Podcasts about millenium

durée : 00:56:32 - Le grand atelier - par : Vincent Josse - Elle vient de publier son recueil de dessins, "Signé Coco", aux éditions Les Arènes BD et elle est accompagnée de la chanteuse Suzane, en tournée avec son dernier album, "Millenium". - réalisé par : Christophe IMBERT Vous aimez ce podcast ? Pour écouter tous les autres épisodes sans limite, rendez-vous sur Radio France.

Dr. Linda Duska and Dr. Kathleen Moore discuss key studies in the evolving controversy over radical upfront surgery versus neoadjuvant chemotherapy in advanced ovarian cancer. TRANSCRIPT Dr. Linda Duska: Hello, and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Linda Duska. I am a professor of obstetrics and gynecology at the University of Virginia School of Medicine.  On today's episode, we will explore the management of advanced ovarian cancer, specifically with respect to a question that has really stirred some controversy over time, going all the way back more than 20 years: Should we be doing radical upfront surgery in advanced ovarian cancer, or should we be doing neoadjuvant chemotherapy? So, there was a lot of hype about the TRUST study, also called ENGOT ov33/AGO-OVAR OP7, a Phase 3 randomized study that compares upfront surgery with neoadjuvant chemotherapy followed by interval surgery. So, I want to talk about that study today. And joining me for the discussion is Dr. Kathleen Moore, a professor also of obstetrics and gynecology at the University of Oklahoma and the deputy director of the Stephenson Cancer Center, also at the University of Oklahoma Health Sciences.  Dr. Moore, it is so great to be speaking with you today. Thanks for doing this. Dr. Kathleen Moore: Yeah, it's fun to be here. This is going to be fun. Dr. Linda Duska: FYI for our listeners, both of our full disclosures are available in the transcript of this episode.  So let's just jump right in. We already alluded to the fact that the TRUST study addresses a question we have been grappling with in our field. Here's the thing, we have four prior randomized trials on this exact same topic. So, share with me why we needed another one and what maybe was different about this one? Dr. Kathleen Moore: That is, I think, the key question. So we have to level-set kind of our history. Let's start with, why is this even a question? Like, why are we even talking about this today? When we are taking care of a patient with newly diagnosed ovarian cancer, the aim of surgery in advanced ovarian cancer ideally is to prolong a patient's likelihood of disease-free survival, or if you want to use the term "remission," you can use the term "remission." And I think we can all agree that our objective is to improve overall survival in a way that also does not compromise her quality of life through surgical complications, which can have a big effect. The standard for many decades, certainly my entire career, which is now over 20 years, has been to pursue what we call primary cytoreductive surgery, meaning you get a diagnosis and we go right to the operating room with a goal of achieving what we call "no gross residual." That is very different – in the olden days, you would say "optimal" and get down to some predefined small amount of tumor. Now, the goal is you remove everything you can see.  The alternative strategy to that is neoadjuvant chemotherapy followed by interval cytoreductive surgery, and that has been the, quote-unquote, "safer" route because you chemically cytoreduce the cancer, and so, the resulting surgery, I will tell you, is not necessarily easy at all. It can still be very radical surgeries, but they tend to be less radical, less need for bowel resections, splenectomy, radical procedures, and in a short-term look, would be considered safer from a postoperative consideration. Dr. Linda Duska: Well, and also maybe more likely to be successful, right? Because there's less disease, maybe, theoretically. Dr. Kathleen Moore: More likely to be successful in getting to no gross residual. Dr. Linda Duska: Right. Yeah, exactly. Dr. Kathleen Moore: I agree with that. And so, so if the end game, regardless of timing, is you get to no gross residual and you help a patient and there's no difference in overall survival, then it's a no-brainer. We would not be having this conversation. But there remains a question around, while it may be more likely to get to no gross residual, it may be, and I think we can all agree, a less radical, safer surgery, do you lose survival in the long term by this approach? This has become an increasing concern because of the increase in rates of use of neoadjuvant, not only in this country, but abroad. And so, you mentioned the four prior studies. We will not be able to go through them completely. Dr. Linda Duska: Let's talk about the two modern ones, the two from 2020 because neither one of them showed a difference in overall survival, which I think we can agree is, at the end of the day, yes, PFS would be great, but OS is what we're looking for. Dr. Kathleen Moore: OS is definitely what we're looking for. I do think a marked improvement in PFS, like a real prolongation in disease-free survival, for me would be also enough. A modest improvement does not really cut it, but if you are really, really prolonging PFS, you should see that-  Dr. Linda Duska: -manifest in OS. Dr. Kathleen Moore: Yeah, yeah. Okay. So let's talk about the two modern ones. The older ones are EORTC and CHORUS, which I think we've talked about. The two more modern ones are SCORPION and JCOG0602. So, SCORPION was interesting. SCORPION was a very small study, though. So one could say it's underpowered. 170 patients. And they looked at only patients that were incredibly high risk. So, they had to have a Fagotti score, I believe, of over 9, but they were not looking at just low volume disease. Like, those patients were not enrolled in SCORPION. It was patients where you really were questioning, "Should I go to the OR or should I do neoadjuvant? Like, what's the better thing?" It is easy when it's low volume. You're like, "We're going." These were the patients who were like, "Hm, you know, what should I do?" High volume. Patients were young, about 55. The criticism of the older studies, there are many criticisms, but one of them is that, the criticism that is lobbied is that they did not really try. Whatever surgery you got, they did not really try with median operative times of 180 minutes for primary cytoreduction, 120 for neoadjuvant. Like, you and I both know, if you're in a big primary debulking, you're there all day. It's 6 hours. Dr. Linda Duska: Right, and there was no quality control for those studies, either. Dr. Kathleen Moore: No quality control. So, SCORPION, they went 451-minute median for surgery. Like, they really went for it versus four hours and then 253 for the interval, 4 hours. They really went for it on both arms. Complete gross resection was achieved in 50% of the primary cytoreduced. So even though they went for it with these very long surgeries, they only got to the goal half the time. It was almost 80% in the interval group. So they were more successful there. And there was absolutely no difference in PFS or OS. They were right about 15 months PFS, right about 40 months OS.  JCOG0602, of course, done in Japan, a big study, 300 patients, a little bit older population. Surprisingly more stage IV disease in this study than were in SCORPION. SCORPION did not have a lot of stage IV, despite being very bulky tumors. So a third of patients were stage IV. They also had relatively shorter operative times, I would say, 240 minutes for primary, 302 for interval. So still kind of short. Complete gross resection was not achieved very often. 30% of primary cytoreduction. That is not acceptable. Dr. Linda Duska: Well, so let's talk about TRUST. What was different about TRUST? Why was this an important study for us to see? Dr. Kathleen Moore: So the criticism of all of these, and I am not trying to throw shade at anyone, but the criticism of all of these is if you are putting surgery to the test, you are putting the surgeon to the test. And you are assuming that all surgeons are trained equally and are willing to do what it takes to get someone to no gross residual. Dr. Linda Duska: And are in a center that can support the post-op care for those patients. Dr. Kathleen Moore: Which can be ICU care, prolonged time. Absolutely. So when you just open these broadly, you're assuming everyone has the surgical skills and is comfortable doing that and has backup. Everybody has an ICU. Everyone has a blood bank, and you are willing to do that. And that assumption could be wrong. And so what TRUST said is, "Okay, we are only going to open this at centers that have shown they can achieve a certain level of primary cytoreduction to no gross residual disease." And so there was quality criteria. It was based on – it was mostly a European study – so ESGO criteria were used to only allow certified centers to participate. They had to have a surgical volume of over 36 cytoreductive surgeries per year. So you could not be a low volume surgeon. Your complete resection rates that were reported had to be greater than 50% in the upfront setting. I told you on the JCOG, it was 30%. Dr. Linda Duska: Right. So these were the best of the best. This was the best possible surgical situation you could put these patients in, right? Dr. Kathleen Moore: Absolutely. And you support all the things so you could mitigate postoperative complications as well. Dr. Linda Duska: So we are asking the question now again in the ideal situation, right? Dr. Kathleen Moore: Right. Dr. Linda Duska: Which, we can talk about, may or may not be generalizable to real life, but that's a separate issue because we certainly don't have those conditions everywhere where people get cared for with ovarian cancer. But how would you interpret the results of this study? Did it show us anything different? Dr. Kathleen Moore: I am going to say how we should interpret it and then what I am thinking about. It is a negative study. It was designed to show improvement in overall survival in these ideal settings in patients with FIGO stage IIIB and C, they excluded A, these low volume tumors that should absolutely be getting surgery. So FIGO stage IIIB and C and IVA and B that were fit enough to undergo radical surgery randomized to primary cytoreduction or neoadjuvant with interval, and were all given the correct chemo. Dr. Linda Duska: And they were allowed bevacizumab and PARP, also. They could have bevacizumab and PARP. Dr. Kathleen Moore: They were allowed bevacizumab and PARP. Not many of them got PARP, but it was distributed equally, so that would not be a confounder. And so that was important. Overall survival is the endpoint. It was a big study. You know, it was almost 600 patients. So appropriately powered. So let's look at what they reported. When they looked at the patients who were enrolled, this is a large study, almost 600 patients, 345 in the primary cytoreductive arm and 343 in the neoadjuvant arm. Complete resection in these patients was 70% in the primary cytoreductive arm and 85% in the neoadjuvant arm. So in both arms, it was very high. So your selection of site and surgeon worked. You got people to their optimal outcome. So that is very different than any other study that has been reported to date. But what we saw when we looked at overall survival was no statistical difference. The median was, and I know we do not like to talk about medians, but the median in the primary cytoreductive arm was 54 months versus 48 months in the neoadjuvant arm with a hazard ratio of 0.89 and, of course, the confidence interval crossed one. So this is not statistically significant. And that was the primary endpoint. Dr. Linda Duska: I know you are getting to this. They did look at PFS, and that was statistically significant, but to your point about what are we looking for for a reasonable PFS difference? It was about two months difference. When I think about this study, and I know you are coming to this, what I thought was most interesting about this trial, besides the fact that the OS, the primary endpoint was negative, was the subgroup analyses that they did. And, of course, these are hypothesis-generating only. But if you look at, for example, specifically only the stage III group, that group did seem to potentially, again, hypothesis generating, but they did seem to benefit from upfront surgery.  And then one other thing that I want to touch on before we run out of time is, do we think it matters if the patient is BRCA germline positive? Do we think it matters if there is something in particular about that patient from a biomarker standpoint that is different? I am hopeful that more data will be coming out of this study that will help inform this. Of course, unpowered, hypothesis-generating only, but it's just really interesting. What do you think of their subset analysis? Dr. Kathleen Moore: Yeah, I think the subsets are what we are going to be talking about, but we have to emphasize that this was a negative trial as designed. Dr. Linda Duska: Absolutely. Yes. Dr. Kathleen Moore: So we cannot be apologists and be like, "But this or that." It was a negative trial as designed. Now, I am a human and a clinician, and I want what is best for my patients. So I am going to, like, go down the path of subset analyses. So if you look at the stage III tumors that got complete cytoreduction, which was 70% of the cases, your PFS was almost 28 months versus 21.8 months. Dr. Linda Duska: Yes, it becomes more significant. Dr. Kathleen Moore: Yeah, that hazard ratio is 0.69. Again, it is a subset. So even though the P value here is statistically significant, it actually should not have a P value because it is an exploratory analysis. So we have to be very careful. But the hazard ratio is 0.69. So the hypothesis is in this setting, if you're stage III and you go for it and you get someone to no gross residual versus an interval cytoreduction, you could potentially have a 31% reduction in the rate of progression for that patient who got primary cytoreduction. And you see a similar trend in the stage III patients, if you look at overall survival, although the post-progression survival is so long, it's a little bit narrow of a margin.  But I do think there are some nuggets here that, one of our colleagues who is really one of the experts in surgical studies, Dr. Mario Leitao, posted this on X, and I think it really resonated after this because we were all saying, "But what about the subsets?" He is like, "It's a negative study." But at the end of the day, you are going to sit with your patient. The patient should be seen by a GYN oncologist or surgical oncologist with specialty in cytoreduction and a medical oncologist, you know, if that person does not give chemo, and the decision should be made about what to do for that individual patient in that setting. Dr. Linda Duska: Agreed. And along those lines, if you look carefully at their data, the patients who had an upfront cytoreduction had almost twice the risk of having a stoma than the patients who had an interval cytoreduction. And they also had a higher risk of needing to have a bowel resection. The numbers were small, but still, when you look at the surgical complications, as you've already said, they're higher in the upfront group than they are in the interval group. That needs to be taken into account as well when counseling a patient, right? When you have a patient in front of you who says to you, "Dr. Moore, you can take out whatever you want, but whatever you do, don't make me a bag." As long as the patient understands what that means and what they're asking us to do, I think that we need to think about that. Dr. Kathleen Moore: I think that is a great point. And I have definitely seen in our practice, patients who say, "I absolutely would not want an ostomy. It's a nonstarter for me." And we do make different decisions. And you have to just say, "That's the decision we've made," and you kind of move on, and you can't look back and say, "Well, I wish I would have, could have, should have done something else." That is what the patient wants. Ultimately, that patient, her family, autonomous beings, they need to be fully counseled, and you need to counsel that patient as to the site that you are in, her volume of disease, and what you think you can achieve. In my opinion, a patient with stage III cancer who you have the site and the capabilities to get to no gross residual should go to the OR first. That is what I believe. I do not anymore think that for stage IV. I think that this is pretty convincing to me that that is probably a harmful thing. However, I want you to react to this. I think I am going to be a little unpopular in saying this, but for me, one of the biggest take-homes from TRUST was that whether or not, and we can talk about the subsets and the stage III looked better, and I think it did, but both groups did really well. Like, really well. And these were patients with large volume disease. This was not cherry-picked small volume stage IIIs that you could have done an optimal just by doing a hysterectomy. You know, these were patients that needed radical surgery. And both did well. And so what it speaks to me is that anytime you are going to operate on someone with ovary, whether it be frontline, whether it be a primary or interval, you need a high-volume surgeon. That is what I think this means to me. Like, I would want high volume surgeon at a center that could do these surgeries, getting that patient, my family member, me, to no gross residual. That is important. And you and I are both in training centers. I think we ought to take a really strong look at, are we preparing people to do the surgeries that are necessary to get someone to no gross residual 70% and 85% of the time? Dr. Linda Duska: We are going to run out of time, but I want to address that and ask you a provocative question. So, I completely agree with what you said, that surgery is important. But I also think one of the reasons these patients in this study did so well is because all of the incredible new therapies that we have for patients. Because OS is not just about surgery. It is about surgery, but it is also about all of the amazing new therapies we have that you and others have helped us to get through clinical research. And so, how much of that do you think, like, for example, if you look at the PFS and OS rates from CHORUS and EORTC, I get it that they're, that they're not the same. It's different patients, different populations, can't do cross-trial comparisons. But the OS, as you said, in this study was 54 months and 48 months, which is, compared to 2010, we're doing much, much better. It is not just the surgery, it is also all the amazing treatment options we have for these patients, including PARP, including MIRV, including lots of other new therapies. How do you fit that into thinking about all of this? Dr. Kathleen Moore: I do think we are seeing, and we know this just from epidemiologic data that the prevalence of ovarian cancer in many of the countries where the study was done is increasing, despite a decrease in incidence. And why is that? Because people are living longer. Dr. Linda Duska: People are living longer, yeah. Dr. Kathleen Moore: Which is phenomenal. That is what we want. And we do have, I think, better supportive care now. PARP inhibitors in the frontline, which not many of these patients had. Now some of them, this is mainly in Europe, will have gotten them in the first maintenance setting, and I do think that impacts outcome. We do not have that data yet, you know, to kind of see what, I would be really interested to see. We do not do this well because in ovarian cancer, post-progression survival can be so long, we do not do well of tracking what people get when they come off a clinical trial to see how that could impact – you know, how many of them got another surgery? How many of them got a PARP? I think this group probably missed the ADC wave for the most part, because this, mirvetuximab is just very recently available in Europe. Dr. Linda Duska: Unless they were on trial. Dr. Kathleen Moore: Unless they were on trial. But I mean, I think we will have to see. 600 patients, I would bet a lot of them missed the ADC wave. So, I do not know that we can say we know what drove these phenomenal – these are some of the best curves we've seen outside of BRCA. And then coming back to your point about the BRCA population here, that is a really critical question that I do not know that we're ever going to answer. There have been hypotheses around a tumor that is driven by BRCA, if you surgically cytoreduced it, and then chemically cytoreduced it with chemo, and so you're starting PARP with nothing visible and likely still homogeneous clones. Is that the group we cured? And then if you give chemo first before surgery, it allows more rapid development of heterogeneity and more clonal evolution that those are patients who are less likely to be cured, even if they do get cytoreduced to nothing at interval with use of PARP inhibitor in the front line. That is a question that many have brought up as something we would like to understand better. Like, if you are BRCA, should you always just go for it or not? I do not know that we're ever going to really get to that. We are trying to look at some of the other studies and just see if you got neoadjuvant and you had BRCA, was anyone cured? I think that is a question on SOLO1 I would like to know the answer to, and I don't yet, that may help us get to that. But that's sort of something we do think about. You should have a fair number of them in TRUST. It wasn't a stratification factor, as I remember. Dr. Linda Duska: No, it wasn't. They stratified by center, age, and ECOG status Dr. Kathleen Moore: So you would hope with randomization that you would have an equal number in each arm. And they may be able to pull that out and do a very exploratory look. But I would be interested to see just completely hypothesis-generating what this looks like for the patients with BRCA, and I hope that they will present that. I know they're busy at work. They have translational work. They have a lot pending with TRUST. It's an incredibly rich resource that I think is going to teach us a lot, and I am excited to see what they do next. Dr. Linda Duska: So, outside of TRUST, we are out of time. I just want to give you a moment if there were any other messages that you want to share with our listeners before we wrap up. Dr. Kathleen Moore: It's an exciting time to be in GYN oncology. For so long, it was just chemo, and then the PARP inhibitors nudged us along quite a bit. We did move more patients, I believe, to the cure fraction. When we ultimately see OS, I think we'll be able to say that definitively, and that is exciting. But, you know, that is the minority of our patients. And while HRD positive benefits tremendously from PARP, I am not as sure we've moved as many to the cure fraction. Time will tell. But 50% of our patients have these tumors that are less HRD. They have a worse prognosis. I think we can say that and recur more quickly. And so the advent of these antibody-drug conjugates, and we could name 20 of them in development in GYN right now, targeting tumor-associated antigens because we're not really driven by mutations other than BRCA. We do not have a lot of things to come after. We're not lung cancer. We are not breast cancer. But we do have a lot of proteins on the surface of our cancers, and we are finally able to leverage that with some very active regimens. And we're in the early phases, I would say, of really understanding how best to use those, how best to position them, and which one to select for whom in a setting where there is going to be obvious overlap of the targets. So we're going to be really working this problem. It is a good problem. A lot of drugs that work pretty well. How do you individualize for a patient, the patient in front of you with three different markers? How do you optimize it? Where do you put them to really prolong survival? And then we finally have cell surface. We saw at ASCO, CDK2 come into play here for the first time, we've got a cell cycle inhibitor. We've been working on WEE1 and ATR for a long time. CDK2s may hit. Response rates were respectable in a resistant population that was cyclin E overexpressing. We've been working on that biomarker for a long time with a toxicity profile that was surprisingly clean, which I like to see for our patients. So that is a different platform. I think we have got bispecifics on the rise. So there is a pipeline of things behind the ADCs, which is important because we need more than one thing, that makes me feel like in the future, I am probably not going to be using doxil ever for platinum-resistant disease. So, I am going to be excited to retire some of those things. We will say, "Remember when we used to use doxil for platinum-resistant disease?" Dr. Linda Duska: I will be retired by then, but thanks for that thought. Dr. Kathleen Moore: I will remind you. Dr. Linda Duska: You are right. It is such an incredibly exciting time to be taking care of ovarian cancer patients with all the opportunities.  And I want to thank you for sharing your valuable insights with us on this podcast today and for your great work to advance care for patients with GYN cancers. Dr. Kathleen Moore: Likewise. Thanks for having me. Dr. Linda Duska: And thank you to our listeners for your time today. You will find links to the TRUST study and other studies discussed today in the transcript of this episode. 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. More on today's speakers:   Dr. Linda Duska  @Lduska Dr. Kathleen Moore Follow ASCO on social media:     @ASCO on X (formerly Twitter) ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures of Potential Conflicts of Interest:    Dr. Linda Duska:   Consulting or Advisory Role: Regeneron, Inovio Pharmaceuticals, Merck, Ellipses Pharma  Research Funding (Inst.): GlaxoSmithKline, Millenium, Bristol-Myers Squibb, Aeterna Zentaris, Novartis, Abbvie, Tesaro, Cerulean Pharma, Aduro Biotech, Advaxis, Ludwig Institute for Cancer Research, Leap Therapeutics  Patents, Royalties, Other Intellectual Property: UptToDate, Editor, British Journal of Ob/Gyn  Dr. Kathleen Moore: Leadership: GOG Partners, NRG Ovarian Committee Chair Honoraria: Astellas Medivation, Clearity Foundation, IDEOlogy Health, Medscape, Great Debates and Updates, OncLive/MJH Life Sciences, MD Outlook, Curio Science, Plexus, University of Florida, University of Arkansas for Medical Sciences, Congress Chanel, BIOPHARM, CEA/CCO, Physician Education Resource (PER), Research to Practice, Med Learning Group, Peerview, Peerview, PeerVoice, CME Outfitters, Virtual Incision Consulting/Advisory Role: Genentech/Roche, Immunogen, AstraZeneca, Merck, Eisai, Verastem/Pharmacyclics, AADi, Caris Life Sciences, Iovance Biotherapeutics, Janssen Oncology, Regeneron, zentalis, Daiichi Sankyo Europe GmbH, BioNTech SE, Immunocore, Seagen, Takeda Science Foundation, Zymeworks, Profound Bio, ADC Therapeutics, Third Arc, Loxo/Lilly, Bristol Myers Squibb Foundation, Tango Therapeutics, Abbvie, T Knife, F Hoffman La Roche, Tubulis GmbH, Clovis Oncology, Kivu, Genmab/Seagen, Kivu, Genmab/Seagen, Whitehawk, OnCusp Therapeutics, Natera, BeiGene, Karyopharm Therapeutics, Day One Biopharmaceuticals, Debiopharm Group, Foundation Medicine, Novocure Research Funding (Inst.): Mersana, GSK/Tesaro, Duality Biologics, Mersana, GSK/Tesaro, Duality Biologics, Merck, Regeneron, Verasatem, AstraZeneca, Immunogen, Daiichi Sankyo/Lilly, Immunocore, Torl Biotherapeutics, Allarity Therapeutics, IDEAYA Biosciences, Zymeworks, Schrodinger Other Relationship (Inst.): GOG Partners

In this episode, Galit sits down with creator and educator Jason Pickett for a real conversation about the shifts happening in today's dance world. Jason shares his path from Utah's freestyle community to building a career outside the traditional LA route, and the mindset behind choosing what actually feels right. They dig into the responsibilities of teachers and influencers online, the short-sightedness that's causing dance studios and conventions business, and a shift in what dancers want to do professionally. Jason and Galit also explore whether competitions are watering down dance, how COVID changed the mentality of young dancers, and why the best teachers don't rely on the “combo.” This episode pulls back the curtain on connecting the generations, talent development, and what it really means to create good dancers - not just good perfectionists. Follow Galit: Instagram - https://www.instagram.com/gogalit Website - https://www.gogalit.com/ On-Demand Fitness Courses - https://galit-s-school-0397.thinkific.com/collections Follow Jason Pickett: Instagram - https://www.instagram.com/heyitspickett/ Jason's Website - https://nsadance.com/

Chris and Amy discuss the demo of the Millenium Hotel site; a new Uber feature for women; Rep Nikki Budzinski on the government shutdown; and Did you see this? Bagpipes in Australia.

This episode we trade Guts for Ganishka, focusing on a major battle between Griffith's demon knights (led by the ridiculously stupidly designed Locus in his apostle mode), which ultimately is a diversion for a certain demi-god to kidnap a certain princess. In the process however, we learn more about Ganishka and his own inhumanity and level of power. Like Guts' dong likely is...IT'S BIG.

Host Anthony Desiato and guest Tim Bruns dig into the second half of John Byrne's 2-year run on the Super-titles — culminating in "The Supergirl Saga," which saw the introduction of Matrix and Superman's cold execution of General Zod & his allies. But first, Anthony and Tim discuss Superman's team-ups with Batman, Booster Gold, and The Spectre; Lana & Smallville's baffling involvement in the "Millenium" crossover; romantic developments between Superman & Wonder Woman, Lois Lane & Jose Delgado, and Clark Kent & Lori Lemaris; a welcome, but ultimately unfulfilling, spotlight on the Krypton part of the story; and the Post-Crisis returns or debuts of Silver Banshee, Toyman, Prankster, and Brainiac.This episode covers: SUPERMAN #12-22, ADVENTURES OF SUPERMAN #436-444 (with Jerry Ordway on art), and ACTION COMICS #594-600.The podcast's Byrne event has concluded! Thanks to all guests and audience members for coming along on this ride. Keep tuning in for new episodes every Tuesday!Support the show and receive exclusive podcast content at Patreon.com/AnthonyDesiato, including the spinoff podcasts BEYOND METROPOLIS and DIGGING FOR JUSTICE!Visit BCW Supplies and use promo code FSP to save 10% on your next order of comics supplies. Get your DFK merch at the podcast's TeePublic storefront!FACEBOOK GROUP: Digging for Kryptonite: A Superman Fan GroupFACEBOOK PAGE: @diggingforkryptonitepodINSTAGRAM: @diggingforkryptonitepodTWITTER: @diggingforkrpodBLUESKY: @diggingforkrpod.bsky.socialEMAIL: flatsquirrelproductions@gmail.comWEBSITE: FlatSquirrelProductions.com Digging for Kryptonite is a Flat Squirrel Production. Theme music by Dan Pritchard. Key art by Isaiah Simmons. Mentioned in this episode:Single Bound PodcastThis Podcast Will Never DieAlways Hold On To SmallvilleFat Moose ComicsAw Yeah ComicsHang On To Your Shorts Film Festival

Dagens avsnitt: 00:00 Start00:12 Hur är läget?03:52 Kommer USA attackera Venezuela?10:01 Förslaget: Millenium ska bort18:19 Roger fick inte köpa en bulle23:38 Butikernas Black friday-fusk28:40 De som dricker som unga tjänar mer pengar33:08 Liberalernas efternamns-kampanj39:11 Indiens mest hatade person42:37 Är lekplatserna för mesiga?49:45 Linneas konsumentrapport55:03 DjurnyheterLinnea Rönnqvist pratar om det nya förslaget: Millennium ska bort, det har en utredning kommit fram till. Istället vill de ersätta det kritiserade systemet med "ett modulärt system" – vad är det och vad kommer allt att kosta? Hon berättar även om Liberalernas nya efternamns-kampanj och om butikernas Black friday-fusk. Ina Lundström ger oss det senaste från konflikten mellan USA och Venezuela. Hon har även läst om en man som heter Roger som är arg på nymodigheter. Och hur hänger supandet i ungdomen ihop med hög lön? Dessutom: Därför ylar hundar mot ambulanser och är lekplatser för mesiga? Hosted on Acast. See acast.com/privacy for more information.

Die 27. Jahrgangsfolge steht für das Millenium. Wie gut sind unsere Erinnerungen? Was muss man aus diesem Jahr gesehen haben? War früher alles besser?Reinhören! Viel Vergnügen! Merch (wenn du noch geiler ausschauen willst: https://www.seedshirt.de/shop/cineswissFeedback oder eure Ideen für weitere Episoden könnt ihr uns gerne über die sozialen Netzwerke oder per Mail an info@cine-swiss.ch zukommen lassen, folgt uns damit ihr nichts verpasst, abonniert uns und empfiehlt uns gerne weiter! Dangge!https://podcasters.spotify.com/pod/show/cineswiss/subscribe Für exklusive Folgen oder einfach so hier: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.buymeacoffee.com/cineswiss⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠    https://www.brugggore.ch  https://outnow.chhttps://www.excelsior-brugg.ch/de/home https://odeon-brugg.ch/ https://www.youtube.com/@cineswiss https://www.facebook.com/cineswiss                   https://instagram.com/cineswiss?igshid=1cjo0dgnqvsrd                  https://boxd.it/10TmB                   https://www.cine-swiss.ch

Vous avez envie de tout savoir sur son admiration pour Diamʹs, ses années de danse au conservatoire dʹAvignon, son envie réalisée de collaborer avec le rappeur Youssoupha, son désamour pour les plateformes qui surclassifient la musique, ses nouveaux titres réunis sur son troisième album " Millenium " ? Suzane répond à toutes vos questions.

Differing views of the millennium

Differing views of the millennium

Send us a text215 Bonus Episode (Thoughts): Little ChickI have been playing with some energy and I also got some insights in how I learn and then adapt and pass along and that it is a way of the energy process. Learn about the egg and the little chick here! Next episode will be 2025-11-11 and it will include a meditation! If you like this podcast please share it with a friend! Share the Light. Spread the Light. Shine!LDS AND MEDIUM PODCAST BACKGROUND:I was born into the Church of Jesus Christ of Latter-Day Saints, or LDS for short. All my life I felt awkward and out of place, not because of my religion, but because of my spiritual gifts. It was hard to combine the idea of what first seemed like two separate worlds. So my whole life I have tried. I have learnt more about my gifts, and stayed faithful to my faith. But then I heard people left the church because it seems impossible to combine the two. So I am here, to try and mend the rift. To show that it is possible to be both LDS and to have, and use, our spiritual gifts. I am not alone on this journey, but my sister, who just is waking up to her spiritual gifts is by my side and she will also share her story.Jesus Christ, our older brother, was a healer. He asked us to love one another. So let´s follow in his footsteps. Please join me on this journey, let´s make a community of strong spiritual LDS, or whatever religion you belong to, and all work together to make this world a better place.If you like what I do, then you can find me here:https://linktr.ee/ldsandmediumIf you have words of support or stories that you anonymously want me to share please write me at ldsandmedium@gmail.com. I will try and answer all your emails BUT I am very busy with my life and I hope you can have some patience with me.If you would like access to the Podcast before it is released, all the bonuses and extra trainings and the meditation prayers as an mp3 you can support me on Patreon: https://www.patreon.com/ldsandmedium or send a Donation through Paypal. It will also be available as an archive that you can subscribe to on https://payhip.com/LDSandMediumDISCLAIMER: This Podcast is not official LDS doctrine, nor is it in any way financially supported by the LDS church. All the content is either our own personal thoughts and reflections or stories from our lives or the lives of others. Any quotes included will come from the Bible, The Book of Mormon or other scriptures, Church publications, hymns, General Conference or spiritual sites. This podcast is also for entertainment purposes only and you are always the one responsible for actions you decide in your own life, as we are all responsible always only for ourselves. Support the show

All you need to know again (two weeks in a row - a first!) is Wolverine from Marvel vs. Capcom saying “BERSERKER (armor) BARRAGE! …BERSERKER (armor) BARRAGE!” over and over for this episode, as we close out the introduction to Guts' fabled cursed armor. Schierke really defines her main role in the series with the help of Flora's fiery force ghost, and we head back to oooooool' Windham to see that it's been taken over by Kushan…with almost every citizen murdered and hanged from the ramparts. Follow No Guts, No Glory on Instagram: https://www.instagram.com/nogutsnoglorypc/ Check out Joey and Ryan's Renaissance Martial Arts organization: https://www.thearma.org/ Check out Steve and Joey's other podcast: https://podcasts.apple.com/us/podcast/probing-ancient-aliens/id1321801647 https://open.spotify.com/show/3aREEXpe4DE37LsNkUxntW Check out Steve and Joey's Patreon for that other podcast: https://www.patreon.com/probingancientaliens

With the establishment of the Millennial Kingdom, Satan will be removed from the earth. Satan is active in his machinations against God and His children. But come the Millennial Kingdom, Satan will be locked up by Christ for the entire Millenium.

Guts gets the f**king Berserker Armor - and that's all you need to know.

Insightful and informative as always, we discuss great losses of different generations, new pop icons in KC, curious listings, and more. In focus are Chappel Roan, D'Angelo, John Lodge, Taylor Swift, Springsteen, Millenium's "top" hits, Gordon Lightfoot, and much more. Always a great musical ride!

In episode 218, host Galit Friedlander and guest Ben “BTEK” Chung (Kinjaz co-founder, Jabbawockeez, America's Best Dance Crew, and entrepreneur/consultant) dig into what happens when you refuse to take the conventional route. Ben shares how he went from production work at MTV to dancing full-time, creating his own lane instead of following someone else's path. We talk about best communication practices, navigating contracts with confidence, and redefining success as your career and even priorities change. Ben opens up about mindset, faith, and finding growth in life's detours, plus what it really takes to stay sharp and inspired over the long game. Follow Galit: Instagram - https://www.instagram.com/gogalit Website - https://www.gogalit.com/ On-Demand Fitness Courses - https://galit-s-school-0397.thinkific.com/collections Follow Ben Chung: Instagram - https://www.instagram.com/btek_benchung Werkflow - https://www.werkflow.us/

O DUCENTÉSIMO QUADRAGÉSIMO TERCEIRO EPISÓDIO do Podcast Dar Voz A esQrever

By Jeff Richards - We often think of the Millenium as a time of great peace and rebuilding. In this message we will look how free will needs to place a central role in bringing peace to the earth. Some will not embrace nor choose peace, and it will be our job to help them to see the light.

Things get even darker, wetter, and more horrifying as our intrepid crew delve deeper into Qliphoth. Farnesse and Isidro gain some much needed confidence thanks to our old pal McGuts the Crime Struggler (80s kids will understand that obscure reference…maybe), and some very powerful beings emerge to both help and hinder our heroes: Slan, Skull Knight, and the essence of Darkness itself!

The older Patreon episodes continue with this entry about sexuality in the 41st Millenium, recorded in 2018

What is the best team of NBA players of the 2000's? Who were the 12 best Celtics of the millenium? Cap and Guillermo end the offseason with a look at which C's they put on their list. Plus, massive injuries for at least two NBA teams before camp even starts, and an end to the Kuminga saga is near in Golden State. #differenthere #celtics #warriors #Kuminga #JaysonTatum #JaylenBrown #Porzingis #JrueHoliday #DerrickWhite #JaylenBrown #Pritchard #HugoGonzalezCheck out all the latest Celtics coverage with our partners at SportSpyder.com: https://sportspyder.com/nba/boston-celtics/news?pid=20906

Invitée : Suzane, pour son album "Millenium" qui sort le 26 septembre, elle interprétera "Je t'accuse" en live Hébergé par Audiomeans. Visitez audiomeans.fr/politique-de-confidentialite pour plus d'informations.

WELCOME BACK TO WHAM! This week, Adam and Andy discuss the changing mood of Dwarf Lords, the confusing nature of bets in the 41st Millenium and why the word "taint" cannot be taken seriously in the modern day.   This Issue Contains:   Inquisitors of the Imperium  Inquisitor Ravenwing  Dwarf Lords Grudgematch

In episode 217, host Galit Friedlander and guest Ana Rokafella Garcia (legendary b-girl, co-founder of Full Circle Productions, choreographer, filmmaker, and adjunct professor at The New School), dive into the history, evolution, and impact of hip-hop. From growing up in New York City during the fires, crack epidemic, and AIDS crisis to discovering her voice in cyphers and clubs, Rokafella shares how dance carved out a future for her. She reflects on commercialization, gender dynamics, and visibility in the scene, while urging today's dancers to stay grounded in the culture's foundations. The conversation also touches on breaking at the Olympics, the tension between competition and community, and why hip-hop's resilience continues to guide her work. Follow Galit: Instagram - https://www.instagram.com/gogalit Website - https://www.gogalit.com/ On-Demand Fitness Courses - https://galit-s-school-0397.thinkific.com/collections Follow Rokafella: Instagram - https://www.instagram.com/larokafella Website - https://larokasoul.com/ Full Circle: https://www.instagram.com/fullcirclesouljahs Behind the Groove: https://www.instagram.com/behindthegroovenyc/ All the Ladies Say: https://www.instagram.com/alltheladiessay Listen to DanceSpeak on Apple Podcasts and Spotify.

These trolls be gettin' WET thanks to the ultra-powerful witch Schierke! Guts is breaking trauma cycles and showing kindness and respect to this magical youngster, while Isidro looks on in shame, feeling that he's worthless to his new crew. We get even more tug of war between the classically religious and the magical/spiritual aspects of reality here as well, ending in a highly unexpected change in our resident annoying priest character. Oh, and Isidro gets his iconic sword! Follow No Guts, No Glory on Instagram: https://www.instagram.com/nogutsnoglorypc/ Check out Joey and Ryan's Renaissance Martial Arts organization: https://www.thearma.org/ Check out Steve and Joey's other podcast: https://podcasts.apple.com/us/podcast/probing-ancient-aliens/id1321801647 https://open.spotify.com/show/3aREEXpe4DE37LsNkUxntW Check out Steve and Joey's Patreon for that other podcast: https://www.patreon.com/probingancientaliens

Oh the trolls they are a cummin'! Uuuuuh, COMIN', I meant, of course... Either way, we get even more fantastical, existential, and occult in these chapters, with the badass of badasses, Schierke, invoking the lords of the east, west, north and south to protect Guts and crew (as well as the villagers and that a-hole priest!) while they take out this horde of nasties...that is, until a giant peepee shaped Ogre enters the scene and puts a wrench in their gears. Enjoy!

The Handsomest Man in 40K is back to help Dave review the return of the short kings of the 41st Millenium in the  Leagues of Votann Codex.  Jake and Dave talk about the 5 new detachments and all of the new and changed datasheets in the book. Huge thanks to Games Workshop for sending us a preview copy of the codex so that we can bring you this episode as soon as possible!

We're getting a beefy-ass lore bomb in these chapters thanks to our new witch friends Schierke and her mistress Flora! What is the astral realm...the interstice...the Godhand...and the nature of Griffith's newly reincarnated powers? All of this is discussed in semi-mindbending detail - plus, Guts's JRPG party gets kitted out with magical weapons and armor for the journey to take out horrific trolls for Morgan, the boring NPC from the previous episode. Enjoy!

Send us a textSpecial guest Victoria joins to cover this crossover episode! Mike finds issue with the scope of the end-times theme and Andrew questions who is a zombie. JOIN OUR SOCIALS!magusmediaproductions.netwww.facebook.com/groups/thisisnothappeningpod/ @TINHXFilesPodCONTACT US!tinhxfp@gmail.com

This week Pastor Brad walks us through the Millenium and its implications for our lives today. He reminds us to exalt the Lord, establish believers, and engage the world with the gospel.

This past year I truly opened myself up to Tantra, after misjudging it for years. Tantra is a Yogic ancient wisdom tradition and now something I practice daily And I found one of the MOST outstanding leaders and Tantra facilitators in the world in my tribe this past year and stoked to talk to him about his empowered love movement. This is my first official tantra interview on Health N Wealth N Wise! ScottieO is the founder and primary facilitator of Ecstatic Hearts. He is an internationally renowned Tantra Teacher and best-selling Author who has touched millions of lives with his message of love. He has personally supported thousands of students manifesting their deepest desires, especially in their love lives, with both wisdom of the ancients and modern self-evolvement techniques. His primary Tantra lineage is through Babaji Nagaraj.  Ecstatic Hearts uses retreats, playshops, one-on-one coaching, online trainings, and Tantra Festivals, to improve every aspect of students' lives so they are truly living with juicy excitement. ScottieO has an MBA and BBA, and has spent over $300K and invested 20 years in personal development and Tantra trainings. His training certifications and experiences include Landmark, Legacy, Lifespring, Millionaire Mind, Tony Robins, Success University, Gratitude, Millenium 3 Education, New Game, Totally Coached, International Coaching Federation, Better Business Bureau, Everyday Tantra, Tantra Heart, Tantric Hearts, Ipsalu International, One Taste, OWTF, Lessin's School of Tantra, Source, ISTA, and Tribal Tantra. ScottieO is a best-selling co-author of “Passion: Living the Life You Love”, and featured in two films "The Answer to Everything" and "The Answer to Health". He has also been featured on media such as the Learning Channel, Daily Mail, Netflix, Men and Women's Health and the New York Post. His interviews in London and Germany have helped raise consciousness and connection for millions of people and his message of love continues to grow.  FIND OUT MORE ABOUT SCOTTIE O AND HIS LOVE MOVEMENT HERE www.ecstatichearts.com  www.electrifyinglove.com www.ecstatichearts.com/live-events     FIND OUT MORE ABOUT MAGDALENA GRACE HERE or TO SIGN UP FOR HER UPCOMING ABUNDANCE ALCHEMIST IN PERSON WORKSHOPS OR HEALTHY N WEALTHY N WISE RETREATS Our Women's Retreat is 9/9 - Build your business and life like a Queen Our Coed retreat is Oct 17-19th BOOK A RUNES READING AND SIGN UP FOR HER WORKSHOPS & MORE! www.MagdalenaGrace.com   JOIN OUR HEALTHY N WEALTHY N WISE ONLINE ACADEMY  www.microdosingforhealth.com    BUY ME A COFFEE OR DONATE FOR SCHOLARSHIP FUND FOR HEALING CLIENTS IN NEED https://venmo.com/u/lotusthrone   MORE ALCHEMY OPPORTUNITIES FOR YOUR BEST HEALTH, WEALTH AND RELATIONSHIPS www.SanDiegoKambo.com  www.KundaliniFallbrook.com  www.LotusThroneSanctuary.com   WANNA SIGN UP AND BE A PLEDGING PATRON FOR HEALTHY N WEALTHY N WISE - SAVING LIVES AND CREATING MORE ABUNDANCE FOR OTHERS?  https://patron.podbean.com/magdalena     SUBSCRIBE TO HER YOUTUBE CHANNEL: https://www.youtube.com/@UC_l0t_6TBbZ1q9Q0wKZz89Q   

Schierke, baby!!! It's the official introduction of everyone's favorite little (and mega powerful) witch in training. Plus, Guts, Farnesse, Isidro, Serpico and the rest of the crew are forced to deal with an ever more "fairy tail-ish" world, fighting off vicious disgusting trolls, and adorable regenerating golems.

FIVE MILLENIUM AFTER THE NEO IMPACT, WHAT CIVILIZATIONS REVIVE AND THRIVE?  4/8: After 1177 B.C.: The Survival of Civilizations by  Eric H. Cline  (Author) 1200 BCE MINOAN

FIVE MILLENIUM AFTER THE NEO IMPACT, WHAT CIVILIZATIONS REVIVE AND THRIVE?  8/8: After 1177 B.C.: The Survival of Civilizations by  Eric H. Cline  (Author) 1200 BCE MINOAN

FIVE MILLENIUM AFTER THE NEO IMPACT, WHAT CIVILIZATIONS REVIVE AND THRIVE?  7/8: After 1177 B.C.: The Survival of Civilizations by  Eric H. Cline  (Author) 1500 BCE MINOAN

FIVE MILLENIUM AFTER THE NEO IMPACT, WHAT CIVILIZATIONS REVIVE AND THRIVE?  6/8: After 1177 B.C.: The Survival of Civilizations by  Eric H. Cline  (Author) 1952

FIVE MILLENIUM AFTER THE NEO IMPACT, WHAT CIVILIZATIONS REVIVE AND THRIVE?  3/8: After 1177 B.C.: The Survival of Civilizations by  Eric H. Cline  (Author) 1200 BCE MINOAN

FIVE MILLENIUM AFTER THE NEO IMPACT, WHAT CIVILIZATIONS REVIVE AND THRIVE?  5/8: After 1177 B.C.: The Survival of Civilizations by  Eric H. Cline  (Author) NOVEMBER 1951

FIVE MILLENIUM AFTER THE NEO IMPACT, WHAT CIVILIZATIONS REVIVE AND THRIVE?  2/8: After 1177 B.C.: The Survival of Civilizations by  Eric H. Cline  (Author) 1200 BCE MINOAN

FIVE MILLENIUM AFTER THE NEO IMPACT, WHAT CIVILIZATIONS REVIVE AND THRIVE?  1/8: After 1177 B.C.: The Survival of Civilizations by  Eric H. Cline  (Author) 1200 BCE MINOAN https://www.amazon.ca/After-1177-B-C-Survival-Civilizations/dp/0691192138 At the end of the acclaimed history 1177 B.C., many of the Late Bronze Age civilizations of the Aegean and Eastern Mediterranean lay in ruins, undone by invasion, revolt, natural disasters, famine, and the demise of international trade. An interconnected world that had boasted major empires and societies, relative peace, robust commerce, and monumental architecture was lost and the so-called First Dark Age had begun. Now, in After 1177 B.C., Eric Cline tells the compelling story of what happened next, over four centuries, across the Aegean and Eastern Mediterranean world. It is a story of resilience, transformation, and success, as well as failures, in an age of chaos and reconfiguration.

In episode 216, host Galit Friedlander and returning guest Liana Blackburn (Britney Spears, Lady Gaga, Taylor Swift, Dancing with the Stars, The Voice, Cirque Du Soleil, and more), explore the evolution from performer to guide and what it means to lead from embodiment, worthiness, and creative sovereignty. Now a somatic practitioner and sought-after teacher, Liana shares how she helps passionate creatives connect more deeply with their body and being, and live in alignment with their values, on and off the dance floor. We also get into money mindset shifts, building supportive creative containers, and how to navigate the emotional side of dance, from learning choreography with confidence to knowing when it's okay to walk out of class. Follow Galit: Instagram - https://www.instagram.com/gogalit Website - https://www.gogalit.com/ On-Demand Fitness Courses- https://galit-s-school-0397.thinkific.com/collections You can connect with Liana Blackburn on Instagram @iamlianablackburn or via iamlianablackburn.com. Learn more about Liana's October 2025 retreat by visiting iamlianablackburn.com/retreats

The Holy Evil War is getting ready to pop off, as we get a lot of world building from Griffith's apostle-infused side of the battle: He has giants, he has superpowered men, he has shadowy supernatural assassins, all set to...liberate Midland? He's trying to be the savior of the world, using his powers of The Prince of Longing to make his new subjects fall in love with him. Also, Farnesse has another existential crisis, but this one is full of hope and acceptance as she navigates her new purpose in life, and, for now, leaves the despair behind her.

*Disclaimer: The audio quality in this episode is unfortunately below our standards but we felt that the content was too valuable not to share it* In episode 215, host Galit Friedlander and guest Stephanie Scull (dancer for Pharrell, Usher, America's Got Talent and founder of her own successful styling/costuming brand) get into the real-talk intersection of dance, identity, and personal style. Stephanie shares how her path took her from competitive dance and the fashion world to working major jobs in LA and what made her say yes to pivoting towards her own business. From audition looks to headshot rules to what “comfortable” really means when you're getting dressed for a career-defining moment, this one is full of practical gems and big-picture energy. We talk about boundaries, burnout, why dancers often forget their power, and how to use clothes to show the world who you are, before you even move. Follow Galit: Instagram - https://www.instagram.com/gogalit Website - https://www.gogalit.com/ Fit From Home - https://galit-s-school-0397.thinkific.com/courses/fit-from-home You can connect with Stephanie Scull on Instagram at https://www.instagram.com/scullysculls/. Stephanie's website is https://www.scullystyles.com. Listen to DanceSpeak on Apple Podcasts and Spotify.

In episode 215, host Galit Friedlander and guest Stephanie Scull (dancer for Pharrell, Usher, America's Got Talent and founder of her own successful styling/costuming brand) get into the real-talk intersection of dance, identity, and personal style. Stephanie shares how her path took her from competitive dance and the fashion world to working major jobs in LA and what made her say yes to pivoting towards her own business. From audition looks to headshot rules to what “comfortable” really means when you're getting dressed for a career-defining moment, this one is full of practical gems and big-picture energy. We talk about boundaries, burnout, why dancers often forget their power, and how to use clothes to show the world who you are, before you even move. Follow Galit: Instagram - https://www.instagram.com/gogalit Website - https://www.gogalit.com/ Fit From Home - https://galit-s-school-0397.thinkific.com/courses/fit-from-home You can connect with Stephanie Scull on Instagram at https://www.instagram.com/scullysculls/. Stephanie's website is https://www.scullystyles.com. Listen to DanceSpeak on Apple Podcasts and Spotify.

This should be a given for Berserk, but these chapters get dark, tragic, and disturbing. Sadly, it's our beautiful, but flawed boy, Berk, himself, who is the perpetrator of this messed up stuff. But it's not that simple! Much to discuss here as the Beast of Darkness begins to take its hold on old Gutsy, causing him to wrestle with (and largely lose against) his deepest desires…resulting in the simple minded, traumatized Casca to recoil from him as a villain for the foreseeable future. Follow No Guts, No Glory on Instagram: https://www.instagram.com/nogutsnoglorypc/ Check out Joey and Ryan's Renaissance Martial Arts organization: https://www.thearma.org/ Check out Steve and Joey's other podcast: https://podcasts.apple.com/us/podcast/probing-ancient-aliens/id1321801647 https://open.spotify.com/show/3aREEXpe4DE37LsNkUxntW Check out Steve and Joey's Patreon for that other podcast: https://www.patreon.com/probingancientaliens

Dr. John Sweetenham and Dr. Erika Hamilton highlight key abstracts that were presented at ASCO25, including advances in breast and pancreatic cancers as well as remarkable data from the use of structured exercise programs in cancer care. Transcript Dr. Sweetenham: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham. Today, we'll be discussing some of the key advances and novel approaches in cancer care that were presented at the 2025 ASCO Annual Meeting. I'm delighted to be joined again by the chair of the Meeting's Scientific Program, Dr. Erika Hamilton. She is a medical oncologist and director of breast cancer and gynecologic cancer research at the Sarah Cannon Research Institute in Nashville, Tennessee.  Our full disclosures are available in the transcript of this episode. Dr. Hamilton, congratulations on a fantastic meeting. From the practice-changing science to the world-renowned speakers at this year's Meeting, ASCO25 really reflected the amazing progress we're seeing in oncology today and the enormous opportunities that lie ahead of us. And thanks for coming back on to the podcast today to discuss some of these advances. Dr. Hamilton: Thanks, Dr. Sweetenham. I'm happy to join you today. It really was an impactful ASCO Annual Meeting. I probably am biased, but some great research was presented this year, and I heard lots of great conversations happening while we were there. Dr. Sweetenham: Yeah, absolutely. There was a lot of buzz, as well as a lot of media buzz around the meeting this year, and I think that's probably a good place to start. So I'd like to dive into abstract number LBA3510. This was the CHALLENGE trial, which created a lot of buzz at the meeting and subsequently in the media. This is the study that was led by the NCI Canada Clinical Trials Group, which was the first randomized phase 3 trial in patients with stage III and high-risk stage II colon cancer, which demonstrated that a post-treatment structured exercise program is both feasible and effective in improving disease-free survival in this patient group. The study was performed over a long period of time and in many respects is quite remarkable. So, I wonder if you could give us your thoughts about this study and whether you think that this means that our futures are going to be full of structured exercise programs for those patients who may benefit. Dr. Hamilton: It's a fantastic question. I think that this abstract did create a lot of buzz. We were very excited when we read it. It was highlighted in one of the Clinical Science Symposium sessions. But briefly, this was a phase 3 randomized trial. It was conducted at 55 centers, so really a broad experience, and patients that had resected colon cancer who completed adjuvant therapy were allowed to participate. There were essentially 2 groups: a structured exercise program, called ‘the exercise group,' or health education materials alone, so that was called just ‘the health education group.' And this was a 3-year intervention, so very high quality. The primary end point, as you mentioned, was disease-free survival. This actually accrued from 2009 to 2024, so quite a lift, and almost 900 patients underwent randomization to the exercise group or the health education group. And at almost 8 years of follow-up, we saw that the disease-free survival was significantly longer in the exercise group than the health education group. This was essentially 80.3% of patients were disease-free in exercise and 73.9% in the health education group. So a difference of over 6 percentage points, which, you know, at least in the breast cancer world, we make decisions about whether to do chemotherapy or not based on these kind of data. We also looked at overall survival in the exercise group and health education group, and the 8-year overall survival was 90.3% in the exercise group and 83.2% in the health education group. So this was a difference of 7.1%. Still statistically significant. I think this was really a fantastic effort over more than a decade at over 50 institutions with almost 900 patients, really done in a very systematic, high-intervention way that showed a fantastic result. Absolutely generalizable for patients with colon cancer. We have hints in other cancers that this is beneficial, and frankly, for our patients for other comorbidities, such as cardiovascular, etc., I really think that this is an abstract that deserved the press that it received. Dr. Sweetenham: Yeah, absolutely, and it is going to be very interesting, I think, over the next 2 or 3 years to see how much impact this particular study might have on programs across the country and across the world actually, in terms of what they do in this kind of adjuvant setting for structured exercise. Dr. Hamilton: Absolutely.  So let's move on to Abstract 3006. This was an NCI-led effort comparing genomic testing using ctDNA and tissue from patients with less common cancers who were enrolled in but not eligible for a treatment arm of the NCI-MATCH trial. Tell us about your takeaways from this study. Dr. Sweetenham: Yeah, so I thought this was a really interesting study based, as you said, on NCI-MATCH. And many of the listeners will probably remember that the original NCI-MATCH study screened almost 6,000 patients to assess eligibility for those who had an actionable mutation. And it turned out that about 60% of the patients who went on to the study had less common tumors, which were defined as anything other than colon, rectum, breast, non–small cell lung cancer, or prostate cancer. And most of those patients lacked an eligible mutation of interest and so didn't get onto a trial therapy. But with a great deal of foresight, the study group had actually collected plasma samples from these patients so that they would have the opportunity to look at circulating tumor DNA profiles with the potential being that this might be another way for testing for clinically relevant mutations in some of these less common cancer types. So initially, they tested more than 2,000 patients, and to make a somewhat complicated story short, there was a subset of five histologies with a larger representation in terms of sample size. And these were cholangiocarcinoma, small cell lung cancer, esophageal cancer, pancreatic, and salivary gland cancer. And in those particular tumors, when they compared the ctDNA sequencing with the original tumor, there was a concordance there of around 84%, 85%. And in the presentation, the investigators go on to list the specific mutated genes that were identified in each of those tumors. But I think that the other compelling part of this study from my perspective was not just that concordance, which suggests that there's an opportunity there for the use of ctDNA instead of tumor biopsies in some of these situations, but what was also interesting was the fact that there were several clinically relevant mutations which were detected only in the circulating tumor DNA. And a couple of examples of those included IDH1 for cholangiocarcinoma, BRAF and p53 in several histologies, and microsatellite instability was most prevalent in small cell lung cancer in the ctDNA. So I think that what this demonstrates is that liquid biopsy is certainly a viable screening option for patients who are being assessed for matching for targeted therapies in clinical trials. The fact that some of these mutations were only seen in the ctDNA and not in the primary tumor specimen certainly suggests that there's some tumor heterogeneity. But I think that for me, the most compelling part of this study was the fact that many of these mutations were only picked up in the plasma. And so, as the authors concluded, they believe that a comprehensive gene profiling with circulating tumor DNA probably should be included as a primary screening modality in future trials of targeted therapy of this type. Dr. Hamilton: Yeah, I think that that's really interesting and mirrors a lot of data that we've been seeing. At least in breast cancer, you know, we still do a biopsy up front to make sure that our markers, we're still treating the right disease that we think we are. But it really speaks to the utility of using ctDNA for serial monitoring and the emergence of mutations. Dr. Sweetenham: Absolutely. And you mentioned breast cancer, and so I'd like to dwell on that for a moment here because obviously, there was a huge amount of exciting breast cancer data presented at the meeting this year. And in particular, I'd like to ask you about LBA1008, the DESTINY-Breast09 clinical trial, which I think has the potential to establish a new first-line standard of care for metastatic HER2+ breast cancer. And that's an area where we haven't seen a whole lot of innovation for around a decade now. So can you give us some of the highlights of this trial and what your thinking is, having seen the results? Dr. Hamilton: Yeah, absolutely. So this was a trial in the first-line metastatic HER2 setting. So this was looking at trastuzumab deruxtecan. We certainly have had no shortage of reports around this drug, initially approved for later lines. DESTINY-Breast03 brought it into our second-line setting for HER2+ disease and we're now looking at DESTINY-Breast09 in first-line. So this actually was a 3-arm trial where patients were randomized 1:1:1 against standard taxane/trastuzumab/pertuzumab in one arm; trastuzumab deruxtecan with pertuzumab in another arm; and then a third arm, trastuzumab deruxtecan alone. And what we did not see reported was that trastuzumab deruxtecan-alone arm. But we did have reports from the trastuzumab deruxtecan plus pertuzumab versus the chemo/trastuzumab/pertuzumab. And what we saw was a statistically significant improvement in median progression-free survival, 26.9 months up to 40.7, so an improvement of 13.8 months, over a year in PFS. Not to mention that we're now in the 40-month range for PFS in first-line disease. Really, across all subgroups, we really weren't able to pick out a subset of patients that did not benefit. We did see about a 12% ILD rate with trastuzumab deruxtecan. That really is on par with what we've seen in other studies, around 10%-15%. I think that this is going to become a new standard of care in the first-line. I think it did leave some unanswered questions. We saw some data from the PATINA trial this past San Antonio Breast, looking at the addition of endocrine therapy with or without a CDK4/6 inhibitor, palbociclib, for those patients that also have ER+ disease, after taxane has dropped out in the first-line setting. So how we're going to kind of merge all this together is, I suspect that there are going to be patients that we or they just don't have the appetite to continue 3 to 4 years of trastuzumab deruxtecan. And so we're probably going to be looking at a maintenance-type strategy for them, maybe integrating the PATINA data there. But how we really put this into practice in the first-line setting and if or when we think about de-escalating down from trastuzumab deruxtecan to antibody therapy are some lingering questions. Dr. Sweetenham: Okay, so certainly is going to influence practice, but watch this space for a little bit longer, it sounds as though that's what you're saying. Dr. Hamilton: Absolutely.  So let's move on to GI cancer. Abstract 4006 reported preliminary results from the randomized phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel versus the chemo gemcitabine/nab-paclitaxel alone in patients with previously untreated metastatic pancreatic cancer. Can you tell us more about this study? Dr. Sweetenham: Yeah, absolutely. As you mentioned, elraglusib is actually a first-in-class inhibitor of GSK3-beta, which has multiple potential actions in pancreatic cancer. But the drug itself may be involved in mediating drug resistance as well as in some tumor immune response modulation. Some of that's not clearly understood, I believe, right now. But certainly, preclinical data suggests that the drug may be effective in preclinical models and may also be effective in combination with chemotherapy and potentially with immune-modulating agents as well. So this particular study, as you said, was an open-label, randomized phase 2 study in which patients with pancreatic cancer were randomized 2:1 in favor of the elraglusib plus GMP—gemcitabine and nab-paclitaxel—versus the chemotherapy alone. And upon completion of the study, which is not right now, median overall survival was the primary end point, but there are a number of other end points which I'll talk about in just a moment. But the sample size was planned to be around 207 patients. The primary analysis included 155 patients in the combination arm versus 78 patients in the gemcitabine/nab-paclitaxel arm. Overall, the 1-year overall survival rate was 44.1% for the patients in the elraglusib-containing arm versus 23.0% in the patients receiving gemcitabine/nab-paclitaxel only. When they look at the median overall survival, it was 9.3 months for the experimental arm versus 7.2 months for chemotherapy alone. So put another way, there's around a 37% reduction in the risk of death with the use of this combination arm. The treatment was overall well-tolerated. There were some issues with grade 1 to 2 transient visual impairment in a large proportion of the patients. The most common treatment-related adverse effects with the elraglusib/GMP combination was transient visual impairment, which affected around 60% of the patients. Most of the more serious treatment-related adverse events included neutropenia, anemia, and fatigue in 50%, 25%, and 16% of the patients, respectively. So the early results from this study show a significant benefit for 1-year overall survival and for median overall survival with, as I mentioned above, a significant reduction in the risk of death. The authors went on to mention that the median overall survival for the control arm in this study is somewhat lower than in other comparable trials, but they think that this may be related to a more advanced disease burden in this particular study. Of interest to me was that right now: there is no apparent difference in progression-free survival between the 2 arms of this study. The authors described this as potentially indicating that this may be related in some way to immune modulation and immune effects on the tumor, which, if I'm completely honest, I don't totally understand. And so, the improvement in overall survival, as far as I can see at the moment, is not matched by an improvement in progression-free survival. So I think we probably need to wait for more time to elapse to see what happens with the study. And so, I think it certainly is an interesting study, and the results are intriguing, but I think it's probably a little early for it to actually shift the treatment paradigm in this disease. Dr. Hamilton: Fantastic. I think we've been waiting for advances in pancreatic cancer for a long time, but this, not unlike others, we learn more and then learn more we don't realize, so. Dr. Sweetenham: Right. Let's shift gears at this point and talk about a couple of other abstracts in kind of a very different space. Let's start out with symptom management for older adults with cancer. We know that undertreated symptoms are common among the older patient population, and Abstract 11002 reported on a randomized trial that demonstrated the effects of remote monitoring for older patients with cancer in terms of kind of symptoms and so on. Can you tell us a little bit about this study and whether you think this approach will potentially improve care for older patients? Dr. Hamilton: Yeah, I really liked this abstract. It was conducted through the Veterans Affairs, and it was based in California, which I'm telling you that because it's going to have a little bit of an implication later on. But essentially, adults that were 75 years or older who were Medicare Advantage beneficiaries were eligible to participate. Forty-three clinics in Southern California and Arizona, and patients were randomized either into a control group of usual clinic care alone, or an intervention group, which was usual care plus a lay health worker-led proactive telephone-based weekly symptom assessment, and this was for 12 months using the validated Edmonton Symptom Assessment System. So, there was a planned enrollment of at least 200 patients in each group. They successfully met that. And this lay health worker reviewed assessments with a physician assistant, who conducted follow-up for symptoms that changed by 2 points from a prior assessment or were rated 4 or greater. So almost a triage system to figure out who needed to be reached out to and to kind of work on symptoms. What I thought was fantastic about this was it was very representative of where it enrolled. There were actually about 50% of patients enrolled here that were Hispanic or Latinos. So some of our underserved populations and really across a wide variety of tumor types. They found that the intervention group had 53% lower odds of emergency room use, 68% lower odds of hospital use than the control group. And when they translated this to actual total cost of care, this was a savings of about $12,000 U.S. per participant and 75% lower odds of a death in an acute care facility. So I thought this was really interesting for a variety of reasons. One, certainly health care utilization and cost, but even more so, I think any of our patients would want to prevent hospitalizations and ER visits. Normally, that's not a fantastic experience having to feel poorly enough that you're in the emergency room or the hospital. And really showing in kind of concrete metrics that we were able to decrease this with this intervention. In terms of sustainability and scalability, I think the question is really the workforce to do this. Obviously, you know, this is going to take dedicated employees to have the ability to reach out to these patients, etc., but I think in value-based care, there's definitely a possibility of having reimbursement and having the funds to institute a program like this. So, definitely thought-provoking, and I hope it leads to more interventions. Dr. Sweetenham: Yeah, we've seen, over several years now, many of these studies which have looked at remote symptom monitoring and so on in this patient population, and many of them do show benefits for that in kinds of end points, not the least in this study being hospitalization and emergency room avoidance. But I think the scalability and personnel issue is a huge one, and I do wonder at some level whether we may see some AI-based platforms coming along that could actually help with this and provide interactions with these patients outside of actual real people, or at least in combination with real people. Dr. Hamilton: Yeah, that's a fantastic point.  So let's talk a little bit about clinical trials. So eligibility assessment for oncology clinical trials, or prescreening, really relies on manual review of unstructured clinical notes. It's time-consuming, it's prone to errors, and Abstract 1508 reported on the final analysis of a randomized trial that looked at the effect of human-AI teams prescreening for clinical trial eligibility versus human-only or AI-only prescreening. So give us more good news about AI. What did the study find? Dr. Sweetenham: Yeah, this is a really, a really interesting study. And of course, any of us who have ever been involved in clinical trials will know that accrual is always a problem. And I think most centers have attempted, and some quite successfully managed to develop prescreening programs so that patients are screened by a health care provider or health care worker prior to being seen in the clinic, and the clinical investigator will then already know whether they're going to be eligible for a trial or not. But as you've already said, it's a slow process. It's typically somewhat inefficient and requires a lot of time on the part of the health care workers to actually do this in a successful way. And so, this was a study from Emory University where they took three models of ways in which they could assess the accuracy of the prescreening of charts for patients who are going to be considered for clinical trials. One of these was essentially the regular way of having two research coordinators physically abstract the charts. The second one was an AI platform which would extract longitudinal EHR data. And then the third one was a combination of the two. So the AI would be augmented by the research coordinator or the other way around. As a gold standard, they had three independent oncology reviewers who went through all of these charts to provide what they regarded as being the benchmark for accuracy. In a way, it's not a surprise to me because I think that a number of other systems which have used this combination of human verification of AI-based tools, it actually ultimately concluded that the combination of the two in terms of chart accuracy was for the most part better than either one individually, either the research coordinator or the AI alone. So I'll give you just a few examples of where specifically that mattered. The human plus AI platform was more accurate in terms of tumor staging, in terms of identifying biomarker testing and biomarker results, as well as biomarker interpretation, and was also superior in terms of listing medications. There are one or two other areas where either the AI alone was somewhat more accurate, but the significant differences were very much in favor of a combination of human + AI screening of these patient charts. So, in full disclosure, this didn't save time, but what the authors reported was that there were definite efficiency gains, and presumably this would actually become even more improved once the research coordinators were somewhat more comfortable and at home with the AI tool. So, I thought it was an interesting way of trying to enhance clinical trial accrual up front by this combination of humans and technology, and I think it's going to be interesting to see if this gets adopted at other centers in the future. Dr. Hamilton: Yeah, I think it's really fascinating, all the different places that we can be using AI, and I love the takeaway that AI and humans together are better than either individually. Dr. Sweetenham: Absolutely.  Thanks once again, Dr. Hamilton, for sharing your insights with us today and for all of the incredible work you did to build a robust program. And also, congratulations on what was, I think, a really remarkable ASCO this year, one of the most exciting for some time, I think. So thank you again for that. Dr. Hamilton: Thanks so much. It was really a pleasure to work on ASCO 2025 this year. Dr. Sweetenham: And thank you to our listeners for joining us today. You'll find links to all the abstracts we discussed today in the transcript of this episode. Be sure to catch up on all of our coverage from the Annual Meeting. You can catch up on my daily reports that were published each day of the Annual Meeting, featuring the key science and innovations presented. And we'll have wrap-up episodes publishing in June, covering the full spectrum of malignancies from ASCO25. If you value the insights you hear on the ASCO Daily News Podcast, please remember 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.   More on today's speakers: Dr. John Sweetenham   Dr. Erika Hamilton @erikahamilton9   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. Erika Hamilton: Consulting or Advisory Role (Inst): Pfizer, Genentech/Roche, Lilly, Daiichi Sankyo, Mersana, AstraZeneca, Novartis, Ellipses Pharma, Olema Pharmaceuticals, Stemline Therapeutics, Tubulis, Verascity Science, Theratechnologies, Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Medical Pharma Services, Hosun Pharma, Zentalis Pharmaceuticals, Jefferies, Tempus Labs, Arvinas, Circle Pharma, Janssen, Johnson and Johnson   Research Funding (Inst): AstraZeneca, Hutchison MediPharma, OncoMed, MedImmune, Stem CentRx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Millenium, TapImmune, Inc., Lilly, Pfizer, Lilly, Pfizer, Tesaro, Boehringer Ingelheim, H3 Biomedicine, Radius Health, Acerta Pharma, Macrogenics, Abbvie, Immunomedics, Fujifilm, eFFECTOR Therapeutics, Merus, Nucana, Regeneron, Leap Therapeutics, Taiho Pharmaceuticals, EMD Serono, Daiichi Sankyo, ArQule, Syros Pharmaceuticals, Clovis Oncology, CytomX Therapeutics, InventisBio, Deciphera, Sermonix Pharmaceuticals, Zenith Epigentics, Arvinas, Harpoon, Black Diamond, Orinove, Molecular Templates, Seattle Genetics, Compugen, GI Therapeutics, Karyopharm Therapeutics, Dana-Farber Cancer Hospital, Shattuck Labs, PharmaMar, Olema Pharmaceuticals, Immunogen, Plexxikon, Amgen, Akesobio Australia, ADC Therapeutics, AtlasMedx, Aravive, Ellipses Pharma, Incyte, MabSpace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pieris Pharmaceuticals, Pionyr, Repetoire Immune Medicines, Treadwell Therapeutics, Accutar Biotech, Artios, Bliss Biopharmaceutical, Cascadian Therapeutics, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, Relay Therapeutics, Tolmar, Torque, BeiGene, Context Therapeutics, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Cullinan Oncology, Bristol-Myers Squib, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetics, Silverback Therapeutics, Stemline Therapeutics

In episode 214, host Galit Friedlander and guest Kwasi Ohene-Adu (dancer, technologist, and founder/CEO of Groovetime) get into a conversation that's part dance history, part tech-forward vision, and fully rooted in the reality of what dancers are navigating today. From street performing and coding his own programs in college to building a platform that connects dance trends, AI, and digital ownership, Kwasi shares what he's learned and where he believes the industry is headed. This episode covers everything from soft power and viral culture to how dancers can create new revenue paths without waiting on the old system to catch up. Expect stories, sharp insights, and future-focused ideas—plus a few unexpected laughs along the way. Follow Galit: Instagram - https://www.instagram.com/gogalit Website - https://www.gogalit.com/ On-Demand Workout Programs -https://galit-s-school-0397.thinkific.com/collections Learn more about investing in Groovetime by visiting https://www.startengine.com/offering/groovetime. Check out Groovetime on Instagram and TikTok. Listen to DanceSpeak on Apple Podcasts and Spotify.

In episode 213, host Galit Friedlander and guest, Gerran Reese (Beyoncé, Kaytranda, Dancing With the Stars, Nike, Monsters of Hip-Hop), deconstruct the topic of virality in the dance world, Gerran's journey from a young working dancer in PDX to becoming a sought-after teacher in LA/globally, and the deeper work of staying true to yourself in an industry that doesn't always make it easy. Follow Galit: Instagram - https://www.instagram.com/gogalit Website - https://www.gogalit.com/ On-Demand Workout Programs -https://galit-s-school-0397.thinkific.com/collections You can connect with Gerran Reese on Instagram. Listen to DanceSpeak on Apple Podcasts and Spotify.

Ask Paul Tripp is a weekly podcast resource from Paul Tripp Ministries. Each week, pastor and best-selling author Dr. Paul David Tripp answers your questions about anything and everything, connecting the transforming power of Jesus Christ to everyday life in the process. Today's question comes from a listener preparing to lead a Bible study on the Book of Revelation. She's wondering if Paul holds to a particular view of Revelation, like Idealism, Preterism, Historicism, or Futurism? And why are there so many different approaches to understanding this book in the first place?If you have a question you'd like to ask Paul, you can email ask@paultripp.com or submit it online at PaulTripp.com/Ask.Paul Tripp's 5-Minute Bible Studyhttps://www.paultripp.com/biblestudy