Podcasts about southwest oncology group

JCO PO author Dr. David R. Gandara at UC Davis Comprehensive Cancer Center, shares insights into his JCO PO article, “Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer,” one of the Top Articles of 2024. Host Dr. Rafeh Naqash and Dr. Gandara discuss how the PROphet® blood test supports first-line immunotherapy treatment decisions for metastatic NSCLC patients. TRANSCRIPT  Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations where we bring you engaging conversations with authors of clinically relevant and highly significant JCOPO articles. I'm your host, Dr. Rafeh Naqash, Podcast Editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma.  Today, we are absolutely thrilled to be joined by Dr. David R. Gandara, Professor of Medicine Emeritus, Co-Director of the Center for Experimental Therapeutics and Cancer and Senior Advisor to the Director at UC Davis Comprehensive Cancer Center and also the senior author of the JCO Precision Oncology article entitled “Plasma Proteome–Based Test for First-Line Treatment Selection in Metastatic Non–Small Cell Lung Cancer.” This was one of the top performing articles of 2024, which is one of the reasons why we wanted to bring it in for a podcast discussion. At the time of this recording, our guest's disclosures will be linked in the transcript.  David, it is an absolute pleasure to have you today. For somebody like you who's led the field of lung cancer over the years, I'm really excited that you are going to be talking to us about this very interesting article, especially given that I think you're one of the big proponents of liquid biopsies and plasma-based testing. So, for the sake of our listeners - which comprises of academic oncologists, community oncologists, trainees - could you tell us where the biomarker landscape for non-small cell lung cancer is currently, and then we can try to take a deeper dive into this article. Dr. David Gandar: Okay. Well, thank you, Rafeh. It's a pleasure to be with you here today. And I think the current landscape for biomarkers for immunotherapy in non-small cell lung cancer is a mess. There's no better way to describe it. That makes this paper describing a new plasma proteomic assay even more important. So I'll just give you a perspective. There are 14 trials, phase three trials, that were done in first line non-small cell lung cancer advanced stage of immunotherapy versus chemotherapy and some other aspects, although they vary tremendously. Some of them were checkpoint monotherapy, some combined with chemotherapy, some combined with CTLA-4 inhibitors and so forth. 12 out of the 14 were positive, 12 got FDA approval. So there are 12 different options that an oncologist could use. Some of them were squamous cell only, some non-squamous, some used PD-L1 as a biomarker driven part of the study. Some used TMB, tumor mutational burden, some were agnostic. So when you put all of this together, an oncologist can pick and choose among all these various regimens. And by and large, it's PD-L1 that is the therapeutic decision maker.  ASCO actually, I think, has done the very best job of making a guideline, and it's, as you well know, called a living guideline, it's dynamic. And it is much easier to interpret, for me and I think for oncologists, than some of the other guidelines. It's got a green light and a red light, it may be kind of orange. And so the green light means this is a strong recommendation by the guideline committee. The orange means it's weak. For this purpose, non-small cell lung cancer, advanced stage, only a very few of the recommendations were green. It's mainly monotherapy and patients with cancers with a PD-L1 over 50%. In our surveys, at our meetings, less than 50% of oncologists in the United States are following these guidelines. Why? Because they don't trust the biomarker. And TMB has the same sort of limitations. They're not bad biomarkers, they're incomplete. They're only looking at a part of the story. So that means we need a new biomarker. And this is one that, I think, the data are quite impressive and we'll discuss it more. Dr. Rafeh Naqash: Absolutely. Like you said, abundance of many therapy options, but not necessarily everything works the same in different subsets of PD-L1 positivity or different subsets of patients with different levels of tumor burden. And like you said, again, difficulty in trying to identify the right biomarker. And that's a nice segue to this PROphet test that you guys ran. So can you tell us a little bit about the plasma proteomic assay? Because to the best of my knowledge, there's not a lot of validated plasma proteomic assays. A lot has been done on the tumor tissue side as far as biomarkers are concerned, but not much on the blood side, except for maybe ctDNA MRD testing. So what was the background for trying to develop a plasma-based proteomic test? And then how did this idea of testing it in the lung cancer setting come into play? And then we can go into the patient population specifics, the cohort that you guys have. Dr. David Gandara: Okay. Well, of course there's a company behind this assay, it's called OncoHost, and I'm a consultant for them. And they came to me two years ago and they said, “We have something different from anyone else.” And they explained the science to me, as well as some other lung cancer experts here in the United States. I'm not a proteomic expert, of course, but they developed an AI machine learning platform to assess plasma proteins in normal people and in people with cancer, and specifically then in people with non-small cell lung cancer. They identified over 7,000 proteins that had cancer implications for therapy, for resistance, for prognosis, etc., and they categorized them based on the literature, TCGA data, etc., and used this machine learning process to figure out which proteins might be most specific for non-small cell lung cancer. And that's where they started. And so out of that 7,000 proteins, where they've identified which ones are angiogenic, which ones are involved with EMT or cell cycle or whatever it might be, they distilled it down to 388 proteins which they thought were worth testing in non-small cell lung cancer. And that's when I became involved.  They had a retrospective cohort of patients that had been treated with various immunotherapies. They looked at the analytic validation first, then applied it to this cohort. It looked good. Then they had a very large cohort, which they split, as you usually do with an assay, into a test set and then a validation set. For the test set, they wanted something more than a response. They wanted some indicator of long term benefit because that's where immunotherapy differentiates itself from chemotherapy and even targeted therapy. And so they picked PFS at 12 months. And I became involved at that point and it looked really good. I mean, if you look at the figures in the manuscript, the AUC is superb about their prediction and then what actually happened in the patient. And then in this paper, we applied it to a validation set of over 500 patients in a prospective trial, not randomized, it's called an observational trial. The investigator got to pick what they thought was the best therapy for that patient. And then in a blinded fashion, the proteomic assay experts did the analysis and applied it to the group.  And so what that means is some of the patients got chemotherapy alone, some got checkpoint immunotherapy monotherapy, some got in combination with chemotherapy. None of the patients in this study got a CTLA-4 inhibitor. That work is ongoing now. But what the study showed was that this assay can be used together with PD-L1 as what I would call a composite biomarker. You take the two together and it informs the oncologist about the meaning of that PD-L1. I'll give you an example. If that patient has a PD-L1 over 50% in their cancer and yet the PROphet test is negative, meaning less than 5 - it's a 0 to 10 scale - that patient for survival is better served by getting chemotherapy and immunotherapy. However, if the PROphet test is positive and the PD-L1 is over 50%, then the survival curves really look equivalent. As I said earlier, even in that group of patients, a lot of oncologists are reluctant to give them monotherapy. So if you have a test and the same sort of example is true for PD-L1 0, that you can differentiate. So this can really help inform the oncologist about what direction to go. And of course then you use your clinical judgment, you look at what you think of as the aggressiveness of the tumor or their liver metastases, etc. So again, that's how this test is being used for non-small cell lung cancer. And maybe I'll stop there and then I'll come back and add some other points. Dr. Rafeh Naqash: I definitely like your analogy of this therapy de-escalation strategy. Like you mentioned for PD-L1 high where the PROphet test is negative, then perhaps you could just go with immunotherapy alone. In fact, interestingly enough, I was invited to a talk at SITC a couple of weeks back and this exact figure that you're referring to was one of the figures in my slide deck. And it happened by chance that I realized that we were doing a podcast on the same paper today.  So I guess from a provocative question standpoint, when you look at the PD-L1 high cohort in the subset where you didn't see a survival difference for chemo plus immunotherapy versus immunotherapy alone, do you think any element of that could have been influenced by the degree of PD-L1 positivity above 50%? Meaning could there have been a cohort that is, let's say PD-L1 75 and above, and that kind of skews the data because I know you've published on this yourself also where the higher the PD-L1 above 50%, like 90% PD-L1 positivity survival curves are much better than 50% to 89%. So could that have somehow played a role? Dr. David Gandara: The first thing to say is that PD-L1 and the PROphet score, there's very little overlap. I know that sounds surprising, but it's also true for tumor mutational burden. There's very little overlap. They're measuring different things. The PD-L1 is measuring a specific regulatory protein that is applicable to some patients, but not all. That's why even in almost all of the studies, people with PD-L1 0 could still have some survival benefit. But in this case they're independent. And not in this paper, but in other work done by this group, the PROphet group, they've shown that the PROphet score does not seem to correlate with super high PD-L1. So it's not like the cemiplimab data where if you have a PD-L1 of greater than 90%, then of course the patient does spectacularly with monotherapy. The other thing that's important here is they had a group of around a little less than 100 patients that got chemotherapy alone. The PROphet score is agnostic to chemotherapy. And so that means that you're not just looking at some prognostic factor. It's actually clinical utility on a predictive basis. Dr. Rafeh Naqash: I think those are very important points. I was on a podcast a couple of days back. I think there's a theme these days we're trying to do for JCO Precision Oncology, we're trying to do a few biomarker based podcasts, and the most recent one that we did was using a tissue transcriptome with ctDNA MRD and you mentioned the composite of the PD-L1 and the PROphet test and they use a composite of the tissue transcriptome. I believe they called it the VIGex test as well as MRD ctDNA. And when your ctDNA was negative at, I believe, the three month mark, those individuals had the highest inflamed VIGex test or highest infiltration of T cells, STING pathway, etc. So are there any thoughts of trying to add or correlate tissue based biomarkers or ctDNA based correlations as a further validation in this research with the company? Dr. David Gandara: Right. So there are many things that are being looked at, various composites looking at the commutations that might affect the efficacy of immunotherapy and how they correlate with profit positivity or negativity. And I'll just give the examples of STK11 and KEAP1. As you know, there's some controversy about whether these are for immunotherapy, whether they're more prognostic or predictive. I'm one of the co-authors among many in the recently published Nature paper by Dr. Skoulidis and the group at MD Anderson which report that for KEAP1 positive especially, but also SDK11 mutated getting immunotherapy, that that's where the CTLA-4 inhibitors actually play the greatest role. So realizing that this is still controversial, there are preliminary data, not published yet, that'll be presented at an upcoming meeting, looking at many of these other aspects, P53, SCK11, KEAP1, other aspects, TMB, that's actually already published, I think in one of their papers. So yes, there's lots of opportunities.  The other cool thing is that this isn't a test, it's a platform. And so that means that the OncoHost scientists have already said, “What if we look at this test, the assay in a group of patients with small cell lung cancer?” And so I just presented this as a poster at the world conference in San Diego. And it turns out if you look at the biology of small cell, where neither PD-L1 nor TMB seem to be very important, if you look at the biology of small cell and you form an assay, it only shares 44 proteins out of the 388 with non-small cell. It's a different biology. And when we applied that to a group of patients with small cell lung cancer, again it had really pretty impressive results, although still a fairly small number of patients. So we have a big phase three study that we're doing with a pharmaceutical company developing immunotherapy where we are prospectively placing the PROphet test in a small cell trial.  The platform can also be altered for other cancer types. And at AACR, Dr. Jarushka Naidoo presented really impressive data that you can modify the proteins and you can predict immunotherapy side effects. So this is not like a company that says, “We have one test that's great for everything.” You know how some companies say, “Our test, you can use it for everything.” This company is saying we can alter the protein structures using AI machine learning assisted process to do it and we can have a very informed assay in different tumor types and different situations. So to me, it's really exciting. Dr. Rafeh Naqash: Definitely to me, I think, combining the AI machine learning aspect with the possibility of finding or trying to find a composite biomarker using less invasive approaches such as plasma or blood, definitely checks a lot of boxes. And as you mentioned, trying to get it to prospective trials as an integral biomarker perhaps would be likely the next step. And hopefully we see some interesting, exciting results where we can try to match or stratify patients into optimal combination therapies based on this test.  So now to the next aspect of this discussion, David, which I'm really excited about. You've been a leader and a mentor to many. You've led ISLC and several other corporate group organizations, et cetera. Can you tell us, for the sake of all the listeners, junior investigators, trainees, what being a mentor has meant for you? How your career has started many years back and how it's evolved? And what are some of the things that you want to tell people for a successful and a more exciting career as you've led over the years? Dr. David Gandara: Well, thank you for the question. Mentoring is a very important part of my own career. I didn't have an institutional mentor when I was a junior investigator, but I had a lot of senior collaborators, very famous people that kind of took me under their wing and guided me. And I thought when I basically establish myself, I want to give back by being a mentor to other people. And you wouldn't believe the number of people that I'm even mentoring today. And some of them are not medical oncologists, they're surgeons, they're radiation oncologists, they're basic scientists. Because you don't have to be an expert in that person's field to be a mentor. It helps, but in other words, you can guide somebody in what are the decision making processes in your career. When is it time to move from this institution onward because you can't grow in the institution you're in, either because it's too big or it's too small? So I established a leadership academy in the Southwest Oncology Group, SWOG. I've led many mentoring courses, for instance, for ISLC, now for International Society Liquid Biopsy, where I'm the executive committee liaison for what's called The Young Committee. So ISLB Society, totally devoted to liquid biopsy, six years old now, we have a Young Committee that has a budget. They develop projects, they publish articles on their own, they do podcasts. So what I'm saying is those are all things that I think opens up opportunities. They're not waiting behind senior people, they are leading themselves.  We just, at our International Lung Cancer Congress, reestablished a fellows program where a group of fellows are invited to that Huntington beach meeting. It's now in its 25th year and we spend a day and a half with them, mentoring them on career building. I'll just give you my first, I have the “Letterman Top 10”. So my first recommendation is if all you have is lemons, make lemonade. And what I'm meaning is find what you can do at your institution if you're a junior person, what you can claim to be your own and make the very best of it. But then as you get further along in my recommendations, one of them is learn when to say ‘no'. Because as a junior investigator the biggest threat to your career is saying ‘yes' to everybody and then you become overwhelmed and you can't concentrate. So I'll stop there. But anyway, yes, mentoring is a big part of my life. Dr. Rafeh Naqash: Well, thank you, David. This is definitely something that I'm going to try to apply to my career as well. And this has been an absolute pleasure, especially with all the insights that you provided, not just on the scientific side but also on the personal career side and the mentorship side. And hopefully we'll see more of this work that you and other investigators have led and collaborated on. perhaps more interesting plasma based biomarkers. And hopefully some of that work will find its home in JCO Precision Oncology. Thank you again for joining us today. Dr. David Gandara: My pleasure. Dr. Rafeh Naqash: And thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts.   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.   Dr. David Gandara Disclosures: Consulting or Advisory Role Company: Henlius USA, Foundation Medicine, Janssen Pharma, Merck & Co, Mirati Therapeutics, Regeneron, AstraZeneca, Guardant Health, Genentech, Exact Sciences  Research Funding Company: Amgen, Genentech, Astex Pharma  

“AYAs are underrepresented in clinical trials and unfortunately have one of the highest rates of being uninsured of any population. So, this is really concerning for a lot of reasons and really impacts our ability to make a difference for their treatment and outcomes,” Stacy Whiteside, APRN, MS, CPNP-AC/PC, CPON®, nurse practitioner and fertility patient navigator in the Department of Hematology, Oncology, and Blood and Marrow Transplant at Nationwide Children's Hospital in Columbus, OH, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a discussion about increasing AYA enrollment in clinical trials. Whiteside is also the nursing representative for the Children's Oncology Group (COG) AYA Committee.  You can earn free NCPD contact hours after listening to this episode and completing the evaluation linked below.   Music Credit: “Fireflies and Stardust” by Kevin MacLeod  Licensed under Creative Commons by Attribution 3.0  Earn 0.75 contact hours of nursing continuing professional development (NCPD), which may be applied to the nursing practice, oncology nursing practice, care of the pediatric hematology and oncology patient, or pediatric hematology and oncology nursing practice ILNA categories, by listening to the full recording and completing an evaluation at myoutcomes.ons.org by January 12, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of NCPD by the American Nurses Credentialing Center's Commission on Accreditation.  Learning outcome: The learner will report an increase in knowledge of clinical trial treatment barriers in adolescents and young adults with cancer.  Episode Notes  Complete this evaluation for free NCPD.   Oncology Nursing Podcast:  Episode 9: How to Support Adolescent and Young Adult Patients With Cancer  Episode 19: The Practical Side of Clinical Trials  Episode 126: Oncology Clinical Trials and Drug Development  Episode 260: Diversity in Cancer Clinical Trials  Episode 276: Support Young Families During a Parent's Cancer Journey  ONS Voice articles:   Balance Hope and Quality of Life for Phase I Clinical Trials  Help Patients Understand Biomarker Test Results and Clinical Trials Options  Nursing Roles in Clinical Trials  Use ClinicalTrials.gov to Find the Right Cancer Research Studies for Your Patients  Clinical Journal of Oncology Nursing articles:   Cancer Clinical Trials: Improving Awareness and Access for Minority and Medically Underserved Communities  Community-Based Clinical Trials: The Role of Nurses in Increasing Enrollment  Disparity of Equitable Representation in Cancer Clinical Trials: Nursing Perspectives  Oncology Nursing Forum article:  Examining Participation Disparities in Cancer Clinical Trials  Perceptions of Clinical Trial Participation Among Women of Varying Health Literacy Levels  Treatment Decision-Making Involvement in Adolescents and Young Adults With Cancer  Clinical Trials ONS Huddle Card  National Cancer Institute's (NCI's) National Clinical Trials Network  National Library of Medicine: Clinical Trials  NCI's Community Oncology Research Program  Children's Oncology Group (COG)  SWOG Cancer Research Network: Clinical Trials  Journal of Clinical Oncology articles about COG and SWOG:   The Children's Oncology Group (COG) Adolescent and Young Adult (AYA) Responsible Investigator Network: An Initiative for Advancing AYA Cancer Research in the National Clinical Trials Network  SWOG S1826, a Randomized Study of Nivolumab-AVD Versus Brentuximab Vedotin-AVD in Advanced Stage Classic Hodgkin Lymphoma  To discuss the information in this episode with other oncology nurses, visit the ONS Communities.   To find resources for creating an ONS Podcast Club in your chapter or nursing community, visit the ONS Podcast Library.  To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org.  Highlights From Today's Episode  “Of the 90,000 newly diagnosed AYA cancer patients diagnosed each year, estimates are about 3%–14% of those patients are actually enrolled on a clinical trial. We know that clinical trials are vital for studying things like disease biology, improving survival, and improving health-related quality of life outcomes for patients. And this low enrollment really limits AYAs' access to novel therapies that are coming through the pipeline and limits research to optimize their treatment protocols, specifically in this age group and can affect their overall outcomes.” TS 1:40  “You know, there's a limited availability of trials just for this age group. This age group encompasses a lot of diagnoses that just there's not a lot of patients. so things like osteosarcoma, Ewing sarcoma, some of the other rare solid tumors. We don't have open clinical trials for these disease entities, and so there's no way for AYAs to enroll. Accessibility of trials can be an issue depending on the location of where the AYAs are treated for their cancer. If they're in an adult center, they may not have access to pediatric trials they may be eligible for based on their age and the disease. And vice versa, with pediatric centers, they may not have accessibility to some adult trials that they could benefit from. Different institutions can have varying degrees of ability to actually access and enroll patients on clinical trials.” TS 2:47  “One of the benefits of the COVID pandemic has been the role of telehealth and how providers and patients can access caregivers that they may not have been able to access before because of challenges with travel and things like that. Now you can make a telehealth appointment with someone who may have information about a clinical trial and access in ways that we never had before.” TS 9:17  “And this study really was important not only from the collaborative efforts, but they really started utilizing patient-reported outcomes measures and health-related quality-of-life measures embedded within the trial itself, because we know how important hearing the patient voice is and the patient experience with how these trials affect patients. We can have the greatest trials in the world, but if it has really negative impacts on a patient's quality of life, what are we really gaining by doing that?” TS 12:57  “It really impacts patients' willingness to participate in clinical trials, understanding that we're not here to just throw things at them without a thought about what the cost is of care. We're really looking at making it tolerable and getting the best outcomes that we can. And so, patients really want to be a part of that because they want things to be better for people that come after them, and they're really invested more in the process when they are a participant and that they're a partner in the process and we're not just doing things to them.” TS 14:27  “One of the biggest things I would encourage nurses to do is become a member of your clinical trials network, whether it's the Children's Oncology Group, the Southwest Oncology Group. All of those networks have nursing members, and you get a lot of information if you're actually a member of that group. Get involved, become a member, or go through the process because it's definitely worth it. Nurses are on all clinical trials committees, so when clinical trials kind of come down the pipeline, there's a committee that helps move that forward, that helps create and implement the trial from the beginning. And nurses really have an important seat at the table with creation of clinical trials. Nurses are in the perfect position to advocate for patients and be the patient voice during the entire process.” TS 16:47  “Follow organizations on social media. Believe it or not, I learned a lot of things about clinical trials through Twitter, or X. A lot of the clinical trials networks put things out on social media about trials, about outcome, and it's a quick and easy way to flip through and just get some information that you may not see otherwise and is quicker than an Internet search.” TS 17:41  “I think there's a couple things that nurses kind of need to be aware of and thinking about AYAs. One we've alluded to a lot is that AYAs typically are in a very transitional time of life, trying to gain independence and needing support. They can have jobs, school, insurance challenges. Relationships and their peers are very important. Fertility is important. And so, there's a lot of factors that weigh in where they receive care, how they receive care, and their response to care. And so sometimes you have to dive a little bit deeper to figure out perhaps what's going on with the patient, rather than assuming that they don't come to an appointment because they don't care or they're not interested.” TS 23:38  “Taking the extra time to really go through why things are important and understand why they're not doing what they need to do and making sure there's a dialogue about why that's happening is really important. Because I think at the end of the day, most patients want their treatment to be successful. They want to kind of balance life and doing well and really will do the things that we ask. But I think the rapport and the relationship is the most important part to really getting them to do what we ask.” TS 25:43  “I think the voice of the patient is very important, and I'm thrilled that patient-reported outcomes really have become such an emphasis in clinical trials because, again, what are we doing if we're curing patients but the price of cure is too high. And I think it's important for people to understand that a caregiver's voice, while important, is not the voice of the patient.” TS 27:17  “Understand nobody knows the answer to every clinical trial question. So, it's really okay to tell a patient, ‘You know what? That's a great question, and I'm going to reach out and get that information for you. And I will circle back with you.' Patients maintain the trust that way, and they know that you're going to be honest with them and you're not going to try to make things up if you don't know the right answer. So, I think how you handle those situations, even if you don't necessarily know the answer and providing that feedback to a patient that you're going to get the answer for them, they really still maintain that trust and integrity of that relationship.” TS 32:30  “You know, it's really important to just remember every case matters. There are very few, you know, even at our institutions, when you're working on the unit and you have a full assignment of all AYA patients and it feels like AYA cancer is everywhere really across the United States and across the world, it's a very small population of cancer patients. And so, the only way we can improve outcomes is by studying the patient experience. And so, trying to get patients enrolled in clinical trials and getting them the most up-to-date, best care we can.” TS 34:52 

ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. 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. Guests' statements on this 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. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. The theme of the 2023 ASCO Annual Meeting was “Partnering With Patients: The Cornerstone of Cancer Care and Research.” From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting and explain what it means for people with cancer. In today's episode, our guests will discuss new research advances in treating non-small cell lung cancer, small cell lung cancer, and mesothelioma.  Dr. Charu Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine in Philadelphia, Pennsylvania. She is also the 2023 Cancer.Net Associate Editor for Lung Cancer. Dr. Melina Marmarelis is an assistant professor at the University of Pennsylvania, the Medical Director of the Penn Medicine Mesothelioma Program, and the co-director of the Molecular Tumor Board at the University of Pennsylvania. She is also the 2023 Cancer.Net Specialty Editor for Mesothelioma. Dr. Kristin Higgins is a radiation oncologist, Professor and Vice Chair in Clinical Research in the Department of Radiation Oncology at Emory University School of Medicine and medical director of radiation oncology of The Emory Clinic at Winship Cancer Institute's Clifton campus location. She is also a 2023 Cancer.Net Advisory Panelist for Lung Cancer. You can view disclosures for Dr. Aggarwal, Dr. Marmarelis, and Dr. Higgins at Cancer.Net. Dr. Aggarwal: Hello and welcome to this Cancer.Net Research Round Up podcast. Today, we will be talking about the latest research from the Annual Meeting of the American Society of Clinical Oncology from June 2023, and I'm joined today by 2 experts in the field of lung cancer. Before I introduce them, I'd like to introduce myself. I'm Dr. Charu Aggarwal. I'm an associate professor for lung cancer excellence at the University of Pennsylvania's Abramson Cancer Center. I'd now like to introduce Dr. Melina Marmarelis. Dr. Marmarelis: Hi, so happy to be here. I'm Melina Marmarelis. I'm an assistant professor at the University of Pennsylvania and the medical director of the Penn mesothelioma program. Dr. Aggarwal: And Dr. Kristin Higgins. Dr. Higgins: Hi, everyone. I'm Kristin Higgins. I am a thoracic radiation oncologist at Winship Cancer Institute of Emory University. I'm a professor and vice chair for clinical research for radiation oncology. Dr. Aggarwal: Fantastic. So today, we'll talk about relevant research as it applies to practical implications in the clinic for practitioners, but most importantly, patients with lung cancer. I'd like to start off by discussing 2 key studies, and I would love for perspectives from our faculty here. The first study I want to highlight is the ADAURA trial. This is a trial that has already sort of changed practice in most recent years when the study was presented at the Annual Meeting of the American Society of Clinical Oncology in 2020, but we have new updates on this study as of 2023. So, in brief, this was a study that looked at the value of administering an oral pill called osimertinib that is a tyrosine kinase inhibitor against the EGFR, or the epidermal growth factor receptor, in patients with non-small cell lung cancer. We know that non-small cell lung cancer is quite a heterogeneous disease with some subsets of patients having mutations that may render them increasingly sensitive to the effects of these tyrosine kinase inhibitors. In fact, these pills have been used in the metastatic setting for several years based on an improvement in overall survival. What the ADAURA study tried to do was ask the question if this pill would add an incremental advantage after receiving curative-intent surgical resection in those with early-stage lung cancer. So this study enrolled patients with stage IB to IIIA non-small cell lung cancer after surgical resection and focused only on those patients that had sensitizing EGFR mutations with EGFR exon 19 deletion or L858R mutations. Patients could receive chemotherapy after having the surgery and then were basically randomized into 2 groups, one of whom received osimertinib at a dose of 80 milligrams once daily for a total of 3 years. Patients were followed up for recurrence. We already know from the earlier results that patients who received osimertinib had a better chance of delaying the recurrence of disease. However, what we found at the Annual Meeting this year is that the administration of this osimertinib also improved overall survival, which is really what we all look for in the oncology world. If you're administering a therapy, especially for a long duration, we want to be able to see a survival benefit, and that's what we saw. In fact, in patients who received osimertinib, there was a 49% less likelihood of dying from lung cancer compared to those who did not receive osimertinib. This, I think, is practice-affirming. It may not be practice-changing because some of the practitioners started using osimertinib after its FDA approval in December of 2020, but I think it just confirms our practice as it delivers an overall survival advantage in these patients. One thing that's increasingly important is to identify patients who have this mutation, so now we have efforts underway locally as well as nationally to perform molecular genotyping on all patients with lung cancer so that we can adequately and appropriately treat those with early-stage lung cancer following curative resection or following surgery. Melina and Kristin, what are your thoughts? Dr. Marmarelis: Well, I think these results are really important because it did, as you say, affirm kind of what we're already doing, but I think the most convincing part of this for me is the prevention of spread of disease to the brain. This is not comparing osimertinib after surgery versus osimertinib ever, which I think is a difficult part about interpreting this trial. But I think the fact that it prevented disease from going to the brain is really meaningful to everyone, to patients, to the physicians that are caring for them, so I think that's a really important endpoint. Dr. Higgins: I agree with Melina. I think this is really exciting for our patients. It's exciting to have more treatment options for early-stage lung cancer. I think patients that are diagnosed with early-stage lung cancer are highly motivated to do everything they can to improve their likelihood of being cured. So I tend to have a lot of conversations about side effects and toxicities with patients that have questions and are sort of wondering how it will affect their quality of life, and of course, that is an important piece of it because patients that do have curable lung cancer are probably starting off with a better overall quality of life, but I think generally speaking, our patients have tolerated it well. I'm also kind of excited from a radiation oncology point of view. We treat patients with stereotactic body radiation therapy [SBRT] that are medically inoperable. And we have another trial with a cohort looking at osimertinib for those patients that have EGFR mutations, too, and that's ongoing, again, applying the same concept of trying to really use these SBRTs that work really well in the advanced setting, moving them into earlier stages of disease to help us care for more patients. So overall, I think it's really exciting, and I think it's a huge win for the clinical research community. Dr. Aggarwal: Well, that's wonderful. And I think this certainly advances the field as this is the first targeted therapy approved for patients with early-stage non-small cell lung cancer. I should add that AstraZeneca, the company that makes this drug, has provided institutional research funding to my institution, and I also serve as an advisor to them, but I was not involved personally in the research of this clinical trial. I'd like to move on but stay within the field of early-stage lung cancer and talk about another study called the KEYNOTE-671 study, and this is important because it really applies the idea of using immunotherapy before and after surgical resection in patients with early-stage lung cancer. Just to give a little bit of background to our listeners, we now have 3 approvals for the use of immunotherapy in patients with early-stage lung cancer. Two of those are in the adjuvant setting, meaning that if a patient undergoes surgical resection or surgery for early-stage lung cancer, they can receive either atezolizumab or pembrolizumab following that surgery, and that has been shown to improve outcomes in terms of reducing the chances of recurrence. We also have another approval, which is the third approval in early-stage lung cancer, where 3 cycles of chemotherapy and immunotherapy are administered prior to surgery, also called as the neoadjuvant chemo-immunotherapy approach. This drug that has been approved in combination with chemotherapy is nivolumab, and this approval came from a clinical trial called CheckMate 816 that showed both that patients who received this neoadjuvant chemo-immunotherapy approach had a higher proportion of patients who had complete response or pathologic complete response in their tumors at the time of surgery and also showed that the chances of the disease coming back after surgical resection was much lower amongst those that had received this intervention. The current study, the KEYNOTE-671 study, builds upon this concept and adds both a before-surgery intervention as well as an after-surgery intervention. So what this study did was it enrolled patients with early-stage, stage II to IIIB non-small cell lung cancer, and patients in the intervention arm received 4 cycles of chemotherapy in combination with pembrolizumab, underwent surgery, and then received immunotherapy with pembrolizumab for up to 13 cycles. Patients in the control arm received only chemotherapy prior to surgery and then placebo for up to 13 cycles after. This was a large study with about 786 patients randomized, and what we found was that those patients that received the intervention had a much higher likelihood of remaining disease-free or event-free following surgical resection as well as in the early analysis, an improvement in overall survival with about a 27% reduction in the risk of death. So I do think that this is the first study that shows us that use of both neoadjuvant as well as adjuvant. So sort of this perioperative approach of using immunotherapy before and after surgical resection can actually lead to improved outcomes. This is ultimately what we want for our patients, improvement in overall survival, improvement in cure rates, etc. The study has been silent on the use of radiation therapy, although it has gone into details in terms of the kinds of surgery that was done. Kristin, what are your views about this? Dr. Higgins: I think postoperative radiation after resection for non-small cell lung cancer has sort of started to fall out of favor because of the Lung ART trial that was published in Europe, a randomized phase III trial that showed no differences in disease-free survival or overall survival. And that's not to say that there aren't more study questions on ways to give it safer and ways to incorporate radiation in with the chemo-IO approach, and there are some novel ways to do that, and we're going to see some data presented at the World Lung Cancer Conference looking at some of those novel approaches. But standardly, when patients receive neoadjuvant chemo-immunotherapy followed by surgery, we typically would not offer radiation. There are instances, though, when patients have positive margins, for example, and in that situation, it's sort of a discussion on a case-by-case basis. But ideally, we're hoping that most of these patients that go to surgery are able to get a complete resection, and that's really the key component of the decision-making for deciding if patients are eligible for this approach. Dr. Aggarwal: I agree. Melina, any additional thoughts on this trial? Dr. Marmarelis: I think it's an exciting trial for the reasons that you mentioned. I think it does bring up a number of questions about whether both neoadjuvant and adjuvant immunotherapy are needed. I tend to like the idea of having immunotherapy present when the tumor is present before surgery, so I like kind of having that on board, but I think we still don't know which is more important. Dr. Aggarwal: So it certainly raises many more questions, which hopefully will be answered in the future. KEYNOTE-671 trial was conducted by Merck that produces the drug Keytruda, or pembrolizumab. We have received institutional research funding for other trials. I was not personally involved in this clinical trial. I do serve as an advisor for Merck. I think we'll bring you more research from the ASCO Annual Meeting. And I'll turn it over to Dr. Marmarelis to discuss some more exciting research. Dr. Marmarelis: Thanks, Charu. So perhaps it's not surprising that one of the exciting things I picked from ASCO has to do with mesothelioma. And I just want to put into context a little bit about why this trial was important. This is IND227. It was a cooperative group trial done across Canada, France, and Italy, and this was chemotherapy plus or minus pembrolizumab in patients with pleural mesothelioma that did not undergo surgery. So this was their first treatment, and they were not undergoing surgery. And the reason this trial was important is that in the last few years, we had results from CheckMate 743, which was looking at IPI/NIVO, so a combination of immunotherapies versus chemotherapy. And there was an improvement in survival for those that received double immunotherapy, and that improvement was most pronounced in the non-epithelioid population, which is actually a smaller subset of pleural mesotheliomas. And so as we've seen in the lung when we look at immunotherapy versus chemo, it raises the question of whether combination immunotherapy plus chemotherapy would actually be better for all and, in particular, for all histologies in pleural mesothelioma. So this was looking at that concept. It took the standard chemotherapy, carboplatin-pemetrexed or cisplatin-pemetrexed, and then combined it with one immunotherapy, so slightly less than the combo immunotherapy seen in CheckMate 743, and that was pembrolizumab. And what they saw was that there was a small overall survival improvement in the group that got pembrolizumab. Again, that was most pronounced in patients in the non-epithelioid group, so those with sarcomatoid or biphasic histology. And this is really a prelude to several other trials that are coming out in mesothelioma, namely the DREAM3R trial, which is looking at chemotherapy plus or minus durvalumab. That control arm also includes IPI/NIVO, so that will be really important to be able to compare those, and then also the BEAT-meso trial, which is looking at chemotherapy-immunotherapy but also with an anti-VEGF agent, bevacizumab. So I think this was an important trial. It's a little bit of proof of concept, but there's still a lot that we're looking forward to. It's not quite practice-changing in the clinic, although I think it's certainly an option that people are using, but I'm looking for more data going forward. Dr. Aggarwal: It's incredible to see how far we've come in mesothelioma within the last decade. We are introducing immunotherapy. We're introducing novel agents in the first-line setting. Dr. Marmarelis: The other trial that I was interested in was KEYNOTE-789, which is looking also at patients with EGFR mutations and those that had the original osimertinib as their first-line treatment or another tyrosine kinase inhibitor and then had disease progression on that TKI. And this is an area of huge need. We have patients that do really well on targeted therapies, and then they have disease progression, and we're looking for additional targeted options, but we're also looking for effective chemotherapy options. And one of the questions that has risen from this is whether there's a role for immunotherapy. We know that immunotherapy alone in patients with EGFR mutations is not very effective when you look at a broad population, but in combination with chemotherapy, it's possible that it can add some benefit. So this trial looked at those that had EGFR mutations, had disease progression after a targeted therapy, and then it randomized them to chemotherapy plus or minus pembrolizumab, so chemotherapy plus or minus immunotherapy, and interestingly, it had no difference in the progression-free survival or the overall survival. So the 2 arms were really similar in terms of outcomes. There was also no difference in the overall response rates of the amount that the drug actually shrinks the tumor. So it really doesn't look like immunotherapy is adding much to chemotherapy for these patients. I think we still need to look a little bit closer because there are probably some patients with EGFR mutations that could benefit from immunotherapy, but we're really not very good at identifying those. One of the questions that comes up in this space is whether to add anti-VEGF treatment in addition to chemotherapy and immunotherapy. So there are some upcoming trials looking at that. Dr. Aggarwal: I think this was a trial that was actually very important and again, practice-affirming that this idea of continuing chemotherapy without adding immunotherapy, patients are not losing much. In fact, they're not gaining anything by adding immunotherapy as shown in this clinical trial. I think continuing immunotherapy, so continuing osimertinib, may be important in this setting also because we know that osimertinib can cross the blood-brain barrier. It can provide that CNS [central nervous system] protection. Dr. Marmarelis: Yeah, I think that's a great point that the comparison here is not chemotherapy plus osimertinib. It's chemotherapy alone. So I agree that the control arm is not quite what some of us do. I agree. I do the same as you do. I also just want to mention that the KEYNOTE trial and the previous trial about mesothelioma used pembrolizumab, which is made by Merck. We have received institutional funding, and I've served as an advisor as well as received honorarium from Merck.   Dr. Aggarwal: Melina, those were 2 very important studies and certainly, I think, answer some very relevant questions in clinic in the management of patients with EGFR-mutant lung cancer, for example. And then I think we look forward to more practice-changing data in mesothelioma. Kristin, I would love to hear research from ASCO from you. What caught your interest? Dr. Higgins: So I have a special interest in small cell lung cancer. And I think there was one important small cell lung cancer trial that I wanted to review with everyone. It was SWOG S1929. And SWOG is the Southwest Oncology Group, and it's a cooperative group that conducts clinical trials in cancer funded by the National Cancer Institute. And this is a randomized phase II trial of atezolizumab and chemotherapy followed by randomization to continuing the maintenance of atezolizumab with a PARP inhibitor. Now, we know from prior data that PARP inhibition is attractive for small cell lung cancer because PARP is expressed frequently in small cell lung cancer, and there is a biomarker called Schlafen-11 that preclinical data and prior data has shown can predict response to PARP inhibition. And this trial was sort of a proof-of-concept trial, a small, randomized phase II trial testing whether or not that Schlafen-11 biomarker could be used to direct therapy. Now, in this trial, there were 309 patients that were registered. They then had to have their tumor samples sent for central testing for the Schlafen-11 expression. One thing that I think is important to bring up is that in small cell lung cancer, there's this belief that it's really hard to get tissue samples from small cell lung cancer and it's a difficult thing logistically because it's just a lot harder to access these tumors. But interestingly, in this trial, 80% of patients had tumors that were evaluable for the biomarker, and the median time to the test result was only 7 days. So patients were able to get their tumor tested, get it sent out, get results in a rapid manner, and then be randomized based on these results. The primary endpoint for this trial was progression-free survival, and the primary endpoint was met. Progression-free survival was 4.2 months versus 2.8 months. Now, I think many people will say the magnitude of benefit here is not very much, but it's small cell lung cancer, and we don't have a lot of positive trials in this space, and we also don't have many trials that have used a biomarker to direct therapy. So I think for those reasons, it's really exciting to see these results. It was also conducted within a cooperative group with multiple different sites across the United States, and the fact of the matter is that we can do trials like this in small cell lung cancer patients, and I think it will sort of serve as a precedent for future trial design. Now, the overall survival for the trial is still premature. It didn't look that much different with the PARP inhibitor, but that doesn't mean that, again, things could change with more follow-up. And I really like the approach of this trial design, and I'm excited to see biomarker-driven trials in small cell lung cancer. Charu and Melina, what do you guys think about this study? And what do you think about our small cell lung cancer patients and our ability to conduct future trials like this? Dr. Aggarwal: I think this is certainly an advance. As you pointed out, Kristin, it shows us that we can conduct trials in the space. I think it offers a lens into the potential of personalized therapy in small cell lung cancer, which has eluded us for a very long time. The standard of small cell lung cancer has not changed significantly for a very long time, so I think this is very exciting and can't wait to see more things come in the future. Dr. Marmarelis: Yeah, I agree. I think we've always been asking for additional biomarkers, especially in such a difficult disease like small cell. And so this is really exciting to see potential biomarkers and that it was feasible to actually pose that question and study it. So that part's really exciting. Dr. Higgins: Great. And I should also say I was not involved in the study, and I'm not associated with any of the pharmaceutical companies that were involved in the study for S1929. And the final study that we wanted to talk about was the phase III LUNAR study, and this is sort of a different type of trial in the setting of advanced non-small cell lung cancer. It was studying tumor treatment fields with standard of care in metastatic non-small cell lung cancer after progression with platinum-based therapies. And first, I just want to step back and explain what tumor treating fields are. Tumor treating fields are applied to a patient with a transducer that's placed on the skin, and what it does is it applies an electrical field, and that disrupts mitosis when the cancer cells are trying to divide. And the mechanism of cell death is a little bit unclear. There are sort of many mechanisms that are postulated, one of which is immunogenic cell death, but we don't really know, I think, what's happening. But there have been studies that show improved results with tumor treating fields and other diseases. For example, particularly in glioblastoma multiforme, tumor treating fields are used in combination with surgery, radiation, and temozolomide (Temodar). So it's something that's being used in other disease sites, and this is some of the early data that we've seen in metastatic non-small cell lung cancer. And so in this trial, 276 patients were randomized to tumor treating fields plus standard of care or standard of care alone. Now, I should mention that this trial began enrolling patients in 2016, and so the standard of care was very different. After platinum-based therapies, the standard was considered docetaxel. Of course, platinum-based therapy alone for frontline treatment of advanced non-small cell lung cancer is also not the standard of care anymore. And so I think with that in the background, it does make interpretation of these results somewhat difficult, and that's probably the major caveat to this study. But nonetheless, patients were randomized, 276 patients. The primary endpoint of the study was overall survival. They were looking at progression-free survival and overall response rates as secondary endpoints as well as overall survival in patients that received immunotherapy versus just chemotherapy alone. And the trial was positive. Overall survival was improved. The median overall survival was 13.2 months for patients that received tumor treating fields with standard of care versus 9.9 months for standard of care alone. If you look at 3-year survival, it was 18% versus 7%. I think this is a new type of therapy for our patients with non-small cell lung cancer. It is somewhat of a difficult thing to wear the transducer, and you have to wear it for many, many hours. So that is one thing that I think can be difficult for patients that are using this treatment, but nonetheless, it is something new for advanced non-small cell lung cancer. I do know that the technology of tumor treating fields is being studied in other settings for non-small cell lung cancer, for stage III non-small cell lung cancer, for example, and also in the frontline setting. I think this trial kind of speaks to the fact that the landscape of advanced non-small cell lung cancer is changing so rapidly, and when we're studying something novel, we have to make sure that we make these trials feasible for enrollment so that we can get them completed rapidly, and we can get a readout and it doesn't become obsolete based on this shift in the standard of care. So I think it just really kind of drives home that we need to make sure that we're taking that into account with trial design. It's not standard of care changing right now, but it'll be interesting to see how the data evolves over time. Melina, I'm interested to hear your point of view because I know that these can be used in mesothelioma, maybe not that frequently. What is your experience with tumor treating fields, if any? Dr. Marmarelis: Tumor treating fields are approved as a device in pleural mesothelioma in the first-line setting in combination with chemotherapy. They have been used off-label in other settings, but that's the device approval. The trial that looked at tumor treating fields in mesothelioma was a single-arm trial, so there was no control arm, and it was really actually just looking at the safety of the device. So I have not used it personally in mesothelioma, although I know of patients and I know of real-world studies looking at its use, and I think it's potentially an interesting modality of treatment, especially in combination with immunotherapy, given that it really doesn't have a lot of additive toxicity. But I think the question is really, which patients are benefiting from it, and which patients are able to actually wear the vest in the case of mesothelioma? Dr. Higgins: Yeah. Any thoughts, Charu? Dr. Aggarwal: I agree, and I think this is going to be largely driven by patient experience. I think this is going to be quite onerous to wear this, carry the suitcase, so I would be very interested in patient reported outcomes as well as patient experiences and stories, which will really drive our use here. Dr. Higgins: Yeah, that's a great point. I should say that this trial was sponsored by Novocure. My institution does have other Novocure studies underway, and we receive research funding, but I was not involved in the study, and I did not personally receive any research funding. Dr. Aggarwal: Thank you, Kristin. This has been a wonderful review of practice-changing and some promising research that came out of the ASCO Annual Meeting. I hope our listeners enjoyed it, and we'll be sure to update you with the next annual research conference. Thank you, everyone. ASCO: Thank you, Dr. Aggarwal, Dr. Marmarelis, and Dr. Higgins. 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ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. 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. Guests' statements on this 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. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. The theme of the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting was “Partnering With Patients: The Cornerstone of Cancer Care and Research.” From June 2 to 6 in Chicago, Illinois, and online, cancer researchers and clinicians from around the world gathered to discuss the latest cancer research and how to ensure that all people receive the cancer care they need. In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field presented at the meeting, and explain what it means for people with cancer. In today's episode, our guests will discuss new research in breast cancer, lymphoma, multiple myeloma, and brain tumors. First, Dr. Norah Lynn Henry discusses new research in early stage and metastatic breast cancer. Dr. Henry is Professor and Interim Chief of the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the 2023 Cancer.Net Associate Editor for Breast Cancer. You can view Dr. Henry's disclosures at Cancer.Net. Dr. Henry: Hi, I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of the most exciting new research in breast cancer that was presented at the 2023 ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. First, I'm going to give a very brief overview of the types of breast cancer, then talk about some research that was presented on both early-stage and metastatic breast cancer. As a reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone receptor-positive or estrogen receptor-positive and are stimulated to grow by the hormone estrogen. We treat those cancers with anti-estrogen or anti-endocrine treatments, which block estrogen or lower estrogen levels. Other breast cancers are called HER2-positive. These are often more aggressive cancers. But because they have extra copies of HER2, they often respond to treatments that block HER2. Finally, there are breast cancers that don't have hormone receptors or HER2. These are called triple-negative breast cancer and are also often aggressive cancers. Most of the results I'm going to highlight today are treatments for estrogen receptor-positive and HER2-negative breast cancer. One of the main stories from the ASCO Annual Meeting was the result of the NATALEE trial. At the present time, for patients with estrogen receptor-positive, HER2-negative early-stage breast cancer who were at high risk of having their breast cancer come back, the currently recommended treatment is anti-endocrine therapy. Based on the results of a prior trial called monarchE, we also consider adding a medicine called abemaciclib, which turns off some enzymes in the cell that are called CDK4 and CDK6, which are known to make estrogen receptor-positive breast cancer cells grow. Abemaciclib can further reduce the risk of cancer recurrence compared to endocrine therapy alone, but it does have some side effects, most commonly, diarrhea. In the NATALEE trial, which was presented for the first time at this ASCO meeting, researchers studied a similar type of medication called ribociclib. It acts similarly to abemaciclib, although it is more likely to cause low blood counts and less likely to cause diarrhea. Ribociclib is currently routinely used in combination with anti-endocrine therapy to treat patients with metastatic estrogen receptor-positive breast cancer but is not yet routinely used in the early-stage setting. In the NATALEE trial, patients with estrogen receptor-positive, HER2-negative early-stage breast cancer who are at high risk of breast cancer recurrence were enrolled. Half the patients were treated with just standard anti-endocrine therapy and half also received ribociclib for 3 years. After the 3-year treatment period, those who received both ribociclib and anti-endocrine therapy were about 25% less likely to have their cancer come back compared to those who received only anti-endocrine therapy. Overall, the medication was quite well tolerated. It is important to note that this drug is not yet FDA-approved in the setting. The remaining trials I will highlight are for treatment of metastatic breast cancer. There were many trials examining how best to use drugs that we are actually already using in the clinic. For example, many presentations were about the CDK4/6 inhibitors that I just mentioned. Typically, patients who have just been diagnosed with estrogen receptor-positive, HER2-negative metastatic breast cancer get treated with anti-endocrine therapy plus a CDK4/6 inhibitor. One trial called SONIA examined whether this is the right approach, or whether patients should just get the anti-endocrine therapy up front and hold off on starting the CDK4/6 inhibitor medication until a later time. It appears that this delayed approach would reduce symptoms as well as cost of the medication, while not reducing benefit from the treatment. Therefore, it appears it is likely fine for some patients to get just anti-endocrine therapy alone initially. However, we don't know how to identify those patients. Researchers are still figuring out which patients should follow this new treatment plan and which should keep getting the double therapy at the beginning. Some more to come in the future. There was a different trial called PADA-1 that included patients taking anti-endocrine therapy and the CDK4/6 inhibitor, palbociclib, upfront. Those patients were monitored using a blood test, looking for a mutation or a change in the estrogen receptor in the cancer. Patients who had that mutation either remained on the same treatment that they'd been on or switched to the next line of therapy, even though their scans didn't show any progression of their cancer. Overall, this switching strategy looks like a very promising approach for managing patients since it may help patients' cancer respond to treatment for a longer period of time. Although this approach is not yet officially recommended according to our guidelines. In another example, many patients with all types of metastatic breast cancer are treated with a drug called capecitabine, also known as Xeloda. Although this drug is effective for many cancers, many patients experience hand-foot syndrome, nausea, diarrhea, and mouth sores. In the X7-7 clinical trial, the researchers compared the official standard FDA-approved dose based on a patient's height and weight and given for 14 days followed by 7 days off. That was compared to a fixed dose of treatment given 7 days on and 7 days off. The trial found that the fixed-dose regimen was easier to tolerate, but importantly, the benefit from the 2 doses and schedules of treatment appears to be similar. Therefore, we will likely be using this lower dose, 7 days on and 7 days off, for most of our patients who receive treatment with capecitabine for metastatic breast cancer, since it is likely to improve their quality of life while not negatively impacting the potential benefit they receive from the therapy. There were a lot of other research findings presented that are related to treatment for both early-stage and metastatic breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer, including a new antibody-drug conjugate against HER2, as well as other new anti-endocrine and targeted treatments. We eagerly await the results of large, randomized trials so the drugs that work can be used to treat patients with breast cancer. But for now, that's it for this quick summary of important research from the 2023 ASCO Annual Meeting. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you. ASCO: Thank you, Dr. Henry. Next, Dr. Christopher Flowers discusses new research in lymphomas and multiple myeloma. Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and Division Head ad interim of Cancer Medicine. He is also the 2023 Cancer.Net Associate Editor for Lymphoma. You can view Dr. Flowers' disclosures at Cancer.Net. Dr. Flowers: Hello. I'm Dr. Christopher Flowers, professor and chair of the Department of Lymphoma and Myeloma and interim division head for cancer medicine at the University of Texas MD Anderson. And it's my pleasure to talk to you today in this Cancer.Net podcast about latest updates in the hematological malignancies focused on lymphoid cancers from the American Society of Clinical Oncology Annual Meeting. The ASCO Annual Meeting every year is an exciting time for latest updates in the care of patients with cancer. And in particular this year, there were 3 abstracts that I'd like to highlight that were presentations at this meeting about lymphoid malignancies that have potential significant impact for patients over time. The first 2 come from a special session that was on late-breaking abstracts that were latest advances from clinical trials. The first is from the ZUMA-7 trial. This is a trial looking at axicabtagene ciloleucel, a chimeric antigen receptor T-cell therapy, or CAR T-cell therapy. The CAR T-cell trial in question here was led by Jason Westin, who's a colleague of mine at MD Anderson. And MD Anderson is a partner with Kite pharmaceutical company that is a manufacturer of this and has a research alliance with that group. In the ZUMA-7 trial, this was a trial that involved the use of CAR T-cell therapy in comparison to standard-of-care therapy, which typically would be aggressive chemoimmunotherapy followed by autologous stem cell transplantation for patients with relapse of large B-cell lymphoma. As many of you may know, large B-cell lymphoma is a kind of lymphoma that is potentially curable with standard frontline therapy. And when patients relapse, the standard of care historically had been for patients to receive autologous stem cell transplantation, which is also potentially a curative therapy. This trial to do a ZUMA-7 trial compared patients who received the typical standard of care, the autologous stem cell transplant following the aggressive chemoimmunotherapy regimen for patients who had relapsed early after their initial therapy, so within 12 months, or were refractory, meaning that they did not respond to their initial therapy. And this was compared to the axicabtagene ciloleucel or axi-cel CAR T-cell therapy. The initial publication of the trial came out in the New England Journal of Medicine in 2022 and showed that the event-free survival for patients who receive CAR T-cell therapy was superior. This update of the ZUMA-7 trial at the ASCO Annual Meeting that was presented by my colleague, Jason Westin, discussed the overall survival of the study, and in this update, it showed that overall survival was also improved for patients who received axi-cel as opposed to standard-of-care therapy. And now with a median follow-up of a little bit more than 47 months, axi-cel demonstrated superiority that was statistically significant and clinically meaningful over the traditional standard of care. In that same session, there was another trial looking at CAR T-cell therapy for patients with multiple myeloma. This was a BCMA-targeted CAR T-cell therapy that was presented by Dr. Dhakal in that session providing results from the CARTITUDE-4 global randomized phase 3 clinical trial. That was a trial that involved 419 patients where patients were randomized to cilta-cel CAR T-cell therapy for myeloma or standard-of-care therapy, which in this case included combination therapy. And in this trial, this showed that single agent with a single cell-to-cell infusion significantly improved progression-free survival versus standard of care for patients with multiple myeloma who had 1 to 3 prior lines of therapy and were refractory to lenalidomide. This is also a meaningful advance for patients with this disease. And the final abstract that I'll mention is an abstract that was presented by Dr. Alex Herrera from City of Hope and was presented in the Plenary session. And it was really exciting to see a Plenary session presentation focusing on lymphomas. So this trial presented by Dr. Herrera was led by the Southwest Oncology Group. Dr. Sara Ahmed from MD Anderson, from my institution, was a participant and actively engaged in this clinical trial. This trial was a success in a number of ways. First, it involved both pediatric and adult patients and is one of the first trials of its kind to involve both large populations of patients with pediatric lymphomas as well as adults with lymphomas. It helps to consolidate the approaches that we use for Hodgkin lymphoma, both in the pediatric population and the adult population. It also represents a major advance in the ways that we conduct clinical trials in the United States in that this clinical trial finished ahead of schedule in terms of completion of the trial with collaboration from the adult and pediatric groups across the National Clinical Trials Network. As I mentioned, this was presented by Dr. Alex Herrera in the Plenary session and involved patients with stage 3, 4 Hodgkin lymphoma, where patients were randomized 1 to 1 either to receive an anti-PD-1 therapy, nivolumab, with chemotherapy, the AVD chemotherapy regimen, or the antibody-drug conjugate, brentuximab vendotin, combined with that same AVD chemotherapy. And what this showed in 994 patients who were enrolled from 2019 to 2022 was that there was a benefit for patients who received the combination of nivolumab AVD or NAVD versus the group that received brentuximab and AVD. It improved the progression-free survival in patients with advanced-stage Hodgkin lymphoma. In this trial, few immune-related adverse events were observed and a lesser number of patients went on to receive radiation therapy, which is also a benefit for patients with Hodgkin lymphoma. And this concludes my presentation of abstracts at the ASCO Annual Meeting and really exciting advances for patients with lymphoma that were presented this year. ASCO: Thank you, Dr. Flowers. Finally, Dr. Roy Strowd discusses new research in treating brain tumors, including those in people with von Hippel Lindau syndrome. Dr. Strowd is a neurologist and neuro-oncologist at Atrium Health Wake Forest Baptist Comprehensive Cancer Center. He is also the 2023 Cancer.Net Associate Editor for Central Nervous System Tumors. You can view Dr. Strowd's disclosures at Cancer.Net. Dr. Strowd: Hello, everyone. This is Roy Strowd. I'm a physician neuro-oncologist at Wake Forest University School of Medicine in our comprehensive cancer center. And I'm really excited to be with you for this podcast on important CNS or brain tumor updates from the 2023 ASCO Annual Meeting. I don't have any relevant disclosures for the research that we'll discuss today. It was a really exciting meeting. It was actually a really fun meeting to be a brain tumor doctor at ASCO this year. So I'm really excited to talk with you about some important updates. And I think it's actually a really important time to be a patient and a caregiver and know some of the things going on in brain tumor care. So I'm going to dive into 3 studies. And one that we just have to talk about, and this was a really exciting study called the INDIGO study. At ASCO, if you present a study, you want to have a Plenary presentation, you want to be up on the big stage presenting your work. And brain tumor studies aren't always on the big stage. We just haven't had enough really good treatments out there for brain tumor patients over the years. And this year, we had a Plenary presentation, a really big study, making a big splash. And that was this INDIGO study. So I'm going to spend a few minutes talking about that study. I want brain tumor patients and caregivers to know about this and know about some of the important updates from the Annual Meeting. The study was called the INDIGO study, and it's a phase 3 study. So when you think about clinical trials, there's a phase 1, phase 2, phase 3. That phase 3 is that last step, that last hurdle that a drug needs to overcome to move towards approval. And a positive phase 3 study is really exciting for the field and means that we may have a new treatment that will change how we take care of brain tumor patients. And that's what this study was. It was also a really unique study. So it's looking at a different group of brain tumor patients, patients that have an IDH mutant glioma. Most common brain tumors that we see are the glioblastomas. And those are often and really, by rule, IDH wild-type. IDH is a gene. It's called the isocitrate dehydrogenase gene. And it's one of these really important genes for us to understand how brain tumors are going to work and how they act and it turns out, with this study, how they may respond to treatment. So this study looked at enrolling patients that had an IDH-mutant low-grade glioma, or a grade 2 glioma. Those are those often slower-growing, but they continuously grow tumors that occur early in life, typically in the 30s or 40s for young people. And we haven't really had a lot of good treatments for these patients. And so this study looked at giving a new drug that's called vorasidenib. It's hard to say vorasidenib. And it's an IDH mutant inhibitor. So it attacks that IDH mutant gene that makes these tumors what they are. And it's been undergoing development for many years. It's an exciting treatment because it's what we call a molecularly targeted treatment. It specifically targets that IDH gene that makes the low-grade tumors low-grade tumors. This study enrolled 331 patients, so a large group of patients. Half of those patients received the drug, the vorasidenib, and half received placebo. And that's pretty uncommon in cancer. We don't often do studies that are placebo-controlled studies. But for these patients, there's often not a good treatment early in the course, they get surgery. And for patients that don't need an additional treatment, we do surgery and then we wait and watch and see what happens. And that gives us an opportunity as a brain tumor community to figure out whether this type of treatment will help prevent the need for a next treatment, prevent the need for radiation and chemotherapy. And so that's what was looked at in this study. And there was some really exciting data. So I'm going to go through a few numbers, but we just got to talk about these numbers because they're really important. So at 14 months, 28% of the patients receiving the drug vorasidenib had progressions. That's about a quarter of patients compared to half that received placebo. So that's a big improvement in the number of patients whose tumor grew. So this drug prevented tumor growth in these patients. And that's exactly what we want. That's why we develop drugs, is to prevent tumor growth. When we look at the time that those patients had until they needed a next treatment or until their tumor grew, it was over 2 years of time patients receiving the drug when their tumor grew versus less than a year, 11 months for those receiving placebo. So it's adding a lot of time for brain tumor patients without tumor growth or without needing another treatment. And typically, these patients with low-grade gliomas would need something like radiation therapy or chemotherapy. And those are good treatments, and we need those treatments. But they can have toxicity. And so this is the type of drug that could prevent that toxicity, cognitive decline, other problems that can happen with chemotherapy that those patients didn't potentially suffer. So there are some important things that we learned from the INDIGO study that I would want you to take away, kind of what do these data mean? The first is that we can target this IDH gene. And that's really important for our field. And it means if you're a brain tumor patient, knowing whether your tumor is IDH mutant or IDH wild-type is important, and that's something I want brain tumor patients to ask me as a neuro-oncologist and ask their cancer doctor because that's important in deciding treatment for them. The second is this medicine vorasidenib, it gets into the brain. And that's one of the big challenges that we have in brain tumor care in developing drugs is we need things that get into the brain. And this study really shows that this is a good medicine. There's a number of IDH inhibitors, but this medicine vorasidenib is one that we want to specifically think about for our patients. And this is a practice-changing study. So for the first time, we now have a treatment that works for grade 2 gliomas and really prevents the need for radiation therapy and chemotherapy. So those are 3 important things to take away from this. There's a number of things that we don't yet know. This medicine is not available. So patients coming in and emailing me and calling me, we don't have it yet. And after a big phase 3 study like this, this is announced. There's still a number of steps that need to happen to make sure that this can be delivered to patients safely and we can get it out there. And that's in partnership with groups like the FDA, the Food and Drug Administration, and others. So this is an important conversation to have with patients, neuro-oncologists, and to know that this is something that's on the horizon. Two other things is we don't know if this is going to work for all brain tumors. In particular, for these IDH wild-type glioblastomas, the most common brain tumor, this probably is not a good therapy that we don't have any data to suggest that it would work. They don't have that IDH mutation. And so this is important for some brain tumor patients but not for everybody. And that needs to prompt a conversation with the cancer doctor. And it may not work at all times. So there's some data to suggest that this is really a drug that's best given early in the course of treatment and not later on. And so it is something that I want my patients to be aware of at the first time that I see them so we can be deciding what kind of the right time is. So I want to give folks 2 take-homes from this study and summarize a few of these things that we heard about because it's such an important study. So what are the 2 take-homes from the INDIGO Study? The first that I wrote down is targeting IDH mutation in glioma works. And that's a groundbreaking discovery from this. This is really important for our field. IDH mutations have been important to diagnose brain tumors but have never been really a therapeutic target. And this changes the landscape, and we can now target IDH mutations in gliomas. And that's really important. The second thing, the second real take-home message, is we can safely delay radiation therapy and chemotherapy in some patients with these lower-grade gliomas, potentially with IDH mutation and IDH inhibition. And that's really important. Chemotherapy and radiation therapy are important, but if we can delay those treatments and prevent side effects, that could be helpful for some of our patients. So really important update from ASCO and what I want to spend most of the time on our podcast focusing on this INDIGO study. But there were a bunch of other things going on in brain tumors at ASCO, as there always are. And I want to highlight 2 studies about some things that the groups of patients may be interested in knowing that happened at the meeting. The first is a study called the INB-200 study. And this is a phase 1 study, so it's earlier in development. But it's an immunotherapy study. And brain tumor patients and caregivers will know that we've really wanted to find an immunotherapy that works for brain tumors. And we haven't yet. And we're still not there, but this study is an important step in that direction. So this study from a group at the University of Alabama looked at something called gamma delta T cells. And T cells are really important. They're part of the anti-tumor response. They're what the body uses to attack the tumor. So we like those T cells. And particularly, these gamma delta T cells are important in targeting tumor cells in glioblastoma cells. They're also unique. They can avoid the toxicity of chemotherapy. Radiation therapy and chemotherapy suppresses the T cells. They make some go down, or decreased in number, which is not what we want. And these gamma delta T cells were genetically created so that they were resistant to chemotherapy. And that's really, really important. We want an immunotherapy that works and one that isn't suppressed by our other treatments. And that's been a real barrier for glioma patients. So in this phase 1 study, they found the right dose of these gamma delta T cells, and that's the goal of a phase 1 study. But there were some early signs that this may be changing the tumor. One of the patients underwent surgery before and after they got this infusion. And we were able to see this. Investigators were able to see the gamma delta T cells up in the tumor. So this doesn't change practice. Patients don't need to go out and seek out the gamma delta T cells yet. But it's one of those early findings that says that we need to keep looking at immunotherapy. And as a community, this is something we need to keep focusing on. And then the last abstract and study I wanted to focus on is for a rare disease. This would not be something that would be relevant for all of our listeners and the brain tumor patients but for a subgroup of patients that have a condition called VHL, or von Hippel-Lindau. And von Hippel-Lindau is a genetic condition. So, most brain tumors are not inherited. You don't get it from a mom or a dad or pass it on, except for these patients, you do. And it comes from a gene that's inherited in families called the VHL or the von Hippel-Lindau gene. And these patients are predisposed to get tumors all throughout the body and the kidneys and the brain and the eye. And this is a lifelong disease where these tumors can really grow slowly over time and cause significant problems. And in the past few years, there's been a new treatment called belzutifan. Belzutifan is the name of this drug that has been shown to be effective in the kidney tumors for patients with VHL. And at ASCO this year, there was a new study showing that it's also effective in treating the brain tumors for these patients. And that's really important. We just haven't had a treatment other than surgery or radiation therapy for these tumors. And oftentimes, they grow after surgery and radiation therapy and we need an additional treatment. So in this study, the investigators looked at, "Does this drug belzutifan work for treating the CNS tumors, hemangioblastoma?" And found that around 50% of patients had a response, so a shrinkage in the size of the tumor. 90% of patients had control of their brain tumor disease, which is really important. And it worked really quickly, so it worked in about 3 to 5 months, which is shorter than what we would see for the kidney tumors. So that's exciting news for VHL patients, patients with von Hippel-Lindau, and another important update from the 2023 ASCO. So thanks for listening to this update of CNS brain tumors at the 2023 ASCO Annual Meeting. Again, I'm Roy Strowd, a neuro-oncologist at Wake Forest University School of Medicine. Delighted to bring you this brief summary of new research in the field. ASCO: Thank you, Dr. Strowd. You can find more research from recent scientific meetings at www.cancer.net. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.

Drs. John Sweetenham and Marc Braunstein discuss advances in hematologic malignancies featured at the 2023 ASCO Annual Meeting, including the potentially practice-changing SWOG-S1826 study in Hodgkin lymphoma, the promise of bispecific antibodies in B-cell malignancies, and a novel approach to deliver vital anti-myeloma medications that could improve patient quality of life and alleviate barriers to care. TRANSCRIPT   Dr. John Sweetenham: Hello, I'm John Sweetenham, the associate director for cancer network clinical affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and the host of the ASCO Daily News Podcast.    The 2023 ASCO Annual Meeting featured some exciting new data on hematologic malignancies. I'm delighted to have Dr. Marc Braunstein return to the podcast to discuss some of these potentially practice-changing studies and new approaches in the heme space. Dr. Braunstein is a hematologist and oncologist at the NYU Perlmutter Cancer Center.    You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the ASCO Daily News Podcast are available on our transcripts at asco.org/DNpod.   Marc, it's great to have you back on the podcast, and thanks for being here again.   Dr. Marc Braunstein: Thank you, John. It's great to be back.   Dr. John Sweetenham: Marc, we already mentioned that there are some potentially practice-changing studies that were reported at ASCO this year. And among those, LBA4, which was presented in the Plenary Session, was a study which explored the treatment of advanced Hodgkin lymphoma. This was the Southwest Oncology Group study S1826. Could you give us your insights on this?    Dr. Marc Braunstein: Sure, happy to discuss S1826. So as background, you know, the ECHELON-1 study, which was published in the New England Journal of Medicine in 2022 showed a 40% decrease in the risk of death at six years follow-up by adding brentuximab to AVD compared to bleomycin AVD. And that was in high risk or advanced-stage patients and that led to adoption of brentuximab for upfront use in patients with classical Hodgkin lymphoma in advanced stage.    Also of note, immune checkpoint inhibitors such as pembrolizumab or nivolumab do have activity in the relapse setting. The SWOG S1826 study was a randomized control study looking at the use of the PD-1 inhibitor nivolumab plus AVD versus brentuximab AVD in patients with advanced stage classical Hodgkin lymphoma who are at least twelve years of age. And the primary endpoint in the study was progression-free survival.     It was a large study which enrolled 976 patients and randomized them one to one to either nivo AVD or brentuximab AVD. The median age in the study was 27 and the median follow-up was 12 months. And what the study found, which could be practice-changing, was that the primary endpoint of progression-free survival was superior in the nivolumab arm with a hazard ratio of 0.8 and a one-year PFS of 94% versus 86%, favoring the nivolumab arm. And while there were side effects associated with the class of medications, for example, hypo or hyperthyroidism was more frequent in the nivolumab group, whereas peripheral neuropathy was higher in the brentuximab group, I think that these results are particularly encouraging for how we can continue to improve outcomes for patients with advanced-stage classical Hodgkin lymphoma. And this may be practice-changing in terms of whether we use upfront immune checkpoint inhibitors in combination with our standard chemotherapy backbone.    Dr. John Sweetenham: Yeah, absolutely. There are a couple of things that occur to me. One in particular which is unique about this study, and the fact that it was for patients who are 12 years and older in many respects represents a first because I can't think of another large, randomized study of this type which has attempted to align pediatric and adult care of patients with Hodgkin lymphoma. So, I think it's something of a landmark in that regard. I don't know if you'd agree with that.    Dr. Marc Braunstein: I agree, especially with the range of ages from 12 to 83. It's a pretty broad population by age, but I agree it does kind of reconcile those two groups in a disease that has a bimodal presentation and clearly shows that immune checkpoint inhibitors are both potent and well tolerated in different age groups.    Dr. John Sweetenham: The other question that I have about this study is we haven't seen so far in this study an overall survival benefit to the nivo arm, which is maybe not surprising, but in terms of the practice-changing potential of this study, do you think that will matter?   Dr. Marc Braunstein:  I think that's an excellent question, John. Initially, the ECHELON-1 study only showed progression-free survival, and then the update did show overall survival. And so if we take the lead from that study, we expect to see an overall survival benefit in the SWOG study as well with nivolumab, but it remains to be seen. But I think that the data presented thus far at the Plenary Session is compelling enough to consider using nivolumab upfront.   Dr. John Sweetenham: Yeah, I absolutely agree. And then I guess the other question that we're going to have to wait probably several years to know is what happens in terms of relapse? So, for the minority of these patients who do relapse, how salvageable, if that's the right word, are they going to be with a second- or third-line regimen? But I think that's clearly something for the future, and it's a very interesting, exciting outcome from this study.   Dr. Marc Braunstein: Absolutely.    Dr. John Sweetenham: Let's move on. Marc, again, we're still in the lymphoma world here, but looking at high-risk follicular lymphoma. And this was Abstract 7506, looking at epcoritamab plus the R2 regimen in patients with follicular lymphoma. Could you walk us through this one?    Dr. Marc Braunstein: Yeah, absolutely. Bispecific T-cell engaging antibodies are showing impressive efficacy in relapsed and refractory non-Hodgkin lymphoma. Epcoritamab is a bispecific antibody that binds to CD3 on T-cells and CD20 B-cells. And this antibody is currently approved for diffuse large B-cell lymphoma patients after two or more prior lines of treatment.    In this study presented by Merryman and colleagues, they explored the addition of epcoritamab to standard lenalidomide-rituximab. In 109 patients with relapsed or refractory follicular lymphoma who had at least one prior therapy, and, of note, the study was enriched for high-risk patients for progression, including those who had progression of disease within 24 months of their initial treatment and those patients who had been refractory to prior anti-CD20 treatment. This study enrolled 109 patients with relapsed refractory follicular lymphoma. The median age was 65 and 56% of patients had FLIPI scores on the higher end of the spectrum from three to five, and 61% had stage 4 disease. Also of note, 38% of patients had progression of disease within 24 months of their prior treatment. So at a median follow-up of 8.8 months, the overall response rate was impressive at 97%, and 82% of patients were still on treatment at that time.     Now, of course, with this mechanism of action of bispecific antibodies, there is a risk of both cytokine release syndrome and immune-related neurotoxicity. The rates of CRS were primarily low grade, there were only 2% grade 3, and of note, most occurred after the first dose. And in terms of ICANS or neurological toxicity, there were no grade 3 adverse events, and those occurred in only two patients. Finally, the estimated six months progression-free survival was 93%. So, if we cross-compare these results historically to the R-squared regimen, which was published to be about 80%, just cross comparing, so it's not exactly the same study, this clearly shows high activity on par or better with R-squared alone. Although this study was not a randomized study, I think the addition of epcoritamab certainly shows high overall response rates and we'll need randomized data to confirm the efficacy, but it's definitely encouraging in high-risk follicular lymphoma patients.   Dr. John Sweetenham: Thanks, Marc. I agree. I think these data are really enticing, in as much as the response rates are so high, but of course, it is follicular lymphoma, so we'll have to wait a while. But the thing that it does make me reflect on is that bispecific antibodies really are turning out to be remarkably effective in a range of B cell malignancies, so, it's very interesting to continue to watch this space.    I'm going to change gears now and talk about something completely different for a moment. And this was Abstract 1536. I think that many of us are in a position where we're now looking at how we deliver our clinical services, and particularly inpatient services, to patients with hematologic malignancy. And this study addressed that very specifically. Can I have your thoughts on that?   Dr. Marc Braunstein: Sure. In the context of how our therapies are improving, our approaches to how we manage patients clinically is changing too, in many ways for the better. So, various models exist for, you know, which practitioners manage oncology patients who happen to be admitted to the hospital. This abstract, which was performed by authors at a large medical center in New York, describes the use of a dedicated hematologic malignancy hospitalist for managing medicine-related issues. And the authors did comparisons of that service to a service primarily managed by oncologists. The authors compared things such as length of stay, whether the patients were discharged by noon, which is a hospital metric that's used for facilitating turnover of patients and space availability, as well as 30-day readmission rates among patients cared for by an oncology attending versus this heme malignancy hospitalist between July of 2021 and July 2022.    The outcomes showed that admissions to the heme malignancy hospitalists were, although less because that service was primarily for patients who required medicine-related issues as opposed to primarily oncologic issues, there were 95 admissions to that service versus 669 to the oncology service. There was a significantly shorter length of stay on the heme malignancies hospitalist service by about 2 to 5 days compared to the oncology hospitalist service. The rates of patients who were discharged by noon or the length of stay were similar between the two groups.    So, while this study is confounded by differences in acuity of disease between the services, using a dedicated heme malignancy hospitalist has many benefits, not just to offload the oncology-managed service, which may have a higher level of acuity, but also allow for a deviation of care for medicine-specific issues, to a hospitalist that's specifically trained in managing patients with hematologic malignancies and then dedicating the oncology specialty service to those who need acute oncologic care, such as those with leukemia or other high acuity diseases.    Dr. John Sweetenham: Thanks, Marc. I think it is really interesting to see some outcome data for this model of care. A number of centers I know are looking at an APP-led inpatient service for these types of patients, too, so it's going to be very interesting to see how further studies of these kinds of approaches continue to develop.    And on a related theme of changes in patterns of care, Abstract TPS1609 looked at home infusion and of course, this is something that really started to attract a lot more attention during the COVID-19 pandemic. But I wonder if you could walk us through some of the details of this poster.    Dr. Marc Braunstein: This study was presented as a poster proposing a prospective study looking at home infusion of the anti-CD38 monoclonal antibody daratumumab, which has a vital role in managing patients with newly diagnosed or relapsed multiple myeloma. And monoclonal antibodies have really revolutionized the care of patients with multiple myeloma, but often their infusion schedule is weekly or biweekly, and it does require relatively frequent visits to an infusion center.    So, this single-arm, open-label study is going to examine whether we can provide home administration of subcutaneous daratumumab and assess whether it improves quality of life and assess its safety. So, in this study, a visiting nurse will come and deliver the medication after patients take their pre-medications at home prior to the arrival of the infusion nurse. And then the investigators will provide quality of life questionnaires prior to and after the infusions and at the end of the study, and they'll be looking at any barriers to adherence, any barriers to the logistics of this home infusion arrangement.    And I think that this has a lot of potential not just to improve quality of life, but also to facilitate care to patients who may be frail, who may not have good caregiver support, who may have barriers in traveling to an infusion center or perhaps in places that are more resource-deprived and don't have local infusion centers. This could be a potential approach to delivering vital anti-myeloma medications at home, and I'm looking forward to seeing the results.    Dr. John Sweetenham: Yeah, I agree. I think a lot of us still have anxieties about the safety of this approach, but I think there are increasing data to suggest that home infusion is not only safe but also, as you mentioned, is a big enhancer of the quality of life of these patients. And so, very interesting to see how this plays out in prospective studies.    So, to close out, I wonder if you could walk us through Abstract 7072, a poster looking at the issue of clonal hematopoiesis.    Dr. Marc Braunstein: Clonal hematopoiesis, which is a phenomenon in which the blood cells acquire somatic mutation, is associated with both cardiovascular disease adverse outcomes as well as hematologic malignancy. It's been shown to be a precursor for diseases such as leukemia. So, this relatively small study from MD Anderson Cancer Center examined clonal hematopoiesis in 78 patients with malignancies, 70% of which had a history of cancer, and the authors described outcomes associated with clonal hematopoiesis.    So, again, 78 patients were examined, and 76% of them had a history of malignancy, and 73% had other comorbidities. And the authors demonstrated clonal hematopoiesis by the finding of specific mutations in the blood associated with clonal hematopoiesis. The authors essentially looked at outcomes such as mortality. They noted that only 20% of the patients developed a myeloid neoplasm, and that's relevant because, again, clonal hematopoiesis is a precursor for myeloid neoplasms. They also noted that most patients had died from a primary malignancy rather than a myeloid neoplasm, which is not too surprising considering that most patients with clonal hematopoiesis will not develop a hematologic malignancy, but it is a marker for the potential transformation.    And so, I think the authors conclude that clonal hematopoiesis is important for monitoring patients who are at risk for potential myeloid transformation and hematologic malignancy, but it's not necessarily the case that patients who have a background of malignancy will often develop a myeloid malignancy. I think there are many implications of clonal hematopoiesis for cancer in general in terms of the risk of secondary malignancies in those treated with adjuvant chemotherapy, in terms of how we monitor patients who actually more and more are going to have this detected as we use more next-generation sequencing and liquid biopsies.     So, I look forward to future studies that are exploring how to actually prospectively assess clonal hematopoiesis and use it for clinical stratification for things like adjuvant chemotherapy or monitoring for risks of hematologic malignancy.    Dr. John Sweetenham: Thanks, Marc. I agree. Very important for the future, especially as we gain more and more sequencing data.    So, Marc, in conclusion, I want to thank you very much for sharing your insights with us today on the ASCO Daily News Podcast. It's been great to talk with you again.    Dr. Marc Braunstein: My pleasure. Happy to be back, and I look forward to a future podcast session.  Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcripts of this episode. Finally, if you value the insights that you hear on ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer:   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.    Find out more about today's speakers:   Dr. John Sweetenham   Dr. Marc Braunstein   @docbraunstein      Follow ASCO on social media:    @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn       Disclosures:   Dr. John Sweetenham:   Consulting or Advisory Role: EMA Wellness   Dr. Marc Braunstein:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb/Celgene, Adaptive Biotechnologies, GlaxoSmithKline, ADC Therapeutics, Janssen Oncology, Abbvie, Guidepoint Global, Epizyme, Sanofi, CTI BioPharma Corp   Speakers' Bureau: Janssen Oncology   Research Funding (Institution): Janssen, Celgene/BMS        

In this episode of Lung Cancer Considered, host Dr. Narjust Florez discusses ROS+1 Fusions in NSCLC, including diagnosis, treatment and new exciting research coming down the pipeline. Her guests are: Dr. Lorenza Landi, Director of Clinical Trials Unit: Phase 1 and Precision Medicine at the National Cancer Institute Regina Elena in Rome. Dr. Landi has extensive experience and is interested in targeted therapy in lung cancer with a focus on ALK, HER-2/EGFR positive and ROS+1 lung cancer. Dr. Shirish Gadgeel, Chief of the Division of Hematology and Oncology, at Henry Ford Cancer Institute in Detroit, Mich. Dr. Gadgeel is also part of the Lung Cancer steering committee for the Southwest Oncology Group and he is the Associate Editor of Clinical Lung Cancer and a reviewer for many journals.

Dr. Ben Corn, professor of Oncology at Hebrew University of Jerusalem Medical School, and deputy director of the Shaare Zedek Medical Center, discusses his current research with NRG Oncology and SWOG on the study of the science of hope, and it's role as a mediator in well-being and health care improvement. Dr. Corn is co-founder and CEO of the NGO, Life's Door, which teaches health professionals, patients and others strategies for hope, meaning and well-being throughout illness and at the end-of-life.   Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Our guest today is Dr. Benjamin Corn, a professor of oncology at the Hebrew University of Jerusalem Medical School and deputy director of the Shaare Zedek Medical Center. Dr. Corn is the co-founder and chairman of the nonprofit organization Life's Door, which teaches health professionals, patients, and caregivers strategies for hope, meaning, and well-being throughout illness and at the end of life. Dr. Corn was honored with the 2021 ASCO Humanitarian Award and joins me to discuss his work, including his current research on the study of the science of hope and its role as a mediator in well-being and health care improvement. Dr. Corn's full disclosures are available in our show notes, and transcripts for all episodes are available at asco.org/podcasts. Dr. Corn, it's great to have you on the podcast. Dr. Benjamin Corn: It's a pleasure to be here, and thank you very much, Geraldine. ASCO Daily News: Dr. Corn, can you tell us about the experiences early on in your personal life and then your medical training that prompted your interest in helping patients find hope and meaning while navigating cancer treatment? Dr. Benjamin Corn: Sure. I think everyone has a story that sent them on their way for a career in medicine, which for many of us is not a job. It's not a career. It's a mission. My personal story had to do with losing a parent, my dad, at a very young age. He died of prostate cancer, left behind three young children and a lovely widow, who was my mom. And I was quite disappointed with the way the system tried to cope with the reality that was now forced upon us. There were no viable options for somebody with metastatic prostate cancer then. But yet, there was not a cognizance of some of the psychological trauma that we would all have in trying to navigate our daily lives. And I was very surprised also the way my dad's death was communicated to the family. And I've spoken about this in a variety of podcast settings and written a piece for the JCO narrative section about 10 years ago on that, some of what I found to be harshness, coldness of telling us that our dad was not going to make it and how the bad news was conveyed (PMID: 24733795). And so, with that, I was an 11-year-old child, and I very much was intent on curing this thing called prostate cancer to make sure other middle-aged men wouldn't suffer from it, and their families wouldn't have to pick up the pieces. And I went to medical school. I entered my residency in oncology at University of Pennsylvania, thinking that that was my destiny. And when I got to the wards, I was quite disillusioned because I saw a variety of scenarios that told me things hadn't changed drastically in 7 or 8 years since losing my dad and initiating my medical studies. I saw many cases of senior attending physicians, who were fantastic scientists, brilliant researchers, and yet didn't seem to pay enough attention to the subtleties of making sure that a family was whole, bringing in other resources. This was right before what I would call a palliative care revolution. We didn't have the Tamil paper, the Zimmermann paper, the Bakitas paper. And we didn't really know the value of early interventions with teams that included not only oncologists but also nurses and psychologists, chaplains, who could help navigate such a difficult period for patients and for the people in the concentric circles around those patients. So it was very important for me to begin to explore those issues. I never found it to be a conflict for pursuing an academic career that asks bread-and-butter questions about disease, areas of interest. I published a lot in gynecologic malignancy, in prostate cancer itself, and in central nervous system tumors. But by the same token, I thought it was very important to be looking at the psychosocial dynamics that are involved. And that's pretty much the genesis of how I got interested in this area. ASCO Daily News: Well, your work integrating hopefulness into cancer care has had an important impact even on communities beyond the medical setting. Can you tell us about this work, about the hope enhancement model, and how you've used this approach to train medical professionals, patients, and caregivers? Dr. Benjamin Corn: Well, first of all, I want to say that, in many ways, even though I've been blessed with having terrific education at outstanding institutions of higher learning, my greatest teachers have really been the patients, and I'll bet you most colleagues would say the same thing. And I noticed there was a subset of patients who were very intuitively aware of what was important to them, patients for whom the prognosis was very bleak and yet managed to maintain hopefulness. And I saw that the common thread for these patients was that, even though they couldn't be hopeful for cure, they could still find other goals, other objectives that they could pursue. And that sent me on a quest of sorts to see if anybody had formally tried teaching people how to become more hopeful. And with not too much effort, I found literature of Professor Rick Snyder from University of Kansas. It basically modeled this notion of hope theory. And without turning this into a lecture, very briefly, Snyder said that there are three conditions that will allow hopefulness to thrive. The first is defining a goal. And by that, he meant some kind of an objective that was not only plausible but also that could provide meaning in one's life. So it would be a good goal in hope theory if I said my goal is to win the lottery tomorrow because that's really not anything I can have an impact on, so it's not really statistically plausible. But likewise, if I took a goal that was just very mundane and didn't add that much purpose to my life, it would be out there, and I'd be interested in pursuing it. But I probably wouldn't have the same degree of motivation if I thought about something that, without too much effort, could really make my day or make the day of the people around me. So, the first thing was the goals that have these two criteria--plausibility and meaning. The second is a pathway to get to the goal. And when Snyder discusses pathways of thinking, he's supposedly speaking to a mature audience and saying none of us were born yesterday. We all realize that on almost every path that we travel on during our lifetimes, we see that there are obstacles. The question is, how do we manage and circumvent those obstacles, or how do we dance with those obstacles if, in fact, it's something very much within me, an obstacle such as anger, an obstacle such as jealousy? How do I deal with those particular factors? A hopeful person is a creative person, is a resourceful person, who finds a way to sally forth even when these obstacles are out there. So we have goals. We have pathways. And finally, the other secret sauce that I mentioned before is motivation. The word that Snyder used for motivation is called "agency." Agentic thinking, like almost an agent that might represent an NBA basketball player or a Hollywood movie star. That agent will do everything on behalf of his or her colleague so that they'll succeed. And so to the person who has an agentic way of seeing the world is going to be an activist, is going to want to set out on those trails, those pathways, to reach those goals. So those are the three components. And what we found is that--and this is based on some work that was done by one of Snyder's proteges, Dr. David Feldman, who's at Santa Clara University--one could actually construct workshops that are very palatable, that take less than 2 hours to conduct, in which a tool called hope mapping is used. Hope maps are basically dependent on those three components. So you can actually sit there in dyads, buddying up with people in this workshop, people who you know before the workshop, or people who you meet in the workshop, because there's a similarity, a selection for those who attend such workshops. People want to work together. And it's a wonderful energy, because let's say, as I said before, I have a goal, and I have a pathway. But there's a big, bad obstacle there, and I don't know how to get around it. What could be that my buddy in the workshop is going to say, "You know what, Ben? Here's a great way. You might not have thought about this. Why don't we contemplate creating a workaround?" And they're very, very instructive. And we've done some of these workshops now, both in Israel, where I practice, as you mentioned at the opening, and with colleagues at Johns Hopkins in Baltimore with really thought leaders in hopefulness--Tom Smith, who has for many years written the ASCO guidelines on palliative care, and Anna Ferguson, who is the coordinator of the hope enhancement program at Hopkins. And together, we've proven, especially in a population of women suffering from stage IV breast cancer, that we really can invest 2 hours or less and make them much more hopeful. Now, you mentioned in your question that some of this has an impact on communities beyond the medical setting, and that's exactly what's been happening. As the word has trickled out, especially during the COVID pandemic, we've been approached by a variety of communities on the international level--communities in London, communities in Athens, communities in South Africa, communities in the Pacific Rim--who are very interested in bringing together different strata within those communities, perhaps people who have recently become married or people who have recently become parents, who have a similar set of struggles, and to help us help them become more hopeful, especially when you add on to that a little something called COVID-19. So I'm an oncologist. I think there's tremendous upside for this in the setting of cancer care for patients and for the health care professionals who have the privilege of treating these patients. But the spillover phenomenon has really been marvelous to behold, especially during 2020. ASCO Daily News: Well, you're also collaborating with the National Cancer Institute groups of NRG Oncology and the Southwest Oncology Group to study the science of hope and its role as a mediator in well-being and health care improvement. Can you tell us about this research? Dr. Benjamin Corn: Sure. So in the context of NRG Oncology, there are two protocols. One is called CC003 (NCT02635009). That's a protocol for patients with small cell lung cancer. And another one is a protocol called BN005, which is a protocol for individuals with, I guess, what we want to call low-grade gliomas, to look at neuroanatomic loci that could constitute a source for hopefulness (NCT03180502). I'll just give you one example, which is from the small cell lung cancer study I mentioned before. So in years past, at least, it's been a standard of care to provide prophylactic cranial irradiation--that is, prevention with radiation--where there's a tumor, small cell lung cancer, that has a proclivity to spread to the brain. And so one of the hot areas that has emerged in radiation research over the last decade is hippocampal avoidance. It seems trivial, but it took us a while to understand how to protect concentric circles, such as, let's say, the spinal cord when treating the vertebral body or to protect the hippocampus when treating the whole brain. So in prophylactic cranial irradiation, we typically treat the whole brain. And a randomized trial was developed by NRG investigators, where the randomization was between prophylactic cranial irradiation itself to 25 Gray in 10 fractions versus that same regimen with hippocampal avoidance. Now, when I saw that study design, I actually put forward the idea that this could be a wonderful model to study the neuroanatomic correlative hopefulness because there are several candidate anatomic structures in the brain, which are thought to be associated with hopefulness. No one, by the way, is saying that the circuitry is so primitive that all of hopefulness resides in one structure. But if I had to say that there's a lead candidate that's been identified in the literature, it's exactly the hippocampus. So the proposal to the NRG committee and to the PI of the protocol, Dr. Vinai Gondi, and the head of the brain tumor committee, Dr. Minesh Mehta, was, could we very simply administer one of the validated scales for hopefulness that was built by Snyder. It has all of 12 questions. It takes about 5 minutes to complete. Give that to a patient at baseline, then have them randomly assigned to either prophylactic cranial irradiation of the whole brain or the same treatment wherein the hippocampus is protected. Re-challenge the patients 6 months after the irradiation is completed, and see if there is less of a decrement in hopefulness on these validated scales among the group that had the hippocampus protected. When you compare the hopefulness among the groups that didn't have the hippocampus protected, that would offer some interesting, at least circumstantial, evidence that the hippocampus is implicated in the hope pathways. And so this has been very interesting to NRG Oncology. We've enrolled now over 250 patients en route to 300 patients. We have very meticulous quality assurance, where the co-investigators sit down once a month and make sure that the hippocampus was properly contoured and protected. And in the other study, we're looking at particular dosimetric analyses in case someone thinks that 25 Gray might be, for instance, below the threshold of hippocampal tolerance. There, we'll look at a variety of doses to see where we might see the correlation with hippocampal toxicity and decrements in hopefulness. So those are two variations of ideas that are on burners in NRG Oncology. SWOG has taken a different tack. And here, I want to truly applaud SWOG leadership, the group chair of SWOG, Dr. Charles Blanke, as well as the leaders in the palliative care movement at SWOG, including Mark O'Rourke, Marie Bakitas, and Ishwaria Subbiah, who have said, "Look, we know that you've got some preliminary pilot data on the impact of a hope workshop for patients with cancer. Can we, first of all, look at this now among the SWOG investigators?" That had never been done before. In other words, we talk all the time about levels of burnout among health care providers who are treating a patient with cancer. It's very gratifying on the one hand, but it's very challenging on the other hand. It can even be demoralizing for some, and as you know, there are very high rates of burnout. So they've been very interested, first of all, in meticulously establishing levels of hopefulness at baseline and correlating that with levels of burnout among SWOG investigators. So by "investigators," I'm talking about physicians, nursing professionals, even patient advocates. And we have some data that were just recently published in JCO Oncology Practice (DOI: 10.1200/OP.20.00990). In addition, we've been very interested in offering now these hope enhancement workshops that I told you about before to the SWOG investigators. So in the month of May, we got together every Monday night--at least for me, it was Monday night at midnight, I have to say, which was about 5:00 PM Eastern time. And we did these 2-hour workshops every week for about a dozen SWOG investigators. And we actually have some data right now that we just submitted to the ASCO Quality Conference, showing the feedback we got from the SWOG investigators. And to me, the most encouraging part was that these investigators were so enamored of these techniques and found them to be so useful that they--almost all wanted to find ways to bring them into their own clinical environment to share them with their patients, wanted to learn how to become facilitators of such workshops to also help prophylax burnout and increase hopefulness among their colleagues. So SWOG has taken the tack of using this intervention to help providers. We're soon going to be trying to do it among the patients and roll it on to our protocols. And there, what we want to do is take meaty, challenging questions. Let's say the question of adherence, a situation where perhaps women who need endocrine therapy are somewhat--want to take the endocrine therapy but are somewhat reluctant to be adherent to the regimen because of all the hormonal side effects. So we want to see if we can use our workshop to align this value of a patient and this motivation with the patient to help them, in fact, become very adherent, because as I'm sure you know, upwards of 40% of these patients just don't want to take these therapies. So we're interested in using this for adherence. And we're also interested in using it as a tool for medical decision making. We give a lot of lip service to the idea of shared decision making between provider and patient, but most of us haven't really been trained in how to have a robust experience that helps me as a provider understanding what my patient wants. When I counsel patients with prostate cancer, it's almost impossible for me to do such a consultation in less than 90 minutes because there's such a range of options. And before I can really get to understanding which of those options might be most appropriate for a patient, I have to really know the patient. I have to know, in the case of prostate cancer, what makes him tick. And so I think there's going to be tremendous upside for these hope enhancement techniques, not just using it for hope's sake but also for these other epiphenomenon in medicine, like adherence and like decision making, that we speak about all the time, but I wonder to what extent we're really committed to doing a better job on those parameters. ASCO Daily News: Right. Do you see a role for technology to grow hope enhancement workshops, to make them accessible to more people in other parts of the world, in other medical settings? How do you think technology has changed the way people confront the experience of illness? And what role do you think you can play in this? Dr. Benjamin Corn: Yeah. Well, I guess all of us were brought in very rapidly, sometimes kicking and screaming, into this new era. And health care providers are smart, and they're resourceful, and they've figured out a way to ride this challenging wave that COVID has brought into our lives, this tsunami, if you will. So COVID has pushed us all into digital health. My organization, Life's Door, which developed an application, a smartphone app, called Hopetimize--kind of a  play on the words "hope" and "optimize"--in other words, the idea is to optimize your life with using these hope techniques I described before. So we had a game plan to get to digital work in the year 2022. That was a strategy that we basically developed about 5 years ago. When COVID came along, we realized that we had this wonderful product called hope enhancement workshops that we thought could really help oncologists who we thought could help their patients. But we couldn't get people together because of the new criteria for social distancing. So what was once a tailor-made concept for intimate settings with 15 people, I can tell you that even in our IRB-approved protocol--and people can see this on nih.gov, clinicaltrials.gov--our protocol specifies the kind of environment one has to have to conduct these workshops when you're doing it face to face. But that just couldn't happen for a full year, maybe a little bit more than that. So we very quickly developed the smartphone app, and we found a way to move our entire workshop to a Zoom platform. And we'll have some data that we'll be sharing that basically says that we can do it just as well with the Zoom platform as doing it face to face. And what's more, it gives more people access to the technology. It allows for more sustainability because we're not only using Zoom, we're using different social media outlets. Most of the literature on hope enhancement--it's sometimes called hope augmentation--can demonstrate a spike in hopefulness after such an intervention. But the challenge then becomes how to sustain that hopefulness, and that's not easy. Well, by creating these digital communities of hopefulness, with the aid of different social media, we think that maybe this is exactly how we can deal with the sustainability question. And finally, this kind of technology gives us scalability. I mentioned before that we've been approached by groups around the world, throughout Europe, now throughout Asia, parts of Africa, not to mention North America. Haven't heard much from South America and Antarctica now that I'm thinking about it, so we're waiting for you guys. But we could never--all of us--I'm a busy physician as well. So there's a limit to how many times my colleagues would have to cover me when I say, "Oh, I'm off on another trip, teaching these hope techniques to people." But once we have it on Zoom platform, and we can bring, let's say, 15 to 20 people into the experience by bringing them into a Zoom room, I don't have to go anywhere. I can do it right from my living room, just like they're in their living room. And it sounds very simple, but I don't think anybody would have really imagined that we could be on our way like this if you sat down to contemplate this upside of 2019. ASCO Daily News: Right. And do you feel the response from the oncology community, from your peers across the world, has been quite positive? Scientists are sometimes skeptical about things such as hope enhancement techniques. Or have you found that not to be the case? Dr. Benjamin Corn: Yeah. That--so there's another example. I think that a barrier is the working assumptions of, let's say, my colleagues--let's say, me myself before I got into it. I mean, we're trained in a truly biological, scientific model. We talk about a biopsychosocial model, sometimes a biopsychosocial narrative model, but at its core, we pride ourselves as being scientists, and this kind of an idea was very off-putting to a lot of people. When we started publishing on this and the word got out that there were actually reproducible results showing that we can enhance hopefulness, people said, "Wait a second. I'm having a problem myself with patients who are just not hopeful." "Wait a second. I'm having a problem myself with my own burnout and my own compassion fatigue." And these colleagues have been seeking this out now in droves. And what our challenge has been right now is to be training facilitators so that we can really fan out and make sure that we answer this need of people saying, "I want to learn these techniques." Again, not just hope for hope's sake--I mean, I'm for hope. But for all the other upsides that we mentioned before--anti-burnout, increased adherence, probably bettered medical decision making--I think these are the motivators for people as opposed to just saying, "Make me more hopeful." So whatever gets you to the workshop, I couldn't care less. Everybody comes with their own reasons. That's always quite fascinating to hear why somebody decided to enroll in one of our workshops. But once people are there, most of them find that they really benefited from it. Typically, if we do a workshop with 20 people, the next day, we'll get a third to 40% of the participants saying, "You know what? I love this so much. I took these techniques, and I called in my children after dinner, and we talked about their goals and what struggles they're having in trying to reach the goals." So to me, that's very touching. And to get through your earlier question about the impact of this thing in communities outside of medicine, I think we're really on the cusp of forming what I like to describe as communities of hopefulness. And I think, again, we saw that in the COVID era. There was, in particular, a community in London that was very interested and brought us in also for a series of four workshops. And one of the things that we're working on right now in a hospital setting is what we call the seal of hopefulness. And that's based on, when I was growing up, this notion of the Good Housekeeping Seal of Approval. Well, we want to be able to approach hospitals and to say, "Just like you like to go through the accreditation process, perhaps you want to go through this process of making your staff more hopeful." Patients pick up on these things. So imagine, Geraldine, a world in which the physicians were taking care of you and the people you love, the nurses, the orderlies who bring them down to CT scans and the MRI. There's a lot of time that a patient in a hospital spends outside his or her bed. Imagine if en route to having a study, which you're very anxious about, you have somebody who's been trained and knows how to speak to you about your goals and your value. I think that would be the kind of environment I'd want to be taken care of in. I mean, of course I want to know that the knowledge base is top shelf. But could you imagine if there was this hope seal on the door that said, "People here really give a damn. They care about you, not just your tumor, and that is their commitment." I think that can be very reassuring. And we've begun to pitch that idea to hospital administrators, both in Israel, where I'm based, and in large-scale hospitals both on the community level and the academic level in the U.S. and Canada. ASCO Daily News: Excellent. Thank you so much, Dr. Corn, for telling us about your innovative work today. You really seem to be having a great impact. And I thank you very much for taking the time today. Dr. Benjamin Corn: Thank you. It was a pleasure. ASCO Daily News: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclosures: Dr. Ben Corn: None disclosed.  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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Hayes interviews Dr. Lawrence Baker on his early involvement with SWOG ANNOUNCER: 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. DANIEL HAYES: Welcome to JCO's Cancer Stories-- The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. Today, my guest on the podcast is Dr. Laurence H. "Barry" Baker. Dr. Baker has a long and distinguished career in oncology. It dates back to the early 1970s, when he was intimately involved in new drug development, including doxirubicin or adriamycin, as we know it. He's also led early studies in preoperative chemotherapy in anal cancers. He was instrumental in advances in sarcoma research, and he led the Southwest Oncology Group-- now designated SWOG-- for eight years in the last decade. Dr. Baker was raised in Brooklyn, and since this interview is taking place just a week after the sad loss of Supreme Court Justice Ruth Bader Ginsburg, Dr. Baker informed me that he and his wife Maxine were married in 1964 in the Midwood Jewish Center, Justice Ginsburg's home synagogue. He received his undergraduate degree from the Brooklyn College at the University of New York, and then he graduated from Des Moines University of Osteopathic Medicine in Iowa. He completed a residency in internal medicine at Flint Osteopathic Hospital in Flint, Michigan, and then he has a curious two-year break in his curriculum vitae during which he was on active duty in Vietnam. Upon discharge from the Army, he returned to Michigan, and he served a three year fellowship at Wayne State University, where he stayed on faculty from 1972 to 1994, serving at various times as the chief of the Division of Hematology and Oncology, the chair of the Department of Medicine, and director of the Cancer Center. In 1994, he moved west about 30 miles to Ann Arbor, where he served as the director for the Clinical Research and Translational and Clinical Research Program for the UM Comprehensive Cancer Center, now called the Rogel Cancer Center. And he was also the associate chief of the Division of Hematology and Oncology and currently is the Laurence H. Baker Collegiate Professor in developmental therapeutics. Dr. Baker has authored hundreds of peer-reviewed papers, and like so many of our guests on this program, he has a list of honors that are just, frankly, too long to recite, except two that I want to highlight. He received the ASCO Distinguished Service Award for Scientific Leadership in 2007, and he was named an ASCO Statesman, now designated as a fellow of ASCO in 2010, for his many services to our society. Dr. Baker, welcome to our program. LAURENCE H. BAKER: Thank you. Nice to be here. DANIEL HAYES: Well, it's really great to have you. A lot of questions, but I want to start out, I just can't help but ask you, to be trite, how does a nice boy from Brooklyn end up in the Midwest for the rest of his life? Can you give us some stories about how you got there? LAURENCE H. BAKER: I graduated high school at 15 and went into what some know-- but not everyone knows-- was a very competitive college. Brooklyn College accepted-- was a free school. The grades used in the New York City school system were numerical. They weren't letters. And you had to have a 90 average on high school and certain scores on the state, New York State examinations to get in. And that was it. It didn't matter where your parents went to school. It didn't matter if you had money. And so it was a school largely of relatively low-income families. But that's the one who took me, and I guess they accepted me at 15. To not make this into a long story, but to drag it out a little bit, I was fascinated that I was 15 and I could date 18-year-old girls, and they didn't know it. So that's how I spent the first two years of college. And my grades showed that that was my focus of attention. I did pretty well on the MCAT examination. I would not have gotten into a medical school in this country, and I didn't speak a language that would be sufficient for me to go to Europe, for example, to school. So osteopathy he was where I went. I went to Iowa, but their admitting question to me is, do you have $2,000 a year tuition? To which, of course, I lied. And that's how I ended up being a DO, and that's how I came to the Midwest. And I actually got to like the-- I didn't know anybody from Iowa, as you make reference to my Brooklyn background, but I actually came to really appreciate the Iowa people, and particularly the community people that I came to know. At the time there were-- the really good programs in residency in medicine were in Michigan. That's the direct answer to your question. That's how I came to Michigan. Just about then, just about could have gone to California and gotten an M.D. degree just by taking the licensure examination. And then, that closed. That opportunity closed. So a long story to your question. So I came to Detroit, into Flint, and then returned back to Detroit, and I've been in Michigan ever since. DANIEL HAYES: Now, that raises the second issue I talked about a minute ago. And that is, many of our guests were so-called Yellow Berets at the NIH in the late 1960s and really changed our practice. But you actually ended up in the Evacuation Hospital at Cu Chi in Vietnam. And I've heard horror stories about this. How did that happen? What did you do there? Enlighten me. LAURENCE H. BAKER: Well, there were good and bad things about being an osteopath. The American Osteopathic Association was always in conflict, was always trying to defend itself. And at the time that the Vietnam War was going on, the DOs were not eligible for military service as an officer. You could go in as an enlisted man, but not as an officer. But there was a great need for primary care physicians in Vietnam, and the understanding of the military physicians was that all DOs were primary care physicians. So a deal was struck between the AMA and the Department of Defense that led to the drafting of everyone in my medical school class. Every one of the men-- not women. Every one of the men was drafted. There was a universal draft. I then-- I was given a choice. I could volunteer for the Army or go to jail. Those were the choices. And I had, at the time, two little children with Maxine, and I was not-- you might guess-- not a big fan of the Vietnam War. The alternative was to go to Canada, and I wasn't secure enough to consider that I could actually practice medicine. It was uncertain. So I went in. When I got there, they asked me, did I have any interest in anesthesiology or radiology, because they were really short of those two. And of course, being who I am, I said, if you need a radiologist or an anesthesiologist, why don't you go draft one and let me go home? That didn't work, and so I became-- I was assigned to radiology. DANIEL HAYES: [LAUGHS] LAURENCE H. BAKER: They sent me to Fort Jackson, where-- no, that was actually a good experience then, because I learned a lot about imaging, and I still have interest in imaging, but I don't qualify anymore. This is before CAT scans and MRIs. This is IDPs and upper GIs, right? So anyhow, barium lower bowel examinations. So I was trained for six months, and I stayed on for another few months on staff there and then, lo and behold, was sent to Vietnam. I was sent for a year, but I volunteered to stay an extra month so that I could return without any further obligation to the military and begin my fellowship on July 1, which I had actually secured before I went to Vietnam. So that's the gory details of that. I was elevated to Major about, oh, a few months before I was discharged. And then, because they weren't nasty enough to me when I got home, into my fellowship, I then got a letter congratulating me on being in the active reserve. So I had to go two weeks every summer. That was my summer vacation during fellowship and beginning of faculty. And I had to go once a month for a weekend to play soldier with a bunch of guys who were lucky enough that they didn't have to go to Vietnam. And now we're even, I think. So it was an interesting experience, as I've shared some of it with you. It still is a painful experience in some ways. I was out the busy [INAUDIBLE]. DANIEL HAYES: If you don't mind, a quick story you've told me before about the child with leukemia. LAURENCE H. BAKER: Yes. So they made me a radiologist. I'm not a great-- it doesn't matter where you call me. I am who I am, and I'm really interested in patient care. And there were already five internists, and there was only so much gonorrhea that the troops could acquire. So I volunteered to open a pediatric clinic. And the Army thought that was a good thing for publicity. They did stories about it. Anyway, I opened the clinic for pediatrics. I knew nothing about pediatrics. I mean, the truth is, I had a month of rotation. My wife sent me my textbook. It was Nelson's Textbook of Pediatrics. Nothing I ever saw in Vietnam was ever in Nelson's Textbook. But I did what I could of trying to treat the children as best I could. And along came a young girl, eight years old, who had acute lymphacytic leukemia. I had a wonderful pathologist who was my hoochmate. "Hooch" is translated, there were eight guys who lived in a place. That was called a hooch. And he was a pathologist, and he made the diagnosis of ALL. I had my books from my mentor teaching me about chemotherapy. So even though I hadn't started the fellowship, I had some resources about chemotherapy. And now I had to find chemotherapy. Treated her with-- I started with steroids and penicillin, and then I went to find drugs. I was able to-- I won't tell all the details, but I was able to get drugs at an old French hospital in Saigon. And so I would visit that hospital pretending great interest in the pharmacy, but of course, I stole whatever drug I could steal when the pharmacy wasn't looking. And that included some alkylating agents, methotrexate, 6MP. And so I tell Jay [INAUDIBLE]-- to get to where you want to be, perhaps-- that I invented the bicycle therapy, which was every month, you changed the drug to try to avoid resistance. So that's what I did by necessity. [LAUGHS] And I actually-- there was a second child that I also treated. When I left, they were both in complete remission. And I think that that's what you're asking me. I was lucky that I didn't get shot or thrown in jail for many of these escapades. But I look back and think that at least I did somebody some good. So-- DANIEL HAYES: Kind of makes the current generation who complains about work hours look in a different light, I think. LAURENCE H. BAKER: Yeah, we worked every day. We worked seven days a week with-- there was no such thing as time off. This was the busiest American hospital, certainly in Vietnam, and some think the busiest hospital since the Atlanta train station in the Civil War. It was in Cu Chi, which was on the way to Cambodia, which is, of course, where the North Vietnamese troops would enter into South Vietnam. So it was a major, major place. It was about an hour, an hour and a half west of Saigon. DANIEL HAYES: Let's move on to the rest of your career. You come back, then, and trained at Wayne State, and at the time, [INAUDIBLE]-- and I can never pronounce his name. I'll have you do it. Dr. Venutius Vicevicius-- I always heard him Dr. V.-- who was, I think, a real character and really was one of the first chemotherapy pioneers. Can you tell us more about him? Because we've heard a lot about the folks on the East Coast and the folks in Texas, but not so much what was going on in the middle of the country at the time. LAURENCE H. BAKER: Yeah, Dr. V, or Dr. Vicevicius, who was Lithuanian, he has a story of his life that certainly makes me look like a slump. He was a guest of the Nazis, and then he was a guest of the Russians when Auschwitz was freed. So this was as a child. He grew up in a very educated and somewhat affluent family in Vilnius. And when he got out of these camps, he actually got to medical school in Frankfurt, Goethe Medical School in Frankfurt. He had major interest in biochemistry and, without speaking more than three words of English, chose to come to the United States. And he landed-- I don't really know why; I've heard so many different versions-- but he landed in Detroit and showed up at the Detroit Receiving Hospital-- this would be like LA County or Bellevue in New York, that sort of thing, knife and gun club-- not speaking any English but wanting to do training. And somebody was smart enough to accept him. And so he did his training. He also trained-- after medicine, he trained with Mike Brennan-- that's another name from the past who is a past president of ASCO, by the way, the second or third person, perhaps. Mike was present of the Michigan Cancer Foundation and was the card-carrying medical oncologist in the Detroit area. He trained Dr. V., and he trained another man named Bob Tally, who had a great deal of history to contribute to oncology. And then, V was recruited by Wayne to come there and started a program. He was an extraordinary person. English was the eighth language he learned, and he actually taught me how to write. I flunked college English. I had to take it twice. But he taught me how to write and, I think, made me a better writer. He certainly was an inspiration. His devotion to patients was extraordinary. His knowledge was extraordinary. And so he was a great, great teacher. And one of his major early contributions was the recognition that you could make the drug float-- they had four drugs or five drugs at this time-- but one of them was 5-fluorouracil, that was developed by Fred Ansfield in Minnesota. The drug was given for five days and then every other day until their mouth fell out or their white count got to zero. And maybe that's a little of an exaggeration, but not much. At any rate, he figured out if you gave the drug by continuous infusion-- because it had a rather short half-life-- you could avoid a great deal of the toxicity. And that's how infusion of fluorouracil got its start. He then went on to combine it with other drugs and with radiation, and that was the backbone of this anal canal achievement that you mentioned in the introduction. I had very little to do with it, but I was a cheerleader. It was a rectal surgeon who came to us at the time, and those familiar with that disease-- which we now know is a virus disease that could be prevented, but at that time, nobody had any of that-- the treatment was abdominal perineal resection, and it had to be among the most horrible things we did to people. And the surgeon came to us and said, listen, you guys always squirt those drugs in after they relapse, and I'm really tired of this. Maybe you could give those drugs first, OK? And that's how neoadjuvant chemotherapy got started. It wasn't our idea. It was a surgeon's idea. That story gets repeated again in orthopedics, but that's how it began in anal canal tumors. And so we gave 5FU infusion, and mitomycin, and radiation preoperatively. That almost always shrunk the tumor, by the way-- almost always significantly shrunk the tumor. The patient then once they went through that operation but was cured. And so you took a horrible disease and changed its natural history with that development. If it works once, you know, in oncology, then you try it a second and third time. And I had very shortly thereafter the opportunity to work with a wonderful Japanese pediatric oncologist in Houston, Watsu Tao. He was looking for a partner because he was tired of seeing osteosarcoma patients die. Cure rate at the time was around 20%, 30%, and the surgery that was done for osteosarcoma was amputation, usually of the lower extremities. So 2/3 of osteosarcomas occur around the knee, and the orthopedics really dislike the idea of taking a child's leg off. Every teenager and child wants to be exactly like every other teenager and child, so you can imagine how disruptive it is to have a high amputation of your leg. It took about three months to make a prosthesis, and everyone knew that you didn't really have to do an amputation. You could just cut out the bad bone and replace it with a prosthetic device. But it took three months to make it, because they were handmade at the time. And so the idea came to several people-- Jim Holland was involved in this; Tom Frei was involved in this as well. Different cities were approaching it in this way. And we all ended up giving chemotherapy to these young people-- children, teenagers-- and then having the operation. And osteosarcoma went a cure rate of 20% to 30% to 70% or 80%. And they didn't lose their legs. DANIEL HAYES: I have two personal comments on this. One is you mentioned Dr. Brennan and the Michigan Cancer Foundation. Just for our listeners, Michigan Cancer Foundation is MCF. And if you've done any breast cancer work at all, you've worked with MCF-7 cells or MCF-10 cells [INAUDIBLE], which came from that organization. I think people have forgotten what MCF stands for, except for you and me. LAURENCE H. BAKER: That cell line that you talked about, MCF-7, that was developed by a man with, I think, a high school degree who just had a green thumb at that growing cells-- a wonderful man. And that came from a patient of ours. When I say "ours," I mean Dr. V. I was just the flunky, but it was his patient. And she had ascites from breast cancer. And we would tap ascites, in those days, with some frequency. And the cells for MCF-7 came out of that patient. That's its actual origins, and more papers have been written about MCF-7 than even you and I could count. DANIEL HAYES: Including by me. LAURENCE H. BAKER: I understand. No, it was incredibly useful. I mean, we learned about hormone receptors from this [INAUDIBLE]. DANIEL HAYES: Yep, that's [INAUDIBLE]. LAURENCE H. BAKER: It's was incredible. DANIEL HAYES: My other personal story related to your stories is, as a fellow at the then Sidney Farber Cancer Institute, Dr. Frei was my boss. And he, as you mentioned, was starting to work with Holland and others that had already worked with neoadjuvants. And he would cite your data all the time. Now, I didn't know Larry Baker for us from all the tea in China, but we heard a lot about the Wayne State experience when we were fellows. I don't know if that would have [INAUDIBLE] or not, but people definitely-- LAURENCE H. BAKER: No, I came to SWOG-- which is really why you wanted, I think, to talk to me-- in '70 or '71, I can't remember exactly. And Dr. V, it was an incredible experience. He took me with him. You ran into Tom Frei. They knew each other. And he said, Tom, I want you to meet my colleague, Larry Baker. I just had never been introduced like that. DANIEL HAYES: [LAUGHS] LAURENCE H. BAKER: And Tom was the friendliest person I think I've ever met in oncology. He had a wonderful smile. He clearly-- I was always paranoid that I'm a osteopath. Maybe I went on too long about that story. But when they tell you in school you're just as good as the MDs, you can quickly figure out if you were just as good, they wouldn't keep saying it, right? So that's socially accepted paranoia, and that's how I was brought up. So here is the wonderful, famous Tom Frei being nice to me! I was just amazed. DANIEL HAYES: He used to come to the lunch room in the Dana Farber two or three times a week and would just sit with us, and was constantly thinking of new stuff. This is not an interview with me, but someday, I'd like to tell the stories he told us. He was really just a fabulous man. I want to segway into your work with adriamycin, which is now, of course, also one of the workhorses of oncology. We've all used it. And I believe you were an author on either the first or one of the first phase II trials of adriamycin in Cancer in 1973. Is that an outgrowth of that introduction you just told us? LAURENCE H. BAKER: Yes. That study-- it's in Cancer, I think, not-- I don't think JCO existed. But that study didn't distinguish what the primary was. So it was a phase II study of cancer. And so there was, I don't know, 800 patients. I worked with Bob or Brian on that study. Bob was at Henry Ford, and there was a student of Bob Tally that I had mentioned, and I was the student of V. And the two of us were basically the schleppers for them. And so it had hundreds of patients in it. And in that study, we recognized that it worked in breast cancer, that it worked in lymphoma, and it worked in sarcoma-- and nothing worked in sarcoma. So that was the study. It's often quoted by Jim Dorshow because he said, we do everything that's disease-specific, but look what came out of one study that, by the way, accrued, as I say, 600 or 700 patients in 18 months. And this is before computers, so you can imagine how much work was done to evaluate the flow sheets. It was an incredible opportunity here to work. But it was an amazing paper, and it changed my life, of course. That's how [INAUDIBLE] and other things. DANIEL HAYES: So at the time, you recognized that this was not just another drug off the shelf, that it really was going to be a game-changer? LAURENCE H. BAKER: Absolutely, absolutely. You saw people getting better. And my experiences were mostly in breast cancer patients getting better, and some lymphoma patients that were refractory. First time I saw solid tumor patients dramatically improve. DANIEL HAYES: So I saw that your name is before another giant in the field who was a young Italian investigator who spent time in the United States named Johnny [INAUDIBLE]. LAURENCE H. BAKER: Yeah, that's how I first met him. I don't know that this story's been told. We were trying to make some level of peace with the Russians, and the Russians, of course, claimed that they discovered adriamycin. I don't know, but if you don't know this, I'll continue. DANIEL HAYES: Please go. LAURENCE H. BAKER: OK, but we all-- everyone knew, and certainly [INAUDIBLE] knew, this was an Italian drug, OK? "Adriamycin" is for the Adriatic Sea. As far as I know, you can't see the Adriatic Sea from Russia. But this was a time when our government wanted to be nice. They cared more about building a relationship with the Soviet Union than they did continuing a friendship with the Italians. Jim Holland was then sent to Moscow to negotiate this. That's where the name doxirubicin came from. In other words, we didn't know generic names, trade names. This didn't exist in the early '70s. So we called it adriamycin, which was not only the generic name, it was the trade name, right? Made by adria-- I think far Pharmitalia is the name of the company, right? And as a result of Jim Holland's diplomacy, it became doxirubicin as the generic name. It's a true story. DANIEL HAYES: Yeah. I know that "adria--" came from the Adriatic Sea, but I've not heard that's where "doxi-" came from. That's a good story. That segways into the next segment of your life that fascinates me, and this is your work in SWOG. When I moved here to the University of Michigan, you were on your way to becoming the chair of SWOG, which you did. And it occurred to me that University of Michigan wasn't even in Southwest Michigan, let alone the Southwest of the United States. Just reminisce a little bit about Dr. Coltman, who ran SWOG, the beginnings of SWOG, even before that, and where you see the [INAUDIBLE] groups now. LAURENCE H. BAKER: So Dr. V brought me to a SWOG meeting in San Antonio, Texas, as you said, in 1970 or '71. At the time, Tom Frei was running the group. J. Freireich was chairman of the Leukemia Committee. Chuck Coltman was chairman of the Lymphoma Committee. V specifically chose to work with this group because of those people. You're right, Michigan is not in the Southwest, obviously, and, there were other groups that wanted-- we had a large population of patients we treated, so there was actually some competition, if you will, for us to join other groups. V was adamant that we would be SWOG and that was it, for reasons that I told you. Tom Frei then was invited to go back to Boston. That's how you came to know him. And there was an election for a replacement. And J. Freireich was somebody that we clearly supported. There was no doubt that J. an absolutely brilliant man-- he still is-- and taught a lot of people, trained a lot of people, and taught us a great deal. But he had one flaw. He could not control his ability to saw inappropriate things. If you knew him, you loved him. If you didn't know him, you were like your reaction to the debate, OK? That's how he ground on people. I grew up with the respect for J., as I told you, as I was introduced to him, and he was always incredibly kind to me. Anyway, so we were actively supporting J. To be the replacement. There were some other people that did not want Freireich. So you had some people who didn't have the same feeling. And that's how Boris Hoogstraten became chairman. Boris Hoogstraten was a hematologist from the University of Kansas. And I remember-- and you'll be very proud of me, Dan-- one of my colleagues from Wayne wanted to do a study of this new drug called tamoxifen-- DANIEL HAYES: [LAUGHS] LAURENCE H. BAKER: --for breast cancer, OK? [LAUGHS] And Hoogstraten said, don't you get it, Baker? We're a chemotherapy group. What's with this hormone stuff? I don't have to tell another story, but that one is true. So SWOG didn't study tamoxifen for a long time. Any rate, Boris was an interesting man. I don't want to cut him short. But there came a time when it was clear that SWOG needed to go in a different direction. And we all thought that the right person for that was Chuck Colton. At the time, I have to tell you, there was two things relevant to this. There were lots of regional cooperative groups that don't exist anymore. I led a revolt-- that's what Colton said-- that included the University of Indiana-- Larry Einhorn was in Detroit plotting against Hoogstraten-- along with the University of Michigan. Al Labulio was in Detroit doing that. So you got the idea. So it was a group of institutions, if you want, that were geographically somehow related to the Great Lakes in some way. There were seven or eight of us. And we represented probably 40% of the [INAUDIBLE] of SWOG. And Coltman came to me and said, listen, stay with the group. Don't do this. Stay with the group. And I said, I can't stand this nonsense. I mean, we're not working anymore. We're just-- Anyway, he said, please stay. And he ended up becoming the chairman. And then he turned to me and he said, listen, Larry, I want you to be the deputy. I don't need a title. I don't want a title. He said, no, no, no, I don't care what you need or what you want. I need you right next to me, because if you led a revolt once, I don't want to see it happen again. DANIEL HAYES: [LAUGHS] LAURENCE H. BAKER: Absolutely true story. And so we abandoned the idea of a regional group. I still think that may have been a dynamite group, by the way. But we all stayed-- Indiana was not [INAUDIBLE] SWOG, so let me be clear. That was ECOG, I think. I think that's right. Anyway, so that's how I came to know Chuck, and I was his deputy for 25 years. I had the best job as deputy, because I had nothing to do. He just wanted me sitting there, and that's what we wanted. Then there was some push from the NCI that maybe to 25 years of being chair is a long time, and maybe there's a reason to move on. From that team the suggestion from Bob Livingston and John Crowley, that I was the natural person to do that. I really didn't want it, to be honest. I still maintain that. But there was a good deal of pressure exerted, both from within the group and from the NCI, for me to do that. So I became the chairman, I think, for a couple of terms. I made some changes in the group. I think as groups go on, institutions either get better or they get worse. I think that's true. And we made a number of different ways of appointing disease chairs and things like that, that the group did get better and started on a better path. But I really didn't want to continue it, and there was a time when I was not only running SWOG, but I was also running this sarcoma group called SARC. And it became overwhelming to me. I was working literally 80 hours a week there. So I gave up SARC first. That really-- University of Michigan was thrilled that I did that-- and stayed with SWOG another year or two. But I knew that I wasn't going to stay at that. And so after two terms, I thought I would set the precedent that, maybe, group chairs should have two terms and move on. Witshoski had two two terms. [LAUGHS] But anyway, being serious, I really think there should be a limited amount of time. There's so many talented people in our field that it's silly to think that one person has to stay in these jobs. And so that's-- I think I answered your question. I'm not sure my [INAUDIBLE]. DANIEL HAYES: I have to tell just a brief-- Nobel laureate Bruce Beutler was my intern when I was a resident at UT-Southwestern. After he won the prize, he came up here as a visiting professor, and we went to dinner. And I said, Bruce, I kind of lost track. I know you did an internship with us, but I never heard if you finished your clinical training. And he said, no, I went-- I loved the lab and went back into it. I never did go back and finish my training [INAUDIBLE]. And then he looked at me and said, but I think I worked down all right, don't you? LAURENCE H. BAKER: [LAUGHS] DANIEL HAYES: And in a similar manner, I would say, for all your humility that you've laid out, I think it worked out all right. SWOG is a powerhouse and has changed practice in so many ways. And part of that, a lot of that, was your doing. So we've actually run out of time. I had hoped, actually, to-- you've done too much in your lifetime, Larry. I was hoping to get into the sarcoma work, but we've run out of time. I think everybody who's listening to this who knows about the work you've done in sarcoma-- and lord knows there's plenty of work to do in sarcoma, so-- LAURENCE H. BAKER: Can I give you just one more anecdote, and you can cut it, and I'll try to be very [INAUDIBLE]? DANIEL HAYES: No, no. Please do, please do. LAURENCE H. BAKER: Remember I told you I became chair of the Sarcoma Committee of SWOG? The man I replaced was a man named Jeff Gottlieb. Jeff was a pediatric oncologist-- little did people know-- who was a student of J and Tom at the NCI. Jeff died in his mid-30s of cancer, by the way, but he was the most brilliant medical oncologist I ever met. He was the originator of combination chemotherapy that became popular in breast cancer, and he was involved in sarcomas in combinations as well. I was handpicked by Jeff to be his replacement, which was probably the nicest thing that ever happened to me. And during that period when Jeff died, I went to Houston to his funeral. And I can give you one-sentence description of J. Freireich going to speak at Jeff's funeral. He stood up, and he said, Jeff-- and he broke down and cried for minutes. And that was his talk. When anyone says something to me critical of J. Freireich, I remember that love he showed to his colleague. So that's worth [INAUDIBLE]. DANIEL HAYES: No, that's-- LAURENCE H. BAKER: Not many people were at that funeral. DANIEL HAYES: --very touching. He also gave Dr. Frei's eulogy in Boston, and he got through it, but just barely. It was very similar. These are the kinds of stories I'm hoping to capture in this series. Larry, I'd really like to thank you for taking time to be on. I'd also like to thank you for all you've done for the field, for me personally, frankly, with my time here in Michigan the last 20 years, and most importantly, for our patients who have benefited from all your contributions, your training of-- we could go on about all the people you've trained. So anyway, thanks a lot. We appreciate it. LAURENCE H. BAKER: Thank you. DANIEL HAYES: And have a nice day. LAURENCE H. BAKER: Thank you very much. I appreciate your kind words. DANIEL HAYES: Until next time, thank you for listening to this JCO's Cancer Stories-- The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts, or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories-- The Art of Oncology podcast is just one ASCO's many podcasts. You can find all the shows at podcast.asco.org

Various cancers are to be closely linked to obesity. Obesity also has ramifications on the management of various cancers. We discuss this intricate relationship in detail with Dr. Sonam Puri.  Dr. Puri is an Assistant Professor in the Division of Oncology, Department of Medicine at the University of Utah. Her area of expertise is the treatment of thoracic malignancies.Her research interests include clinical research in thoracic malignancies, with emphasis on immunotherapy, targeted therapy, and other novel treatment strategies for non-small and small cell lung cancer.She is an active member of various national and international organizations including the Lung Cancer Disease Center of Excellence at the Huntsman cancer institute, the American Society of Medical Oncology, Southwest Oncology Group, Society of Immunotherapy of Cancer, and International Association of study of lung cancer.She also serves on the National Network Clinical guideline panel for small cell lung cancer.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In this podcast, Cancer.Net Associate Editor Dr. Michael Williams will discuss some of the new research in lymphoma that was presented at the 2019 American Society of Hematology Annual Meeting, held December seventh through tenth in Orlando, Florida. Dr. Williams is the Chief of the Hematology/Oncology Division and Director of the Hematologic Malignancies Program at the UVA Cancer Center. He is also the Byrd S. Leavell Professor of Medicine and Professor of Pathology at the University of Virginia School of Medicine. View Dr. Williams’ disclosures at Cancer.Net. ASCO would like to thank Dr. Williams for discussing this research. Dr. Williams: Hello, and thanks for joining us for this podcast. My name is Michael Williams. I'm Professor and Chief of Hematology/Oncology at the University of Virginia in Charlottesville. And I'm pleased to discuss some exciting advances in lymphoma that were presented at the American Society of Hematology meeting held in Orlando in December 2019. My disclosures are that my research group here at the university, through the university, has received research support from pharmaceutical companies AbbVie, Pharmacyclics, and Janssen, and I have received honoraria for speaking at conferences from Xian-Janssen in China. So what I'm going to talk about today are 2 reports about the management of localized diffuse large B-cell lymphoma, an update on a novel therapeutic approach for relapsed mantle cell lymphoma. And then, I'll finish with a brief introduction of an agent that is showing promise for treating highly resistant relapsed lymphoma that was presented in the plenary session during the ASH meeting. So let's start with localized diffuse large B-cell lymphoma. So DLBCL is the most common subtype among the many forms of non-Hodgkin lymphoma. Usually, people present with advanced stage disease. But as many as 25 to 30 percent may have a disease that's localized to just 1 site or a very localized area of lymph nodes, so these would be stage I or stage ll patients. And the first report that I'll comment upon was presented by Dr. Laurie Sehn at the BC Cancer Agency in Vancouver, British Columbia. So they did a retrospective review looking at 319 patients treated in British Columbia over the past 15 years. So these were patients who had a nonbulky mass, they were localized disease. And the treatment currently for this disease is that people get either 6 cycles of a regimen such as rituximab and CHOP chemotherapy or more limited chemotherapy. Typically, 3 cycles of R-CHOP followed by radiation therapy. The importance of this study is that it is exploring a mechanism to de-escalate therapy, if you will, by avoiding the use of the radiation therapy. So what they did, is patients with localized disease received 3 cycles of rituximab plus CHOP therapy and then underwent a PET scan. So PET scans, unlike CT scans, are nuclear-medicine imaging that shows the functional uptake of radioactive glucose by the sites involved by lymphoma. So if you become PET negative after the three cycles of rituximab, CHOP therapy, then it seems likely that you've got a very highly responsive disease, and you may be able to avoid radiation therapy. So they did the PET scan after 3 cycles, and for those who were PET negative, then those patients received 1 additional cycle of rituximab CHOP, and that was the end of their therapy. If they were still PET positive, then they moved on to radiation therapy to the involved area. So what they found was quite interesting that of the 319 patients, 254 were negative after their PET scan. And so went on, virtually all of them, to just getting 1 more cycle of rituximab CHOP as planned. The outcomes for those patients were that very few of them relapsed over the next several years. They followed patients now, for about four years or more, in most cases, and they found that the overall, 5-year progression-free survival was 88% for those who were PET negative. For the subset of patients who were still PET positive, and got the radiation therapy, their outcome was somewhat worse, in that there was only 74% who were still progression free. The overall survival for these patients was 90%, at 5 years, for those who were PET negative and 77% for PET positive. So what this study shows us, is that a PET scan after 3 cycles, can inform us about patients who are 90% likely to have good control of their disease, with just 4 treatments, and you can avoid the exposure to radiation therapy. Those who were still PET positive still did well: 3 out of 4 were still in remission beyond 5 years but not quite as good an outcome. So these are patients who may be candidates for an alternative approach to try to do better with their long-term cure rates. So that leads us to the second presentation that I want to discuss. This was presented by Dr. Daniel Persky on behalf of the Southwest Oncology Group, which is part of the National Clinical Trials Network, in the United States. So they had a very similar approach. They studied patients with localized Stage 1 or 11, nonbulky diffuse large B-cell lymphoma, and they got standard rituximab CHOP therapy, and then a PET scan after the third cycle. Just as in the paper I discussed from British Columbia. Those who had negative PET scans got one additional cycle of rituximab CHOP. Those who were still PET positive got involved-field radiation therapy and treatment with a radio-labeled monoclonal antibody. Essentially, a radioactive form of rituximab, which has given us a single dose about a month after they'd finished their involved-field radiation therapy and then they got a follow-up PET scan, thereafter. So this study went on for several years, at multiple sites around the country. They enrolled 132 patients, and of those patients, 110 were PET negative after their third cycle. So only 18 needed to go on to this additional radiation therapy and the systemic treatment with the radio immuno therapeutic called Ibritumomab tiuxetan. They followed these patients now for 4 and a half years, and only 5 patients have progressed, and only 2 have died of their lymphoma. So of those who progressed, 3 of them had gotten just the R-CHOP alone. There was another patient who was PET positive but declined getting the radiation therapy who progressed. And then, another patient who had only 1 treatment was rituximab CHOP but then went off treatment due to toxicity. So similar, and in fact, almost identical to the British Columbia report. Five-year freedom from progression of their disease was 87%, and the overall survival was 90%. So these patients can do quite well, since many times, the location for localized DLBCL is in the head neck. There can be significant late effects of radiation therapy. So I think these studies reassure us that patients with localized disease can have very durable outcomes and cure rates. It's important to note that there's a higher rate of late relapse beyond three years in patients with localized DLBCL compared to more diffuse extensive disease suggesting that there may be some differences in the biology of a localized disease. So very important data, and data that gives us the opportunity to de-escalate treatment in localized large cell lymphoma. So let's switch gears and talk about mantle cell lymphoma. There's been a lot of progress in this disease over the past decade. Much of it related to the use of nonchemotherapy targeted agents such as Bruton’s tyrosine kinase inhibitors including ibrutinib and the Bcl-2 inhibitor, venetoclax. There was a study reported last year by an Australian group led by Dr. Constantine Tam. This study was updated at the ASH meeting with a longer follow up. So these were patients with Relapsed/Refractory disease, heavily pretreated. Many of them, previously, having had intensive chemotherapy and a stem cell transplant. And half of them had mutations in a gene called TP53, which is correlated with frequent chemotherapy resistance and high relapse rate. And what they found by combining the targeted agents ibrutinib and venetoclax, that they got very high response rates. The majority of patients responded although, there were a few who were primarily resistant, and about a third of patients, actually, got very deep remissions. PET negative and negative for minimal residual disease detection. If you look at the subset, of the highest risk patients, with the TP53 mutation, half of them achieved a complete response rate, and some of these patients have had durable responses. There have been a few patients who've had deep responses, who've been able to come off treatment. And overall, the duration of response at 2 and a half years is 74%. But what this study shows us, is yet again, that these novel targeted drugs that are typically better tolerated than cytotoxic chemotherapy can have very good and indeed dramatic responses, and so is showing a lot of promise. It reminds us that in mantle cell, whether it's newly diagnosed or relapsed, that talking to your oncologist about clinical trial opportunities can often avail you of some of the most promising new approaches. And indeed, that's true for all forms of lymphoma, that clinical trial options should be part of the discussion with treatment planning. I'm going to finish by just mentioning another novel agent that is being applied to patients with highly resistant relapsed disease. This is a molecule called mosunetuzumab, and this is a bispecific antibody. So there are a number of these now that are in clinical development, and some are FDA approved for treating leukemias and certain lymphomas. This one is designed to basically connect a body's immune system, the T cells, with the B-cell lymphomas by using an antibody that can recognize each of those and bring them physically together. So this was presented by Dr. Steven Schuster; it was a multinational study of this bispecific antibody in patients with very aggressive relapsed/refractory lymphomas including, diffuse large B-cell and transformed follicular lymphoma. And what they found in this study, is that response rates were 64%, with 42% of patients achieving a complete remission. So it's still early, but quite promising because these are patients who had failed CAR T-cell therapy. They may have failed transplant, or they were patients who needed a treatment to bridge them over to get to a CAR T or another treatment such as an allogeneic stem cell transplant. The toxicities were generally manageable and similar to those seen with other bispecific antibodies. So it's early, but across subtypes of patients with aggressive and relapsed lymphoma, I think this is another promising molecule, that may well provide good therapeutic options via a clinical trial for patients who have very limited other options to manage their disease. So thanks again for joining this podcast. There was a lot of other exciting data that we didn't have time to go through, so I encourage you to continue learning about what's new in the field, discussing with your oncologist, or with a consulting specialist in lymphoma, to make sure you can avail yourself of the best in current diagnostics and therapeutics. Thanks very much. ASCO: Thank you, Dr. Williams. Learn more about lymphoma at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by the Conquer Cancer Foundation of ASCO, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

TRANSCRIPT 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Rachna Shroff from the University of Arizona Cancer Center, lead author on "Adjuvant Therapy for Resected Biliary Tract Cancer: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Shroff. Thank you so much for having me. So what does this guideline recommend? This is a guideline that is basically looking at the role of post-operative therapy in patients who undergo surgical resection for biliary tract cancers. Biliary tract cancers are a somewhat heterogeneous group of malignancies that include intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancer. And so the question always in most cancers are, if you are able to undergo surgical and curative treatment, is there a role for post-operative chemotherapy or radiation therapy to help improve the chance of cure and decrease the risk of recurrence? So that is exactly what we investigated as an expert panel. So our recommendations are actually twofold. The first one is that we are clearly recommending that patients with resected biliary tract cancer should be offered adjuvant chemotherapy with capecitabine for a total of six months. Within that recommendation, we do acknowledge that this is based on the BILCAP phase III randomized controlled trial and that there was a specific dosing and treatment schedule that was done in that study, but that we are allowing for institutional and regional variances that we've noted in terms of dosing of capecitabine. And so as a result, we're recommending adjuvant capecitabine, and we're allowing practitioners to determine what the best and safest dosing would be, based on their experience. The second recommendation is more specifically for patients with extrahepatic cholangiocarcinoma or gallbladder cancer who undergo resection and have a microscopically positive surgical margin, which is an R1 resection. And in those patients, we are recommending that we could consider offering these patients chemoradiation therapy. Now, again, this is not as strong of a recommendation, because we do not have prospective randomized phase III data to support it. This was based more on a prospective single-arm study out of the Southwest Oncology Group, as well as some other retrospective studies. And so we do go on to qualify that that recommendation should really be made in a shared decision-making approach, with a multidisciplinary conversation to decide the risks and benefits of radiation in these patients-- and that we acknowledge that a prospective study would really help clarify that question a little bit more. So can you tell us about the research that informed these recommendations? There have been a number of studies that have looked at the role of adjuvant therapy in biliary cancers. And up until very recently, a lot of these studies were small retrospective series, single-institution or multi-institution, but everything in retrospect-- no prospective or randomized data. And so I think a lot of the reasons that we decided to have these guidelines come out now is that in the last two to three years we do finally have prospective randomized data that helps guide the recommendations. And the majority of the recommendations that we made are based on one randomized phase III, which is BILCAP study. This was a study that was done in the UK and was presented at ASCO in 2018 and is currently in press. And it is basically a randomized controlled trial that compares adjuvant capecitabine by itself versus surveillance alone in patients who undergo surgery for biliary tract cancers. And so our recommendations, which include that study as well as a couple others, is primarily hinged on that, since that is the largest prospective data we have so far. And based on that study, we did in fact recommend that there was a role for adjuvant chemotherapy with capecitabine after complete resection for biliary tract cancers. And based on that research that was done in that trial that was completed, we do believe that the role for capecitabine for six months is pretty strong and that the data supports that now. So why is this guideline so important, and how will it change practice? Well, I think it's going to be practice-changing because up until now there has not been a clear consensus on how we approach these patients. And I will say that even now, it's really just this one study that has helped guiding these recommendations. There were a number of other studies that we looked at as part of the expert panel. And these were all prospective studies as well that looked at things like gemcitabine and oxaliplatin in the adjuvant setting, or single-arm phase II studies that came out of the Southwest Oncology Group that also explored the role of radiation. But really, nothing was a positive study other than the BILCAP study. And so up until now, I would say it was a little bit all over the place in terms of how medical oncologists approached resected biliary cancers. I think the majority of us felt that there was probably a role for adjuvant chemotherapy or perhaps chemoradiation. But there was no rules that we could follow, and there was no clear study that we could turn to that would tell us what we should give, how long we should give it for, and whether it should be a combination of chemotherapy or chemoradiation. And so I think it will be practice-changing because now, as part of the expert panel, we are making a very clear recommendation that patients with resected biliary tract cancer should be offered adjuvant capecitabine chemotherapy for a total of six months, hopefully eliminating that kind of regional or specialist-based variation that has been happening up until this point. And finally, how will these guideline recommendations affect patients? Again, I think that the main way it's going to affect them is that there's going to be a little bit less gray area, in terms of medical oncologists having conversations with the patients and saying, well, you know, I think that there's probably a role for agent therapy here, but I can't show you the data that supports why I think that. And as a result, I would hope that patients will have a little bit more faith and confidence in knowing that there is a large study that has looked at and proven the benefit of adjuvant capecitabine and that that decreases the chance of recurrence and improves overall survival. The improvement in overall survival was dramatic in this study. And we had not seen a survival of 51 months, which is what we saw in this study, in a very long time. So for patients, not only does it make clear what they should be doing after surgery, but I would hope it also gives them additional hope that we have really changed the bar by doing this adjuvant capecitabine, and that the chance for cure is even higher when we can offer adjuvant chemotherapy. I think the only other thing that may still be a gray area, and that is kind of what we allude to in our second recommendation, and that is in patients who undergo resection and have a microscopically positive margin or an R1 resection. And that's typically patients with extrahepatic cholangiocarcinoma or gall bladder cancer. In those patients, we suggest that they could be offered chemoradiation therapy, but the evidence is not as strong there. Again, it's more retrospective studies that we looked at. There is no prospective study that answers the question of whether or not there's a role for radiation. And so as a result for patients, I think that is still the one area that's a little bit of a gray zone in terms of knowing whether chemoradiation would benefit them if they undergo surgery and have a microscopically positive resection. But I do think that there is a definitive benefit to giving adjuvant chemotherapy, and that, hopefully, will clarify things not only from the physician perspective but also from the patient perspective. Great. Thank you for your work on these important guidelines, and thank you for your time today, Dr. Shroff. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello and welcome to the ASCO Guidelines Podcast series. My name is Shannon McKernin, and today I'm interviewing Dr. Rachna Shroff from the University of Arizona Cancer Center, lead author on "Adjuvant Therapy for Resected Biliary Tract Cancer: ASCO Clinical Practice Guideline." Thank you for being here today, Dr. Shroff. Thank you so much for having me. So what does this guideline recommend? This is a guideline that is basically looking at the role of post-operative therapy in patients who undergo surgical resection for biliary tract cancers. Biliary tract cancers are a somewhat heterogeneous group of malignancies that include intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gall bladder cancer. And so the question always in most cancers are, if you are able to undergo surgical and curative treatment, is there a role for post-operative chemotherapy or radiation therapy to help improve the chance of cure and decrease the risk of recurrence? So that is exactly what we investigated as an expert panel. So our recommendations are actually twofold. The first one is that we are clearly recommending that patients with resected biliary tract cancer should be offered adjuvant chemotherapy with capecitabine for a total of six months. Within that recommendation, we do acknowledge that this is based on the BILCAP phase III randomized controlled trial and that there was a specific dosing and treatment schedule that was done in that study, but that we are allowing for institutional and regional variances that we've noted in terms of dosing of capecitabine. And so as a result, we're recommending adjuvant capecitabine, and we're allowing practitioners to determine what the best and safest dosing would be, based on their experience. The second recommendation is more specifically for patients with extrahepatic cholangiocarcinoma or gallbladder cancer who undergo resection and have a microscopically positive surgical margin, which is an R1 resection. And in those patients, we are recommending that we could consider offering these patients chemoradiation therapy. Now, again, this is not as strong of a recommendation, because we do not have prospective randomized phase III data to support it. This was based more on a prospective single-arm study out of the Southwest Oncology Group, as well as some other retrospective studies. And so we do go on to qualify that that recommendation should really be made in a shared decision-making approach, with a multidisciplinary conversation to decide the risks and benefits of radiation in these patients-- and that we acknowledge that a prospective study would really help clarify that question a little bit more. So can you tell us about the research that informed these recommendations? There have been a number of studies that have looked at the role of adjuvant therapy in biliary cancers. And up until very recently, a lot of these studies were small retrospective series, single-institution or multi-institution, but everything in retrospect-- no prospective or randomized data. And so I think a lot of the reasons that we decided to have these guidelines come out now is that in the last two to three years we do finally have prospective randomized data that helps guide the recommendations. And the majority of the recommendations that we made are based on one randomized phase III, which is BILCAP study. This was a study that was done in the UK and was presented at ASCO in 2018 and is currently in press. And it is basically a randomized controlled trial that compares adjuvant capecitabine by itself versus surveillance alone in patients who undergo surgery for biliary tract cancers. And so our recommendations, which include that study as well as a couple others, is primarily hinged on that, since that is the largest prospective data we have so far. And based on that study, we did in fact recommend that there was a role for adjuvant chemotherapy with capecitabine after complete resection for biliary tract cancers. And based on that research that was done in that trial that was completed, we do believe that the role for capecitabine for six months is pretty strong and that the data supports that now. So why is this guideline so important, and how will it change practice? Well, I think it's going to be practice-changing because up until now there has not been a clear consensus on how we approach these patients. And I will say that even now, it's really just this one study that has helped guiding these recommendations. There were a number of other studies that we looked at as part of the expert panel. And these were all prospective studies as well that looked at things like gemcitabine and oxaliplatin in the adjuvant setting, or single-arm phase II studies that came out of the Southwest Oncology Group that also explored the role of radiation. But really, nothing was a positive study other than the BILCAP study. And so up until now, I would say it was a little bit all over the place in terms of how medical oncologists approached resected biliary cancers. I think the majority of us felt that there was probably a role for adjuvant chemotherapy or perhaps chemoradiation. But there was no rules that we could follow, and there was no clear study that we could turn to that would tell us what we should give, how long we should give it for, and whether it should be a combination of chemotherapy or chemoradiation. And so I think it will be practice-changing because now, as part of the expert panel, we are making a very clear recommendation that patients with resected biliary tract cancer should be offered adjuvant capecitabine chemotherapy for a total of six months, hopefully eliminating that kind of regional or specialist-based variation that has been happening up until this point. And finally, how will these guideline recommendations affect patients? Again, I think that the main way it's going to affect them is that there's going to be a little bit less gray area, in terms of medical oncologists having conversations with the patients and saying, well, you know, I think that there's probably a role for agent therapy here, but I can't show you the data that supports why I think that. And as a result, I would hope that patients will have a little bit more faith and confidence in knowing that there is a large study that has looked at and proven the benefit of adjuvant capecitabine and that that decreases the chance of recurrence and improves overall survival. The improvement in overall survival was dramatic in this study. And we had not seen a survival of 51 months, which is what we saw in this study, in a very long time. So for patients, not only does it make clear what they should be doing after surgery, but I would hope it also gives them additional hope that we have really changed the bar by doing this adjuvant capecitabine, and that the chance for cure is even higher when we can offer adjuvant chemotherapy. I think the only other thing that may still be a gray area, and that is kind of what we allude to in our second recommendation, and that is in patients who undergo resection and have a microscopically positive margin or an R1 resection. And that's typically patients with extrahepatic cholangiocarcinoma or gall bladder cancer. In those patients, we suggest that they could be offered chemoradiation therapy, but the evidence is not as strong there. Again, it's more retrospective studies that we looked at. There is no prospective study that answers the question of whether or not there's a role for radiation. And so as a result for patients, I think that is still the one area that's a little bit of a gray zone in terms of knowing whether chemoradiation would benefit them if they undergo surgery and have a microscopically positive resection. But I do think that there is a definitive benefit to giving adjuvant chemotherapy, and that, hopefully, will clarify things not only from the physician perspective but also from the patient perspective. Great. Thank you for your work on these important guidelines, and thank you for your time today, Dr. Shroff. Thank you. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer this show to a colleague.

Bladder cancer is the 4th-most common cancer among men, but when detected early, it can be managed and often cured.  Dr. Lambros Stamatakis discusses how we find and treat this disease, and what we do if it comes back.   TRANSCRIPT Intro: MedStar Washington Hospital Center presents medical intel where our healthcare team shares health and wellness insights and gives you the inside story on advances in medicine. In today’s episode, we talk to Dr. Lambros Stamatakis, Director of Urologic Oncology at MedStar Washington Hospital Center about bladder cancer. Dr. Stamatakis discusses bladder cancer symptoms, how treatment has advanced over the years, including techniques unique to MedStar Washington Hospital Center and what patients can expect during treatment and recovery. Host: Thanks for joining us today. Dr. Stamatakis: Thanks for having me. Host: So, let’s get started on bladder cancer. How common is it, what do people need to know? Dr. Stamatakis: So, bladder cancer is often considered a bit of an orphan cancer because it doesn’t get as much press as some of the other cancers out there. But it’s actually the fourth most common cancer in men. So if we compare this to prostate cancer, there’s about 160,000 new cases estimated to occur in 2017, bladder cancer we’re estimating around 60,000 to 65,000 in men. So, it’s a relatively common cancer in men, overall about 78,000 cases a year. So, it’s less common in women and the reason for that is a bit unclear, but it is something that we predominantly see in men. Host: And how common is it in the D.C. area? How many cases do you see in a month or year? Dr. Stamatakis: Estimates from the National Cancer Institute suggest that there are around 3,000 total new cases in the D.C. metropolitan area, so I’m including Maryland and Virginia in those numbers. I usually, because I am a referral center for bladder cancer, I often see around 10 to 20 cases a month. We do more bladder cancer than any other institution in the District of Columbia. So, being a high-volume center, we’re very experienced in the nuances of the surgical treatment of this disease, which is paramount for how you manage bladder cancer. Because of that, we also have higher expertise in knowing how to stage the disease and also how to manage it moving forward. We also have a multidisciplinary clinic where surgical folks like myself work with medical oncologists and our partners from Lombardi Cancer Institute over at Georgetown to provide systemic therapy in patients that need it or require that. Also, again, clinical trials are another option for some of our patients who are interested, and that can provide therapies that are not otherwise available as standard-of-care yet. Host: And, what are the most common symptoms? Dr. Stamatakis: So, blood in the urine is the number one symptom that typically prompts referral to a urologist. Blood in the urine can also be caused by other benign conditions. For example, somebody having a kidney stone or an enlarged prostate. But for the urologists, we need to make sure that we rule out bladder cancer or other malignant causes of blood in the urine. So that’s certainly something that most of our patients won’t present with, but not all. Other patients can have irritating voiding symptoms, meaning they’re going to the bathroom more frequently or they’re having a sense of extreme urgency and that’s not getting better with the traditional therapies that we give for those types of symptoms. Every once in a while now, with modern day imaging, we’re also able to pick these things up incidentally. So, a patient gets a cat scan for another reason and the radiologist sees a little tumor in the bladder that then prompts the referral to us.  Host: So typically, when somebody comes in and they had blood in their urine, is that a sign that it’s usually already advanced a little ways? Dr. Stamatakis: Not necessarily. Not necessarily. But what it will signal to the urologist is that a specific workup needs to be completed. So, that includes getting imaging of the kidneys and upper urinary tract, so that includes the tubes that connect the kidneys to the bladder, called the ureters. And that’s most typically done using a CT scan and specifically something called a CT urogram. In addition, a cystoscopy will often be offered to the patient and that’s a procedure where we stick a small camera inside the patient’s bladder to directly visualize the surface of the bladder; make sure that they don’t see anything that’s abnormal. Host: And, most bladder cancers are diagnosed relatively late though, correct? Or … Dr. Stamatakis: Not necessarily. About 75 percent of them actually are present in the quote non-muscle invasive state. So, that’s a big differentiator when we talk about bladder cancer staging is whether the disease is muscle invasive or non-muscle invasive. And, to go back a little bit, the bladder is essentially a muscular sac that just stores urine. The bladder itself has multiple layers and these cancers derive from the inner layer of the bladder, known as the urothelium. So as these tumors grow, they tend to grow from the urothelium towards the outside of the bladder. And right sandwiched in between is the quote muscle or detrusor muscle of the bladder. So, when we see a bladder tumor on a cystoscopy on somebody who’s been worked up for blood in the urine, the next step will be to take them to the operating room to resect that tumor. That procedure will accomplish two goals. Number one, it’s diagnostic, so we get it out, the pathologist does their exam under the microscope, tells us what it is and how deep it’s invading into the bladder. And then the second thing is that it’s potentially therapeutic. So if it’s non-muscle invasive, often we can then watch those patients very closely and may offer select patients intravascular therapy, which basically means different types of drugs inside the bladder to prevent further recurrence or treat any remaining microscopic disease that’s left behind. If it’s muscle invasive, then we’re a little bit more aggressive. Host: And how has bladder cancer treatment, how has it advanced over the years? Dr. Stamatakis: In many different ways. Initially, the treatment of bladder cancer, or traditionally, has, for muscle invasive disease, has been removal of the entire bladder with a urinary diversion. And a urinary diversion basically means being able to figure out a way to somehow get the urine out, for that particular patient. The most common thing that’s done in the United States is something called an ileal conduit urinary diversion, or otherwise known as a urostomy, where, essentially, we plug the kidney tubes into a small piece of intestine which then gets tunnelled through the abdominal wall and creates a small stoma, and the urine will then basically drain into a bag. But as time has gone on, we’ve now developed other methods for urinary diversions. We can even create what’s called a neobladder, using a much longer piece of intestine but being able to connect that pouch that we create to the patient’s native urethra, so then they can basically void through their natural orifice. So, that does help to prevent the need for an external appliance and is more cosmetically pleasing for select patients. In addition, another thing that’s really changed is the kind of something that I eluded to before, was a multidisciplinary approach to treating these cancers, and that is no better highlighted than in the use of chemotherapy up front before radical surgery for these conditions. In a big randomized control trial done by the Southwest Oncology Group in the early 2000s, getting upfront chemotherapy actually was shown to confer an overall survival advantage compared to patients who went to cystectomy directly or bladder removal directly. So, that is something that we do offer all of our patients, upfront chemotherapy, and ultimately, hopefully, be able to confer that survival advantage for them. One thing that we do differently is something called blue light cystoscopy. Blue light cystoscopy is an enhanced cystoscopic technique and essentially what it involves is the administration of a dye into the bladder about an hour prior to going back to the operating room for a bladder biopsy. And what will happen is that this dye essentially gets preferentially retained within the cancer cells as opposed to the normal bladder tissue. So, when we shine a specific wavelength of light, which looks blue, the areas of abnormality will appear to fluoresce. It almost looks like a fluorescent pink little spot on the screen. So, the benefit is that—is several. First off, we are able to identify tumors that otherwise you may miss on traditional cystoscopy. And it’s not that you have a bad urologist that misses it, it’s just the fact that some of these lesions can be so small that they’re really hard to perceive with the naked eye. In addition, when you have a tumor in place, we have a theory that when you end up excising that tumor through that procedure that perhaps you may be leaving some tumor behind. So, using this technique, we can actually evaluate the edges of the tumor resection site and make sure that we got everything out. And, if we need to, we resect a little bit more to make sure that we have a negative margin, meaning that we got all the tumor out as we possibly can. So, this doesn’t really add that much to the patient experience, other than the fact that they have to have this dye put inside their bladder about an hour before, and we really feel that it adds an additional piece of information to us when we’re making the diagnosis and performing these procedures for these bladder tumors. Host: When a patient comes in, what should they expect? Dr. Stamatakis: So, again, I’ll kind of break this up into sort of the non-muscle invasive and the muscle invasive group. So, in patients with non-muscle invasive, otherwise known as superficial, bladder cancer, the one thing that patients need to understand is that recurrence is unfortunately the rule with bladder cancer. These tumors, depending on the stage and the grade, which is something that’s determined by the pathologist, the recurrence rates can be quite high. So, in order to identify those recurrences, we have to routinely perform cystoscopies, again looking inside their bladder, to be able to identify those recurrences early. So, a patient that is being treated for non-muscle invasive bladder cancer needs to realize that they’re going to be getting occasional procedures to look inside their bladder. And often that can be just done in the office as an outpatient procedure with relatively little discomfort to the patient, if any at all. In addition, there are multiple therapies that we use inside the bladder to, again, in certain patients, to help prevent these tumors from coming back. In patients with muscle invasive disease, again, that’s when we get our multidisciplinary folks involved and we’ll have them work together with our medical oncologists to select a therapy that’s personalized to their particular disease state and also for their preferences. And often we will offer radical surgery, and, when it’s appropriate, do it through a minimally invasive approach. I typically use the DaVinci robot for bladder removal, and that’s something that will be offered to many of our patients in our practice. So, those are the sort of, the things that we, that we end up offering to our patients. Host: What can a survivor expect during recovery and beyond? Dr. Stamatakis: So, after radical surgery for bladder cancer, again for muscle invasive or locally advanced disease, the surgery itself is a big surgery. I mean, usually, typically, four to five days in the hospital and often it can be several months before they feel really back to normal. And after that, we will be very vigilant about performing imaging studies to make sure that their bladder cancer doesn’t come back. If they have not received chemotherapy up front, we may offer it to them after the surgery, depending on the results from pathology from the bladder removal. And that’s something, again, that we’ll get our medical oncologists involved with. For non-muscle invasive bladder cancer, again, it’s really just being vigilant about seeing each other over and over again and making sure that they get the surveillance that they need with periodic cystoscopies. Host: As a final thought, maybe, with bladder cancer being so prevalent, why do you think it’s not top-of-mind as much as other cancers? Dr. Stamatakis: Yeah. Well, again, it hasn’t gotten as much press and also, I think, because the symptoms that we discussed that are associated with bladder cancer are the same symptoms that patients often get with many benign urologic diseases. Again, if somebody has blood in the urine, the first thought to a primary care provider isn’t bladder cancer. It’s “Is the patient having a kidney stone? Do they have a urinary tract infection?” And often, I think our primary care providers don’t like to jump to conclusions because you don’t want to create fear within your patients. We see this a lot in women. Women are more prone to urinary tract infections. They’ll come to their doctor and have blood in the urine and they’ll treat them for a urinary tract infection almost reflexively. And the blood keeps coming back, and they keep throwing different antibiotics at them. It’s often part of the reason why, despite the fact that bladder cancer occurs less frequently in women, it actually presents at a more advanced stage in women compared to men. And that’s because, we think, that primary care providers often will be misdiagnosing them. So, it is something that I think, from our perspective as educators, to be able to educate the future generations of primary care physicians to understand the appropriate workup for blood in the urine and I think that will help to increase awareness. The other thing that’s also changed is that there’s more advocacy groups out there now, particularly something called the Bladder Cancer Advocacy Network, that actually started in the D.C. metropolitan area. They are now doing a lot to increase awareness of bladder cancer and become advocates for patients and their families. And that’s something that never really existed before and we’ve really been following suit and the folks that have created these sorts of organizations for prostate cancer and breast cancer, which are really the more popular, or more well-known, cancers out there. So, we’re hoping that bladder cancer is going to become something that, really, people know more about as time goes on. Host: Great. Thank you so much for joining us. Dr. Stamatakis: Yeah, no problem. Thank you so much. Conclusion: Thanks for listening to Medical Intel with MedStar Washington Hospital Center. Find more podcasts from our healthcare team by visiting medstarwashington.org/podcast or subscribing in iTunes or iHeartRadio.