Podcasts about ncri

Chris Bishop is the President of the National Concrete Refinement Institute.   In this episode of Specified Growth Podcast, Chris talks about the background of the NCRI and some of the challenges and opportunities in the concrete industry. He also discusses the importance of self-awareness, refining standards and introducing measurable benchmarks in the concrete industry, and more. Don't miss this episode of Specified Growth Podcast!     Please reach out if you have any feedback or questions. Enjoy!    Twitter: @TatsuyaNakagawa Instagram: @tats_talks LinkedIn: Tatsuya Nakagawa  YouTube: Tats Talks www.tatstalk.com www.castagra.com Learn more about your ad choices. Visit megaphone.fm/adchoices

ONLINE HATE: ASSASSINATION CULTURE. JOEL FINKELSTEIN, NCRI. MALCOLM HOENLEIN @CONF_OF_PRES @MHOENLEIN1 1910 GAZA

Dr. John Sweetenham and Dr. James Foran discuss the evolving treatment landscape in acute myeloid leukemia, including new targeted therapies, advances in immunotherapy, and the current role for allogeneic transplantation. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast. There has been steady progress in the therapies for acute myeloid leukemia (AML) in recent years, largely based on an increasing understanding of the molecular mechanisms which underlie the disease. On today's episode, we'll be discussing the evolving treatment landscape in AML. We'll explore risk group stratification, new targeted therapies, advances in immunotherapy for AML, and also a little about the current role for allogenic transplantation in this disease.  I'm delighted to welcome Dr. James Foran to this discussion. Dr. Foran is a professor of medicine and chair of the Myeloid Malignancies and Blood and Marrow Transplant Disease Group at the Mayo Clinic Comprehensive Cancer Center. He's based in Jacksonville, Florida.  Our full disclosures are available in the transcript of this episode.  James, it's great to have you join us on the podcast today, and thanks so much for being here. Dr. James Foran: I'm delighted and thank you for the invitation. Thank you very much. Dr. John Sweetenham: Sure, James, let's get right into it. So, our understanding of the molecular mechanisms underlying AML has resulted not only in new methods for risk stratification in this disease, which have added refinement to cytogenetics, but also has resulted in the development of many new targeted agents. Understanding that this is a complex area of investigation, and our time is somewhat limited, can you give us a high-level update on the current state of the art in terms of how risk factors are being used for treatment selection now? Dr. James Foran: Absolutely. I think in the past, you know, we had things broken down pretty simply into make a diagnosis based on morphology, do cytogenetics, break patients into the groups of those who were more likely to benefit from therapy – so-called favorable risk – those where the intensive therapies were less likely to work – so-called poor adverse risk, and then this large intermediate group that really had variable outcomes, some better, some worse. And for a long time, the progress was in just identifying new subtle cytogenetic risk groups. And then, late 1990s, we began to understand that FLT3 mutations or NRAS mutations may be more adverse than others that came along. In the first part of this millennium, in the, you know, 2000-2010 range, a lot of work was being done to understand better or worse risk factors with single genes. The ability to do multiplex PCR, and then more recently NGS platforms, have allowed us to really look at many genes and identify many mutations in patients. At the beginning that was used just to sort of refine – who did a little better, who did a little worse with intensive therapy – helped us decide who may benefit more from an allogeneic transplanter for whom that would not be necessary.  But the good news is that really, we're now starting to target those mutations. One of the first molecularly targeted treatments in leukemia was FLT3 mutations, where we knew they were adverse. Then along came targeted treatments. I was involved in some of those early studies looking at sunitinib, sorafenib, more recently midostaurin, now quizartinib, FDA approved, and gilteritinib in the relapse refractory setting.  So we're moving into a state where we're not just refining prognosis, we're identifying targets. You know, it's been slow progress, but definite incremental progress in terms of outcomes by looking for FLT3 mutations, then looking for IDH mutations, and more recently, mutations involving NPM1 or rearrangement of what we used to call the MLL gene, now the lysine methyltransferase 2A or KMT2A rearrangement, where we now have targets. And it's not just for refinement of prognosis, but now we're identifying therapeutic targets for patients and ways to even look for measurable residual disease which is impacting our care. Dr. John Sweetenham: That's great, James. And I'm going to expand on that theme just a little bit and perhaps ask you to elaborate a little bit more on how the introduction of these new therapies have specifically impacted frontline therapy. And a couple of ancillary questions maybe to go along with that: First of all, is ‘7+3' a standard therapy for anybody in 2025? And maybe secondly, you know, could you comment also maybe briefly on older patients with AML and how you think maybe the treatment landscape is changing for them compared with, say, 5 or 10 years ago? Dr. James Foran: I'll start with the therapy and then work my way back. So we've had ‘7+3' cytarabine daunorubicin or cytarabine anthracycline since 1976, and we're still using it as the backbone of our intensive therapy. There is still an important role for it, particularly in younger or fitter patients, and particularly for those with intermediate or favorable risk genetic groups or cytogenetic risk groups just because we achieve high rates of remission. Our 30-day induction mortality rates are lower now than they were 10 and 20 years ago. Our supportive care is better. And we still have a busy inpatient hospital service here at Mayo Florida and my colleagues in Rochester and Arizona as well giving intensive therapy. So that remains the backbone of curative therapy for younger adults. We are trying to be a little more discriminating about who we administer that to. We are trying to add targeted agents. We know from, now, two different randomized trials that the addition of a FLT3 inhibitor, either midostaurin or more recently quizartinib, has a survival advantage in patients with a FLT3 mutation, or for quizartinib, a FLT3/ITD mutation. And so yes, ‘7+3' remains important.  Off protocol for somebody who just comes in with acute leukemia in a 40-year-old or 30-year-old or even early 60s and fit, we would still be considering ‘7+3' therapy and then waiting for an expedited gene mutation panel and an expedited cytogenetics panel to come back to help us discriminate is that a patient for whom we should be giving a FLT3 inhibitor? I think there's a little more nuance about when we do a day 14 bone marrow, do they really matter as much anymore? I still do them. Some of my colleagues find them less important. But we're still giving intensive therapy. We're still giving high-dose ARA-C consolidation for younger patients who achieve complete remission.  In older adults, it's a different story. You know, it was only in the early part of the 2000s – 2004, 2007 range – where we really got buy-in from randomized studies that low-dose therapy was better than no therapy. There was a lot of nihilism before then about therapy for older adults, especially over age 75. We know that low-dose ARA-C is better than nothing. It looked like azacitidine was better than ARA-C or at least equivalent or slightly better. But with the advent of venetoclax it was a game changer. I ran a national randomized study of intensive therapy in AML. It was the last national randomized study of intensive therapy in older patients right before venetoclax got approved. And we were very excited about our results, and we thought we had some really interesting clinical results. And suddenly that's a little bit obsolete in patients over 70 and particularly over age 75 because of the high remission rates with azacytidine venetoclax or hypomethylating agents, so-called HMAs and venetoclax and the survival advantage. Now, it's not a home run for everybody. We quote 60% to 70% remission rates, but it's a little different based on your cytogenetics and your mutation profile. You have to continue on therapy so it's continuous treatment. It's not with curative intent, although there are some people with long-term remission in it. And the median survival went from 10 months to 15 months. So home run? No, but definitely improved remissions, meaningful for patients off transfusions and better survival. So right now it's hard to find an older adult who you wouldn't give azacitidine and venetoclax or something similar, decitabine, for instance, and venetoclax, unless somebody really was moribund or had very poor performance status or some reason not to. And so ‘7+3' is still relevant in younger adults. We're trying to get better results with ‘7+3' by adding targeted agents and azacitine and venetoclax in older adults.  I think the area of controversy, I guess there are two of them, is what to do in that overlap age between 60 and 75. Should people in that age still get intensive therapy, which we've used for years – the VIALE-A trial of aza-venetoclax was age 75 plus – or with cardiac comorbidities? And I think if you're 68 or 72, many of us are starting to bias towards aza-venetoclax as generally being better tolerated, generally being more outpatient, generally being slow and steady way to get a remission. And it doesn't stop you from going to transplant for somebody who might still be a candidate.  The other area of controversy is somebody under 60 who has adverse cytogenetics where we don't do very well with ‘7+3,' we still give it and we might do just as well with decitabine venetoclax. A lot of us feel that there's equipoise in the 60 to 75 group where we really can ask a question of a randomized study. Retrospective studies might suggest that intensive therapy is a little better, but there are now a couple of randomized studies happening saying, “Can we replace ‘7+3' in that intermediate age with aza-venetoclax?” And for younger adults similarly, we're looking to see how we apply that technology. Those are the areas where we're really trying to investigate what's optimal for patients and that's going to require randomized trials. Dr. John Sweetenham: Oh, that's great, thank you. And I'll just extend that question a little bit more, particularly with respect to the new targeted therapies. How much are they impacting the treatment of these patients in the relapse and refractory setting now? Dr. James Foran: Oh, they're definitely impacting it. When I trained and probably when you trained, AML was still a medical emergency. But that was the thing that you admitted to the hospital immediately, you started therapy immediately. The rule was always that's the one thing that brings the fellow and the consultant in at night to see that new patient on a Friday or Saturday. Now, we'll still admit a patient for monitoring, but we try not to start therapy for the first three or five or seven days if they're stable, until we get those genetics and those genomics back, because it helps us discriminate what therapy to pursue. And certainly, with FLT3 mutations, especially FLT3/ITD mutations, we're adding FLT3 inhibitors and we're seeing a survival advantage. Now, on the surface, that survival advantage is in the range of 7% or 10%. But if you then pursue an allogeneic transplant in first remission, you're taking disease where we used to see 30%, 40% long-term survival, maybe less, and you're pushing that to 60%, 70% in some studies. And so we're now taking a disease that– I don't want to get off topic and talk about Ph+ ALL. But that's a disease where we're actually a little excited. We have a target now, and it used to be something really adverse and now we can do a lot for it and a lot about it.  The other mutations, it's a little more subtle. Now, who knew until 2010 that a mutation in a sugar metabolism gene, in isocitrate dehydrogenase, or IDH was going to be so important, or even that it existed. We know that IDH1 and IDH2 mutations are still a minority of AML, certainly less than 10% to 15%, maybe overall. But we're able to target those with specific IDH1 and IDH2 inhibitors. We get single-agent responses. There are now two approved IDH1 inhibitors on the market. We don't yet have the randomized data that adding those to intensive therapy is better, but we're getting a very strong hint that it might be better in older adults who have an IDH mutation, maybe adding those is helpful and maybe adding those to low-intensity therapy is helpful. Those studies are ongoing, and we're also trying with low-intensity treatments to add these agents and get higher remission rates, deeper remissions, longer remissions. I think a lot of work has to be done to delineate the safety of that and the long-term efficacy. But we're getting hints it's better, so I think it is impacting.  The other area it's impacting is when you pick up adverse mutations and those have crept into our classification systems like an ASXL1 mutation or RUNX1 mutation for instance, or some of the secondary AML mutations like BCOR and others, where that's helping us discriminate intermediate-risk patients who we think aren't going to do as well and really helping us select a group who's more likely to get benefit from allogeneic transplant or for whom at least our cure rates without allo transplant are low. And so I think it's impacting a lot. Dr. John Sweetenham: Great. And I'm going to pick up now, if I may, on a couple of things that you've just mentioned and continue the theme of the relapsed and refractory setting. We've started to see some reports which have looked at the role of immune strategies for patients with AML, in particular CAR T or NK cells. Can you comment a little on this and let us know whether you think either these two strategies or other immune strategies are likely to have a significant role in AML in the future? Dr. James Foran: They are, but I think we're still a step behind finding the right target or the right way to do it. If you think of allogeneic transplantation as the definitive immune therapy, and we know for adverse AML we can improve survival rates and cure rates with an allotransplant, then we know inherently that immune therapy matters. And so how do we do what they've done in large cell lymphoma or in CD19 targeting for B cell malignancies? How do we bring that to acute myeloid leukemia? There have been a number of efforts. There have been at least 50 trials looking at different targets. CD33, CD123, CD7, others, CLL-1. So, there have been a number of different trials looking at how to bind a CAR T or a CAR T construct that can be active. And we have hints of efficacy. There was kind of a provocative paper in the New England Journal of Medicine a year ago in April of last year from a Chinese group that looked at a CD7-based CAR T and it was 10 patients, but they used CD7 positive acute leukemia, AML or ALL and had a CD7-targeted CAR T and they actually incorporated that with a haploidentical transplant and they had really high remission rates. People tolerated it quite well. It was provocative. It hasn't yet been reproduced on a larger scale, but the strong hints that the strategy is going to work.  Now, CD33 is a little tricky to have a CAR T when CD33 is expressed on normal hematopoietic cells. CD123 likewise. That's been something where there's, I think, still promise, but we've struggled to find the trials that make that work. Right now, there's a lot of interest in leveraging NK cells and looking, for a couple of reasons, but NK cells are attractive and NK cell markers might be attractive targets. NK cells might have similar degrees of immune efficacy. It's speculative, but they are likely to have less cytokine release syndrome and less neurotoxicity than you see with CAR T. And so it's kind of attractive to leverage that. We have had some ongoing trials looking at it with bispecifics and there certainly are trials looking at it with CAR NK-based strategies. One of the antigens that people looked at is the NK group 2D. NK group 2D or NKG2D is overexpressed in AML and its ligands overexpressed. And so that's a particular potential target. So, John, it's happening and we're looking for the hints of efficacy that could then drive a pivotal trial to get something approved.  One of the other areas is not restricting yourself just to a single antigen. For instance, there is a compound that's looking at a multi-tumor-associated antigen-specific T-cell therapy, looking at multiple antigens in AML that could be overexpressed. And there were some hints of activity and efficacy and actually a new trial looking at a so-called multi-tumor associated antigen-specific T cell therapy. So without getting into specific conflicts of interest or trials, I do think that's an exciting area and an evolving area, but still an investigational area. I'll stop there and say that we're excited about it. A lot of work's going there, but I'm not quite sure which direction the field's going to pivot to there. I think that's going to take us some time to sort out. Dr. John Sweetenham: Yeah, absolutely. But as you say, exciting area and I guess continue to watch this space for now.  So you've mentioned allogeneic stem cell transplants two or three times during this discussion. Recognizing that we don't have an imatinib for AML, which has kind of pushed transplant a long way further back in the treatment algorithm, can you comment a little on, you know, whether you think the role of stem cell transplantation is changing in AML or whether it remains pretty much as it was maybe 10 years ago? Dr. James Foran: By the way, I love that you use imatinib as an introduction because that was 6 TKIs ago, and it tells you the evolution in CML and you know, now we're looking at myristoyl pocket as a target, and so on. That's a great way to sort of show you the evolution of the field.  Allogeneic transplant, it remains a core treatment for AML, and I think we're getting much smarter and much better about learning how to use it. And I'm just going to introduce the topic of measurable residual disease to tell you about that. So I am a little bit of a believer. Part of my job is I support our allogeneic transplant program, although my focus is acute myeloid leukemia, and I've trained in transplant and done it for years and did a transplant fellowship and all that. I'm much more interested in finding people who don't need a transplant than people who do. So I'm sort of looking for where can we move away from it. But it still has a core role. I'll sidestep and tell you there was an MDS trial that looked at intermediate or high-risk MDS and the role of allogeneic transplant that shows that you about double your survival. It was a BMT CTN trial published several years ago that showed you about double your three-year survival if you can find a donor within three months and get to a transplant within six months. And so it just tells you the value of allotransplant and myeloid malignancy in general. In AML we continue to use it for adverse risk disease – TP53 is its own category, I can talk about that separately – but adverse risk AML otherwise, or for patients who don't achieve a really good remission. And I still teach our fellows that an allotransplant decreases your risk of relapse by about 50%. That's still true, but you have to have a group of patients who are at high enough risk of relapse to merit the non-relapse mortality and the chronic graft versus host disease that comes with it. Now, our outcomes with transplant are better because we're better at preventing graft versus host disease with the newer strategies such as post-transplant cyclophosphamide. There are now new FDA-approved drugs for acute and chronic graft versus host disease, ruxolitinib, belumosudil, axatilimab now. So we have better ways of treating it, but we still want to be discriminating about who should get it.  And it's not just a single-minded one-size-fits-all. We learned from the MORPHO study that was published in the JCO last year that if you have FLIT3-positive AML, FLIT3/IDT-positive AML, where we would have said from retrospective studies that your post-transplant survival is 60% give or take, as opposed to 15% or 20% without it, that we can discriminate who should or shouldn't get a transplant. Now that trial was a little bit nuanced because it did not meet its primary endpoint, but it had an embedded randomization based upon MRD status and they used a very sensitive test of measurable residual disease. They used a commercial assay by Invivoscribe that could look at the presence of a FLT3/ITD in the level of 10 to the minus 5th or 10 to the minus 6th. And if you were MRD-negative and you went through a transplant, you didn't seem to get an advantage versus not. That was of maintenance with gilteritinib, I'll just sort of put that on there. But it's telling us more about who should get a transplant and who shouldn't and who should get maintenance after transplant and who shouldn't.  A really compelling study a year ago from I don't know what to call the British group now, we used to call them the MRC and then the NCRI. I'm not quite sure what to call their studies at the moment. But Dr. Jad Othman did a retrospective study a year ago that looked at patients who had NPM1 mutation, the most common mutation AML, and looked to see if you were MRD positive or MRD negative, what the impact of a transplant was. And if you're MRD negative there was not an advantage of a transplant, whereas if you're MRD positive there was. And when they stratified that by having a FLT3 mutation that cracked. If you had a FLT3 mutation at diagnosis but your NPM1 was negative in remission, it was hard to show an advantage of a transplant. So I think we're getting much more discriminating about who should or should not get a transplant by MRD testing for NPM1 and that includes the patients who have a concomitant FLT3 mutation. And we're really trying to learn more and more. Do we really need to be doing transplants in those who are MRD-negative? If you have adverse risk genetics and you're MRD-negative, I'll really need good data to tell me not to do a transplant, but I suspect bit by bit, we'll get that data. And we're looking to see if that's really the case there, too. So measurable residual disease testing is helping us discriminate, but there is still a core role of allogeneic transplant. And to reassure you, compared to, I think your allotransplant days were some time ago if I'm right. Dr. John Sweetenham: Yes. Dr. James Foran: Yeah. Well, compared to when you were doing transplants, they're better now and better for patients now. And we get people through graft versus host disease better, and we prevent it better. Dr. John Sweetenham: That's a great answer, James. Thanks for that. It really does help to put it in context, and I think it also leads us on very nicely into what's going to be my final question for you today and perhaps the trickiest, in a way. I think that everything you've told us today really emphasizes the fact that the complexity of AML treatment has increased, primarily because of an improved understanding of the molecular landscape of the disease. And it's a complicated area now. So do you have any thoughts on what type of clinical environment patients with AML should be evaluated and treated in in 2025? Dr. James Foran: Yeah, I want to give you a kind of a cautious answer to that because, you know, I'm a leukemia doctor. I work at a leukemia center and it's what we focus on. And we really pride ourselves on our outcomes and our diagnostics and our clinical trials and so on. I am very aware that the very best oncologists in America work in private practice and work in community practice or in networks, not necessarily at an academic site. And I also know they have a much harder job than I have. They have to know lung cancer, which is molecularly as complicated now as leukemia, and they have to know about breast cancer and things that I don't even know how to spell anymore. So it's not a question of competence or knowledge. It's a question of infrastructure. I'll also put a little caveat saying that I have been taught by Rich Stone at Dana-Farber, where I did a fellowship a long time ago, and believe Rich is right, that I see different patients than the community oncologists see with AML, they're seeing different people. But with that caveat, I think the first thing is you really want to make sure you've got access to excellence, specialized hematopathology, that you can get expedited cytogenetics and NGS testing results back. There was a new drug, approved just a few months ago, actually, for relapsed AML with a KMT2A rearrangement, revumenib. We didn't talk about the menin inhibitors. I'll mention them in just a second. That's a huge area of expansion and growth for us. But they're not found on NGS platforms. And normal cytogenetics might miss a KMT2A-rearrangement. And we're actually going back to FISH panels, believe it or not, on AML, to try to identify who has a KMT2A-rearrangement. And so you really want to make sure you can access the diagnostic platforms for that.  I think the National Referral Labs do an excellent job. Not always a really fast job, but an excellent job. At my institution, I get NGS results back within three days or four days. We just have an expedited platform. Not everybody has that. So that's the key, is you have to be able to make the diagnosis, trust the pathologist, get expedited results. And then it's the question of trying to access the targeted medications because a lot of them are not carried in hospital on formulary or take time to go through an insurance approval process. So that's its own little headache, getting venetoclax, getting gilteritinib, getting an IDH1 inhibitor in first line, if that's what you're going for. And so I think that requires some infrastructure. We have case managers and nurses who really expedite that and help us with it, but that's a lot of work. The other piece of the puzzle is that we're still with AML in the first month and maybe even the second month. We make everybody worse before we make them better. And you have to have really good blood bank support. I can give an outpatient platelet transfusion or red cell transfusion seven days a week. We're just built for that. That's harder to do if you're in a community hospital and you have to be collaborating with a local blood bank. And that's not always dead easy for somebody in practice. So with those caveats, I do find that my colleagues in community practice do a really good job making the diagnosis, starting people on therapy, asking for help. I think the real thing is to be able to have a regional leukemia center that you can collaborate with, connect with, text, call to make sure that you're finding the right patients who need the next level of diagnostics, clinical trial, transplant consults, to really get the best results.  There was some data at ASH a couple of years ago that looked at – the American Society of Hematology and ASCOs had similar reports – that looked at how do we do in academic centers versus community practice for keeping people on therapy. And on average, people were more likely to get six cycles of therapy instead of three cycles of therapy with azacitidine venetoclax at an academic center. Now, maybe it's different patients and maybe they had different cytogenetics and so on, but I think you have to be patient, I think you have to collaborate. But you can treat those patients in the community as long as you've got the infrastructure in place. And we've learned with virtual medicine, with Zoom and other platforms that we can deliver virtual care more effectively with the pandemic and beyond. So I think we're trying to offer virtual consults or virtual support for patients so they can stay in their home, stay in their community, stay with their oncologists, but still get access to excellent diagnostics and supportive care and transplant consults, and so on. I hope that's a reasonable answer to that question. It's a bit of a nuanced answer, which is, I think there's an important role of a leukemia center, and I think there's a really fundamental role of keeping somebody in the community they live in, and how we collaborate is the key to that. And we've spent a lot of time and effort working with the oncologists in our community to try to accomplish that.  John, I want to say two other things. I didn't mention in the molecular platforms that NPM1 mutations, we can now target those on clinical trials with menin inhibitors. We know that NPM1 signals through the Hoxa9/Meis1 pathway. We know that similar pathways are important in KMT2A rearrangements. We know that there are some other rare leukemias like those with NUP98 rearrangement. We can target those with menin inhibitors. The first menin inhibitor, revuminib, was approved by the FDA for KMT2A. We have others going to the FDA later this year for NPM1. There are now pivotal trials and advanced expanded phase 1/2 studies that are showing 30% response rates. And we're looking to see can we add those into the first-line therapy. So, we're finding more targets.  I'll say one last thing about molecular medicine. I know I'm a little off topic here, but I always told patients that getting AML was kind of like being struck by lightning. It's not something you did. Now, obviously, there are risk factors for AML, smoking or obesity or certain farm environments, or radioactive exposures and so on. But bit by bit, we're starting to learn about who's predisposed to AML genetically. We've identified really just in the last five or eight years that DDX41 mutations can be germline half the time. And you always think germline mutations are going to cause AML in a younger patient, but the median age is 60 to 70 just like other AMLs. They actually might do pretty well once they get AML. We've reported that in several papers. And so we're trying to understand who that has a RUNX1 mutation needs germline testing, who with a DDX41 needs germline testing. And we're trying to actually come up with a cleaner pathway for germline testing in patients to really understand predisposition, to help with donor selection, to help with family counseling. So I think those are other areas where a leukemia center can contribute for somebody in who's community practice to understand genomic or genetic complexity in these patients. And we're starting to develop the databases that support that. Dr. John Sweetenham: Yeah, great. Thanks, James. I loved your answer about the clinical environment too. And I know from a patient-centric perspective that I know that patients would certainly appreciate the fact that we're in a situation now where the folks taking care of them will make every effort to keep them close to home if they possibly can.  I want to thank you, James, for an incredible review of a very complex subject and I think you did a great job. I think we all will have learned a lot. And thanks again for being willing to share your insights with us today on the ASCO Daily News Podcast. Dr. James Foran: John, it's my pleasure. And as you know, I'll do anything for a latte, so no problem at all. Dr. John Sweetenham: Okay. I owe you one, so thank you for that.  And thank you to our listeners for your time today. You'll find links to the studies we've discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement. Find out more about today's speakers:  Dr. John Sweetenham  Dr. James Foran Follow ASCO on social media: @ASCO on Twitter ASCO on Bluesky ASCO on Facebook  ASCO on LinkedIn  Disclosures:    Dr. John Sweetenham:    No relationships to disclose Dr. James Foran: Stock and Other Ownership Interests: Aurinia Pharmaceuticals Consulting or Advisory Role: Peerview, CTI BioPharma Corp, Remix Therapeutics, Cardinal Health, Medscape, Syndax, Autolus Therapeutics Research Funding (Inst.): Chordia Therapeutics, Abbvie, Actinium Pharmaceuticals, Kura Oncology, Sellas Life Sciences, Novartis, Roivant, Celgene/Bristol-Myers Squibb, Astellas Pharma, SERVIER Travel, Accommodations, Expenses: Peerview

Thousands of opponents to Iran's authorities rallied in Paris, organized by the National Council of Resistance of Iran (NCRI), to call for the fall of the government in Tehran. The protest coincides with President Trump's maximum pressure campaign against Iran. Alireza Jafarzadeh, deputy director of NCRI, discusses the Iranian resistance, highlighting the regime's use of its space program to camouflage nuclear weapons development and the importance of international support for the Iranian opposition. Their conversation covers the history of Iran's political landscape, the role of the NCRI in exposing the regime's activities, and the potential for significant change in Iran through internal resistance and external pressure.See omnystudio.com/listener for privacy information.

Security analyst for NCRI and investigative journalist Travis Hawley has been tracking the online reaction to the  shooting of  US health insurance CEO Brian Thompson and subsequent revelation of the shooters identity. 

ANTISEMITISM: K-12 across the nation. Joel Finkelstein is Chief Science Officer and Cofounder of NCRI. Ph.D. in Psychology from Princeton; Fellow at the Miller Center for Community Protection and Resilience, Rutgers, the State University of New Jersey. Tova Plaut, NYC Public School Alliance. 1929 

GOOD EVENING: The show begins in  the Black Sea basin and the challenges of Ukraine at war and Georgia in disorder. 1900 Tblisi Georgia CBS EYE ON THE WORLD WITH JOHN BATCHELOR FIRST HOUR 9-915 #UKRAINE:  Trump and the Kremlin. Anatol Lieven Quincy Institute 915-930 #GEORGIA: Celebrity protests. Anatol Lieven Quincy Institute 930-945 Scala Report:  Ohio has a deep bench. Chris Riegel, #STRATACACHE 945-1000 AFGHANISTAN: Trump Administration and return to AL QAEDA IN AFGHANISTAN. . Bill Roggio, FDD SECOND HOUR 10-1015 #ISRAEL:  Rocketed everyday in the hundreds. Lieutenant Colonel (Res.) Sarit Zehavi.  Founder and president of Alma – a nonprofit and an independent research and education center specializing in Israel's security challenges on its northern border. 1015-1030 JIHADISTS: And governance.  Devorah Margolin is the Blumenstein-Rosenbloom Senior Fellow at The Washington Institute and an Adjunct Professor at Georgetown University. Her research primarily focuses on terrorism governance, terrorism financing, the role of propaganda and strategic communications, countering/preventing violent extremism, and the role of women and gender in violent extremism.    1030-1045 ANTISEMITISM: K-12 across the nation. Joel Finkelstein is Chief Science Officer and Cofounder of NCRI. Ph.D. in Psychology from Princeton; Fellow at the Miller Center for Community Protection and Resilience, Rutgers, the State University of New Jersey. Tova Plaut, NYC Public School Alliance. 1045-1100 #IRAN:  2:15 PM Behnam Ben Taleblu is a Research Fellow where he focuses on Iranian security and political issues. Mr. Taleblu previously served as a Senior Iran Analyst at FDD. Prior to his time at FDD, Mr. Taleblu worked on non-proliferation issues at an arms control think-tank in Washington. THIRD HOUR 1100-1115 #NewWorldReport: Trump, Sheinbaum, and the USMCA. Latin American Research Professor Evan Ellis, U.S. Army War College Strategic Studies Institute. @revanellis #NewWorldReportEllis 1115-1130 #NewWorldReport: Managing the Rogue, Failed  State of Cuba and Trump. State of Cuba. Latin American Research Professor Evan Ellis, U.S. Army War College Strategic Studies Institute. @revanellis #NewWorldReportEllis 1130-1145 #NewWorldReport: Argentine's success so far.  Latin American Research Professor Evan Ellis, U.S. Army War College Strategic Studies Institute. @revanellis #NewWorldReportEllis 1145-1200 #NewWorldReport: Bolivia troubles. Lula's health.  Paraguay promise. Latin American Research Professor Evan Ellis, U.S. Army War College Strategic Studies Institute. @revanellis #NewWorldReportEllis FOURTH HOUR 12-1215 #FRANCE: NVDA replaces  NTC, the relentless competition in the Dow. Simon Constable, wsj 1215-1230 #DRONES: The surprising limitations of drone defense. Henry Sokolski, NPEC 1230-1245 AUSTRALIA: Spaceport building. Bob Zimmerman  1245-100 AM #MARS: Theory of Liquid Water on Mares.  Bob Zimmerman 

In this crucial episode of Scam Rangers, we explore the dark and disturbing world of Sextortion. This crime occurs when online predators trick individuals, often teens, into sharing nude images or videos and then use these compromising materials to extort money, more images, or other demands. These predators threaten to share the images with the victim's friends and family if they don't comply. Our guest, Paul Raffile, a Senior Intelligence Analyst with a career dedicated to investigating online crimes and financial scams, joins us to shed light on this pressing issue.Key Discussion Points:Paul explains how sextortion scams unfold, the social media platforms commonly used by predators, and the emotional impact on victims, particularly teens. He shares advice for social media companies on preventing these scams, drawing on strategies from financial institutions that detect account takeovers. We also explore how money is transferred to criminals and the risk signals financial institutions can monitor to spot suspicious activities.Resources:Follow Paul on LinkedIn: https://www.nbcnews.com/tech/internet/sextortion-yahoo-boys-snapchat-tiktok-teen-wizz-rcna134200NCRI Report: https://networkcontagion.us/reports/yahoo-boys/New York Times: https://www.nytimes.com/2024/05/15/nyregion/social-media-scam-sextortion.htmlArticle on WIRED: https://www.wired.com/story/yahoo-boys-scammers-facebook-telegram-tiktok-youtube/Training materials on NBC News: https://www.nbcnews.com/tech/internet/sextortion-yahoo-boys-snapchat-tiktok-teen-wizz-rcna134200This podcast is hosted by Ayelet Biger-Levin who spent the last 15 years building technology to help financial institutions authenticate their customers and identify fraud. She believes that when it comes to scams, the story starts well before the transaction. She has created this podcast to talk about the human side of scams, and to learn from people who have decided to dedicate their lives to speaking up on behalf of scam victims and who take action to solve this problem.Be sure to follow her on LinkedIn and reach out to learn about her additional activities in this space. https://www.linkedin.com/in/ayelet-biger-levin/ScamRanger: https://scamranger.ai/

Michael Morrison is the Chief Revenue Officer at NCRI Inc. He is based in Toronto, Canada. Peter called Michael to talk about CX and BPO in Canada and how Canada has played a dual role as a nearshore BPO destination for the US as well as being an important market for customer service itself... come and listen to a discussion about the great white north!

In this episode of the podcast, join host Burke Jones for an engaging chat with Katy Timken and Carl Maxson from NCRI. On this episode we discuss all the things that keep facility managers awake at night - flooding, storm damage, fire damage...those types of disasters. Main Topics Covered: Unseen dangers that may linger after a disaster Why its important to have a relationship established with a disaster restoration partner Some of the crazy things they have seen in the field. Listen here: https://lnkd.in/esYWUye8 or anywhere you listen to podcastsApple: https://lnkd.in/gM2MrHG2Spotify: https://lnkd.in/gUHw5C85 --- Send in a voice message: https://podcasters.spotify.com/pod/show/schoolfacilities/message

La sextorsión financiera, un delito que ha escalado rápidamente, pone en jaque la seguridad de los jóvenes en internet. Mark Zuckerberg se disculpa en el Senado de EE.UU. mientras un estudio del NCRI destaca el papel de los "Yahoo Boys" en este crimen creciente. Las plataformas digitales luchan por implementar medidas efectivas ante la presión legislativa y la demanda de seguridad por parte de los padres. La prevención, a través de la educación y la comunicación, emerge como una herramienta clave frente a este desafío. ¿Serán suficientes las acciones actuales para proteger a nuestros jóvenes?Conviértete en un seguidor de este podcast: https://www.spreaker.com/podcast/geeks-y-gadgets-con-luisgyg--909634/support.

Welcome to this edition of the NCRI Women's Committee podcast. Every year, December 7 marks the Day of Students in Iran. On December 7, 1953, three students were killed by military forces on the campus of Tehran University's College of Engineering. Since then, this day has been known as Students' Day in Iran, honoring the struggles of Iranian university students.Iranian universities have long served as hubs of knowledge. Alongside knowledge, there emerges a deep longing for freedom. Consequently, many leaders of opposition movements in Iran have risen from universities, drawing from the most informed sectors of Iranian intellectuals.Today, we explore the pivotal role of female students within universities and their involvement in the 2022-2023 uprising in Iran.***It's fitting to remember dozens of young women who paid the ultimate price during the 2022 protests. Let's remember Donya Farhadi, a 22-year-old student of Architecture at Azad University of Ahvaz, in the southwest Khuzestan province. Donya had been missing since December 7 after she had an argument with Basij militia members on the campus that day. Her body was found on the 15th of December on the banks of Karun River in Ahvaz. Her chest had been pierced by three bullets. However, the regime initially claimed that she had jumped down from the Karun bridge and committed suicide.We also had the case of Nasrin Qaderi from Marivan, Kurdistan. She was 38 years old and a student of Ph.D. in philosophy. Security forces hit her on the head during a protest in Tehran on the 4th of November. She slipped into a coma and died the next day in a hospital. Again, the state media claimed that she had died due to a chronic disease. There was also Negin Abdolmaleki who was only 21. She came from Qorveh, Kurdistan, but studied medical engineering at the Industrial University of Hamedan. She was repeatedly hit on the head by batons during a protest on October 11 in the city. She was severely injured. When she returned to the dormitory, she died due to severe bleeding. The authorities claimed that she had been intoxicated by expired canned fish!!Let us also remember Behnaz Afshari, a 23-year-old woman from Pakdasht, in Tehran Province. She left home on the 26th of October to participate in protests in Tehran but never returned home. Her body was found after five days in forensics medicine.  Episode: Podcast: https://www.buzzsprout.com/1908986

Today, Shivam talks about how AI could be coming to replace many white-collar jobs and how the NCRI has exposed the influence of Twitter bots on cryptocurrency prices. Topics discussed: How AI is affecting white collar jobs How the NCRI has exposed the influence of Twitter bots on cryptocurrency prices Links mentioned in this episode: https://invstr.com/ai-taking-white-collar-jobs/ https://invstr.com/twitter-crypto-price-actions/ https://invstr.com/market-recap-august-1st-2023/

Dr Joel Finkelstein is a Princeton expert on Artificial Intelligence and cognitive science who has done pioneering research on Hinduphobia. His predictive model tracks the nexuses that advocate hatred and violence against Hindus. This is the first episode of a multi-part series in which Rajiv Malhotra uncovers his research, including facets explained publicly for the first time. The mini-series will cover the Khalistan movement, violence against Hindus in Britain, a global Islamist movement originating in Pakistan to support a terrorist mastermind now in a US prison, among other specific details. An eye-opener you must watch and share with every concerned person. Snakes in the Ganga - http://www.snakesintheganga.com Varna Jati Caste - http://www.varnajaticaste.com The Battle For IIT's - http://www.battleforiits.com Power of future Machines - http://www.poweroffuturemachines.com 10 heads of Ravana - http://www.tenheadsofravana.com To support Infinity Foundation's projects including the continuation of such episodes and the research we do: इनफिनिटी फ़ौंडेशन की परियोजनाओं को अनुदान देने के लिए व इस प्रकार के एपिसोड और हमारे द्वारा किये जाने वाले शोध को जारी रखने के लिए: http://infinityfoundation.com/donate-2/ --- Support this podcast: https://podcasters.spotify.com/pod/show/rajivmalhotrapodcast/support

Host L Todd Wood speaks with Ali Safavi of the National Council of Resistance in Iran on the uprising happening across the country.

You don't want to miss this one!

Steve visits with Volunteer Kansas.org Executive Director Nola Brown about a great opportunity to support our troops with Christmas cards.  Simply purchase holiday cards (or better yet, make them), write a message to our deployed troops and sign the cards. Cards can be sent in a large envelope to Volunteer Kansas, PO Box 781598, Wichita, KS 67278 or dropped off at NCRI at 8447 E 35th St N, Wichita, KS, 67226. All cards need to be received by November 10th. See omnystudio.com/listener for privacy information.

No one wants to imagine a catastrophic event at their home, but unfortunately they can and do happen.  Fires, floods, storms, and even equipment failure can create significant damage to your home, often beyond the obvious.  In this episode, Elaina Huffman with NCRI walks Jen & Erik through how companies can respond to these situations, techniques used to mitigate problems, and things to watch out for if disaster occurs.  

It is not marked on maps. Men with automatic weapons guard its border. Few outsiders have ever visited the heavily guarded enclave in rural Albania that is home to the People's Mujahidin, or MEK.For its supporters, MEK is the biggest and most resilient Iranian opposition group, a government-in-waiting. Others see it as a bizarre and secretive cult led by a zealot with no chance of replacing Iran's ruthless theocracy.Sunday Times foreign correspondent Matthew Campbell goes in search of the truth – the first British journalist to be allowed inside the camp.This podcast was brought to you thanks to the support of readers of The Times and The Sunday Times. Subscribe today and get one month free at: thetimes.co.uk/storiesofourtimes. Guest: Matthew Campbell, foreign correspondent, The Sunday Times.Host: David Aaronovitch.Clips: Al Jazeera, BBC News, Channel 4 News, France 24, Fox Business, NCRI. See acast.com/privacy for privacy and opt-out information.

Photo: The stamped acronym of the Iranian state-owned and operated Shahid Hemmat Industries Group (SHIG) appears on an Iranian Qiam class missile guidance component remnant on display at Joint Base Anacostia-Boling in Washington, D.C. Jan. 29, 2018. United Nations Security Council members viewed the display Jan. 29, 2018 along with a multi-national collection of evidence proving Iranian weapons proliferation in violation of United Nations resolutions 2216 and 2231. (DdoD photo by EJ Hersom)CBS Eye on the World with John BatchelorCBS Audio Network@BatchelorshowSuspect Iran floods Twitter with hatred; & What is to be done? Joel Finkelstein (@ncri_io); Malcolm Hoenlein @Conf_of_pres @mhoenlein1 Joel Finkelstein is the Director and Cofounder of the Network Contagion Research Institute (NCRI). NCRI  is a neutral and independent third party whose mission it is to track, expose, and combat misinformation, deception, manipulation, and hate across social media channels. Joel holds a Ph.D. in Psychology from Princeton and is a fellow at the Miller Center for Community Protection and Resilience at Rutgers, the State University of New Jersey. Related Articles https://www.foxbusiness.com/technology/pro-iran-twitter-accounts-anti-semitic-hate-trending-israeli-hamas https://nypost.com/2021/05/24/17000-tweet-hitler-was-right-and-big-tech-barely-reacts  https://time.com/6071615/iran-disinformation-united-states/ https://jewishjournal.com/commentary/336892/antisemitic-twitter-is-trending-as-violence-against-jews-escalates/ 

Host L Todd Wood talks with Ali Safavi of the National Council of Resistance in Iran (NCRI). What can Americans learn from 40 years of Iranians fighting for freedom?

In this episode of Data Brilliant, Joe DosSantos speaks with Joel Finkelstein, Co-Founder and Director of the Network Contagion Research Institute to further explore the need to tackle the rise of misinformation across society. Talking to the dangerous impact misinformation can – and has - had around the world, Joe and Joel discuss how NCRI is using data to track and expose this epidemic of virtual deception. Throughout the discussion, they also stress the need to create a data-literate world, so everyone can have access to the tools that will help them improve their critical thinking skills, question and challenge the information they’re given. As they explain, this ultimately needs to start in schools so that everyone growing up today has the ability to make sense of online manipulation to encourage and drive transparency and trust. See acast.com/privacy for privacy and opt-out information.

In Episode 66 of the CounterVortex podcast, Bill Weinberg interviews Alexander Reid Ross, author of Against the Fascist Creep and a fellow at the Network Contagion Research Institute (NCRI), who has faced threats of litigation as well as relentless online harassment for his exposés of Russian propaganda and Red-Brown Politics. After his recent piece in the Daily Beast on leftist flirtation with the far right around conspiracy theories concerning COVID-19 and the war in Syria, the odious Max Blumenthal quickly retaliated with a piece on his Grayzone website charging in its headline that Reid Ross "works with ex-cops, CIA spies, and DHS agents." This refers to the fact that former CIA, Homeland Security and NYPD officials are now also researchers with the NCRI. The accusation is hilariously ironic given that Blumenthal himself has shared platforms with former CIA analyst (and now a star of the conspiracy set) Ray McGovern. As well as (of course) avidly cooperating with Russian and Chinese state propaganda efforts. Among examples discussed in the interview... A new report from the Australian Strategic Policy Institute (ASPI), "Strange bedfellows on Xinjiang: The CCP, fringe media and US social media platforms," names Grayzone as "amplified by Chinese and Russian state-affiliated entities" in "state-sponsored disinformation...campaigns." In addition to practicing "junket journalism" to serve the propaganda interests of the Bashar Assad regime, Blumenthal's tweets have blatantly poked perverse fun at Syrian chemical attack victims. But apart from the dizzying hypocrisy of Blumenthal painting Reid Ross as a CIA collaborator, it constitutes what was known in the COINTELPRO era of the 1960s as "snitch-jacketing"—a phenomena that led to the cannibalization of the radical opposition movements of the day. Listen on SoundCloud or via Patreon. Production by Chris Rywalt (with help from Dawn Rywalt) We ask listeners to donate just $1 per episode via Patreon. We have made it to our initial goal of $30 per episode! Thank you for your support, and please keep it coming!

This month, Oren Segal spoke to Joel Finkelstein at the Network Contagion Research Institute. “I hate my job. I don't want to do this” says Joel. A neuroscientist by training, Joel found himself obligated to the work of dismantling hate and polarization knowing that brain science could drive solutions. In his work at NCRI, Joel tracks how hate and virtual deception spreads between social media communities and into the real world.Joel warns that we must stay connected to our purpose in this work. “If it becomes an addiction, we become defined by the things we hate.” In today's episode, we discover the lie that humans are obsolete and the truth that we are needed now more than ever. How and why will be driven by our compassion and, of course, science.More on Joel's work here: https://networkcontagion.us/about/First collaboration between ADL and NCRI:https://www.adl.org/blog/when-twitter-bans-extremists-gab-puts-out-the-welcome-matStay engaged and follow along for more on Twitter at @OrenSegal @ADL and @PERIL_AU

Justin Maxson is the Senior Executive Vice President of NCRI – National Catastrophe Restoration Inc, which is a national property damage restoration contractor. Within a decade, Justin has climbed the corporate ladder to become a successful young executive, focusing his efforts on growth within the organization. He holds certifications and awards from The Construction Infection Control Training Institute, Restoration Consultants, American Osage Consultants, Claims Training Services, Restoration Sciences Academy, and the Institute of Inspection Cleaning and Restoration Certification. As the third generation of a family business, Justin is determined in proving stereotypical statistics wrong. His proven strategies over the last decade, with a resilient entrepreneur mindset, are setting NCRI apart from their competition. Justin currently sits as Chapter President of Disaster Kleenup International – one of the oldest and largest property restoration organizations. He is also a member of the National Catastrophe Committee, developing plans of action during the nation’s most devastating weather events. Justin and his wife, Karley, reside in the Kansas City area and thrive off each of their passions for helping and being of service to others.

Alireza Jafarzadeh is Deputy Director of the National Council of the Resistance of Iran. July 17th 2020 The NCRI will be holding a Online Confernce Event #FreeIran2020 with many world leaders including Mayor Rudy Giuliani. You can find the link on @A_Jafarzadeh on Twitter

Alireza Jafarzadeh is Deputy Director of the National Council of the Resistance of Iran. July 17th 2020 The NCRI will be holding a Online Confernce Event #FreeIran2020 with many world leaders including Mayor Rudy Giuliani. You can find the link on @A_Jafarzadeh on Twitter

Iran is the subject of our 196th episode. Our guest is Alireza Jafarzadeh, deputy director in the US Representative office of the National Council of Resistance of Iran (NRCI), their parliament-in-exile. In this conversation we examine how Iran is doing economically and with the coronavirus, how ending the Iran Deal has changed things, what life is like for the average Iranian, what NCRI hopes to accomplish with the Free Iran Summit on July 17, and how Iran will become a free country in the future.

Data is at the centre of so much of the discussion about COVID-19. Think of those daily press conferences from the government as well as newspaper reports and scholarly articles; our eyes are drawn to the statistics to explain the story of this pandemic. Our actions and health care are determined by what we take from the information so it's of particular significance to cancer patients. Join me for this 11th edition of Ripples and a great conversation involving Emma Kinloch, consumer lead for NCRI, Chris Carrigan, expert data advisor for Usemydata and James Peach of DATA CAN.

Hobbs talks with the /k/razy Ivan crew about their inclusion in the NCRI paper.

Hobbs talks without Thicc Boog Line about their mention in NCRI: Memetic Warfare paper. We're officially on a government list now....yay.

During a week of high drama between the U.S. and Iran, a top Iranian general was assassinated by the U.S. Americans on military bases in Iraq had to run for cover from Iranian launched ballistic missiles, and the leaders of both nations have warned that more attacks could be coming. But what kind of attacks could Iran be planning? Alireza Jafarzadeh, deputy director of the Washington office of the National Council of Resistance of Iran, and Adam Meyers of Crowdstrike break down the threat for us.

See omnystudio.com/listener for privacy information.

Hashim Ahmed takes us through the COMPARE study – presented at NCRI 2018 – which showed that men with localized prostate cancer are willing to accept lower survival odds for a better quality of life. He outlines the key findings, the implications of the results for physicians, and the next steps for research. Find more on Medicine Matters oncology This content was originally published on Medicine Matters oncology (https://oncology.medicinematters.com/) on November 15, 2018.

Prof Treasure talks to ecancertv at NCRI 2014 about recurrent colorectal cancer which has spread to the lungs or liver and the questions raised over the efficacy of current treatment practices involving surgery, which may or may not be beneficial.

Dr Koller talks to ecancertv at NCRI 2014 about cancer metaphors, such as those relating to journeys or war, and their psychosocial impacts on patients and their families.

Prof Laskey talks to ecancertv at NCRI 2014 about the Lifetime Achievement Prize he received from Cancer Research UK, and gives us an insight into some of the valuable research he's done to earn it.

Prof Fitzgerald talks to ecancertv at NCRI 2014 about the results of a study which looked at a novel detection device for cancer of the oesophagus. The test was found to be well-tolerated and highly accurate.

Roger Wilson talks to ecancertv at NCRI 2014 about patient advocacy at the conference and the concept of a "Dragon's Den"-esque competition to pitch research ideas, a proposal on stratified medicine being his personal choice.

Prof Kuhn talks to ecancertv at NCRI 2014 about a multidisciplinary approach to oncology involving maths, physics, biology, medicine and engineering, with a particular focus on lung cancer screening.

Prof Marais talks to ecancertv at NCRI 2014 about the highlights of this year's conference and what the future may hold.

Dr Parada talks to ecancertv at NCRI 2014 about the ways in which mice can be used to investigate the causes of malignant brain tumours.

Prof Cree talks to ecancertv at NCRI 2014 about the possibility of blood-based screening for cancer behalf of the Early Cancer Detection Consortium.

Dr Lewis talks to ecancertv at NCRI 2014 about the therapeutic benefits brought about by singing in a choir, based on research carried out on participants of Tenovus-initiated choirs in Wales.

Dr Cagan talks to ecancertv at NCRI 2014 about the use of fly models to sequence and develop treatments for cancers.