Podcasts about chemoradiation

Dr. Vamsi Velcheti and Dr. Nate Pennell discuss novel treatment approaches in small cell and non-small cell lung cancer that were featured at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host of the ASCO Daily News Podcast. I'm a professor of medicine and chief of hematology and oncology at the Mayo Clinic in Jacksonville, Florida. The 2025 ASCO Annual Meeting featured some exciting advancements in small cell lung cancer, targeted therapies for non-small cell lung cancer, and other novel [treatment] approaches. Today, I'm delighted to be joined by Dr. Nate Pennell to discuss some of the key abstracts that are advancing the lung cancer field. Dr. Pennell is the co-director of the Cleveland Clinic Lung Cancer Program and also the vice chair of clinical research at the Taussig Cancer Institute. Our full disclosures are available in the transcript of this episode. Nate, it's great to have you back on the podcast. Thanks so much for being here. Dr. Nate Pennell: Thanks, Vamsi. Always a pleasure. Dr. Vamsi Velcheti: Let's get started, and I think the first abstract that really caught my attention was Abstract 8516, “The Randomized Trial of Relevance of Time of Day of Immunotherapy for Progression-Free and Overall Survival in Patients With Non-Small Cell Lung Cancer.” What are your thoughts about this, Nate? Dr. Nate Pennell: I agree. I thought this was one of the most discussed abstracts, certainly in the lung cancer session, but I think even outside of lung cancer, it got some discussion. So, just to put this in perspective, there have been a number of publications that have all been remarkably consistent, and not just in lung cancer but across multiple cancer types, that immunotherapy, immune checkpoint inhibitors, are commonly used. And all of them have suggested, when looking at retrospective cohorts, that patients who receive immune checkpoint inhibitors earlier in the day – so in the morning or before the early afternoon – for whatever reason, appear to have better outcomes than those who get it later in the day, and this has been repeated. And I think many people just sort of assumed that this was some sort of strange association and that there was something fundamentally different from a prognostic standpoint in people who came in in the morning to get their treatment versus those who came later in the afternoon, and that was probably the explanation. The authors of this randomized trial actually decided to test this concept. And so, about 210 patients with previously untreated advanced non-small cell lung cancer were randomly assigned to get chemo and immune checkpoint inhibitor – either pembrolizumab or sintilimab – and half of them were randomly assigned to get the treatment before 3 PM in the afternoon, and half of them were assigned to get it after 3 PM in the afternoon. And it almost completely recapitulated what was seen in the retrospective cohorts. So, the median progression-free survival in those who got earlier treatment was 13.2 months versus only 6.5 months in those who got it later in the day. So, really enormous difference with a hazard ratio of 0.43, which was statistically significant. And perhaps even more striking, the median overall survival was not reached in the early group versus 17.8 months in the late group with a hazard ratio of 0.43, also highly statistically significant. Even the response rate was 20% higher in the early patients; 75% response rate compared to 56% in the late-time-of-day patients. So very consistent across all measures of efficacy with pretty good matched characteristics across the different groups. And so, I have to tell you, I don't know what to make of this. I certainly was a skeptic about the retrospective series, but now we have a prospective randomized trial that shows essentially the same thing. So, maybe there is a difference between getting treated in the morning, although I have yet to hear someone give a very good mechanistic explanation as to why this would be. What were your thoughts on this? Dr. Vamsi Velcheti: It's indeed fascinating, Nate, and I actually think this was a very interesting abstract. Really, I was caught off guard looking at the data. I mean, if it were a drug, we would be so excited, right? I mean, with those kind of survival benefits. I don't know. I think circadian rhythm probably has something to do with it, like different cytokine profiles at the time of administration. I mean, who knows? But I think it's a randomized trial, and I think I would expect to see a mad rush for treatment appointments early in the morning given this, and at least I want my patients to come in first thing in the morning. It'll be interesting to see. Dr. Nate Pennell: It's important to point out that in this study, everyone got chemo and immunotherapy. And, at least in our cancer center, most patients who are getting platinum-doublet chemotherapy and immunotherapy actually do get treated earlier in the day already, just because of the length of the infusion appointment that's needed. So it really is oftentimes people getting single-agent immunotherapy who are often getting the later, shorter visits. But if you have a choice, I think it would be very reasonable to have people treated earlier in the day. And I do think most of the impressions that I got from people about this is that they would like to see it reproduced but certainly well worth further investigation. And I personally would like to see more investigation into what the rationale would be for this because I still can't quite figure out, yes, if you got it at, say, you know, 5 PM, that's later in the day and I can understand that maybe your immune system is somewhat less receptive at that point than it would be in the morning. But because these checkpoint inhibitors have such long half-lives, it's still in your system the next morning when your immune system is supposedly more receptive. So I don't quite understand why that would be the case. Well, let's move on to the next study. I would like to hear your thoughts on Abstract 8515, “Plasma-Guided, Adaptive First-Line Chemoimmunotherapy for Non-Small Cell Lung Cancer.” Dr. Vamsi Velcheti: Yeah, this was another abstract that seems to be really interesting in my opinion. I think there's kind of a lot of emphasis lately on ctDNA and MRD-based assays to monitor disease. In the lung cancer space, we haven't had a lot of clinical trials looking at this prospectively, and this was one of those pilot studies where they looked at circulating free DNA (cfDNA)-based response-adaptive strategy for frontline patients who are PD-L1 positive. So, patients started with pembrolizumab monotherapy, and based on plasma molecular response after 2 cycles, those patients without response received early treatment intensification with a platinum doublet. So the approach essentially was to reduce the chemotherapy exposure in patients who respond to immunotherapy. And only about 17.5% of the patients on the trial received chemotherapy based on lack of molecular response. So, in this trial, what they found was patients with the cfDNA response had a markedly improved PFS of 16.4 months versus 4.8 months. So essentially, like, this is a really nice study to set a foundation on which we have to do larger studies to incorporate molecular markers trying to look at cfDNA response to inform treatment strategy, either escalation or de-escalation strategies. So, I thought it was a very interesting study. Dr. Nate Pennell: Yeah. I mean, we always have this question for patients, “Should they get immunotherapy alone or combined with chemo?” and I think this certainly is intriguing, suggesting that there may be ways you can monitor people and perhaps rescue those that aren't going to respond to single agent. I'd like to see a randomized trial against, you know, this strategy, perhaps against everyone getting, say, chemoimmunotherapy or make sure that you're not potentially harming people by doing this strategy. But I agree, it's time to move beyond just observing that cell-free DNA is prognostic and important and start using it to actually guide treatment. Dr. Vamsi Velcheti: Yeah, and I would just caution though, like, you know, I think we need more data, but, however, it's certainly a very interesting piece of data to kind of help inform future trials. So, there was another abstract that caught my attention, and I think this would be a very interesting abstract in the EGFR space. Abstract 8506, "Patritumab Deruxtecan (HER3-DXd) in Resistant EGFR-Mutant Advanced Non-Small Cell Lung Cancer Patients After Third-Generation EGFR TKI," it's the HERTHENA-Lung02 study. What do you think about the results of this study? Dr. Nate Pennell: Yeah, this was, I would say, very widely anticipated and ultimately a little disappointing, despite being a positive trial. So, these are patients with EGFR-mutant non-small cell lung cancer who have progressed after a third-generation EGFR TKI like osimertinib. This is really an area of major unmet need. We do have drugs like amivantamab in this space, but still definitely an area where essentially patients move from having a highly effective oral therapy to being in the realm of chemotherapy as their best option. So, this HER3 antibody-drug conjugate, patritumab deruxtecan, had some good single-arm data for this. And we're sort of hoping this would become an available option for patients. This trial was designed against platinum-doublet chemotherapy in this setting and with a primary endpoint of progression-free survival. And it actually was positive for improved progression-free survival compared to chemo with a hazard ratio of 0.77. But when you look at the medians, you can see that the median PFS was only 5.8 versus 5.4 months. It was really a modest difference between the two arms. And on the interim analysis, it appeared that there will not be a difference in overall survival between the two arms. In fact, the hazard ratio at the interim analysis was 0.98 for the two arms. So based on this, unfortunately, the company that developed the HER3-DXd has withdrawn their application to the FDA for approval of the drug, anticipating that they probably wouldn't get past approval without that overall survival endpoint. So, unfortunately, probably not, at least for the near future, going to be a new option for these patients. Dr. Vamsi Velcheti: Yeah, I think this is a space that's clearly an unmet need, and this was a big disappointment, I should say. I think all of us were going into the meeting anticipating some change in the standard of care here. Dr. Nate Pennell: Yeah, I agree. It was something that I was telling patients, honestly, that I was expecting this to be coming, and so now, definitely a bit of a disappointment. But it happens and, hopefully, it will still find perhaps a role or other drugs with a similar target. Certainly an active area. Well, let's leave the EGFR-mutant space and move into small cell. There were a couple of very impactful studies. And one of them was Abstract 8006, “Lurbinectedin Plus Atezolizumab as First-Line Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer, Primary Results from the Phase III IMforte Trial.” So, what was your impression of this? Dr. Vamsi Velcheti: Yeah, I think this is definitely an interesting study, and small cell, I remember those days when we had barely any studies of small cell at ASCO, and now we have a lot of exciting developments in the small cell space. It's really good to see. The IMforte trial is essentially like a maintenance lurbinectedin trial with atezolizumab maintenance. And the study was a positive trial. The primary endpoint was a PFS, and the study showed improvement in both PFS and OS with the addition of lurbinectedin to atezolizumab maintenance. And definitely, it's a positive trial, met its primary endpoint, but I always am a little skeptical of adding maintenance cytotoxic therapies here in this setting. In my practice, and I'd like to hear your opinion, Nate, most patients with small cell after 4 cycles of a platinum doublet, they're kind of really beaten up. Adding more cytotoxic therapy in the maintenance space is going to be tough, I think, for a lot of patients. But also, most importantly, I think this rapidly evolving landscape for patients with small cell lung cancer with multiple new, exciting agents, actually like some FDA-approved like tarlatamab, also like a lot of these emerging therapeutics like I-DXd and other ADCs in this space. You kind of wonder, is it really optimal strategy to bring on like another cytotoxic agent right after induction chemotherapy, or do you kind of delay that? Or maybe have like a different strategy in terms of maintenance. I know that the tarlatamab maintenance trial is probably going to read out at some point too. I think it's a little challenging. The hazard ratio is also 0.73. As I said, it's a positive trial, but it's just incremental benefit of adding lurbi. And also on the trial, we need to also pay attention to the post-progression second-line treatments, number of patients who received tarlatamab or any other investigational agents.  So I think it's a lot of questions still. I'm not quite sure I'd be able to embrace this completely. I think a vast majority of my patients might not be eligible anyway for cytotoxic chemotherapy maintenance right away, but yeah, it's tough. Dr. Nate Pennell: Yeah. I would call this a single and not a home run. It definitely is real. It was a real overall survival benefit. Certainly not surprising that a maintenance therapy would improve progression-free survival. We've known that for a long time in small cell, but first to really show an overall survival benefit. But I completely agree with you. I mean, many people are not going to want to continue further cytotoxics after 4 cycles of platinum-doublet chemo. So I would say, for those that are young and healthy and fly through chemo without a lot of toxicity, I think certainly something worth mentioning. The problem with small cell, of course, is that so many people get sick so quickly while on that observation period after first-line chemo that they don't make it to second-line treatment. And so, giving everyone maintenance therapy essentially ensures everyone gets that second-line treatment. But they also lose that potentially precious few months where they feel good and normal and are able to be off of treatment. So, I would say this is something where we're really going to have to kind of sit and have that shared decision-making visit with patients and decide what's meaningful to them. Dr. Vamsi Velcheti: Yeah, I agree. The next abstract that was a Late-Breaking Abstract, 8000, “Overall Survival of Neoadjuvant Nivolumab Plus Chemotherapy in Patients With Resectable Non-Small Cell Lung Cancer in CheckMate-816.” This was a highly anticipated read-out of the OS data from 816. What did you make of this abstract? Dr. Nate Pennell: Yeah, I thought this was great. Of course, CheckMate-816 changed practice a number of years ago when it first reported out. So, this was the first of the neoadjuvant or perioperative chemoimmunotherapy studies in resectable non-small cell lung cancer. So, just to review, this was a phase 3 study for patients with what we would now consider stage II or stage IIIA resectable non-small cell lung cancer. And they received three cycles of either chemotherapy or chemotherapy plus nivolumab, and that was it. That was the whole treatment. No adjuvant treatment was given afterwards. They went to resection. And patients who received the chemoimmunotherapy had a much higher pathologic complete response rate and a much better event-free survival. And based on this, this regimen was approved and, I think, at least in the United States, widely adopted.  Now, since the first presentation of CheckMate 816, there have been a number of perioperative studies that have included an adjuvant component of immunotherapy – KEYNOTE-671, the AEGEAN study – and these also have shown improved outcomes. The KEYNOTE study with pembrolizumab also with an overall survival benefit. And I think people forgot a little bit about CheckMate-816. So, this was the 5-year overall survival final analysis. And it did show a statistically and, I think, clinically meaningful difference in overall survival with the 3 cycles of neoadjuvant chemo-nivo compared to chemo with a hazard ratio of 0.72. The 5-year overall survival of 65% in the chemo-IO group versus 55% with the chemo alone. So a meaningful improvement. And interestingly, that hazard ratio of 0.72 is very similar to what was seen in the peri-operative pembro study that included the adjuvant component. So, very much still relevant for people who think that perhaps the value of those neoadjuvant treatments might be really where most of the impact comes from this type of approach. They also gave us an update on those with pathologic complete response, showing really astronomically good outcomes. If you have a pathologic complete response, which was more than a quarter of patients, the long-term survival was just phenomenal. I mean, 95% alive at 5 years if they were in that group and suggesting that in those patients at least, the adjuvant treatment may not be all that important.  So, I think this was an exciting update and still leaves very much the open question about the importance of continuing immunotherapy after surgery after the neoadjuvant component. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think the million-dollar question is: “Is there like a population of patients who don't have complete response but like maybe close to complete response?” So, would you like still consider stopping adjuvant IO? I probably would not be comfortable, but I think sometimes, you know, we all have patients who are like very apprehensive of continuing treatments. So, I think that we really need more studies, especially for those patients who don't achieve a complete CR. I think trying to find strategies for like de-escalation based on MRD or other risk factors. But we need more trials in that space to inform not just de-escalation, but there are some patients who don't respond at all to a neoadjuvant IO. So, there may be an opportunity for escalating adjuvant therapies. So, it is an interesting space to watch out for. Dr. Nate Pennell: No, absolutely. Moving to KRAS-mutant space, so our very common situation in patients with non-small cell lung cancer, we had the results of Abstract 8500, “First-Line Adagrasib With Pembrolizumab in Patients With Advanced or Metastatic KRASG12C-Mutated Non-Small Cell Lung Cancer” from the phase 2 portion of the KRYSTAL-7 study. Why was this an interesting and important study? Dr. Vamsi Velcheti: First of all, there were attempts to kind of combine KRASG12C inhibitors in the past with immune checkpoint inhibitors, notably sotorasib with pembrolizumab. Unfortunately, those trials have led to like a lot of toxicity, with increased especially liver toxicity, which was a major issue. This is a phase 2 study of adagrasib in combination with pembrolizumab, and this is a study in the frontline setting in patients with the G12C-mutant metastatic non-small cell lung cancer. And across all the PD-L1 groups, the ORR was 44%, and the median PFS was 11 months, comparable to the previous data that we have seen with adagrasib in this setting. So it's not like a major improvement in clinical efficacy. However, I think the toxicity profile that we were seeing was slightly better than the previous trials in combination with sotorasib, but you still have a fair amount of transaminitis even in the study. At this point, this is not ready for clinical primetime. I don't think we should be using sotorasib or adagrasib in the frontline or even in the second line in combination with checkpoint inhibitors. Combining these drugs with checkpoint inhibitors in the clinical practice might lead to adverse outcomes. So, we need to wait for more data like newer-generation G12C inhibitors which are also being studied in combination, so we'll have to kind of wait for more data to emerge in this space. Dr. Nate Pennell: I agree, this is not immediately practice changing. This is really an attempt to try to combine targeted treatment with immune checkpoint inhibitor. And I agree with you that, you know, it does appear to be perhaps a little bit better tolerated than some of the prior combinations that have tried in this space. The outcomes overall were not that impressive, although in the PD-L1 greater than 50%, it did have a better response rate perhaps than you would expect with either drug alone. And I do think that the company is focusing on that population for a future randomized trial, which certainly would inform this question better. But in the meantime, I agree with you, there's a lot of newer drugs that are coming along that potentially may be more active and better tolerated. And so, I'd say for now, interesting but we'll wait and see. Dr. Vamsi Velcheti: Yeah, so now moving back again to small cell. So, there was a Late-Breaking Abstract, 8008. This is a study of tarlatamab versus chemotherapy as second-line treatment for small cell lung cancer. They presented the primary analysis of the phase III DeLLphi-304 study. What do you think about this? Dr. Nate Pennell: Yeah, I thought this was really exciting. This was, I would say, perhaps the most important lung study that was presented. Tarlatamab is, of course, the anti-DLL3 bispecific T-cell engager compound, which is already FDA approved based on a prior single-arm phase II study, which showed a very nice response rate as a single agent in previously treated small cell lung cancer and relatively manageable side effects, although somewhat unique to solid tumor docs in the use of these bispecific drugs in things like cytokine release syndrome and ICANS, the neurologic toxicities. So, this trial was important because tarlatamab was approved, but there were also other chemotherapy drugs approved in the previously treated space. And so, this was a head-to-head second-line competition comparison between tarlatamab and either topotecan, lurbinectedin, or amrubicin in previously treated small cell patients with a primary endpoint of overall survival. So, a very well-designed trial. And it did show, I think, a very impressive improvement in overall survival with a median overall survival in the tarlatamab group of 13.6 months compared to 8.3 months with chemotherapy, hazard ratio of 0.6. And progression-free survival was also longer at 4.2 months versus 3.2 months, hazard ratio of 0.72. In addition to showing improvements in cancer-related symptoms that were improved in tarlatamab compared to chemotherapy, there was actually also significantly lower rates of serious treatment-related adverse events with tarlatamab compared to chemotherapy. So, you do still see the cytokine release syndrome, which is seen in most people but is manageable because these patients are admitted to the hospital for the first two cycles, as well as a significant number of patients with neurologic side effects, the so-called ICANS, which also can be treated with steroids. And so, I think based upon the very significant improvement in outcomes, I would expect that this should become our kind of standard second-line treatment since it seems to be much better than chemo. However, tarlatamab is definitely a new drug that a lot of places are not used to using, and I think a lot of cancer centers, especially ones that aren't tied to a hospital, may have questions about how to deal with the CRS. So, I'm curious your thoughts on that. Dr. Vamsi Velcheti: Yeah, thank you, Nate. And I completely agree. I think the data looked really promising, and I've already been using tarlatamab in the second-line space. The durability of response and overall, having used tarlatamab quite a bit - like, I participated in some of the early trials and also used it as standard of care - tarlatamab has unique challenges in terms of like need for hospitalization for monitoring for the first few treatments and make sure, you know, we monitor those patients for CRS and ICANS. But once you get past that initial administration and monitoring of CRS, these patients have a much better quality of life, they're off chemotherapy, and I think it's really about the logistics of actually administering tarlatamab and coordination with the hospital and administration in the outpatient setting. It's definitely challenging, but I think it definitely can be done and should be done given what we are seeing in terms of clinical efficacy here. Dr. Nate Pennell: I agree. I think hospital systems now are just going to have to find a way to be able to get this on formulary and use it because it clearly seems to be more effective and generally better tolerated by patients. So, should move forward, I think. Finally, there's an abstract I wanted to ask you about, Abstract 8001, which is the “Neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone in resectable epidermal growth factor receptor-mutated non-small cell lung cancer: The NeoADAURA Study”. And this is one that I think was also fairly highly anticipated. So, what are your thoughts? Dr. Vamsi Velcheti: You know, I wasn't probably surprised with the results, and I believe we were all expecting a positive trial, and we certainly were handed a positive trial here. It's a phase III trial of osimertinib and chemotherapy or osimertinib in the neoadjuvant space followed by surgery, followed by osimertinib. It's a global phase 3 trial and very well conducted, and patients with stage II to stage IIIB were enrolled in the study. And in the trial, patients who had a neoadjuvant osimertinib with or without chemotherapy showed a significant improvement in major pathologic response rates over chemotherapy alone. And the EFS was also positive for osimertinib and chemotherapy, osimertinib monotherapy as well compared to chemotherapy alone. So overall, the study met its primary endpoint, and I think it sheds light on how we manage our patients with early-stage lung cancer. I think osimertinib, we know that osimertinib is already FDA approved in the adjuvant space, but what we didn't really know is how was osimertinib going to work in the neoadjuvant space. And there are always situations, especially for stage III patients, where we are on the fence about, are these patients already close to being metastatic? They have, like, almost all these patients have micrometastatic disease, even if they have stage III. As we saw in the LAURA data, when you look at the control arm, it was like a very short PFS. Chemoradiation does nothing for those patients, and I think these patients have systemic mets, either gross or micrometastatic disease at onset. So, it's really important to incorporate osimertinib early in the treatment course. And I think, especially for the locally advanced patients, I think it's even more important to kind of incorporate osimertinib in the neoadjuvant space and get effective local control with surgery and treat them with adjuvant. I'm curious to hear your thoughts, Nate. Dr. Nate Pennell: I am a believer and have long been a believer in targeted adjuvant treatments, and, you know, it has always bothered me somewhat that we're using our far and away most effective systemic therapy; we wait until after they go through all their pre-op treatments, they go through surgery, then they go through chemotherapy, and then finally months later, they get their osimertinib, and it still clearly improves survival in the adjuvant setting. Why not just start the osimertinib as soon as you know that the patient has EGFR-mutant non-small cell lung cancer, and then you can move on to surgery and adjuvant treatment afterwards? And I think what was remarkable about this study is that all of these patients almost - 90% in each arm - went to surgery. So, you weren't harming them with the neoadjuvant treatment. And clearly better major pathologic response, nodal downstaging, event-free survival was better. But I don't know that this trial is ever going to show an overall survival difference between neoadjuvant versus just surgery and adjuvant treatment, given how effective the drug is in the adjuvant setting. Nonetheless, I think the data is compelling enough to consider this, certainly for our N2-positive, stage IIIA patients or a IIIB who might be otherwise surgical candidates. I think based on this, I would certainly consider that. Dr. Vamsi Velcheti: Yeah, and especially for EGFR, like even for stage IIIB patients, in the light of the LAURA study, those patients who do not do too well with chemoradiation. So you're kind of delaying effective systemic therapy, as you said, waiting for the chemoradiation to finish. So I think probably time to revisit how we kind of manage these locally advanced EGFR patients. Dr. Nate Pennell: Yep, I agree. Dr. Vamsi Velcheti: Nate, thank you so much for sharing your fantastic insights today on the ASCO Daily News Podcast. It's been an exciting ASCO again. You know, we've seen a lot of positive trials impacting our care of non-small cell lung cancer and small cell lung cancer patients. Dr. Nate Pennell: Thanks for inviting me, Vamsi. Always a pleasure to discuss these with you. Dr. Vamsi Velcheti: And thanks to our listeners for your time today. You will find links to all of the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, subscribe wherever you get your podcast. 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. Vamsi Velcheti   @VamsiVelcheti    Dr. Nathan Pennell   @n8pennell   Follow ASCO on social media:     @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn   ASCO on BlueSky   Disclosures:   Dr. Vamsi Velcheti:   Honoraria: ITeos Therapeutics   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus   Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Nathan Pennell:     Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron    Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi 

Our Editor-in-Chief Dr. Sue Yom co-hosts with Dr. Henning Willers, our journal's Biology Section Editor and Associate Professor of Radiation Oncology at Massachusetts General Hospital. Guests are Dr. Simon Powell, Chair of Memorial Sloan Kettering Cancer Center Department of Radiation Oncology, who joins us as the co-last author of a new publication, Increased synthetic cytotoxicity of combinatorial chemoradiotherapy in homologous recombination deficient tumors, and Dr. Kerstin Borkmann, Professor of Radiobiology at the University Clinic Hamburg Eppendorf and Biology Associate Editor for our journal. She is the co-author of the accompanying editorial, BRCAness identifies synthetic cytotoxicity between cisplatin and RT.

The addition of preoperative chemoradiation therapy to perioperative chemotherapy did not improve overall survival as compared with perioperative chemotherapy alone in patients with resectable gastric or gastroesophageal junction adenocarcinomas. The multi-continent, Phase III randomized TOPGEAR trial has definitively found no benefit from adding radiation before surgery in terms of overall or progression-free survival. This clear finding was reported simultaneously in the New England Journal of Medicine and at the ESMO 2024 Congress held in Barcelona, Spain. After presenting the findings , first author Trevor Leong, MD, Radiation Oncologist at the Peter McCallum Cancer Centre in Melbourne, Australia, met up with Oncology Times reporter Peter Goodwin.

Dr. Rick Greene discusses with Dr. Dana Dominguez the association of adjuvant chemoradiation in resected biliary cancer with improved overall survival compared to chemotherapy alone, as reported in her article, "Adjuvant Chemoradiation in Resected Biliary Adenocarcinoma: Evaluation of SWOG S0809 with a Large National Database.” Article: Adjuvant Chemoradiation in Resected Biliary Adenocarcinoma: Evaluation of SWOG S0809 with a Large National Database | Annals of Surgical Oncology (springer.com)

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Dr. Anuja Jhingran to discuss the role of chemotherapy following chemoradiation after radical hysterectomy. Dr. Anuja Jhingran is a Professor of Radiation Oncology specializing in gynecologic cancers. Her clinical focus includes advanced ovarian, cervical, and endometrial cancers, utilizing advanced radiation techniques to reduce toxicity. Dr. Jhingran is actively involved in research with the Radiation Therapy Oncology Group (RTOG) and Gynecologic Oncology Group (GOG), serving as the national Principal Investigator for several studies. She is passionate about women's health and works internationally to improve healthcare in developing countries.   Highlights: This study assessed the impact of adding adjuvant chemotherapy to chemoradiotherapy (CRT) in patients with high-risk early-stage cervical cancer post-radical hysterectomy.  A total of 212 patients were analyzed, with 109 receiving CRT alone and 103 receiving CRT plus chemotherapy.  The 4-year disease-free survival (DFS) was 76% for the CRT group and 77% for the CRT plus chemotherapy group (HR = 1.05, 90% CI: 0.65-1.68, p = 0.56).  Overall survival (OS) rates at 4 years were 87% for CRT and 89% for the CRT plus chemotherapy arm (HR = 0.91, 90% CI: 0.49-1.69, p = 0.40).  The addition of chemotherapy did not significantly improve DFS or OS.  

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Dr. Ann H. Klopp to discuss radiation alone vs chemoradiation in endometrial cancer recurrence. Dr. Ann H. Klopp is a Professor of Radiation Oncology at MD Anderson Cancer Center, the head of the Gynecologic Oncology Section and a physician-scientist specializing in the treatment of gynecologic cancers. Her research focuses on improving outcomes for women with gynecologic cancers by enhancing tumor directed immune response in combination with radiation therapy and using advanced techniques to increase precision of radiation treatment delivery. Highlights: NRG0238 compared chemoradiation to radiation alone for patients with locally recurrent endometrial cancer and found that the addition of chemotherapy did not improve progression-free survival. Radiation therapy is highly effective for treatment for local recurrences of endometrial cancer. The nuances of patients enrolled and treatment delivered are discussed.

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Dr. Domenica Lorusso to discuss the KEYNOTE A18 clinical trial. Dr. Domenica Lorusso, MD, PhD, directs the Gynaecological Oncology Unit at Humanitas Hospital, Milan, and holds a Full Professorship in Obstetrics and Gynaecology at Humanitas University, Rozzano, Milan. She has led/participated in approximately 250 phase I-IV clinical trials. Currently overseeing more than 60 studies as Principal Investigator, Dr. Lorusso also chairs the Clinical Trials Committee of the MITO Group. She serves on the Board of Directors of the GCIG and is an active member of ENGOT, where she chairs the Gynecological Cancer Academy. Additionally, she sits on the Board of Directors of the ESGO. With around 300 international oncology publications and contributions to national and international treatment guidelines, her primary objectives are to ensure optimal patient care, foster clinical research, and advance international collaborations and education in the field.   Highlights: - Concurrent chemoradiation plus brachiterapy represent the standard of care treatment in locally advanced cervical cancer providing up to 70% 5 years OS - Modern radiotherapy technique (IMRT and VMAT) has reported to further increase OS and reduce toxicity  - Immunotherapy has reported to increase OS in advanced or recurrent cervical cancer when compared to standard treatment - Immunotherapy in combination with concurrent high quality chemoradiation in the treatment of locally advanced high risk cervical cancer further increase PFS and OS with respect to standard chemoradiotherapy and should be considered the new standard of care - The combination appears manageable and no substanciad additional toxicity has been reported

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Professor Gemma Kenter to discuss EORTC 55994. Prof. Kener is emeritus professor in gynae-oncology and was head of the department gynae-oncology in Center of Gynaecological Oncology Amsterdam (Amsterdam University Medical Center and Dutch Cancer Center). Her scientific interest concerns treatment and translational research of carcinoma of the cervix.     Highlights: In Trial EORTC 55994 we found no difference in overall survival between neoadjuvant chemotherapy followed by radical surgery and concomitant chemoradiation in case of bulky cervical cancer.  Regions in the world with a high incidence of cancer of the cervix might have poor access to radiotherapy. For patients in these centers as well as for young women who want to perceive their ovarian function, neoadjuvant chemotherapy followed by radical surgery can be a good alternative.

In de podcastserie proefschriften spreekt AIOS Interne geneeskunde dr. Tessa Steenbruggen met promovendi. In deze aflevering spreekt zij met onderzoeker Lisa van Hoogstraten over haar proefschrift, getiteld “Bladder cancer care in the Netherlands | Guidelines and practice: are they in harmony?”. Aan bod komen de resultaten verkregen uit verschillende studies binnen het BlaZiB, Blaaskankerzorg In Beeld, naar de behandeling van blaaskanker in Nederland. Lisa zal op 19 december a.s. haar proefschrift verdedigen aan de Radboud Universiteit Nijmegen.Referenties Mukherjee S. (2011). The emperor of all maladies - Siddhartha Mukherjee. Simon & Schuster. BlaZiB: Insight into bladder cancer care: study protocol of a large nationwide prospective cohort study (BlaZIB) | BMC Cancer | Full Text (biomedcentral.com) Neoadjuvante behandeling blaaskanker: Low adherence to recommended use of neoadjuvant chemotherapy for muscle-invasive bladder cancer | World Journal of Urology (springer.com) Blaassparende behandelingen: Chemoradiation for muscle-invasive bladder cancer using 5-fluorouracil versus capecitabine: A nationwide cohort study - ClinicalKey

Oncologist Yee Pei Song and editor Mike Leveridge talk about bladder cancer, and how chemoradiotherapy can help preserve the bladder.

Dr Katz discusses the implications of a recently published phase 2 study investigating neoadjuvant mFOLFIRINOX with or without hypofractionated radiation therapy results for patients with borderline resectable pancreatic ductal adenocarcinoma.

A new research paper was published in Oncotarget on July 28, 2022, entitled, “Chemoradiation-induced alteration of programmed death-ligand 1, CD8+ tumor-infiltrating lymphocytes and mucin expression in rectal cancer.” DNA damage and resulting neoantigen formation is considered a mechanism for synergy between radiotherapy and PD-1/PD-L1 pathway inhibition to induce antitumor immune response. In a new research study, by Marina Baretti, Qingfeng Zhu, Wei Fu, Jeffrey Meyer, Hao Wang, Robert A. Anders, and Nilofer S. Azad from Johns Hopkins University School of Medicine, researchers investigated neoadjuvant chemoradiotherapy (nCRT)-induced changes in CD8+ tumor infiltrating lymphocyte, PD-L1 and mucin expression in rectal cancer patients. “The synergistic effects of CRT and PD-1/PD-L1 immunotherapy has been supported by several retrospective analyses in different cancer types, including esophageal cancer, bladder cancer, and lung cancer also support[ed] [14, 21, 22]. However, the role of nCRT to interact synergistically with immune checkpoint inhibitor treatment to improve tumor control in rectal cancer remains uncertain.” Full press release - https://www.oncotarget.com/news/pr/oncotarget-chemoradiation-induced-alteration-of-programmed-death-ligand-cd-tumor-infiltrating-lymphocytes-and-mucin-expression-in-rectal-cancer/ DOI: https://doi.org/10.18632/oncotarget.28255 Correspondence to: Marina Baretti – Email: mbarett1@jh.edu Keywords: programmed death ligand 1, tumor-infiltrating lymphocytes, immune checkpoints, colorectal cancer, neoadjuvant chemoradiotherapy About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com

July 15, 2022 RJ podcast: Who Rescues Who? Lung Cancer Hypofractionation and Proton Therapy. The latest podcast by Sue Yom, MD, Editor-in-Chief of the International Journal of Radiation Oncology, Biology, Physics addresses the status of hypofractionation in radiation therapy for locoregonally advanced lung cancer. Articles discussed include Hoppe et al.'s article "Chemoradiation with Hypofractionated Proton Therapy in Stage II-III Non-Small Cell Lung Cancer: A Proton Collaborative Group Phase 2 Trial", Contreras et al.'s article "Phase I Study of Accelerated Hypofractionated Proton Therapy and Chemotherapy for Locally Advanced Non Small Cell Lung Cancer", and Brownstein and Salama's editorial, "Moderately Hypofractionated Proton Beam Therapy for Locally Advanced Non-Small Cell Lung Cancer: A New Way Forward for Dose Escalation?" which is available in the July 15, 2022 issue.

Rick Greene, MD, and Nicole Lopez, MD, discuss a watch and wait approach to treating rectal cancer with complete clinical response after neoadjuvant therapy, which reduces overall costs and increases effectiveness compared with radical resection. Dr. Lopez is author of, “Cost Effectiveness of Watch and Wait Versus Resection in Rectal Cancer Patients with Complete Clinical Response to Neoadjuvant Chemoradiation.” Dr. Lopez is Director of the UC San Diego National Accreditation Program for Rectal Cancer (NAPRC), and is an Associate Professor of Surgery at UC San Diego Health, San Diego, CA.

Commentary by Dr. Bonnie Ky

This podcast highlights original research published in the October 2021 issue of Otolaryngology–Head and Neck Surgery, the official journal of the American Academy of Otolaryngology—Head and Neck Surgery (AAO-HNS) Foundation. Pathologic extranodal extension (ENE) is an important adverse feature for human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC), but the prognostic significance of microscopic ENE (ENEmi) and role of adjuvant concurrent chemoradiation (CRT) for ENEmi remain unclear. This study evaluates (1) the prognostic significance of ENEmi in HPV-negative HNSCC and (2) whether adjuvant CRT is associated with improved overall survival (OS) for these patients. In conclusion, for patients with HPV-negative HNSCC, pN+ with ENEmi is associated with worse OS than pN+ without ENE. However, for patients with ENEmi, concurrent CRT is not associated with improved OS relative to RT. The optimal adjuvant paradigm for ENEmi requires additional investigation.   Click here to read the full article.

Listen to a soundcast of the February 22nd 2021 FDA approval of Libtayo (cemiplimab-rwlc) for first-line treatment of patients with advanced NSCLC (locally advanced who are not candidates for surgical resection or definitive chemoradiation or metastatic) whose tumors have high PD-L1 expression

In this episode of the IJGC podcast, Editor-in-Chief, Dr. Pedro Ramirez, is joined by Dr. Simone Marnitz-Schulze and Dr. Christhardt Köhler to discuss the outcomes of UTERUS-11 Trial. Drs. Marnitz-Schulze and Köhler are authors of “Surgical versus Clinical Staging prior to primary Chemoradiation in Patients with Cervical Cancer FIGO Stages IIB-IVA: Oncologic Results of a Prospective Randomized International Multicentre (Uterus-11) Intergroup Study,” which is the Lead Article of the December 2020 issue of the International Journal of Gynecological Cancer. Highlights: -Surgical staging prior to chemoradiation in locally advanced cervical cancer is safe, feasible, does not delay chemoradiation -Lead to an upstaging in 33% of the patients -Resulted into a statistically significant improvement of DFS in FIGO stage IIB patients -Resulted into a trend for improved OS and DFS for all subgroups -Because of high rates of distant metastases, systemic treatment has to be intensified

Host: Jennifer Caudle, DO Guest: Kristin Higgins, MD Concurrent chemoradiation therapy is the recommended treatment for unresectable Stage III NSCLC patients. Dr. Jennifer Caudle is joined by Dr. Kristin Higgins to discuss advances in radiation that optimize the treatment plan and her best practices to help patients receive a full course of curative-intent treatment. US-32345 Last Updated 12/19

Host: Jennifer Caudle, DO Guest: Kristin Higgins, MD Concurrent chemoradiation therapy is the recommended treatment for unresectable Stage III NSCLC patients. Dr. Jennifer Caudle is joined by Dr. Kristin Higgins to discuss advances in radiation that optimize the treatment plan and her best practices to help patients receive a full course of curative-intent treatment. US-32345 Last Updated 12/19

Host: Jennifer Caudle, DO Guest: Kristin Higgins, MD Concurrent chemoradiation therapy is the recommended treatment for unresectable Stage III NSCLC patients. Dr. Jennifer Caudle is joined by Dr. Kristin Higgins to discuss advances in radiation that optimize the treatment plan and her best practices to help patients receive a full course of curative-intent treatment. US-32345 Last Updated 12/19

Pablo Kelly is a long term survivor of a glioblastoma multiforme brain tumour. Here we discuss how and why he decided to attempt to manage his disease with the aid of metabolic therapies.

Dr. Rick Greene and Dr. Basem Azab discuss the relationship of the interval between neoadjuvant chemoradiation-to-surgery in the treatment of esophageal cancer, and associated pathological complete response rate and overall survival rate. Dr. Azab is author of the Annals of Surgical Oncology article “Impact of Chemoradiation-to-Surgery Interval on Pathological Complete Response and Short- and Long-Term Overall Survival in Esophageal Cancer Patients.” Dr. Azab is a surgical oncology specialist at Sentara Healthcare, Newport News, VA.  His clinical expertise includes but is not limited to Esophageal Cancer, Endocrine Tumors, Gastrointestinal Oncology, Hepatobiliary Tumors.

GreenRanger has a packed episode of The Duel Assessment Podcast. This episode goes over the entire miniBOX, Lords of Shining, new cards from Duelist Chronicles, the new Extra Deck +, as well as the latest esports from Duel Links Meta. The question of the week discusses whether the current Ranked Duels is worth play at […]

Prof Corry talks to ecancertv at IAOO 2015 about chemoradiation in head and neck cancer and the difference in survival outcomes from big centres compared to small ones. She also notes the need for investigator-driven trials which look into aspects of treatment that are not a pharmaceutical company's top priority.

Prof Özsahin talks to ecancertv at IAOO 2015 about his work looking at chemoradiotherapy versus radiotherapy in head and neck cancer.

Dr Ridge talks to ecancertv at IAOO 2015 about the role of induction chemotherapy and concurrent chemoradiation in treating unresectable head and neck cancer. He also discusses his therapy and treatment recommendations for doctors.

Prof Perry talks to ecancertv at ASCO 2016 about a phase III randomised controlled trial of short-course radiotherapy with or without concomitant and adjuvant temozolomide in elderly patients with glioblastoma.

Dr. Nasser Hanna, Indiana University Health, discusses the possible role of immunotherapy in locally advanced NSCLC.

Dr. Nasser Hanna, Indiana University Health, discusses the possible role of immunotherapy in locally advanced NSCLC.

Dr. Nasser Hanna, Indiana University Health, discusses the possible role of immunotherapy in locally advanced NSCLC.

Dr. Nasser Hanna, Indiana University Health, lists chemo regiments appropriate for use with radiation in locally advanced NSCLC.

Dr. Nasser Hanna, Indiana University Health, lists chemo regiments appropriate for use with radiation in locally advanced NSCLC.

Dr. Nasser Hanna, Indiana University Health, lists chemo regiments appropriate for use with radiation in locally advanced NSCLC.

Dr. Nasser Hanna, Indiana University Health, reviews efforts to utilize targeted therapies as consolidation after chemoradiation in locally advanced NSCLC.

Dr. Nasser Hanna, Indiana University Health, reviews efforts to utilize targeted therapies as consolidation after chemoradiation in locally advanced NSCLC.

Dr. Nasser Hanna, Indiana University Health, reviews efforts to utilize targeted therapies as consolidation after chemoradiation in locally advanced NSCLC.

Dr. Nasser Hanna, Indiana University Health, considers the use of induction or consolidation chemotherapy for unresectable stage III NSCLC.

Dr. Nasser Hanna, Indiana University Health, considers the use of induction or consolidation chemotherapy for unresectable stage III NSCLC.

Dr. Nasser Hanna, Indiana University Health, considers the use of induction or consolidation chemotherapy for unresectable stage III NSCLC.

Dr. Nasser Hanna, Indiana University Health, discusses the development of chemoradiation as a standard of care for unresectable stage III NSCLC.

Dr. Nasser Hanna, Indiana University Health, discusses the development of chemoradiation as a standard of care for unresectable stage III NSCLC.

Dr. Nasser Hanna, Indiana University Health, discusses the development of chemoradiation as a standard of care for unresectable stage III NSCLC.

Dr. Mark Socinski, University of Pittsburgh Medical Center, discusses the benefits of giving two additional cycles of chemotherapy in combination with radiotherapy for stage III NSCLC.

Dr. Mark Socinski, University of Pittsburgh Medical Center, discusses the benefits of giving two additional cycles of chemotherapy in combination with radiotherapy for stage III NSCLC.

Dr. Mark Socinski, University of Pittsburgh Medical Center, discusses the benefits of giving two additional cycles of chemotherapy in combination with radiotherapy for stage III NSCLC.

Dr. Mark Socinski, University of Pittsburgh Medical Center, describes strategies for treatment of the elderly and frail patient with locally advanced NSCLC.

Dr. Mark Socinski, University of Pittsburgh Medical Center, describes strategies for treatment of the elderly and frail patient with locally advanced NSCLC.

Dr. Mark Socinski, University of Pittsburgh Medical Center, describes strategies for treatment of the elderly and frail patient with locally advanced NSCLC.

Dr. Mark Socinski, University of Pittsburgh Medical Center, compares the use of chemotherapy to chemo/radiation in the preoperative setting in stage IIIA lung cancer.