular accurate response. At twelve months were seventy percent and forty eight percent respectively among patients who entered the study with the BBC are able one of zero point one one percent or less at baseline a deep molecular response was achieved or maintained in sixty percent. During the study dose limiting toxic effects wchs included a symptomatic elevations in the light pace level and clinical pancreatitis. Common adverse events included fatigue headache or thriller hypertension Shen and Thrombosis Subpoena as seminar was active in heavily pre treated patients with C. m. l.. Who had resistance to or unacceptable side effects from tk okay is including patients? In whom punitive had failed and those the T.. Three one five. I'm mutation targeted. Temperature Management for cardiac arrest. With non shock. -Able Rhythm by Joan Baptiste lasker. Who from the University Hospital Centre? Not France moderate therapeutic hypothermia is currently recommended to improve neurologic outcomes in adults with persistent. Coma after resuscitated out of hospital. Oh cardiac arrest. However the effectiveness of moderate therapeutic hypothermia in patients with non shock -able rhythms a Sicily or pulse? Lewis Electrical collectively is debated this randomized trial compared moderate therapeutic hypothermia. Thirty three degrees Centigrade during the first twenty four hours with targeted normal Thoraya thirty seven degrees centigrade in five hundred eighty one patients with coma who had been admitted to the intensive care unit after resuscitation from cardiac arrest with non-chargeable Rhythm on Day Ninety ten point two percent of patients in the Hypothermia Group were alive the cerebral performance category scale score of one or two as compared with five point seven percent of those in the normal Thoraya Group mortality at ninety days did not differ significantly between the Hypothermia Group and the normal thermes group eighty one point three percent and eighty three point two percent end respectively the incidence of pre specified adverse events did not differ significantly between groups among patients with coma who had been resuscitated Acetate from cardiac arrest with non shock. -ABLE RHYTHM MODERATE THERAPEUTIC HYPOTHERMIA AT thirty three degrees Centigrade for twenty four hours led to a a higher percentage of patients who survived with a favourable neurologic outcome at day. Ninety than was observed with targeted norm author Mia Penicillin Allergy a review article by Mariana castells from Brigham and women's Hospital. Boston penicillins have been the most common cause cause of drug induced fatal and nonfatal. NFL AXIS in the United States and the United Kingdom the first case of fil access associated with penicillin was reported in one thousand nine hundred forty five and a report from the World Health Organization in one thousand nine hundred sixty eight stated that the rate of death from NFL axis was zero point. Zero Duro two percent. No data suggests that the frequency of allergic reactions has increased in the past sixty years and there is convincing. Evidence that penicillin penicillin sensitization is lost over time. A label of penicillin allergy is commonly acquired in childhood when allergic symptoms can and be confused with symptoms of viral or bacterial illness. Up to twenty percent of persons in the general population are labeled as allergic to penicillin penicillin by the time they reach adulthood each year. Approximately ten percent of persons with true I immediately penicillin reactions as evidenced inst- by a history of an immediate reaction and a positive skin test lose skin test reactivity after formal allergy assessment with skin skin testing and ingestion challenge less than five percent of persons with a remote and low risk history of penicillin. Allergy are found to be truly truly allergic a penicillin. Allergy label that is acquired in childhood is frequently not questioned and may lead to multiple non Beta lifetime exposures adverse effects and additional antibiotic allergy labels. The label of penicillin allergy should be analyzed with skin testing contest. Exposure patients with true penicillin allergy can be desensitized with a slow escalation protocol under physician observation. A twenty year old man with Disney and abnormalities on chest imaging a case record of the Massachusetts General Hospital by Robert Hollowell. Yeah Well and colleagues a twenty year old man with a history of e cigarette use also known as vaping presented to the hospital because of a history of Disney intermittent fever ever joint stiffness and nasal congestion approximately six point five months earlier fatigue fever chills and cough productive of rust colored sputum mm developed. He was evaluated by a physician who advised him to discontinue use of e cigarettes and of course of Zip through my son was prescribed. Despite the Empirical Antibiotic Bayada Treatment the symptoms persisted chest. Imaging showed ground glass non-euro passages that were most prominent in the lower lungs on presentation to this hospital. The patient reported Reinerio's with Yellow White Mucus. Disney intermittent fever joint stiffness and nasal congestion the persistence of fever and development of nasal and sinus symptoms arose suspicion of systemic process such as vascular disease the Perry Bronco Vascular distribution and basil or prominence of the ground. Glass opacity is seen in. This patient were consistent with areas of Alveoli hemorrhage that often accompany these symptoms surgical lung biopsy showed diffuse pulmonary hemorrhage the patient also had high tigers of Anti Cardio Life in I G- antibodies anti phospholipids Syndrome was diagnosed the temporal association between the patients e cigarette use and his pulmonary symptoms suggested suggested that exposure to e cigarettes may be linked to his disease process machine learning and the cancer diagnosis problem. MM-HMM NO GOLD STANDARD A perspective article by Ottawa. Adamson from Del Medical School University of Texas Austin Machine Learning has has the potential to be extremely useful in Madison particularly in the interpretation of medical images. Although machine learning has a great deal of promise it also has has inherent limitations particularly when it comes to diagnosing early stage cancer to understand why it's important to appreciate how the technology works works. Most machine learning algorithms used in medicine are trained by means of a process called supervised learning in which the computer is presented with images images that have been labelled using an external standard that serves as the ground truth. Supervised machine learning requires a set of images that pathologists adjusts have categorized as either cancer or not cancer. The Algorithm is developed on the basis of machine identified discriminating factors in a a subset of those images that training set and its performance is assessed with the remaining images which the machine has not previously seen the test best set the algorithm may then be tested on additional images and can be fine tuned and revised at each step the validity of the algorithms rhythms conclusions is dependent on the quality of the external standard of pathological interpretation. Reliance on this. External Standard is problematic however since machine learning doesn't solve the central problem associated with cancer diagnosis the lack of a histo-pathological the logical gold standard kicking the can down the road when medical schools fail to self regulate a perspective article article by Sally Santan from Virginia Commonwealth University School of Medicine Richmond every spring at. US Medical School Commencement Deans of Student Student Affairs and curriculum stand on stage. Pledge along with the graduating class to do no harm and hood. They're students shake their hands and confer further medical doctorate degrees all the while they know in their hearts that there are one or two or possibly more of these new doctors whom they would not allow to care for their family. Aware of these students academic limitations or unprofessional behaviour. The Dean's nonetheless allow them to graduate. These authors believe that allowing inadequate or inappropriate candidates to become doctors is unacceptable and we cannot continue Tinubu to neglect our responsibility. In this way it's natural of course for some students to struggle and for medical schools to work with them to overcome their difficulties with academics. That makes or professionalism though there are no data on students there is evidence that some unprofessional behavior on the part of practicing physicians can be remediated. Aided in rare cases however students who are permitted to graduate despite unprofessional behaviour go on to become disruptive or incompetent clinicians it is our duty as leaders in medical education to develop a competent workforce that will provide safe and compassionate care these authors. Believe do that. Medical schools will need to partner with accreditation bodies create degree. Granting off ramps and make some tough decisions my patients prolonged goodbye. A Perspective article by China I K. D. O. B. From Yale University School of Medicine New Haven Connecticut. Do you know how to say OV- well in Swedish the patient asks his eyes light up like miniature moons cataracts shimmering with with childish joy. His mind having churned thought afterthought for ninety five years can't keep up now so he asks Dr E. K. D. O. B. This same question at every clinic visit. She smiles and pretend she is answering for the first time every time. No how do you say it. In Swedish over over the years his visits to the clinic have become less about the monotony of re staging his medical diagnoses. They don't spend as much time reviewing his Chart Dr. It feels a certain lack of direction in managing the care of a patient who has surpassed the average life expectancy in Igbo Culture in Nigeria Syria where Dr UK deal grew up men. His Age are called elders. On celebratory occasions. Elders would be arrayed in elaborate traditional. The tire native jewels and beads decorating their wrists and neck says they stood stoic strong and tall while talking drums reverberated berated in the background. Elders were revered and surrounded by members of their community. They were never alone Dr Welby marvels marvels at how different. Her patient's life is from those of the Igbo Elders. She lacks the words to ameliorate the painful silence that surrounds her a patient but she is aware of the reprieve offered by these clinic visits when he can share his jokes and memories and feel the attention of an audience audience even an audience of one so she listens patiently in our images in clinical medicine physical examination of a one day old girl. Born by vaginal delivery thirty six weeks gestation revealed a soft mass protruding from the External Genitalia. Ah The mass was noted to increase in size. When the infant cried she was able to pass urine and feces regularly? And Renal function was normal an L. tra- sound examination performed during the third trimester of pregnancy had revealed a pelvic mass in the fetus but further follow up investigations had not been performed warmed before delivery ultrasonography of the infant's abdomen. Confirmed Hydro culpas with vaginal distension. A normal uterus and no urinary retract delimitation neonatal. Hydro Post is an accumulation of secretions caused by vaginal obstruction usually related to an imperfect. Hi Man it is not often as large or as readily apparent on physical examination as it was in this case the infant underwent a high manal incision under general anesthesia on day. Three and the mass resolved follow up ultrasonography performed after two months revealed a normal urinary tract and Internal Genitalia and no residual mass a sixty nine year old woman presented to the rheumatology clinic for the treatment of severe joint deformities formalities. She had received a diagnosis of rheumatoid arthritis. Eighteen years earlier and the disease had been refractory to various treatments physical examination showed all nar deviation of both hands there was tenderness and swelling in the METACARPAL Falantil joints in both hands and in the wrists elbows knees and left ankle. Ankle examination of the hands also showed shortened fingers with loss of active finger reflection and an inability to make a fist traction action applied at the distal fallon. jeez allowed the digits to be stretched and the digits returned to their original positions when the fallacies were released see. See the video at any J. M. Dot Org plane radio graphs of the hands showed severe osteoporosis of the distant owner and radius and the carpal metacarpal and Fallon Geel bones. The observed telescoping phenomenon is a consequence of this bone resorption. The patient received treatment treatment with Tofa Sydney methotrexate low dose prednisone and I bend Roenick acid which reduced the pain and swelling but did not change hand functionality. This concludes our summary. Let us know what you think about our audio summaries. Any comments or suggestions may be sent to audio at Nj m dot org. Thank you for listening.

COPD penicillin Medical School Ebola Disney New England Journal of Medicin Betablockers Coma Mark Transfield United States Dr Michael Beer Rim Desa Vir Jen Ibi Safety Monitoring Board Biomedical Democratic Republic Congo Mottola Baltimore Sabu Mulago
Azra Raza on how we're failing cancer patients

The Current

25:28 min | 1 year ago

Azra Raza on how we're failing cancer patients

"Do you ever find yourself wading through your news feed on facebook or twitter wishing you could just call someone up and ask. What do I really need to pay attention to the try? What next a Daily News? PODCAST from slate every weekday host. Mary Harris tackles the news of the day going deep behind the headlines Lines. What next gives you news? You can't get by just scrolling on your phone. Subscribe wherever you get your podcasts. This is a CBC podcast Galloway. This is a podcast cast from the January twenty third edition of the current. This is fully shut my week. My father used to say you always hide behind your hair. I always had very very long hair. I've never been one. That's very creative with my hair. It's always been the theme length. The moment they told me I was GONNA lose my hair with devastating and it started falling out of my my head in folks Tracy be. Mitch is forty two years old. She lives in Halifax and was diagnosed with breast cancer three years ago. Naming naming her WIG Felicia for a laugh was just one of the ways. She said she survived. That ordeal wasn't cancer that she found those difficult. It was the treatment chemotherapy and twenty five rounds of radiation. It was probably one of the most horrifying things in my life. Never in my life today ever understand the word fatigue. My home at the time time had three levels and I had to stop halfway up my first level of stairs and couldn't make head to take a break. You'd be watching things on television Asian. And they they call it chemo fog and you lose your ability to pay attention. You're just in the almost fog throughout this treatment that the medicine send knocks you out the thought of ever having to go through chemo. Again with terrify me Tracy beam issues now in remission and feeling positive about her health but stories like hers. Hers are familiar to US Raza. She isn't oncologist who's watched thousands of patients and her own husband suffer from both the disease and the treatment and she'd I'd like to see the whole system change doctor. Rosza is a professor of Medicine Columbia University and the author of the first cell and the human cost of pursuing cancer to the last doctor. Good Morning Good Morning Matt. What do you think when you hear stories like that one from Tracy be mish about what she's been through and and how how she coped or tried to cope with the treatment that she received the primary rule of medicine is first do no harm and it's absolutely horrifying to hear be historian something that I see multiple times a day for the last thirty five years us? What she described is so true because literally like as someone said taking a baseball bat and hitting a dog with it to get rid of its fleas? That's how bad the treatment we are. Currently using to treat cancer is what is really most host. ghostly and unbelievable to me is that I landed in America and one thousand nine hundred. Seventy seven started treating a bone marrow. Cancer Acute myeloid leukemia. We were using to drugs popularly known as seven and three today in twenty twenty. I'm using they exactly same to drugs. Would they exact same tread for results are the results. The more difficult thing for for the patient to cope with or is or is it the disease itself because the there's the moment of diagnosis and that relaying bad news but as you're describing it it'd been the baseball bat. can be horrifying and incredibly debilitating as well. It's not just the diagnosis which carried its own stigma having cancer and its own Scary and life threatening consequences that one imagines but the treatment makes things even more grisly and the problem is that not only are we continuing to give the same treatment despite hundreds hundreds of billions of dollars spent and trying to find new drugs for the last sixty years. We even don't know how these drugs dugs work when they work for example. What is the exact mechanism of action of tha mock Sutphin? The most commonly used therapy in breast gums. Nobody nobody knows precisely how these things we think. We know that it's going to kill the salon. It's going to modify the behavior of that but really couldn't knowledge is lacking completely so the idea is that we have now a situation where curing sixty eight percent of cancers is that a newly diagnosed. That's great news. But it's not because we are using or have developed any grand new therapies. Most of it is still still being treated with chemotherapy. Radiation Therapy and surgery. What I call the slash poison and burn approach we have seen a decline in mortality from from cancer one percent a year which is nothing to write home about but it still is better than nothing because in the last three decades that means we have dropped the cancer mortality by by twenty six percent? But once again it's not because we are finding any great new therapies. It's because of two things one. Because of anti-smoking campaigns began to show awesome results and to because we're diagnosing cancer earlier and earlier in instituting therapy earlier and everyone knows that if there is a diagnosis sources of cancer. The first thing people say all but don't worry was found early so it's curable in the book you write that. This is an embarrassment and he used very strong language. You've used that language which already in our conversation. Why would you say that? The lack of progress is an embarrassment. Because why are we not looking at the overall picture and trying to do something different instead of repeating the same old same old. This is why it's an embarrassment. Why haven't we been able to do better for acute myeloid leukemia? For example. The reason is that the diseases horrendously complicated. And it's a moving talk talk it so all cancers beginning a single sale when this divides into two new cells it is likely to make more war. DNA copying errors which normally occur in cells as they divide because cancer cells are dividing faster and faster they make more errors which can translate how it responds to therapy. So potentially two new cancers every time leukemia sailors dividing into two. So why do do we think what gives us great confidence than that trying to reproduce this disease in animals. Hell the animals who don't get it spontaneously and then testing drugs against this Artificially produced cancer will work when it's extrapolated to humans. What is giving us this confidence for the last fifty sixty years yet? I mean in light of what you're saying we will often see headlines. I mean it's almost daily or weekly that you'll see them in the newspaper saying that there has been an extraordinary breakthrough in treatment of some form of cancer. Are you suggesting that the headlines and the stories behind the headlines lines aren't true. I'm not suggesting I'm declaring. That they are absolutely most of them are false so there are two main explanations for this kind of delusional unusual headlines. The first is that even improvement in survival by a matter of weeks is proclaimed from the rooftops as if it's a game game changer under pressure from advocacy groups from patients the FDA America is willing to approve a drug ugh if it improves survival by as little as two and a half months you told me for twenty two year old has cancer waters two and a half month. Survival improvement mean to that person specially when it comes with horrendous side effects and a second important reason is the fine fine print will always show something like new. Drug cubing pancreatic cancer and then in the fine print it will be in mice and you don't believe there. I mean if something is cured in mice certainly doesn't mean that it's cured human beings. Well these drugs that we find which are curative in animals we bring them. I'm to the patient's bedside and ninety five percent of these drugs fain the five percents that get approved should have failed because they're doing precious just little and financially winning people and yet there is a huge cohort within the medical community. That will say that progress is being made. Dr Len Lipton Feld is the deputy deputy chief medical officer for the American Cancer Society have a listen to what he says about advances and research and treatment. I certainly can agree that. For some MM cancers we have not made much progress however we've averted close to three million premature deaths from cancer over the past twenty seven years That's nothing to be ignored. We can do better but let's not ignore the we have had success. We have put a tremendous amount of research research. Effort tremendous amount of research dollars stimulating new ideas so we can have new approaches and to reduce the burden of cancer. Let's true for every successful drug there eight or nine drugs that have not been successful in clinical trials. But that doesn't mean the researches failed and that doesn't mean that everything we do up to that point is necessarily flawed. It's also fair to say that are more traditional treatments have had some success and our ability to screen for cancer is not something to be ignored. A tremendous amount of effort gone to finding the first cell finding the first signals of cancer and then deciding how best to treat it. Billions of dollars are being spent right now as we speak nick and we are making progress in that arena. So I think it's a little presumptuous to say that all we're doing is poisoning people are burning people or cutting people hustler arosa. What do you make of that? I agree with him completely. We are curing sixty eight percent of patients at. That's nothing to be found it but he seems to be looking at the glass a bit more than half full than half empty. I know this is the issue. That people are quite S- So a family friend of ours. One stoled my younger brother that if the sun rose from the West today everybody will stop and stare at it and wonder why button there are some people who watch the sunrise in the East every day and wonder why I want to bring to attention all that we've been taking for granted why in This Day and age of Supreme mm-hmm technology are we using such primitive measures still to treat cancer so where have all the billions of dollars gone that that are being invested to develop new therapies. Everything we bring to the bedside literally has just petered out into disappointments. So I'm not saying we haven't developed most fantastic by logic insights into the pathology of cancer. Of course we have. I'm not saying all the researches she's wasted of course it isn't. I completely agree with doctor. Looked and felt in everything he's saying and yes. A lot of money is being spent in finding the first cell but not enough. I understand we have patients. We have to treat today so we can't give up doing all the things that we are trying to do for them. All I'm asking is what about future patients. One in two men and one in three women are going to get cancer. Are we going to continue on this spot spot of slash poison. Burn and keep pumping our chests and giving ourselves gold medals goes. Nobody's trying to denigrate. What has is being done until now but how can we do better? The only thing that seems to work is identifying cancer early. I'm seeing. Why aren't we using the latest technology to try and identify cancer at its inception? How do you take down criminal middle network hidden in the shadows? I tell them that I know that they're the ones who are running the largest child abuse website on the dark nets the journalists working mm to expose the darkest corners of the Internet. That's your playroom for that's your baby's clothes. That's my house. The police who hunt down online predators the rate the environment. They're using no we didn't we didn't make it. They made it hunting. MOORHEAD subscribe wherever you get your podcasts. You write in the book about a number of patients that you you have encountered over the course of your career. One of them happens to be your husband Harvey who is also an oncologist. How prepared were were you for what he had to go through? After his diagnosis I had already been treating cancer patients for twenty years almost and yet until I shared a bed with a patient. I had no idea how deeply painful this disease can be. What do you mean I I mean literal pain? There is almost nor organ or tissue that was not affected by pain in Harvey's RV's case he suffered such scorching blistering episodes of wrecking pain and it was just unbelievable. His body was complete ravaged and even he was shocked being on college. Est I at the tools that cancer takes at so many levels one of them being that no sooner did you get adapted to one new condition. Things changed radically the agonizing combat that we saw between cancer cells the immune Munin system trying to fight it the treatments we are giving it all becomes so confusing. I was going to say I mean between that and watching your daughter's waters best friend Andrew. go through his experience with a tumor that was on his spinal cord. He's just in his twenties and he dies Just over a year earn a bit after. He's diagnosed as somebody who sees this close up. What is it like to know of the disease and know so much about the disease but also also watch somebody in the grips of the disease but this is what brought home the whole issue of me in one fell swoop when Andrew woke up from anaesthesia and turn to his mother and said? Don't worry about it. Just call. Ezra she's on the cutting edge. He's GonNa find a cure in in that moment. I realize how badly we have failed. Andrews of this world we have no right to go around prancing and posturing about all the wonderful things we are doing for Kansas. As long as there's even one andrew dying this miserable death every three on colleges new from days zero that this poor boy's chances of survival zero point zero zero the second level at which we failed ultimate kept offering him confusing treatments. You can take this. You don't have to take this. Why are we offering even these choices to a twenty two year old and then in the midst of all this Matt you see the expression of human ability you experience Rian Grace and the presence of someone like Andrew do weeks before this booth young man at twenty three years of each is dying? They brought to him a form to assign that is called a do not resuscitate form which means that if he stops breathing they will not do anything about it or does he want them to in to be an he immediately told them to go away is not gonNa sign it but that evening. His father came to the hospital to relieve the mother and sister who had been indoor all day Andrew. Soon as his father was alone with him call the people back. Signed the form saying I could not do it in front of if my mother she wouldn't be able to take this twenty-three-year-old was dying is protective of his mother. This is a moment of race. That humbles you like nothing else can. What does your daughter want from you? Not as a mom but has has a doctor and a cancer expert when it came to the situation that her best friend found himself in my daughter Andrew and Sheherazade other friends they they were also confused. Andrew's mother and grandmother have survived cancer. How is he dying at twenty two n insurers art pointedly told me once in the middle of the night when she called almost hysterical? She said Moore my heard all my life that you and dad help cancellations solutions. But you're not helping Andrew why it's a sobering moment for not just a doctor but but but for a mother I decided I have to really know double my efforts firts back in one thousand nine hundred eighty four. I turned my attention to trying to find cases at the pre-leukemic state and try to prevent the appearance of this end. Stage terminal monstrosity called acute myeloid leukemia by intercepting. It early so this is not something that I just decided to say. After I experienced the ghastly scenes with Andrew. This is something I they have been saying repeatedly since nineteen eighty-four and trying to do it not just saying it started banking cells from my patients. Today I have a shooter positively with sixty thousand samples in it and this to shoot repository has yielded a huge number the insights what has become very clear. Is that going after one. Gene studying one part where to part ways in a few patients this reductionist approach is not working what we need is a more pluralistic approach by which I mean. Try to use the latest take -nology ways of studying the proteins and the genome of the cell and then all the imaging and scanning devices we have redirecting our funds or resources in such a way that it brings the competition that was seen doing the Landing of Man on the moon between America and Russia and a cooperation that was seen between scientists around the world doing the human and genome project. As you say we're in some ways looking at the last cells if you want to get to the first cancer cell how do you get at that. What are the technologies that might offer some promised promised you say are already almost on our doorstep? The fact is that it's very clear. The treatment alone is not going to be sufficient to address the cancer. The problem we need to develop techniques just like rexine just like we have a prevention for infectious disease. We will need to find preventive measures. How how we do it? Well this is where I am asking for. Redirection of funds being wasted in doing A useless clinical trials or trials that are yielding a five percent success rate to trying to develop for example ways of Ah finding the presence of cancer in any secretion through a liquid biopsy blood sweat saliva tears a urine unilateral. The two Sheba just announced last month that from one drop of blood with ninety nine percent confidence they can now detect the presence of thirteen different common government types of cancers just based on detection of micro aurigny signatures that they have identify. When did you start that testing? How early life this this desk can start from birth to death and why are we again once again? Why are we only using screening measures on a once a year basis and screening measures that were developed fifty years ago? We should be using these kinds of sophisticated technologies to monitor the human woman body continuously from but to death. And you don't you. Don't worry about the cost or the concerns that people raise around issues of false positives and then that could create more strain Not just on on the healthcare system but on the the the mental health of those patients who are being tested. Of course I worry about it. Of course they'll be a lot of over diagnosis John over treatment. Isn't there now and guess finding that you have Early cancer present in your body can be very scary emotionally me but then if we have a solution for treatment of that early cancer then it won't remain. That's scary so I think all this will call evolve simultaneously Genia sleep. That is once we find that this is actually a potentially lethal threat to the body. Only then are we going to direct some kind of of treatment the many treatments that are failing today maybe because they are being used when the diseases far too advanced. I want to ask you about that. We're death Often the stories that we will hear of cancer are the stories of survivors And those are used Inspirational racial ways. They're used for fundraising. There used to generate hope Among those who would be facing a bleak diagnosis. Why did you want to tell the stories of patients who died? It was not to revel in their suffering or pain. The reason I told the stories of patients who died is to bring the patient back into every conversation about cancer front and center and to look at everything through the prism of human anguish. I have interviewed patient families sometimes ten years after did they lost a beloved member. Probably the most important part of the book is the Voice of these families. A mother of a twenty two year roll Andrew saying that even if there was a one in a million chance we would have taken it and we would not give up doing everything that we did because they are mothers. This is hard reading. And there's there's a lot in the book that mean given the prevalence of these diseases Ziza's Can drive people down can make people feel as though it is bleak that the outlook is not optimistic. Where do you find hope in the work that you do well? I'm very optimistic. Optimistic and in fact this is not gloom and doom book yes I have written about to patients who have died but also there are twice as many stories of the patients nations who are alive and who have defied all odds the idea is to also tell cancer patients that you're not alone. Most of us are at risk of getting cancer tomorrow tomorrow. And that there are hundreds of thousands of amazing researchers and amazing oncologists who are working very very hard to try and find a solution so it should bring a modicum of relief to the people who are anxious about it and it would be the best thing for cancer survivors. I do insist upon more funding and resources being directed towards the identification of the earliest stage of cancer. So that they don't don't have to go through the same thing all over again. I'm hundred percent. Sure that we will in the very near future have the technology at least to find the earlier footprints of cancers and that along with that revolution will come Better treatment adoption so. I'm very optimistic. Dr Rosza it's great to speak with you about this is its powerful reading and so familiar to so many of us Who have friends and family who have gone through this? Thank you for joining us. Thank you very much for having meet. Dr Raza is non columnist and the author of the first cell and the human cost of pursuing cancer to to the last. She was in New York for more C._B._C.. PODCASTS GO TO C._B._C. Dot C._A. Slash podcasts.

cancer Andrews American Cancer Society Tracy beam Dr Rosza leukemia Daily News baseball facebook America Mary Harris Mitch US Halifax CBC twitter Galloway chemo mechanism of action infectious disease
SALAMAT, EMMAN | NOT YOUR ORDINARY PODCAST

NOT YOUR ORDINARY PODCAST

16:25 min | 10 months ago

SALAMAT, EMMAN | NOT YOUR ORDINARY PODCAST

"In This episode is sponsored by inker. podcasting is so much fun, and now it's easier than ever to start your own podcast with anger. Everyone is passionate about something. Now thanks to anchor. You can spread the word about the things you love and maybe even make some money doing it. Scarred your podcast for free with anger using the anger APP or by going to anchor them. They'll even distribute your show for you. You'll be heard on spotify apple podcasts and many more of your favorite podcast in platforms. Anger also provides tools to allow you to record and edit your show from your computer and even from your phone. And no matter how big or small your audience is you can make money from your podcast. It's everything you need to make a podcast in one place. I using her and it's been the best podcasting platform. I've been a part of. So Join Me Start Your podcast today by downloading the anchor APP or go to anchor dot. FM. We all have something to say. Thanks anchor. Hello extraordinary people this again, your host rap saying welcome back to Dr Ordinary off cast. Hour episodes for today will be a little bit of a sad topic. I will try my best to leave a positive vibe. Indian. So, as you can see, this episode is entitled. Salamat. One of Ilippines Ogi youtuber content creator and Blogger. And basic artists. Name address. has passed away this August, sixteen, thousand and twenty. He died at the age of twenty seven. Due to cancer. Or Acute myeloid leukemia to be in particular. She's dead laughed many of the Field Pinos. Especially, those in the youtube industry in the entertainment industry. In shock because nobody. In Nike Nothing's among been opposed Deng Empire, mind the and miss more nippy. Nine Nanyang girlfriend. Nagging all am. Gagnon Kalugin. Balusha guten. Chemotherapy. May keep the nothing among detainees Internet and recently he if he even released, he's third song which is entitled WHO and. We, all thought Nah. Nah. Kina high in your PA. But not in the not in alarm to Adam Domini. MAYBE ESPN enduring a lot of pain. For sure not boss I don't been done in Nepal site them being la but. And No, be no. Sir Twitter. Some social media accounts new peachy Gumede Dome. Miss more the. Using Woodside ICU. and. Kosei long kidney failure in out an uncle implications. Sotho. Don't belong Bella Gong Narita. You grabbing support. The monopoly been all alum Lilo name off a beacon Ya. Manasseh team amand. NASA tier. One. More sit Peron Parramatta Greece now up on. 'EM and Mobile Your Hospital Bill Nafta Marketing, Amelio honest not. But sadly. lagaan. Miami's small. Not. Buying. Indian. Shah. Did, not, in shop reading. Guide going by. Going on Hindi, National Mahbub, Alam nothing that he has injured a lot. Lamar Bun he fought a good fight with cancer. INDICIA so more. DISHES, removal. On Gun Saturday. And doggone. Long. About borriello skipping Ghana by. Allegation Melilla Man when organ Kasuga Doohan Columbus. So Buddha's held a COUPLA. Gumbo us. Weak-. Might as well. Let us enjoy our lives to the fullest as leave day by day spend quality time with our friends with her family doctor once. especially with ourselves, make ourselves happy contended. Without destroying our health our future let's be happy that we are alive because. Now by number ammon is twenty seven years old. He is such a young man now papa. Go WLAC Niemann. Not by enthusiastic young Dow NEPAD I'm young alums subway yen under Shah say and yet, but I'll get the line up. You'll empire impairment see la she posted bargains in our Giraffe cicle. Salah your solovy John Tila now. Luma Musyoka Camale Ya. and. Then, Dr Martin don't say. Didn't Ala Moana Paiko Nick moment no they knocked up are and The more superior mentioned. So those were the good times. Those were the good memories, Namie in Amazon. And even Yuma and Tanya Natalegawa among the trending on Pena's knocked the top ones a charts. The top top one trending say Youtube tweeter spotify. Go home out ramming views like streams download. Anthony. Anthony and. Owning up on unreleased Nah dake along. Grab a Napa Duncan and then Panam. Dhillon. DOPP ETO young. Lincoln. Town and eighty lease. So mob belong. Boo. Hoo. Compound. Mar Than it has the chill vibe in need. Comments I cantata. Ma Baio. Moss. Again then only earaches second don't be together. No harm woman boss Nah. Gone in Demo Alkali in on nomad on concert leukemia don't say. We're. GonNa go dinner Philippine Snow Bigler showing the UPLOADS Youtube China Kilonzo neutering melamine. Cancer. Just after nine. One million subscribers milestone. Going be bought in announced, intimate cancer shut again. Not Bakaray, not by here up up in sound fan or personally be some fan knocked him by a man. Now. Vigils Baking Cima Music. On. A Handgun a union, the Omar. The Shah. But even though GONNA Noonan Yari. Let's all be strong. For the sake of some on E. M.. Alum go young. Team by a magnon bone tier one. Mama a beacon am online in London guidance that Louis. Girlfriend and sixty. Am GonNa they are in deep vein right now and they're in agony. But I know now. Along attack. So diabetes among offense. Defense Name and Bill Maher. So by by Young Empire Man Nicotine. Devi home setlements of Emmanuel. Delay Small. Indigo Manila gunfire payroll kilolam AC- Emma Napoleon my mom music Nah and. Google at NASA tangerines belief Anina Omega. US just try to be strong. Let us be strong for 'em on Piton, at the now. He will be gone basically, but he will never be forgotten. Econo-. If I die I'm a legend Tonight Ammon Sutton. He died a solid and. He has a on of tree. New Six three songs in one, hundred eighty plus. Youtube contents. And Not Bottoming Memories Not Bottoming Mama a Don KNAPP. Dial. Eighteen patio big titan. Vibes. And we should be thankful for that. which brings me to say to you guys. Now let's all try our best to be healthy a strongest relief Guy Gano Taio Batte. Guy That Merrin fire. Let's stay healthy because in the united alum. Benito. Guy. DACA NOTHING Not they're not Young Mirror noma preservatives ninety, nine alarm. Mustered. Up. In Santa May Massana effect silence will not and so might as well. Let's take double precaution on our health Adam Lallana my own. Title. Condemn Mia. Let's stay healthy guide violent in that Agung Melissa Potato Manassas battle digressing not in Messiah be. So the. Exercise. Putting. Compared to Tulip data and of rammed them when the time guida checkup dyal mcnutt nothing in a in an umbrella and on. And of course, then a gun injury. Boo. Day, by day but PRISCILA McMaster only know will ECOMOG SAYING By Guam to lube. Salama. Naomi bus boy. Now. Middleton boggled bogging and a go up every day try to be productive. Try something every day try something new every day. Now, Bhagwan to look may boggling my island bugging and ago are more and create memories as long as you can S- possible as you can every day every moment create memories Kosei Yanyan along barbeque polical elegant. Egypt. I don't know right now on. Maguire move forward at don't. Even Amazon but I know. Indian up by is. Diabetes fans. By man mayhem on. Indian nothing Salah one for sure and. signed along long. Long number ORB This my personal message. To. All of those friends than when the onus team biomass I know family a peachy now. Works. SEALANT. thou- even though they are in a great loss right now. Nedoma had long. You. Don't put by some foul to say go NASA antsy Amazon Google was doing. But only Diabolica your. Arm In petroleum possessor million million Philippine on why is an honored saying? No. Let us also continue to support the family of airman man. Kosei, Nebraska Vina's tweeter suppposed me V now hallows two million. Hey, get your calendar long. Hospital by Bossy airman. So Unhappy Milan geise Internet. Twitter facebook. Account. EP bitchy. Navy and young by account details DONATE DIAPER DONATE BARA Mobile Hospital Bill Airman, and let us continue to support his work your music among our container nine young. at, let us continue to stream eight going sound platform moments in a parking participatory I recommend to you now gone more. UNTARRED. airmont relate. Don't take along compared the loud we and. And I'm telling you. It will hit two different right now combined Moody Mark on on. EBONI mugging effect to say on my own. So I gave my deepest condolences to the new mayor this family to team. And condense push annual Latte. And Bloods? Man? On May rest in peace rest easy. You're a legend. You will begun basically, but you will never be forgotten because you are a legend and Menendez Lung Malaga's. So blogging writing Don Geiss. Lantis try to leave as happy as we can. Every, day every single moment of our lives, create new memories everyday learn, and do something new every day. So that, before you go to bed before you go to sleep. You can come to think of. Can deaconess Ieng Mayo Nebo Maimuna Bargo on Ngong Bagai Mughal. Memories. Allah. And I'm telling you guys snap passer ups a feeling none. So longer and along Muna Barisa. Episode Nettle. Again. This is your host trap and thank you for listening to not your ordinary podcast.

Cancer Youtube NASA Shah Amazon Ammon Sutton Google spotify Anthony Ilippines Ogi dot Bill Maher content creator Ghana Bloods Gagnon Kalugin Young Mirror noma ESPN Adam Domini Sir Twitter
Democracy Now! 2019-12-23 Monday

Democracy Now! Audio

59:48 min | 1 year ago

Democracy Now! 2019-12-23 Monday

"Hi I'm Amy Goodman. If you're tuning in right now democracy now is probably your source for news you can trust. Democracy now is independent. Which means we're funded by you? The oil gas and coal companies when we're covering climate change or the weapons manufacturers when we cover warren piece. If you everyone who tunes into this podcast may just just one ten dollar donation right now. We could cover operating costs for twenty twenty the most critical election year. The United States has seen in decades. I think the the media can be the greatest force for peace on earth. That's how we come to understand each other. If you feel the same way make your tax deductible donation today by visiting us a democracy now dot org have a wonderful holiday season happy new year and thank you so much. I'm from New York. This is democracy now. Cancer is a disease where the strategy of treatment so far has been to try and kill every last cancer cell in the body and why does cure a lot of patients. It produces talk doc. Society and doesn't cure everybody but one way of killing everybody would be to catch it early and prevent it from becoming at this stage monstrosity where we have to be constantly chasing it down slash poison burn. That's what a leading cancer. Cancer Doctor Calls the protocol of surgery. Chemotherapy and radiation we spent one hundred fifty billion dollars each year treating cancer. Sir You had a patient with cancer is as likely to die of it. Today with a few exceptions as one was fifty years ago today. Okay we spend the hour with renowned cancer. Doctor Dr Ostra Rossa author of the new book the First Cell and the human costs of pursuing cancer earth to the last all that and more coming up welcome to democracy now democracy now dot Org Warren Peace Report. I'm Amy Goodman. The Pentagon has released new emails revealing. How the White House Budget Office ordered the Pentagon to halt all military aid to Ukraine only ninety one minutes after President Trump's the July twenty fifth telephone call with the Ukrainian precedence Alinsky the heavily redacted? Email show senior budget official Michael Duffy telling pulling Pentagon officials trump had become personally interested in aid and had ordered the hold. The emails were released after the Center for Public Integrity. Integrity filed a freedom of information. Act Request over the weekend. Democratic lawmakers renewed demands for witnesses including Michael Duffy to testify fi at trump's senate impeachment trial this is Senate minority leader. Senator Chuck Schumer if there was ever an argument that we need Mr Duffy to come testify. This is that information. This email is explosive. Top Administration Ministration official one that we requested saying. Stop the aid. Ninety one minutes after trump called Celeski and said keep it hush hush. What more do you need to request a witness in Immigration News? The trump administration's considering a controversial plan to deport Mexican asylum seekers to Guatemala. The proposal comes after the United States is already begun to deport Hondurans End Salvadorans who've arrived at the US border seeking asylum in the United States. Guatemala under a quote safe third country agreement brokered with outgoing going Guatemalan president. Jimmy Morales human rights advocates say deporting asylum-seekers to Guatemala is dangerous particularly for female and LGBTQ. Oh Gee Btcu asylum-seekers Guatemala has one of the highest rates of femicide the murder of women in the world. The Washington Post has revealed hold a secret White House plan push for by trump's immigration adviser. Stephen Miller sought to use the US refugee agency to expand. Trump's mass. Ask deportation efforts. The plan would have included embedding immigration agents inside the program responsible for caring for unaccompanied children. One part of the plan was rejected by Department of Health and Human Services officials but the Department of Health and Human Services is allowing ice. That's immigration an and customs enforcement agents to collect fingerprints from adults seeking to claim custody of migrant children it government shelters. I can use this information to a target. The adults for deportation meaning undocumented immigrants will be far less likely to claim custody of migrant children and therefore prolonged the detention of children and the separation of families Saudi Arabia's sentenced five people to death for the killing of the prominent journalists the Washington in post columnist. Joe Malca showed three additional. People were sentenced to prison over the brutal murder carried out inside the Saudi consulate in Istanbul. Turkey which sparked international outrage. Saudi Arabia has not announced who's been sentenced to death or imprisoned the CIA has concluded the Saudi Crown Prince Himself Self Mohammed bin Salman ordered Kashogi. She's assassination but the prince remains a close ally of the US government. The International Criminal Court has taken a major step toward investigating Israel for war crimes against Palestinians on Friday the ICC's prosecutor asked judges to outline outlined the territorial jurisdiction of the investigation while Israel's not a party to the International Criminal Court and indictment could subject Israeli officials those two international arrest warrants Israeli Prime Minister Benjamin Netanyahu slam the investigation is anti-semitic while Palestinian President Mahmoud Abbas welcomed. The News Radio who I am but y'all want today is a great day for us because we accomplished all that we need because from today to start except issues in India. Widespread protests are continuing against the controversial L. New Citizenship Law. which many say is a major step toward the official marginalization of India's two hundred million Muslims? The law provides a path apt to citizenship for immigrants from Afghanistan Bangladesh and Pakistan. Unless they're Muslim on Sunday Indian Prime Minister Narendra Modi tried ride to quell the protests by claiming the law is not aimed at marginalising. Muslims already living in India Hindustan Bigham that Muslims who were born on Indian soil or whose ancestors are children of mother. India brothers and sisters. They have nothing to do with the citizenship law. The National Register of citizens the Muslims are not being sent to any detention centers nor are there any detention centers India has launched a crackdown. Crackdown against the protests. At least twenty five people have been killed so far and over fifteen hundred. People arrested many of the demonstrators. Say The law goes against India's secular constitution during the constitution Tomorrow they're going to change something else so this is basically fight for democracy. There's not fight for mu for Jan.. You're awesome fight individual fight for anybody. This fight for India. This fight for democracy taking India's Supreme Court has agreed to hear a constitutional challenge to the law in late January in Iraq doc thousands of protesters poured into the streets of cities across southern Iraq. Sunday demanding the appointment of an independent prime minister after the former the prime minister at allow the melody was forced to resign. Amidst massive anti-government protests security forces and militias have killed over five hundred protesters and injured nearly twenty thousand people since the protests erupted in October there are also reports that prominent Iraqi human rights activists have been been disappeared. Reuters is reporting the death toll from Iran's brutal crackdown on antigovernment protests November was significantly higher than previously reported reported. With as many as fifteen hundred people killed during the two weeks of demonstrations the figure which provided by Iranian interior ministry officials. It says the victims victims included at least four hundred women and more than a dozen teenagers. Reuters also says the orders for the crackdown came directly from Iran's supreme leader Ayatollah Ali Ali Khomeini who reportedly told a gathering of high level officials quote the Islamic Republican endanger. Do whatever it takes to end it you have my order unquote wrote the Pentagon says A. US soldier was killed in Afghanistan today in a second. US soldier was injured. The Taliban claimed responsibility for the killing rolling in Kunduz province. These soldiers death comes as Afghan officials released long-awaited preliminary results from September's election which show President Ashraf Schrafft's Connie one just over half the vote his challenger Abdullah Abdullah is contesting the election which he says was marred by fraud. Voter turnout is is low. And some residents of the capital Kabul said they supported neither candidate plug you. The dog bottled up both Ashraf Ghani and Abdullah haven't done anything for us in the past five years. They just deceived the people. We don't want them anymore. They both have committed fraud and the court must try them the French. The President Emmanuel macron is asking unions for Christmas truce as the massive strike against microns proposed pension plan heads into its third week. Strikes are justifiable and protected by the Constitution. But I think there are moments in the nation's life when it is good. Serve a truce out of respect for families and family life. So I'm calling on everyone to have this sense of responsibility. President Macron has also said he will give have a his own presidential pension as a concession to demonstrators who've launch nationwide strikes over macron's effort to overhaul the French pension system and effectively raise the retirement age for younger workers. The unions have ruled out Christmas truce and are instead demanding macron scrap the pension overhaul in California newly released body camera. Video shows a Sonoma's county sheriff. Deputy fatally slamming immense head head into his own car. The Sheriff Deputy Charles Blount and his partner deputy. Jason Little apparently thought the driver David Glenn Ward had stolen the car but it was in fact his own car to officers pulled him over and then Deputy Blount reach through the window and pulled ward by the hair slamming his head into the car's frame. Deputy little taste him and then deputy blount put him in a restraint until he became unconscious. Word was declared dead. Shortly afterwards Deputy Blount has been fired and in Texas a grand jury has indicted former Fort Worth police officer Aaron Dean for Murdering Tatsiana Jefferson in a case that sparked widespread outrage over police killings of African Americans particularly women officer. Deen who is white. Eight was responding to a non emergency call by a neighbor for a wellness check. The neighbor saw Jefferson's front door. It was open on a warm night. October the twenty eight year old graduate student. Jefferson was in her bedroom. babysitting her eight-year-old your old nephew. Soon after the officers arrived Dean shouted through Jefferson's bedroom window to put her hands up then immediately opened and fire killing her. He never identified himself as a police officer on Friday. A Tatyana smother celebrated the murder Indictment Tana's and his father died in November a heart attack at the age of fifty eight less than one month after her daughter's murder and those are some of the headlines. This is democracy now democracy now or of the Warren Peace Report. I mean he couldn't then and I mean shaef welcome to our listeners viewers around the country and around the world why has there been so little progress in the war on cancer. According to the director of the National Institutes of Health Dr Francis Collins and quote Americans are living longer healthier lives. Life expectancy for a baby born in the. US has risen from forty seven years in one thousand nine hundred two more than seventy eight years today. Among the advances. That have helped to make this. Possible are a seventy percent decline in the US death rate from cardiovascular killer disease over the past fifty years and a drop of more than one percent annually in the cancer death rate over the past couple of decades a drop trump of just over one percent for the trillions of dollars that have been poured into council research just over one percent today we spend the hour with a renowned oncologist who says we should be treating the disease differently in her new book the First Cell and the human costs of pursuing cancer to the last our guest for the hour Dr Oscar Rosza notes we spent a hundred fifty billion dollars each year treating cancer yet. A patient with cancer is as likely to die today. With a few exceptions as one was fifty years ago she argues experiments and the funding for a routing advocating cancer look at the disease when it's in its later stages when the cancer has grown and spread instead she says the focus should be on the very first stages the first cell as her book is titled. She says this type of treatment would be more effective cheaper and less toxic. Dr Criticizes what she calls the quote protocol. Cole of Surgery Chemotherapy and radiation the slash poison burn approach to treating cancer which she says has remained largely unchanged for decades. It's she calls for a transformation in the orientation of cancer research writing quote. Little has happened in the past fifty years and little will happen in another other fifty if we insist on the same old same old the only way to deal with cancer problem is to shift our focus away from exclusively developing treatments achievements for end stage disease and concentrate on diagnosing cancer at its inception and developing the science to prevent its further expansion from. I'm chasing after the last cell to identifying the footprints of the first doctor reserve rates. Well for more Dr Asher. Russia joins us to speak in her own words. Ivanka Logistics and professor of Medicine at Columbia University. She's also the director of the center and es is my largest plastic syndromes a form a bone marrow cancer in her book she notes again that we spend a hundred fifty billion dollars each year treating cancer. You had a patient with cancerous as likely me to die of it today than one fifty years ago it is an astounding fact with a few exceptions doctor asks for Rasa Welcome back to democracy. Now it's great to have you with us. How can this be? How can it be a lack of progress that has been made in this last half century? Thank you for having me again. Amy Delighted to be here since one thousand nine hundred three Eh. It has been well appreciated. Actually that it's not cancer that kills. It's the delay in treatment that kills so forever forever we have been making attempts to try and diagnose the disease early in the last three decades. We've seen a twenty six percent decline in cancer mortality which is about one percent percenter year as you pointed out but that's not happened because we have developed some grand new treatment strategy. It has happened because of two main main things. One is the anti-smoking campaign. So the incident started going down and second news because we started using screening greening measures to diagnose cancers earlier and earlier this approach of Preventive Medicine Way. You catch the disease early in interceptor. Is what caused the drop in cans in cardiovascular disease by seventy percent because they're the cardiologists were smarter than on colleges. They realize that if they allow myocardial infarction or heart attack back to damage the heart muscle then the only treatment would be a heart transplant which is sold draconian and so terrible did did started to diagnose not only earlier and earlier try and prevent the appearance by using anti cholesterol drugs for example. That's a very very clear case of early detection. But then even prevention of the disease and seventy percent decline in mortality. Why damnedest doing the same in cancer? So what does the answer to that. The answer is that we have been trying to do it. And the screening measures that were put in place like Kamal Graffiti colonoscopy. PSAT'S STINK PAP smears. They're the ones that caused the decline by twenty six percent mainly mainly in addition. Listen to anti-smoking campaigns but those measures were put in fifty years ago. Imagine in this day and age of technology we are still putting a tube into someone's got and looking to find cancer that is primitive that's Paleolithic for today and the alternative is the alternative is that we have milk. These technologies as much as we could they have yielded the twenty six percent decline in mortality. They're not going anywhere else. We need to invest in developing technology based on current imaging scanning devices detection of biomarkers for example from blood sweat tears saliva art urine stool samples and find the F- earliest footprint of cancer. And see how we can intervene and this. This is a strategy that is not limited to just cancer. Amy This is a strategy that is going to apply every single chronic disease in the coming. Yes so what has prevented that from happening. I wish there was a very neat kind of onset about this. But it's something like this you take a frog and put it in gold water and start eating it slowly. Nothing is going to happen on the other hand. You throw a frog into Bir boiling water. It will jump out but if you heated slowly the frog dies. Why is without jumping on? Because it's Louis gets used to it. This is an apocryphal story. By the way scientifically and correct. That's the one he always. I have to add that but the analogy is true. That things have happened so slowly that we keep getting desensitized to the next step one one thing is that there is so much hyperbole around cancer treatment every if a few months of survival are added by drug drug it is welcomed as a game. Changer let me end of life. Yes exactly let me give you just a few statistics. I want to be very clear that using the slash boys and burn approach. We are killing sixty eight percent of cancers that are diagnosed today we are killing them. Thirty two percent that present with advanced disease their outcome is the same exact outcome that it was fifty years ago. The sixty eight percent year curing. Why are we still using these stone-age treatments? You know how general it is to get. Chemotherapy and radiation therapy. Explain what happens. The first rule rule of medicine is first. Do No harm in fact when a patient is diagnosed with cancer. It's a silent killer. That's the problem it can reach stage four disease without producing symptoms. So somebody she comes to us. I recently saw forty two year. Old Young Man who has just finished the game of tennis and come to see me and suddenly because he was exhausted Ostad and feeling so tired and now I diagnose him acute myeloid leukemia. I look at this toned and tanned young. Oh Man and the first thought that comes to me is about what we are going to do to him with the chemotherapy we are going to get. It is unconscionable that in twenty nine teen I am still going to give if this young man the same combination of two drugs that we popularly known as seven three that I was giving in nineteen seventy seventy seven. When I arrived in this country? I feel ashamed of myself having to repeat the same side side effects that you're going to lose all your he'll throw your guts out and your council going to tank. Your blood counts will go down to essentially zero for weeks on end where you're going to be some susceptible to all kinds of terrible infections. You will be in the hospital. Suffering with shivering shivering night sweats and fevers and all kinds of Aches and pains and constitutional symptoms. And then there is a chance on so that a percentage of those patients will improve. This is what we do just therapy alone. We're going to break and then come back to this discussion and also hear about about your personal story with your own husband. Also renown cancer doctor who died of the very disease that he was studying and hear the stories of your patients. We're talking to the renowned cancer doctor. The college is professor of Medicine at Columbia University city. Doctor Ashraf Rasa. She has a new book. It is called the first cell and the human costs of pursuing cancer to the last stay with us turns Opus twenty-seven number two in D Flat Major Lentil Anto Sebastian. You to perform by Abbey Simon Abbey. Simon passed away. December eighteenth at the age of ninety. Nine this is democracy see now democracy now dot org the warrant piece report. I'm Amy Goodman with nermeen shape as we spend the hour with Dr Ausra Rossa a renown oncologists is professor of Medicine at Columbia University where she is also the director of the MDIS center a form of bone marrow. Cancer her new book just out titled Titled the First Cell in the human cost of pursuing cancer to the last So as RAPA doctor. You we were talking earlier in the first. This part of the program about the slash poison burn approach to treating cancer which you've been very critical of which involves surgery chemotherapy. Therapy and radiation. You say that this has been responsible for curing sixty eight percent of cancers so a couple of questions would would it have been possible even though this has counterfactual to cure such a high number of counselors using alternative methods and to what kinds of advances have been in made in the how a chemotherapy is administered and how the effects of that of changes in the way that it's administered mustard have had on patients both very good questions so the first question you asked is what could have been really don. And what have we mean aiming at doing so sure. We started by using these blunt approaches. It's literally like taking a baseball bat to hit a dog to get rid of its fleas. That's how bad this kind of treatment is but we had to do it. Because we had no alternatives in the meantime we invested billions of dollars lose in trying to study the biology of cancer. Hoping that we will identify some intricate signaling part-way some genetic defect that is going to allow us to target it specifically and this did happen in two diseases and chronic myeloid leukemia developed a targeted therapy because one gene in had gone wrong and one magic bullet could target and cure the disease. Now just to know. You're one of the world's leading authorities on am L. at this kind of cancer. Uh on this year. I'm talking about chronic myeloid leukemia. But yes you're absolutely right. I am an expert in my Lloyd diseases and chronic myeloid leukemia. Something I've treated for decades now. This was a huge advancement. That happened in the two thousand that we could now use a targeted tapie which is not chemotherapy. which only goes in attacks the normal cell which is expressing this protein while it helps patients? It's also put the field behind by twenty thirty years. Why because we felt that this now stab wishes a paradigm every cancer will be caused by one genetic defect for which we just have to develop one drug so one gene one targeted therapy? Everybody in their grandmothers. been trying to find the one gene for pancreatic cancer. The one ORANGINA for acute myeloid leukemia turns out that unfortunately for all other cancers most of them really there are too many genes. That are mutated simultaneously Ashley. And so the targeted therapies. We developed even for those Multiple protein one protein that is dominant. It turns out it works works for a little bit so let me give you some statistics again. Ninety five percent ninety five percent of the new you drugs that we are bringing experimental drugs we bring to the bedside ninety five percent of them feel and to bring one of those drugs to the best. This bedside is a billion dollars almost so imagine how much we are losing five percent. That's succeed should have failed. In my opinion opinion. Why because it only prolonging survival by few months so for example? There's a drug that extends the life of a pancreatic cancer patients by twelve days and the cost of twenty six thousand dollars a year and not every pancreatic cancer patient just a fraction so think of the financial talk society we are causing to be spacious now for very little prolongation and survival. We are financially ruining forty two percent of cancer patients diagnosed newly diagnosed with cancer today by its year to the are they lose every penny of their life savings speaking of which before we go onto the incredible stories you describe in the first cell Your thoughts on Medicare for. Aw I have spent a lot of time accompanying Family and friends for example. What Sloan Kettering who are dealing with cancer the astounding devastation? The station of People's aside from lives financial destruction Medicare for. What would that mean for cancer patients? Amy I'm not an expert on these issues. I have common sense and one thing I can say is that the current situation is completely untenable. We are on the verge of collapse with the healthcare system. We can't continue it the way it it is going and to me. The only solution seems to be but again. It's not speaking as an expert is to have medicare available for everybody. I think that's the only compassionate and humane solution. What I WANNA ask you about another incident that you mentioned in the book before going on to the the longer case histories of patients in their own words as well as in the words of their family members? I mean the cost of cancer cancer treatment as you say in the US is exorbitant and many families have been driven to financial ruin. But what about in places where player cancer treatment is so prohibitive that it entirely deprives patients of access you talk about Arriving in Karachi and meeting in Karachi Pakistan which is where you're from and talking to Zeynab A cancer patient about whom you write quote. How just one go in and talk to thirty five year old woman? For whom dying from. Leukemia is only her second. Biggest problem could could you talk about that access to cancer. Treatment and who the people are who are entirely deprived of any treatment at all. This is a subject which is very close to my heart nermeen because obviously I am from that part of the world. The entire world looks to America for leadership. What kind of leadership are providing leadership where we are developing developing drugs or cellular therapies? Now that will cost over a million dollars per patient for helping very few few patients. These are rarefied cases for whom this kind of treatment will work as you said. Vulnerable the twenty million new cancer patients nations being diagnosed universally all around the world. We just don't have a compassionate solution for them. Why aren't we thinking? Not just those even in America in the remote areas and and many many places where healthcare is becoming harder and harder to access just because hospitals are closing down from financial ruin themselves. Why aren't we thinking of them? Why aren't we thinking beyond the beyond American borders for humanity as a whole? And when you think about that solution I mean you don't have to to be a genius. Look the only thing that works in cancer if you have someone who gets diagnosed with cancer the first thing you can say is was it advanced was it quarterly newer early. So there's hope we know that early detection helps right why odd. We'd investing money in chasing down the last cell in in which with drugs which have a ninety five percent failure rate today because the pre clinical testing platforms. We're using our so artificial and that's why we are bringing up drugs. That are known not going to be successful instead of doing that. Why aren't we simply improving on techniques? We know work. What worked early detection? How do you do early detection? Mammography colonoscopy PAP smear etcetera Oh has been reached to maximum limits. Let's develop the new technology so that from one drop of blood you can put it on a a little chip which can be read by a cell phone which caused some eighty dollars for twelve cancers to be diagnosed early. This is something that was just announced by Japanese company so these are things that are a pie in the sky. These are things that are happening. Now accept how fast will it happen to reach the rest of the world. It depends on the Mount of resources we invest. We're talking to Dr Nassar Rasa. Her book is called called the first cell. She is a leading on college EST in the world. She is a Pakistani American. Unless slum a woman you talk about your own story in the book the story of your husband also a leading oncologist Dr Harvey Chrysler died of Lymphoma Ma in two thousand and two you write. Cancer is what I had been treating for two decades yet until I shared a bed with a cancer patient. I had no the idea how unbearably painful disease could be. Let's I turn to your daughter to Sheherazade Raza Chrysler speaking at at the memorial service for her father your husband about his cancer diagnosis in the effect. His condition had on the family. The Fifteenth Harvey Price Memorial Memorial Symposium was held in New York in two thousand seventeen. What a cruel? Twist of irony was that as he was directing the Rush University Cancer Center in Chicago. Although he was cut down in the prime of his life by the very disease he had dedicated life to cure. I was only three when he was diagnosed an eight when he died. My parents took great pains to never mentioned the C word in my ear shot and yet most of my memories of our related at least in part to the presence of this nameless other in our lives and even though I was too young to know what was going on at any tangible level I had some sort of instinctual the knowledge that something was terribly wrong I could sense. My mother's struggle as she was navigating through stages of optimism pain dread despondency and eventually hopelessness as my dad underwent a seemingly endless stream of experimental treatments. These stages are most cancer patients and their caregivers and families experience. That was Sheherazade. Raza Chrysler the daughter of our guest today. Dr Haass Rawson College as Professor of Medicine at Columbia University talking about her dad who died of the one of the cancers that he specialized in he was this head. Dr Harvey Pressler of the Rush Cancer Institute in Chicago. Tell us as you begin your book. What happened to your husband? What happened to her? The first of all women. I started writing this book I had no intention of putting hobby into the book. I was writing about. What my other patients? But when I wrote about them in such detail and with such a painful granularity I felt. It would be dishonest dishonest. If I held back my own story and so at that point I decided to add and once I decided that this this story became like a red line running throughout the whole book because then I couldn't escape at every level where Harvey came in. I'll give give you just one example. I mean he was ahead of the cancer center he gets the very disease he's trying to kill and now he dies after after it very very exceedingly painful. Almost five years battle shares was eight years old when he died and a couple of weeks after he died she developed a terrible cold and flu and was pretty sick for a few days and then started getting better. One morning I was sitting in the living room reading and and she suddenly comes out crying inconsolably. I was sure that she's had a relapse and his much worse. But when I was able tacoma down this what she said she said actually I feel perfectly fine now but I know what it feels feels like to be so sick and how good it is to get better and my dad never got better. which brought on a second fruit of trying so eight-year-old at a visceral level is able to new experience the gyn of anguish that cancer patients suffer being the cancer widow? Did it make me into a different kind of Dr. No but my perceptions changed entirely marsal Prusse said that real voyage does not line finding new landscapes but in having new who is and so it became a voyage of discovery for me and having new ice and that issue of prevention of catching early. What happened in your husband's case who I mean? He was head of a major cancer institute. The same thing that happens to all of their cancer patients he was diagnosed way too late and actually the lymphoma didn't kill him. The treatment we gave killed him. The chemotherapy we gave destroyed his immune hyun system so that he died eventually of Sepsis he didn't do the lymphoma. There's a family friend of ars who once told my younger brother. He said a boss if the sun rose suddenly from the West one day hey the entire world will stop and stare at it but there are some people who watch the sunrise from the East every day. Hey and they wonder why and he said. Those are the only kinds of people who can make a difference in the world. And that's that's the kind of person Harvey was. It was an extremely thoughtful person with a great curiosity about life in general Andrew but specifically scientific issues yet what I learned from taking care of him and sharing a bed with him as a cancer patient was a deeply deeply humbling acceptance of his condition basically is to was. I'm a man and a man is responsible. Vote himself even though. I know that this is not going anywhere. You right at the beginning of your book and your introduction from last to first talking about that idea of the first cell. I've learned new things about what I thought I already knew. Like the difference between illness and disease between what it means to cure and to heal between what it means to feel no pain and to feel well. Can you elaborate on this. I mean really the the whole concept of this is it can be expressed better in poetry. If you don't mind recite short piece by Emily Dickinson. I measure every grief. I meet with analytic is I wonder if it feels like mine or has a different size. I wonder if they bought it long or did did just begin. I cannot find the date of mine. It's been so long a pain. I wonder if it hurts to live. And if they have to try and whether they choose between Wean they would not rather die. I WANNA ask about another patient nations Who you profile in the book? Who is in fact subjected to a particularly brutal form of this slash burn and poison And that's Andrew Slutsky who died in two thousand seventeen at the age of only twenty three. The book includes food's a testimonial from his mother Elena who criticizes the attitude of the oncologists. Who treated him but says she would have wanted Andrew to undergo any any treatment that might have extended his life? So could you talk about. Andrew was also one of the best friends of your donor share. Could you talk about the the treatment that he was subjected to what happened. And also your decision one of the most remarkable things about this book is not just of course your expertise. He's in in cancer and cancer treatment. But also these stories that you we've into the narrative of patients you've treated of patients The families who've witnessed their family members being treated in this way and and ultimately dying and this is Elena Andrew's was mother saying that she would have Andrew go through all of this treatment even if it meant the slightest possibility of extending his life. Yes actually Andrew is the impetus for me to write this book in Two Thousand Sixteen And he gets diagnosed with cancer. He has weakness in his arm. He goes to the emergency room. They do an MRI defined an inoperable triple brain tumor nine centimeter long. They couldn't remove it from the day. One every on colleges that treated Andrew knew that his his chance of survival is zero point zero zero beyond what is to be expected. No matter what we give him he was going to die. We we all knew it this boy and he opened his eyes coming out of anesthesia. He turned to his mother and he said mom don't what he called Astro. She's on the cutting edge. She will find the best. Thank you for me and Halina called me. This young man who's been lean in and out of my house since he's fifteen years old because he's best friends with my daughter. I felt so ashamed of myself that there is nothing nothing I can offer this boy and the fact that we are failing the Andrews and the xenophobes and the harveys and the owners of this this world so spectacularly and instead of feeling embarrassed we go around coming our chest claiming that we are building in sixty eight percent patients sixteen percent with water again and again I ask and what we do to Andrew in the next sixteen months. Even though we knew his John's survivor is we give him chemotherapy. Radiation therapy surgery after surgery. More Chemo. More radiation more immune therapy and he suffered the side effects of every one of them without benefiting from anything but then the converse is also a problem. Let's say we didn't treat him and let the brain tumor takeover that debt from advanced. Cancer is just horrendous. Friend is so basically the treatment what what are the choices we offered Andrew at this point. Either you die of cancer or the treatment but you're going to die and the question. I asked myself as why why Andrew diagnosed when he was nine centimeter long. We know that cancer is a silent killer. We know Noise Ages Immune to getting cancer at twenty two. This boy got cancer and specifically in his case how could it have been undetected earlier. Talk about the tests that you think need to be developed and are actually already there but somehow missed him so amy. I'm calling for a complete paradigm shift. What I'm saying is that even the screening measures that we are using and newly for for example? Doing a mammogram is too late for some people. What we need to do is consider the human body as a machine and continuously learn to to monitor it for the detection of diseases whether it's Alzheimer's or cancer or diabetes? We need to catch all of these diseases. Leeann try to nip them in the bud. This is what I'm asking for. What has to be done for that? Children get cancer not that many but certainly they do and again we treat them with these draconian measures and they end up with developmentally shoes fertility. Shoes all kinds of problems. So what I'm asking for is as we need to develop those markers that can identify cancer at its inception. It is doable. It is possible a lot of research is going on in this country and elsewhere also to fine footprints of cancer for example. I'll give you couple of examples when when cancer starts. It divides fast it sends device fast. Divide foster the normal sales which means it needs more nutrition so it start makes starts making new blood lead vessels as soon as that happened. Area becomes hot because of new blood going into that one. Eighty this what area can be detected. People are developing bedsheets. Beats and mattresses where you can go to sleep and you're overnight. You'll being scanned for hot areas. Let's say a hot areas detected in my pancreas doesn't mean the next morning. I should have an open abdominal surgery Iverson rated and removal of former. No it means that. Now there's something abnormal which needs to be monitored. I am now considered someone at high risk. So I should be monitored for other biomarkers these cells which are developing in my pancreas will be shedding adding their proteins into the bloodstream. If they are not shedding you know one thing we can do. We can yell at them. How you yell at them? you use sound waves literally truly ultrasound to hit them and they start shivering and they start shedding their proteins into the blood and we get the blood and detect the biomarker is. Is there a cancer industrial complex. That's preventing this kind of research and development of the preventive and the early detection approaches to cancer. Absolutely not me. In fact my contention and Mike seaters that. If here's an industry that is investing being in an enterprise that has a ninety five percent chance of failure but they keep investing billions of dollars because one of their drugs. Mix It if it improves survival. Reliable by ten seconds more than so. You're saying there is a cancer industrial complex. That was there's not preventing it they don't know what's a better thing to do. So what I'm saying. I guess we just set a new goal and be financially incentivize the goal then all these people will turn around and come to the first cell instead of going after the lasted wanted. What about Vice President Biden's moonshot challenge around curing cancer? I I was one of the fortunate people to meet vice-president Biden in his Across his dining room table for the cancer moonshot and had a very wonderful discussion discussion with the vice-president Biden his heart in the right place and there is a certain fraction of that billion dollar. The money that he has allocated for cancer research is definitely towards prevention and early detection of cancer. But it's not enough that obtained a vision is what we really need and but we need. I'm not saying all entries. Search should stop. Nobody should miss scored or miss. Hear me I'm saying we have got impatience. Of course we have to worry about them and we have to keep developing better treatments and better understanding of biology. But I think at at least half of the resources and all the resources going into these failing clinical trials these billions and billions of dollars can be redirected corrected for future patients to try and detect the disease early a solution which will be applicable university. We have to break them. We're coming back to our guest. Dr Jasser Ross oncologist professor of Medicine at Columbia University where she directs the center of form of bone marrow cancer. Her new book is out. It's called the first cell and the human costs of pursuing cancer till last stay with us was birds birds so march for a You thank in in New York. By Saint Vincent the photos and the video were compiled by cats Lutsky for her brother. Andrew when the patients profiled and Dr Oz Ross's book the first cell and the human costs of pursuing cancer to the lask. He died when he was twenty three years old of a particularly aggressive form of brain cancer. I made me Goodman with nermeen shape. We're spending the hour with Dr Astro. Rasa the renown oncologist professor of Medicine at Columbia University. versity you're mean so I want to ask you about one of the criticisms that your book has come under in The New York Times Dr Henry Marsh Praises the book. But says you're too optimistic about the solutions you propose. Marsh writes quote her diagnosis of the ills from which cancer treatment suffers strikes me as accurate but her solution seem infused with the same unrealistic optimism. Optimism she identifies as the cause of so much suffering. This is Dr Henry Marsh writing in The New York Times. Are you guilty of too much optimism. nope that's the short on their mean. You know I started my career in oncology basically soclean one thousand nine hundred seventy seven. I was twenty four years old. FRESH OUT OF MED school had come here. I started working at Roswell Park Cancer Institute because I was going to kill cancer so very quickly I taught and Within seven eight years it was very clear to me the disease that I had invested. Did all my energies in acute myeloid leukemia. That in my lifetime this disease will not be cured. It is so complicated so at that point I turned my attention towards studying an earlier form of the disease because many of my patients who came with acute view Kimia gave a history of having had some low blood counts and being anemic photo few months before the developer Yukimi. And so I said to myself why not catch this disease Aziza Yukimi of fees and intercept then and not let it become this stage monstrosity. So I started collecting. This is where we're being. An immigrant helped me because had I gone to school in this country. If I started to study acute leukemia my next step would have been to make a mouse model of this disease which are very artificial which just for drug development at least they're very good models for studying biology but not for drug development but because Ause I was an immigrant I simply started saying oh I have to study cancer. So let's let me save these cells and I started banking sales on my patients today. I have a tissue repository which has sixty thousand samples from thousands of cancer. Patients followed Longitudinal. Well annotated with all their clinical Michael and but that logic data in the computerized forms and this is a very precious resource one of a kind. Not One single cell comes comes from another physician. I still do the bone marrows with my own hands which I'm going to do in the next hour when I get to my clinic but the idea I had was was that earlier detection will help. That was many years ago. Where's my solution? So the question. You asked me in the criticism that Dr Marshes giving gain can be applied to me. Yes that thirty five years ago. I felt that detecting the disease. Early pre leukemia would help me. It hasn't helped me. Because PRILUKI amihai itself is a very malignant disease and can kill so then I realized that by you using these samples of acute leukemia. Give me a working my way. Back to pre -pedia I can then ask the question. Why some people get Cumia to begin with why did they get? MD S and and one sign weakened. Discover that by using these tissue samples and the latest technology of proteome. Ix Genomics transcript Oh makes meta law makes expansional mix. We will find the same kind of thing you have safer breast cancer. The Bracha gene can be find something. That's making people susceptible boo because of their inherited in what about targeted immunotherapy. People think that it has gone so far to help cancer patients. What is it and what Do you see are the prospects for the answer to that is i. You have to understand what. What is the cell therapy? So there are many many different forms of immune therapies fourteen. Fifteen different kinds but the ones that are receiving all the attention are basically two types. Checkpoint inhibitors are drugs which cancer cells so every cell expresses proteins. that either say eat me or don't it me. Cancer Cels cels learn to express only protein. Say don't eat. Don't eat me don't so. This is how they deflect immune we have less than a minute and so we tried drugs to to do that we succeeded. The response doesn't lost. The other. Form of therapy is self therapy's that we use immune therapy using cells Dell's T.. Cells for example cannot distinguish between a normal CELENA cancer cell. In the organ. All we can do is weekends active. These cells was and say go. Kill the whole organ and cancer will die with it so the only sell we have succeeded. In killing. All the only organ we have succeeded in killing. So far is B. Cells which which are kind of lymphoid cells in the body and killed them and then we please be cell function by giving immunoglobulins for the rest of their time. We can't do that for deliver. We can't kill the liver and expect to replace it. That's why immune therapy using cells is not going to work. Well we're going to have to leave it there but people can pick up the book and take it from their doctor. Ostra Rasa oncologist professor of Medicine at Columbia University heads up the MDIS center a form of bone marrow. Cancer her new book the First Sal and the human cost of pursuing cancer to the last with nermeen shape.

Cancer professor of Medicine United States Columbia University Amy Goodman pancreatic cancer Elena Andrew New York murder brain cancer Saudi Arabia Roswell Park Cancer Institute Rush University Cancer Center official Michael Duffy Pentagon president Center for Public Integrity
NEJM This Week - November 8, 2018

NEJM This Week - Audio Summaries

32:33 min | 2 years ago

NEJM This Week - November 8, 2018

"Welcome. This is the New England Journal of medicine. I'm Dr Lisa Johnson. This week November eighth twenty eighteen we feature articles on treatment for lymphatic. Filariasis combination therapy for relapsed. Maya Loma increasing calorie delivery in the critically ill Zola, Florida sin for gonorrhea Darah Toomey MAB for transplant related pure red cell. A pleasure and suppression of casing kind as one alpha in AM L A review article on ethical issues in the neonatal ICU. A case report of a woman with Paris Theberge. And weakness of the foot and domino wall and perspective articles on getting rid of stupid stuff on immunotherapy combinations in multiple myeloma on gonorrhea and on terra Nova. A trial of triple drug treatment for lymphocytic. Philly riotous by Christopher king from case. Western Reserve University school of medicine Cleveland. The World Health Organization has targeted lymphatic filariasis for global illumination by twenty twenty with a strategy of mass Drug administration in a randomized trial involving adults from Pappa when NEW GUINEA with Wu Carreira, Ben Crofty microfilm premia one hundred eighty two participants were assigned to receive a single dose of three drug regimen of either Mactan plus diethylene car-bomb Zine plus album, dissol a single dose of a two drug regimen of DFL car-bomb Zine, plus L, Ben dissol or the two drug regimen. Once a year for three years. The three drug regimen cleared micro Filaret Mia in ninety six percent of participants at twelve months twenty four months and thirty six months. A single dose of the two drug regimen cleared microfilm Mia in thirty two percent of. Participants at twelve months in fifty six percent at twenty four months and in eighty three percent at thirty six months. The two drug regimen administered once a year for three years cleared microfilm premia in thirty four percent of participants at twelve months. Seventy five percent at twenty four months and in ninety eight percent at thirty six months. Moderate adverse events were more common in the group that received the three drug regimen. Then in the combined to drug regimen groups twenty-seven percent versus five percent. There were no serious adverse events the three drug regimen induced clearance of microphones area from the blood for three years in almost all participants who received the treatment and was superior to the two drug regimen administered once and non inferior to the to drug regimen administered once a year for three years. In an editorial David Molly new from Pembroke place Liverpool. United Kingdom writes that the WHO has recommended that annual triple drug treatment with Ivermectin plus Diafoil car-bomb Zine, plus L, Ben dissol can be used for mass Drug administration rather than annual treatment with two drug regimen of DFL car-bomb Zine, plus L Ben dissol in areas where implementation has not started in areas where fewer than four effective rounds of treatment with the two drug regimen have been performed and in areas where epidemiologic targets in surveys have not been met. And hence, local transmission might be ongoing the new triple drug treatment, however is not recommended in areas were uncle Circe. Asus is endemic because of the potential adverse effects that result from the action of diethylene car-bomb Zine against the encore circa. Parasite or in areas where low Ayas is co endemic also because of the potential serious adverse events that are caused by the antisemitic affect of Ivermectin in persons with high Paris A-Team levels of Loa Loa this precludes the use of the triple drug treatment. In many African countries were all three filarial parasites are endemic and present of public health challenge. However elsewhere, the triple drug treatment provides significant promise for the elimination of transmission within a much shorter timescale, and at less cost the manufacturers of Ivermectin have agreed to increase the donation of the product and in August, some moa became the first country to implement the triple drug treatment with the intent of eliminating the infection that has persisted for more than one hundred years. Elo Tuesday, MAB plus pummeled him I'd index methicillin from multiple myeloma by militias Dimopoulos from the national and Kappa district university of Athens, Greece in this study one hundred seventeen patients with multiple myeloma that was refractory or relapsed and refractory to lend a litt- Meyde and uproarious OMB inhibitor were randomly assigned to receive the immuno stimulatory monoclonal antibody ELO Tuesday mob, plus the immunomodulating agent poma might and decks medicine Ella. Two-zone that group or pummeled him. I'd and decks Memphis, own alone control group after a minimum follow up period of nine point one months. The median progression free. Survival was ten point three months in the ELO Tuesday map group and four point seven months in the control group the overall resp-. Monserate was fifty three percent in the ele- Tuesda map group as compared with twenty six percent in the control group, the most common great three or four adverse events were neutral. Genia thirteen percent in the ELO Tuesday map group. I twenty seven percent in the control group anemia. Ten percent versus twenty percent and hyperglycemia eight percent versus seven percent. A total of sixty five percent of the patients in each group had infections infusion. Reactions occurred in five percent of patients in the ele- Tuesday map group among patients with multiple myeloma in whom treatment with lenna litt- MIDA and uproarious OMB inhibitor had failed the risk of progression. Or death was significantly lower among those who received ELO Tuesday mob plus pummeling amid and ex methadone then among those who received poma Lyneham I'd plus dex own alone. Immunotherapy combinations in multiple myeloma known. Unknowns a perspective article by Nicole Gormley from the food and Drug administration, Silver, Spring, Maryland. In November twenty seventeen the FDA required labeling changes for the commercially marketed programmed cell death, one PD one inhibitor Pembrey Lizzy MAB and the thalidomide analog immunomodulating agents. These changes included information regarding increased mortality observed in two randomized trials of Pembrey Lizzy MAB with an immunomodulating agent. Lenna litt- might or pummeled him. I'd and ex Memphis zone in patients with multiple myeloma in August and September of twenty seventeen the FDA had placed approximately thirty clinical trials investigating these combinations on hold and issued a safe. The alert although three immune related deaths had occurred. There were no unifying causes of death or unique adverse event patterns that could explain the observed effects on overall survival. Similarly, neither trial revealed differences in time to progression. That would indicate that adding Pembrey Lizzy MAB, accelerated cancer progression. Now Dimopoulos and colleagues report the results of a phase two trial of ELO Tuesday mob which showed a positive effect on progression free survival and a trend toward improved overall survival. When the agent was added to pummeled him. I'd decks methicillin this experience in multiple myeloma. Sounds a cautionary note, how a combinations components interact in a complex immunologic tumor, micro environment will need to be thoroughly investigated, but the. Role of PD one therapy in multiple myeloma may not be a closed book. Energy dense versus routine enter nutrition in the critically ill by the target. Investigators for the ends IX clinical trials group the effect of delivering nutrition at different calorie levels during critical illness is uncertain and patients typically receive less than the recommended amount. This randomized trial involving three thousand nine hundred fifty seven adults undergoing mechanical ventilation in forty six. Australian and New Zealand intensive care units evaluated energy, dense one point five K Cal per milliliter as compared with routine one K Cal per milliliter. Enter all nutrition at a dose of one milliliter per kilogram of ideal body weight per hour commencing at or within twelve hours of the initiation of nutrition support and continuing for up to twenty eight days. As while the patient was in the ICU the volume of interim nutrition delivered during the trial was similar in the two groups, however patients in the one point five K Cal group received a mean of one thousand eight hundred sixty three K cows per day as compared with one thousand two hundred sixty two cake house per day in the one K cow group by Dane ninety a total of twenty six point eight percent of patients in the one point five. K Cal group and twenty five point seven percent of patients in the one K cow group had died. The results were similar in seven predefined subgroups higher calorie delivery did not affect survival time receipt of organ support number of days alive and out of the ICU and hospital or free of Oregon support or the incidence of infective complications or adverse events in patients undergoing mechanical ventilation. The ray. Eight of survival at ninety days associated with the use of an energy dense formulation for internal delivery of nutrition was not higher than that with routine. Enter a nutrition. Single dose Zola floats in for treatment of euro genital gonorrhea by Stephanie Taylor from the Louisiana state University Health sciences center, New Orleans, antibiotic resistant nicer area, gonorrhea has prompted the development of new therapies Zola. Florida sin is a new antibiotic that inhibits DNA bio, synthesis in this study, one hundred seventy nine men and women who had signs or symptoms of uncomplicated euro, genital, gonorrhea or untreated euro genital gonorrhea or who had had sexual contact in the preceding fourteen days with a person who had gonorrhea were randomly assigned to receive a single oral dose of Zola Florida sin or a single intramuscular dose of Seth Triax zone. Among the one hundred forty one participants in the micro biologic intention to treat population. Who could be valuated microbiological cure at euro genital sites was documented in ninety six percent of those receiving two grams or three grams of Zola Florida sin and in one hundred percent in those receiving Seth Triax zone. All rectal infections were cured in all five. Participants receiving two grams of Zola Florida sin and all seven receiving three grams as compared with three of three participants in the group receiving Steph Triax zone, Farren Geel infections were cured in fifty percent. Eighty two percent and one hundred percent of participants in the groups receiving two grams of Zola Florida's in three grams of Zola Florida sin and Steph Triax zone respectively. Eighty four adverse events were reported, according to investigators Twenty-one adverse events were thought to be related to Sola Florida sin and most such events were gastrointestinal. The majority of uncomplicated, urogenital and rectal Ghana. Cockle infections were successfully treated with oral Zola Florida sent but this agent was less efficacious in the treatment of Farren Geel infections. Nice Syria gonorrhea rising infection rates dwindling treatment options up perspective, article by Susan blank. From the New York City department of health and mental hygiene gonorrhea infection is the second. Most commonly reported notifiable condition in the United States and case rates have been increasing since two thousand nine in twenty seventeen a total of five hundred fifty five thousand six hundred eight cases of gonorrhea were reported nationally, the largest number since nineteen Ninety-one and in eighteen point six percent increase over twenty sixteen in twenty fifteen the Obama administration deemed C difficile carbon PanAm resistant Entra battery C A and N gunnery a the most urgent infectious public health threats to national security, given the accelerating. Emergence of an. Antibiotic resistance in these organisms without a concerted global effort to mitigate antibiotic resistance infected persons, primarily sexually active young adults who tend to be otherwise healthy may require extended hospital stays and additional follow up visits for an infection. That can currently be managed on an outpatient basis such a shift could impose a series burden on healthcare systems and societal productivity internationally studies like the one reported on by Taylor are a step forward in the quest to identify new antimicrobial options for gonorrhea treatment. Given the challenges in clinical follow up in this patient population. The single dose regimen is promising though the study was small the efficacy shown is encouraging and Zola Florida's in has the potential to be an effective antibiotic for treating gonorrhea though the limit. It'd activity observed in key anatomical sites of infection such as the firings will need to be better defined. Darah tomb Yuma for delayed read selling graph -ment after allogeneic transplantation by Claudia shep-. We from the Dana Farber Cancer Institute at Saint Elizabeth's medical center, Boston allogeneic stem cell transplantation, is a curative treatment option for patients with malignant hematological diseases, including Milo dysplasia syndromes in twenty five to fifty percent of transplantations HLA, matched allogeneic stem. Cell donors have some degree of abo blood group incompatibility with the recipient a consequence of abo incompatibility caused by persistent recipient antibodies directed against donor red cells is that red cell recovery may be delayed for several months. The recipients bone marrow is characteristically devoid of arith- Royd precursors pure red cell. A pleasure. Darah Toomey MAB. A human. I g g one Kappa monoclonal antibody targeting CD. Thirty eight is used to treat. Multiple myeloma these authors describe successful treatment with Darah to MAB in a case of treatment refractory pure, red cell, a pleasure after abo mismatched, allogeneic stem cell transplantation. The patient was a seventy two year old man with the Milo dysplasia syndrome who received a transplant from an H L. A matched unrelated donor with a major abo incompatibility blood group. A in the donor and blood group o in the recipient. The patient had persistent circulating anti antibodies and no red cell recovery. Two hundred days after transplantation standard treatments had no effect within one week after the initiation of treatment with Darah to MAB. He no. Longer required. Transfusions? Ethical problems in decision making in the new Natal ICU a review article by John Lantos from children's mercy Kansas City, Missouri in the neonatal intensive care unit. Nick you disagreements about whether life sustaining treatment can be ethically withheld or withdrawn are not uncommon usually the dilemma comes down to questions about the value of life with severe physical or cognitive impairments. Disagreements can go in both directions, sometimes doctors recommend treatments and parents refuse. Sometimes parents request continue treatment that doctors think inappropriate such conflicts have occurred in cases of hypotheses encephalopathy, degenerative neurologic diseases and even brain death these disagreements can cause moral distress among doctors, and nurses and debates about the ethical justifiability. Of unilateral decisions that treatment is futile. And should be withdrawn. Usually disagreements are resolved by ongoing discussion between doctors and parents by bringing in other family members, or by consulting an ethics committee. Most intensive ists. Learn how to negotiate with families in these situations occasionally disagreements become intractable and cases end up in court attention to the process by which decisions are made rather than to the result of the decision. Making process has changed the way we think about Neo Natal bioethics recognition of the role that doctors play as choice architects suggest that there might be new ways to think about the ethical responsibilities that go along with that role. A fifty eight year old woman with Paris, thea and weakness of the left foot and domino wall. A case record of the Massachusetts General Hospital by Tim Reta and colleagues a fifty eight year old woman from New England presented to the outpatient neurology clinic in early autumn because of Hypo Sesia Paris, these ya and weakness ten weeks earlier back pain developed between the shoulder blades. The pain resolved without an intervention six weeks before this presentation, numbness developed in a band like distribution around her trunk one week later, the numbness extended to the upper abdomen. Paris Thenia developed in the third fourth and fifth fingers of the left hand and the fourth and fifth fingers of the right hand. M R I of the spine was scheduled, however, two weeks before this presentation the numbness extent. Ended to the genital area. And urinary incontinence developed prompting the patient to present to the emergency department overall, this patient syndrome was most consistent with a sub acute. Polly ridiculous Pathy or poly ridiculous neuropathy. There are several disorders that can cause or mimic sub acute Polly ridiculous Pathy or poly ridiculous neuropathy patients who have Lima ninja ridiculous typically present to eighteen weeks after infection during the early disseminated phase with pain sensory loss and a reflexive weakness over half of patients with Lima ninja ridiculous present with seventh cranial nerve palsy a manifestation of Lyme disease that many recognize, but any cranial or spinal nerve root may be involved. Inhibition of casing kind as one alpha in acute myeloid leukemia. A clinical implications of basic research article by Benjamin Ebert from the Dana Farber Cancer Institute, Boston acute myeloid leukemia. AM L is genetically heterogeneous cancer that arises in Hamadeh poetic stem cells for the past forty years standard treatment for AM L has consisted of a combination of two chemo therapeutic agents site, Tara bean and an anthracite Clint this regimen results in high rates of remission. But in the majority of cases fails to Aratu, Kate, the residual lewke MC stem cells that are the reason for relapse and poor outcomes. In patients with AM L, the comprehensive genetic analysis of AM L in the past ten years has revealed recurrent, somatic Lee MU. -tated genes leading to the development of new targeted therapies, including inhibitors of FMS like tyrosine kinase three an ice. Oh citrate. Dehydrogenation one and two however monotherapy with these drugs does not result in durable responses and combination with chemotherapy has only modestly improved outcomes, thus new drug targets in patients with AM L are needed the authors of a recent report synthesized highly potent inhibitors of casing kindness. One alpha and tested them for activity in AM L casing kind as one alpha targets, the ape hop toasts inducing protein, p fifty three for degradation and a positive of functional p fifty three underlies the neoplastic behavior of cancers, including acute myeloid leukemia. Suppression of this. Kindness is a candidate pathway for drug development. Expression of concern by Jeffrey raisin editor in chief in the issues of June seven two thousand one and January three two thousand and two. We published articles from the laboratory of Dr Piero end versa. At that time. The laboratory was located at the New York Medical College in two thousand seven and versa. Moved his laboratory to Brigham and women's hospital. A major teaching hospital of Harvard Medical School an institutional investigation into work done in the laboratory while en versa was at Brigham and women's hospital has found evidence consistent with fabrication of data and image manipulation during the investigation. Evidence was uncovered that is consistent with image manipulation. In the two thousand one article noted above we're communicating with the authors of the two thousand one and two thousand and two articles and with institutional officials at the New York. Medical College concerning the veracity of the data presented therein while we await the results of these communications. We are publishing this expression of concern to indicate that the data presented in the articles named above may, not be reliable. Getting rid of stupid stuff up perspective article by Melinda Ashton from Hawaii Pacific health, Hon. Lulu many healthcare organizations are searching for ways to engage employee's and protect against burnout and involvement in meaningful work has been reported to serve both functions. According to Bailey and Madden. It is easy to damage employee's sense of meaningfulness by presenting them with pointless tasks that lead them to wonder why am I bothering to do? This an increase in administrative tasks has resulted in less time for the activity that clinicians find most important interacting with patients, some commentators have recently suggested that it may not be the electronic health record e HR per se that leads to burn out, but rather the approach to documentation that has. Has been adopted in the United States, although Dr Ashton's health system, like most in the United States cannot magically eliminate the documentation required for billing and regulatory compliance. She and her colleagues had reason to believe that there might be some documentation tasks that could be eliminated. They asked all employees to look at their daily documentation experience and report anything in the ER that they thought was poorly designed unnecessary or just plain stupid. The stupid stuff program has been embraced throughout their organization over the past year, and has extended beyond removing unnecessary documentation from the e HR as an organization, they are searching for and finding work that should simply be retired. Terra Nova a perspective article by C alissandria Kalyani from Massachusetts. I n ear Boston. A few months before she started her surgical residency. Dr Kalyani became obsessed with tales of polar exploration how early twentieth century Englishman attacked the problem of the great unknown seeking the extreme reaches of the earth for the benefit of science and the glory of their country, the idea of explorers, bidding farewell to their wives and children to set out in flimsy wooden boats. Knowing that they might not return compelled by deeply felt duty to see to know to map this sheer act of enduring slogging forwarding. Gale force winds dutifully, documenting their expeditions in temperatures well below zero being the first person to stand. On a particular bit of earth in the middle of an icy hell made all manner of discomfort and suffering worthwhile. The idea of undergoing true physical hardship for a greater goal spoke to Dr kalaiana their surgical residency here. Comprised twelve rotations lasting four weeks each they became a close. Knit crew setting their alarms for four in the morning. Six days a week, Dr Kalyani distress tolerance rose to astronomical heights. When her resolve faltered, she reminded herself that her suffering was trivial compared with out of her patients. This dubious bravery cominated one day in her unceremoniously fainting in a patient's room while gowned up and performing a sterile procedure. Smacking her head on a heavy middle cart on her way to the ground. Dr Kalyani remembers waking up concussed with a prickly feeling all. For her body. Her neurosurgery attending crouched over her. Our images in clinical medicine features. A fifty one year old woman who was brought to the emergency department from a local international airport after reporting the ingestion of thirty packs of opium weighing fifty grams, each the patient had no symptoms and the results of physical examination were normal. C T of the abdomen pelvis revealed several oval structures with visible passageways. There was no evidence of bowel obstruction ingestion of lead contaminated drug packs was suspected Orel polyethylene glycol was administered and the patient passed all packs without complication laboratory analysis of the contents of one pack confirmed the presence of opium. No other drugs were detected the lead concentration in an opium. Sample was three thousand two hundred parts per million because opium is often sold. According to wait, heavy metals such as lead, maybe added to the opium during manufacturing or at the time of packing to increase its weight exposure to let at such high concentrations can cause severe toxic effects that can manifest as neurologic and guestroom intestinal signs and symptoms, including encephalopathy altered mental status, seizures abdominal pain, vomiting, constipation and anorexia the patient remained a symptomatic at the time of discharge but the use and smuggling of lead contaminated drugs is a public health concern. A thirty nine year old man presented to the emergency department with a four week history of increasing abdominal pain and constipation physical examination of the abdomen. And the results on domino imaging including ultrasonography and CT were normal laboratory investigations revealed a hemoglobin level of twelve point five grams per deciliter findings on upper endoscopy and colonoscopy were normal since the cause of the gastrointestinal symptoms was unclear laboratory investigations for poor fear were performed a twenty four hour. Urine. Tests showed an excretion level of delta Amina level Inuk acid of five hundred forty five micro moles per day, and the lead level in blood was markedly elevated at one hundred thirty six micrograms per deciliter, physical examination was repeated and a gray line. Along the margins of the lower gums known as Burton's line was noted Burton's line is a sign of chronic lead. Intoxication that develops when lead reacts with oral bacteria metabolites the patient, then confirmed a ten year history of chewing opium analysis of a sample of the patients opium revealed, a lead concentration of seventeen milligrams per one gram of opium lead may sometimes be added to opium to increase its weight when it sold the patient was treated with keeling agents and was counseled about the importance of oral hygiene, he also stopped chewing opium at follow up seven months after the initiation of treatment. The patient's of domino pain and constipation had resolved and Burton's line was markedly diminished. This concludes our summary. Let us know what you think about our audio summaries. Any? Comments or suggestions may be sent to audio at any J M dot org. Thank you for listening.

multiple myeloma Zola Florida opium Pembrey Lizzy MAB Florida Ben dissol Dr Kalyani United States New England Journal of medicin Dana Farber Cancer Institute Memphis methicillin Boston Farren Geel Paris OMB Stephanie Taylor World Health Organization
NEJM This Week  August 13, 2020

NEJM This Week - Audio Summaries

26:44 min | 11 months ago

NEJM This Week August 13, 2020

"Welcome. This is the New England Journal of Medicine I'm Dr Michael Bearer. This Week August Thirteenth Two, thousand twenty, we feature articles on as society and plus Magneto in Am L. Compression for recurrent Salvia light. So the leg decreased population-based mortality from lung cancer, the United States and the WHO the need for a tighter particulate matter air quality standard and Billy Rubin in IBD and pancreatitis. A review article on epigenetics therapies for cancer a case report of a woman with a lung mass and perspective articles on whether we spend too much on healthcare on people with Hepatitis C. who inject drugs on Hepatitis C. Treatment in correctional facilities and on a national medical response to crisis. A new interactive medical case entitled caught in a flare features a woman with systemic lupus Erythematosus who presents with a one month history of worsening fatigue diffuse arthritis Arash on her face and arms swelling in her legs and frequent urination. Test your diagnostic and therapeutic skills at any J. M. Dot Org. As excited in Veneta classics in previously untreated acute myeloid leukemia by Courtney Denardo from the University of Texas Md. Anderson. Cancer Center Houston. Older patients with acute myeloid leukemia am L. have a dismal prognosis even after treatment with a Hypo methylated agent. As is cited in added to Veneta classics had promising efficacy in a previous phase one B study. In this study four, hundred, thirty, one previously untreated patients with confirmed aml who were ineligible for standard induction therapy because of coexisting conditions because they were seventy five years of age or older, or both were randomly assigned to as exciting deemed plus either Veneta cracks or placebo at a median follow up of twenty point five months the median. Survival was fourteen point seven months in the as exciting Veneta class group and nine point six months in the control group. The incidents of complete remission was higher with as assiting. Veneta classics than with the Control Regimen thirty, six point seven percent versus seventeen point nine percent as was the composite complete remission, sixty, six, point, four percent versus twenty eight point three percent. The most common adverse events in both groups were gastrointestinal and humid logic with a higher frequency of neutral Pena and Febrile Neutrogena in the as aside a dean Vendetta Class Group. In previously, untreated patients who were ineligible for intensive chemotherapy overall survival was longer and the incidence of remission was higher among patients who received as exciting plus Veneta classics than among those who received as society alone. Charles Schiffer from Wayne State University School of Medicine Detroit writes in an editorial that am L. is a molecular -ly heterogeneous disorder characterized by symptoms related to pan site a Pina, and by an accumulation of poor myeloid precursors that is a consequence of a blockage in normal cellular differentiation although the therapeutic approach to aml has remained largely unchanged for the past few decades, it is notable more than thirty percent of children and young. Adults with this disease are cured after receiving chemotherapy alone with variations in the combination of an anthracite clean and sight tarabin the three and seven regimen without stem cell transplantation. The outcome in adults older than sixty years of age is markedly inferior to that in younger persons with a lower incidence of complete remission and long term disease free survival of approximately ten percent given this background frustration. The trial by Denardo in colleagues is welcome. US alone. Veneto class has modest activity in patients with am L. However as. By denardo, noteworthy synergism was associated with the combination of as exciting and Veneto clocks with meaningfully higher responses. Then those with is assigning alone. Compression therapy to prevent recurrent savvy lettuce of leg by Elizabeth Webb, from the Calgary Public Hospital Bruce Australia. Chronic Dima of the leg is a risk factor for cellulitis. Daily use of compression garments on the leg has been recommended to prevent the recurrence of cellulitis but there is limited evidence from trials regarding its effectiveness in this small single center non blinded trial eighty, four participants with chronic Dima of the leg and recurrent cellulitis were randomly assigned to receive leg compression therapy plus education on cellulitis prevention, compression group, or education alone control group at the time of a planned interim analysis when twenty three episodes of cellulite has had occurred fifteen percent of participants in the compression group and forty percent in the control group had had an episode of Cellulitis and the trial was stopped for efficacy. Seven percent of participants in the compression group and fourteen percent in the control group were hospitalized for cellulitis. Most quality of life outcomes did not differ between the two groups. No adverse events occurred during the trial in this small trial involving patients with chronic dima of the leg and cellulitis compression therapy resulted in a lower incidence of recurrence of cellulitis then conservative treatment. The effect of advances in Lung Cancer Treatment on population mortality by Nadia. How later from the national? Cancer Institute the Maryland. This study describes trends in mortality among patients with different subtypes of lung cancer in the context of changing incidents and survival patterns in the US general population. Mortality from non small cell lung cancer and Seo. Elsie decreased even faster than the incidence of this subtype and this decrease was associated with a substantial improvement in survival over time that corresponded to the timing of approval of targeted therapy among men incidents base mortality from Ns, ELC decreased six point three percent annually from two thousand, thirteen through two, thousand sixteen whereas the incidents decreased three point one percent annually from two thousand, eight through two thousand sixteen corresponding lung cancer specific survival improved from twenty six percent among men with an S. c. l. c. that was diagnosed in two thousand, one to thirty five percent among those in whom it was diagnosed in two thousand fourteen. This improvement in survival was found across all races and ethnic groups. Similar patterns were found among women with seal see in contrast mortality from small cell lung cancer s ELC declined almost entirely as a result of declining incidents with no improvement in survival. This result Carlos with limited treatment advances for Seo Elsie in the timeframe examined, this analysis suggests that reduction in incidents along with treatment advances particularly approvals for and use of targeted therapies is likely to explain the reduction in mortality observed during this period. epigenetics therapeutics for Cancer Review. Article by Susan Bates from Columbia University Irving Medical Center New York. Cancer Cell Biology is impacted by alterations in EPI genetic regulation of gene. Expression. cro-magnon is one of the earliest identified targets for Cancer Therapeutics Drug Development aimed at altering chrome ten can be traced to the differentiating agents of the nineteen seventies and they're linked to DNA methylation a more precise understanding of the complexity of chromosome and its role in uncle genesis began to emerge when sequencing of the cancer genome revealed mutations in numerous genes, encoding proteins that regulate cro-magnon. In many cases these mutations proved to be critical in maintaining the malignant process and observation that lead to new therapeutics. epigenetics begins with DNA and histone proteins to macromolecules structurally and functionally intertwined in. Chrome. DNA and histone proteins are modified in ways that regulate. Ability and function and an alteration in these modifications is one hallmark of cancer epigenetics. Therapies seek to normalize DNA methylation patterns and post translational modifications on his stones that promote or maintain a malignant phenotype. This review summarizes approved agents and their clinical activity describes therapies in development and delineates challenges in the field of epigenetics. A, forty seven year old woman with a lung mass a case record of the Massachusetts, General Hospital by Amita Sharma and colleagues. A forty, seven year old woman presented during the early weeks of the covid nineteen pandemic with cough and shortness of breath two months prior intermittent non-productive call. Developed two days before this evaluation, the cough worsened in frequency and severity and new shortness of breath developed the next day the patients sought evaluation at the Emergency Department because of worsening shortness of breath with ambulation a review of systems was notable for Reina Ria, my ounces and dizziness ct of the chest revealed a mass in the right lower lobe with ground glass attenuation, and to reverse halo sign the initial findings on cat suggested a possible diagnosis. Of Cancer in particular lung at no Carcinoma Orleans Foam and oncology consultation was requested and the patient was discharged three days later fever persisted and the patient return to the hospital she reported that the cough had become productive of yellow green sputum and she also reported dizziness weakness Nausea and an episode of vomiting portable x ray of the chest revealed increased faint patchy opacity is in the right lower lobe the discrete mass was no longer a parent. Similar, symptoms were identified in several family members in her home. This suspected underlying of the patient's illness shifted from cancer toward an infectious process, a nasal fragile swab tested positive for SARS covy to are in A. WHO's next the United States and the World Health Organization an editorial by Barry Bloom from the Harvard t h Chan School of Public Health. Boston. Suppose a large forest fire hits, California millions of acres are burning and many towns or threatened. The forest service firefighters are cutting breaks and dropping water from helicopters. They plan their strategy using weather models that predict which way wind patterns will push the fire. Unfortunately, the models are imperfect. The wind turns in an unexpected direction. As a result, several towns are destroyed and there are billions of dollars in damage. What's the proper response to such a disaster if you were the current US government. You would shut down the forest service in the midst of the fire at least that's what's happening. Now with the World Health Organization on July seventh the president notified the United Nations that the United States plans to withdraw from the WHO the full implications of this decision are not yet clear. The United. States is responsible for the largest amount of funding for the WHO twenty two percent of assess stews and provides the largest voluntary contributions to polio eradication nutrition and vaccine programs, for example. The WHO in its staff have many roles in global health today in the middle of an outbreak in the United States we must take stock of where we are and how we can do better. To do that effectively, we need the. WHO The need for a tighter particulate matter air quality standard a sounding board article by the Independent Party matter. Review Panel. The Environmental Protection Agency EPA proposes to retain the current national ambient air quality standards in a Q. S. for fine particulate matter particles with a diameter of two point, five micrometres or less pm two point five that is levels not exceeding an annual average of twelve micrograms per cubic meter and a twenty four hour average of thirty five micrograms per cubic meter the current Nasdaq S. Were set in two thousand twelve on the basis of a scientific review that was largely completed in two thousand ten at that time available epidemiologic evidence supported by toxicological evidence and a risk assessment conducted by ETA staff indicated that annual exposure to pm two point five caused premature death at ambient concentrations as low as eleven micrograms per cubic meter however on the basis of more recent. As described in this article exposure to ambient pm two point five at the levels of the current standards will result in tens of thousands of premature deaths. Annually, the independent particulate matter review panel delivered their findings in a report submitted to the administrator and the EPA docket on October twenty second two, thousand, nineteen, the panel unequivocally, and unanimously concluded that the current pm two point five standards do not adequately protect public health and annual standard between ten micrograms per cubic meter and eight micrograms per cubic meter with protect the general public and at risk groups however, even at the lower end of the rage risk is not reduced to zero. Billy Ruben Intestinal Integrity The microbiome and inflammation a clinical implications of basic research article by Lebron v Tek from the Charles University Prague Czech Republic. Data from two preclinical studies one involving a mouse model of inflammatory bowel disease and the other mouse model of pancreatitis support the therapeutic effects of administrations of Billy Ruben containing nanoparticles engineered to target inflammatory areas in the intestine and pancreas respectively Hans Fischer who won the Nobel Prize for chemistry in Nineteen thirty and whose work led to the synthesis of billy. Rubin. Would be astounded by revolution in our understanding of the biology of billy. Rubin originally viewed only as a waste product of him catabolism Billy Rubin is now known to be a powerful endogenous antioxidant intensive research has shown that Billy Rubin is a versatile biologic effector. With Site Oh, protective anti pop, todic anticancer, and even endocrine like activities. It is known to affect the immune system in many ways such as boosting the generation of regulatory t cells and type seventeen helper t cells. These types of t cells have been shown to suppress the pathogenesis of inflammatory bowel disease in an experimental model. Thus, the recent reports on the anti inflammatory effects of Ruben containing nanoparticles are not surprising and especially notable finding however is the effect on the Gut microbiome home. This effect is consistent with recent data supporting that Billy Reuven as has been shown for bile acids exerts a selective pressure uninterrupted bacteria. Do, we spend too much on healthcare a perspective article by Katherine Baker from the University of Chicago. There's no question that the United States spends a great deal on healthcare both in absolute dollars and relative to other high income countries in two thousand, eighteen US healthcare spending totalled three point, six, trillion dollars which amounted to seventeen point seven percent of the Gross Domestic Product and eleven thousand two, hundred dollars per capita almost twice as much as many other high income countries the details of where that money comes from and where it goes are instructive and they highlight misperceptions that often skew the public debate. Most privately insured Americans get their insurance through their jobs with a small share getting coverage through the affordable care act marketplaces. The biggest expenditure categories are physicians and hospitals rather than prescription drugs although the amount going to prescription drugs is growing the proportion of healthcare spending going to drugs is fairly stable. Many people view more spending as inherently undesirable and wasteful. There's a kernel of truth to this shorthand given the evidence that we. Could achieve the same outcomes but spend less if we spent more effectively or that we could achieve better health at current spending levels. But this insight doesn't tell us what to do about it. Many strategies have been deployed for reducing spending, but policies focused only on spending less may do more harm than good. The options available to policy makers must be assessed on the basis of their effects on both spending and health outcomes. People with Hepatitis C. who inject drugs. Served not undeserving a perspective article by Gregory Dory from the Kirby Institute. Sydney Australia. The development of Highly Curative Direct. Acting. Antiviral DA therapy for Hepatitis C virus H. Infection has transformed clinical management of. And provided the impetus for the world health organizations and Bishops H C related targets for two thousand, thirty of seventy one million people with chronic hepatitis. C. Globally, an estimated six point one million are people who inject drugs and injection drug use is responsible for most new infections in many countries to reduce the burden of HDTV public health and clinical responses should focus on key populations people with advanced liver disease to reduce H. C be related mortality and those at high risk for transmitting h CV to reduce the incidence of HIV infection although. These populations overlap. The latter is younger is more highly marginalized and tends to lack access to care a comparison of h CB responses in Australia Canada and the United States is informative. The countries diverge when it comes to political leadership development of National H C strategies, and Public Health Responses to HDTV the. Australian government developed a model under which it received unrestricted access to DA's over a five year contract period with an annual expenditure cap the so called Netflix's model, their high treatment uptake has reduced the prevalence of active infection in people who inject. Hepatitis C. Treatment in prisons incarcerated people's uncertain right to direct acting antiviral therapy a perspective article by Alexandra Daniels from the Stanford Law School. California. People incarcerated in prisons account for approximately one third of HDTV cases in the United States an estimated seventeen percent of them are infected as compared with one percent of the general population. But only a small minority have received d. a treatment untreated H C may lead to cirrhosis Hypolito cellular. Carcinoma liver failure and death because people flow in and out of jails and prisons H. C prevalence in these institutions also affects prevalence in the community for most prison systems offering da's to all heb infected people would be enormously perhaps prohibitively expensive and few have done. So instead, some prisons rely on ad hoc decisions about may receive this treatment unlike most other wealthy countries, the United States recognizes no general legally enforceable right to health. Certain groups do have a circumscribed right to healthcare however and incarcerated people are one such group courts have interpreted the eighth amendment of the constitution which prohibits cruel and unusual punishment as requiring the government to provide medical care to people who have been convicted and incarcerated Eighth Amendment Law has evolved to require proof of two distinct elements to establish a right to health care a serious medical need and deliberate indifference to that need the question of whether failure to provide D.. A. As in correctional settings meets these requirements is the subject of a growing body of litigation. A national medical response to crisis the legacy of World War Two, a perspective article by Justin Bar from Duke University Durham North Carolina. This August marks the seventy fifth anniversary of the conclusion of World War Two in history's largest most destructive war, an estimated eighteen, million people or roughly three percent of the world's population died nearly four, hundred, twenty, thousand Americans were killed and six, hundred, seventy thousand were wounded. These grim numbers were mitigated however by an incalculable number of lives saved as a result of medical care. Many of the advances that were made would persist long after the war concluded a silver lining that we hope we'll have parallels in our current struggle with covid nineteen. A reductive argument that war is good for medicine would minimize the horrific human cost of combat. Yet, multiple scholars have highlighted how the urgency aura of crisis national attention and material resources inherent in organized armed conflict have catalyzed developments in medicine and surgery. The unprecedented scale and intensity of the Second World War created particularly fertile environment for US medical and surgical innovation. Moreover, whereas government involvement had generally dissipated after previous wars World War Two marked the commencement of a long-term deeply integrated relationship between government and medicine that continues to shape the US research agenda. Our images in clinical medicine features a thirty six year old woman gravitated to power one with a Mono Corey onic mono, amniotic twin pregnancy who was admitted to the hospital at thirty two weeks of Jazz station for a plan to Caesarian section. The antenatal course had been unremarkable routine cardio cog raphy before the procedure showed severe variable deceleration of the fetal heart rate in one of the twins, the tracing in the other twin was normal. Caesarian. Section was subsequently performed and twin girls were delivered. The APP Gar scores for both twins were seven at one minute and eight at five minutes. Complex knots in the umbilical cords were seen after delivery results of blood gas analysis of cord blood were normal true cuts in the umbilical cord are associated with intra-party complications and fetal distress complex nodding to the extent seen in this case in the umbilical cords of Monaco twins is uncommon. The twins were admitted to the Neonatal Intensive Care Unit and both were discharged from the hospital after forty days. In another image a sixty year old woman presented to the oral surgery clinic with Ginger swelling. She had a history of colorectal cancer which had been diagnosed a year earlier for which she had undergone surgery and received chemotherapy she I noticed the mass after leading occurred while she was brushing her teeth on examination a large non tender Padang mask was seen extending from the buckle. Jinja will border of the lower right second premolar to the lingual border. The surface was fry -able and dental indentations on the ACLU aspect suggested chronicity and Biopsy was performed and histo-pathological analysis showed infiltrating tumor consistent with Adna no carcinoma probably of colorectal origin at a follow up visit two weeks later further debunking of the tumor was performed Positron Emission Tomography showed multiple visceral metastasis. The most common sites of metastases of Colorectal Adenocarcinoma are the liver and lungs metastatic lesions in the oral cavity are unusual. The patient was enrolled in clinical trial of a chemotherapy regimen but was eventually lost to follow up This concludes our summary. Let us know what you think about our audio summaries. Any comments or suggestions may be sent to audio at any am dot org. Thank you for listening.

United States Billy Rubin World Health Organization Veneta classics Cancer Cellulitis Courtney Denardo cough Lung Cancer Billy Ruben California New England Journal of Medicin lupus Erythematosus bowel disease J. M. Dot Org IBD Anderson Cancer Therapeutics Drug Devel
77 | Azra Raza on The Way We Should Fight Cancer

Sean Carroll's Mindscape: Science, Society, Philosophy, Culture, Arts, and Ideas

1:22:05 hr | 1 year ago

77 | Azra Raza on The Way We Should Fight Cancer

"Hello everyone and welcome to the mindscape. PODCAST I'm your host Sean Carroll. And today we're talking about a somewhat difficult subject which is cancer and how we can try to treat and prevent cancer from taking lives. It's a difficult subject of course because I and I'm sure many other people in the audience are familiar with the people who had passed away because of cancer the two leading causes of any kind of death in the United States or heart disease and cancer by a wide margin. These two things and I think at least you know informally. I don't have any data and I WANNA valorize one way dying over another but my informal impression is that cancer is much crueler in heart disease in many ways. can come on people who are otherwise perfectly healthy it can appear in relatively young people in their forties and fifties who've been diagnosed And the way that we have of treating it is not very good. It involves a very painful process for redrawn L.. Long process that often fails veils that often. Even though we do everything we can Cancer still claims a victim so today's guest on Mindscape is Rosza. Who is the John Soon? Shiong professor of Medicine at Columbia University. She's an oncologist. She's been doing cancer research for a long time. She has a new book out called. The I sell the human costs US pursuing cancer to the last and as I said we all know people who have died of cancer as Ras husband who is also an oncologist. I was diagnosed with cancer and eventually claimed his life so no matter how much you know no matter how expert you are in the field this can come to get you in this really nothing you can do about it. So Authors Angle is that we should shift a lot of our resources from fighting cancer once it's already spread through the body Eh to finding cancer as soon as it appears. That's the name of the book. The first cell the first cell in the body that goes cancerous of course many people would agree. Many doctors many oncologists would agree that that would be great if we could do it but the argument is that we can do it. There are things that we know that would improve the rates. It's at which we find cancer very very early though. Were just not putting in the resources to doing that. That we could and one of the wonderful things but others book and it'll come out in the conversation one is that she's a very warm human kind of doctor and there's a lot of stories in the book about individual people and their struggles with cancer and we talk a little bit. What about the fact that I would be? I would have a tough time being a an oncologist talking with people who had cancer all the time but other really appreciates it thinks. It's it's a privilege that she gets to you know help people in this crucial moment in their lives going one way or another so it's a very kind of uplifting conversation despite the gloomy topic overall so this is the last mindscape podcast Last regular one anyway of twenty nineteen I take a two week break for the holidays There may or may not be another holiday message like I did last time but One way or the other. I wanted to thank everyone who's been listening Patriot supporters especially really anyone who is listening to mindscape once or every single week My thanks goes out to you. It's sort of amazing to me that I can sit here and talk and I can send an email to some brilliant accomplished person somewhere in the world and say can I talk to you for an hour or two and they will say yes because I have this podcast. I hope you're enjoying it as much which is I am and I know that I have some really good guests lined up for the schedule next year already. So twenty twenty be another great year for mindscape. Enjoy your holidays days and let's go okay Baraza. Thanks for coming on the MINDSCAPE. PODCAST delighted to be here. Sean this is just so everyone there in podcast land knows we've never met before but we have no knowledge of each other over the Internet for many years. Now you're part of the collective that makes three quirks daily. The famous blog site is right. Yes my younger brother. Basra's the chief editor in chief of it. And what kind of things do you contribute there for the last fifteen years I've been posting thing Do Stories daily very occasionally one And one of them is a story related to some kind of scientific News that's good just being released or a scientific article but the other is general interest because I have many other injuries so it could be literature. Philosophy music art anything. But that's what's great about the website. It really does bring things together in a way that is reminiscent. Reminiscent the MINDSCAPE podcast here. So that makes you a perfect guest and also what makes you perfect guesses. You have a book that just came out. Is that right or is it coming up called the first cell and it's not about the origin of life it's about cancer and you're an oncologist and I thought I want to get into what cancer there is how we treat it and so forth but I can't help but ask about the very moving personal story that you open the book with. Could you tell the audience about that. Well the book is titled the First Cell But equally important is the subtitle of the book which is and the human costs of pursuing cancer. Insert to the last so. This is a book not about cancer it is about cancer patients. Yes and the purpose of this book. Sean is to bring back the patient front and center into every discussion. We have about cancer. No matter how deeply and rigorously scientific it is we have to ask the question at every point. Where where does the patient benefit from this or is hurt by it and so as it is out of having this goal in mind and I have a door many patients stories as well as a patients who are under treatment with me right now their stories they have golden their own words but after I started to write it I realized that it would be insincere of me if I did not include my anyone right because if I'm going into such granularity about people's suffering and pain it's not fair to shield myself Sir? You're asking other people to open up this way. Then yes that's exactly right and saw it has been eighteen years now since my husband. Hobby price'll died right. I have never spoken about to anyone or written about it. But what made me come out and write it and then right right in as much detail as possible. Because that's what. I was demanding of my other patients and their families. Now the S- personal story became like red line running throughout the book. Do every chapter. And then there's a whole chapter opted voted to Harvey. You asked me to tell you something about this personal story. I opened the book with so this is the background of why put and then of course how Ribas my mentors since I'm twenty. Four years of age We later got married. He was the head of the Cancer Center in an ironic and cruel twist of fate. He got the very disease e had dedicated his life to cure since he was fifteen years old cancer leukemia Nia and he suffered inexplicable indignities at the hands of this this disease over the course of almost five years. Our daughter was three years old when he was diagnosed in eight years old when he died and so so in this sort of dizzying disorienting beard. What I experienced a needed some distance? Silence of time as well even in even to verbalize some of those things so in a way the book is a combination of my personal smell story but that of the people I take care of and that of the disease I study so it several books. Yeah I also had a very good friend Michael who wasn't oncologist and was diagnosed with cancer and eventually died of it and nothing else. It reminds us that we really don't know much about the disease. The people who know the most are still helpless in the face of it and there's something about cancer that is especially cruel. How it happens apparently randomly so you can be relatively young takes years and the reach a point where there's not much you can do? And the greatest treatise to cruelty is that it is a silent killer that it can grow to advance stage within your body. And you had no inkling bolt in fact. There's a very very interesting study. That was done some years ago. Sean where people have been long-term smokers tried to quit many many times James and when they finally managed to quit and not go back because they quit quit finally when they managed to quit and inordinately high a number of them end up with lung cancer. Really so the study was done to show why and it turns The conclusion was that most likely they could stop only because something internal finally orange. Does this election. So there is something but we tend to ignore it completely and because it's such a such a subconscious level so when you say that something very terrible about cancer very unique think about it is that it is a silent killer and just so hopefully many people in the audience have not seen cancer up close or how to deal with it. So let's back up explain. What cancer is? It's not a simple thing to explain what it is right. There's many varieties and many manifestations to begin with the very simple thing is that every living cell which is normal has a limited number of proliferations or divisions it can undergo. This is known as the hair flicked flicked limit that after forty to forty five cell divisions it will either undergo a process of committing suicide or be killed by other things or it will die down all its activities and enter a state of senator and be useful longer. I mean by the way that's worth a podcast all by itself that fact because you know amoeba 's don't have that property they can just keep dividing forever. So we complicated. multicellular organisms had built in a lifetime a suicide mechanism for our own selves. That's just fascinates me but let's strategy and cancer cells else overcome the safely climate and become immortalized. That they don't die. saw the to me. The definition of cancer is just that that a cell which is now gable off infinite number of divisions and what Causes Cancer Really There are some very specific events that can give rise to it about Most of the time. It's a random event and probably I would say say at least sixty percent of all cancers happen because of DNA copying errors as the sun is dividing and is it correct to say that one thing we do know about cancer is that it involves a change in the DNA at some sort of genetic mutation one way or the other only partly correct okay because genetic change is one thing but In inside the cell itself but also control of those A cellular function could come from an external source however Ultimately it is the cell gone gone rogue doug by itself running amok so in the end. You're right that there has to be a genetic component to every cancer sale and is it just merely early that it grows without bound or does the size and functionality of the shape of the cell also change probably as alter the cancerous changes everything goes haywire really serves no useful function anymore and It does change size shape form when you have. I guess since I you know so little about this. Ignorance is going to show when you have a tumor for sort of cancer that is stationary in your body. He does that grow because the cells simply keep dividing or because the individual cells puff up or is it a mixture of both. It's because cells are dividing and making a big moss around them. I think think of cancer is something which tends is to evolve like life itself The same constraints and the same principles that apply to evolution Lucien apply to initiation expansion growth of cancer also so one cancer cell. Let's say divides and becomes to each time. A cell divides it has to copy its entire DNA. which is about three billion base pairs so on the a whole at each division? A cell will retain three to four new mutations now most of these mutations are passive passive which means that not the harmless but some of these if one of these happened to occur in a vital gene for example donahue which is controlling proliferation which is responsible for growth control which is known as tumor suppressor genes these mutations happen in one of those world wide genes then the function of the cell is affected but then let's say now overcomes growth control because of this mutation and that is mutation which will be termed as the driver or the founder mutation so the first cell will have the founder mutation but each diamond divides into two Sean. That's the problem. It's going to pick up new passenger mutations that may not change its proliferative or doubling Ling ability but it can change its metabolism response to drugs. Its ability to be more aggressive and it's dividing so so much more rapidly than normal cells that it starts making a mosque getting more and more blood supply to self becomes a hot area because it needs nutrition visteon to To help itself but the point is that this massive cells now after like thirty doubling things Mu have nothing or very little in common except the founding mutation with the original cell so in other words it's a constantly metamorphasized metamorphosing fools ing mutating transforming dividing selectively evolving sort of Collection of cells. So what I say. Is that treating cancer as one disease is like treating Africa is one country it is. It's a moving target because let's see I remove what do you move from my lungs today to studied sensitivity to fifty drugs and find to drugs which is very effective. By the time I found the two drugs at six weeks slater because of all the tests I did. Cancer has moved on the drug. Was the drugs would have worked six weeks ago and this is one of the reasons that we we have not been able to control advanced guesses until now the outcome for a patient with advanced disease is no different than it was in. Nineteen Nineteen Thirties. Is there if he put into an evolutionary context biological context. Is there any reason why cancer happens. Observe serve some purpose Biologically I have this vague feeling that elephants don't get cancer or something like that they're different stories about different species having having different susceptibilities. Is there a grand theory of all this. No short answer is known. That's gone petro's paradox. Because was the idea would be that if the number of mutations increase each time cell divides then a larger organism organism should have a higher chance of having cancer right right just by that long process. It's exactly not true because and it's not the opposite either because for example mice and humans. Humans should have more candidates not true Wills almost never get cancer for a different reason than elephants. Don't think we know why elephants are not getting cancer because they've twenty copies of a tumor suppressor gene called P fifty three and had those genes are redundant so that one is mutated another one exits place and another one in Seoul tumor suppressor gene P fifty three which is known as the guardian of the genome. Because it's constantly surveying the genome for Mutations and forcing the cell which shows mutation mutation to commit suicide if that gene gets mutated and it stops performing it's normal guardian function then the Silken become cancerous. But if you have redundant copies of the gene then the opposite would happen. That is you know the next copy be would kick in even if one is mutated however when this was replicated in animal models to produce to over express this gene in order to have insert multiple copies of these genes results. Were not so great. Because you know what happened. The animals number one. It didn't get cancer but age. Dramatically died of aging was GONNA ask because I did. I've never heard of the tumor suppressor gene again. I'm not an expert in this area but it sounds like yeah we should just have lots of suppressor genes. But it's not that simple. It's not that simple and so it would be simplistic to think that elephants were large animals and it should be getting lots of Kansas. Don't get it is all because they have twenty copies of p fifty three. We'd like to think so. Let me pause for a second talk about policy policy genius Dot Com. I know the probably shopping for insurance is something that if you haven't already done it doesn't seem that exciting. It seems like one of those things you're going to put low. Oh on your list of priorities especially the holidays are coming up. You have other things on your mind so policy genius makes it easy to shop for insurance whether it's life insurance health insurance earns disability insurance. Or what have you. You can go to one website type in what you want and you can get a list of different options with all the prices explicitly there and once. It's you apply. The policy genius team will handle all the paperwork and red tape. You can save up to fifteen hundred dollars or more per year by using policy genius to compared life insurance policies alone so if you need life insurance but aren't sure where to start. Why not start a policy? Genius Dot Com. It only takes a few minutes to find the right insurance policy Z.. Apply Cross another thing of your end of the year to do list policy genius. It's nice to get it right so Aside from the grand biological theories what about human beings cancer is quite common on the scale of things that kill us in the world today writing. What are their typical American? Let's say sorry. Let me back up or the numbers very different from the US to Europe to Africa to Asia Etcetera. Uh actually no okay. The only difference numbers that appears is because someplace escape good statistics other storms or the only numbers weekend rely lie on unfortunately are only Western countries and a few countries in Asia and Africa but in general wherever it has been look at a few things that are very clear number one no age is immune from cancer so from birth to death. A person is can get cancer anytime however it's much more common as each at once so not just because you're older but because the likelihood per year goes up when you're older I actually really call in the midst of aging remember it easily. It's an acronym missed 'em stance. Were mutations so just remember that by the time you're older each cell l.. Has Now gone through multiple mutations so each cell has more mutations in it and if you think about this great eight sandpile game that peer bark one of my patients that I describe in great detail in the book came up with. was that if you are awed dropping grains of sand it forms a little pile but this sandpile after you keep dropping the sand will eventually prolapse collapse. The last grain of sand which caused the pilot to collapse was no different than thousands of grain. That came before it. It was the pile that had become unstable. So it's not necessarily something a mutation that causes cancer. It could just be that with age. Many things are becoming unstable in the body so one of them is. The number of mutations have increased for a second one is the immune system maybe maybe a little more decrepit now. It's not as efficient in eliminating the abnormal misbehaving since then so I in missed yes and then the SS stands for Sensens- which We mentioned this briefly earlier. That after the hair flip limit is reached and sells dialed down their activities and enter quiescent spirit in which are really not performing any more useful functional. They're incapable of dividing anymore so they'll never become cancerous but they have a minimal level of metabolic function going on to stay alive so now more in more cells are entering sentences with age. And what is happening is the are producing a ton of garbage and the garbage system in the body's becoming and fueled in the garbage system is now becoming overwhelming. And what happens then is that more and more of this Talk sick material. Starts Collecting and poisons the soil or the micro environment in which the sea or the cell is living so the S. really is not sensens- but the soil is of the body becomes more pro inflammatory. Which means these inflammatory proteins? CYTOKINES are accumulating and causing normal cells to have less than robust existence whereas supporting the proliferation and growth off something which is even slightly out of balance. ORLANDS BOT has a selective growth advantage in that setting. So it's fitness off the landscape to the seed that's existing in it and the last story just to make that clear the senescence cells as you say they're not the ones who are going to become cancerous but they make all the cells around them more prone to it by weakening them in some sense yes. We're poisoning the atmosphere in which living poisoning the soil in which they exist. That's exactly right and the last thing D.. That do you see one of the problems. Is that alleviated example of the bone marrow in normal healthy adult off off of the marrow is fat cells and the other half is him Adeboye excels which means the centers which make blood. which do all the things blood is supposed to do by the time we are? Let's say seventy years old. This ratio changes changes so that seventy percent of it is now just empty. Space which is filled with fat cells and only thirty percent are active sales so so in this setting what happens. Is that every living cell is under the control draw off signals from other sales from within itself from the soil in Wichita exists from blood vessels. That are coming from nerve endings. that are are feeding onto it. The increase in distance between controlling cells. And those that are the targets effector and the effector cells and just by increasing that The geographic distance. You know that can also lead to slight slight change. In for example. A suppressive behavior for sale is growing too much than it would be controlled and it would be told not to and yet it's suddenly taking off so I do think that With each the incidents of cancer increase. Because you asked me about Is Is it the same all over the world and is it the same disease all over the world What we see is in America for example one point seven seven million new cancer cases are diagnosed in adults in children? Fourteen thousand different. That each me there. There's a big difference. Yeah Yeah So. There is a big difference in age and But as I said new age is really mean from it. I mean all these facts facts about aging ten generally to this conversation but I've had previous conversations with experts on aging and there are people out there who who want to stop or reverse aging. This reminds us how hard it is. How many things are going on under the umbrella of we call aging? No I don't think I mean of course it's it's going to be very hard like curing cancer is like you're going to kill reaching basically but one thing we can talk it is instead of always running running off to disease and treating disease preventing it right short absolutely. I want to get there just to drive at home. How important that is again for the folks in the audience who haven't had to go through this personally? How do we treat cancer in a typical patient these days? Is there a standard way of. We've you heard of radiation therapy and chemotherapy and so forth. Yes so the good news that sixty eight percent cancers we are That are diagnosed. Today are cured but cured with what the same things we were using. Sixty seventy years ago slash spoils and burn surgery chemotherapy. Radiation therapy the same thing. So of course there are some very small pockets of rare cancers for which other things argues two of them have targeted therapies. One is chronic myeloid leukemia being treated with the matinee. which is one gene causing housing problem and one magic bullet that targets it? That's the one cancer that has been really paradigmatic in the the sense that it seemed to stab wish a model. That cancer is a disease that is caused by a genetic change which can be targeted by a drunk successfully. Sadly turned out that for all other cancers. Many many genetic mutations and no single drug seems to be working so basically chemotherapies and indiscriminate killing of normal as well as abnormal cells. And that's what we're still using the thirty two percent patients nations that we are not killing their outcome. Today is as bad as it was fifty years ago and so do what should we do. What you part of the message of your book is that of course? We don't have all the answers you don't have all the answers either. But we do choose to suspend or resources trying different things and you have a specific angle. You think that we should be pushing toward yes the angle is of course that of the first sell that instead of forever chasing and trying to kill the last sale. We have been trying to do that for fifty years. We've done it successfully in a very small number of rare rear Kansas but for the majority of patients who present with the common types of cancers you know Gi caloric of Lung thank Ovarian Kidney cancer in for these types of cancers. We really haven't made a big striking blow against them in a using the same slash poison burn approaches. The maybe I should have asked earlier but we speak of cancer being in remission. We typically don't speak cancer being cured right. Can you explain the difference there. I mean it's the technicality where oncologists insists that if someone has been cancer free for five years at least then we call them cure okay but otherwise as if there is no evidence of even microscopic disease we only will call it mission and that's because we're never sure whether it's a little cancer there yes is that it may recur but after five years if it recurs. The chances are headed to new cancer okay. That's fair is it. If there are genetic components turning sell into a cancer cell is it just one mutation would be enough. You need a combination of mutations uh-huh because if the ladder than you can imagine that even if you get rid of all the actually cancerous cells there's still a bunch of cells. Leftover that are ready to become cancerous because they have all but one of the mutations nations yes that's the answer is yes there is always that danger so you were talking about We have a certain amount of resources. This is how are we going to spend them. I think before we get into it. I want to give you a few statistics for the first is as I said. Our strategy satiety has been since dime memorial to get rid of the cancer somehow so we see a disease is already developed. Once it's already developed. Yes we we see it. We want to get rid of it. And if we get rid of what we can see then we still as you that microscopic disease may be present so we try to kill it with supplemental insurance. You Win Tired of chemotherapy radiation therapy so we not only remover women's breast. We now give her tons of these as well over time we have learned to use these things better and that has changed. But I'm honored to give you some statistics. First of all patients were diagnosed with early stage disease. Ninety percent can be cured but those were advanced with advanced disease ninety percent or more hundred percent. Are I'm going to die. But the common kinds of cancers really make sense but it's a dramatic shift so we know that early detection is more amenable to treatment and it's true for every disease earlier you detect the better. You are able to treated before you let things go completely out of fan now. I started my career Sean. In one thousand nine hundred seventy seven buy studying and treating patients with acute myeloid leukemia today. In twenty one thousand nine hundred. I'm using the exact same combination of two chemotherapy. Drugs popularly known as seven and three to treat acute myeloid. Would you keep me up. I was using seven and three then. I'm using it now. Can you imagine I see thirty to forty patients every week for all these years. Can you imagine the same conversation with the same side effects and the same dreadful results over and over honestly I cannot imagine being in our colleges. I think that you need us. What a strength of will and generosity that would tax me a little bit but I give you credit for having those conversations? Thank you for saying saying that but I have the opposite view you have such exquisite sensitivity. Because I listened to your all your credit courses as well as your podcasts and I think you have exquisite sensitivity and you would make an excellent doctor and we all have to do what we have to do in life. That's right and when a human being needs us than it is actually an immense privilege sean to be there for someone to through and help them if we got to help them live a better life. We help them have a better. Did we help them. At every step of the way and to me that is the most sublime form grease that you can see the most the greatest acts that you witness in. I've seen in the nobility of endurance that is manifested by these patients and a corresponding level of frustration. That you're having the same conversation with them about the same treatments forty years later we should be able to do better. You think I'll give you one example. My daughter should his best friend Andrew Three years ago nickel at twenty two years of each got diagnosed because he had been in tingling in an arm by the time he reached the emergency room when he was already quadriplegic the neurosurgeons when the operated on him found a nine centimeter brain tumor which they could only partly remove so every oncologists new from these zero that this board boys chances of survival or zero point zero zero. Do you know the first first thing he said when he woke up Sean from the anesthesia he said was mom. Don't worry just Azra. She's on the cutting edge. She's GonNa find a cure for me. How a shamed I felt? How can I ever look at myself in the mirror that this poor boy has stood stood by his bedside realizing how badly we have field Andrew and the question I asked myself is how many Andrews take and to address that last point I wanted to bring you up to date about Andrew three weeks before he died which was two years ago now? They brought him a form to sign. Do not resuscitate we call it a a dnr form and how old was he. Twenty three no diagnosed at twenty two twenty three. How is twenty-three-year-old supposed to sign his his own death certificate he sent it away at? I'm not signing it. So they took it away that night. His father came over to spend the night with him as soon as the game. He called the people back to bring this form signed it saying I could not sign Linux in front of my mother and sister. This is great talking about that twenty three year old young man who's dying is protecting as well. We were all going to die Sunday. We all know it intellectually but you can certain point you reach as a cancer cancer patient. Do you know it in a slightly different way more visceral way that it's coming and how you react. How you behave says something about who you are? Definitely it is in my opinion that the kind of lonely courage that this boy and all the patients that I'm taking care of really short one point or another another in the course of business. That's the kind of garbage that needs nations to dedicate monuments to you know. Some of it is. It's the kind of courage. That Harper Lee has defined beautifully. She says Sean Gutteridge is knowing that you're licked before you start you start anyway and you see through to. We'll be in and that is what Andrew did from the start. He knew his licked but he went through round. Owned upon round of demoralization more surgery. Immune therapy more chemo radiation more. Immune therapy more surgery. He he went through everything and soy to the very end. And that's the kind of courage that really is what I'm talking about. After after my husband died we found in his wallet. A beautiful saying beautiful line that he had written something to the fact that I know there is no good end for what I'm going through but I have to to do it because I'm a man and a man is responsible for him say and it's difficult because we don't either are sort of narrowly as a medical establishment or broadly as a society. Deal very well with how to die right how to help. People people dying how to admit that Earth is coming how to face it. There's individual moments of courage and grace but there's not we. We tend to avoid it to to live in denial. Do you think you think we can change. Do you think how bad is it or is there. Is it better than I think it is. I I want to go to emily. Dickinson beautiful beautiful writer. I measure every grief. I meet with analytic is I wonder if it weighs like mine or has a different size. I wonder if they boarded long or did it just begin. I cannot find the date of mine. It's been so long the pain the I wondered if it hurts to live and if they have to try and whether good good day choose between they would not rather die you see debt is not an option that is not a a choice as you say debt is coming so for all of us but for those individuals who start hearing the footsteps of debt approaching what goes through their minds is impossible for us to imagine unless we are in those else shoes so I think it is impossible for us to switch places aces easily however one of the main reasons to write the book for me was exactly what you said that I'm getting tired of everyone only promoting morton the positive anecdote as if dying is a failure. Dying is not a failure denying debt as a failure and the main difference between humans and Greek gods is that we accept mortality in the final analysis. Look at Andrew at twenty three. He accepted good mortality and is trying to protect the living because he knows his dying. But he's trying to shield his mother and his sister that is the sublime sublime grace of humanity and that is what makes my life of privileged to live instead of people's feeling. Sorry that I have to take. It goes dying patients. They should be envious that I get to see humanity in its noblest forms. Basically basically boils down to are. We prolonging life for prolonging debt by the current techniques. That's the question I'm asking being in the book that if the sixty eight percent patients we are curing today with cancer why are we curing them with Paleolithic treatments that belong along in the storage. Why are we still using chemotherapy? For God's sake it's like taking a baseball bat to a dog to get rid of its fleas. It's it's so horrifying the toxic effects and the thirty two percent patients present with advanced disease. Who We nor- New Orleans not benefiting? We are being bringing drugs to their bedside which have a failure rate of ninety five percent and the five percents and that are FDA approved and are ostensibly great successes. This should have failed because they're only leap prolonging survival by a few months for a small minority. Soy hundred patients are given this drug X.. Twenty to thirty percent will respond for a few months. Seventy to eighty percent will never respond and suffered all the toxic side effects. Hundred percent will suffer. Offer physical toxicity of the drug and financial toxicity. Do you know Sean Today. In America forty two percent individuals who are diagnosed with cancer forty two percent become financially ruined by two plus years. I was Gonna ask what do that. And that's astonishing number. It is untenable it is unsupportable. It is unconscionable you'll be one something if and then they lived happily ever after yes they are not even living. So why are we bringing drugs to the market or to the bedside in which are benefiting a small fraction of patients for a few days and hurting everybody and ruining forty two percent not just themselves their next generation took come so the question is what should we do then we have presentations to worry about. And then what our plans for the future. Either we can keep doing the same thing and there is some benefit to hanging onto your ideas forever but sometimes giving better ideas can also help okay. We have milk. The most out of Chemo and radiation. Even for the sixty eight percent we are curing. There should be better solutions. In my opinion we don't have to torture people and for this thirty two percent. We shouldn't be saying either. You Die of cancer or you die of the drugs we give you and also be financially ruined so but we have an limited number of resources. How are we going to spend it? Actually let me interrupt you just there because I want to. I don't WanNa let this terrible facts about financial ruin and the Mortality Rates go by without wondering about just a little bit Let me just put this on the table or are some people or groups benefiting financially elite from the current regime. Do they have a vested interest in keeping it like this. My answer is not some people but everyone is benefiting except except cancer patient. Why do I say this? I think it's very easy for the public to imagine the worst possible things about the evil pharmaceutical Sudoku companies. But I ask you this question if you go to the corner drugstore and by one hundred packet of hundred bandits you will cost you the three nine thousand nine or something if you go to a hospital and they put a band-aid on new one. Bandied will cost seventy five dollars. So where's the drug company this equation Shen. And what about all the extra imaging or extra scanning people are getting. What about all the therapies? BSB that oncologists are giving to patients who they know will not be benefited eighty percent. John's is they will not benefit. Why aren't we holding them responsible? The question is I'm one of them. Every criticism applies to me as much as it does to any other colleges. Why am I doing it when I know seven entries so bad why am I giving it because otherwise I'll go to Jane because a group of key opinion leaders in the field have reviewed all the the data and come up with guidelines? And it's a good thing to try to make something more uniform. Try to bring some method to the madness so that let's say for pancreatic cancer patient is diagnosed with stage four disease. These three drugs will be used in first line treatment than these three in second blind these two in third line treatment that is the guideline if I deviate from doing that. Then I'm opening myself to legal challenges so I'm also also giving those drugs knowing full. Well that it will only hurt. Eighty percent of the people practically hundred percent in the end for a benefit of a few months. The other thing is we tell everything to the patient. It's not like we are doing it without sign consent forms and beer the ones choosing it also because life is so precious and dying so scary that most of my patients will tell me. Even if there's one a million one in a million chance what do I have to news news. Let me sign up for it and do it. So it's a very strange kind of system where everyone is to be blamed but no one can actually assumed the blame. So where does individual responsibility end and society's responsibility begin. These are the fundamental questions. I'm raising in the book and it's it is fundamentally difficult. If you're told there's a one percent chance of survival nine percent chance that you will die and your family will be financially eventually ruined saying no not even GonNa try to take that one percent is difficult or more in terms of policy saying saying well we should spend less because most of overspending is being wasted. People are going to worry that if you're spending less you're not doing a good job Honestly hard to balance these. So here's the thing I'm saying that if ninety five percent of the drugs we bring to the bedside are failing the first question is why are they failing because whatever we did to bring them to the bedside is a failing model. What is that failing platform where we are even even developing these drugs to bring to the bedside mostly in animals or in in vitro petri dishes all in extremely artificial conditions additions that we keep insisting we'll be extrapolated to humans well over and over? It's been shown that doesn't happen so there's a time to simply take off the blinders and admit the truth. Cancer is too complicated for us to understand every intracellular signaling pathway and then try to fix it because it keeps it has moved on also. I know you have strong opinions about studies being done on mice very strong opinions and and mice are the model organism which we test or ideas about cancer right so I don't want to be misquoted. Here's I'll make myself very clear Because very often I am misquoted. And then I get hit me for months years now. No I was not the the main point I want to make is. This animal. Models are excellent biologic tools. Where did we can test a large number of very intricate questions about all sorts of biologic phenomenon? There's no question shouldn't voted. All most of the advances have occurred even in cancer because of studying animals. The only thing I object to which I try to be as specific Pacific as possible. I'm glad you're giving me this chance to explain my point of view accurately the only thing I object to is. You can't create a tumor in an animal treated with some drug and think now when you use the same drug in the human tumor it's going to have seemed seemed results so for drug development animal models have not been hope for this time but the are used in these preclinical little testing platform. In fact you can't bring a drug to the market unless you've tested it in a mice and my question is why why is that giving the FDA any level of confidence that if we don't see toxicity in mice we won't see toxicity in humans or if we see efficacy my swansea swansea efficacy Newman's because the actual evidence is contrary to that that there is no possibility of this flip flop exchange of information from one species to another. You're no longer doing. The twitter account called in mice takes headline lines. Study shows eating ice cream cures heart disease and then it just re re tweeted with the words in my head. It's that time of year when you're doubtless buying presents for the people you care about in your life so why not by president for yourself in the form of an audible membership now is the best time to treat yourself to some audio books another audio specials with an offer fifty three percent off your first three months you can get of course all of my books on audible most of them at least the last to read by myself. You can get Olivarez book the first cell on audible you can listen on any device anytime anywhere with the audible app you can choose three titles every month one audio book in two exclusive audible originals. You can't hear anywhere else And right now for a limited time three months of audible for just six ninety five a month. More than half off the regular price visit audible dot com slash mindscape escape or text mindscape to five hundred five hundred. That's five zero zero dash five zero zero go to audible dot com slash mindscape. Get my books. Get whatever book that you've been thinking about treat yourself. It's the end of the year. Your worth it. Yes so I got tired of the promotion promotion of this Anecdotal person who has had remission for serve for four years on this drug that had failed and everybody the question question I ask is that yes. It's true that there are Unicorns who have superb inexplicable responses even to targeted therapies. That have failed in every other patient. And we don't have an explanation of why they are responding so well but we keep taking and that is the anecdote that we count over and over to say. Well that could happen. The question I'm asking is at the expense of what at at the expense of ninety nine out of one hundred patients suffering unbearable toxicities and medicines one rule that we begin begin with this first. Do No harm. So how can we justify ourselves in an enterprise where ninety five percent and drugs are going to just harm and the five percent. We think more Tom will still the majority of patients so instead of Gunston trying trying to improve the typewriter we have to invent something like the word processor to make that obsolete in order to make the paradigm shift to a better one. We need to show show a better way because no one is going to willingly give up there too and there is sort of naive logic about testing things on mice in the sense that if it goes terribly wrong in the mouse dies. It's not as bad as it happening to human being but I think that you're you have this idea that we can test task things on human cells or human tissues without testing them when human beings. And maybe that's a better way to go. Yes that's exactly. Well said you should be giving this podcast eloquent. No I think that's exactly right that yes there are some things. We can't do in humans that we can do an in animals. We don't have to do them. There are the things that we can do that. We haven't even interrogated yes yet. So how do we do that. How do we test things out on human tissues or cells without the whole human? I think it was In nineteen forties. I think that Somebody said the best model forget is another cat preferably Fridley the same. They are different. Yes so in other words what we need is we need to test individual humans for their disease and if we want to diagnose we know that the only thing that works in cancer is not in fact nineteen or three adopt children in England said this it's not the cancer that kills put delete treatment that kills me nor that the earlier we detect cancer the higher the chances of cure why not try and develop better techniques to detect cancer early. Well this is not a new idea. Screening screening measures for cancer. Were put into place fifty years ago screening how by mammography by colonoscopy by Batsman and by BSA measurements these are the full. Most common screening measures used and mortality from cancer has dropped by twenty eighty six percent in the last thirty years. Not because we invented some new magic bullet but because overhearing it no because of two things. one anti-smoking campaigns and do screening measures even with these four old screening measures. We have brought brought down the mortality. But these have been milt dry now. This is the maximum benefit we will get the present rate for cancer mortalities only declining declining by one percent a year and only that is happening again not because of new drugs coming on market but learning to use existing chemotherapy. Tapie radiation therapy better and diagnosing cancer earlier and earlier through more sophisticated imaging scanning etcetera techniques. So what my point. The book is simply we've done and nuff by trying to chase the last celebi abused artificial jesting platforms clinical the drug development platforms. These have been and Spectacular failures and buy the last sell. We mean the most recent cancer cell in this cancerous growth rather than the first one that appeared the last cell means that after you have given all the treatment you still think some residue residue disease may be left behind and that is the last sale. I'm talking about keep trying to develop sophisticated techniques to molecular Lee identified allow Astle I'm saying why not go for minimal residual disease but developed techniques to determine minimal initial disease and diagnose it in cancer early in fact and try to prevent it so instead of using the standard screening measures I described why not in this day the in each of godlike technology cutting and pasting the DNA why not develop technologies like you go to sleep in a in bed sheets that that scan you overnight for the presence of hotspot because remember. I told you cancel. It begins debates foster the normal cell so it needs more nutrition. It attracts small blood. Supply area becomes hot can be picked up by scanning techniques so the phrase hotspot is not metaphorical literally hotter. Part of your body that is higher than average temperature yes for example a smart brise now in clinical trials which is fitted with two hundred hundred. Nancy sensors that detect changes in in temperature and Circadian Rhythms. So the point is or you can sit up on something in the toilet in the morning. It's called the fit Lou. Deke's Mardi Art of Union and examines it for the presence of biomarkers of malignancy that are being met metabolites that may be secreted. All you can do a liquid acquit biopsy. Somebody has Golan cancer as soon as cancer cells. Beginning start proliferating they start shedding their DNA into into the blood. You know where it started actually started with Mother Child placental cental Bridge because it turns out that since developmental abnormalities in an Andrew in an embryo new increase with increasing maternal each so in order woman becoming pregnant has a higher chance of having an abnormal developmentally abnormal baby in order to diagnose those kinds of syndromes like down syndrome etc.. We used to put a long needle into the uterus of the mother. Draw neurotic fluid and look at it. I underwent amniocentesis when I was pregnant because I was fourteen years old when I was pregnant but then this it was discovered that the fetus is shedding its DNA into maternal blood so cell free fetal DEC FDA is now all the standard routine thing. All we need is a few drops of the mother's blood now and we have the health of the fetus reflected in those those few drops of blood or UC's of blood the same techniques have been applied to cancer and cancer start it also sheds zoff cell free DNA see FDA into the blood and so you DNA that is that you can pick up sir ends and just two weeks ago. It was announced by the company Greeley which is really going after early detection of cancer. D- announced that not only can the the detect cell free DNA reliably ninety nine percent of the time they can also see which organises coming from. Is it coming. I'm from fan careers. Is it coming from the liber. Is it coming from the lungs based on the kind of mutations so this is the beauty of very different disciplines disciplines of knowledge coming together in a conciliation sort of cross disciplines to yield this kind of information because the human genome all sequence twenty years ago practically but now we are seeing the dividends of it because we know what the normal DNA should look like. We can pick up a mutation we can now how detect I mean. Think about it. Twenty years ago it took fifteen years and two point. Seven billion dollars to do the first human genome sequencing today. It costs a few thousand dollars in three weeks of sequencing. We've become efficient very quickly. And I think that if we start being more attention to these new types of techniques we need to develop strategies to detect gases footprints in any secretion for example blood sweat tears urine stool you can do. You can find Biologic Marcus of DNA for example some cancers which are beginning. Let's say your bed sheets detected spot in my head of Vancouver's one night the next morning. Earning it isn't necessary for me to have an open abdominal procedure in a whipple procedure. And Iverson rate my whole belly. Know what it means this I I should be monitored and then taken for maybe even more sophisticated to focus scanning measures to make sure that this thing is growing. It's a unreal prisons if it is confirmed it's real prisons. One thing we can do is do a liquid biopsy see it's shedding anything in the blood in the urine into into tears and saliva if we don't find it then we can stem to another thing. We can yell at that spot. How do we yell using ultrasound? We hit it with ultra zone. When ultrasounds hit this little moss it wiggles it shakes and they shut off more protein? So you hit it years back and then you just do another test of these liquid biopsies from various places. And now chief you're detecting it and once you detected then you really confirm it's potentially Paletti because it may not necessarily be very aggressive with me not need to be removed right away. It may not kill someone who's not not years for another thirty years so there's no need to go in so all these markers of initial malignancy it's potentially talapity not its ability to become invasive aggressive. Those are all pieces of information that can actually be investigated gated with the current topic sophisticated technology. So my point is we have presentations and we have future patients. We should divide up. Resources isn't half and half half. We should be indicating to the prison patients. Half to developing better technologies to prevent an to detect early and prevent the disease from becoming its end stage monstrosity whereas right now it's fifty fifty five and ninety five right now. Five percent for future patients future for for early detection and for present patients. What we need to do? Also Sean which I feel very strongly about is we have to stop hurting them. That is something we need to stop giving everybody and simple. The most obvious thing to do is try. I identify which patients are likely to respond to which drugs. How do you do that? Well anytime a sponsor wants to propose a clinical trial an experimental trial. They should be made to save every sample from every patient. Going going on that I try and then you'll have some patients who respond some. Who Do now? You compare the responders and non responders using every technique you you have available genomics proteome. Strong Script Omits Mental Law makes panel mix desk by and try to enrich the next trial for patients who are likely to respond and so on and so forth today that clinical trials are done the same way they were being done in nineteen seventy seven seven and it is horrifying to me that the agencies which have been charged with protecting patients and demanding. This kind of rigor are not not doing it. I think that the this sounds very provocative and promising and so forth the idea. That is the scientific idea idea that I that I get from it. That is most exciting Amisi Eddie of the footprints of the cancer. I mean the wearing a blanket and finding hotspot sounds interesting. But that's literally looking forward the tumor in your body whereas this sort of indirect idea that once. There's a tumor in your body. It leaves traces either from DNA in. Correct me if I'm wrong from reading your book but you can find tracers of the fact that your immune system is beginning to fight it also in your blood. Is there another way of doing it. Guess definitely definitely in fact. I have the best way that would emerge eventually is a collection of all of this technology which is imaging and scanning and devices yes and biomarkers and genetic markers all these put together and all being read by something bigger than your cell phone and all the information nation available on this but then even implantable devices. I mean I'm working with Biomedical Engineers at Columbia University on a chip that we want to implant under the skin from birth to death which constantly should be monitoring the idea is that even the screening techniques we used so far brought down on the mortality considerably. But it's not happening anymore because they have reached their limit but those were done annually at best we want to treat the human body as if it is a machine and constantly monitor it for even the appearance of Berta Bay Shins and disease caused networks. Works and you see that and you step in and try to intervene so this many of the same drugs which are failing today can be applied in earlier stages of the disease and may be far more effective and this has been shown as a paradigm and chronic myeloid leukemia. The disease I mentioned to you for which targeted therapy be is the ideal for every cancer. While in that cancer itself as long as it is chronic myeloid leukemia that drug is all is security security but if the disease starts to accelerate becomes acute leukemia the same drone is useless so early stages the same drugs can work well. That's this is what I wanted to pinpoint. Also so I mean it seems obviously true that if you can find the disease earlier yet a better chance of curing during it but how far can we go and saying that if we find it very very early does our chances of curing disease go very very high or does it increase increased by ten percent my ancestors it will be hundred percent curable. Why because of all the statistics six that are available the earlier? You find cancer the better. You're able to cure it but the issue is. How quickly are we able to do it? And then technologies will also evolve for treatment of early disease so if you like of things totally disease yes yes. So let's say you have a million cents to kill rather than one hundred fifty billion cents to kill. There's a big difference so I think for example if a few needed radiation therapy to kill a hundred billion cells you may need just targeted laser to knock off a few million cells quite Confidently or you can use. Immune cellular therapies that. If we have a biomarker we can arm the killer cells of the immune system with it it and it will be able to distinguish between the cancer and the normal cells. The current cellular therapies using are unable to distinguish anguish between cancer cells and normal cells. That's why the dock societies of Safeguards Because it will kill every cell that it's expressing that mark which means normal cells as well as cancer cells. I'm saying that once we have biomarkers specific floor cancer cells. We may have an address by the cancer cell. Also that is more usable by these The same techniques which are causing so much talk society and it sounds like like this is great because it's not just an aspiration. It's not just a sort of feel good motto that. If he found the cancer earlier we could help cure it. Quicker more effectively but that there are very concrete steps being taken is this. How popular is this view in the community? Is this a plucky minority or is it catching on as this. This is what we should be concentrating on right now. It so all of these things I described you are in various stages of development so everyone has known for fifty years the best strategies to go early and people have spent a lot of time in screening and trying to make those as accurate as possible and in the last ten fifteen eighteen years. People have started developing all this new technology based on day. One being Genomic Information and Proteome X. etc that's becoming available lucile clearly. Those things are all in various stages of development. It's not a pie in the sky. But the MAW resources we need the more people people will get interested in young minds today wasting their time and talent intellect on failing models because they're working with mentors who thirty years have used those failing models and they're the ones sitting in every granting agency deciding who gets the grant and who gets to graduates graduates back. This is all has to stop and young minds and youngest the intellect as well as resources should be better better. Used I think and new technology new idea I knew therapies will bring their own set of problems. So I'm not someone who's going to do. Our problems will be resolved because I'm an old hag. I've been been there done that in all kinds of things but I do think that it is time to recognize at least where we are fairly dime to take off our blinders dime to at least describe the problem in its detail and see the problem for what it is right now. We are not even willing to see the problem. It's not that we are just not finding the solution via fuse to look at the details. Details of what we are doing wrong. My insistence is to look at all of this through the prism of human anguish because this is not just some gotten dried signs this involves humans this involved a twenty two year old Andrew a thirty year old Omar all my patient. JC WHO died at thirty four or harvey who was diagnosed for witness. I answer and then at thirty four in his second chance Ansett fifty seven and this is one thing I want to also recount to you Sean. That my life has been committed to early detection since since one thousand nine hundred eighty four you know why because I started by studying acute myeloid leukemia and treating patients with it within a short space of seven veneers. It became clear to me that in my lifetime. This disease is so aggressive we will not be able to cure it and I was right. Unfortunately we were using using seven and three then we are using seven three now in nineteen eighty-four because of a patient J. C.. I realized that the best last week to handle acute myeloid leukemia is to stop the disease before it becomes so aggressive are their patients like that. Yes it's a whole CDs of syndromes called mildest plastic syndromes which are pre leukemia. Because a third of these patients can develop acute myeloid leukemia. My idea will well. Then we should study pre-leukemic and follow these patients through and had I gone to school in this country. At this point I would have invested the rest of my life into making a mouse model of this freely but coming from Pakistan is a fresh immigrant. I trusted my instinct instinct rather than followed custom and I decided. Oh I'm going to study these patients. Let me save their samples so I just started. Banking blood bone marrow. Aspiration I spread my ABC's normal buckle smears a germline controls on all my patients taking them saving the data you mean literally saving tissues the load. Both I mean both the data as well as the actual samples. It's the most well not to to shoot a positively which today has more than sixty thousand seven and boost from thousands of patients and not one cell has come from a different doctor. Every patient is my patient. Do you one other doctors to contribute to this. is they're very expensive. They can't afford to it. I'm the only one who does it because I pay for it. And how do I pay footed no grant of four can support it my patient support for me. I ask them and they they want to give me money and I said No. I don't want I money. Give it to the tissue repository because it costs almost a million dollars a year just to maintain the tissue repository. So point is that I have these samples which were obtained in a longitudinal fashion seed really on these thousands of patients as they progress from pre rookie. Immune to acute leukemia. Now if we go in and study these samples and worker we back we can ask the question. Why did this a healthy individual? Even pre Yukimi was their genetic mutation. That made them susceptible or a tight risk for it. What was it about their exposal environment exposure? What was there about the Background did inherited. DNA and sold those kinds of questions we can then take to the DNA sequences that are in the public domain from hundreds of thousands of volunteers and find out how many people booth fit our bill for being at higher risk of developing even pre-leukemic and then following those head of the individuals to find and whether they develop it or not. And how quickly can we stop it. This is the kind of thing we need to do. The problem is so it took me so long to amass the samples even today. I'm doing five to ten bone marrow every week in my clinic in my with my own handsome. Do the bone marrow and banking them so I have all this to shoot. That technology has gotta be need resources right. Who's going to give the resources? The government can't afford it because I need one hundred million dollars to study studied hold repository. It isn't as if I haven't been studying at short of course over the last thirty years. I have over three hundred original publications publications which are reporting on the results. We find from limited samples. We take out studied for one gene or that signaling pathway or this drug doug or that kind of thing with limited questions clearly now that all the technology has arrived and we need to go in and studied and died to shoot a positive story. That is a thing that no one can No government grant can support hundred million dollars to one ritual And I don't need the money to set up you know Building seventy scientists working in north. This is money that's needed to pay for the actual chill tests for the sample to do the proteome. Ix on two hundred patients boss four million dollars this is the kind of. That's that's where the money will cool so that idea that occurred to me if there are any mindscape listeners out there who like to donate one hundred million dollars to the tissue tissue repository will will encourage them to do that. I mean can you just I like to try to give the audience sort of visceral feel for what it's like like to be doing this kind of work number one. Let me just mention this kind of longitudinal studies the gold standard in sciences social sciences. especially in really hard and expensive to do because you have to start young and continue to be dedicating the resources but how like where is it. Where are these issues in a room room somewhere? They kept a cold or are they. Do they still duplicate the cells finding number of cells that we use up so then diet to shoot positively he is host at Columbia University. Cancer Center It moved with me from buffalo to Cincinnati to Chicago to Massachusetts. It's to New York now and it has since one thousand nine hundred four struggled with me and these are samples which are Indra in freezers but in addition we have frozen viable tissue also which can be brought out and re grown in plates and animals. In Vitro in Vivo. So Send Men's collection of samples. Everything belongs to Columbia University. Yeah I don't have any companies to my name. I don't mean any personal money. This is all going to go through Columbia University. So one thing that occurred to me Sean. Is that the people who should be most interested in. Finding the first cell are the people who are at risk of getting cancer. Who are those people? There are people like Harvey my late husband people who have won canceled. I don't want to scare your listeners at all but I do want to say that at one in five new cancer is diagnosed in cancer survivor. Because whatever was there to cause the first cancer is still there their conditions are still the conditions there and probably with our treatment for some of them. We've made the conditions worse. Because harby did not die of his cancer. He died because we wiped wiped out his immune system with the horrible chemotherapy. We gave him so. The point is the people at highest risk. Should be the most interested today in this country country. There are twenty million survivors from cancer. Even one million of them just get ten dollars a month for a year. That's it that will the whole shooter poetry people. Ask Me doctor as a why should we give you money and not to the American Cancer Society. My onset is where's the tissue for American can cancer society talk is cheap Sean. But I'm the one who has the tissue. I'm the one who has commitment to early detection because I've been going being after. Not just acute leukemia but pre-leukemic since one thousand nine hundred eighty four. I've been saying the same thing since one thousand nine hundred thousand four. How much more credibility ability can I give? People are very quick to start criticizing your shoes talking about the first sale. She she doesn't know how much screening measures have fee. I know nobody needs to lecture me about these things because not only do I see purdy to forty cancer patients. Every week I have had a cutting edge research LAB FOR THIRTY FIVE PLUS years and I'm against widow so I have stood on both sides of the bed of a cancer patient. Tient as well as a family member as well as oncologists so there is really very little that I have not experienced directly in firsthand stand and I have been consistently committed to finding cancer at its earliest possible sale and try to take take care of it to prevent the disease from happening. And if people don't trust me by now and don't want to support this tissue repository than I don't know who will and as long as there is one breath left in my body. I will keep saying the same thing trying to work as hard as ever for my positions nations. I can't think of a better place to end up than that. Very eloquently said after other Rosza. Thanks so much for being on the MINDSCAPE podcast. Thank you sean. It has been an honor being England. PODCAST

cancer Sean Cancer Center Andrew Kidney cancer United States FDA lung cancer mindscape Kansas Sean Carroll Harper Lee Columbia University America scientific News Mindscape Patriot Africa professor of Medicine Basra
NEJM This Week  August 27, 2020

NEJM This Week - Audio Summaries

25:56 min | 10 months ago

NEJM This Week August 27, 2020

"Welcome, this is the New England Journal of Medicine I'm Dr Lisa Johnson this week August twenty, seventh twenty twenty, we feature articles on sulphur cabinet in red fusion positive lung cancer cell for Catnip for measure Larry Thyroid cancer a closed loop system in children with type one diabetes sticky findings in breast cancer and reconsidering the use of race correction in clinical. Algorithms or review article on atherosclerotic plaque healing a case report of a woman with headache and gate imbalance and perspective articles on improving the quality of US healthcare on Covid nineteen and immunity in aging populations and on. Efforts to curb antibiotic resistance. visit any J. M. Dot org or open your print issue to view the new graphic perspective titled My Blue Sky. This graphic perspective tells the story of a pregnant nurse who goes into Labor in the midst of the covid nineteen pandemic wanting to minimize her inpatient time her husband and Otolaryngology delays their departure for the hospital until it's a bit too late. Efficacy. Of. Sulphur CATNIP in red fusion positive non small cell lung cancer by Alexander. Drill on from Memorial Sloan Kettering. Cancer Center new. York. Red fusions are genyk drivers in one to two percent of non small cell lung cancers, and CLC's in this study patients with advanced red fusion positive. Ns. CLC WHO had previously received platinum based chemotherapy, and those who were previously untreated were enrolled separately in a phase. One two trial of the selective read inhibitor separa- catnip in the first one, hundred, five consecutively enrolled patients who had previously. received at least platinum based therapy, the percentage with an objective response was sixty four percent. The median duration of response was seventeen point, five months, and sixty. Three percent of the responses were ongoing at a median follow up of twelve point one months among thirty nine previously untreated patients. The percentage with an objective response was eighty, five percent and ninety percent of the responses were ongoing at six months. Among eleven patients with measurable central nervous system metastasis at enrollment. The percentage with an objective intra cranial response was ninety one percent the most common adverse events of grade three or higher hypertension and increased Alan aminotransferase level and increased aspartame aminotransferase level HYPO NUTRI MIA and l'info Pina two percent of patients discontinued sell catnip because of drug related adverse event. Self or CATNIP had durable kissy including intra cranial activity with mainly low grade toxic effects in these patients with red fusion positive NFC LC. EFFICACY OF SULPHUR CATNIP in red altered thyroid cancers by Laurie worth from Massachusetts General Hospital Boston. Red Mutations occur in seventy percent of men, Larry, thyroid cancers and red fusions occur rarely in other thyroid cancers in this study patients with red. Mutant Maja Larry thyroid cancer with or without previous VENDETTA NIB or Cabos Santa NIB treatment as well as those with previously treated Rhett fusion positive thyroid cancer were enrolled in phase one, two trial of sulfur catnip in the I fifty five consecutively enrolled patients with Red Mutant measure thyroid cancer who had previously received vendetta. NIB. Kabo Xanten or both the percentage who had a response was sixty nine percent and one year progression free survival was eighty two percent in eighty eight patients with Rhett mutant. Thyroid cancer who had not previously received vendetta NIB or Cabo Santa Nip the percentage who had a response with seventy three percent and one year progression free survival was ninety, two percent. In nineteen patients with previously treated red fusion positive thyroid cancer the percentage who had a response was seventy, nine percent and one year progression free survival was sixty four percent the most common adverse events of grade three or higher were hypertension increased Alan aminotransferase level increased aspertain aminotransferase level hypo tree. And diarrhea two percent discontinued self or CATNIP oing drug related adverse events in this phase one, two trial seller cat NIB showed durable efficacy with mainly low grade toxic effects in patients with. Thyroid cancer with and without previous treatment. Roselle Kerr's rock from the University of California. San Diego writes in an editorial that taken together these results show that sulphur catnip had marked and durable anti tumor activity in most patients with red altered thyroid cancer or non small cell lung cancer read abnormalities. Now join other genomic alterations such as Ntr K. Fusions, tumor mutational burden, and efficient mismatch repair genes across cancers and ALC- be Raff Egfr met and Roz one alterations in nfl see that warrant molecular screening strategies. Next Steps may include introducing these agents earlier in the course of the disease addressing genome co alterations with customized combination therapy strategies, and using additional techniques such as transcript. Dome analysis in order to fully understand the molecular landscape of cancer. A. randomized trial of closed loop control in children with type one diabetes by Mark Bretton, from the University of Virginia Center for Diabetes Technology Charlottesville. A closed loop system of insulin delivery also called an artificial pancreas may improve glycemic outcomes in children with type one diabetes in this sixteen week trial one, hundred, one children six to thirteen years of age who had type one diabetes were assigned to receive treatment with the use of either a closed loop system of insulin delivery or a sensor augmented insulin pump control group. The gleich hated hemoglobin levels at baseline ranged from five point. Seven to ten point one percent. The mean percentage of time that the glucose level was in the target range of seventy to one hundred, eighty milligrams per deciliter increased from fifty three percent at baseline to sixty seven percent the mean over sixteen weeks of treatment in the closed loop group and from fifty one percent to fifty five percent in the control group mean adjusted difference eleven percentage points equivalent to two point, six hours per day. In both groups, the median percentage of time that the glucose level was below seventy milligrams per deciliter was low one point, six percent in the closed loop group and one point eight percent in the control group in the closed loop group. The median percentage of time that the system was in the closed loop mode was ninety three percent, no episodes of diabetic Kito acidosis or severe hypoglycaemia occurred in either group. In this Sixteen Week Trial, the glucose level was in the target range for a greater percentage of time with the use of a closed loop system then with the use of a sensor augmented insulin pump. ATHEROSCLEROTIC plaque healing a review article by Rocco Virgo from fun doubts. Yoni Polyclinic. Otouna versus Tarot a Meli IRCS Rome. ATHEROSCLEROTIC, plaques typically develop over a period of years or decades in contrast the thromboembolic complications of atherosclerotic disease occur suddenly often without warning the notion that acute coronary syndromes developed from the rupture or superficial erosion of an atherosclerotic plaque is an over simplification of a process involving plaque activity, blood, thrombosis necessity, and healing. Pathological studies have shown that many if not most atherosclerotic plaques destabilize without resulting in a clinical syndrome, the occurrence of an acute coronary syndrome probably depends on the disruption of a balance between instability activation and healing pacification of an atherosclerotic plaque during the past thirty. Years, research efforts have mostly been focused on the mechanisms of plaque instability yet the risk of acute myocardial infarction or sudden death from coronary causes remains difficult to predict suggesting that other pathogenic mechanisms should also be investigated. Recently, the notion that plaque healing may play a key role in the natural history of atherosclerotic disease has been gaining attention in part because of the development of new imaging techniques allowing in Vivo Study of the morphological features of unauthorized sclerotic plaque. This review examines the mechanisms and Pheno typic- features of plaque healing its role in clinical events and therapeutic implications. A fifty three year old woman with headache and gate imbalance a case record of the Massachusetts General Hospital by Jeffrey Gottlieb and colleagues. A fifty, three year old woman originally from West Africa presented with progressive headache. Gait instability and weight loss two months earlier, vertigo developed and resolved spontaneously one day before the current evaluation sheets care at another hospital for recurrent dizziness and difficulty walking on examination. The patient was alert and oriented with slow speech bilateral endpoint point Horizontal Nasdag Mus and mild dismay Tria on the right side on finger to nose to finger testing MRI. Showed in enhancing interact axial lesion two centimeters by one point eight. Centimeters by one point, seven centimeters in the right cerebellar hemisphere, she was transferred to this hospital for a specialized neurosurgical consultation. Review of systems was notable from a lesbian lethargy, as well as unintentional weight loss of fifteen kilograms. During the past year, the patients reported that thirteen years earlier, she had received a diagnosis of HIV and was treated with an unknown Aarp Regiment and then several years. Later, testing revealed an error and a RT was discontinued on the current admission, a screening essay for antibodies to. And HIV two and HIV ONE P twenty four antigen was reactive and the CD four t cell count was quite low at thirty nine per micro leader. However, the plasma HIV ONE RN A lot was undetectable the patients, neurologic symptoms, and the findings were considered it in the context of a likely diagnosis. Of V., two associated AIDS. Several features of this case favored the diagnosis of Taco Plasma Gandhi in Litis. When E had herein becomes unstuck in cancer a clinical implications of basic research article by Lorraine o'driscoll from Trinity College? Dublin. Loss of E had hearing mediated adhesion between cells in cancer has often been associated with increases in their local invasion and assumptions have been made that this loss is routinely followed by increased numbers of tumor cells progressing through the extra cellular. Matrix in Travis aiding into the bloodstream surviving as circulating tumor cells and extravasated at a secondary site where they established metastasis. However, a recent study involving mouse models of metastatic breast cancer showed that although loss of Eke had hearing is indeed associated with increased local invasion. It is also associated with decreased metastasis. A finding that supports Eke had hearing as. An experimental target to prevent metastasis in another preclinical study, the investigators obtained data supporting the idea that we had here in becomes inactivated by factors in the tumor pro environment, and that adhesion can be restored by a monoclonal antibody that activates e had hearing intern preventing metastases chemical antibodies targeting Eke had herein and end cut here and have been developed through the use of a synthetic form of peptide of the kid hear an echo domain as template. These synthetic antibodies also known as molecular really imprinted polymer nanoparticles have been used to successfully block can't hear mediated adhesion of cells in. Vitro. Hidden in plain sight reconsidering the use of race correction in Clinical Algorithms, a medicine and society article by Dr Shefali visas from Massachusetts. General Hospital Boston. One subtle insertion of race into medicine involves diagnostic algorithms and practice guidelines that adjust or correct their outputs on the basis of patients. Race or ethnicity physicians use these algorithms to individualize risk assessment and guide clinical decisions by embedding race into the basic data and decisions of healthcare. These algorithms propagate race based medicine, many of these race adjusted algorithms, guide decisions in ways that May. Direct more attention or resources to white patients than to members of Rachel and minorities to illustrate the potential dangers of such practices. These authors compiled a partial list of race adjusted algorithms and explore several of them in detail in this article, given their potential to perpetuate or even amplify race-based health inequities. They merit thorough scrutiny to be clear. The authors do not believe that physicians. Race doing so would blind us to the ways in which race and racism structure our society however, when clinicians insert race into their tools, they risk interpreting racial disparities as immutable facts rather than as injustices that require intervention researchers and clinicians must distinguish between the use of race in descriptive statistics where it plays a vital role in epidemiologic analyses and in prescriptive clinical guidelines where can exacerbate inequities? Improving the quality of US healthcare. What will it take a perspective article by Elizabeth maclennan from Kaiser Permanente? Research Pasadena California Despite nearly two decades of experimentation with standardized measurement, public reporting and reward in penalty programs. Average quality performance in US healthcare remains about the same. So what will it take to improve the quality of care? Recently, the attention of health care leaders has returned to the structure and Organisation of Health Services Delivery, and it's operation within the larger social and economic context of the United States these social factors or social determinants such as housing food, income education, and safety may have a greater effect on health outcomes than the number of hospital beds or doctors per capita or the proportion of institutions and providers that have implemented electronic health records. Given the limited progress to date the path to higher quality care in the United. States requires reconsidering approaches to measurement financing and organizational structures and a new emphasis on social needs. We need to redesign for success, spread what works and stop doing what does not work. This author believes we should start by creating the financial and organisational conditions for changing care delivery from a reactive fragmented enterprise to one at that is coordinated and longitudinal reflecting the need for systems that can effectively manage chronic disease. We need to modernize measurement systems and use them more effectively. covid nineteen and immunity in aging populations. A new research agenda A perspective article by Wayne Cough from the Human Vaccines Project New York. covid nineteen has highlighted the vulnerability of aging populations to emerging diseases. This susceptibility to disease and death is also a major challenge for the development of vaccines and Immuno therapeutic agents. Numerous studies have shown that vaccine efficacy decreases significantly with age a reduction that is thought to be driven by the progressive age related decline of innate and adaptive immune responses. Yet, we know that some older people are protected by generally poorly performing vaccines and some vaccines work very well in elderly populations. The shingle vaccine for shingles for example, is ninety percent effective in people over seventy. What counts for the variability in immune responses from one elderly person to another? How can we use our understanding of this variability in developing new and improved vaccines and therapies far from being mere academic exercises the answers to these questions are critical to the future of global health. The covid nineteen experience in aging populations offers a window into the profound long-term global demographic challenges the world is facing. US EFFORTS TO CURB ANTIBIOTIC RESISTANCE ARE WE SAVING LIVES A perspective article by Samir Qadri from the National Institutes of Health Clinical Center. Bethesda Maryland. Antibiotic Resistance represents a major crisis that limits the care of many patients demonstrating that large scale efforts to control this problem have saved lives would help secure the ongoing and expanded funding and support needed to sustain. However data causally linking national and global efforts to the burden of Antibiotic Resistance and two outcomes are lacking. The centers, for disease, control and Prevention estimated in two thousand, thirteen that there were two million infections and twenty three thousand deaths attributable to antibiotic resistant pathogens in the United. States each year the CDC acknowledges that its estimates were limited by a lack of certain types and sources of contemporaneous data in November twenty nineteen. The CDC released an updated version of its antibiotic resistance report that overcomes some previous limitations. The report revealed an eighteen percent reduction in deaths attributable to antibiotic resistance since twenty thirteen with a current rate of thirty, five, thousand, nine, hundred deaths per year, which suggests that some efforts are working. The CDC findings offer a conservative best available estimate and represent an important step forward deaths associated with antibiotic resistance are unlikely to fall to zero in the united. States. But we can strive to optimize efforts that we know are effective and continue our quest to better understand what is unknown. Are Images in clinical medicine features of fifty nine year old man who presented to the primary care clinic with a three month history of abdominal pain after eating he had a history of immune thrombosis opinion and acute myeloid leukemia and had undergone allogeneic kamata poetic stem cell transplantation two years before presentation analysis of a bone marrow biopsy sample performed four months before presentation had revealed one hundred. PERCENT, donor chimerism physical examination of the abdomen showed diffuse tenderness on deep palpitation findings from laboratory studies included a white cell count of three, thousand, six, hundred, forty per cubic millimetre, a hemoglobin level of ten point, six grams per deciliter, a platelet count of sixteen thousand per cubic millimetre esophagus gastro do at Nas copy was performed and multiple poliploid masses were observed in the stomach and duodenal them. A biopsy specimen was obtained and histo-pathological findings were consistent with myeloid Sarcoma. The diagnosis was confirmed by flow Saitama Trie and Immuno, history chemical staining, which showed evidence of disease relapse. Additional. Genetic testing revealed T P fifty three variants which were detected in a previous bone marrow sample anu somatic mutations with nf one and s excel one variants. myeloid sarcoma is a solid tumor manifestation of acute myeloid leukemia and can occur without blood or bone marrow disease. The patient started treatment with as aside a dean and Vanita. At a local cancer, center. In another image a thirty year old pregnant woman presented to the Emergency Department at Thirty four weeks of just station with a five day history of an itchy rash. The rash had erupted across the abdomen and had spread to the thorax and to the arms and legs. Physical examination revealed fluent papier and blisters on the arm and across the abdomen. A blood test indicated an anti bullets pen full void one, eighty antibody level of greater than two hundred units per milliliter the upper limit of detection. A skin biopsy specimen showed modest inter PAPPA, Larry Spongy Oasis that extended to the skin at Nexia and a mild Luc Acidic infiltrate with a few ES cinefils around superficial vessels I. G. M I G G and C three were detected by Immuno fluorescence testing on the Sub Dermal Basil Membrane a diagnosis of Pentagon just stay Shenice formerly herpes justice. was made pence just station is an uncommon autoimmune skin disorder that is characterized by blistering and typically manifests in mid to late pregnancy. The patient was treated with systemic Google corticoids and the rash resolved within three months. She had a spontaneous vaginal delivery at thirty eight weeks of just station. The infant was healthy and had no rash. This concludes our summary Let. US know what you think about our audio summaries. Any comments or suggestions maybe sent to audio at any J. M. Dot Org. Thank you for listening.

thyroid cancer US J. M. Dot Org headache Alan aminotransferase Cancer Center New England Journal of Medicin acute coronary syndrome CLC York PERCENT Larry Thyroid leukemia Covid Memorial Sloan Kettering acute myocardial infarction CDC Eke Maja Larry
Episode 25: In the shadow of T cells

Novel Targets

41:08 min | 2 years ago

Episode 25: In the shadow of T cells

"Jeff miller. I think the tumors are so smart in escaping immune control. You can imagine an orchestration of INCE directed therapies with tesol directed therapies me be alternately. What's gonna have the best long term disease free survival? Nick huntington. I'm one hundred percent convinced that natural killer cell Therapy's will have a role in cancer. Mike Calgary, my whole life spend, you know, in the shadow of t cells, and obviously that's because we really understand how a T cell sees. Right. We know the t cell receptor. We know how it sees. We know it it's looking for alterations and image C and really for the longest time. We didn't understand how in case sales. See? And so if you don't understand what they're seeing you can't understand what they're doing. I'm Petri foot and fifth is novel targets bring into life. The science around innovative new drugs, gene. Therapies in this episode would take closer look natural killer cells delta, Mike Kelly cherry who in spite of a title of episode is that the city of hope national medical center in California. He started his research on K cells over thirty years ago back then there was a whole of people didn't believe in K sales existed. And so, you know, you're trying to work on something that some people are doubting as to the legitimacy in the and the immune spectrum, the potential of k cells cancer immunotherapy is an exciting and emerging area. One of reasons we haven't heard as much about them compared to cells off off year. Researchers literally there's like five hundred people in the world that might work on K cells and half of them are pre dachshund post docs, so the biology and the mechanism of recognition, etc. Killing is so. In its infancy for an case sales compared to cells that we're just now beginning understand. So what does an case L do? So the Killa in natural killer is based on the fact that they do kill a variety of virus, infected cells and cancer cells. So they kill in a similar fashion to CDI to a slight Tayo in that they bind to chew also and secrete perforate which puts a hall in the cell and then secrete brands, I'm which is like a molecular scissors, which helps up all the proteins inside the cell and kills that's still to Nick Huntington from Walter and allies, a whole instituted Melbourne and case sells like being T-cells type of white blood cell lymphocyte. They troll our buddy looking to spontaneously kill cells. They don't recognize being part of us the role of incase cells in Munich Valence has been really well established in mouse models. And I think that they're doing the exact same thing in humans, and do you have a low activity in case sales. You'll more likely to develop cancer that would indicate that natural killer cells are impose. Constantly recognizing transform cells mutated cells and killing them quickly. So they don't start proliferating and result in a tomb if MK cells can kill concepts than one cancer immunotherapy approach is to give a large number of them as a self therapy. Is it Washington University instant Louis n que cells don't have the tunnel vision of T cell. He sell sees primarily one antigen. And so instead, and k cells are a lot more flexible. They can see a very popular of tumor cells, for example, cartesian L if that be cell leukemia down regulate CD nineteen or it's spliced where it can't be recognized those cartesian are blind. They could be sitting next to a leukemia cell, and they have no idea, I think N case cells just naturally through their expression of a large number of activating receptors might have a better ability to see targets in a more nuanced way and cells don't see cancer cells the same way that t cells to but research is looking at. Innovative ways to target them. Did you is that the university of Minnesota? We have some success in case therapies, predominantly impatience with refractory AML's. But one of the limitations of the therapy is the fact that not everybody response number one in that in cases are not antigen specific. So what I've learned from cars is would makes them so successful as antigen specificity and proliferation in response to antigen, and that's really what we're trying to do know with these try specific killer. Engage your molecules to get the best of both worlds with a simple protein that can be violent in off the shelf without genetic modification, and hopefully that will have a bigger exportable potential in heaven impacting cancer care, and if you're a fan of T cells, then how about Carin K cells. Don't jury on our lab, we've developed car in case cells that brecca is and can treat effectively Glebe last Doma. We've looked multi Aloma. We have data and acute myeloid leukemia. So putting the car onto the case L seems to be working. I think you're gonna see NextWave clinical trials are going to be Carin K cells. I think you're gonna see that. And then you're going to see in combination with checkpoint inhibitors us, we'll hear the ability of n que cells to kill depends on the balance of signals they receive from activating and inhibitory receptors. So another approach is to talk and catch points checkpoints in tesol cancer therapy, the hottest topic in the last thirty is let's be honest in cancer therapy, natural killer cells also have checkpoints in that. They have inhibitory receptors that do accumulate with activision on the surface antibodies against some of these receptors being investigated such as anti-seizure nine. Six which is an inhibitor septa, and they also have intracellular checkpoints and these proteins that increased to stop them from responding to side a kind to really try to put a brake on the natural killer cell response. Delta Huntington discovered a novel interest and k point two SIS cited useful essays to contain protein. More later on the potential of SIS as novel target one company looking and k points, it's Maasais based in each fomer professor via it's the chief scientific officer vision is that would entirely Saudi humor leukemia. So my buddy, I don't think he's going to do this. I think that's stimulating case sales would be the essential spoke to foods of firesuits speak on the immune response that will involve many different humus types leading to protective immunity Indians. With anyone in directed approach will be a game. Changer. We won't know until we see clinical data in the next few years. I believe in that. I am a scientist. I think what should not TC pay too much try to predict too much one should do experiments to try to the answer. Our motto in the lab is the dead derives what the new truth will be. And we do have the burden to prove that these therapies are going to work into a level of of nece. And if that's going to really have an impacting cancer care compared to what other things are available to plenty to talk about stay with me for more. This episode is sponsored budget tech. We're grateful for that support as a reminder sponsors have no control of who interview. But topics we have other questions we asked if we do mention a sponsor product, we might own independent decision to do. So. If we want to understand how best to use K sells for cancer. Immunotherapy then we first have to understand. How say we don't want our immune system to react against normal. Tissues auto, immunity is not a good thing. So like military jets cells in buddy, have transponders signator immune system. I'm a friend. They do this is fresh major histocompatibility or MAC proteins MAC class will molecules signal friend part of our normal self, and k sells a part of the native museum and can sense the absence of this indicating something that's foreign should be killed. My name is Michael jury. I'm physician scientist in and president of the city of hope national medical center over the years. It's become clear that the way in case sales see is by the absence of certain molecules on the surface of a cell, and those are, you know, for example, class one molecules when they're missing and kale's wake up they have kind of a negative regulatory system. That's always on. So when that negative signals missing they become turned on. And so when you think about tumors, virtually all of them expressed class one. And so there's two is you could look at that tumors. Don't get class one the other way to look at it as. Tumors without class one are eliminated. And I think that's the proper way to think about things because there are several infectious disease molecules like v that work hard to down regulate class one probably scape T cells, and they are in case cell sitting there. But I think they're complementary to t- cells or T cells are looking at an alteration class one for recognition and k cells are looking for the absence of class one. And I'm using class. One is one example of of an an K ligon d- that it recognizes. And so I think there's been some beautiful studies by David relate in mice that show that when you have two minute loses class one it's eliminated immediately by an K cells. So I think that's the way they survey it's finding molecules and be they infectious or malignant that have lost their class one and other such molecules and the N K inhibitory receptors are there for turned off such that, you know, the kill is on of a raunchy research paper published. Last year caught my attention as an illustration of this area late last night and courage to the interaction of Zeke Avars immune system. And it turns out the Zeke Avars escapes being sensed by ANC as cells by up regulating MAC class one proteins. It's like a military jet setting its transponder to falsely signal friend, not fo-, viruses, like cancer can be clever enemies. My name's Todd vinegar, Minnesota professor at Washington University. This concept of missing south put forward by Ralph key slang and Clough Shahrae many many years ago now and the idea is that K cells recognize a diseased cell not based on a positive change in this L. But instead a loss of some of that cell that tells our own immune systems that that is indeed part of us and should be there and case cells have inhibitory receptors, there's families of them the best described or the killer immunoglobulin like receptors or the inhibitory receptor. There's and those cells recognize the presence of m h c class one which is a protein that's on all of ourselves, and it allows T cells to respond so when a cell in my body, your body gets infected or malignantly transformed oftentimes c class one will be lost that cell becomes invisible. To for example, CD AT cells, and our adaptive immune cells cannot see those cells, and k cells lose their break in that setting that inhibitory receptor no longer sees its again, and they actively survey for those types of situations. And so if a cancer cell, get smart and mutates beta to micro and therefore loses class one that opens them up to case L attack. There's a flip side to that. There's also activating receptors on and k cells and those activating receptors recognize stress induced lie Ganz, and so there's also a whole family of activating receptors and their ligon that can be induced in those disease states. And that's probably a combination of those two things that have to happen for the most robust case recognition to occur. N caso cling tippety depends on the balance of signals from activating and inhibitory receptors on the surface of the k sell and simple Thames. I think of like a risk that way you can control the amount of electric current by varying resistance inhibitory receptors recognize the MAC class one proteins on normal cells and suppress the activation signal the more resistant shoe provide real estate the low of the amount of current that passes Fru in contrast activating percents on K sells incense molecules expressed on the surface of cancer cells. And when this activation signal riches certain fresh, hold and k cells light w seven on licensed to kill. So can we modulate the tippety of an cells by playing with the RIA set to attempt to answer this question? That's delve deeper into MK selective ation with don't finish. And k cells. Have a constituent of inhibitory receptors are the things that allow them not to attack your own tissues like Kear and cagey to a they also have induce -able checkpoints, just like T-cells. They can be do sticks press, for example, Tim three or lag three or some of these alternative checkpoints on T cells that you might be familiar with. There have been some studies looking at well, if we can block inhibitory Kear one of the natural sort of long standing tonic inhibitory signals to an L could that potentially wake up a patient's own cells and have it respond to leukemia? I think that's a spectacular idea conceptually. But so far the clinical data that I'm aware of has really shown not a lot of activity and part of the reason why that may be because k cells depend on those same inhibitory signals over the long term for their functionality. We've heard this then K field education or licensing. And so if an case L is licensed by that inhibitory or sceptre. To become functionally competent than you might imagine that by chronically eliminating that licensing signal that signal that tells the case L, hey, it's okay to respond. If you actually see that cell that has the missing self that that might result in chronic reductions and case L activity in general, I think that N cagey to a represents a less tested inhibitory receptor. And I think those trials should be done. In addition. I think we really have to pay attention to each individual case L product. So, you know, my own conventional in case probably have very different checkpoints, and that's some of the data. That's emerging now than for example, memory like an K cells or other case L products that have been optimized in the laboratory. And so the example with N K G to A if you look at conventional K cells and ask them to respond to Kenya targets blocking K G to A doesn't do a whole lot. It doesn't change that dynamic, however memory like in case cells because they're induced express much higher level, suddenly become. Much more sensitive to that motive in addition. So if you can identify that and then block it I think for each individual case L type or product that it's going to be important to describe the inhibitory receptors lions that are present on the disease, you're treating and the receptors that are on the case cells themselves, so you have to be specific to the case L product who said targeting K checkpoints was easy. The first Antica monitoring antibody was liberal map. However, despite pretend co promise to trials and had an cancer ended up as MRs as we heard from Todd vinegar completely removing the inhibitory signal may not be answer when it comes to encase licensing and h pharma a now targeting B and K G H point via explains why so energy to as a very nice target because it's Xpress on. Both cases and sells looking of energy twin nicely complements. Blocking of PD one pedia one axis. We have made it very seeming survey Shen that t cells infiltrating humor when they express high level of p one though swing highway mpg to we think is from gresh. To try. The combination therapy of brooking PD one pedia one axis in commission with the booking of mpg to itchy inpatient and signal thing which is very interesting consuming kitschy today that inches is nothing in between molecule that's Xpress sales. But he's also inhibitory molecule that expressed on subset of teasers. But there's more to it in g to also embarrassed into the can be extremely important. I mean, we know of drugs and others relying on the, and so we have a very strong picnic would baggage showing the fact ADC she can be stimulated quite will. When you brought interaction between G to H E E as we just heard monitoring antibodies control concepts. ATC antibody dependent cycle -sity. One way antibody achieves this it's activation of K cells. So if you're looking at combinations where one of the drugs by ADC, you may need to make sure combination doesn't have any negative effect on an K cells. My name is Deepak Sampath principal scientist at Genentech. And currently. I'm also the translational research leader for Veneta clocks in K cells. Does the need to have an effect on them narrative eighty no we actually have data for that. So last time we spoke we were talking about the post we had e OTC in two thousand thirteen where we had very nice gotta suggesting that Annetta clocks can be combined with open a Tuesday, ma'am. And so as, you know, naked antibodies function through MK cells and so- ex vivo we don't see any detrimental effects on an K self-survival, and that's large private think because they're probably either dependent other profile proteins such as MC L one, for example. But most importantly clinical data, which we know that we're combining well with say. Twos. A mad and clocks, and so there's clearly activity we can combine with toxin and we're seeing activity, so if we were actually impacting case cells, we wouldn't be seeing this clinical affect with drugs that are clear dependent upon in K sells for NY dependence. Your talk city, or sell you dependence. I talk city. So to me, the clinical data, always Trump's pretty clinical. I n k cells are fine in terms of treating within a class. I think they're still remained functional or else. We wouldn't be seeing that that we do. Let's continue our journey into an cell biology and hear about a potential novel target. Hi, I'm Nick Huntington from the world allies a hole institute in Melvin and lab is dedicated to the research on natural killer, cell development and their role in cancer. Immunotherapy we published a high impact paper on the discovery of an intracellular checkpoint cold SIS, and this is the sign of kind juice S H two containing protein, which means that as the site of kind fifteen binds to the case, sells it activates them. But then as a consequence desist protein accumulates to turn this activation off it goes to the surface to the receptor and degrades the receptor degrades the kinds inhibits signaling and then K sell stopped responding. We found that if we generically deleted this this protein, the incase sales became exquisitely sensitive twelve fifteen and so to the T cells, in fact, both CD IT cells, officiant, facetious and. In case, sufficient assists, where extremely sensitive twelve fifteen and had superior proliferation and functional qualities in vitro in response to our fifteen now translating this into Chuma model, we found that sedation in a mouse, actually, rented them largely resistant to any metastatic black six, which is a mouse train Chuma cells that were totally resistant to metastasis at doses of tumors, which caused a lot of metastases enormous to try and think of the best treatment setting for assists, inhibitor, we developed a model of spontaneous breast cancer, and the model of where we inject breast cancer cell line into the memory fat and really remarkably in the knockout mice. We'll sister fission lies when we removed the primary Chuma. There was no metastases found in the lung now in contrast for the control mice had many metastases in the lung. So we think as a treatment regime, maybe when you detect primer you remove that treat that with the first line of thera. And then the patient on this inhibitor to increase the activity to prevent metastases or increase the control of metastases in the periphery all where metastases might already exists. But they're so small in number that you can't detect them traditional medical detection systems now in K cells don't last so long as T-cells does that mean that you potentially would have to keep giving this type of therapy for a long period of time over it be just give it and get this affect natural killer cells do not have a extended half life. They persist in patients when they're transferred to patients and also when we transfer them to mice that have no in cases, they can survive, but they don't proliferate and expand and and reconstitute the incase L. So they do have a very short compared to see DAT cells. So if trying to think of a way of treating patients with an inhibitor forces, we would think about weekly injections because the pending on the half life of the Sisson Hibba, we think that we can activate in case cells over a couple of day period than. Would actually have to start trading them. Again. Do we think this will work better in some kind says, Robert and others to try and start a fi where assistant hitter would be beneficial? We're currently looking at the role of fifteen being made by the tumor and whether treatments that have a high expression of fifteen like going to be more likely to respond to assist inhibitor because there's no point in hibbing SIS if there's no fifteen around because this won't be in the cell. So it really would depend on how much fifteen is at the tumor site and many different cells can make off fifteen macrocosm Milo. It sells Troy mall cells Chuma, so we're currently trying to work out what source of fifteen isn't how important the levels of fifteen to have an effective response. When you inhibits this one of the things in K sell see as they can detect the presence of cited kinds in their environment. So why is into Lucan fifteen important for encase cells into Lucan fifteen really is the the food the growth factor. The the nourishment for CIT cells and natural killer cells. They both highly dependent on this factor. It drives the stasis their slope for the formation in terms of in case, it reduces their threshold to be activated by activating Loggins expressed on Chuma sales. And it does increase the amount of psychiatry and Silat granules that they can secrete. So it really is the key factor in natural killer cell therapy. So term we give fifteen to generate some more activity from an Casals several companies I've along period. Now if being looking at ways of modifying fifteen and delivering fifteen to patients to increase natural numbers and function. Unfortunately, there's many cells in the human body that bind activated by this fifteen and when you increase some of these cells there is a lot of toxicity including vascular leakage and saw kind released injury. So it has been proven not to be safe. That said there are companies that are trying to. Define improve the specificity of fifteen to preferentially bind and activate natural killer cells and this work is ongoing one. I'll fifteen Atkinson in development attracting, a lot of the tension is all to a biosciences eight hosts three it's being investigated in multiple types, including hematological malignancies at I seventeen don't offend. You told me about some of the clinical data. There's other ways that we try to optimize a patient's own and case cells against their cancer. And so in another abstract that was presented here. Rizwan Romi from our group at Washington University described a study that we did in collaboration with Jeff Miller's group in university of Minnesota where we used an I'll fifteen super agonists called alternate eight oh, three to activate the N K cells of patients with various blood cancers that relapsed after an allergy neck transplant, and this was really the first test of this new class of immuno-stimulant ori- or activating. Inside a kind type therapies fifteen is one of the exciting sight of kinds because it activates n k cells and CD AT cells. However, does far there's very little information that they can up regulate t rags or other negative regulators immune response. So that puts it in contrast. I'll to that really does both things activates affect. But then also activates regulatory t cells in this small clinical study between at thirty three patients and the biological data. That came out of that the Corlett of science was really fascinating showed that this drug doesn't deed activate K cells and CD cells they expanded inside these patients and at the same time. This drug wasn't inducing a lot of toxins like we had seen in previously published fifteen reports, for example, the report on intravenous infusion of recombinant humanized fifteen that was published and J C O by the age group. So when we did the coral of phenotype being we saw in. Suction of some checkpoints on these n cells and t cells that were consistent across patients. However, there were some unique aspects to for example, one patient, regulated quite dramatically lag three and hepatoma receptor. And so as we give someone a therapy eventually we may have to profile their own unique checkpoint repertoire and then choose the right drug moving forward. And I think this probably goes beyond even case cells think we'll see the same thing and various approaches that are seeking to augment he sells or even provide T cells such as Kartini cells that for each disease state and potentially patient there might be different barriers to their affective nece don't to raise one room is now the Dinah fob Cancer Institute in Boston, you can find links on Lovato's dot com to Lovie obstr-. Some papers that we mentioned Altay three is also attracting attention outside of blood tenses. I'm James gully. I'm chief of the genital urinary malignancies branch and director of the medical. Oncology service at the National Cancer Institute. So we have ongoing study where we're combining a break Yeary vaccine that is over expressed in prostate cancer and other tumors that is inserted with epithelium transition, plus m seventy eight twenty four and then we're also adding that with out eight oh three the fifteenth super agonised to try and expand the number of cells to when I think of fifty I tend to think of as a ruck fuel MK cells. We've seen a lot of vile fifteen in human malignancies in particular, the rationale for going after INCE cells and prostate cancer. So I think we won't know until we try it. But there's some reason to believe that it could be very important player. There is data. Probably fifteen years old now suggesting that prostate cancer, especially metastatic prostate cancer is associated with a decrease in h LA. So if you can't have the molecules that are on the surface of the cells, then that doesn't matter how many sales you get there. They're never gonna be able to see that. So I think that by combining A N K cell component to your anti tumor regimen. You bring in another arm of the immune system that can help with tesol response and lead to hopefully, better clinical activity. We look forward to hearing more data on fifteen Agnes in development. If we want to optimize yet, Theresa K cells. We may need to much the site to signal to but don't seventeen we've been very interested in cytokines protein hormones used by the mean system to communicate between different immune cells, we've discovered a cocktail combination of cytokines. Interleukin twelve fifteen and eighteen that highly activate in case else. And then in turn if you allow those cells to differentiate they become a memory like sell a distinct cell type from the conventional K cells in your blood, and these are really functionally defined. So these cells are now better able when you ask them to respond to another stimuli say a leukemia target to functionally respond to kill those cells to produce different gamma to activate other aspects of the immune system. So this goes back to publication in blood from two thousand twelve where we really define the biology of those cells, and then a little over a year ago, we publish some of the preclinical results identifying that site, a kind induced memory like in case cells have a large number of really favorable, anti tumor, anti leukemia properties. Some of these include their ability to persist that after activated and they rate they're able to pass on enhanced functionality to their daughter cells that they're better able to kill or lice. Kimia targets in the Petri dish, including primary leukaemia blasts that we collect from patients. So based on that we translated this to the clinic in a first in human phase, one study Levin patients were treated in the phase one cohort. And we saw some pretty exciting results. More than half of the patients, and these are AM L patients who have poor prognosis their treatments, sailed them more than half, the patients obtained complete remissions which we thought was very exciting first step forward. And most importantly, they were safe. We saw no graphics host disease of these donor N K cells. We saw no set of kind really syndrome there is really no major toxins from this treatment. So based on that experience, we identified a phase two dose, and we have a face to study. We're trying to understand in a larger number of patients now by somewhere around thirty or forty what is the ability of these cells to induce complete remissions. And how does this compare to you know, what we'd expect with standard approaches? Like chemotherapy. So why is an attractive for encase offer? Appease, I think the short answer that question is it comes down to targeting. We understand some of the biology of the case, L recognition receptors. And when you take an case L from a happily dental donor within the that donor in case L pool, some fraction of those n que cells will react leukemia reactive is how we would call it to the patients leukemia cells. Now, how many cells are there reactor gonna depend on a lot of the variables in the donor and the patient, but experience transplantation field and more recent work from for example, Jeff billers group has really shown that allergy AM, and k cells can recognize ammo blasts, don't color jury y n que cells seem to have a predilection for acute myeloid leukemia. For example, I don't know the answer that, but it is very very interesting that in the hapless identical. Splints when you take away class one boom there goes the dynamite. So that's one aspect, but you know, that's not the only aspect. Maybe don't need a hapless transplant. We just block the receptor that sees class one that's essentially taking class one off of the tumor should work and that didn't prove to be successful, which tells us that it's more complex shock. There's a lot of interest. Everybody's doing Happel transplants now to understand the immune recognition. But on the other hand when we blocked the Keer by itself doesn't seem to do it. So mother nature's trying to tell something we need to spend more time studying that so I think that also brings up one of the challenges in the field is moving beyond my Lloyd, malignancies K cells in particular good at recognizing through their combination of activating and inhibitory receptors this. How do we target case sells to other types of cancers that they might not naturally respond as robustly too. If we want to Joe beyond allergenic office shelf sailor therapy for AML L. How can we potentially talk and K cells don't is doing pioneering work on by specific and Troy specific clearing gauges we first Boca twenty sixty EMT tend to meeting in Honolulu. My name is Jeff Miller. I am from the university of Minnesota and deputy director of the masonic cancer center, presented to the here at tendom with idea of getting rid of. 'cause why should we get rid of Kati cell Therapy's? So the therapy that we talked about today is really to try to. Attain. The same goals as cars with simple exportable office shelf molecules that were can dodge Nestle in the patients, what is try. It's a try specific killer engage her, and we have made bikes and trikes to compete with the cars in a bike is very simply to single chain of fees that one side is targeted to the receptor CD sixteen. So it's an anti-seizure sixteen Agnes stick single Chena fee. The other side could be any tumor antigen. We've most explored entice CD thirty three and Anchin on AM L cells and my legit plastic syndrome. So, but we've also made this to f- Cam things that are on carcinomas. So the difference between the bike and the trunk is tha. Get to single chain of fees to be functional you have to have a link or so that they fall correctly in Khanin dependent -ly bind to the Casal to the tumor target to make an immunological logic synapse in when you make these bikes in engage CD sixteen hundred in Casals, they have no proliferative signal whatsoever. They do engage tumor killing, but they have no proliferative signals. So what we've done with the tricks is we've taken the inert Lincoln and replaced it with the fifteen sequence in. Now, we have antigen specificity because we have two single chain of fees, and we have an fifteen molecule to give you the proliferative signal to survival signal in our data shows in vitro in an animal models at this is gonna be I superior than the bikes which only do the engagement piece, but don't give the proliferative signal. Seventeen to Miller presented a post on a second generation trike. He's developed avenue antibody construct. The link has been modified to shorten immune sign ups between the K selling Chuma cell with the idea that this will enhance efficacy. I hope we'll his clinical data ash moving on T cells have to lot of interest to recent FDA approvals within the with idea of inserting American Jim receptive into t cell in order to target antigens CD nineteen. So can we put a car into an encase cell, and k cells can also be modified by antigen receptors, you can generate car, and k cells today, most of the work that's been done on car in case cells has been done either in cell lines or cells that have been differentiated from either Jimeta poetic or pluripotent stem cells that they provide important proof of concept that you can modify an case L genetically and redirected. It just like you would t cell to a specific tumor type. I think that's one of the ways that we're gonna see an K cells expand beyond human logic malignancies and have the potential to be targeted to solid tumors or many different cancer types. If you can get the N K sell to be activated. It can kill the most chemo resistant tumor known to man. And so, you know, there's gold in them hills. And so learning how to mind our lab, we've developed Carin case cells that we've published recognized and can treat effectively globe. Last doma. We've looked multiply Aloma. We have data in acute myeloid leukemia. So, you know, putting the car onto the case L seems to working taking each piece and starting to combine these developing and harnessing technology, I e we can affect case with lengthy fires retrovirus we can start to really create our own tools. We can begin to outsmart in the tumors. Think you're gonna see NextWave clinical trials are going to be Carin K cells. I think you're gonna see that. And then you're gonna see in combination with checkpoint inhibitors, we await more clinical data. But we shouldn't forget what we're trying to do is optimize choreography immune system. It's all about generating optimal anti-cancer immune response based on what an individual patients needs and this may request. Both Nate an adaptive parts of our immune system. Let's close with some final from Delta's Mila Feni jury where we're at where we're going. I think that as the teak her space gets more crowded those wanting to be pert of immunotherapy and cancer, which is essentially every big firma, suitable company is of declaring their T so verses in case interest in whether the Kissel interest is to antibodies through trikes or combination of products. I think that's what we're gonna learn in the next two years, you know, the bar. Or for any immunotherapy in the future is very definitive trials where nobody wants an incremental affect you have to have a profound effect and some randomized control arm to make that point. And I still think that that's going to take even with the new incase therapeutics that are going to enter the field in the next couple of years. You know, we'll know that answer in five years, but whether in cases has a competitive place in the market or not I think in my mind that doing one intervention with one type of case cells choosing one drug that does one thing to k sell isn't going to be the way to lead us to successful and k cell therapy against cancer. It's really going to require a combined approach you're going to choose the best and k cells, the ones that might be the most functional and persist along if you're going to add on ways to better target them to cancer cells. You're going to provide support for those cells, for example, by administering homeostat, excited kinds like fifty. Eighteen and others. And you're going to want to turn off those negative signals like the N K G to a checkpoint that we just talked about. And it's probably through combining all of those different modular. Tori approaches on K cells that we're going to really see their potential emerge. That's where we're at with. Immunotherapy we're in the infancy. We're going to spend decades figuring this out, but we will figure it out, and it will become the fifth pillar beyond surgery radiation, chemo and targeted therapy. It'll become the fifth pillar of cancer therapy. I'm totally convinced it, but I'm also convinced. Hang onto your horses. We got a lot to learn we can't abandon basic science. We have to push on the basic science of malignant transformation based cancer biology, the basic science of immune recognition and work or decades with teams that require lots and lots of funding that sadly will become the rate limiting enzyme the funding in this episode. We've only had time to send the equivalent of a few post from truffles we still have a long way to go on journey. But if you're not socialist, then you should definitely take your close. Look potential of MK sells the cancer. Immunotherapy? This is no we'll talk it's bring to life the thighs around innovative new trucks, gene therapies is production of blue is publishing. Sully churches. Executive producer music is by David Shulman for Cuevas health may sound good to studios. Thanks to Elspeth Morrison coaching script advice. I'm patriot put thanks for listening.

cancer leukemia Jeff miller cell Therapy Washington University scientist Nick huntington prostate cancer hope national medical center David Shulman university of Minnesota Mike Kelly Todd vinegar professor Agnes National Cancer Institute INCE
Azra Raza on The First Cell

EconTalk

1:24:42 hr | 1 year ago

Azra Raza on The First Cell

"Welcome to contact part of the Library of economic liberty. I'm your host Russ Roberts of Stanford University's Hoover Institution our website is ECON- Talk Dot. Org or you can subscribe comment on this podcast and find links and other information related to today's conversation. They'll also find archives. We listened to every episode. We've ever done going back to two thousand and six or email addresses melody contact dot org. We'd love to hear from today's January. Twenty four twenty twenty and my guest is position. Author oncologist and Renaissance Woman Aswa Rosza. She's Professor Medicine Director of the Center at Columbia University in New York. Her book is the highly acclaimed. The first cell Rosza welcomed ECON. Talk thank you so much. Russ and this book is not what I expected. It's it's a moving and inspiring mix of the personal side of being an ecologist along with the policy issues surrounding the way we fund in Do Cancer. Research is a book about death and despair. It's also book about hope in life. It's beautifully written. It's a powerful. Look at what. It's like to have cancer to work with cancer patients and probably more than anything else. A book about being human being and all that that entails. I found it to be a hard book to read and hard book to put down and along the way There's a lot of policy about how we currently do cancer research. So we're going to. I hope get into both sides of that Your personal story as a practicing physician and then also the policy issues surrounding cancer research Let's start with just mdis which is Your specialty what is it. And what's its relationship to leukemia cancer? Generally that's a good place to begin. Russ because my career started with this In fact when I came to the US in nineteen seventy seven as a fresh medical graduate. I was hell bent on studying and treating acute myeloid leukemia. Liquid cancer which is easier to study than a solid tumor like lung cancer variant cancer et Cetera by Nineteen eighty-four. It had become very clear to me that in my lifetime we will not be able to find the solution for acute myeloid leukemia because it is a costly disease and tremendously complicated. But then my many of the patients would give a history of having had a pre new p make fees in which blood counts. Were falling. They were developing anemia. Their white count was going down and these syndromes but eventually gathered under the umbrella of myelodysplasia. Stick syndromes or MD s which is really Disease by itself that can kill but third of these patients can develop acute myeloid leukemia and die so I turn my attention towards catching patients disease or acute myeloid leukemia early by trying to catch them at them. Ds Stage So. I was really interested in the pre leukemia. Part of this. Mdis to begin with you. Summarize our current approach to cancer as a slash poison and burn What do you mean by that? What does each of those mean slash means? Surgery POISON MEANS. Chemotherapy and bird means radiation therapy. And would you say is the mix of those three in our current you know that that's her arsenal of of weapons. Arsenal shifted over time or has it changed. Your we still doing a lot of each. This is one of the main reasons for me to an author. Suddenly because I'm not a writer I really am an oncologist and a scientist and I've dedicated my whole life to treating patients and trying to study their disease in the laboratory but I was forced to take The pen on because while it is very true that we are killing sixty eight percent of cancers we see today the reason we are curing them is mostly because of early detection and the treatments we are them are by and large the same treatment that we have been giving for fifty years which is the slash poison burn. Now many of my oncology colleagues then to have this attitude towards me saying Azra. We're looking at the glass being half full and you're looking at at it being half empty which means why am I asking even the question that sixty eight percent patients are being killed? We should be pumping our chests. We should be giving ourselves gold medals. We should be proclaiming this from the rooftops that we are curing almost seventy percent of cancers diagnosed today but. I think that would be unfair to patients coming the future. One of our family friends once told my younger boss that look if the sun rose from the West everyone will stop and stare at it and wonder why But there are a few people who see the sun rise in the East every day and wonder why in other words there are people who refuse to take things for granted so I am questioning number one. Why is it that we are continuing to use the same old same old same old treatments despite billions of dollars being invested in trying to develop new targeted non toxic? Non Chemotherapy therapies. Why are we not looking to determine the reasons for ninety five percent of clinical trials failing and cancer today? What preclinical platforms? Are we using to bring those drugs to market? And then on the other hand the thirty percent patients that we are not curing because they were diagnosed with advanced stage of their disease did outcome. Today is the same as it was fifty years ago even with this slash poison burn. We have made no difference to them so basically. What is the glass half empty? And what is the glass half full here? Well using the same treatment we are benefiting the patients we would have cured only because of earlier detection and thirty percent are dying jetblue debts. I would say your book is Is a shout from the rooftops that sixty eight percent is not enough And the other point which you're painfully makes clear. Is that for those thirty percent the slash poison and burn is it's a cruel is a cruel approach unbearable approach for a doctor who has pledged to first. Do NO HARM A. We should probably explain it. You know people who have had experience with cancer or loved ones with cancer understand but you should explain why it's why use the ripois on the technique of of chemotherapy which is The poison part of your trio white. Why do you call the poison? What IS ITS MODUS OPERANDI? How does it? How does it work literally as somebody described taking a baseball bat and hitting a dog with to get rid of its fleas? That's what giving chemotherapy is. Chemotherapy can not distinguish between a normal cell and CAM system. But it kills rapidly dividing cells. That's why side effects of chemotherapy affect rapidly dividing normal cells. The most for example here fallout because here. Follicles grow very fast off. We have severe nausea vomiting because gi tract is sloughing cells and dividing very rapidly. So chemotherapy basically is a sledge that goes in and starts killing selden because cancer cells are dividing faster than normal cells. In an organ we kill more of the cancer cells and less of the normal cells but still normal cells die and by the waitress. Let me stop it and tell you one other thing. We were talking a lot about immune therapies these days and there are multiple kinds of immune therapies but the most dramatic ones are those that use body's own immune cells to activate them and attack the cancer. You might have heard of Gardez. Nowhere to investigators point out that while Guardi cellular therapies the most dramatically effective form of killing every last cancer cell in the body. I acknowledge all of that. It is a fabulous feet of scientific achievement credible incredible achievement to take the body's own T. cells which are kind of immune cells and engineer them in such a way that they are now carrying part of a B. Cell which is another lymphoid Immune sale and it's activated to kill any solit- meets which is expressing a B. Cell receptor CD nineteen. This is the most common carty therapy used for B. Cell Lymphoma or leukemia but nowhere to investigators point out that these t-cells also cannot differentiate between a normal cell and cancer cell. So what they actually do is kill the whole organ. But specifically that organ still there are off target effects which means other cells in the brain or somewhere else which are expressing the same macher. These engineered cells are so effective. They will seek out and kill. Every cell that he even has a molecule of that receptive being expressed sorry. I saw the movie Breakthrough which I recommend listeners So documentary about Jim. Allison who was a pioneer in these techniques and It's a it's a very interesting movie for a bunch of reasons. I think some of them will come up through the course of our conversation but the one I want to focus on is. It's very celebratory movie. It is it is. It is yelling from the rooftops that we've made an enormous amount of progress in it highlights. Wonderful Miraculous heartwarming stories of people who had a death sentence it was revoked. And they. They're they're fine. It's not just like they're they're alive. They're doing well and what the movie leaves out as the Economist. I had to notice to two things the most important things that lease out. One is doesn't help that many people. It's a very small group that unfortunately it's a group that these techniques are working on with that kind of effectiveness. Second thing they don't talk about the cost In fact the the pharmaceutical company In in the film the courageous one that keeps a trial going. That was a failure. There's some great wonderful things there. But of course they have to compensate for their enormous risks. They take in extending trial way beyond. It's it's normal time. Which of course could have failed and cost him hundreds of millions of dollars. It turned out it worked which is great but it costs. Us ignored which it often. Is these kind of stories and then It ignores the fact that it's a small group and that that's the tragedy that you're focusing on the breakthroughs that we have made have been as you cite. Some of them have been just glorious but unfortunately they don't apply very widely at least yet So react to that and also the possibility that it might expand to treat other cancers right that we don't know about right now. There might be other forms of this therapy that could reach a wider range of people or is that not the case for us. One of the big problems we have faced in cancer is that despite looking for sixty years we have not been able to find. Molecules expressed only by cancer cells. And Not by normal cells in other words we can't find the address the unique zip code of cancer cells so far so at best. What we are trying to do is basically kill sells more effectively irrespective of whether they're cancer cells or normal. When you ask me that will this. Immune therapy applicable to other cancers absolutely should be applicable. But right now it is not so because if we tried to kill liver cancer cells with this kind of Cardi therapy it will destroy the whole level not just livers cancer cell or it would destroy the whole. Gi Tract the whole colon so the entire organ would be killed because normal cells are expressing the same marcus as the cancer cells however when we learned to identify by means of whatever biomarkers we develop in the future as technology's evolving then not only would be able be able to Specifically target cancer cells. But the other thing is that we would be able to use these therapies in earlier stages so that right now when we give these therapies the only patients who respond are the ones who experienced the most severe side effects goal decide to kind storm which basically puts the patient's life at stake that if they survive it they will enter mission those patients who don't experience this horrendous cytokine storm. They don't even eventually respond to this kind of therapy in other words. What I'm saying is that we are going in the right direction. We have made some significant dramatic advances in these kinds of immune therapies. But the way they're talked about the hyperbolic language that is used minimizing not just the financial toxicity but actual physical docks the city of immune therapies. And then let's stay just chemotherapy. You asked me why do I call it as this poison? It's because recently I saw forty two year old Beautiful woman who came to see me because suddenly she had Developed weakness and fatigue and had was Seen by her primary care physician and found to have low blood counts. I do a bone marrow and I find that she has acute myeloid. Up Me Yeah. No I look at this gorgeous young woman who stormed and tanned and I shudder to think what I will be doing to watch. You will look like in another six weeks off to the chemotherapy. Given so the question I'm asking is I was giving the same two drugs in nineteen seventy seven to treat a patient like that. I'm using today in twenty twenty seem to drugs with this same dreadful results. How long will we continue to do it? What is there for the future? How can we change it and one of the worst things in the last thing I want to say about it is that do you know to this day? We don't know how those two drugs work. We have no mechanism of action. Precisely laid out for them. So what is that once we have made an acute myeloid? Upenn so part of your book is an indictment of the and then what you want to call it. The the intellectual infrastructure of the pharmaceutical industry and the research behind it that both private and public that uses a set of Clinical trials typically on mice and then it goes up to a larger animal. Typically I think dog Before it goes to human and we understand that it's hard to experiment on humans for lots of reasons but your point about my says that it's not just well not every time it works out that it works on a mouse. It doesn't work on him and in fact it almost never works on human if it works on a mouse and this is This whole intellectual structure is is a mistake in your view. It's a reductionist attempt to hone in on the the micro cellular level for for this causal. We're trying to close the door on this one little entry when in fact that whole approach you're suggesting is is wrong because cancer is so complex and it's not just complex meaning. It's hard to figure out complex. Meaning it's multi variant and. It's different every person even and so the whole approach we're using of this mouse. Driven reductionist approach at the cellular level is unlikely has failed more or less and is unlikely to get any better and we're throwing hundreds of billions of dollars in you said it upset really read. Your Book. Ready have a convert worried about. It will go ahead. No I was going to say that scientists succeeded with magic fee because we are interested in understanding things and we think that we learned to control nature and that ball would will be the byproduct of understanding and that is why I think the intent to try and study and understand. Cancer is Got To be applauded. The problem is that there. Aren't that many cancer cells available coming from humans for basic scientists to study so they have gone ahead and made More loose and again. The intent is very good and to study the biology of cancer. Animal models are fantastic. So I want to make this distinction very clear over and over that. I'm not against the Yuzo. Fundamental models and mouse models to try and understand mechanisms the biological basis for phenomena that we observe. That's on exactly what these models should be used for. But this seems to be like an emotional Mason Dixon. Line clearing on colleges from basic scientists. When it comes to developing new chemo head. Appease my contention is that all research on cancer should have one and only one goal which is to benefit the cancer patient. It's all very well to study biology in mice and rabbits and fruit fly and Zebra Fish. But if it is not therapy driven. If it's not going to help my patient than for me. It is of no use and spending hundreds of billions of dollars to identify the next intracellular signaling pathway. In a tumor that is artificially created in. A MOUSE IS COMPLETE. Waste of money for me especially when we talk about drug development. The idea that we can create a tumor in an animal model treated with a given agent. And then bring those results to human bedside. When this is made met with unmitigated disaster and the reasons that you have very clearly pointed out is that yes. Cancer begins in one cell but the cell dividing it's covering one generation within hours which it should normally cover in months if if not even longer so that these rapidly dividing cells meet DNA COPING ERRORS. Which are known as mutations every time a cancer cell divided into it picks up new mutations which means now there are potentially two entirely new cancers. It's something like the brain has one hundred billion cells but one QUADRILLE IAN connections. The same cancer begins in a selves. But then it has the potential of constantly moving constantly changing and undergoing metamorphoses. So that within days there is now a mixture of heterogeneous biologically distinct populations of cells within a tumour. And I always say that treating cancer like diseases like treating Africa's one country it's not the same even into sites and the same patient or two days in the same patient the same that humorous changed. So how can we apply? Reductionist approach in the Su- Nami scale within a Touma along with its micro environment the intracellular signaling the response. The blood supply the angiogenesis taking all of this complexity and trying to bring reductionist scissors to it and trying to find one molecule and developed one more magic bullet for it. It hasn't worked for fifty years. His wife Soda. Good no go ahead finish your thought I was saying this is why fifty years later we're still using slash poison and burn and the thirty percent. Patients are still dying the same way and to sixty percent seventy percent we are using slash poison burn. We don't even understand how those things are working is. I was just GonNa say I think you're wrong. You said I said it better than you but I think that that was not true. That was beautifully said The other part of this of course we've talked about this on other episodes Related to these issues and. Let me try to summarize. This is the way I see it as an economist. We have a medicare system which is for old people which does not Negotiate drug prices and as a free market economist. I love that. We don't negotiate drug prices. I don't think the government. Excuse me I. I don't think the government should be setting the price of drugs. I don't think that's a good thing. However at the same time and these two things don't work well together. At the same time any increase in efficacy no matter how tiny an increase in lifespan. Immediate increase of two months is now becomes the the Gold Standard of treatment and is paid for by Medicare so basically there's an enormous in which the drug companies have pharmaceutical industry to make marginal improvements at enormous cost creating new drugs that can be patented which they of course have An incentive to find debt are paid for by a third party me the tax payer Without regard to whether that money is worth it. There's no skin in the game or I would say differently. It's the wrong skin in the game. For the pharmaceutical company. They are motivated by profit. Which is a glorious thing you you say so in the book at one point in a sentence. I'm not good quote. But its role said that basically say they people goal and an incentive defined it though they'll work at it and we yet we've created a set of incentives for the industry that is not healthy and that combination of patent protection marginal and I mean marginal meaning small increases in efficacy. Paid for at virtually without any restraints is an enormous waste of money in your book. You're not in the Communists but much of your book is is could be summarized as saying the cost benefit of this is out of whack. This is not an effective. Use Down that story. You just told a why the current perch doesn't work. Well you could react to that with despair You could say certainly at a minimum. Don't WanNA throw good money after bad to continue that approach which is what we're doing in your view that put the question would also then be but what would replace it other than despair if the current approach is an utter failure in your view and I'm going to maybe push back on that in a minute but let's start with that if it's a matter failure and it's financially and mistake the way it's structured to waste resources relative to return what might replace it. What could do better? I think again. Excellent analysis of healthcare Doldrums right now. It's no surprise that only twenty percent Americans have any confidence in the healthcare system. Today in fact twenty percent Americans are being hounded by collectors for medical bills and we had a recent. We had a recent episode on that It hasn't aired yet but With Marty mccarey on this problem of of unpaid bills I would say though is ready to be fair I think most Americans love their healthcare system. And that's I think it's actually a quite high number There it's in the I think recent polls I saw I don't know if it's a good polar not have to be careful in something in the eighties. Eighty percent or more like there are satisfied with their with their healthcare. We have extraordinary healthcare in the United States for most Americans that all many Americans have horrible access to it but to many but but the but so many have gloriously fabulously innovative and technologically advanced amazing set of options. And they're delivered without waiting and it's it's an and you get access to incredible minds like yours at training and experience and it's not it's it's time to sit down with compassion so it's a wonderful system but the price that we pay for it seems to be way out of whack for what we get in return and that's simply reason. I think we're so happy with it is that we don't have to pay the price directly. We don't realize what the full price is. But want I want you to? I want to move away from the ADS on. I want to move away from this issue of the overall system and just focus on what you think the best. Your books called the first cell for reason. What do you think we should be doing differently? We need a different approach. Yes thank you so much for bringing me back to them on the optimistic part of Europe although Ross I have to say that The subtitle of my book is almost as important as the title subtitled list. The human cost so off of trying to continue to persist in the same old same old because this is why I look at everything. You're doing in cancer. Through the prism of Human Anguish Water. The patients and their families going through When we practiced the current form of treatment I mean. Clearly if we treat disease anytime retreated disease. We have a fifty percent chance of winning and fifty percent chance of losing but the way I have tried to look at it in the book is if we treat the person and then we have one hundred percent chance of winning. We have to stop the Self deception that is limiting audit ability to risk new idiots of research and give up the Sclerotic old ones one thing. We learned in medicine over the years of practice and seeing as I do. Thirty to forty cancer patients every week for the last forty years. One thing you learn. Is that how you want things to be makes no difference at all and at every step of the way I have to stop and ask myself. What is the categorical imperative at this point? What should I be doing for this patient? That would should become nor tomorrow As gone categorical imperative is and this is what keeps brings me to look at the whole cancer issue in a different light now so far strategy has been as you and. I have been discussing for the past. Forty five minutes is that we tried to kill every last cancer cell in the body but the only thing that's really worked for cancer in the last fifty years is that we have brought down cancer mortality by one percent a year which is no laughing matter nothing to frown at because that has translated in the last three decades into a twenty seven percent decline in mortality but most of that has happened for two reasons one because the anti-smoking campaign finally began to show some result. So that kinds of cancers we were seeing associated with that have declined but more importantly or equally importantly is that we are detecting cancers earlier and earlier instituting. Whatever terrible treatments we have but at least instituting them early so we know clearly since nineteen or seven that it's not cancer that can kill but it's The d lene. The treatment that kills and earlier we detected disease the better and then we have to try and Colibri loss sell. Yes but we are not detecting cancer early so the question is why in this day and age of Supreme Technological advances magnificent scanning and imaging devices and hand held devices and cellular phones etc and self driving cars. Why are we still using fifty year old methods? to look at PSA to look at mammograms or to put a tube into someone's got to try and find a cancer by looking for it? Those learn really have to be changed. So how do we change them before before you do that? I WanNa say that when I first heard the title of Your Book and I read a paragraph description of it. I thought I'M GONNA hate this book because you know this idea that we need to screen more effectively which is a big theme of the last twenty-five years. Get your get your colon. Colonoscopy wants turn fifty. Get Your mammogram when she turned thirty. Maybe even forty Get the PSA test these screening techniques as. We've talked about many times on the program in his. You talk about in the book. They've led to more harm than good. They've we're not going to talk about each one individually or and I'm not. We're not giving medical advice on the program but I think listeners know well what some of these tests are and you should read about them before you just a thoughtfully. Just get one because you hear that. It's a good idea. Many of these tests the false positives the test itself the anguish the The damage is done is is is worse than the disease. The net effect is often zero or negative on mortality. And so when I first heard about your book I thought well this is going to be an easy book to dislike because The idea that we should screen earlier and often and of course there are people who sell such scans say you have cancer right now. Go Look and you know my views. I always been most times better to look at least under current technology so I was relieved reading your book that you know all that of course So when you talk about earlier detection and screening. You don't necessarily mean the current arsenal. Which is I think a tragedy in many cases. I've been a persad coming on the program soon and he's written very powerfully on twitter. He's got a new book. Coming out we're going to read for interview called Malignant. Which is very aware of these These failed screenings so we knew advocate for the first cell meaning the beginning of the very beginning of cancer nipping in the bud. You're not saying we need to do more of the current set of screening. What do you have in mind? So what I have in mind is that we I myself just talked about the failure of the reductionist approach that basic scientists and oncology researchers have used to try and look for one gene and And and try to find a magic bullet to undo the harm that gene is doing but in fact we are all guilty of this reductionist approach. So if you think about cancer the cancer cells then the cells have DNA in the genes DNA Transcribes AUDEN A and this is translated into proteins and proteins are metabolize so now we have five compartments. Sales are innate. Dna proteins metabolites. Why should we look at any one of them or any one gene and DNA or any one protein signature? We should be looking at everything simultaneously so with this kind of an approach which is more pluralistic using the latest technology. What I'm proposing is that data patients who are who have cancer today many times. I'm asked this question. Ross if you have acute myeloid leukemia Dr Rosa. You're being so critical about the treatments have been. Would you take the treatment? My answer is of course. I'll take the treatment because every human wants to have hope. I WANT TO BE THAT ONE UNICORN. Who's going to be? The exception and thirty percent patients with acute myeloid. Leukemia will survive five years even today. So I'll take that chance sure but the question I'm asking is. Why is this the only a choice being offered? How can we do better tomorrow? So now it comes to two issues. One is that we have patients today for whom we need treatments and we need to invest resources to try and improve those treatments and find better runs. I'm saying that the other half of resources need to go to improve the technology we have for earlier detection which means a really serious toddle overall analysis off cells audited. Dna proteins metabolites from CD. Lee sequentially studied actual human samples not animal models. And the last thing I want to say about this is that this is where real large scale studies will have to evolve to provide the sample size for machine learning and artificial intelligence since nineteen eighty-four when I turn my attention towards studying pre leukemia and following these patients as they either died of. Mdx or developed. Leukemia. I started banking born marrow and blood samples of my patients today. Russ this may sound like a very ordinary thing. But I have I have now collected over sixty posing samples from thousands of patients. North One cell in my tissue bank has come from another investigator all of these patients. Something to me because I personally taken care of them. Most of them have done with my own hands. This is to shoot repository where today I can go in look at the sales look at our DNA proteins and metabolites in a serial fashion as the fish and progress from pre-leukemic to acute. Up Man. This is how we can work our way back and then ask the question. Why did some patients get me out? What were risk factors that made this individual or BSB people susceptible to getting pretty you keep me even and this will take us then to a group that is at high risk of developing pre leukemia. And then we can start monitoring those individ- healthy individuals who are tied. Risk Edna targeted fashion. So I can do this for pre leukemia and acute myeloid leukemia. The resources are needed. I'm making this appeal to everybody that we should not rely on any one test done annually which was developed fifty years ago rather we need to develop using the latest scanning imaging bio marking Gino. Make proteome Metabolic technologies to find maybe five hundred different tests that can be amassed in a barcode fashion or can be done rapidly quickly To identify individuals in the earliest stages of cancer the resources half the resources go to treating current cancer patients and developing and improving treatments for them. The other half must be invested with early detection through the latest technology and prevention and nipping the incident. The Bud so the way I would think about it and you talk about in passing and a number of places in the book is that we use the word reductionist. You're focusing in on A. You're not focused. My research is focused in on a Small causative window that does not capture the full building and you have amazing storage. I just WanNa read because I loved it so much You were talking with George. Washington University Dr a Ugo Maya under no surgeon and he was talking about the brain and you asked him What would be the final level of reductionism needed to cite the root of consciousness? Meaning where we're GONNA find consciousness in the brain. Is it over here. Is it over? There is the the amid delays at frontal CORTEX. Is it the way that? And he's what? His answer is a deep insight. That is very relevant for economics. In life he said the following quote. Ostra taking apart the Taj Mahal brick by brick to discover the source of its beauty will yield only rubble. It is the same with the brain the emergent complexity from simple individual parts accounts for its central mystery. And you add it is also the reason why cancer will not yield secrets through a reductionist approach. Of course. That reduction approach is how people are trained. It's how people grow up in medical schools how they grow up in pharmaceutical research. It is the It's the default and by the nature of our scientific funding system Where existing scientists approved grants to new scientists typically in the place of bureaucrats. It's SORTA better But it's got the problem of group thing and you're you're demanding. It's a beautiful. You are demanding an not an end to that group thing because you can see and I think you have to concede that there. There have been advances through that I was going to push back against earlier and say you know this animal model at least if we hadn't followed it we wouldn't have gotten to these therapy techniques that they have led to a lot of good things and even if it's only thirty percents thirty percent better than nothing whether it's worth it to different question. Your point is is that we need to try. Some different approaches and the current system is not designed for imagination. It is not designed for creativity mentioned. Jim Allison earlier Who was a key part of this in the in the documentary breakthrough? It's pretty obvious when you watch the film that Jim Allison's not normal. Thank God. Allison is is a maverick he. He's he was a crusader. Who was overconfident could have been wrong but believed in a set of observations and a strategy for fighting cancer. That people has seen fail over and over and over again. This idea of immune therapy it'd failed. It's not just like oh. He tried this and it worked. It failed over and over again and he yet he persisted he started that rooftop in and said. I think this is going to make a difference and he did and I would argue that. The current system needs a lot more trial and error. It's the wrong kind of trial and error. We're using now this reductionist animal mice based approach. We need a a world where there's a bunch of islands where people are trying radically different approaches. That you're talking about and I know we have listeners. Dekom talk we're capable of funding such approaches. And I know you know about some of those aren't listeners. But it seems to be a very wealthy person who doesn't who sees the world through your eyes and says enough. We need to stop spending as much money as we're currently spending on this and the current system is not designed to change so we need to have an end around and so. That's the way I see. Her book is a I mean. It's possible that the FDA and and others will you know the National Cancer Institute and I h will see that the you're right but it's also I think we're likely in history science to me bears this out that someone will say Something different. Let's try something radically different. Let's dream and most of those dreams will fail just the nature things but as you point out you have a wonderful day to set this tissue repository. It just needs some money to help lead. Shed some light on things not just. Somebody needs a quite a bit of money. Money's very easy to raise actually because one thing I would like to point out. Is that one in five new chances of a occur. And I don't want to scare anyone dress but statistics are important in some places and unless we are aware of the tiger in the bush. We're not going to be careful. So this is why I point this out to you. That one in five new cancers appeared in a cancer survivor and the worst case was my husband. He had the first cancer at thirty four years of age and a different one at fifty seven of which he died because the underlying reasons that led to the first cancer still and then we have also created more damage by giving chemotherapy for that first cancer but luckily we are success. Swollen treating seventy percent of cancers almost today so that there are a lot of cancer survivors twenty sixteen to seventeen million now and by twenty twenty five. They'll be twenty million cancer survivors. They are the ones who should be most carefully watched and monitored for the appearance of the first sale if only one million of them give ten dollars a month for a year. That is all I would need to study the tissue the poetry. That's kind of Public Awareness. That could really help do this. Sort of thing And the other model is what you suggested that. Great philanthropist with a big heart suddenly realizes that yes here is some tissue that has been collected for thirty five years. And it's sitting in freezers right now Whereas if we invest this money within a few years we will have all of these multiple compartments when studied that. I talked about and And surely Even if we don't find I cell within the next two years we will have so many new insights into how this disease is progressing and Expanding and killing that on of this would be worth worth our while. I do think that It's very important for for the public at large to understand that Not the kind of Smoke and mirrors approach. We have used to convey cancer. News seems to have created an impression in the public. The great advances have been made. Unfortunately I don't agree that great advances have been made while fully admitting and there's no reason to deny I'm very much on the front lines myself for us so there's no question that I'm doing this every day. It's not like I'm some author. Who's writing this research? I am seeing forty patients of week. I am a cancer widow and I am in a lab doing basic research for thirty five years. So I don't need to be lectured by anybody about how much advance have occurred and cancer. Of course I appreciate that my practice them. I told you I would the same treatment that's offered if I get acute leukemia. Today my husband took the treatment I gave it to him the same treatment that killed his entire immune system and eventually call such as a beer infection that he died of Sepsis but I gave it to him because it gave him a chance of survival also and he did survive for five years. Thanks to the treatment we gave but two years. Yeah it was very tough and the point I make now is that it's just unfair to patients coming in the future to keep insisting that we are making great advances and this incremental successes fine and we should keep investing hundred and fifty billion dollars a year to treating cancer and whatever number we spend in doing research and the same old same old way. No I do think that We can see clearly what is failing and instead of investing. I'll give you one last example. Let's say that this immune therapies working in lung cancer and one drug gets seems to be seems to be doing some and let's say it gets approved. The one one chemo. Immunotherapy gets approved. This same immune therapy has also worked in. Let's save a melanoma now. They do a trial in multiple myeloma another bone marrow cancer and what happens. Is that instead of one trial. Better not five hundred. Trials are not one thousand. There are two thousand two hundred trials going on to ask the same question now. Each clinical trial cost millions of dollars. Phase one cost twenty five million and faced three costs anywhere from five hundred million to two point. Five billion dollars. Why do we need two thousand two hundred trials to ask the same question? Instead of all this redundant waste of resources in trying to make a quick buck. We are Through which we are stifling. Creativity beer stifling research and development of novel talk. It's because we are just trying to rush and make money by me to me to kind of approach. I'm insisting that we stop all of that and redirect better so there's plenty of money for God's sake America's the most affluent country in the most affluent of times. We should be able to invest in this properly and really make sure that the future cancer patients are a better or Wanna. Come back to emergency. I mean I think one of the challenges here is that you may see that as wasteful the current incentives encourage it Some good things come out of it But for all of its flaws it might be better than Does a cancers are who allocates money unless you're desire and and if you are are you might start acting differently Once you became the czar and czars tend to stifle creativity generally as well so it strikes me when I think of the institutional changes that I would think about to get us closer to your vision than than the current one Set of prizes. Would maybe a better idea. There are set of prizes of course built into the system. Right now just that. Those prices are structured in ways. That encourage Another slice of the Salami rather than a different approach. That might have a much bigger impact. So I think it's It's a very tough problem and I think politically very hard to change that current system and your book is an attempt to raise consciousness about it. I think that's great listeners. To this program. Maybe we'll down a little bit differently about it. But I. It's a hard problem and I think the the end around approaches ultimately Probably where we need to get to You know we see this already. In in the way technology is being used for medicine in creative ways outside of the current system whether the current system will prove those ways for funding etc of course remains to be seen but Let's let's which if we might to the personal side of the book which was really Devastating and inspiring at the same time you have a lot of stories about the suffering of patients and When I first started reading that those parts of the book I actually thought you know. Why is this in here? Do I really need? I mean I. It's depressing It's sad twenty-three-year-old. Dying of cancer surrounded by friends and parents. It's it's unbearably sad and I think there's two things about it that are that I think are important. One is beautifully written. It's inspiring the way people can love in those settings But more than that. It it reminds you and you have to remind people of of what's going on in behind closed doors in the halls of the buildings that you're in every day and that the rest of US principally or not which is that human toll and it is It's very very difficult. Very POWERFUL SO I. WanNa talk a little bit about the personal side. you mentioned the death of your husband you write about in the book You talk about in the aftermath of that you were. I would describe it you're in a daze and you talked about how fiction and reading helped you tell us about that yeah You're so right about this that the science can finish but the human stories gone and I do think that the most important part of my book relates to the patients were living today who agreed to write in the book Their own wonderful experiences through terrible times That are the only beacons of hope in this terrifying darkness that cancer brings with it and the fact that families of these stations would willing to be viewed and when I asked them to cast backward blonde some their experience and see what parts they could have changed what decisions they could have altered. What now with the Luxury of time and with acceptance. That comes eventually with time. What can point to that? They should have done differently. And I think those are the most powerful and moving statements coming from the families when they talk about. They loved ones dying. It's true that the dizzying and disorienting Daily challenges of cancer can really bring a fog down upon you days upon you and and no sooner. Do you get used to one situation that suddenly everything changes and now you have to adapt to completely new findings and new test results and new challenges and new physical symptoms etc. It's very difficult so important. Part of the book is looking back trying to bring some method to the madness and eventually coming to the conclusion that in fact the only answer is that there is no answer that we are trying to bring Some sort of rationality to randomness and disease and none of it makes sense and at some level one needs to accept it. How do you develop this ability to continuously witness the kind of pain and suffering and anguish? That people are going through at one point for me. Three has been very important to us because I come from an intensely and deeply oral culture where reciting poetry and memorizing poetry is Chris Byrd into our DNA but and we Growing up at home and Rachi Pakistan. My parents made it a point that all seven of their children were meet to memorize hundreds and hundreds of verses. Do Ending Latian sometimes inpatient as well and very often that The kind of two lines of Gazal which is a form of A very stylized Of Poetry in my language would do Two lines of a of this form of forum are to me like two strands of the detainee in microcosm is contained a microcosm of meeting and it teaches you things that are impossible to verbalize often and at one point. I remember when I was thirty. Two years old and faced with One of my patients. Jc who was extremely ill and she was only thirty four so we will practically the same age and one day instead of dellinger jokes. Trying to distract her. I read a piece of a poem that I had memorized. Which I'll recite for you just now And for your listeners is It's a boy and by so posh party who was a Bengali poet. And it's an translation. This condition off. Life is not for whole year only for the few months when it rains the blazing fire of the drive would will cook rice in no time and whatever is there will come back into view. Sharp and clear. When the rains depart we will put out in the Sun. Everything that is wet wood chips and all put out in the Sun Be. Shell even our hearts and reading the sport to J. C. We bought just burst out crying at the end and it was some form of a catharsis for both of and you know. Jc was someone who's dying at thirty four and a half twinned two and a half year old twin daughters and the I mean. She didn't give me any lectures. She did not have any Books that she wrote. She did not have gold medals that she had one in her academic career. Nothing like that and yet she allowed me to witness an expedience Greece in its truest form and the way she accept the disease and the way she accepted her death. It was as if she rejoiced in her death in that she met the challenges of life with all the passion that she could bring into those last few months and the Noble Wayne which she boss through those those last few months. Ah for life became indelibly tattooed on my cerebrum forever and so much of what we should. We should a lot of poetry together. We should and and with other patients also. I mean just reading. Fiction is so important because it allows one to poach on the experience of others it allows one to stand in the shoes of others it allows one to see who lives in war and consequences of decisions that they made examined intrigues on. And it teaches you learn about yourself because you declare your feelings for one character not for another you like this one. You hit that one and this gives you insight into yourself so for me. Learning to deal with real human tragedies has been tremendously helped by the create writers afforded Far Literature and listening to you talk about JC right about beautifully in the book as well. And you're talking about the. She had no tangible accomplishments like a book. No tangible signifier is like a gold medal but the way I think about her and people like her people. We know like that is that she's an artist. Her raw material was the tragedy of her disease and she somehow molded and crafted into something extraordinary and I think that's the privilege that a doctor can have a nurse can have I was. I was recently visiting my dad in the hospital. And WHO's there for five days and not very good shape at eighty nine and the nurses who I saw every day at this great gift They have the gift to give and they have the gift to receive that gift of receiving often forgotten that that I asked one of the media to such a hard job. Why is said what's rewarding He said more than that but it but for him. It was a Clearly Labor love which is the highest level. I think someone in a caring profession can can bring to that. I have to quote Emory Austin in your book. You you quote her saying some days. There won't be a song in your heart sing anyway and I think you know someone who's who's dying or and of course we're all trying to some extent but someone who's dying extremists. Someone who's dying in pain and loss of dignity and and anguish To Sing Anyway is the highest. Form Art to me is absolutely. You're so right and saying the things you just said for me. I'll tell you that my one of my most favorite fiction books of all times is of course Moby Dick by Melville for one reason. It Help me understand this. Storms and the souls of men that make them go wailing but for another at one point he he says something to the effect. I don't remember the exact quote but something to the affect that be Gordon was is The Sh the whaling ship on bitchy was standing and he said something like the deck of peak. What was my harbored and my year which means that experience can teach you in an instant So much more about the mystery and essential wonder of what makes us such complicated human beings and how each of us deals with the questions of mortality and questions of living and dying. I do think that The patients corporal language the right books in instances for us if we have the is not just eyesight but the insight to appreciate what they are telling us talk about the role of listening as a doctor And why it's important. I think it's a lost art. Lost Start for all of us but I think particularly for doctors who are filling out their their electric forms and racing to the next patient and I think the luxury of listening is frequently lost. We've had doctors talk about it before here on the program but I'd like to hear from you. What role does it play in your practice? You know about a study Where if you put a finger in front of your eyes and move start moving it. Let's say to the right events and keep staring straight and from eventually the finger would move out of your pedophile vision and then it will disappear right at some point but not for the deaf. I doesn't disappear in the better for the vision that quickly for the death which means that they are seen more seemingly than us and the same way I insist to the younger doctors were in training with me that they have to hear more hearing. -Ly it's not enough to just sit silently and And let the patient. But how do you hit more hearing lease a question right now? The doctors doctor-patient relationship is such that eighty percent of our time is spent in front of computers and twenty percent is is spent in face to face interactions and when there are deep concerns that are torturing patient big gone to express it immediately. An average of two minutes of conversation has to occur uninterrupted before the patient will start to express even what is keeping them up at night or what they really issues are and yet doctors are known to interrupt patient every eighteen seconds so I think I mean everyone means well. It's not that spear heartless on colleges who are just trying to do everything for a paycheck and just finish the twelve patients. We have seen the morning and rush show and finish the people. It's not that Somehow it's disorienting. It's very distressing. It's terrifying to have to look so deeply into the the agony that is in front of I and I do think that it has to be done though it. We have if we can't help our patients to live better lives. We don't have to to let them have to be a wreck emotional wrecks we have to help them and that comes from Really taking a human interest which means you have to bring all your emotional spiritual physical intellectual abilities to bear and learn how to concentrate and focus on what is The patients really shoot Not just the cure part but the healing part of it is act as important. I hope that answers your question in the aftermath of Your loss of your husband. You're right about the profusion of inappropriate things that people say and temps of consolation. I think about this From time to time I think people blunder Badly in in Jewish practice when you go to the home of a minor Jewish law says that. You're not to speak until the mourners speaks and I think people find this very difficult Our silence makes us uncomfortable and we tend to blur out things that often or worse than being silent. And you talk about that. Is it example on your own personal situation? But I've always thought about. This is one of those rare examples. Where a black and white rule like that is actually quite helpful. Sometimes those rules are just the best we can do. But the idea that to sit in silence with a person who's suffering saying nothing which the that silence yelling at. Us Often Talk Talk. Talk say something and just to sit there. And what the other person's speak I and I've always thought that injunction as being about allowing the is to keep you from saying something inappropriate but I think it also has a deeper meaning. Which is it's to get to listen. It's not just don't talk. It's listen and I'm curious. I I liked that rule. I think it's a really helpful rule to start but I'm curious what advice you would give people in situations of tragedy for how to behave and how you you don't have to go into the ones that didn't help you but I'd be curious if you would talk about some of the ones that that did help. I mean they were some wildly absurd reactions from people like Somebody gave after how he died and offered to take me out to singles bars and other person Wanted to Console me in a way but the manner in which she did. It was quite outlandish. Ezra I'm so sorry. Harvey died. But don't worry you'll join him soon. And you too can live happily. Ever after in heaven that was really breathtakingly strange to me And then there was that one of his gone but you look great that one. Don't be sad. You look fabulous. I think there's a terrible challenge in our culture is days that no one's allowed to be unhappy already. You know morning is against the rule so if if you look sad. I've got to try to cheer you up. I can't ever just let you be sad. GotTa find something. Your food's delicious. Your House looks great but lovely outfit. Yeah but it's actually the inability of people to communicate with each other. It's not particularly. I mean especially emotionally. So what you see around. You are people who are unable in fact not just to communicate with each other but then do give sympathy and to receive sympathy also in a way. It reminds me very much off the sound of silence by Simon and Garfunkel because basically that is the meaning of what is the sound of silence. is it the rustling of leaves. The sound of silence is is. Is it a flowing water? Brooke when you're sitting in a forest and listening to the sounds of silence. What is the sound of silence between two individuals and specially one one is A caregiver and the other is a patient. Very important to be able to take advantage of this kind of of syntax. I think that some of the Best Times I. I'm very lucky. Actually Russ because the tree the disease that I treat Mine Otis Plastic Syndrome as you know the pre-leukemic condition so patients live a long time off and then We have a very unique way of developing long term relationships. Because I'm seeing them every week or every other week and taking them. Through many many physically demanding situations like severe profound. Anemia compromising the quality of life Deeply and yet giving them blood transfusions which suddenly reverts them back to an energetic sell for a few days and when I see them during those days there's so different than where their hemoglobin was six grams and taking them through this for sometimes ten and twenty years and meeting them regularly. Every two weeks is a very unique privilege and in this In these interactions There are many times when we are just listening to music listening to things together or silence actually but being together and then suddenly speaking up and communicating at a level Which is so profoundly different. I think silence is underrated. One of the advantages of being the host of this program is I've become a better listener and forced myself to become silent us. Thinking about the Episode I did recently with Ryan holiday where we talked about Marina Brahma Veg. Who Sat in silence for days across from Stranger set of hundreds of strangers at the Museum of Modern Art for an exhibition a few years ago. That documentary was made of it. It's an extraordinary documentary. And I think we have a tendency to think silence is. Nothing sounds wasted. Silences is when nothing happens and yet for me increasingly as get older and get better at silence. I'm not great at it. I get a little better there the deepest times. The most unforgettable times are often just being present for someone And that was a big part of your daily life is a SA- cancer doctor. Yeah absolutely I mean I think the many people who are devastated by silence and cannot tolerate it Have to be distracted by all sorts of devices or general Things in life find that once they learn how to appreciate it. It's silences responsiveness. We can listen to things behind the clamor of the world. I want to try something a little bit strange at the end of this conversation but before he don't WanNa let you close and and talk about If you have much optimism and you've seen a lot of suffering and a lot of joy you write about this book in a Beautiful Way There's some despair at the state of things which I think listeners have heard in our conversation. Are you optimistic about the future? Do you think Think there's hope for a better approach to to these challenges. I almost feel like life nets that the world is the best of all possible worlds because I do feel very optimistic. I think that's Voltaire. Does I think that's Voltaire's is candidate is is it also live? Does he say that too? So all tare rotate Candied as a parody of life. Okay he made fun of life since he was poking fun at okay absolutely doctor. Pangloss is in candied. That's who live. Knits is supposed to be because doctor pangloss forever declaring in canty that always the best of all possible worlds but noses dare because the spectacle had to rest on it. Yeah that's So I but at the risk of sounding like lions I do think that the technology's super bright dolorous I mean I could not have imagined Twenty years ago that I would be living in a world when I go back to Karachi and I'm caught in a traffic jam and when you're caught in traffic German in Karachi at the red light often the homeless people and beggars will start knocking at your door. This started happening to me recently but in Karachi beggar started knocking on the door and before I could bring the window down. His cell phone rang and the onset the cell phone and look very concerned so when he got off the phone I said is everything. Okay now I got worried about it. And he said no no. Everything is fine. That was my wife on the cell phone telling me that there's a bigger traffic jam near the universe. She's telling me to take and Lubar to get there. Technology has such Bala to transform entire daily. Lives I mean been new asked me or commented earlier on that survey difficult insurmountable almost problem. I beg to differ with you on that now because I think that the paradigm shift overnight like it did from typewriter to a word processor from having a telephone boots to make calls to even homeless Beggars in the most impoverished countries in the world having access to the To to computers whose GAVIR carrying in their hands with powers that were unimaginable. Just two years ago so all. I'm saying is instead of going after the last cancer cell all the time yes. We should continue doing that for our current patients but at the same time. Let's turn to the first settled. Let's set the new goal. Let's incentivize the school financially and let the race begin and then what we have seen can happen. Is that the human genome acquired collaboration and competition simultaneously between hundreds of thousands of investigators. But then what? Twenty years ago took fifteen years to do to sequence the first genome and cost over a billion dollars. Today can be done in a few weeks for the cost of a few hundred dollars. This is where technology can transform. Everything within a decade is. What I'm saying and at the RE technology's moving it will be faster and faster going ahead. I'm fairly optimistic for the future of cancer. I WANNA close said trending a little bit different. I want to close with a Actually GonNa sing something which Lata character. I don't know if I've ever Sung entirely Sung something on this program before but There's a paradox in your book which is is. I've made it clear I think there's there's a lot of Despair and sadness in the book and yet there's an immense amount of joy and you've really all the patients who many of them Who passed away the one who passed away our immortal because they're in your book. Their song is is out there. answer really Credible thing one of the things that you're forced me to think about is The preciousness of life. And how somehow how is it possible that we have this great gift? We know it's finite we don't like to think about that. It's fine but we don't. It's our great tragedy and our great knowledge are great insight. We we go through life knowing it won't last forever and we think about it often as if it does which allows us to get annoyed at traffic jams and home repairs that don't work and all the petty disagreements we have with the people we love and It's strange that we can go through life that way for not careful While we all go through it to some extent that way so when I was thinking about that reacting emotionally to your book I was struck by a song by Susan Werner. It's called May I suggest and it's Open a link to it. It's a beautiful version that she does. But this is the way it ends which yearbook inspired me to think about more intensely. Even then I usually do it like this. This is a song comes from the West. Hugh comes from the West comes from the slowly settings on this is a song with a request of you to see how very short the endless days will run. And when they're gone. And when the dark descends. Oh He'd give anything for one more hour of light and I suggest this is the best part of your life so this is the best part of life. Oh beautiful this is the best part is me talking to you? And whoever's listening and It's hard to remember. That and your book reminds me to remember it. So thank you so much. Thank you russet speed absolutely wonderful experience talking to you and thank you for all you do. I love your podcast. By the way my guest today has been Raza. Her book is the First Cell Ostra. Thanks for being part of ECON talk. Thank you this is ECON- talk part of the Library of Economics and Liberty for Mauri. Contact cody contact dot. Org where you can also comment on. Today's podcast and find links and readings related to today's conversation. Sound engineer. Free. Come talk is rich yet. I'm your host Russ Roberts. Thanks for listening talk to you on Monday.

Cancer leukemia United States scientist gold medal Russ Roberts Chemotherapy Jim Allison leukemia MD Leukemia investigator Renaissance Woman Aswa Rosza baseball chemo Arsenal New York Columbia University