ASCO Education

Dr. Pedro Barata and Dr. Giuseppe Curigliano discuss the rapid paradigm shift of antibody-drug conjugates into frontline advanced and curative-intent perioperative settings and the clinical challenges of optimal sequencing, target selection, and cross-resistance. LINK TO FULL TRANSCRIPT

Dr. Hope Rugo and Dr. Peter Lee discuss frailty, geriatric assessments, and personalized care for older adults with genitourinary cancer. They highlight screening guidelines, treatment considerations, multidisciplinary interventions, and the emergence of AI and digital health tools in geriatric oncology. LINK TO FULL TRANSCRIPT

Dr. Pedro Barata and Dr. Kathryn Schmitz discuss evidence-based exercise oncology programs, how to incorporate exercise into cancer care and connect the right patient to the right program, and ultimately build a culture of exercise in oncology. TRANSCRIPT Dr. Pedro Barata: Hello, and welcome to By the Book, a podcast series from ASCO that features compelling perspectives from authors and editors of the ASCO Educational Book. I'm Dr. Pedro Barata. I'm a medical oncologist and a clinical trialist at the University Hospital Seidman Cancer Center and an associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also happy to serve as a deputy editor for the ASCO Educational Book. Today, we'll be talking about exercise. We have plenty of evidence that exercise benefits symptoms, improves the quality of life of patients, and actually has been shown to reduce risk of recurrence of cancer but also improve survival. And I think that's increasingly clear as data emerges. Today, I'm delighted to be speaking to Dr. Kathryn Schmitz. She's a leading expert on integrating exercise into cancer care. Dr. Schmitz serves as the deputy director of the University of Pittsburgh Hillman Cancer Center and also a professor of hematology-oncology at University of Pittsburgh Medical School. She's the senior author of a fantastic article in the ASCO Educational Book that's titled "Implementation Science as the Secret Sauce for Integrating Exercise Screening and Triage Pathways in Oncology." She also led a really compelling piece that just got published in JCO titled "If Exercise Were a Pill, We'd All Prescribe It to Patients With Cancer. But It's Not" So I'm thrilled to have Dr. Schmitz joining us today and helping us explore evidence-based exercise oncology programs, how to incorporate exercise into cancer care, and also how to connect the right patient to the right program. So with that, welcome, Dr. Schmitz. Thank you so much for taking the time to chat with us. Dr. Kathryn Schmitz: Thank you for the opportunity. Dr. Pedro Barata: One of the highlights of ASCO last year and practice changing, in my opinion, data out of The New England [Journal of Medicine] is called the CHALLENGE trial. It did provide high level evidence that a structured, supervised exercise program could improve both disease-free survival and overall survival. This is a study in the GI world, but I think it got a lot of attraction and attention beyond the GI world, across solid tumors, really. Could you give us a little brief recap of that trial and what have you seen as being the impact in practices around oncology? Dr. Kathryn Schmitz: So, CHALLENGE was very exciting. Prior to CHALLENGE, there were any number of observational studies that indicated that there was a relationship between being more physically active and reduced recurrence and improved overall survival for colon cancer in particular. You know, notably, in 2006, Jeff Meyerhardt published two papers in the same journal, of the same issue of JCO, showing very, very similar data from two very large studies. And those were studies number five and six in this area. You know, there's a lot of evidence observationally, but we don't generally change clinical practice on the basis of observational data. So, we were all waiting very impatiently for the results of the CHALLENGE trial. And it was very exciting to be in the front row when the results were reported out and to be part of the group with a standing ovation for the authors when it was presented. To summarize, 889 colon cancer patients, stage II and III, were randomized into either a structured exercise program or a health education control comparison group and followed for an average of 7.9 years. And the structured exercise group had a 27% reduced risk of recurrence and a 38% improvement in overall survival. One of the things that's really notable about this is that what we typically expect is that when we go from the observational literature to the clinical trial literature, that we expect effects to go down. We expect to see a larger effect in the observational than in the RCT land, and that did not happen here. We actually see an effect that matches what we've seen in observational literature, which is really, really exciting. And, you know, one of the reasons why this has been so exciting across not just GI but other cancers is the notable finding of a reduced risk of second primaries. So, they only observed two breast cancer second primaries in the treatment group and 12 in the comparison group. And overall, they reduced the second primaries occurrence, hazard ratio was 0.5, a 50% reduction of second primaries, which is just remarkable. It really got everybody very, very excited. And now the big question, of course, is, all right, how do I do this? How do I make this happen? The thing to note is that what they did in CHALLENGE is probably not doable in your clinic tomorrow. It's a heavy intervention. The number of touchpoints from staff is extensive, and the amount of time needed from staff for the coaching and supervised exercise is extensive as well. The criteria for getting people into the program required that people go through a series of blood tests and imaging tests that would just simply not be possible for the average community oncologist. So I'm guessing that you're going to ask me some questions about how we do this. Dr. Pedro Barata: Right. That's a fantastic segue. That's exactly right. Walk us through maybe starting by, what does that mean? Dr. Kathryn Schmitz: The first thing to say is I have to go back to the observational literature. And the observational literature shows really compellingly that we have a strong reduction of breast cancer recurrence and mortality from being more physically active, prostate cancer recurrence and mortality, and colon cancer recurrence and mortality. I find it very difficult to believe in this day and age, in our current environment, if you will, that we are ever going to have the equivalent of CHALLENGE for prostate or for breast cancer. There is an ongoing study in prostate that's led by some Australian researchers, but I just don't think that it's likely that we're going to mount something similar for another tumor site. We have tremendous correlative data that indicates that there are a number of biomarkers and biological pathways through which breast, colon, and prostate cancer would be reduced in recurrence if people were more physically active. And so, there is really, from my thinking, very little to state that it would be just a colon cancer effect. And so this is something we probably can enact in more than just the colon cancer community, overall, which is great news, and it makes it easier for us to be able to enact this type of programming. Dr. Pedro Barata: One of the things that comes up perhaps often is, if I were the leader of the cancer center and were to incentivize the different care teams to implement an exercise program at each level: GI team, GU, breast, thoracic, etc. How do we do that? Dr. Kathryn Schmitz: So, I want to give you an analogy. You're a medical oncologist, and you prescribe your patients chemotherapy. Now, just imagine, if you will, what would happen and how likely it would be for your patients to get chemotherapy if there was no chemoinfusion suite. If the chemoinfusion suite disappeared tomorrow and you were to tell your patients, "Go get some chemotherapy," what proportion of those patients do you think would go find all of the equipment necessary and all of the drugs necessary and understand how to dose the chemotherapy for themselves and get that all done? Very few people would do it. So with exercise, why would we be surprised then that our patients don't actually do a whole lot if we just simply tell them to go get some exercise? Exercise is a medicine. It is effective like a medicine. We've shown this through the CHALLENGE trial and many other correlative studies and an ocean of observational data as well. So the question is, how do we build the infrastructure that is necessary in order for your patients to do this? So the very first thing that has to happen is that somebody has to tell the patient to exercise. We currently do not have a culture of exercise in oncology. We do in heart disease. If you ask the average person on the street, "Is exercise good for your heart?" Anybody with an eighth-grade education is going to say, "Yes, of course," because the American Heart Association has done an amazing job telling everybody that exercise is good for your heart. But what has ASCO done, frankly? Can I be that bold? What has ASCO done to tell patients that they should be exercising during and after their cancer treatment? I'm not sure that I know more than a guideline. There is a guideline, and that's great. And the guideline is very helpful, but I'm not sure that patients know that there's a guideline. In fact, I can tell you that patients don't know that there is a guideline. So, you know, making sure that there's a paradigm shift in the country that says exercise is good for patients during and after their cancer treatment is the first step. The second step is getting a medical professional to say something to the patient about the exercise. And I'm very careful with the two words that I just chose: medical professional. I do understand medical oncologists are very busy. I understand that there's a whole lot to say in that 15 minutes when you're with the patient. And so maybe it isn't the medical oncologist. Ideally, it would be, but I get it that there's limited time. So it could be a nurse practitioner, it could be a nurse, there could be a social worker, it could be somebody else on the team that says, "Hey, you know, we want you to do an exercise program. We want to connect you to an exercise program." And then there's what is the program itself? You know, I'm very interested in this happening across the entire country. And so I've been working with the leadership of the Commission on Cancer on the question of, well, how would you do this in community oncology? You know, it's not enough to do it in academic medicine, but how do you do this in community oncology? And you can't expect that every community hospital is going to build a gym for their cancer patients. That is just not reasonable to do. So, we start to try to figure out some phone counseling. Could we give people Fitbits and follow them? Could we use technology to help us? Are there telehealth opportunities for us to do? Are there apps that have been built? In fact, there is a [free] app called Cancer Exercise that's on, you know, all of the platforms and available to patients. So there are programs. I've developed a directory of over 2,000 programs that exist across the country for exercise oncology that patients can find, medical oncologists can find. So there are a lot of people trying to figure out how best to get the information to medical oncologists and other medical professionals so that they can have an 'easy button' to be able to connect their patients to existing programming so that you don't feel like you have to build a whole new program. Dr. Pedro Barata: If I don't have the resources around me, what would be your advice for the care team or for the providers that might not have that available at their site? Where do they start? Who do they reach out to? Who should they be looking at to get more information on how to set it up? Dr. Kathryn Schmitz: I lead an international consortium called Moving Through Cancer. You can find us at movingthroughcancer.org. That's where you'll find the map of all of the programs across the country and the directory. We actually have a triage tool that sits at the front of the directory that allows people to discern what type of exercise they're safe to do. We do recognize that, you know, the 80-year-old that fell last week doesn't need the same program as the 35-year-old that was playing pickleball the day before diagnosis. So, you know, there are different kinds of programs for people at different levels of acuity. We're happy to be helpful to folks to help them set up programs. But the number one thing is to really be very aware of the power of saying something about doing exercise, just simply the power of saying, "I want you to be moving." Because frankly, I don't think anybody listening to this would disagree, no one benefits from sitting on the couch all day, no one. No one, no one. It doesn't matter how acute their medical issues are. We get people out of bed. We try to move people even when they're in the hospital. So I think saying something is huge. And then, if you can, applying a triage tool, if you can get something embedded within your clinical flow so that you can understand who it is that needs to go to physical therapy as opposed to who's ready for an exercise program. Those are the two things. So triage and referral is kind of step one. And if you can get that done, the rest will fall into place. Dr. Pedro Barata: This is really powerful message, where one, awareness of the care teams. Number two, bring it up to the patient. And then working on the referral, triage and referral process. That's fantastic. Another aspect that comes up quite a bit is like, "Look, this is great, but we have a system that relies on payers to make things happen, or at least to get them approved." And that can be very different or heterogeneous. The coverage can be different. Sometimes already going through a system programs for interventions, therapeutic interventions, let alone probably the insurance is not going to cover that. Is that true? Is it not true? How do you walk through the different insurance supports, perhaps, depending on where you're practicing? Dr. Kathryn Schmitz: You've just hit on the hot button. I've been working on this issue for about nine years now, trying to figure out using efforts to talk to CMS and see if we can get third party payer coverage going. We were making good progress there, and there was a change of administration and a new focus on "Make America Healthy Again," the MAHA movement. And, you know, CMS is really no longer interested in one-off national coverage determination. They instead, they want to know, "How do we make exercise happen for every American over 65?" And my question is, "Well, wait a minute, cancer patients are not just older patients. There's a lot going on there. They need something special." So I've been working on that. It's been working with accrediting bodies for policy with a little p. Very proud of the work that I've done in collaboration with the National Accreditation Program for Breast Centers, trying to get standards to get exercise referrals for breast patients. And I'm currently holding my breath to see whether the CoC is going to try to make some forward motion in this area as well, crossing all period appendages, waiting for news there. So it's not paid for unless it's done by a physical therapist. And, you know, there's published evidence and I have plenty of evidence from UPMC as well, that people don't really want to go to the physical therapist for this. I'm not saying physical therapists aren't great. Physical therapists are great, and there are people who really need to go to physical therapy, and we try hard to get those patients connected. But for the patients that are ready for something more than physical therapy, we really have an uphill battle to try to figure out what insurers are willing to pay for and what the return on investment is. One of the challenges with the return on investment is that the timeline, time course for return on investment for American insurers is about one year. And I'll remind you that the time course for return on investment for CHALLENGE was 7.9 years. So we have a mismatch there. So we're trying to figure out if we can produce the evidence to show that there is an improvement in unplanned health care utilization. We have documented that for breast cancer. We're working on it for other cancers. If we can document that it is worthwhile to the insurer to pay for these programs, then I believe that they will pay for them. You know, my conversations are very positive with UPMC, which is a very large insurer and a large health plan. We're slowly working our way towards the middle, where there's a program that they can pay for and a program that is efficacious. That's the puzzle we're trying to solve for right now. Dr. Pedro Barata: This has been wonderful and super helpful. Before we wrap it up, is there anything else you would like to share with our listeners? Dr. Kathryn Schmitz: I want to make sure that your audience is aware that there are a variety of ways that exercise oncology is practiced. The program that most oncologists will be familiar with is LIVESTRONG, which is a program at the YMCA. It's a free program. At one point, there were over 800 locations across the U.S. They have contracted since COVID, probably because of COVID. So they still do exist but imagine, if you will, telling your patients that chemo is only available Tuesdays and Thursdays at 7:00 p.m. It would be difficult for patients to get there and get the chemotherapy. The same thing is true for the LIVESTRONG program. It's a fantastic, fantastic program for people who are able to get there, but that's one option. Another option for patients is there are a variety of online opportunities. I'll call out 2Unstoppable for women's cancers. It's literally the number 2Unstoppable.org. It's a free program available to women with cancer to have live, small group training programs. And they're based in Virginia, but they have programs all over the country. And then finally, I just want to overemphasize the app, the Cancer Exercise app. It's literally called Cancer Exercise in the app store. And that is a super duper easy button, very comprehensive, developed by a nurse scientist, Anna Schwartz. And then there are a variety of books. I wrote a book called Moving Through Cancer. There's a new book out [MyExerciseMedicine for Cancer] by Dr. Rob Newton as well, who's an Australian author. And there are certifications for exercise professionals that folks can look into as well through the American College of Sports Medicine. Dr. Pedro Barata: Dr. Schmitz, this is fantastic. Thank you for sharing those great insights with us. Super, super helpful. Thank you for taking the time. Dr. Kathryn Schmitz: Thank you so much. Dr. Pedro Barata: Thank you to our listeners for your time today. Remember, you'll find links to Dr. Schmitz's fantastic Educational Book as well as the JCO articles in the transcript of this episode. I'll invite all of you to go and read. And we'll also include a link to Dr. Schmitz's book titled Moving Through Cancer: An Exercise and Strength Program for the Fight of Your Life, which empowers patients and caregivers in simple five steps. So with that, please join us again next month on By the Book for more insights on key advances and innovations that are shaping modern oncology. Thank you very much for your attention. 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. Follow today's speakers: Dr. Pedro Barata @PBarataMD Dr. Kathryn Schmitz @fitaftercancer Follow ASCO on social media: @ASCO on X (formerly Twitter) ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Pedro Barata: Stock and Other Ownership Interests: Luminate Medical Honoraria: UroToday Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck Dr. Kathryn Schmitz: Patents, Royalties, Other Intellectual Property: Fees from the educational program developed by Dr. Schmitz that is now offered through Klose Training and Consulting.

Dr. Hope Rugo and Dr. Vivek Subbiah discuss innovative trial designs to enable robust studies for smaller patient populations, as well as the promise of precision medicine, novel therapeutic approaches, and global partnerships to advance rare cancer research and improve patient outcomes. TRANSCRIPT Dr. Hope Rugo: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center [in Los Angeles]. The field of rare cancer research is rapidly transforming thanks to progress in clinical trials and treatment strategies, as well as improvements in precision medicine and next-generation sequencing that enable biomarker identification. According to the National Cancer Institute, rare cancers occur in fewer than 150 cases per million each year, but collectively, they represent a significant portion of all cancer diagnoses. And we struggle with the appropriate treatment for these rare cancers in clinical practice. Today, I am delighted to be joined by Dr. Vivek Subbiah, a medical oncologist and the chief of early-phase drug development at the Sarah Cannon Research Institute in Nashville, Tennessee. Dr. Subbiah is the lead author of a paper in the ASCO Educational Book titled "Designing Clinical Trials for Patients with Rare Cancers: Connecting the Zebras," a great title for this topic. He will be telling us about innovative trial designs to enable robust studies for small patient populations, the promise of precision medicine, and novel therapeutic approaches to improve outcomes, and how we can leverage AI now to enroll more patients with rare cancers in clinical trials. Our full disclosures are available in the transcript of this episode. Dr. Subbiah, it is great to have you on the podcast today. Thanks so much for being here. Dr. Vivek Subbiah: Thank you so much, Dr. Rugo, and it is an honor and pleasure being here. And thank you for doing this podcast for rare cancers. Dr. Hope Rugo: Absolutely. We are excited to talk to you. And congratulations on this fantastic paper. It is such a great resource for our community to better understand what is new in the field of rare cancer research. Of course, rare cancers are complex and multifaceted diseases. And this is a huge challenge for clinical oncologists. You know, our clinics, of course, cannot be designed as we are being very uni-cancer focused to just be for one cancer that is very rare. So, oncologists have to be a jack of all trades in this area. Your paper notes that there are approximately 200 distinct types of rare and ultra-rare cancers. And, by definition, all pediatric cancers are rare cancers. Of course, clinical trials are essential for developing new treatment strategies and improving patient outcomes, and in your paper, you highlight some unique challenges in conducting trials in this rare cancer space. Can you tell us about the challenges and how really innovative trial designs, I think a key issue, are being tailored to the specific needs of patients with rare cancer and, importantly, for these trials? Dr. Vivek Subbiah: Rare cancers present a perfect storm of challenges. First, the patient populations are very small, which makes it really hard to recruit enough participants for traditional type trials. Second, these patients are often geographically dispersed across multiple cities, across multiple states, across multiple countries, across multiple zip codes. So, logistics become complicated. Third, there is often limited awareness among clinicians, which delays referrals and diagnosis. Add to that regulatory hurdles, funding constraints, and you can see why rare cancer trials are so tough to execute. To overcome these barriers, we are seeing some really creative novel trial designs. And there are four different types of trial designs that are helping with enrolling patients with rare cancers. The first one is the basket trial. So let us talk about what basket studies are. Basket studies group patients based on shared genetic biomarkers or shared genetic mutations rather than tumor type. So instead of running separate 20 to 30 to 40 trials, you can study one therapy across multiple cancers. The second type of trial is the umbrella trial. The umbrella trials flip that concept of basket studies. They focus on one cancer type but test multiple targeted therapies within it. The third category of innovative trials are the platform studies. Platform trials are another exciting innovation. They allow new treatment arms to be added or removed as the data matures and as the data evolves, making trials more adaptive and efficient. The final category are decentralized tools in traditional trials, which are helping patients participate closer to where they are so that they can sleep in their own bed, which is, I think, a game changer for accessibility. These designs maximize efficiency and feasibility for rare cancer research and rare cancer clinical trials. Dr. Hope Rugo: I love the idea of the platform trials that are decentralized. And I know that there is a trial being worked on with ARPA-H (Advanced Research Projects Agency for Health) funding in triple-negative breast cancer as well as in lung cancer, I think, and others with this idea of a platform trial. But it is challenged, I think, by precision medicine and next-generation sequencing where some patients do not have targetable markers, or there isn't a drug to target the marker. I think those are almost the same thing. We have really seen that these precision medicine ideas and NGS have moved the needle in helping to identify genetic alterations. This helps us to be more personalized. It actually helps with platform studies to customize trial enrollment. And we hope that this will result in better outcomes. It also allows us, I think, to study drugs even in the early stage setting more effectively. How can these advances be best applied to the future of rare cancers, as well as the challenges of not finding a marker or not having a drug? Dr. Vivek Subbiah: Thank you so much for that question. I think precision medicine and next-gen sequencing, or NGS, are truly the backbone of modern precision oncology. They have transformed how we think about cancer treatment. Instead of treating based on where the tumor originated or where the tumor started, we now look at the genetic blueprint of cancer. The NGS or next-gen sequencing allows us to sequence millions of DNA fragments quickly. Twenty, 30 years ago, they said we cannot sequence a human genome. Then it took almost a decade to sequence the first human genome. Right now, we have academic centers and commercial sequencing companies that are really democratizing NGS across all sites, not just in academic centers, across all the community sites, so that NGS is now accessible. This means that we can identify these actionable alterations like picking needles in haystacks, like NTRK fusions, RET fusions, or BRAF V600E alterations, high tumor mutational burden. This might occur across not one tumor type, across several different tumor types. So for rare cancers, this is critical because some of these mutations often define the best treatment option. Here is why this matters. Personalized therapy, right? Instead of a one-size-fits-all approach, we can tailor treatment to the patient's unique molecular profile. For trial enrollment, this can definitely help because patients can join biomarker-driven trials even if their cancer type is rare or ultra-rare. NGS technology has also helped us in designing rational studies. Many times monotherapy does not work in these cancers. So we are thinking about rational combination strategies. So NGS technology is helping us. Looking ahead, I see NGS becoming routine in clinical practice, not just at major niche academic centers, but everywhere. We will see more tumor-agnostic approvals, more molecular tumor boards guiding treatment decisions in real time. And I think we are seeing an expanded biomarker setup. Previously, we used to have only a few drugs and a handful of mutations. Now with homologous recombination defects, BRCA1/2 mutation, and expanding the HRD and also immunohistochemistry, we are expanding the biomarker portfolio. So again, I personally believe that the future is precision. What I mean by precision is delivering the right drug to the right patient at the right time. And for rare cancers, this isn't just progress. It is survival. And it is maybe the only way that they can have access to these cutting-edge precision medicines. Dr. Hope Rugo: That is so important. You mentioned an important area we will get to in a moment, the tumor-agnostic therapies. But as part of talking about that, do you think that the trials should also include just standard therapies? You know, who do you give an ADC to and when with these rare cancers? Because some of them do not have biomarkers to target and it is so disappointing for patients and providers where you are trying to screen a patient for a trial or a platform trial where you have one arm with this mutation, one arm with that, and they do not qualify because they only have a p53 loss, you know? They just do not have the marker that helps them. But we see this in breast cancer all the time. And it is tough because we don't have good information on the sequencing. So I wonder, you know, just because for some of these rare cancers it is not even clear what to use when with standard treatments. And then that kind of gets into this idea of the tumor-agnostic therapies that you mentioned. There are a lot of new treatments that are being evaluated. We have seen approval of some treatments in the last few years that are tumor-agnostic and based on a biomarker. Is that the best approach as we go forward for rare cancers? And what new treatment options are most exciting to you right now? Dr. Vivek Subbiah: Tumor-agnostic therapies, really close to my heart, are real breakthrough therapies and represent a major paradigm shift in oncology. Traditionally, for the broad listeners here, we are used to thinking about designing clinical trials and therapy like where the cancer originated, breast cancer, kidney cancer, prostate cancer, lung cancer. A tumor-agnostic therapy flips that model. Instead of focusing on the organ, they target the specific genetic alteration or biomarker that drives cancer growth regardless of where the tumor started, regardless of the location of the tumor, regardless of the zip code of the tumor. So why is this so important for rare cancers? Because many rare cancers share molecular features with more common cancers. For instance, NTRK fusion might occur in pediatric sarcoma, a salivary gland tumor, or a thyroid cancer. Historically, each of these would require separate trials, which is nearly impossible, unfeasible to conduct in these ultra-rare cancers like salivary gland cancer or pediatric sarcomas. Tumor-agnostic therapies allow us to treat all those cancers with the same targeted drug if they share that biomarker. Again, we are in 2025. The first tissue-agnostic approval, the historic precedent, was in fact an immunotherapy. Pembrolizumab was approved in 2017, May 2017, as the first immunotherapy to be approved in a tumor-agnostic way for a genomic biomarker, for MSI-High and dMMR cancers. Then came the NTRK inhibitors. So today we have not one, not two, but three different NTRK inhibitors: larotrectinib, entrectinib, and repotrectinib, which show response rates of nearly more than 60 to 75% across a handful of dozens and dozens of cancer types. Then, of course, we have RET inhibitors like selpercatinib, which is approved tissue-agnostic, and pralsetinib, which also shows tissue-agnostic activity across multiple cancers. And more recently, combination therapy with a BRAF and MEK combination, dabrafenib and trametinib, received tumor-agnostic approval for all BRAF V600E tumors with the exception of colorectal cancer. And even recently, you mentioned about antibody drug conjugates. Again, I think we live in an era of antibody drug conjugates. And Enhertu, trastuzumab deruxtecan, which was used first in breast cancer, now it is approved in a histology-agnostic manner for all HER2-positive tumors defined by immunohistochemistry 3+. So again, beyond NGS, now immunohistochemistry for HER2 is also becoming a biomarker. So again, for the broad listeners here, in addition to comprehensive NGS that may allow patients to find treatment options for these rare cancers for NTRK, RET, and BRAF, immunohistochemistry for HER2 positivity is also emerging as a biomarker given that we have a new FDA approval for this. So I would say personally that these therapies are game changers because they open doors for patients who previously had no options. Instead of waiting for years for a trial in their specific cancer type, they can access a treatment based on their molecular profile. I think it is precision medicine at its finest and best. Looking ahead, the third question you asked me is what is exciting going on? I think we will see more of these approvals. My hope is that today, I think we have nine to ten approvals. My hope is that within the next 25 to 50 years, we will have at least 50 to 100 drugs approved in this space based on a biomarker, not based on a location of the tumor type. Drug targeting rare alterations like FGFR2 fusions, FGFR amplifications, ALK fusions, and even complex signatures like high tumor mutational burden. I think we will be seeing hopefully more and more drugs approved. And as sequencing becomes routine, we will identify more patients for these therapies. I think for rare cancers, this is not just innovative approach. This is essential for them to access these novel precision medicines. Dr. Hope Rugo: Yeah, that is such a good point. I do think it is critical. Interestingly in breast cancer, it hasn't been, you know, there is always like two patients in these tumor-agnostic trials, or if that. You know, I think I have seen one NTRK fusion ever. I think that highlights the importance for rare cancers. And you know, I am hoping that that will translate into some new directions for some of our rarer and impossible-to-treat subtypes of breast cancer. It is this kind of research that is really going to make a difference. But what about those people who do not have biomarkers? What if you do not fit into that? Do you think there is a possibility of trying to do treatments for rare cancers in some prospective way that would help with that? You know, it is really a huge challenge. Dr. Vivek Subbiah: Absolutely. I think, you know, you're right, usually many of these rare cancers are driven by specific biomarkers. And again, some of the pediatric salivary gland tumors or pediatric sarcomas like fibrosarcomas, they are pathognomonic with NTRK fusions. And again, given that we have a tumor-agnostic approval, now these patients have access to these therapies. And I do not think that we would have had a trial just for pediatric fibrosarcomas with NTRK fusions. So that is one way. Another way is SWOG, right? The SWOG DART [1609] had this combination dual checkpoint, it was called the DART study dual combination chemotherapy with ipi/nivo. Now here the rare cancer subtype itself becomes a biomarker and they showed activity across multiple rare cancer subtypes. They didn't require a biomarker. As long as it was a rare or ultra-rare cancer, these patients were enrolled into the SWOG DART trial and multiple arms have read out. Angiosarcoma, Kaposi sarcoma, even gestational trophoblastic disease. Again, they have shown responses in these ultra-rare, rare cancers. Sometimes they might be seeing one or two cases a whole year. And I think this SWOG effort, this cooperative group effort, really highlighted the need for such studies without biomarkers as well. Dr. Hope Rugo: That is such a fantastic example of how to try and treat patients in a collaborative way. And in the paper, you also emphasize the need for collaborative research efforts, you know, uniting resource expertise across different ways of doing research. So cooperative groups, advocacy organizations that can really help advance rare cancer research, improve access to new therapies, and I think importantly influence policy changes. I think this already happened with the agnostic approvals. Could you tell us more about that? How can we move forward with this most effectively? Dr. Vivek Subbiah: Personally, I believe that collaboration is absolutely critical and essential for rare cancer research. No single institution, no single individual, or no single state or entity can tackle these challenges alone. The patient populations are small and dispersed. So pooling resources is the only way to run these meaningful trials. Again, it is not like singing, it is like putting a huge, huge, I would say, an opera piece together. It is not a solo, vocal therapy, but rather putting a huge opera piece like Turandot. You know, you mentioned cooperative groups. Cooperative groups, as I mentioned earlier, the SWOG DART program, the ASCO [TAPUR study]. ASCO is doing a phenomenal work of the TAPUR study. Again, this ASCO TAPUR program has enrolled so many patients with rare cancers who otherwise would not have treatment options. NCI-MATCH, the global effort, right? NCI-MATCH and the ComboMATCH are great examples. They bring together hundreds of sites, thousands of clinicians to run large-scale trials that would be impossible for any individual center or institution. These trials have already changed practice. For instance, the DART demonstrated the power of immunotherapy in rare cancers and influenced NCCN guidelines. One of the arms of the NCI-MATCH study from the BRAF V600E arm contributed towards the BRAF V600E tissue-agnostic approval. So, the BRAF V600E tissue-agnostic approval was by a pooled analysis of several studies. The ROAR study, the Rare Oncology Agnostic Research study, the NCI-MATCH dataset of tumor-agnostic cohort, and another pediatric trial, and also evidence from literature and evidence of case reports. And all this pooled analysis contributed to the tissue-agnostic approval of BRAF V600E across multiple rare cancers. There are several patient advocacy organizations which are the real unsung heroes here. Groups like, for instance, we mentioned in the paper, Target Cancer Foundation, don't just raise awareness for rare cancer research, they actively connect patients to trials providing financial, emotional support, and even run their own studies like the TRACK trial. They also influence policy to make access easier. On a global scale, initiatives like DRUP in the Netherlands, the ROME study in Italy, the PCM4EU in Europe are expanding precision medicine across these borders. These collaborations accelerate research, improve trial enrollment, and ensure patients everywhere can have access to these cutting-edge therapies. Again, it is truly a team effort, right? It is a multi-stakeholder approach. Researchers, clinicians, investigators, industry, regulators, academia, patients, patient advocates, and their caregivers all working together. And it takes a village. Dr. Hope Rugo: Absolutely. I mean, what a nice response to that. And I think really exciting and it is great to see your passion about this as well. But it helps all of us, I think, getting discouraged in treating these cancers to understand what is happening moving forward. And I think it is also a fabulous opportunity for our junior colleagues as they rise up in academics to be involved in these international collaborative efforts which are further expanding. One of the things that comes up for clinical trials for patients, and I think it is highlighted with rare cancers because, as you mentioned, people are all over the place, you know, they are so rare. They are all far away. Our patients are always saying to us, "Should I go here for a phase 1 trial?" Can you talk a little bit about how we can overcome these financial and geographic burdens for the patients? You talked about having trials locally, but it is a big financial and just social burden for patients. Dr. Vivek Subbiah: Great point. Financial cost is a major barrier in rare cancer clinical trials. It is a major barrier not just in rare cancer clinical trials, but in clinical trials in general. The economics of rare cancer research are one of the toughest challenges we face. Developing a new drug is already expensive, often billions of dollars. On an average, it takes 2 billion dollars or 2.8 billion dollars according to some data from drug discovery to approval. For rare cancers, the market is tiny, which means the pharmaceutical companies have really little financial incentive to invest. That is why initiatives like the Orphan Drug Act were created to provide tax credits, grants, and market exclusivity to encourage development for rare diseases. Clinical trials themselves are expensive because the small patient populations mean longer recruitment times and higher per-patient costs. Geographic dispersion, as you mentioned, for the patients adds travel, coordination. That is why we need to think out of the box about decentralized trial infrastructure so that we can mitigate some of these expenses. Complex trial designs like basket or platform trials sometimes require sophisticated data systems and regulatory oversight. That is a challenge. And I think some of the pragmatic studies like ASCO TAPUR have overcome those challenges. Advanced technologies like next-gen sequencing and molecular profiling also add significant upfront cost to this. Funding is also limited because rare cancers receive less attention compared to common cancers. Public funding and cooperative group trials help a lot, but I think they cannot cover everything. Patient advocacy organizations sometimes step in to bridge these gaps, but sustainable financing remains a huge challenge. So, the bottom line is without financial incentives and collaborating funding models, many promising therapies for rare cancers would never make it to patients. That is why we need system-wide policy changes, global partnerships, and innovative, effective, seamless trial designs which are so critical so that they can help reduce the cost and make research feasible so that we can deliver the right drug to the right patient at the right time. Dr. Hope Rugo: There is a lot of excitement about the future integration of AI in screening. Just at the San Antonio Breast Cancer meetings, we have a number of different presentations about AI to find markers, even like HER2, and using AI where you would screen and then match patients to clinical trials. Do you have any guidance for the rare cancer community on how to leverage this technology in order to optimize patient enrollment and, I think, identification of the best treatment matches? Dr. Vivek Subbiah: I think artificial intelligence, AI, is a game-changer in the making. Right now, clinical trial is clunky. Matching patients to trial is often manual, time consuming, laborious. You need a lot of personnel to do that. AI can automate this process by analyzing genomic data, medical records, and trial eligibility criteria to find the best matches quickly, accurately, and effectively. For the community, the key is to invest in data standardization and interoperability because AI needs clean, structured data to work effectively. Dr. Hope Rugo: Thank you so much, Dr. Subbiah, for sharing these fantastic insights with us on the podcast today and for your excellent article. Dr. Vivek Subbiah: Thank you so much. Dr. Hope Rugo: We thank you, our listeners, for joining us today. You will find a link to Dr. Subbiah's Educational Book article in the transcript of this episode. And please join us again next month on By the Book for more insightful views on key issues and innovations that are shaping modern oncology. Thank you. 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. Follow today's speakers: Dr. Hope Rugo @hoperugo Dr. Vivek Subbiah @VivekSubbiah Follow ASCO on social media: ASCO on X ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Hope Rugo: Honoraria: Mylan/Viatris, Chugai Pharma Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx Dr. Vivek Subbiah: Consulting/Advisory Role: Loxo/Lilly, Illumina, AADI, Foundation Medicine, Relay Therapeutics, Pfizer, Roche, Bayer, Incyte, Novartis, Pheon Therapeutics, Abbvie Research Funding (Inst.): Novartis, GlaxoSmithKline, NanoCarrier, Northwest Biotherapeutics, Genentech/Roche, Berg Pharma, Bayer, Incyte, Fujifilm, PharmaMar, D3 Oncology Solutions, Pfizer, Amgen, Abbvie, Mutlivir, Blueprint Medicines, Loxo, Vegenics, Takeda, Alfasigma, Agensys, Idera, Boston Biomedical, Inhibrx, Exelixis, Amgen, Turningpoint Therapeutics, Relay Therapeutics Other Relationship: Medscape, Clinical Care Options

Dr. Pedro Barata and Dr. Aditya Bagrodia discuss the evolving landscape of testicular cancer survivorship, the impact of treatment-related complications, and management strategies to optimize long-term outcomes and quality of life. TRANSCRIPT: Dr. Pedro Barata: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I'm Dr. Pedro Barata. I'm a medical oncologist at University Hospitals Seidman Cancer Center and associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also an associate editor of the ASCO Educational Book. We all know that testicular cancer is a rare but highly curable malignancy that mainly affects young men. Multimodal advances in therapy have resulted in excellent cancer specific survival, but testicular cancer survivors face significant long term treatment related toxicities which affect their quality of life and require surveillance and management. With that, I'm very happy today to be joined by Dr. Aditya Bagrodia, a urologic oncologist, professor, and the GU Disease Team lead at UC San Diego[KI1] Health, and also the lead author of the recently published paper in the ASCO Educational Book titled, "Key Updates in Testicular Cancer: Optimizing Survivorship and Survival." And he's also the host of the world-renowned BackTable Urology Podcast. Dr. Bagrodia, I'm so happy that you're joining us today. Welcome. Dr. Aditya Bagrodia: Thanks, Pedro. Absolutely a pleasure to be here. Really appreciate the opportunity. Dr. Pedro Barata: Absolutely. So, just to say that our full disclosures are available in the transcript of this episode. Let's get things started. I'm really excited to talk about this. I'm biased, I do treat testicular cancer among other GU malignancies and so it's a really, really important topic that we face every day, right? Fortunately, for most of these patients, we're able to cure them. But it always comes up the question, "What now? You know, scans, management, cardio oncology, what survivorship programs we have in place? Are we addressing the different survivorship piece, psychology, fertility, et cetera?" So, we'll try to capture all of that today. Aditya, congrats again, you did a fantastic job putting together the insights and thoughts and what we know today about this important topic. And so, let's get focused specifically about what happens when patients get cured. So, many of us, in many centers, were fortunate enough to have these survivorship programs together, but I find that sometimes from talking to colleagues, they're not exactly the same thing and they don't mean the same thing to different people, to different institutions, right? So, first things first. What do you tell a patient perhaps when they ask you, "What can happen to me now that I'm done with treatment for testicular cancer?" Whether it's chemotherapy or just surgery or even radiation therapy? "So, what about the long term? What should I expect, Doctor, that might happen to me in the long run?" Dr. Aditya Bagrodia: Totally. I mean, I think that question's really front and center, Pedro, and really appreciate you all highlighting this topic. It was an absolute honor to work with true thought leaders and the survivorship bit of it is front and center, in my opinion. It's really the focus, you know, we, generally speaking should be able to cure these young men, but it's the 10, 15, 20 years down the way that they're going to largely contend with. The conversation really begins at diagnosis, pre-education. Fortunately, the bulk of patients that present are those with stage one disease, and even very basic things like before orchiectomy, talking about a prosthetic; we know that that can impact body image and self esteem, whether or not they decide to receive it or not. Actually, just being offered a prosthetic is important and this is something, you know, for any urologist, it's kind of critical. To discussing fertility elements to this, taking your time to examine the contralateral testicle, ask about fertility problems, issues, concerns, offer sperm banking, even in the context of a completely normal contralateral testicle, I think these things are quite important. So if it's somebody with stage one disease, you know, without going too far down discussing adjuvant therapy and so forth, I will start the conversation with, "You know, the testes do largely two things. They make testosterone and they make sperm." By and large, patients are going to be able to have acceptable levels of testosterone, adequate sperm parameters to maintain kind of a normal gonadal state and to naturally conceive, should that be something they're interested in. However, there's still going to be, depending on what resource you look at, somewhere in the order of 10-30% that are going to have issues. Where I think for the stage one patients, it's really incumbent upon us is actually to not wait for them to discuss their concerns, particularly with testosterone, which many times can be a little bit vague, but to proactively ask about it every time. Libido, erectile quality, muscle mass maintenance, energy, fatigue. All of these are kind of associated symptoms of hypogonadism. But for a lot of kids 18-20 years old, it's going to be something insidious that they don't think about. So, for the stage one patients, it absolutely starts with gonadal function. If they are stage two getting surgery, I think the counseling really needs to center around a possibility for ejaculatory dysfunction. Now, for a chemotherapy-naive, nerve-sparing RPLND, generally these days we should be able to preserve ejaculatory function at high volume centers, but you still want to bring that up and again kind of touch base on thinking about sperm banking and so forth before the operation, scars, those are things I think worth talking about, small risk of ascites. Then, I think the intensity of potential long term adverse effects really ramps up when we're talking about systemic therapy, chemotherapy. And then there's of course some radiation therapy specific elements that come up. So, for the chemotherapy bits of it, I really think this is going to be something that can be a complete multi-system affected intervention. So, anxiety, depression, our group has actually shown using some population resources that even suicidality can be increased among patients that have been treated for germ cell tumor. You know, really from the top down, tinnitus, hearing changes, those are things that we need to ask about at every appointment. Neuropathy, sexual health, that we kind of talked about, including ED (erectile dysfunction), vertigo, dizziness, Raynaud's phenomenon, these are kind of more the symptoms that I think we need to inquire about every time. And what we do here and I think at a lot of survivorship programs is use kind of a battery of validated instruments, germ cell tumor specific, platinum treated patient specific. So we use a combination of EORTC questions and PROMIS questions, which actually serves as like a review of systems for the patient, also as a research element. We review that and then depending on what might be going on, we can dig into that further, get them over to colleagues in audiology or psychology, et cetera. And then of course, screening for the hypertension, hyperlipidemia, metabolic syndrome with basically you or myself or somebody kind of like us serving, many times it's the role of the PCP, just making sure we're checking out, you know, CBC, CMP, et cetera, lipid parameters to screen for those kind of cardiac associated issues along with secondary malignancies. Dr. Pedro Barata: So that's super comprehensive and thorough. Thank you so much. Actually, I love how you break it down in a simple way. Two functions of the testes, produce testosterone and then, you know, the problem related to that is the hypogonadism, and then the second, as you mentioned, produce sperm and of course related to the fertility issues with that. So, let's start with the first one that you mentioned. So, you do cite that in your paper, around 5-10% of men end up getting, developing hypogonadism, maybe clinical when they present with symptoms, maybe subclinical. So, I'm wondering, for our audience, what kind of recommendations we would give for addressing that or kind of thinking of that? How often are you ordering those tests? And then, when you're thinking about testosterone replacement therapy, is that something you do immediately or are there any guidelines into context that? How do you approach that? Dr. Aditya Bagrodia: So, just a bit more on digging into it even in terms of the questions to ask, you know, "Do you have any decrease in sexual drive? Any erectile dysfunction? Are your morning erections still taking place? Has the ejaculate volume changed? Physically, muscle mass, strength? Have you been putting on weight? Have you noticed increase in body fat?" And sometimes this is complicated because there's some anxiety that comes along with a cancer diagnosis when you're 20, 30 years old, multifactorial, hair loss, hot flashes, irritability. Sometimes they'll, you know, literally they'll say, "You know, my significant other or partners noticed that I'm really just a little bit labile." So I think, you know, there's the symptoms and then checking, usually kind of a gonadal panel, FSH, LH, free and total testosterone, sex hormone binding globulin, that's going to be typically pretty comprehensive. So if you've got symptoms plus some laboratory work, and ideally that pre-orchiectomy testosterone gives you some delta. If they started out at an 800, 900, now they're 400, that might be a big change for them. And then, when you talk about TRT (Testosterone Replacement Therapy) recommendations, you know, Pedro, yourself, myself, we're kind of lucky to be at academic centers and we've got men's health colleagues that are ultra experts, but at a high level, I would say that a lot of the TRT options center around fertility goals. Exogenous testosterone treats the low T, but it does suppress gonadal function, including spermatogenesis. So if that's not a priority, they can just get TRT. It should be done under the care of a urologist, a men's health, an endocrinologist, where we're checking liver chemistries and CBCs and a PSA and so forth. If they're interested in fertility preservation, then I would say engaging an endocrinologist, men's health expert is important. There's medications even like hCG, Clomid, which works centrally and stimulate the gonadal access. Niche scenarios where they might want standard TRT now, and then down the way, 5, 7 years, they're thinking about coming off of that for fertility purposes, I think that's really where you want to have an expert involved because there's quite a bit of nuance there in recovery of actual spermatogenesis and so forth. To kind of summarize, you got to ask about it. Checking it is, is not overly complicated. We do a baseline pre-orchiectomy and at least once annually, you can tag it in with the tumor markers, so it's not an extra blood draw. And if they have symptoms of course, kind of developed, then we'll move that up in the evaluation. Dr. Pedro Barata: Got it. And you also touch base on the fertility angle, which is truly important. And I'm just curious, you know, a lot of times many of us might see one, two patients a year, right, and we forget these protocols and what we've got to do about that. And so I'm interested to hear your thoughts about when you think about fertility, and how proactive you get. In other words, who do you refer for the fertility clinic, for a fertility preservation program? You know, do all cases despite getting through orchiectomy or just the cases that you're going to, you know you're going to seek chemotherapy at some point? What kind of selection or it depends on the chemo, like how do you do that assessment about the referral for preservation program that you might have available at UCSD? Dr. Aditya Bagrodia: Yeah, I mean I feel really fortunate to sit on the NCCN Testis Cancer Guidelines. It's in there that fertility counseling should be discussed prior to orchiectomy. So 100% bring it up. If there are risk factors, undescended testicles, previous history of fertility concerns, atrophic contralateral testicle, anything on the ultrasound like microlithiasis in the contralateral testicle, you kind of wanna get it there. And then again, there's kind of niche scenarios where you're really worried, maybe get a semen analysis and it doesn't look that good, arrange for the time of orchiectomy to have onco-testicular sperm extraction from the, quote unquote, "normal" testis parenchyma. You know, I think you have to be kind of prepared to go that route and really make sure you're doing this completely comprehensively. So pre-orchiectomy all patients. Don't really push for it too hard if they've got a contralateral testicle, if they've had no issues having children. There's some cost associated with this, sperm banking still isn't kind of covered even in the context of men with cancer. If they've got risk factors, absolutely pre-orchiectomy. Pre-RPLND, even though the rates of ejaculatory dysfunction at a high-volume center should be low single digits, I'll still offer it. That'd be a real catastrophe if they were in that small proportion of patients and now they're going to be reliant on things like intrauterine insemination, where it becomes quite expensive. Pre-chemo, everybody. That's basically a standard these days where it should be discussed and it's kind of amazing currently, even if you don't have an accessible men's health fertility clinic, there are actually companies, I have no vested interest, Fellow is one such company where you can actually create an account, receive a FedEx semen analysis and cryopreservation kit, send it back in, and all CLIA certified, it's based out of California. The gentleman that runs it, is a urologist and very, very bright guy who's done a lot of great stuff for testis cancer. So, even for patients that are kind of in extremis at the hospital that kind of need to get going like yesterday, we still discuss it. We've got some mechanisms in place to either have them take a semen analysis over to our Men's Health clinic or send it off to Fellow, which I think is pretty cool and that even extends to some of our younger adolescent patients where going to a clinic and providing a sample might be tricky. So, I think bringing it up every stage, anytime there's an intervention that might be offered, orchiectomy, chemo, surgery, radiation, it's kind of incumbent on us to discuss it. Dr. Pedro Barata: Gotcha. That's super helpful. And you also touch base on another angle, which is the psychosocial angle around this. You mentioned suicidal rates, you mentioned anxiety, perhaps depression in some cases as well as chronic fatigue, not necessarily just because of the low testosterone that you can get, but also from a psychological perspective. I'm curious, what do the recommendations look like for that? Do these patients need to see a social worker or a psychologist, or do they need to answer a screening test every time they come to see us and then based on that, we kind of escalate, take the next steps according to that? Do they see a psychologist perhaps every so often? How should that be managed and addressed? Dr. Aditya Bagrodia: It's an excellent question and again, these can be rather insidious symptoms where if you don't really dig in and inquire, they can be glossed over. I mean, how easy to say, "Your markers look okay, your scans look okay. See you in six months," and keep it kind of brief. First off, I think bringing it up proactively and normalizing it, that, "This may be something that you experience. Many people do, you're not alone, there's nothing kind of wrong with you." I also think that this is an area where support groups can be incredibly useful. We host the Testicular Cancer Awareness Foundation support group here. They'll talk about chemo brain or just like a little bit of an adjustment disorder after their diagnosis. Support groups, I think are critical. As I mentioned, we have a survivorship program that's led by a combination of our med oncs, myself on the uro-onc side, as well as APPs, where we are systematically asking about essentially the whole litany of issues that may arise, including psychosocial, anxiety, depression, suicidality. And we've got a nice kind of fast path into our cancer center support services for these young men to meet with a psychologist. If that isn't going to be sufficient, they can actually see a psychiatrist to discuss medications and so forth. I do think that we've got to screen for these because, as anticipated from diagnosis, those first 2 years, we see a rise. But even 10, 15 years out, we note, compared to controls, that there is an increased level of anxiety, depression, suicidality that might not just take place at that initial acute period of diagnosis and treatment. Dr. Pedro Barata: Really well said. Super important. So I guess if I were to put all these together, with these really amazing advances in technology, we all know AI, some of us might be more or less aware of biomarkers coming up, including microRNA for example, and others, like as I think of all these potential long term complications for these patients, look at the future, I guess, can we use this as a way to deescalate treatment where it's not really necessary, as a way to actually prevent some of these complications? Like, how do we see where we're heading? As we manage testicular cancer, let's say, within the next 5 or 10 years, do you think there's something coming up that's going to be different from what we're doing things today? Dr. Aditya Bagrodia: Totally. I mean, I think it's as exciting as a time as there's ever been, you know, maybe notwithstanding circa 1970s when platinum was discovered. So microRNAs, which you mentioned, you know, there's a new candidate biomarker, microRNA-371. We are super excited here at UCSD. We actually have it CLIA-certified available in our lab and are ordering these tests for patients kind of in their acute stage, you know, stage one and surveillance, stage two, post-RPLND, receiving chemotherapy. And essentially this is a universal germ cell tumor specific biomarker, except for teratoma, suffice it to say 90% sensitive and specific. And I think it's going to change the way that we diagnose and manage patients. You know, pre-orchiectomy, that's pretty straightforward. Post-orchiectomy, maybe we can really decrease the number of CT scans that are done. Maybe we can identify those patients that basically have occult disease where we can intervene early, either with RPLND or single cycle chemo. Post-RPLND, identify the patients who are at higher risk of relapse that may benefit from some adjuvant therapy. In the advanced setting, look at marker decline for patients in addition to standard tumor markers. Can we modulate their systemic therapy? So, the international interest is largely on modifying things. There's really cool clinical trials that we have for stage one patients, that treatment would be prescribed based on a post-orchiectomy microRNA. I think the microRNAs are really exciting. Teratoma remains an outstanding question. I think this is where maybe ctDNA, perhaps some radiomics and advanced imaging processing and incorporating AI may allow us to safely avoid a lot of these post-chemo RPLNDs. And then identification using SNPs and so forth of who might be most susceptible to some of the cardiac toxicity, autotoxicity and personalizing things in that way as well. Dr. Pedro Barata: Super exciting, right, what's about to come? And I agree with you, I think it's going to change dramatically how we manage this disease. This has been a pleasure sitting down with you. I guess before letting you go, anything else you'd like to add before we wrap it up? Dr. Aditya Bagrodia: Yeah, first off, again, just want to thank you and ASCO for the opportunity. And it's easy enough to, I think, approach a patient with the testicular germ cell tumor as, "This is an easy case. We're just going to do whatever we've done. Go to the guidelines that says do X, Y, or Z." But there's so much more nuance to it than that. Getting it done perfectly, I think, is mandatory. Whatever we do is an impact on them for the next 50, 60, 70 years of their life. And I found the germ cell tumor community, people are really passionate about it. If you're ever uncertain, there's experts throughout the country and internationally. Ask somebody before you do something that you can't undo. I think we owe it to them to get it perfect so that we can really maximize the survivorship and the survival like we've been talking about. Dr. Pedro Barata: Aditya, thanks for sharing your fantastic insights with us on this podcast. Dr. Aditya Bagrodia: All right, Pedro. Fantastic. Appreciate the opportunity. Dr. Pedro Barata: And also, thank you to our listeners for your time today. I actually encourage you to check out Dr. Bagrodia's article in the 2025 ASCO Educational Book. We'll post a link to the paper in the show notes. Remember, it's free access online, and you can actually download it as well as a PDF. You can also find on the website a wealth of other great papers from the ASCO Educational Book on key advances and novel approaches that are shaping modern oncology. So with that, thank you everyone. Thank you, Aditya, one more time, for joining us. Thank you, have a good day. 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. Follow today's speakers: Dr. Pedro Barata @PBarataMD Dr. Aditya Bagrodia @AdityaBagrodia Follow ASCO on social media: @ASCO on X (formerly Twitter) ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Pedro Barata: Stock and Other Ownership Interests: Luminate Medical Honoraria: UroToday Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck Dr. Aditya Bagrodia: Consulting or Advisory Role: Veracyte, Ferring

Dr. Pedro Barata and Dr. Rana McKay discuss the integration of innovative advances in molecular imaging and therapeutics to personalize treatment for patients with renal cell and urothelial carcinomas. TRANSCRIPT Dr. Pedro Barata: Hello, I'm Dr. Pedro Barata, your guest host of By the Book, a podcast series featuring insightful conversations between authors and editors of the ASCO Educational Book. I'm a medical oncologist at University Hospitals Seidman Cancer Center and an associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also an associate editor of the ASCO Educational Book. Now, we all know the field of genitourinary cancers (GU) is evolving quite rapidly, and we have new innovations in molecular imaging as well as targeted therapeutics. Today's episode will be exploring novel approaches that are transforming the management of renal cell and urothelial carcinomas and also their potential to offer a more personalized treatment to patients. For that, joining for today's discussion is Dr. Rana McKay, a GU medical oncologist and professor at University of California San Diego. Dr. McKay will discuss her recently published article titled, "Emerging Paradigms in Genitourinary Cancers: Integrating Molecular Imaging, Hypoxia-Inducible Factor-Targeted Therapies, and Antibody-Drug Conjugates in Renal Cell and Urothelial Carcinomas." Our full disclosures are available in the transcript of this episode. And with that, Rana McKay, great to have you on the podcast today. Dr. Rana McKay: Oh, thank you so much, Dr. Barata. It's really wonderful to be here with you. So, thanks for hosting. Dr. Pedro Barata: No, thanks for taking the time, and I'm looking forward to this conversation. And by the way, let me start by saying congrats on a great article in the Educational Book. Really super helpful paper. I'm recommending it to a lot of the residents and fellows at my own institution. I would like to first ask you to kind of give our listeners some context of how novel approaches in the molecular imaging as well as targeted therapeutics are actually changing the way we're managing patients with GU, but specifically with renal cell carcinoma and urothelial carcinoma. So, what are the areas you would call out as like being big areas for innovation in this context, and why are they important? Dr. Rana McKay: Very good question. And I think this is really what this article highlights. It highlights where are we going from an imaging diagnostics standpoint? Where are we going from a therapeutic standpoint? And I think if we have to step back, from the standpoint of diagnostics, we've seen PET imaging really transform diagnostics in prostate cancer with the advent of PSMA PET imaging, and now PSMA PET imaging is used as a biomarker for selection for theranostics therapy. And so, we're starting to see that enter into the RCC landscape, enter into the urothelial cancer landscape to a lesser extent. And I think it's going to potentially be transformative as these tools get more refined. I think when we think about therapeutics, what's been transformative most recently in the renal cell carcinoma landscape has been the advent of HIF2α inhibition to improve outcomes for patients. And we have seen the approval of belzutifan most recently that has reshaped the landscape. And now there's other HIF2α inhibitors that are being developed that are going to be further important as they get refined. And lastly, I think when we think about urothelial carcinoma, the greatest transformation to treatment in that context has been the displacement of cisplatin and platinum-based chemotherapy as a frontline standard with the combination of enfortumab vedotin plus pembrolizumab. And we've seen antibody-drug conjugates really reshape treatment and tremendously improve outcomes for patients. So, I think those are the three key areas of interest. Dr. Pedro Barata: So with that, let's focus first on the imaging and then we'll get to the therapeutic area. So, we know there's been a paradigm shift, really, when prostate-specific targets emerged as tracers for PET scanning. And so, we now commonly use prostate-specific membrane antigen, or PSMA-based PET scanning, and really transform how we manage prostate cancer. Now, it appears that we're kind of seeing a similar wave in renal cell carcinoma with the new radiotracer against the target carbonic anhydrase IX. What can you tell us about this? And is this going to be available to us anytime soon? And how do you think that might potentially change the way we're managing patients with RCC today? Dr. Rana McKay: First, I'll step back and say that in the context of PSMA PET imaging, we have actually been able to better understand RCC as well. So, we know that PSMA is expressed in the neovasculature of tumors, and it can actually be used to detect renal cell carcinoma tumors. It has a detection rate of about 84% when used for detection. And so, you know, I don't think it's just restricted to carbonic anhydrase IX, but we will talk about that. So, PSMA expressed in the neovasculature has a detection rate of around 84%, particularly if we're looking at clear cell RCC. CAlX is overexpressed in clear cell RCC, and it's actually used in diagnosing renal cell carcinoma when we think of CAlX IHC for diagnosing clear cell RCC. And now there are CAlX PET tracers. The first foray was with the ZIRCON study that was actually an interestingly designed study because it was designed to detect the likelihood of PET imaging to identify clear cell RCC. So, it was actually used in the early diagnostics setting when somebody presents with a renal mass to discriminate that renal mass from a clear cell versus a non-clear cell, and it was a positive study. But when I think about the potential application for these agents, you know, I think about the entire landscape of renal cell carcinoma. This is a disease that we do treat with metastasis-directed therapy. We have certainly seen patients who've undergone metastasectomy have long, durable remissions from such an approach. And I think if we can detect very early onset oligometastatic disease where a metastasis-directed therapy or SABR could be introduced - obviously tested in a trial to demonstrate its efficacy - I think it could potentially be transformative. Dr. Pedro Barata: Wonderful. It's a great summary, and I should highlight you are involved in some of those ongoing studies testing the performance of this specific PET scanning for RCC against conventional imaging, right? And to remind the listeners, thus far, for the most part, we don't really do FDG-PET for RCC. There are some specific cases we do, but in general, they're not a standard scanning. But maybe that will change in the future. Maybe RCC will have their own PSMA-PET. And to your point, there's also emerging data about the role of PSMA-PET scanning in RCC as well, as you very elegantly summarized. Wonderful. So, let me shift gears a little bit because you did, in your introduction, you did highlight a novel MOA that we have in renal cell carcinoma, approved for use, initially for VHL disease, and after that for sporadic clear cell renal cell carcinoma. We're talking about hypoxia-inducible factor 2-alpha inhibitors, or HIF2α inhibitors, such as belzutifan. But there's also others coming up. So, as a way to kind of summarize that, what can you tell us about this breakthrough in terms of therapeutic class, this MOA that got to our toolbox of options for patients with advanced RCC? Tell us a little bit what is being utilized currently in the management of advanced RCC. And where do you see the future going, as far as, is it moving early on? Is it getting monotherapy versus combinations? Maybe other therapies? What are your thoughts about that? What can you tell us about it? Dr. Rana McKay: Belzutifan is a first-in-class HIF2α inhibitor that really established clinical validation for HIF2α as a therapeutic target. When we think about the activity of this agent, the pivotal LITESPARK-005 trial really led to the approval of belzutifan in patients who were really heavily pretreated. It was patients who had received prior IO therapy, patients who had received prior VEGF-targeted therapy. And in the context of this study, we saw a median PFS of 5.6 months, and there did seem to be a tail on the curve when you looked at the 12-month PFS rate with belzutifan. It was 33.7% compared to 17.6% with everolimus. And then when we look at the response rate, it was higher with belzutifan on the order of 22-23%, and very low with everolimus, as we've previously seen. I think one of the Achilles heels of this regimen is the primary PD rate, which was 34% when used in later line. There are multiple studies that are testing belzutifan in combination across the treatment landscape. So, we have LITESPARK-011, which is looking at the combination of belzutifan plus lenvatinib in the second-line setting. We've got the MK-012 [LITESPARK-012] study, which is looking at belzutifan in various combinations in the frontline setting. So there is a combination with IO plus belzutifan. And so this is also being looked at in that context. And then we also have the LITESPARK-022 study, which is looking at pembrolizumab with belzutifan in the adjuvant setting. So there's a series of studies that will be exploring belzutifan really across the treatment landscape. Many of these studies in combination. Additionally, there are other HIF2α inhibitors that are being developed. We have casdatifan, which is another very potent HIF2α inhibitor. You know, I think pharmacologically, these are different agents. There's a different half-life, different dosing. What is going to be the recommended phase 3 dose for both agents, the EPO suppression levels, the degree of EPO suppression, and sustainability of EPO suppression is very different. So, I think we've seen data from casdatifan from the ARC-20 trial from monotherapy with a respectable response rate, over 30%, primary PD rate hovering just around 10%. And then we've also seen data of the combination of casdatifan with cabozantinib as well that were recently presented this year. And that agent is also being tested across the spectrum of RCC. It's being looked at in combination with cabozantinib in the PEAK-1 study, and actually just at the KCRS (Kidney Cancer Research Summit), we saw the unveiling of the eVOLVE-RCC trial, which is going to be looking at a volrustomig, which is a PD-1/CTLA-4 inhibitor plus casdatifan compared to nivo-ipi in the frontline setting. So, we're going to see some competition in this space of the HIF2α inhibitors. I think when we think of mechanism of action in that these are very potent, not a lot of off-target activity, and they target a driver mutation in the disease. And that driver mutation happens very early in the pathogenesis. These are going to be positioned much earlier in the treatment landscape. Dr. Pedro Barata: All these studies, as you're saying, look really promising. And when we talk about them, you mentioned a lot of combinations. And to me, when I think of these agents, it makes a lot of sense to combine because there's not a lot of overlapping toxicities, if you will. But perhaps for some of our listeners, who have not used HIF2α inhibitors in practice yet, and they might be thinking about that, what can you tell us about the safety profile? How do you present it to your patients, and how do you handle things like hypoxia or anemia? How do you walk through the safety profile and tolerability profile of those agents like belzutifan? Dr. Rana McKay: I think these drugs are very different than your traditional TKIs, and they don't cause the classic symptoms that are associated with traditional TKIs that many of us are very familiar with like the rash, hand-foot syndrome, hypertension, diarrhea. And honestly, these are very nuanced symptoms that patients really struggle with the chronicity of being on a chronic daily TKI. The three key side effects that I warn patients about with HIF2α inhibitors are: (1) fatigue; (2) anemia; and (3) hypoxia and dysregulation in the ability to sense oxygen levels. And so, many of these side effects - actually, all of them - are very dose-dependent. They can be very well-managed. So, we can start off with the anemia. I think it's critically important before you even start somebody on belzutifan that you are optimizing their hemoglobin and bone marrow function. Make sure they don't have an underlying iron deficiency anemia. Make sure they don't have B12 or folate deficiency. Check for these parameters. Many patients who have kidney cancer may have some hematuria, other things where there could be some low-level blood loss. So, make sure that those are resolved or you're at least addressing them and supplementing people appropriately. I monitor anemia very closely every 3 to 4 weeks, at least, when people start on these medications. And I do initiate EPO, erythropoietin, should the anemia start to worsen. And I typically use a threshold of around 10g/dL for implementing utilization of an EPO agent, and that's been done very safely in the context of the early studies and phase 3 studies as well. Now, with regards to the hypoxia, I think it's also important to make sure that you're selecting the appropriate individual for this treatment. People who have underlying COPD, or even those individuals who have just a very high burden of disease in their lung, lymphangitic spread, pleural effusions, maybe they're already on oxygen - that's not an ideal candidate for belzutifan. Something that very easily can be done in the clinic before you think about initiating somebody on this treatment, and has certainly been integrated into some of the trials, is just a 6-minute walk test. You know, have the patient walk around the clinic with one of the MAs, one of the nurses, put the O2 sat on [measuring oxygen saturation], make sure they're doing okay. But these side effects, like I said, are very dose-dependent. Typically, if a patient requires, if the symptoms are severe, the therapy can be discontinued and dose reduced. The standing dose is 120 mg daily, and there's two dose reductions to 80 mg and 40 mg should somebody warrant that dose modification. Dr. Pedro Barata: This is relatively new, right? Like, it was not that we're used to checking oxygen levels, right? In general, we're treating these patients, so I certainly think there's a learning curve there, and some of the points that you highlight are truly critical. And I do share many of those as well in our practice. Since I have you, I want to make sure we touch base on antibody-drug conjugates as well. It's also been a hot area, a lot of developments there. When I think of urothelial carcinoma and renal cell carcinoma, I see it a little bit different. I think perhaps in urothelial carcinoma, antibody-drug conjugates, or ADCs, are somewhat established already. You already mentioned enfortumab vedotin. I might ask you to expand a little bit on that. And then in renal cell carcinoma, we have some ADCs as well that you include in your chapter, and that I would like you to tell us what's coming from that perspective. So, tell us a little bit about how do you see ADCs in general for GU tumors, particularly UC and RCC? Tell us a little bit about the complexity or perhaps the challenges you still see. At the same time, tell us about the successes. Dr. Rana McKay: Stepping back, let's just talk about like the principles and design of ADCs. So, most ADCs have three components. There's a monoclonal antibody that typically targets a cell surface antigen, which is conjugated by a linker, which is the second component, to a payload drug. And typically, that payload drug has been chemotherapy, whether it be topoisomerase or whether it be MMAE or other chemotherapeutic. We can start in the RCC space. There's been multiple antibody-drug conjugates that have been tested. There's antibody-drug conjugates to CD70, which is expressed on clear cell RCC. There's been antibody-drug conjugates to ENPP3, which is also expressed on RCC. There's antibody-drug conjugates to CDH6. And they have different payloads, like I said, whether it be topoisomerase I or other microtubule inhibitors. Now, when we think about kidney cancer, we don't treat this disease with chemotherapy. This disease is treated with immunotherapy. It is treated with treatments that target the VEGF pathway and historically has not been sensitive to chemo. So, I think even though the targets have been very exciting, we've seen very underwhelming data regarding activity, and in some context, seen increased toxicity with the ADCs. So, I think we need to tread lightly in the context of the integration and the testing of ADCs in RCC. We just came back from the KCRS meeting, and there was some very intriguing data about a c-Kit ADC that's being developed for chromophobe RCC, which is, you know, a huge unmet need, these variant tumors that really lack appropriate therapeutics. But I just caution us to tread lightly around how can we optimize the payload to make sure that the tumor that we're treating is actually sensitive to the agent that's targeting the cell kill. So, that's a little bit on the ADCs in RCC. I still think we have a long way to go and still in early testing. Now, ADCs for UC are now the standard of care. I think the prototypical agent, enfortumab vedotin, is a nectin-4-directed ADC that's conjugated to an MMAE payload and was the first ADC approved for advanced urothelial, received accelerated approval following the EV-201 trial, which was basically a multicenter, single-arm study that was investigating EV in cisplatin-ineligible patients with advanced urothelial carcinoma, and then ultimately confirmed in the EV-301 study as well. And so, that study ended up demonstrating the support superiority of EV from an overall survival standpoint, even PFS standpoint. Building on that backbone is the EV-302 study, which tested EV in combination with pembrolizumab versus platinum-based chemotherapy in the frontline setting. And that was a pivotal, landmark study that, like I said, has displaced platinum therapy as a frontline treatment for people with advanced urothelial carcinoma. And when we think about that study and the median overall survival and just how far we've come in urothelial cancer, the median OS with EV-pembro from that trial was 31 and a half months. I mean, that's just incredible. The control arm survival was 16 and a half months. The hazard ratio for OS, 0.47. I mean this is why when this data was presented, it was literally a standing ovation that lasted for several minutes because we just haven't seen data that have looked that good. And there are other antibody-drug conjugates that are being tested. We've all been involved in the saga with sacituzumab govitecan, which is a trophoblast cell surface antigen 2 (Trop-2) targeted ADC with a topoisomerase I payload. It was the second ADC to receive approval, but then that approval was subsequently withdrawn when the confirmatory phase 3 was negative, the TROPiCS-04 trial. So, approval was granted based off of the TROPHY-U-01, single-arm, phase 2 study, demonstrating a response rate of around 28% and a PFS of, you know, about 5 and a half months. But then failure to show any benefit from an OS standpoint. And I think there's a lot of controversy in the field around whether this agent still has a role in advanced urothelial carcinoma. And I think particularly for individuals who do not have molecular targets, like they're not HER2-amplified or have HER2-positivity or FGFR or other things like that. Dr. Pedro Barata: Fantastic summary, Rana. You were talking about the EV, and it came to mind that it might not be over, right, for the number of ADCs we use in clinical practice in the near future. I mean, we've seen very promising data for ADC against the HER2, right, and over-expression. It also can create some challenges, right, in the clinics because we're asking to test for HER2 expression. It's almost like, it's not exactly the same to do it in breast cancer, but it looks one more time that we're a little bit behind the breast cancer field in a lot of angles. And also has vedotin as a payload. Of course, I'm referring to disitamab vedotin, and there's very elegant data described by you in your review chapter as well. And it's going to be very interesting to see how we sequence the different ADCs, to your point as well. So, before we wrap it up, I just want to give you the opportunity to tell us if there's any area that we have not touched, any take-home points you'd like to bring up for our listeners before we call it a day. Dr. Rana McKay: Thank you so much. I have to say, you know, I was so excited at ASCO this year looking at the GU program. It was fantastic to see the progress being made, novel therapeutics that really there's a tremendous excitement about, not just in RCC and in UC, but also in prostate cancer, thinking about the integration of therapies, not just for people with refractory disease that, even though our goal is to improve survival, our likelihood of cure is low, but also thinking about how do we integrate these therapies early in the treatment landscape to enhance cure rates for patients, which is just really spectacular. We're seeing many of these agents move into the perioperative setting or in combination with radiation for localized disease. And then the special symposium on biomarkers, I mean, we've really come a long, long way. And I think that we're going to continue to evolve over the next several years. I'm super excited about where the field is going in the treatment of genitourinary malignancies. Dr. Pedro Barata: Oh, absolutely true. And I would say within the Annual Meeting, we have outstanding Educational Sessions. And just a reminder to the listeners that actually that's where the different teams or topics for the Educational Book chapters come from, from actually the educational sessions from ASCO. And your fantastic chapter is an example of that, right, focusing on advanced GU tumors. So, thank you so much, Rana, for taking the time, sharing your insights with us today on the podcast. It was a fantastic conversation as always. Dr. Rana McKay: My pleasure. Thanks so much for having me, Dr. Barata. Dr. Pedro Barata: Of course. And thank you to our listeners for your time today. You will find the link to the article discussed today in the transcript of this episode. I also encourage you to check out the 2025 ASCO Educational Book. You'll find an incredible wealth of information there. It's free, available online, and you'll find, hopefully, super, super important information on the key science and issues that are shaping modern oncology, as we've heard from Dr. McKay and many other outstanding authors. So, thank you, everyone, and I hope to see you soon. 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. Follow today's speakers: Dr. Pedro Barata @PBarataMD Dr. Rana McKay @DrRanaMcKay Follow ASCO on social media: @ASCO on X (formerly Twitter) ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Pedro Barata: Stock and Other Ownership Interests: Luminate Medical Honoraria: UroToday Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck Dr. Rana McKay: Consulting or Advisory Role: Janssen, Novartis, Tempus, Pfizer, Astellas Medivation, Dendreon, Bayer, Sanofi, Vividion, Calithera, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly, Blue Earth Diagnostics, Ambrx, Sumitomo Pharma Oncology, Esiai, NeoMorph, Arcus Biosciences, Daiichi Sankyo, Exelixis, Bristol Myers Squibb, Merck, Astrazeneca, Myovant Research Funding (Inst.): Bayer, Tempus, AstraZeneca, Exelixis, Bristol Myers Squibb, Oncternal Therapeutics, Artera

Drs. Hope Rugo, Sheri Brenner, and Mikolaj Slawkowski-Rode discuss the struggle that health care professionals experience when terminally ill patients are suffering and approaches to help clinicians understand and respond to suffering in a more patient-centered and therapeutic way. TRANSCRIPT Dr. Hope Rugo: Hello, and welcome to By the Book, a monthly podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I'm your host, Dr. Hope Rugo. I'm director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center, and I'm also the editor-in-chief of the Educational Book. On today's episode, we'll be exploring the complexities of grief and oncology and the struggle we experience as healthcare professionals when terminally ill patients are suffering. Our guests will discuss approaches to help clinicians understand and respond to suffering in a more patient-centered and therapeutic way, as outlined in their recently published article titled, "Oncology and Suffering: Strategies on Coping With Grief for Healthcare Professionals." I'm delighted today to welcome Dr. Keri Brenner, a clinical associate professor of medicine, palliative care attending, and psychiatrist at Stanford University, and Dr. Mikołaj Sławkowski-Rode, a senior research fellow in philosophy in the Humanities Research Institute at the University of Buckingham, where he also serves as director of graduate research in p hilosophy. He is also a research fellow in philosophy at Blackfriars Hall at the University of Oxford and associate professor at the University of Warsaw. Our full disclosures are available in the transcript of this episode. Dr. Brenner and Dr. Sławkowski-Rode, thanks for being on the podcast today. Dr. Keri Brenner: Great to be here, Dr. Rugo. Thank you so much for that kind introduction. Dr. Mikołaj Sławkowski-Rode: Thank you very much, Dr. Rugo. It's a pleasure and an honor. Dr. Hope Rugo: So I'm going to start with some questions for both of you. I'll start with Dr. Brenner. You've spoken and written about the concept of suffering when there is no cure. For oncologists, what does it mean to attune to suffering, not just disease? And how might this impact the way they show up in difficult conversations with patients? Dr. Keri Brenner: Suffering is something that's so omnipresent in the work of clinical oncology, and I like to begin by just thinking about what is suffering, because it's a word that we use so commonly, and yet, it's important to know what we're talking about. I think about the definition of Eric Cassell, who was a beloved mentor of mine for decades, and he defined suffering as the state of severe distress that's associated with events that threaten the intactness of a person. And my colleague here at Stanford, Tyler Tate, has been working on a definition of suffering that encompasses the experience of a gap between how things are versus how things ought to be. Both of these definitions really touch upon suffering in a person-centered way that's relational about one's identity, meaning, autonomy, and connectedness with others. So these definitions alone remind us that suffering calls for a person-centered response, not the patient as a pathology, but the panoramic view of who the patient is as a person and their lived reality of illness. And in this light, the therapeutic alliance becomes one of our most active ingredients in care. The therapeutic alliance is that collaborative, trusting bond as persons that we have between clinician and patient, and it's actually one of the most powerful predictors of meaningful outcomes in our care, especially in oncologic care. You know, I'll never forget my first day of internship at Massachusetts General Hospital. A faculty lecturer shared this really sage insight with us that left this indelible mark. She shared, "As physicians and healers, your very self is the primary instrument of healing. Our being is the median of the medicine." So, our very selves as embodied, relationally grounded people, that's the median of the medicine and the first most enduring medicine that we offer. That has really borne fruit in the evidence that we see around the therapeutic alliance. And we see this in oncologic care, that in advanced cancer, a strong alliance with one's oncologist truly improves a patient's quality of life, treatment adherence, emotional well-being, and even surpasses structured interventions like psychotherapeutic interventions. Dr. Hope Rugo: That's just incredibly helpful information and actually terminology as well, and I think the concept of suffering differs so much. Suffering comes in many shapes and forms, and I think you really have highlighted that. But many oncologists struggle with knowing what to do when patients are suffering but can't be fixed, and I think a lot of times that has to do with oncologists when patients have pain or shortness of breath or issues like that. There are obviously many ways people suffer. But I think what's really challenging is how clinicians understand suffering and what the best approaches to respond to suffering are in the best patient-centered and therapeutic way. Dr. Keri Brenner: I get that question a lot from my trainees in palliative care, not knowing what to do. And my first response is, this is about how to be, not about knowing what to do, but how to be. In our medical training, we're trained often how to think and treat, but rarely how to be, how to accompany others. And I often have this image that I tell my trainees of, instead of this hierarchical approach of a fix-it mentality of all we're going to do, when it comes to elements of unavoidable loss, mortality, unavoidable sufferings, I imagine something more like accompaniment, a patient walking through some dark caverns, and I am accompanying them, trying to walk beside them, shining a light as a guide throughout that darkness. So it's a spirit of being and walking with. And it's so tempting in medicine to either avoid the suffering altogether or potentially overidentify with it, where the suffering just becomes so all-consuming like it's our own. And we're taught to instead strike a balance of authentic accompaniment through it. I often teach this key concept in my palli-psych work with my team about formulation. Formulation is a working hypothesis. It's taking a step back and asking, "Why? Why is this patient behaving in this manner? What might the patient's core inner struggle be?" Because asking that "why" and understanding the nuanced dimensions of a patient's core inner struggle will really help guide our therapeutic interactions and guide the way that we accompany them and where we choose to shine that light as we're walking with them. And oftentimes people think, "Well Keri, that sounds so sappy or oversentimental," and it's not. You know, I'm just thinking about a case that I had a couple months ago, and it was a 28-year-old man with gastric cancer, metastatic disease, and that 28-year-old man, he was actually a college Division I athlete, and his dad was an acclaimed Division I coach. And our typical open-ended palliative care questions, that approach, infuriated them. They needed to know that I was showing up confident, competent, and that I was ready, on my A-game, with a real plan for them to follow through. And so my formulation about them was they needed somebody to show up with that confidence and competence, like the Division I athletes that they were, to really meet them and accompany them where they were on how they were going to walk through that experience of illness. Dr. Hope Rugo: These kinds of insights are so helpful to think about how we manage something that we face every day in oncology care. And I think that there are many ways to manage this. Maybe I'll ask Dr. Sławkowski-Rode one question just that I think sequences nicely with what you're talking about. A lot of our patients are trying to think about sort of the bigger picture and how that might help clinicians understand and support patients. So, the whole concept of spirituality, you know, how can we really use that as oncology clinicians to better understand and support patients with advanced illness, and how can that help patients themselves? And we'll talk about that in two different ways, but we'll just start with this broader question. Dr. Mikołaj Sławkowski-Rode: I think spirituality, and here, I usually refer to spirituality in terms of religious belief. Most people in the world are religious believers, and it is very intuitive and natural that religious beliefs would be a resource that people who help patients with a terminal diagnosis and healthcare professionals who work with those patients appeal to when they try to help them deal with the trauma and the stress of these situations. Now, I think that the interesting thing there is that very often the benefit of appealing to a religious belief is misunderstood in terms of what it delivers. And there are many, many studies on how religious belief can be used to support therapy and to support patients in getting through the experience of suffering and defeating cancer or facing a terminal diagnosis. There's a wealth of literature on this. But most of the literature focuses on this idea that by appealing to religious belief, we help patients and healthcare practitioners who are working with them get over the fact and that there's a terminal diagnosis determining the course of someone's life and get on with our lives and engaging with whatever other pursuits we might have, with our job if we're healthcare practitioners, and with the other things that we might be passionate about in our lives. And the idea here is that this is what religion allows us to do because we sort of defer the need to worry about what's going to happen to us until the afterlife or some perspective beyond the horizon of our life here. However, my view is – I have worked beyond philosophy also with theologians from many traditions, and my view here is that religion is something that does allow us to get on with our life but not because we're able to move on or move past the concerns that are being threatened by illness or death, but by forming stronger bonds with these things that we value in our life in a way and to have a sense of hope that these will be things that we will be able to keep an attachment to despite the threat to our life. So, in a sense, I think very many approaches in the field have the benefit of religion upside down, as it were, when it comes to helping patients and healthcare professionals who are engaged with their illness and treating it. Dr. Hope Rugo: You know, it's really interesting the points that you make, and I think really important, but, you know, sometimes the oncologists are really struggling with their own emotional reactions, how they are reacting to patients, and dealing with sort of taking on the burden, which, Dr. Brenner, you were mentioning earlier. How can oncologists be aware of their own emotional reactions? You know, they're struggling with this patient who they're very attached to who's dying or whatever the situation is, but you want to avoid burnout as an oncologist but also understand the patient's inner world and support them. Dr. Keri Brenner: I believe that these affective, emotional states, they're contagious. As we accompany patients through these tragic losses, it's very normal and expected that we ourselves will experience that full range of the human experience as we accompany the patients. And so the more that we can recognize that this is a normative dimension of our work, to have a nonjudgmental stance about the whole panoramic set of emotions that we'll experience as we accompany patients with curiosity and openness about that, the more sustainable the work will become. And I often think about the concept of countertransference given to us by Sigmund Freud over 100 years ago. Countertransference is the clinician's response to the patient, the thoughts, feelings, associations that come up within us, shaped by our own history, our own life events, those unconscious processes that come to the foreground as we are accompanying patients with illness. And that is a natural part of the human experience. Historically, countertransference was viewed as something negative, and now it's actually seen as a key that can unlock and enlighten the formulation about what might be going on within the patient themselves even. You know, I was with a patient a couple weeks ago, and I found myself feeling pretty helpless and hopeless in the encounter as I was trying to care for them. And I recognized that countertransference within myself that I was feeling demoralized. It was a prompt for me to take a step back, get on the balcony, and be curious about that because I normally don't feel helpless and hopeless caring for my patients. Well, ultimately, I discovered through processing it with my interdisciplinary team that the patient likely had demoralization as a clinical syndrome, and so it's natural many of us were feeling helpless and hopeless also accompanying them with their care. And it allowed us to have a greater interdisciplinary approach and a more therapeutic response and deeper empathy for the patient's plight. And we can really be curious about our countertransferences. You know, a few months ago, I was feeling bored and distracted in a family meeting, which is quite atypical for me when I'm sharing serious illness news. And it was actually a key that allowed me to recognize that the patient was trying to distract all of us talking about inconsequential facts and details rather than the gravitas of her illness. Being curious about these affective states really allows us to have greater sustainability within our own practice because it normalizes that human spectrum of emotions and also allows us to reduce unconscious bias and have greater inclusivity with our practice because what Freud also said is that what we can't recognize and say within our own selves, if we don't have that self-reflective capacity, it will come out in what we do. So really recognizing and having the self-awareness and naming some of these emotions with trusted colleagues or even within our own selves allows us to ensure that it doesn't come out in aberrant behaviors like avoiding the patient, staving off that patient till the end of the day, or overtreating, offering more chemotherapy or not having the goals of care, doing everything possible when we know that that might result in medically ineffective care. Dr. Hope Rugo: Yeah, I love the comments that you made, sort of weaving in Freud, but also, I think the importance of talking to colleagues and to sharing some of these issues because I do think that oncologists suffer from the fact that no one else in your life wants to hear about dying people. They don't really want to hear about the tragic cases either. So, I think that using your community, your oncology community and greater community within medicine, is an important part of being able to sort of process. Dr. Keri Brenner: Yes, and Dr. Rugo, this came up in our ASCO [Education] Session. I'd love to double click into some of those ways that we can do this that aren't too time consuming in our everyday practice. You know, within palliative care, we have interdisciplinary rounds where we process complex cases. Some of us do case supervision with a trusted mentor or colleague where we bring complex cases to them. My team and I offer process rounds virtually where we go through countertransference, formulation, and therapeutic responses on some tough cases. You know, on a personal note, just last week when I left a family meeting feeling really depleted and stuck, I called one of my trusted colleagues and just for 3 minutes constructively, sort of cathartically vented what was coming up within me after that family meeting, which allowed me to have more of an enlightened stance on what to do next and how to be therapeutically helpful for the case. One of my colleagues calls this "friend-tors." They coined the phrase, and they actually wrote a paper about it. Who within your peer group of trusted colleagues can you utilize and phone in real time or have process opportunities with to get a pulse check on where what's coming up within us as we're doing this work? Dr. Hope Rugo: Yeah, and it's an interesting question about how one does that and, you know, maintaining that as you move institutions or change places or become more senior, it's really important. One of the, I think, the challenges sometimes is that we come from different places from our patients, and that can be an issue, I think when our patients are very religious and the provider is not, or the reverse, patients who don't have religious beliefs and you're trying to sort of focus on the spirituality, but it doesn't really ring true. So, Dr. Sławkowski-Rode, what resources can patients and practitioners draw on when they're facing death and loss in the absence of, or just different religious beliefs that don't fit into the standard model? Dr. Mikołaj Sławkowski-Rode: You're absolutely right that this can be an extremely problematic situation to be in when there is that disconnect of religious belief or more generally spiritual engagement with the situation that we're in. But I just wanted to tie into what Dr. Brenner was saying just before. I couldn't agree more, and I think that a lot of healthcare practitioners, oncologists in particular who I've had the pleasure to talk to at ASCO and at other events as well, are very often quite skeptical about emotional engagement in their profession. They feel as though this is something to be managed, as it were, and something that gets in the way. And they can often be very critical of methods that help them understand the emotions and extend them towards patients because they feel that this will be an obstacle to doing their job and potentially an obstacle also to helping patients to their full ability if they focus on their own emotions or the burden that emotionally, spiritually, and in other ways the illness is for the patient. They feel that they should be focusing on the cancer rather than on the patient's emotions. And I think that a useful comparison, although, you know, perhaps slightly drastic, is that of combat experience of soldiers. They also need to be up and running and can't be too emotionally invested in the situation that they're in. But there's a crucial difference, which is that soldiers are usually engaged in very short bursts of activity with the time to go back and rethink, and they often have a lot of support for this in between. Whereas doctors are in a profession where their exposure to the emotions of patients and their own emotions, the emotions of families of patients is constant. And I think that there's a great danger in thinking that this is something to be avoided and something to compartmentalize in order to avoid burnout. I think, in a way, burnout is more sure to happen if your emotions and your attachment to your patients goes ignored for too long. So that's just following up on Keri's absolutely excellent points. As far as the disconnect is concerned, that's, in fact, an area in which I'm particularly interested in. That's where my research comes in. I'm interested in the kinds of connections that we have with other people, especially in terms of maintaining bonds when there is no spiritual belief, no spiritual backdrop to support this connection. In most religious traditions, we have the framework of the religious belief that tells us that the person who we've lost or the values that have become undermined in our life are something that hasn't been destroyed permanently but something that we can still believe we have a deep connection to despite its absence from our life. And how do you rebuild that sense of the existence of the things that you have perceivably lost without the appeal to some sort of transcendent realm which is defined by a given religion? And that is a hard question. That's a question, I think, that can be answered partly by psychology but also partly by philosophy in terms of looking at who we are as human beings and our nature as people who are essentially, or as entities that are essentially connected to one another. That connection, I believe, is more direct than the mediation of religion might at first suggest. I think that we essentially share the world not only physically, it's not just the case that we're all here, but more importantly, the world that we live in is not just the physical world but the world of meanings and values that helps us orient ourselves in society and amongst one another as friends and foes. And it is that shared sense of the world that we can appeal to when we're thinking about retaining the value or retaining the connection with the people who we have lost or the people who are helping through, go through an experience of facing death. And just to finish, there's a very interesting question, I think, something that we possibly don't have time to explore, about the degree of connection that we have with other people. So, what I've just been saying is something that rings more true or is more intuitive when we think about the connections that we have to our closest ones. We share a similar outlook onto the world, and our preferences and our moods and our emotions and our values are shaped by life with the other person. And so, appealing to these values can give us a sense of a continued presence. But what in those relationships where the connection isn't that close? For example, given the topic of this podcast, the connection that a patient has with their doctor and vice versa. In what sense can we talk about a shared world of experience? Well, I think, obviously, we should admit degrees to the kind of relationship that can sustain our connection with another person. But at the same time, I don't think there's a clear cutoff point. And I think part of emotional engagement in medical practice is finding yourself somewhere on that spectrum rather than thinking you're completely off of it. That's what I would say. Dr. Hope Rugo: That's very helpful and I think a very helpful way of thinking about how to manage this challenging situation for all of us. One of the things that really, I think, is a big question for all of us throughout our careers, is when to address the dying process and how to do that. Dr. Brenner, you know, I still struggle with this – what to do when patients refuse to discuss end-of-life but they're very close to end of life? They don't want to talk about it. It's very stressful for all of us, even where you're going to be, how you're going to manage this. They're just absolutely opposed to that discussion. How should we approach those kinds of discussions? How do we manage that? How do you address the code discussion, which is so important? You know, these patients are not able to stay at home at end-of-life in general, so you really do need to have a code discussion before you're admitting them. It actually ends up being kind of a challenge and a mess all around. You know, I would love your advice about how to manage those situations. Dr. Keri Brenner: I think that's one of the most piercing and relevant inquiries we have within our clinical work and challenges. I often think of denial not as an all-or-nothing concept but rather as parts of self. There's a part of everyone's being where the unconscious believes it's immortal and will live on forever, and yet we all know intellectually that we all have mortality and finitude and transience, and that time will end. We often think of this work as more iterative and gradual and exposure based. There's potency to words. Saying, "You are dying within days," is a lot higher potency of a phrase to share than, "This is serious illness. This illness is incurable. Time might be shorter than we hoped." And so the earlier and more upstream we begin to have these conversations, even in small, subtle ways, it starts to begin to expose the patient to the concept so they can go from the head to the heart, not only knowing their prognosis intellectually but also affectively, to integrate it into who they are as a person because all patients are trying to live well while also we're gradually exposing them to this awareness of mortality within their own lived experience of illness. And that, ideally, happens gradually over time. Now, there are moments where the medical frame is very limited, and we might have short days, and we have to uptitrate those words and really accompany them more radically through those high-affective moments. And that's when we have to take a lot of more nuanced approaches, but I would say the more earlier and upstream the better. And then the second piece to that question as well is coping with our own mortality. The more we can be comfortable with our own transience and finitude and limitations, the more we will be able to accompany others through that. And even within my own life, I've had to integrate losses in a way where before I go in to talk to one of my own palliative care patients, one mantra I often say to myself is, "I'm just a few steps behind you. I don't know if it's going to be 30 days or 30 years, but I'm just a few steps behind you on this finite, transient road of life that is the human experience." And that creates a stance of accompaniment that patients really can experience as they're traversing these tragedies. Dr. Hope Rugo: That's great. And I think those are really important points and actually some pearls, which I think we can take into the clinic. I think being really concrete when really the expected life expectancy is a few days to a couple of weeks can be very, very helpful. And making sure the patients hear you, but also continuing to let them know that, as oncologists, we're here for them. We're not abandoning them. I think that's a big worry for many, certainly of my patients, is that somehow when they would go to hospice or be a 'no code', that we're not going to support them anymore or treat them anymore. That is a really important process of that as well. And of course, engaging the team makes a big difference because the whole oncology team can help to manage situations that are particularly challenging like that. And just as we close, I wanted to ask one last question of you, Dr. Brenner, that suffering, grief, and burnout, you've really made the point that these are not problems to fix but dimensions that we want to attend to and acknowledge as part of our lives, the dying process is part of all of our lives. It's just dealing with this in the unexpected and the, I think, unpredictability of life, you know, that people take on a lot of guilt and all sorts of things about, all sorts of emotions. And the question is now, people have listened to this podcast, what can they take back to their oncology teams to build a culture that supports clinicians and their team at large to engage with these realities in a meaningful and sustainable way? I really feel like if we could build the whole team approach where we're supporting each other and supporting the patients together, that that will help this process immeasurably. Dr. Keri Brenner: Yes, and I'm thinking about Dr. Sławkowski-Rode's observation about the combat analogy, and it made me recognize this distinction between suppression and repression. Repression is this unconscious process, and this is what we're taught to do in medical training all the time, to just involuntarily shove that tragedy under the rug, just forget about it and see the next patient and move on. And we know that if we keep unconsciously shoving things under the rug, that it will lead to burnout and lack of sustainability for our clinical teams. Suppression is a more conscious process. That deliberate effort to say, "This was a tragedy that I bore witness to. I know I need to put that in a box on the shelf for now because I have 10 other patients I have to see." And yet, do I work in a culture where I can take that off the shelf during particular moments and process it with my interdisciplinary team, phone a friend, talk to a trusted colleague, have some trusted case supervision around it, or process rounds around it, talk to my social worker? And I think the more that we model this type of self-reflective capacity as attendings, folks who have been in the field for decades, the more we create that ethos and culture that is sustainable because clinician self-reflection is never a weakness, rather it's a silent strength. Clinician self-reflection is this portal for wisdom, connectedness, sustainability, and ultimately transformative growth within ourselves. Dr. Hope Rugo: That's such a great point, and I think this whole discussion has been so helpful for me and I hope for our audience that we really can take these points and bring them to our practice. I think, "Wow, this is such a great conversation. I'd like to have the team as a whole listen to this as ways to sort of strategize talking about the process, our patients, and being supportive as a team, understanding how we manage spirituality when it connects and when it doesn't." All of these points, they're bringing in how we process these issues and the whole idea of suppressing versus sort of deciding that it never happened at all is, I think, very important because that's just a tool for managing our daily lives, our busy clinics, and everything we manage. Dr. Keri Brenner: And Dr. Rugo, it's reminding me at Stanford, you know, we have this weekly practice that's just a ritual where every Friday morning for 30 minutes, our social worker leads a process rounds with us as a team, where we talk about how the work that we're doing clinically is affecting us in our lives in ways that have joy and greater meaning and connectedness and other ways that might be depleting. And that kind of authentic vulnerability with one another allows us to show up more authentically for our patients. So those rituals, that small 30 minutes once a week, goes a long way. And it reminds me that sometimes slowing things down with those rituals can really get us to more meaningful, transformative places ultimately. Dr. Hope Rugo: It's a great idea, and I think, you know, making time for that in everybody's busy days where they just don't have any time anymore is important. And you don't have to do it weekly, you could even do something monthly. I think there's a lot of options, and that's a great suggestion. I want to thank you both for taking your time out for this enriching and incredibly helpful conversation. Our listeners will find a link to the Ed Book article we discussed today, which is excellent, in the transcript of this episode. I want to thank you again, Dr. Brenner and Dr. Sławkowski-Rode, for your time and for your excellent thoughts and advice and direction. Dr. Mikołaj Sławkowski-Rode: Thank you very much, Dr. Rugo. Dr. Keri Brenner: Thank you. Dr. Hope Rugo: And thanks to our listeners for joining us today. Please join us again next month on By the Book for more insightful views on topics you'll be hearing at the education sessions from ASCO meetings and our deep dives on new approaches that are shaping modern oncology. 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. Follow today's speakers: Dr. Hope Rugo @hope.rugo Dr. Keri Brenner @keri_brenner Dr. Mikolaj Slawkowski-Rode @MikolajRode Follow ASCO on social media: @ASCO on X (formerly Twitter) ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Hope Rugo: Honoraria: Mylan/Viatris, Chugai Pharma Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx Dr. Keri Brenner: No relationships to disclose Dr. Mikolaj Slawkowski-Rode: No relationships to disclose

Host Dr. Nate Pennell and his guest, Dr. Chloe Atreya, discuss the ASCO Educational Book article, "Integrative Oncology: Incorporating Evidence-Based Approaches to Patients With GI Cancers," highlighting the use of mind-body approaches, exercise, nutrition, acupuncture/acupressure, and natural products. Transcript Dr. Nate Pennell: Welcome to ASCO Education: By the Book, our new monthly podcast series that will feature engaging discussions between editors and authors from the ASCO Educational Book. We'll be bringing you compelling insights on key topics featured in Education Sessions at ASCO meetings and some deep dives on the approaches shaping modern oncology. I'm Dr. Nate Pennell, director of the Cleveland Clinic Lung Cancer Medical Oncology Program as well as vice chair of clinical research for the Taussig Cancer Institute. Today, I'm delighted to welcome Dr. Chloe Atreya, a professor of Medicine in the GI Oncology Group at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, and the UCSF Osher Center for Integrative Health, to discuss her article titled, "Integrative Oncology Incorporating Evidence-Based Approaches to Patients With GI Cancers", which was recently published in the ASCO Educational Book. Our full disclosures are available in the transcript of this episode. Dr. Atreya, it's great to have you on the podcast today. Thanks for joining me. Dr. Chloe Atreya: Thanks Dr. Pennell. It's a pleasure to be here. Dr. Nate Pennell: Dr. Atreya, you co-direct the UCSF Integrative Oncology Program with a goal to really help patients with cancer live as well as possible. And before we dive into the review article and guidelines, I'd love to just know a little bit about what inspired you to go into this field? Dr. Chloe Atreya: Yeah, thank you for asking. I've had a long-standing interest in different approaches to medicine from global traditions and I have a degree in pharmacology, and I continue to work on new drug therapies for patients with colorectal cancer. And one thing that I found is that developing new drugs is a long-term process and often we're not able to get the drugs to the patients in front of us. And so early on as a new faculty member at UCSF, I was trying to figure out what I could do for the patient in front of me if those new drug therapies may not be available in their lifetime. And one thing I recognized was that in some conversations the patient and their family members, even if the patient had metastatic disease, they were able to stay very present and to live well without being sidelined by what might happen in the future. And then in other encounters, people were so afraid of what might be happening in the future, or they may have regrets maybe about not getting that colonoscopy and that was eroding their ability to live well in the present. So, I started asking the patients and family members who were able to stay present, "What's your secret? How do you do this?" And people would tell me, "It's my meditation practice," or "It's my yoga practice." And so, I became interested in this. And an entry point for me, and an entry point to the Osher Center at UCSF was that I took the Mindfulness-Based Stress Reduction Program to try to understand experientially the evidence for this and became very interested in it. I never thought I would be facilitating meditation for patients, but it became a growing interest. And as people are living longer with cancer and are being diagnosed at younger ages, often with young families, how one lives with cancer is becoming increasingly important. Dr. Nate Pennell: I've always been very aware that it seemed like the patients that I treated who had the best quality of life during their life with cancer, however that ended up going, were those who were able to sort of compartmentalize it, where, when it was time to focus on discussing treatment or their scans, they were, you know, of course, had anxiety and other things that went along with that. But when they weren't in that, they were able to go back to their lives and kind of not think about cancer all the time. Whereas other people sort of adopt that as their identity almost is that they are living with cancer and that kind of consumes all of their time in between visits and really impacts how they're able to enjoy the rest of their lives. And so, I was really interested when I was reading your paper about how mindfulness seemed to be sort of like a formal way to help patients achieve that split. I'm really happy that we're able to talk about that. Dr. Chloe Atreya: Yeah, I think that's absolutely right. So, each of our patients is more than their cancer diagnosis. And the other thing I would say is that sometimes patients can use the cancer diagnosis to get to, "What is it that I really care about in life?" And that can actually heighten an experience of appreciation for the small things in life, appreciation for the people that they love, and that can have an impact beyond their lifetime. Dr. Nate Pennell: Just in general, I feel like integrative medicine has come a long way, especially over the last decade or so. So, there's now mature data supporting the incorporation of elements of integrative oncology into comprehensive cancer care. We've got collaborations with ASCO. They've published clinical practice guidelines around diet, around exercise, and around the use of cannabinoids. ASCO has worked with the Society for Integrative Oncology to address management of pain, anxiety, depression, fatigue – lots of different evidence bases now to try to help guide people, because this is certainly something our patients are incredibly interested in learning about. Can you get our listeners up to speed a little bit on the updated guidelines and resources supporting integrative oncology? Dr. Chloe Atreya: Sure. I can give a summary of some of the key findings. And these are rigorous guidelines that came together by consensus from expert panels. I had the honor of serving on the anxiety and depression panel. So, these panels will rate the quality of the evidence available to come up with a strength of recommendation. I think that people are at least superficially aware of the importance of diet and physical activity and that cannabis and cannabinoids have evidence of benefit for nausea and vomiting. They may not be aware of some of the evidence supporting these other modalities. So, for anxiety and depression, mindfulness-based interventions, which include meditation and meditative movement, have the strongest level of evidence. And the clinical practice guidelines indicate that they should be offered to any adult patient during or after treatment who is experiencing symptoms of anxiety or depression. Other modalities that can help with anxiety and depression include yoga and Tai Chi or Qigong. And with the fatigue guidelines, mindfulness-based interventions are also strongly recommended, along with exercise and cognitive behavioral therapy, Tai Chi and Qigong during treatment, yoga after treatment. And some of these recommendations also will depend on where the evidence is. So, yoga is an example of an intervention that I think can be helpful during treatment, but most of our evidence is on patients who are post-treatment. So, most of our guidelines separate out during treatment and the post-treatment phase because the quality of evidence may be different for these different phases of treatment. With the pain guidelines, the strongest recommendation is for acupuncture, specifically for people with breast cancer who may be experiencing joint pain related to aromatase inhibitors. However, acupuncture and other therapies, including massage, can be helpful with pain as well. So those are a few of the highlights. Dr. Nate Pennell: Yeah, I was surprised at the really good level of evidence for the mindfulness-based practices because I don't think that's the first thing that jumps to mind when I think about integrative oncology. I tend to think more about physical interventions like acupuncture or supplements or whatnot. So, I think this is really fantastic that we're highlighting this. And a lot of these interventions like the Qigong, Tai Chi, yoga, is it the physical practice of those that benefits them or is it that it gives them something to focus on, to be mindful of? Is that the most important intervention? It doesn't really matter what you're doing as long as you have something that kind of takes you out of your experience and allows you to focus on the moment. Dr. Chloe Atreya: I do think it is a mind, body and spirit integration, so that all aspects are important. We also say that the best practice is the one that you actually practice. So, part of the reason that it's important to have these different modalities is that not everybody is going to take up meditation. And there may be people for whom stationary meditation, sitting and meditating, works well, and other people for whom meditative movement practices may be what they gravitate to. And so, I think that it's important to have a variety of options. And one thing that's distinct from some of our pharmacologic therapies is that the safety of these is, you know, quite good. So, it becomes less important to say, "Overall, is Tai Chi better or is yoga better?" for instance. It really depends on what it is that someone is going to take up. Dr. Nate Pennell: And of course, something that's been really nice evidence-based for a long time, even back when I was in my training in the 2000s with Jennifer Temel at Massachusetts General Hospital, was the impact of physical activity and exercise on patients with cancer. It seems like that is pretty much a universally good recommendation for patients. Dr. Chloe Atreya: Yes, that's absolutely right. Physical activity has been associated with improved survival after a cancer diagnosis. And that's both cancer specific survival and overall survival. The other thing I'll say about physical activity, especially the mindful movement practices like Tai Chi and Qigong and yoga, is that they induce physiologic shifts in the body that can promote relaxation, so they can dampen that stress response in a physiologic way. And these movement practices are also the best way to reduce cancer-associated fatigue. Dr. Nate Pennell: One of the things that patients are always very curious about when they talk to me, and I never really feel like I'm as well qualified as I'd like to be to advise them around dietary changes in nutrition. And can you take me a little bit through some of the evidence base for what works and what doesn't work? Dr. Chloe Atreya: Sure. I do think that it needs to be tailored to the patient's needs. Overall, a diet that is plant-based and includes whole grains is really important. And I often tell patients to eat the rainbow because all of those different phytochemicals that cause the different colors in our fruits and vegetables are supporting different gut microbiota. So that is a basis for a healthy gut microbiome. That said, you know, if someone is experiencing symptoms related to cancer or cancer therapy, it is important to tailor dietary approaches. This is where some of the mindful eating practices can help. So, sometimes actually not just focusing on what we eat, but how we eat can help with symptoms that are associated with eating. So, some of our patients have loss of appetite, and shifting one's relationship to food can help with nutrition. Sometimes 'slow it down' practices can help both with appetite and with digestion. Dr. Nate Pennell: One of the things that you said both in the paper and just now on our podcast, talking about how individualized and personalized this is. And I really liked the emphasis that you had on flexibility and self-compassion over rigid discipline and prescriptive recommendations here. And this is perhaps one of the real benefits of having an integrative oncology team that can work with patients as opposed to them just trying to find things online. Dr. Chloe Atreya: Yes, particularly during treatment, I think that's really important. And that was borne out by our early studies we called "Being Present." So, after I was observing the benefits anecdotally among my patients of the ability to be present, we designed these pilot studies to teach meditation and meditative practices to patients. And in these pilot studies, the original ones were pretty prescriptive in a way that mindfulness-based stress reduction is fairly prescriptive in terms of like, "This is what we're asking you to do. Just stick with the program." And there can be benefits if you can stick with the program. It's really hard though if someone is going through treatment and with GI cancers, it may be that they're getting chemotherapy every two weeks and they have one week where they're feeling really crummy and another week where they're trying to get things done. And we realized that sometimes people were getting overwhelmed and feeling like the mindfulness practice was another thing on their to-do list and that they were failing if they didn't do this thing that was important for them. And so, we've really kind of changed our emphasis. And part of our emphasis now is on incorporating mindfulness practices into daily life. Any activity that doesn't require a lot of executive function can be done mindfully, meaning with full attention. And so, especially for some of our very busy patients, that can be a way of, again, shifting how I'm doing things rather than adding a new thing to do. Dr. Nate Pennell: And then another part I know that patients are always very curious about that I'm really happy to see that we're starting to build an evidence base for is the use of supplements and natural products. So, can you take us a little bit through where we stand in terms of evidence behind, say, cannabis and some of the other available products out there? Dr. Chloe Atreya: Yeah, I would say that is an area that requires a lot more study. It's pretty complicated because unlike mindfulness practices where there are few interactions with other treatments, there is the potential for interactions, particularly with the supplements. And the quality of the supplements matters. And then there tends to be a lot of heterogeneity among the studies both in the patients and what other treatments they may be receiving, as well as the doses of the supplements that they're receiving. One of my earliest mentors at Yale is someone named Dr. Tommy Chang, who has applied the same rigor that that we apply to testing of biomedical compounds to traditional Chinese medicine formulas. And so, ensuring that the formulation is stable and then formally testing these formulations along with chemotherapy. And we need more funding for that type of research in order to really elevate our knowledge of these natural products. We often will direct patients to the Memorial Sloan Kettering 'About Herbs, Botanicals, and Other Products' database as one accessible source to learn more about the supplements. We also work with our pharmacists who can provide the data that exists, but we do need to take it with a grain of salt because of the heterogeneity in the data. And then it's really important if people are going to take supplements, for them to take supplements that are of high quality. And that's something in the article that we list all of the things that one should look for on the label of a supplement to ensure that it is what it's billed to be. Dr. Nate Pennell: So, most of what we've been talking about so far has really been applying to all patients with cancer, but you of course are a GI medical oncologist, and this is a publication in the Educational Book from the ASCO GI Symposium. GI cancers obviously have an incredibly high and rising incidence rate among people under 50, representing a quarter of all cancer incidence worldwide, a third of cancer related deaths worldwide. Is there something specific that GI oncologists and patients with GI cancers can take home from your paper or is this applicable to pretty much everyone? Dr. Chloe Atreya: Yeah, so the evidence that we review is specifically for GI cancers. So, it shows both its strengths and also some of the limitations. So many of the studies have focused on other cancers, especially breast cancer. In the integrative oncology field, there are definitely gaps in studying GI cancers. At the same time, I would say that GI cancers are very much linked to lifestyle in ways that are complicated, and we don't fully understand. However, the best ways that we can protect against development of GI cancers, acknowledging that no one is to blame for developing a GI cancer and no one is fully protected, but the best things that we can do for overall health and to prevent GI cancers are a diet that is plant-based, has whole grains. There's some data about fish that especially the deep-water fish, may be protective and then engaging in physical activity. One thing I would like for people to take away is that these things that we know that are preventative against developing cancer are also important after development of a GI cancer. Most of the data comes from studies of patients with colorectal cancer and that again, both cancer specific and overall mortality is improved with better diet and with physical activity. So, this is even after a cancer diagnosis. And I also think that, and this is hard to really prove, but we're in a pretty inflammatory environment right now. So, the things that we can do to decrease stress, improve sleep, decrease inflammation in the body, and we do know that inflammation is a risk factor for developing GI cancers. So, I think that all of the integrative modalities are important both for prevention and after diagnosis. Dr. Nate Pennell: And one of the things you just mentioned is that most of the studies looking at integrative oncology and GI cancers have focused on colorectal cancer, which of course, is the most common GI cancer. But you also have pointed out that there are gaps in research and what's going on and what needs to be done in order to broaden some of this experience to other GI cancers. Dr. Chloe Atreya: Yeah, and I will say that there are gaps even for colorectal cancer. So right now, some of the authors on the article are collaborating on a textbook chapter for the Society for Integrative Oncology. And so, we're again examining the evidence specifically for colorectal cancer and are in agreement that the level of evidence specific to colorectal cancer is not as high as it is for all patients with adult cancers. And so even colorectal cancer we need to study more. Just as there are different phases of cancer where treatments may need to be tailored, we also may need to tailor our treatments for different cancer types. And that includes what symptoms the patients are commonly experiencing and how intense the treatment is, and also the duration of treatment. Those are factors that can influence which modalities may be most important or most applicable to a given individual. Dr. Nate Pennell: So, a lot of this sounds fantastic. It sounds like things that a lot of patients would really appreciate working into their care. Your article focused a little bit on some of the logistics of providing this type of care, including group medical visits, multidisciplinary clinics staffed by multiple types of clinicians, including APPs and psychologists, and talked about the sustainability of this in terms of increasing the uptake of guideline-based integrative oncology. Talk a little bit more about both at your institution, I guess, and the overall health system and how this might be both sustainable and perhaps how we broaden this out to patients outside of places like UCSF. Dr. Chloe Atreya: Yes, that's a major focus of our research effort. A lot of comprehensive cancer centers and other places where patients are receiving care, people may have access to dietitians, which is really important and nutritionists. In the article we also provide resources for working with exercise therapists and those are people who may be working remotely and can help people, for instance, who may be in, in rural areas. And then our focus with the mind-body practices in particular has been on group medical visits. And this grew out of, again, my 'being present' pilot studies where we were showing some benefit. But then when the grant ends, there isn't a way to continue to deliver this care. And so, we were asking ourselves, you know, is there a way to make this sustainable? And group medical visits have been used in other settings, and they've been working really well at our institution and other institutions are now taking them up as well. And this is a way that in this case it's me and many of my colleagues who are delivering these, where I can see eight or ten patients at once. In my case, it's a series of four two-hour sessions delivered by telehealth. So, we're able to focus on the integrative practices in a way that's experiential. So, in the clinic I may be able to mention, you know, after we go over the CT scans, after we go over the labs and the molecular profiling, you know, may be able to say, "Hey, you know, meditation may be helpful for your anxiety," but in the group medical visits we can actually practice meditation, we can practice chair yoga. And that's where people have that experience in their bodies of these different modalities. And the feedback that we're receiving is that that sticks much more to experience it then you have resources to continue it. And then the group is helpful both in terms of delivery, so timely and efficient care for patients. It's also building community and reducing the social isolation that many of our patients undergoing treatment for cancer experience. Dr. Nate Pennell: I think that makes perfect sense, and I'm glad you brought up telehealth as an option. I don't know how many trained integrative oncologists there are out there, but I'm going to guess this is not a huge number out there. And much like other specialties that really can improve patients' quality of life, like palliative medicine, for example, not everyone has access to a trained expert in their cancer center, and things like telemedicine and telehealth can really potentially broaden that. How do you think telehealth could help broaden the exposure of cancer patients and even practitioners of oncology to integrative medicine? Dr. Chloe Atreya: Yes, I think that telehealth is crucial for all patients with cancer to be able to receive comprehensive cancer care, no matter where they're receiving their chemotherapy or other cancer-directed treatments. So, we will routinely be including patients who live outside of San Francisco. Most of our patients live outside of San Francisco. There's no way that they could participate if they had to drive into the city again to access this. And in the group setting, it's not even safe for people who are receiving chemotherapy to meet in a group most times. And with symptoms, often people aren't feeling so well and they're able to join us on Zoom in a way that they wouldn't be able to make the visit if it was in person. And so, this has really allowed us to expand our catchment area and to include patients, in our case, in all of California. You also mentioned training, and that's also important. So, as someone who's involved in the [UCSF] Osher Collaborative, there are faculty scholars who are at universities all over the US, so I've been able to start training some of those physicians to deliver group medical visits at their sites as well via telehealth. Dr. Nate Pennell: I'm glad we were able to make a plug for that. We need our political leadership to continue to support reimbursement for telehealth because it really does bring access to so many important elements of health care to patients who really struggle to travel to tertiary care centers. And their local cancer center can be quite a distance away. So, sticking to the theme of training, clinician education and resources are really crucial to continue to support the uptake of integrative oncology in comprehensive cancer care. Where do you think things stand today in terms of clinician education and professional development in integrative oncology. Dr. Chloe Atreya: It's growing. Our medical students now are receiving training in integrative medicine, and making a plug for the Educational Book, I was really happy that ASCO let us have a table that's full of hyperlinks. So that's not typical for an article. Usually, you have to go to the reference list, but I really wanted to make it practical and accessible to people, both the resources that can be shared with patients that are curated and selected that we thought were of high-quality examples for patients. At the bottom of that table also are training resources for clinicians, and some of those include: The Center for Mind-Body Medicine, where people can receive training in how to teach these mind-body practices; The Integrated Center for Group Medical Visits, where people can learn how to develop their own group medical visits; of course, there's the Society for Integrative Oncology; and then I had just mentioned the Osher Collaborative Faculty Fellowship. Dr. Nate Pennell: Oh, that is fantastic. And just looking through, I mean, this article is really a fantastic resource both of the evidence base behind all of the elements that we've discussed today. Actually, the table that you mentioned with all of the direct hyperlinks to the resources is fantastic. Even recommendations for specific dietary changes after GI cancer diagnosis. So, I highly recommend everyone read the full paper after they have listened to the podcast today. Before we wrap up, is there anything that we didn't get a chance to discuss that you wanted to make sure our listeners are aware of? Dr. Chloe Atreya: One thing that I did want to bring up is the disparities that exist in access to high quality symptom management care. So, patients who are racial and ethnic minorities, particularly our black and Latinx patients, the evidence shows that they aren't receiving the same degree of symptom management care as non-Hispanic White patients. And that is part of what may be leading to some of the disparities in cancer outcomes. So, if symptoms are poorly managed, it's harder for patients to stay with the treatment, and integrative oncology is one way to try to, especially with telehealth, this is a way to try to improve symptom management for all of our patients to help improve both their quality of life and their cancer outcomes. Dr. Nate Pennell: Well, Dr. Atreya, it's been great speaking with you today and thank you for joining me on the ASCO Education: By the Book Podcast and thank you for all of your work in advancing integrative oncology for GI cancers and beyond. Dr. Chloe Atreya: Thank you, Dr. Pennell. It's been a pleasure speaking with you. Dr. Nate Pennell: And thank you to all of our listeners who joined us today. You'll find a link to the article discussed today in the transcript of the episode. We hope you'll join us again for more insightful views on topics you'll be hearing at the Education Sessions from ASCO meetings throughout the year and our deep dives on approaches that are shaping modern oncology. Disclaimer: The purpose of this podcast is to educate, 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. Follow today's speakers: Dr. Nathan Pennell @n8pennell @n8pennell.bsky.social Dr. Chloe Atreya Follow ASCO on social media: @ASCO on X (formerly Twitter) ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Nate Pennell: Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron Research Funding (Institution): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi Dr. Chloe Atreya: Consulting or Advisory Role: Roche Genentech, Agenus Research Funding (Institution): Novartis, Merck, Bristol-Myers Squibb, Guardant Health, Gossamer Bio, Erasca, Inc.

Resources such as facilities, equipment, medications, and trained healthcare professionals are essential to provide proper care. Yet, many areas in the US and around the globe have challenges providing some of such resources. This ASCO Education podcast will explore oncology practice in low resource settings. Dr. Thierry Alcindor, a medical oncologist at the Dana-Farber Cancer Institute and Brigham and Women's Hospital in Boston, Dr. Richard Ingram, a Medical Oncologist at Shenandoah Oncology in Winchester, Virginia, and Chair of the Appalachian Community Cancer Alliance and Dr. Sana Al Sukhun, an Adjunct Professor of Medical Oncology and Director of Oncology Practice at Al-Hayat Medical Center in Jordan will discuss the barriers they face providing cancer care in low resource areas in the US (1:48) and Jordan (11:52) and the one challenge that is key to solve in order for proper treatment to be administered in the US (29:07) and Jordan (31:42). Speaker Disclosures Dr. Sana A. Al-Sukhun: Honoraria – Novartis; Speakers' Bureau – Novartis, Roche, Pfizer; Travel, Accommodations, Expenses – Roche, BMS Dr. Richard Ingram: None Dr. Thierry Alcindor: Consulting or Advisory – Merck, Bayer, BMS, Astra Zeneca, Astellas Scientific and Medical Affairs Inc.; Research Funding – Epizyme, EMD Serono, Karyopharm Therapeutics, Springworks, Astellas Pharma, Deciphera Resources If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at [email protected]. TRANSCRIPT Disclosures for this podcast are listed on the podcast page. Dr. Thierry Alcindor: Hello, dear ASCO audience, welcome to this episode of the ASCO Education podcast. Today, we will examine practicing oncology in a low-resource setting. Managing cancer patients is a multifaceted challenge. Resources such as facilities, equipment, medications, and trained healthcare professionals are essential to provide proper care. Yet, many areas in the US and around the globe have challenges providing some of such resources. I'm Dr. Thierry Alcindor. I'm a medical oncologist at the Dana-Farber Cancer Institute and Brigham and Women's Hospital in Boston. Joining us are Dr. Richard Ingram, a Medical Oncologist at Shenandoah Oncology in Winchester, Virginia, and Chair of the Appalachian Community Cancer Alliance. He is, as well, the current president of the Virginia State Oncology Society. We are also very pleased to be joined by Dr. Sana Al Sukhun. She is an Adjunct Professor of Medical Oncology and Director of Oncology Practice at Al-Hayat Medical Center in Jordan. She is also the past president of the Jordanian Oncology Society. So, I'll begin with Dr. Ingram. You have experience with patients in the Appalachian region of the US by practicing medical oncology in rural northwestern Virginia for the past 25 years. Can you describe this unique region for our listeners and detail some of the challenges you face when providing care there? Dr. Richard Ingram: I have been practicing here in Northwestern Virginia for the past 25-ish years, and have seen over time barriers to care that I think could be applied anywhere. And, I think we'll hear some interesting stories today from our colleague from Jordan also, in that regard. The main barriers I think are somewhat slightly stereotypical but real where I am. There is a diverse population here, meaning a big geographic area and a somewhat underpopulated area. So, resources are scattered and scarce sometimes and located in concentrated areas. So, patients have difficulty with access to cancer screening, imaging, and sometimes downstream or tertiary care where I am. I have patients that will travel an hour and a half to two hours one way i.e., a three to four-hour round trip - sometimes over some difficult terrain, meaning some difficult roads out our way, both with mountains and some geographic challenges just to get to us. You can imagine the difficulty that is with either coordination of care with a multidisciplinary patient having to see multiple providers or more practically, a patient receiving radiotherapy on a daily basis. And, this not only is time but money because you're trying to make a decision about follow-up appointments and missing work at an hourly wage versus working that week and paying your bills. I have patients currently who are working around that. I have several concurrent chemo-radiotherapy patients - currently, actually two I saw this morning - in clinic, both of which live in a town called Petersburg, West Virginia, which is about an hour and 45 minutes one way. So, three and a half hours from us. And, we've had to connect them appropriately with resources around transportation to make sure they stay compliant with their care. You have this empathy and drive to care for patients and try to apply the same care you would across the continuum. That socioeconomic status is not unique to Appalachia but I think is somewhat emblematic in our area - lovely, hardworking people and diligent in their craft. But, when you have barriers such as cancer diagnosis and now superimposed strain and stress on your family life and work life, it can throw things out of balance. A similar patient of mine that I saw today actually in clinic, same area, same concurrent diagnosis, their big access issue is that they're also the primary caregiver for some grandchildren that are staying at home. They've taken in their grandchildren and, not unique to Appalachia, but somewhat in that we have a lot of multigenerational families living together. So, you're trying to help that person get through their therapy and still be the homemaker for grandchildren and try to battle their cancer diagnosis and at the same time not bankrupt them financially from a socioeconomic standpoint. Dr. Thierry Alcindor: What's the insurance coverage pattern like? Dr. Richard Ingram: In my area, about half to 60% of our patients are on either uninsured or they are on public insurance, whether that be Medicare or state Medicaid or exchange programs. From the private sector, there are private plans, but a lot of those are self-funded, meaning they are local municipalities, teachers' unions, first responders, and then a small pocket of what you and I would call traditional commercial insurance coverage. And so, for us, we for a lot of our patients have built relationships, for instance, we know this gastrointestinal group will take that insurance of a Medicaid or uninsured patient and this one won't, or vice versa. So, there is some fragmentation of care if you're not very conscious and deliberate at the medical oncology and radiation oncology side, which is in my practice about making sure the patient can get access to care. Dr. Thierry Alcindor: I understand. So you talked about the lack of adequate or complete primary care coverage. Do you have enough medical oncologists? Dr. Richard Ingram: Excellent question. I appreciate that. Yes. So we do, in that my group does and my region does. So we are very strong, as I like to say, the end of the funnel. You know, I consider cancer care screening a funnel you've got to screen through. I imagine you have a giant funnel of trying to screen through patients for the screening program appropriately and then the positive screens come out at the end of the funnel. At the end of the funnel, we can receive these patients and take care of them and provide all of the touch points of surgical, radiation, medical oncology, genetic counseling, survivorship. My biggest passion and what I've tried to do in the Appalachian Community Cancer Alliance is raise awareness on the screening and getting the screening activities out into these rural communities so we can get stage migration to an earlier stage of cancer. Still take care of the people who develop positive screens and downstream disease, obviously, but it'd be nice to start getting stage migration to the left, meaning to earlier stages for patients. What we really have out here is a lack of primary care doctors and stability of primary care doctors because it's a very difficult area to practice primary care with geography, very difficult area, with the payer mix and the socioeconomic status, and a difficult area for people to desire to live in when you're trying to practice primary care, not surrounded by every specialist. A rural primary care provider really has to be, in essence, a true solo practitioner in Appalachia. They have to have a broad skill set because they just don't have a cardiologist sitting next door or a neurosurgeon immediately available. We have a full complement of surgical oncology specialists, radiation, three-dimensional stereotactic, clinical trials, genetic counseling, eight medical oncologists, a well-equipped ICU, and care. But our catchment area we serve is a geographic radius of two to two and a half hours, of which there's not much in between. There are some rural clinics, some community outposts, some critical access hospitals. And really creating that infrastructure of navigation has been the key success in our area of trying to navigate a patient through the system and trying to support these single clinics or smaller critical access hospitals from afar, support them intellectually with cognitive capabilities over the telephone to help work a consult up and trying to navigate the patient in. But again, the physical or the geographic, or distance barriers are real, and the socioeconomic barriers are real. Even once we can make a link with the primary care doctor and be more than willing to see the patient, sometimes just physically getting them to us can be a challenge. Dr. Thierry Alcindor: So what is the Appalachian Community Cancer Alliance doing to improve cancer screening, cancer care outcomes in the region? Dr. Richard Ingram: Excellent question. So the Appalachian Community Cancer Alliance started organically. So myself, as president of Virginia, got together with other state presidents, West Virginia, Tennessee, South Carolina, North Carolina, Kentucky, and said, "Gosh, what could we do collectively? Or what are our collective issues and problems?" Because we kind of serve a similar population and geography. And out of that was born kind of a homebrewed alliance, which formalizes the Appalachian Community Cancer Alliance. And I want to kind of just start with a quick story, and then I'll explain where we launched. I had a patient that really resonates with me personally. So it was a patient I met in the emergency room, happened to actually be kind of mid-pandemic. I was on call, very nice patient, presented with severe dyspnea orthopnea platypnea, came to the ER, had a large pleural effusion lung mass, medial spinal mass, worked them up, ended up being metastatic non-small cell lung cancer stage IV. Got them plugged into treatment and took care of them. And then when I had a moment, I went back through their files as we usually do when we're taking a history and I had noticed that they had had a low-dose chest CT several years earlier at a community center out in their rural area of West Virginia. And I asked the patient about it and he kind of recalled getting the CAT scan. But bottom line, the area had set up a screening program but had not set up an actual mechanism or a flow of navigation. And/or if they had, the patient was unaware. So basically, the patient dutifully went through a screening program. There was the pandemic, there was a turnover of staff and it wasn't the patient was forgotten, but the patient never got navigated to work things up. And lo and behold, that positive low-dose CT screen turned into stage four cancer years later. So I wanted to focus on cancers we could make an intervention with in Appalachia and what was formed was called the Lung Cancer Screening Task Force. That was our first successful endeavor of the alliance. So this task force was formed after about a year and a half or so of work of the states I mentioned. It has become its own task force that reports to the alliance and we're very proud of it because it has been recognized in President Biden and Jill Biden's Moonshot Initiative for Cancer. It's actually obtained funding and we've worked backward to work on a navigation program as well as screening in the most underserved and lowest-screened areas in Appalachia. Dr. Thierry Alcindor: Well, that sounds exciting. Like, I feel that there is a nice infrastructure as well as projects coming along and I'm quite eager to hear from Dr. Al Sukhun whose practice is based in Jordan. Dr. Alsukhun, in 2022 you gave a presentation where you highlighted how low-income countries had experienced greater increases in breast cancer incidence and mortality compared to high-income countries in the last decade. What challenges are patients and doctors facing and what should be prioritized? Dr. Sana Al Sukhun: Interesting question. First, thank you so much for inviting me to take part in this very interesting discussion. Pleasure to join, listen, learn, and reflect. Indeed, I've enjoyed listening to Dr. Ingram very much. He was speaking about his area and indeed discussing most of the issues, believe it or not, we face in different parts of the world referred to as countries with limited resources. When you refer to limited resource environments or countries, you're really referring to two different types of limited resources: very low-income countries or middle-income countries. The challenges are a bit different. The first challenge we generally face is access to the application of knowledge. For example, in Jordan, we have access to the knowledge. We have excellent infrastructures, we have an excellent health workforce. The problem is the application of the knowledge, application of what we have learned to help our patients. However, the challenge in different limited resources goes across the theme of a multidisciplinary approach. It starts from prevention, early detection, where, as you mentioned, we are facing a significant increase in the number of cases diagnosed with breast cancer. The proportion of patients diagnosed with breast cancer in countries of limited resources is 62% of the worldwide new cancer cases. Why do we have such a significant increase in the number of cases? Most countries undergoing what's called socioeconomic transition, they are facing increasing risk factors to develop breast cancer. One of those which is significant not only when it comes to breast cancer but to most kinds of cancers is indeed a significant increase in the proportion of the population suffering from obesity. The highest absolute increase in the prevalence of obesity worldwide over the past couple of decades has been seen in the Middle East, Central Asia and North America. That by itself is a significant risk factor for the development of breast cancer and other long lists of cancers. In addition, of course, to smoking. For example, last year, unfortunately, and I'm not proud to say Jordan ranked among the highest in terms of smoking prevalence among men in the region. So these two important risk factors, in addition to the westernization of lifestyle, less physical activity, you know, all these risk factors, most important is awareness that these risk factors are important in terms of attributing to cancer. This is not common knowledge across all countries. We do not have enough campaigns across all countries to emphasize the importance of prevention. Then comes early detection. When it comes to early detection, you know, the challenge is not homogeneous. For example, in Jordan, a couple of decades back, most cases with breast cancer were diagnosed at an advanced stage. Barely one-quarter to one-third of cases were diagnosed at stages I to II. Right now, almost 60% of the cases diagnosed annually are really stage I or II early breast cancer. Thanks to the campaigns from government, non government organizations, NGOs, college society, all people are working together to emphasize the importance of prevention and early detection. That was quite successful in Jordan, and as you can see here almost two-thirds of cases are diagnosed early. However, contrast that with neighboring countries. I'm referring to Iraq, Sudan, Yemen, and if you notice I'm mentioning countries with conflict. Those countries not only suffer from limited resources but also instability. And when Richard was referring to the access transportation challenge, indeed, we in Jordan treat so many of the patients diagnosed with cancer coming to Jordan seeking treatment from Iraq, from Yemen, from Sudan, that by itself is a challenge. And at the same time, it reflects the status they suffer from, they suffer from lack of health workforce, lack of enough oncologists. Very few, if any, oncologists are available there. And not only you're referring to oncologists, you need pathologists, enough well-trained pathologists, surgeons, radiation oncology service. Those are quite limited when it comes to many of the surrounding countries and many countries actually with limited resources. For example, in Africa, same challenges, the multidisciplinary approach that's quite vital for the proper treatment of patients with cancer is indeed also lacking in many countries. The infrastructure takes not only having hospitals but also a multidisciplinary workforce. Then when it comes to treatment, you are faced by a common belief across many cultures that a diagnosis of cancer is equated to a death sentence. Very few, if any, believe that they can be treated from cancer or at least live with cancer in some situations. With breast cancer, patients with metastatic breast cancer deserve to be treated and can survive for years with excellent quality of life as well, still contributing to their society. Especially more than 50% of patients in countries of limited resources when diagnosed with breast cancer, they are younger than age 55, which is ten years younger than patients diagnosed in countries of high income. So they are still in the prime time of their life. They are needed by their family, their society. That's a huge actual economic impact on society and not only on the family. So these are issues to be tackled, to be emphasized across societies so that they can seek treatment when they have access to it. Dr. Thierry Alcindor: Can you tell us about access to cancer medicine, whether chemotherapy, targeted therapy, or immunotherapy? Dr. Sana Al Sukhun: We are living in a fantastic area where precision medicine has really revolutionized our approach to the treatment of many tumors. But at the same time, while we are talking about equity, improving access, it created another challenge and it created, unfortunately, disparity and made equity even more difficult. Right now, we do have, there is a huge difference between access, availability, and affordability. Most of these new medications, whether basic chemotherapeutics or recently approved targeted therapeutics or immunotherapy are available, but the problem is they are not affordable. Some of them are available in certain institutions, while in the same country, other institutions, if the patient's insurance happens to be in another institution, they cannot access it. So even within the same country, across different institutions, so many of the recently approved targeted therapeutics or immunotherapeutics are not offered. So equity is lacking even within the same country, in many countries with limited resources. Sometimes the irony is you will have the very highly-priced medications while out of the blue you are faced with the challenge of shortage of basic therapeutics, platinums, for example. And I learned from colleagues, the states suffered from a similar shortage the last few weeks. And you can imagine not being able to access platinum to treat your patients can make a huge difference and impact. Even if you have immunotherapy, you don't have it. That's ironic. And another challenge, most patients with the availability of social media and Google, thanks to Dr. Google, you check Dr. Google, and the first option you get is very pricey options, immunotherapy, targeted therapy. So the patient comes to you and he's getting the recommendation of having basic chemotherapy, sometimes because the indication is chemotherapy, sometimes because they cannot afford- you offer them the higher price medications, but they cannot afford it still. You still advise chemotherapy because it does work, but the patients are under the belief that if they do not take the very pricey medication, they are doomed and they cannot be treated. So they put treatment off altogether. These are conflicting concepts. They need awareness campaigns, they need explanation. Social media needs to do a better job improving what it markets. It usually markets the very pricey medications as life-saving, while talking about chemotherapy as something that really hurts patients, while in reality, sometimes this is all we have and it does make a difference. Another challenge we face, our region, for example, it's a conflict region with so many refugees. To give you a very simple example, I had a patient coming from a Syrian camp, hemoptysis, worked her out, and it looks like lung cancer, and I managed - she cannot afford any kind of treatment - but I managed with the hospital to get the CT scan free. We got the biopsy, and the good news is that companies, pharmaceuticals can and do help. They offered to test the biopsy for EGFR, and it turned out to be positive. Of course, we have no access to EGFR-targeted therapy. So what can we do? Indeed, that patient, we offered her platinum, but at that time we didn't have platinum. Within a couple of months, she presented with a very advanced-stage disease. And unfortunately, we lost her before we could start treatment because platinum was not available. Not only EGFR inhibitors, but we're talking about the simple things. Basic chemotherapeutics are important, those we need to emphasize availability. We keep talking about cutting-edge therapeutics. They're very fascinating to use, to treat, they made a huge difference, but still, our old friend, basic chemotherapy can and does make a difference, something we need to talk about more and more. Dr. Thierry Alcindor: I agree with you, and that's true of even high-resource countries. I mean, cytotoxic chemotherapy remains the backbone of treatment for many cancers, even in 2023. But I'd like to ask you a question following up on what you just described so well regarding availability, access. Do you have research infrastructure that would allow you, like for example, they have done in India at Tata Memorial Hospital, to conduct research with lower doses of those expensive agents? I think that this is quite a promising direction for low-resource countries. What do you think? Dr. Sana Al Sukhun: You touched on a very dear subject to my heart, actually. Right now we're working with ASCO discussing a policy, discussing clinical trials in limited resource environments. Indeed, this is one of the very important aspects that can improve truly access to medications and contribute to the knowledge worldwide. Unfortunately, there are so many barriers. A short answer to your question is very few centers, if any, in the region do have infrastructure that can facilitate enrollment in phase three randomized trials. Investigator-initiated trials, particularly like the ones you're alluding to, more or less similar to the FinHer trial when we learned that short courses of trastuzumab six months versus twelve months can be reasonable for patients with a limited number of risk factors. Such trials, unfortunately, so far the infrastructure does not allow having such investigator-initiated trials. Not only the infrastructure, pharma needs to be more open for the support of such trials in these environments. Most governments in the region are still struggling with the concept of having human subjects enrolled in clinical trials. That needs awareness, not only at the level of the society or the patients or the physicians, by the way, who also, we struggle because we do not have protected time or appreciation. Dr. Thierry Alcindor: So you're talking with such passion about those challenges, and I feel that there is quite a lot of effort that you're putting in. So maybe you can tell us about the improvements that you have noted. Dr. Sana Al Sukhun: It's interesting when you look over the past couple of decades how things have moved. Particularly in Jordan, having a cancer center, the first comprehensive cancer center in the region, really set a good example for Jordan itself where other institutions improved to try and compete, improve their services similar to what King Hussein Cancer Center currently has. Also, they managed to have an infrastructure for clinical trials. And as I mentioned, they do have some of the phase III clinical trials already running, participating in large multinational clinical trials. That's a huge improvement, a huge step. Still, investigator-initiated clinical trials is something we are working with the government to support and start and encourage. Our screening program really succeeded and we are more or less similar to high-income countries when it comes to the rate of early detection. Still, we are working on improvement. We don't have a national screening problem. We have a national awareness campaign problem. Dr. Thierry Alcindor: Okay, so that's a lot of success. Dr. Sana Al Sukhun: That's huge success. Not only that, in October, now you come to Jordan. It's not only one government-run program. You see all clinics offering mammography services, either free or 50% off for patients across the kingdom. That actually did reflect positively on neighboring countries. Egypt, for example, right now started the last couple of years a similar national awareness downstaging program with excellent numbers of cases caught up early. The region is really improving - I'm talking about our region in the Middle East - if it were not for the conflicts. That's not the case when it comes to, unfortunately, countries with conflict, we all struggle. Jordan, Lebanon, even Syria, we all struggle with the refugee problem. Still, the refugees do not have enough funding, but a lot of NGOs are trying to help them. Along with what Richard described, you find many NGOs, they start themselves to help with access, to help with transportation, to help with medical fees for early detection. I believe we are moving far ahead when it comes to cancer, in particular over the past decade or so, as compared to many other diseases. Still, I believe we need contribution or cooperation between all stakeholders. That's what we still need. Dr. Thierry Alcindor: Okay, excellent. So I have a couple of questions that I would like to address to the two of you. Which barrier do you feel is the most difficult to solve when providing cancer care in low-resource settings? Is that the infrastructure? Is that the personnel who has not been properly trained? Equipment? Which would it be? Dr. Richard Ingram: Yeah. I appreciate it. And I really have been reflecting on Dr. Al Sukhun's heartfelt passion and comments. And thank you for sharing that, Sana. I think that's something we all need to be aware of. And a compliment to you and your team for being so inclusive in that region. I mean, cancer is a difficult enough diagnosis, but yet alone in a conflict zone, I can only applaud and empathize with you and a sincere tip of the cap to you and your team. That's incredible work. Dr. Sana Al Sukhun: Thank you. Dr. Richard Ingram: In general, you have to change the culture. You have to build trust in the process, the medical process, because that medical system may have let patients, family members, or neighbors down previously. So, I think building trust around screening and building trust around that there is an infrastructure that's going to take care of you if you have a positive screen. I have several patients, but one comes to mind a very complicated trimodality disease, esophageal cancer. But the long and the short of it is, the patient presented to a rural outside emergency room with obstructive symptoms. The emergency room doctor was savvy enough to have some resources in their area but stabilize the patient. The test they could get; they could just get really kind of a barium swallow at the facility, saw there was a problem, but then called an oncology nurse navigator program that we've instituted in our region to cover this wide footprint. The nurse navigator was able to basically navigate this patient very successfully into a GI endoscopy program, which then got them in the cancer program and worked hand in hand with a social worker arm that we've instituted also to help assist the nurse navigation program. So the social worker was able to work on food insecurity, getting the patient actually applied for and got them Medicaid and got them transportation, barriers lifted. So, it was a very successful anecdote compared to my unsuccessful anecdote earlier around lung cancer. So, to me, it's an example of a playbook that the Appalachian Community Cancer Alliance is trying to develop. So, maybe we can aggregate best practices in some way, shape, or form as the alliance and get those across the world, get those to Dr. Al Sukhun and the King Hussein Center in Jordan, and get it to wherever we need to in the world to help patients because the patient's problems are not unique to Appalachia. They're just unique to under-resourced and geographically spread out areas. Dr. Sana Al Sukhun: Absolutely. Dr. Thierry Alcindor: Yeah. That's well explained. Dr. Thierry Alcindor: Sana, which barrier would you say is the most difficult one for you? Dr. Sana Al Sukhun: We all get involved and cancer is an emotional diagnosis. It's completely different from all other diagnoses. No matter what, all illnesses are challenging, but the word 'cancer', nobody can deny it. It still carries a lot within those few letters. So, good infrastructure, not only in terms of building - this is very important - it's also a multidisciplinary team within that infrastructure. The other day, a patient came to the emergency room of the hospital across the street from where I practice. He was 25 years old, healthy, just some fatigue lately, and he collapsed. Actually, they found him pancytopenic. So, looking at the blood film, long story short, was highly suspicious for acute leukemia. The patient cannot afford admission to a private hospital, but he had insurance in the Royal Medical Services. In Jordan, we have different kinds of insurance depending on which section you belong to. It's more like the VA in the States. I talk to my colleague over there, tell them high suspicion for leukemia and he's like, "Send him right away." He was admitted simply because he had coverage; he had insurance. They do have also a good cancer center there. So, they had him admitted, had his bone biopsy done, diagnosed, and started treatment. That is an excellent example of how a good infrastructure, when available with good access to that infrastructure - so it's infrastructure and good access to that infrastructure - can make a huge difference. Dr. Thierry Alcindor: That's right. So, the two of you have offered plenty of potential solutions, which is, in fact, to a certain extent, the point of this podcast. But if you had to state what would be your first step, which one would it be? Rich? Dr. Richard Ingram: I think if I could not pick one thing but a collection of things, it really would be, top of mind, would be just an awareness that we have gaps in our infrastructure. Cancer care and navigation, even in the most resourced areas of probably the most resourced country in the world here in the United States, yet alone in some of our under-resourced portions of the United States. So you can only imagine in an underserved or under-resourced other part of the world. So I think awareness of the issues, awareness that we need to create a somewhat seamless infrastructure throughout the entire continuum from the screening of cancer to diagnostic studies to therapeutic studies to survivorship to palliative care and counseling. And then along the way layer in clinical research, which is the only way we're going to move the needle, and services such as genetic counseling along the way. So I would say awareness of the issues and then starting with the key stakeholders in your area, all coming around to the awareness of the issues, then you can start to build the infrastructure. And I think once you build the infrastructure, it will become easy to recruit and retain healthcare staff in a sound infrastructure - meaning I think that will get over the barrier of understaffing rural areas like Appalachia or other underserved areas in this country, in that if you have a great infrastructure, I think I know, as Sana alluded to, once you create this infrastructure, you as a provider want to practice there. You want to be part of something that has a great infrastructure because A) you're proud of the work done, B) the patient gets state-of-the-art comprehensive care, and C) you're making a difference in your community. Patients aren't having to travel, patients are safe and have their arms around them with a program right in their backyard. Dr. Thierry Alcindor: Excellent. Sana, what would be your first step? Dr. Sana Al Sukhun: Thank you, Thierry, and thank you, Richard. You know Richard, every time you speak, you speak my mind. It just speaks for how much we are alike across the globe rather than we are different. We share the same challenges, we share similar barriers, and indeed solutions are more or less similar. After all, we're all human. If I were to think of one important thing, it's awareness. Awareness campaigns targeting the society, discussing the importance of early detection, prevention, and treatment. Awareness campaigns targeting all stakeholders, policymakers, number one, emphasizing the importance of infrastructure to be supported, to be environment-attractive for a good workforce to work together, build it forward, treat patients in a safe environment. Also targeting industry to collaborate with other NGOs in the society to support that infrastructure and empower it to start clinical trials for each community. Not only targeting the community needs but also the way you describe it, Thierry, using the new therapeutics in a society-adapted approach to improve access to treatment. Those infrastructures, once empowered and doesn't have to be one, once empowered, they can be infectious. They can contribute to elevating the medical care in different settings in each society. So, one good infrastructure can set the example for other institutions to improve their care and collaborate as well. So, it's awareness campaigns putting all key stakeholders together including the society. Dr. Thierry Alcindor: Okay. Well, I think we had a very insightful and lively discussion so I would like to thank both Dr. Sana Al Sukhun and Dr. Richard Ingram for having joined us for a discussion about practicing oncology in low-resource settings. And for the audience to know, the ASCO Education podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncologist well-being and professional development. If you have an idea for a topic or a guest you'd like to see on the ASCO Education podcast, please email us at [email protected] and to stay up to date with the latest episodes and explore other educational content, please visit education.asco.org. Many thanks again. A pleasure to talk with you. 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.

There was time during the early 70's when the field of oncology began to take hold where the singular focus was to extend the patient's life. In this ASCO Education podcast, our guest was one of the first to challenge that notion and rethink methods that focused the patient's QUALITY of life. Dr. Patricia Ganz joins us to describe her transition from cardiology to oncology (6:00), the moment she went beyond treating the disease and began thinking about treating the WHOLE patient (10:06) and the joy of the increasing numbers of patients who survive cancer (21:47). Speaker Disclosures Dr. David Johnson: Consulting or Advisory Role – Merck, Pfizer, Aileron Therapeutics, Boston University Dr. Patrick Loehrer: Research Funding – Novartis, Lilly Foundation, Taiho Pharmaceutical Dr. Patricia Ganz: Leadership - Intrinsic LifeSciences Stock and Other Ownership Interests - xenon pharma, Intrinsic LifeSciences, Silarus Therapeutics, Disc Medicine, Teva, Novartis, Merck. Johnson & Johnson, Pfizer, GlaxoSmithKline, Abbott Laboratories Consulting or Advisory Role - Global Blood Therapeutics, GSK, Ionis, akebia, Rockwell Medical Technologies, Disc Medicine, InformedDNA, Blue Note Therapeutics, Grail Patents, Royalties, Other Intellectual Property - related to iron metabolism and the anemia of chronic disease, Up-to-Date royalties for section editor on survivorship Resources If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at [email protected]. TRANSCRIPT Disclosures for this podcast are listed on the podcast page. Pat Loehrer: Welcome to Oncology, Etc., an ASCO Education Podcast. I'm Pat Loehrer, Director of Global Oncology and Health Equity at Indiana University. Dave Johnson: And I'm Dave Johnson, a Medical Oncologist at the University of Texas Southwestern in Dallas. If you're a regular listener to our podcast, welcome back. If you're new to Oncology, Etc., the purpose of the podcast is to introduce listeners to interesting and inspirational people and topics in and outside the world of oncology. Pat Loehrer: The field of oncology is relatively new. The first person treated with chemotherapy was in the 1940s. Medical oncology was just recognized as a specialty during the 1970s. And while cancer was considered by most people to be a death sentence, a steady growth of researchers sought to find cures. And they did for many cancers. But sometimes these treatments came at a cost. Our next guest challenged the notion that the singular focus of oncology is to extend the patient's duration of life. She asked whether an oncologist should also focus on addressing the patient's quality of life. Dave Johnson: The doctor asking that question went to UCLA Medical School, initially planning to study cardiology. However, a chance encounter with a young, dynamic oncologist who had started a clinical cancer ward sparked her interest in the nascent field of oncology. She witnessed advances in cancer treatment that seemingly took it from that inevitable death sentence to a potentially curable disease. She also recognized early on that when it came to cancer, a doctor must take care of the whole patient and not just the disease. From that point forward, our guest has had a storied career and an incredible impact on the world of cancer care. When initially offered a position at the West LA VA Medical Center, she saw it as an opportunity to advance the field of palliative care for patients with cancer. This proved to be one of her first opportunities to develop a program that incorporated a focus on quality of life into the management of cancer. Her work also focused on mental, dietary, physical, and emotional services to the long-term survivors of cancer. That career path has led to many accomplishments and numerous accolades for our guest. She is a founding member of the National Coalition for Cancer Survivorship, served as the 2004 Co-chair of ASCO's Survivorship Task Force, and currently directs UCLA's Cancer Survivorship Center of Excellence, funded in part from a grant from Livestrong. Our guest is Dr. Patricia Ganz. Dr. Patricia Ganz: It's great to be with both of you today. Dave Johnson: We always like to ask our guests a little about their background, where they grew up, a little about their family. Dr. Patricia Ganz: Yes. I grew up in the city of Beverly Hills where my parents moved when I was about five years old because of the educational system. Unlike parts of the East Coast, we didn't have very many private schools in Los Angeles, and so public education was very good in California at that time. So I had a good launch and had a wonderful opportunity that many people didn't have at that time to grow up in a comfortable setting. Dave Johnson: Tell us about your mom. I understand she was a businesswoman, correct? Dr. Patricia Ganz: Yes, actually, my parents got married when my mom was 19 and my dad was 21. He was in medical school at the University of Michigan. His father and mother weren't too happy with him getting married before he could support a wife. But she worked in a family business in the wholesale produce business in Detroit. One of six children, she was very involved with her family in the business. And they were married, and then World War II started, my father was a physician in the military, so she worked in the family business during the war. After finally having children and growing up and being in Beverly Hills, she sat back and was a homemaker, but she was always a bit restless and was always looking for something to do. So wound up several years later, when I was in my early teens, starting a business with one of my uncles, an automobile parts business. They ultimately sold it out to a big company that bought it out. Pat Loehrer: Where did your father serve in World War II? Dr. Patricia Ganz: He was actually D-Day Plus 21. He was in Wales during the war. They had to be stationed and moved down into the south before he was deployed. I have my parents' correspondence and letters from the war. He liberated some of the camps. Actually, as I have learned about the trauma of cancer and post-traumatic stress that happens in so many people, our military veterans, most recently, I think he had post-traumatic stress. He didn't talk very much about it, but I think liberating the camps, being overseas during that time, as it was for that silent generation, was very profound in terms of their activities. He wound up practicing medicine, and Los Angeles had a practice in industrial medicine, and it was a comfortable life. He would work early in the morning till maybe three or four in the afternoon and then go to the gym, there were moonlighting physicians who worked in the practice. But I kind of saw an easy kind of medicine, and he was always very encouraging and wanted me to go into medicine -- that I could be an ophthalmologist or a radiologist, good job for a woman. But I didn't really see the tough life of some of the internists and other people who were really working more 24/7, taking care of patients in the way medicine used to be practiced. Dave Johnson: Yeah. So you were interested in, early in your career, in cardiology. Could you tell us about that, and then a little bit more about the transition to oncology? Dr. Patricia Ganz: I went away to college, I went to Harvard Radcliffe and I came home during the summers. And was interested in doing something during the summer so I actually in a pediatric cardiology research laboratory as a volunteer at UCLA for a couple of summers between my freshman and sophomore year then my sophomore and junior year. And then I actually got a California Heart Association Fellowship between my junior and senior year in college. And this pediatric cardiology lab was very interesting. They were starting to give ketamine, it had an identification number, it wasn't called ketamine. But they were giving it to children in the cardiac cath lab and then were very worried about whether it would interfere with measuring the pressures in the heart. So we had intact dogs that had catheters implanted in the heart, and the drug would be given to the animals and we would then measure their pressures in the heart. That cardiology experience in 1970, the summer between my first and second year of medical school, the Swan-Ganz catheter was being tested. I worked at Cedars that summer and was watching them do the various studies to show the value of the catheter. And so by the time I was kind of finishing up medical school, I'd already invested all this time as an undergraduate. And then a little bit when I was in medical school and I kind of understood the physiology of the heart, very exciting. So that's kind of where I was headed until we started my internship. And I don't know if any of you remembered Marty Cline, but he was the oncologist who moved from UCSF to Los Angeles to start our hem-onc division. And very exciting, a wonderful bedside teacher. And so all of a sudden, I've never been exposed to oncology and this was very interesting. But at the same time, I was rotating through the CCU, and in came two full-arrest patients, one of whom was a campus cop who was very obese, had arrested at his desk in the police station. And we didn't have emergency vehicles to help people get on campus at that time. This was 1973 or 1974, something like that. And he came in full arrest, vegetable. And then another man had been going out of his apartment to walk his dog and go downstairs, and then all of a sudden his wife saw him out on the street being resuscitated by people. And he came in also in full arrest. So those two experiences, having to deal with those patients, not being able to kind of comfort the families, to do anything about it. As well as taking care of patients in my old clinic who had very bad vascular disease. One man, extremely depressed with claudication and angina, all of a sudden made me feel, "Well, you know what? I'm not sure I really want to be a cardiologist. I'm not sure I like the acute arrest that I had to deal with and the families. And also, the fact that people were depressed and you couldn't really talk to them about how serious their disease was." Whereas I had patients with advanced cancer who came in, who had equally difficult prognoses, but because of the way people understood cancer, you could really talk about the problems that they would be facing and the end-of-life concerns that they would have. So it was all of those things together that made me say, "Hmm." And then also, Pat, you'll appreciate this, being from Indiana, we were giving phase II platinum to advanced testicular cancer patients, and it was miraculous. And so I thought, "Oh my gosh, in my lifetime, maybe cancer is going to be cured! Heart disease, well, that's not going to happen." So that was really the turning point. Pat Loehrer: When many of us started, we were just hoping that we could get patients to live a little bit longer and improve the response rate. But you took a different tack. You really looked at treating the whole patient, not just the disease. That was really a novel approach at the time. What influenced you to take that step forward? Dr. Patricia Ganz: Well, it was actually my starting– it was thought to be in a hospice ward. It would turn out it was a Sepulveda VA, not the West LA VA, but in any case, we have two VAs that are affiliated with UCLA. And it was an intermediate care ward, and there was an idea that we would in fact put our cancer patients there who had to have inpatient chemotherapy so they wouldn't be in the acute setting as well as patients who needed to travel for radiation. Actually, the West LA VA had a hospice demonstration project. This is 1978. It's really the beginning of the hospice movement in England, then in Canada, Balfour Mount at Montreal and McGill was doing this. And so I was very much influenced by, number one, most of our patients didn't live very long. And if you were at a VA Hospital, as I was at that time, you were treating patients with advanced lung cancer, advanced colon cancer, advanced prostate cancer, other GI malignancies, and lung cancer, of course. So it was really the rare patient who you would treat for curative intent. In fact, small cell lung cancer was so exciting to be treating in a particularly limited small cell. Again, I had a lot of people who survived. We gave them chemo, radiation, whole brain radiation, etc. So that was exciting. This was before cisplatin and others were used in the treatment of lung cancer. But really, as I began to develop this ward, which I kind of thought, "Well, why should we wait just to give all the goodies to somebody in the last few weeks of life here? I'm treating some patients for cure, they're getting radiation. Some of them are getting radiation and chemo for palliation." But it was a mixed cancer ward. And it was wonderful because I had a team that would make rounds with me every week: a pharmacist, a physiatrist, a psychologist, a social worker, a dietitian. This was in 1978 or '79, and the nurses were wonderful. They were really available to the patients. It wasn't a busy acute ward. If they were in pain, they would get their medication as soon as possible. I gave methadone. It was before the days of some of the newer medications, but it was long-acting. I learned how to give that. We gave Dilaudid in between if necessary. And then we had Brompton solution, that was before there was really oral morphine. And so the idea was all of these kinds of services should really be available to patients from the time of diagnosis until death. We never knew who was going to be leaving us the next few days or who was going to be living longer and receiving curative intent. We had support groups for the patients and their families. It was a wonderful infrastructure, something that I didn't actually have at UCLA, so it was a real luxury. And if you know the VA system, the rehabilitation services are wonderful. They had dental services for patients. We had mostly World War II veterans, some Korean, and for many of these individuals, they had worked and lived a good life, and then they were going to retire and then they got cancer. So this was kind of the sadness. And it was a suburban VA, so we had a lot of patients who were in the San Fernando Valley, had a lot of family support, and it was a wonderful opportunity for me to learn how to do good quality care for patients along the continuum. Dave Johnson: How did you assemble this team? Or was it in place in part when you arrived, or what? Nobody was thinking about this multidisciplinary approach? Dr. Patricia Ganz: I just designed it because these were kind of the elements that were in a hospice kind of program. And I actually worked with the visiting nurses and I was part of their boards and so forth. And UCLA didn't have any kind of hospice or palliative care program at that time. But because the VA infrastructure had these staff already, I didn't have to hire them, you didn't have to bill for anything. They just became part of the team. Plus there was a psychiatrist who I ultimately began doing research with. He hired a psychologist for the research project. And so there was kind of this infrastructure of interest in providing good supportive care to cancer patients. A wonderful social worker, a wonderful psychologist, and they all saw this patient population as very needy, deserving, and they were glad to be part of a team. We didn't call it a hospice, we called it a palliative care unit. These were just regular staff members who, as part of their job, their mission was to serve that patient population and be available. I had never been exposed to a physiatrist before. I trained at UCLA, trained and did my residency and fellowship. We didn't have physiatry. For whatever reason, our former deans never thought it was an important physical medicine, it wasn't, and still isn't, part of our system. Pat Loehrer: Many decisions we make in terms of our careers are based on singular people. Your dad, maybe, suggesting going into medicine, but was there a patient that clicked with you that said, "Listen, I want to take this different direction?" Or was it just a collection of patients that you were seeing at the VA? Is there one that you can reflect back on? Dr. Patricia Ganz: I don't know if you all remember, but there was something called Consultation Liaison Psychiatry where, in that time, the psychiatrist really felt that they had to see medical patients because there were psychological and sometimes psychiatric problems that occurred on the medical ward, such as delirium. That was very common with patients who were very sick and very toxic, which was again due to the medical condition affecting the brain. And so I was exposed to these psychiatrists who were very behaviorally oriented when I was a resident and a fellow, and they often attended our team meetings in oncology on our service, they were on the transplant service, all those kinds of things. So they were kind of like right by our side. And when I went to the VA, the psychiatry service there also had a couple of really excellent psychiatrists who, again, were more behaviorally focused. Again, you have to really remember, bless her heart, Jimmie Holland was wonderful as a psychiatrist. She and Barrie Cassileth were the kind of early people we would see at our meetings who were kind of on the leading edge of psychosocial oncology, but particularly, Jimmie was more in a psychiatric mode, and there was a lot of focus on coping. But the people that I began to work with were more behaviorally focused, and they were kind of interested in the impact of the disease and the treatment on the patient's life and, backwards, how could managing those kinds of problems affect the well-being of the patient. And this one psychiatrist, Richard Heinrich, had gotten money from the VA, had written a grant to do an intervention study with the oncology patients who I was serving to do a group intervention for the patients and their families. But, in order to even get this grant going, he hired a project manager who was a psychologist, a fresh graduate whose name was Anne Coscarelli, and her name was Cindie Schag at that time. But she said, "I don't know much about cancer. I've got to interview patients. I've got to understand what's going on." And they really, really showed me that, by talking to the patient, by understanding what they were experiencing, they could get a better handle on what they were dealing with and then, potentially, do interventions. So we have a wonderful paper if you want to look it up. It's called the "Karnofsky Performance Status Revisited." It's in the second issue of JCO, which we published; I think it was 1984. Dave Johnson: In the early 90s, you relocated back to UCLA. Why would you leave what sounds like the perfect situation to go back to a site that didn't have it? Dr. Patricia Ganz: Okay, over that 13 years that I was at the VA, I became Chief of the Division of Hem-Onc. We were actually combined with a county hospital. It was a wonderful training program, it was a wonderful patient population at both places. And we think that there are troubles in financing health care now, well, there were lots of problems then. Medicaid came and went. We had Reagan as our governor, then he became president, and there were a lot of problems with people being cared for. So it was great to be at the VA in the county, and I always felt privileged. I always had a practice at UCLA, which was a half-day practice, so I continued there, and I just felt great that I could practice the same wherever I was, whether it was in a public system, veteran system, or in the private system. But what happened was, I took a sabbatical in Switzerland, '88 to '89. I worked with the Swiss International Breast Cancer Consortium group there, but it was really a time for me to take off and really learn about quality of life assessment, measurement, and so forth. When I came back, I basically said, "I want to make a difference. I want to do something at a bigger arena." If I just continue working where I am, it's kind of a midlife crisis. I was in my early 40s, and my office was in the San Fernando Valley at the VA, but my home was in West Los Angeles. One day I was in UCLA, one day I was at the VA, one day I was at the county, it was like, "Can I practice like this the next 20 years? I don't know that I can do this. And I really want to have some bigger impact." So I went to Ellen Gritz who was my predecessor in my current position, and I was doing my NCI-funded research at UCLA still, and I said, "Ellen, I really would like to be able to do research full time. I really want to make a difference. Is there anything available? Do you know of anything?" And she said, "Well, you know, we're actually recruiting for a position that's joint between the School of Public Health and the Cancer Center. And oh my goodness, maybe I can compete for that, so that's what I did. And it was in what was then the department called Health Services, it's now called Health Policy and Management. I applied, I was competing against another person who I won't name, but I got the position and made that move. But again, it was quite a transition because I had never done anything in public health, even though UCLA had a school of public health that was right adjacent to the medical school. I had had interactions with the former dean, Lester Breslow, who I actually took an elective with when I was a first-year medical student on Community Medicine. So it kind of had some inklings that, of what I was interested in. I had actually attendings in my medical clinic, Bob Brook, a very famous health policy researcher, Sheldon Greenfield. So I'd been exposed to a lot of these people and I kind of had the instinctive fundamentals, if you will, of that kind of research, but hadn't really been trained in it. And so it was a great opportunity for me to take that job and really learn a lot and teach with that. And then took, part of my time was in the cancer center with funding from the core grant. And then, within a year of my taking this position, Ellen left and went to MD Anderson, so all of a sudden I became director of that whole population science research group. And it was in the early '90s, had to scramble to get funding, extramural funding. Everybody said to me, "How could you leave a nearly full-time position at the VA for a soft money position?" But, nevertheless, it worked out. And it was an exciting time to be able to go into a new career and really do things that were not only going to be in front and center beneficial to patients, but to a much larger group of patients and people around the world. Pat Loehrer: Of all the work that you have done, what one or two things are you most proud of in terms of this field? Dr. Patricia Ganz: Recognizing the large number of people who are surviving cancer. And I think today we even have a more exciting part of that. I mean, clearly, many people are living long-term disease-free with and without sequelae of the disease. But we also have this new group of survivors who are living on chronic therapy. And I think the CML patients are kind of the poster children for this, being on imatinib or other newer, targeted agents over time, living with cancer under control, but not necessarily completely gone. And then melanoma with the immunotherapy, lung cancer, all of these diseases now being converted to ones that were really fatal, that are now enjoying long-term treatment. But along with that, we all know, is the financial toxicity, the burdens, and even the ongoing symptoms that patients have. So the fact that we all call people survivors and think about people from the time of diagnosis as potentially being survivors, I think was very important. And I would say that, from the clinical side, that's been very important to me. But all of the work that I was able to do with the Institute of Medicine, now the National Academy of Medicine, the 2013 report that we wrote on was a revisit of Joe Simone's quality of care report, and to me was actually a very pivotal report. Because in 2013, it looked like our health care system was in crisis and the delivery of care. We're now actually doing a National Cancer Policy Forum ten-year follow-up of that report, and many of the things that we recommended, surprisingly, have been implemented and are working on. But the healthcare context now is so much more complicated. Again, with the many diseases now becoming rare diseases, the cost of drugs, the huge disparities, even though we have access through the Affordable Care Act and so forth, there's still huge disparities in who gets care and treatment. And so we have so many challenges. So for me, being able to engage in the policy arena and have some impact, I think has been also very important to me. Dave Johnson: 20 years ago, the topic of survivorship was not that common within ASCO, and you led a 2004 task force to really strengthen that involvement by that organization, and you also were a founding member of the National Coalition for Cancer Survivorship. I wonder if you might reflect on those two activities for us for a moment. Dr. Patricia Ganz: In 1986, Fitzhugh Mullen, who in 1985 had written a really interesting special article for the New England Journal called "Seasons of Survivorship" - he was a young physician when he was found to have a mediastinal germ cell tumor and got very intensive chemotherapy and radiation therapy and survived that, but realized that there was no place in the healthcare system where he could turn to to get his questions answered, nor get the kind of medical care that was needed, and really wrote this very important article. He then, being somebody who was also kind of policy-oriented and wanting to change the world, and I would say this was a group of us who, I think went to college during the Vietnam era - so did Fitz - and we were all kind of restless, trying to see how we could make a difference in the world and where it was going. And so he had this vision that he was going to almost develop an army of survivors around the country who were going to stand up and have their voices heard about what was going on. Of course, most people didn't even know they were a survivor. They had cancer treatment, but they didn't think about themselves as a survivor. And so he decided to get some people together in Albuquerque, New Mexico, through a support group that he had worked with when he was in the Indian Health Service in New Mexico. And there were various people from the American Cancer Society, from other support organizations, social workers, and a couple of us who are physicians who came to this meeting, some Hodgkin survivors who had been treated at Stanford and were now, including a lawyer, who were starting to do long term late effects work. And we gathered together, and it was a day and a half, really, just kind of trying to figure out how could a movement or anything get oriented to try and help patients move forward. So that's how this was founded. And they passed the hat. I put in a check for $100, and that was probably a lot of money at that time, but I thought, well, this is a good investment. I'll help this organization get started. And that was the start. And they kind of ran it out of Living Beyond Cancer in Albuquerque for a few years. But then Fitz, who was in the Washington, DC. area decided they weren't going to be able to get organizations all over the country organized to do this, and they were going to have to do some lobbying. So Ellen Stovall, who was a Hodgkins survivor living in the Washington area, beginning to do policy work in this area, then became the executive director and took the organization forward for many years and championed this, got the Office of Cancer Survivors established at the NCI in the 1990s, and really did a lot of other wonderful work, including a lot of the work at the Institute of Medicine. She was very involved with the first Quality of Care report and then ultimately the survivorship report, the Lost and Transition report in 2005, 2006, I was on that committee. So that was really how things were evolving. And by that time, I was also on the ASCO board, 2003 to 2006. And so all of these things were kind of coming together. We had 10 million survivors. That was kind of an important note and a lot of diseases now - lymphoma, breast cancer, multi-agent therapy had certain benefits, but obviously toxicities. We lived through the horrible time of high-dose chemotherapy and transplant for breast cancer in the '90s, which was a problem, but we saw a lot of toxicities after that. And so there were people living after cancer who now had sequelae, and the children obviously had been leading the way in terms of the large number of childhood cancer survivors. So this was this idea that the children were kind of the canary in the coal mine. We saw them living 20, 30 years later after their cancer diagnosis, and we were now beginning to see adults living 10, 15, 20 years later, and we needed to think about these long-term and late effects for them as well. Dave Johnson: I'm glad you mentioned Fitz's article in the New England Journal that still resonates today, and if listeners have not read it, "Seasons of Survivorship" is a worthwhile five-minute read. What do you think the most pressing issues and challenges in cancer survivorship care today? Dr. Patricia Ganz: Many people are cured with very little impact. You can think of somebody with T1 breast cancer maybe needing endocrine therapy for five years, and lumpectomy radiation. That person's probably not going to have a lot that they're going to be worried about. But if they're a young breast cancer patient, say they're 35 or 40, you're going to get five years of ovarian suppression therapy. You're going to be put into acute menopause. You're going to lose bone density. You're going to have cardiac risk acceleration. You may have cognitive changes. You may have also problems with cognitive decline later. I mean, all of these things, the more intense treatments are associated, what we're really thinking about is accelerated aging. And so a lot of what I've been studying the last 20-25 years in terms of fatigue and cognitive difficulties are related to neuroinflammation and what happens when somebody has intensive systemic therapy and that accelerated process that's, again, not everyone, but small numbers of patients, could be 10-15-20%. So I worry a lot about the young patients. So I've been very focused on the young adult population who are treated intensively for lymphoma, leukemia, and breast. And that's, I think, something that we need to be looking out for. The other thing is with the newer therapies, whether it's immunotherapy or some of the targeted therapies, we just don't know what the late effects are going to be. Where we're very schooled now in what the late effects of radiation, chemo, and surgery could be for patients, we just don't know. And another wonderful part of my career has been to be able to do quality-of-life studies within the Clinical Trials Network. I've been affiliated with NSABP, I was SWOG previously, but NSABP is now NRG Oncology doing patient-reported outcomes and looking at long-term outcomes in clinical trials. And I think we're going to need this for all of these new agents because we have no idea what the long-term toxicities are going to be. And even though it's amazing to have people surviving where they wouldn't have been, we don't know what the off-target long-term effects might be. So that's a real challenge right now for survivorship. And the primary care doctors who we would want to really be there to orchestrate the coordinated care for patients to specialists, they are a vanishing breed. You could read the New England Journal that I just read about the challenges of the primary care physician right now and the overfilled inbox and low level of esteem that they're given in health systems. Where are we going to take care of people who really shouldn't be still seeing the oncologist? The oncologist is going to be overburdened with new patients because of the aging of the population and the many new diagnoses. So this is our new crisis, and that's why I'm very interested in what we're going to be looking at in terms of a ten-year follow-up report to the 2013 IOM report. Dave Johnson: The industry-based trials now are actually looking at longer-term treatment. And the trials in which interest is cancer, we cut it down from two years of therapy down to nine weeks of therapy, looking at minimizing therapy. Those are difficult trials to do in this climate today, whereas the industry would just as soon have patients on for three to five years worth of therapy as opposed to three to five months. Talk a little about those pressures and what we should be doing as a society to investigate those kinds of therapies and minimizing treatments. Dr. Patricia Ganz: Minimizing treatments, this is the place where the government has to be, because we will not be able to do these de-escalation studies. Otherwise, there will be countries like the UK, they will be able to do these studies, or other countries that have national health systems where they have a dual purpose, if you will, in terms of both financing health care and also doing good science. But I think, as I've seen it, we have a couple of de-escalation trials for breast cancer now in NRG Oncology, which is, again, I think, the role that the NCTN needs to be playing. But it's difficult for patients. We all know that patients come in several breeds, ones who want everything, even if there's a 1% difference in benefit, and others who, "Gee, only 1 out of 100 are going to benefit? I don't want that." I think that's also the challenge. And people don't want to be denied things, but it's terrible to watch people go through very prolonged treatments when we don't know that they really need it for so long. Dave Johnson: Pat and I both like to read. I'm wondering if there's something you've read recently that you could recommend to us. Dr. Patricia Ganz: It's called A Gentleman in Moscow by Amor Towles. I do like to read historical fiction. This one is about a count at the time of the Bolshevik Revolution who then gets imprisoned in a hotel in Moscow and how constrained his life becomes, but how enriched it is and follows him over really a 50-year period of time and what was happening in the Soviet Union during that time. And of course, with the war in Ukraine going on, very interesting. Of course, I knew the history, but when you see it through the drama of a personal story, which is fictional, obviously it was so interesting. My husband escaped from Czechoslovakia. He left in '66, so I had exposure to his family and what it was like for them living under communism. So a lot of that was interesting to me as well. Dave Johnson: Thank you for joining us. It's been a wonderful interview and you're to be congratulated on your accomplishments and the influence you've had on the oncology world. We also want to thank our listeners of Oncology, Etc., and ASCO Educational Podcast where we will talk about oncology, medicine and beyond. So if you have an idea for a topic or a guest you'd like us to interview, by all means, email us at [email protected]. To stay up to date with the latest episodes and explore other ASCO educational content, please visit education.asco.org. 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.

Increasing diversity in the field of oncology is an ongoing task. Our next guest has made it her mission to increase those ranks as well as becoming the first African American woman to be a Brigadier General in the US Air Force. Dr. Edith Mitchell describes her early years growing up in rural Tennessee (2:52), the motivation for joining the Air Force in the 70's (7:33) and strategizing to increase ethnic diversity in medicine and oncology (16:53). Speaker Disclosures Dr. David Johnson: Consulting or Advisory Role – Merck, Pfizer, Aileron Therapeutics, Boston University Dr. Patrick Loehrer: Research Funding – Novartis, Lilly Foundation, Taiho Pharmaceutical Dr. Edith Mitchell: Leadership – Corvus; Honoraria - Sanofi, Exelixis; Consulting or Advisory Role Company - Genentech, Novartis, Merck, Bristol Myers Squib; Speakers' Bureau – Ipsen; Research Funding Company - Genentech, Sanofi Resources (related podcasts, courses or articles) If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at [email protected]. TRANSCRIPT Disclosures for this podcast are listed on the podcast page. Pat Loehrer: Welcome to Oncology, Etc., an ASCO Education Podcast. I'm Pat Loehrer, Director of Global Oncology and Health Equity at Indiana University. Dave Johnson: And I'm Dave Johnson, a Medical Oncologist at the University of Texas Southwestern in Dallas. If you're a regular listener to our podcast, welcome back. If you're new to Oncology, Etc., the purpose of the podcast is to introduce our listeners to interesting and inspirational people and topics in and outside the world of oncology. Pat Loehrer: Imagine knowing in your heart what you wanted to be in life. It usually takes people decades to figure that out, but our next guest knew at age three that she wanted to be a doctor and, later in high school, to be an oncologist. She's achieved much in her lifetime and has incorporated the "pay it forward" by mentoring many others. Dave Johnson: Our guest today is Dr. Edith Mitchell. I first met Edith over 40 years ago when we were both starting out our careers as junior faculty. She grew up in rural Tennessee, and as Pat mentioned, remarkably, she chose a career in oncology at a very early age in high school, despite the fact that oncology was barely a specialty at that time and the lack of role models, particularly role models of color, and women in particular. She received a Bachelor of Science degree in Biochemistry with distinction from Tennessee State University and a medical degree from the Medical College of Virginia and Richmond. In 1973, while still attending medical school, Edith joined the Air Force, receiving a commission through the Health Profession Scholarship Program, and eventually rose to the rank of Brigadier General. She completed a residency in internal medicine at Meharry Medical College in Nashville and a fellowship at Medical Oncology at Georgetown University. Her research interests are broad and involve new drug evaluation, development of new therapeutic regimens, combined modality therapy strategies, patient selection criteria, and supportive care for patients with gastrointestinal malignancies. She is the leader of the GI oncology program at Jefferson Medical College, Director of the Center to Eliminate Cancer Disparities, and Enterprise Vice President for Cancer Disparities at Jefferson's Sidney Kimmel Cancer Center. She's held a number of leadership positions, including those in ASCO, and she's a former president of the National Medical Association. I could go on forever. So, Edith, welcome, and thanks for joining us on Oncology, Etc. Dr. Edith Mitchell: And thank you so much for the invitation, Dave and Pat, it is a pleasure. Dave Johnson: You grew up on a farm, as I recall, in Tennessee. Perhaps you could tell us a little about your early life. Dr. Edith Mitchell: I grew up on a farm that my great grandfather's mother received about 1863 when the Emancipation Proclamation was made. I was the fifth child in my family. My parents were working, my older siblings were in school, so my great-grandparents were my babysitters, so I spent a lot of time with them. He was 89 at the time, became ill, and I overheard family members and neighbors say that they couldn't take him to the hospital because Blacks were not treated properly in the hospital, so they were going to take care of him at home. A physician made a house call. When he left, I told my great-grandfather, "Pa, when I grow up, I'll be a doctor just like Dr. Logan and I'll make sure you get good health care." So, at three years, I decided I would become a doctor and I would make sure that Blacks received good health care. My work in disparity started when I was three. So, after my sophomore year in high school, there was a National Science Foundation program in Memphis at LeMoyne-Owen College. So, I applied and was accepted. And part of the time in Memphis that year, we were given opportunities to go to St. Jude. So my time at St. Jude made the decision that I would become an oncologist. I became really fascinated by cancers and in pathology, use of the microscope, and how cancers were all different, how they varied from the normal tissue for areas such as the colon or the stomach or the pancreas. Dave Johnson: It's amazing that that early in your life you made that kind of decision. Can I back up just one moment? I want to ask you briefly about the doctor that visited your great-grandfather, Dr. Logan. Dr. Edith Mitchell: Dr. Logan was a family physician, African American, and he had a great interest in Blacks being healthy. In fact, when the polio vaccine was made public, Blacks could only go one day per week because you couldn't go the times when whites were there. Dr. Logan obtained the vaccine and he would line the children up at his office. He gave me my first polio vaccine. He was a very handsome man. And, you know, Dave, I found out later that the medical school that he attended in Memphis was one of the ones closed as a result of the 1910 Flexner Report. So he had to go to Meharry in Nashville and take other courses to maintain his license to practice medicine. Pat Loehrer: Were you the first one to go into medicine? Tell me about that background and how your family influenced you personally. Dr. Edith Mitchell: Neither of my parents finished 8th grade, but they were very smart. They pushed their seven children to do well. They provided educational materials in our home and encouraged us to work and to take advantage of opportunities. Dave Johnson: Let's move forward a little bit. I thought I knew a lot about you, Edith, but I didn't realize that you were a Brigadier General. What was the motivation for joining the service in the '70s when you were at med school? Was it scholarship funding, or was there just patriotic zeal or a little of both? Dr. Edith Mitchell: My main objective was, for financial reasons - a scholarship covering all expenses of medical school, plus a monthly stipend. When I was in medical school, one of my laboratory instructors told me about this new scholarship program, and I said, "Okay, I just want to graduate from medical school." So he says, "Well, I know people in the surgeon general's office. I'll have them send you the information." He did, and I looked at it and didn't remember David, that my husband filled out the application. After my neurosciences final exam, I came home, and he says, "Your commission came in the mail today." So I said, "Okay." He says, "Well, I can swear you in. We can't do it at home because you have to have a witness. You take a nap, and then we're going out to job control, which was where all the aircraft controlled, the control room." We went there. We've got a picture of the swearing-in, and we then went to the officers club. It was Friday, and there were lots of people in his group from the Air Force Academy, from Citadel, Virginia Tech, and others. And they were all talking. "Yeah, Edith got a mail-order commission." So I owed the Air Force two years, and I practiced at Andrews Air Force Base, which was the presidential squadron. You hear the president always leaving Andrews Air Force Base. So I think I was 29 maybe, but I was young, and here I was taking care of senators and other important people in government, and these are people I'd only seen on TV before. So I had a really good experience. I received many accolades, but also many letters from people for whom I cared for. And I was therefore invited to stay on in the Air Force, either go to Walter Reed or to San Antonio. I said, "No, I'm going to Georgetown." So one of the VIPs, if I mentioned his name, you would know, said and wrote a letter for me that the Air Force should give me whatever I wanted and whatever I needed to continue in the Air Force. So I received my Air Force pay while I was a fellow at Georgetown. So I stayed on. I got promoted early and engaged in Air Force work. I loved it, and I did well in that atmosphere and stayed on. After my second child was born, I decided I could not continue active duty and take care of two kids. So I left the Air Force, went to the University of Missouri, and someone called me one day and said, "You know, I hear you are at the University of Missouri now. Would you consider joining the National Guard?" I went, " Joining the National Guard? Why would the National Guard want an oncologist?" And the information was, the Air National Guard wants good doctors, and you've got a great record. They invited me to St. Louis to just see the National Guard squadron there. I filled out the application while I was there and in a few days was appointed to the National Guard. So after being there for a few years, I was discussing with one of the higher-ranking people in the National Guard who was in Washington, but visiting St. Louis. He said to me, "You know, you've done great work." He had gone through my record, and he said, "And you know, you're one of the people being considered to be in a group for promotion. Promotion at that time meant that it was a higher rank." So he said, "There's one thing you don't have in your records, however, and other competitors in your group have." I said, "What's that?" "You haven't been to flight school." I said, "Okay." He said, "And everybody who is going to be competing with you will have gone to flight school, and having a flight record will be an important part." So I was in my 40s. My oldest child was 14. I went to flight school and I got my certification, and obviously, I got promoted. And I am the first woman doctor to become a General in the history of the Air Force. And it was really interesting. I'm a Brigadier General. I'm invited to give a talk someplace, and there were lots of people there. So the person introducing me said, "And she is the first African American woman to become a General in the history of the United States Air Force." So I get up to speak and I thank him for this introduction. And I said, "Yes, I was the first Black woman physician to become a General. I said, but, you know, my ancestry says that I'm 30% something white. So I guess I was the first white woman, too." There was a big roar. But I loved every opportunity, and I worked hard at every opportunity. So when I was in the active duty Air Force, I was chief of the cancer center at Travis Air Force Base. So I made my application for research with the Northern California Oncology group, got, they said, one of the highest ratings of the applicants at that time. And I received a phone call from Air Force administration saying "Congratulations, but the Air Force cannot accept this funding from the National Cancer Institute." There is a law saying you can't transfer money from one area of the government to the other, as they called it, a "gift," but it was a grant. So I call Phil Schein and I tell him about the situation. And he already knew that I had received a top report, and he knew that I had the grant before I knew. So he says, "Well, let's see what we can do." Now, remember, Vince DeVita was the NCI Chair at that time and Dr. Rosenberg. At every ASCO meeting Phil, Vince, and Dr. Rosenberg would get together and they would bring their fellows. And Bill said, "Let me see what I can do.'" So somebody at NCI made some things happen. And I got this call from Saul Rosenberg. "Edith, congratulations." So I said, "Well, thank you, but I didn't expect a phone call from you." And he says, "Well, there have been some changes. Your grant, the face sheet has been changed." I said, "Oh." Pat Loehrer: Your husband again. Dr. Edith Mitchell: I can't say who or what, but it had Stanford on it. So my grant went to Stanford. I'm sure they appreciated the kick you get. But Dr. Rosenberg said, "Your grant is now Stanford. We're setting up an account for you at Stanford, and the funding goes to Stanford." So I had people working for me at the Air Force Cancer Center who were Stanford employees. Dave Johnson: Edith, there are still too few African American and particularly African American men in medicine. What's your perspective on that? Dr. Edith Mitchell: I think that many people are not given opportunities, and I've been concerned about Blacks and other racial and ethnic minorities not entering medicine, and particularly regarding oncology. So fewer than 5% of all practicing physicians in this country identify as Black. Little more than 5% identify as Hispanic. And I've been trying to do something about that. So ECOG-ACRIN has been very good about allowing me, and I set up with others, but I was the lead, a program for individuals - they could either be medical students, residents, fellows, or early faculty - to attend ECOG-ACRIN. And as a result of that program, we identified 12 individuals for each of the two ECOG-ACRIN annual meetings. We bring people in, and that has been a success. There's one person I introduced when she was a resident, she then did a fellowship in oncology, and it is now in her first year as faculty. And we have students mainly from Tennessee State. I do maintain very close relationships with Tennessee State, and I have the first Tennessee State student who has just been admitted to medical school at Jefferson. So trying to work with them. As a result of my work with the National Medical Association and the International Myeloma Foundation, we have a group of medical students that have been mentored for oncology. Whether they will become oncologists, I don't know, but they all 12 are doing well in medical school, and with some anticipation they might select oncology as their area of specialty. We set them up with an individual mentor, various oncologists around the country, and they have conducted research with their mentor. So I'm doing things that I think will be helpful to individuals. And I think we're not giving Blacks enough opportunities. Even in entering medical school, the number of Blacks entering most majority medical schools is still very low. Somewhere nine or ten students per year, Blacks entering medical schools. And also there has been a study conducted by the ACGME, which is the Accreditation Council for Graduate Medical Education, looking at graduate studies in oncology. Do you know that most of the oncologists have been trained at a few medical schools? And there are, I think it was 109 programs did not have a single minority student in the fellowship program. And that's terrible. I think that all fellowship programs should have some racial or ethnic fellows in their programs. Dave Johnson: Yeah. One of the disturbing statistics that I've read from the AAMC is that the number of African American men applying to medical school in 2023 and 2022 is actually less than the number that applied in the '70s. It's puzzling to me why we've not been able to attract young men into the medical profession, and perhaps it's because there's a sense of not being wanted or encouraged into the profession. More African American women are applying, but even that number is small, at least in terms of the increase in what we've seen. Pat Loehrer: Edith. You're also the Associate Director of Diversity Affairs at the Sidney Kimmel Cancer Center. What does the recent Supreme Court decision against Harvard in terms of admissions policy, how are you viewing that now at Jefferson? Dr. Edith Mitchell: So I think that the Supreme Court decision certainly was disappointing, but it is what it is, and we've got to deal with it. That is the Supreme Court. So my suggestion and what I am telling students that they have to do, you do have the essay. So when I applied to medical school, I did not talk about Dr. Logan, my growing up on the farm, or my parents not finishing 8th grade. But if I were applying to medical school now, I would use all of that background to include in my essay. And the Supreme Court didn't say that you couldn't include that information in your essay. It said the schools could not use your racial background as a part of the equation, but your letter is still there, and therefore, I would include all of that in the essay, so that you do have an advantage. We've just got to be able to do what we've got to do, not put the university or the medical school at risk because of the Supreme Court decision. But there's nothing in that decision that says you can't include that information in your letter. Dave Johnson: I have one question. What career advice would you offer your younger self? If you could speak to your 30-year-old self based on your knowledge, experience, what career advice would you give yourself? Dr. Edith Mitchell: So the one thing that I did not do when I was about 30 years old and I'm not sure I even knew about it, I think I could have done more in health policy, and the one thing that I have not done is become a White House fellow. And that's usually early in your career plan. But I think my research would have suffered had I done that. And I still say I don't know that I made bad choices. Dave Johnson: No, you didn't make bad choices. Knowing you, you could have been a White House fellow and done everything else you did. Pat Loehrer: And your husband did not make a bad choice either. Dave Johnson: Evidently not. Pat Loehrer: Edith, thank you so much for joining us. You've had such an incredible life, and it's so rich, and we deeply appreciate your spending time with us. I want to also thank all our listeners of Oncology, Etc, which is an ASCO Education Podcast. This is as you know, where we talk about oncology medicine and everything else. If you have an idea for a topic or guest you'd like to see on the show, please email us at [email protected]. To stay up to date with the latest episodes and explore other educational content, visit education.asco.org. 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.

There are many treatments available for cancer but how do you make csre delivery equitable? Given the various types of cancers how can you allocate the right resources to create equal outcomes? Dr. Lori Pierce has made equity a primary focus of her career. She describes how physics and radiology inspired her to be an engineer (6:06), and the moment she decided to transition from engineer to oncologist (12;54) and achieving the position of Vice-provost at the University of Michigan (23:01). Speaker Disclosures Dr. David Johnson: Consulting or Advisory Role – Merck, Pfizer, Aileron Therapeutics, Boston University Dr. Patrick Loehrer: Research Funding – Novartis, Lilly Foundation, Taiho Pharmaceutical Dr. Lori Pierce: Stock and Other Ownership Interests Company - PFS Genomics; Patents, Royalties, Other Intellectual Property Company - UpToDate, PFS Genomics; Uncompensated Relationships - Bristol-Myers Squibb, Exact Sciences Resources If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at [email protected]. Disclosures for this podcast are listed in the podcast page. Pat Loehrer: Welcome to Oncology, Etc. This is an ASCO Education Podcast. I'm Pat Loehrer, Director of Global Oncology and Health Equity at Indiana University. Dave Johnson: Hi, I'm Dave Johnson at UT Southwestern in Dallas, Texas. I'm a Medical Oncologist. If you're a regular listener to our podcast, welcome back. If you're new to Oncology, Etc., the purpose of the program is to introduce listeners to interesting people and topics in and outside the world of oncology; hence the 'et cetera' in our name. Pat, we've got a great guest today. And we've got a great guest today. Pat Loehrer: Our next guest was able to do this despite living at a time when in the United States, certain groups of people faced tremendous barriers to achieve even the basic hint of equality. Our next guest is Lori Pierce. Dr. Pierce attended Duke University School of Medicine and completed a radiation oncology residency and chief residency at the Hospital of the University of Pennsylvania. She was then appointed as a senior investigator at the National Cancer Institute, the National Institutes of Health in Bethesda, Maryland, from 1990 to 1992. And in 1992, she joined the faculty at the University of Michigan, where she currently is a professor with tenure in Radiation Oncology. Since coming to Michigan, she has served as Residency Director and Clinical Director in the Department of Radiation Oncology. In August of 2005, she was appointed by the University Board of Regents to be the Vice-Provost for Academic and Faculty Affairs, a position she still holds. In 2020, she was ASCO President, and while she ascended to the ASCO Presidency, that year COVID descended upon the Earth, and we may hear some stories about that. She's dedicated her career to the treatment of breast cancer patients. She's published over 200 manuscripts and book chapters and has received numerous teaching awards from the University of Michigan, multiple national organizations, and many national awards. Dr. Pierce, thank you so much for joining us today. Dr. Lori Pierce: I am so happy to join you both today. What an incredibly nice introduction. Thank you so much. Pat Loehrer: You were born and raised in Washington, DC. And the family eventually moved to Philadelphia when I think you were in junior high school. Can you paint a picture of what schooling was like for you growing up? Dr. Lori Pierce: Well, schooling, education was just so important to my family and myself. And so, as you said, I was born and raised in DC. Moved to Philadelphia when I was just entering high school. And my parents, who are just the best people on the planet, didn't have an opportunity to go to college. At that point, a lot of people of color didn't really have that opportunity. So education was so important in my family. So if you think about the important issues in my life, there was our faith, our family, and education. And so my sister, who is four years older, she went to college first. After about two years, I transferred and actually graduated from the University of Pennsylvania, and I did that. It was my idea. My parents at that point were living in Philadelphia. My mother was working at Penn, and so I would have free tuition if I went to Penn. And Penn is a great place as is Brown. My parents didn't ask me to transfer, but I did. And I received, obviously, an excellent education at both institutions. I majored in biomedical engineering and I minored in chemical engineering and was pre-med. I had to be strategic in how I was going to pay for my education because my parents and they took out loans, they covered everything, almost everything. My sister and I had some loans, but they took out most of the loans. But they always had an agreement. And the agreement was that both my sister and I would have our college education covered by them. But anything in the graduate arena, we had to cover. So I had to be kind of strategic about that. So I actually applied to medical school and, as you know, got in, and deferred my admission so I could work and earn some money so I could pay for medical school. And I tell you, I did that specifically for the reason, for financial issues. But now this kind of thing is called a gap year. And in retrospect, it was the smartest thing I could have ever done because I took some time away, and during that time away, it made me even more motivated to apply my full attention to medicine. And so education was very important. But I think sometimes you have to kind of step away to then regain the commitment that you need to move forward. And so by the time I started Duke, I was more than ready to be in medical school. Pat Loehrer: I know we talk about underrepresented minorities. I was a mechanical engineer at Purdue. And I can tell you, I don't think there was a single woman in engineering in most of my classes. There were just a few. So to be a woman in engineering is extraordinarily unique. So tell me a little bit about that decision-making and how you got into that. It may have been different in 10 or 15 years later, but were there a lot of women in engineering? Dr. Lori Pierce: No, not at all. And while there may have been two or three in biomedical engineering, there were hardly any in chemical engineering, and as you said, very few in mechanical engineering. So no. But I always was interested in physics. I liked those kinds of things, and hence I went into radiation oncology. It was a perfect blend of my studies and my interest. But no, I often was the only woman, or maybe one of two or three women in my classes, and I was certainly the only person of color in my classes. It taught you things though. It taught you to be comfortable being in that position and to know that you could do it just like anyone else could, and to know that probably a lot of eyes were on you to succeed. Some of that was self-imposed, but some of that was real. But I think learning those lessons then certainly came in handy when I went into medicine because while there are more women in medicine, especially now, compared to what it was when I came through, still, at that point, we were in the minority. And there were very few people of color in medical school where I went to. I was at Duke, and very few people there. You learned lessons early on, right? Dave Johnson: Where did this interest in engineering originate? Dr. Lori Pierce: So it was really more of physics and radiology. So I, as a kid was a really thin kid, and I broke a couple of bones, and I ended up going to get X-rays. And I was fascinated by the X-rays. I was fascinated by this physics. I was fascinated by how you could push this button and these images would appear and I could see my broken bone. So that was really where it came from. So I was pre-med. I did a lot of my pre-med work at Brown, and during the summers I was working in an industry. I was actually in Scott Paper Products industry outside of Philadelphia. And a couple of the other people there who I worked with closely were engineers. And I was just fascinated by it and seemed to be a good way of moving forward my own interest in the physics and the machinery and how it all worked. So I actually switched into engineering. So I switched from Brown to Penn. And being an engineer, it was a great way to make a good living for a year and a half. And I think as an engineer, and Pat, you can probably attest to this, you think in a certain way; you become very methodical in how you approach things. And while I'm sure there are a lot of other disciplines that will give you a similar type of approach, engineering really does—you're very objective in how you make decisions, and I think that serves well. And then, as I said, going into radiation oncology it was just a match made in heaven, so it all worked out great, I think. Pat Loehrer: I think I read that your sister was also into math, is that right? Dr. Lori Pierce: My sister's a systems engineer with IBM. Incredibly gifted. Pat Loehrer: Yeah. Tell me about your parents. How did they guide you? What were your role models in terms of both you and your sister, in terms of math, physics, engineering? Dr. Lori Pierce: I already said my parents were incredibly hardworking and good people. They both had high school graduation education. My mother went straight through, but my father had to get an equivalency for his high school diploma because he was born and raised in North Carolina, had to work on the farm, and didn't get a chance to stay in school. But he got the equivalency of his high school degree. It was interesting, my dad was just incredibly gifted for math. My father was just amazing in math. And my father and I always hung out. He was like my best friend and so I think my emphasis on math in part came from my dad. And I'll say that both my parents didn't, weren't able to get a college education, but they were two of the smartest people I ever knew. My father and my mother, but I just hang out more with my dad, had amazing common sense and whipsmart math. I'm sure that a lot of where I ended up is because of my dad. Dave Johnson: You mentioned that you had family in North Carolina. I remember reading that you were influenced by some of the people you met in North Carolina with respect to your medical career. Can you tell us a little bit about that? I think a Dr. Weaver, was it? Dr. Lori Pierce: That's right. Doc Weaver. That's right. So I used to spend a lot of my summers in North Carolina with my father's family. And Dr. Weaver was an African American family medicine doctor who took care of the vast majority of people of color in the town of where my father's family is from. Whenever anyone had issues and needed medical care, he came to the house. He was the doctor for people of color. I sat back- and take it in a lot when you're young - people never really know how much you're listening and seeing, but you take in a lot. And you see just how revered he was, and he should have been, because he was largely the face of medicine that a large part of that town saw. And that stuck with me. A couple of times, I went with him when he would see patients. Without a doubt, this factored into my wanting to go into medicine. I think that coupled with my interest in those x-rays and the physics of the x-rays, I think that's how it all came together, but Doc Weaver. Pat Loehrer: So you mentioned you did a gap year, which was somewhat unusual at that point. I did a gap year as well for the exact same reason - I wanted to not incur a lot of debt or at least try to defer the debt as much as possible. What did you do in your gap year, and how did that impact your medical training or did it? Dr. Lori Pierce: It definitely did. My gap year was actually 18 months. I moved to Austin, Texas, and I worked in Round Rock, Texas, that was at a time when Round Rock was just a sleepy little town just north of Austin. I haven't been back since. I know Dell computers is now there and now it's almost you can't see a difference between Austin and ROund rock, but that was not the way it was on those days. And I worked in Round Rock because McNeil Consumer Products was there. I worked at McNeil Consumer Products, they make Tylenol. I was the second-shift Glatt supervisor for Tylenol. So Glatt is the machine that mixes up all of the ingredients for Tylenol and it was something that I knew going in that it was only going to be short-lived so I could probably live almost anywhere. And I thought, okay, I'd been on the east coast all my life, let me see what the rest of, another part of the country is like. It was an amazing experience. To go from Brown to the University of Pennsylvania, DC, and Philadelphia, to Round Rock, Texas. In retrospect, I couldn't have picked a better place. I mean I soaked up a little local color, went to some things that the Texans do, and rodeo, that kind of thing. But more importantly, I met people who I would've never met on the east coast. These were people who largely had not been outside of the Austin area. One person said she'd never seen a black person before. That kind of surprised me. So it was a swath of America that I had not been exposed to. It was not easy. But in the end, it was the best thing, because you realize, people are people. And while you might be put off at first because they're put off with you and you put off with them, at the end of the day, it was a great experience of getting to know people who can further enrich your life. And I think that has helped me in medicine in terms of interacting with patients no matter where they're from, no matter what their background, what their financial situation is, people are people. I was on my own. I was truly on my own. And that gap year was invaluable far more than helping me pay off medical school loans. Pat Loehrer: You've focused into radiology and obviously there's diagnostic radiology and therapeutic radiology. How did you end up choosing the career that you eventually championed so well? Dr. Lori Pierce: At the time I went to medical school at Duke, at Duke, radiation oncology was a division of radiology so they had not separated yet. While I was at Duke, they recruited in their first chair of radiation oncology into separation. So long story short, when you're at Duke in medical school, your third year is all research. You could go into a lab and do research. And so when I met with my radiology advisor and looked at the list of options of projects I could sign on to, the one that happened to be most interesting was being done by a radiation oncology researcher in radiology. And I thought, well, it looks interesting, but I don't want to do that because I want to go in radiology so I need to have a radiology project. And my advisor said, "No, it's okay. Radiology programs, they'll take radiation experiments. You can still use that and apply to radiology." So I said "Okay, that looks really interesting." So I opted to go with that choice and it was during that year that radiation oncology separated. A chair came in, Dr. Lenny Prosnitz from Yale, and he said, "Why don't you just come down and see what it is that we do?" So when my experiments were set up, I would run down into the basement because we're always in the basement, and I would follow him around and I just loved it because it gave me the physics that I wanted, I got really interested in cancer biology. And I think with my personality, I work well with patients. I love patients. That patient interaction is when I'm at my best. And I wouldn't have had that in radiology. With all due respect, radiology is so important, but you have to do what you gravitate toward, and those interactions when I was following him around with patients. So I never looked back, I changed at that point and decided to go into radiation technology. So I was at Penn for residency and chief residency. When I was getting ready to leave to go to the NCI, the person, Barbara Fowble, who was a well-known breast radiation oncologist, took a sabbatical and asked if would I stay the year she was taking sabbatical to run the breast service. So I deferred going to the NCI to stay at Penn for an additional year as an attending and then went to the NCI when she came back from her sabbatical. I worked with Eli when I got to the NCI. Pat Loehrer: And Norm Coleman, too? Dr. Lori Pierce: And Norm from a distance. He's great. He came in for comedic relief. It was in a while, but he and Eli and Tom Delaney. It was a great time to be at the NCI. It was shortly after that, about a year or so into that when things started changing, Eli left to go to UT Southwestern. But it was a great time to be at the NCI. Dave Johnson: So you've worked with some of the giants of radiation oncology for sure? Dr. Lori Pierce: I did. And the NCI was known as the places where the giants launched. So the Allen Lichters, the Joel Teppers. I mean, I could go through a list. They all had worked with Eli, and Allen was no longer there. Allen had already gone to the University of Michigan. He subsequently recruited me to Michigan. But the radiation oncology branch, the Marc Lippmans of the world, it was a magic time. Even though some of them weren't there, their footprint, their stamp was on the program, and it was really good. And working with Eli was just great. Dave Johnson: So is that where you're working with Barbara where your interest in breast cancer or was it that you mentioned you had an interest in the biology? Where did that interest in breast cancer originate? Dr. Lori Pierce: It came from working with Barbara. So it was a combination. Barbara, who is one of the most amazing people to this day, that I've ever worked with, her command of the data, her synthesis of the data, her interaction with patients. Most people don't appreciate of just how great a clinician Barbara Fowble was. And so it was admiration for that. So she was a part of it, but John Glick was the other part. So John, of course, who everyone knows, the giant in the field, and I think at the time, not sure if when I was a resident, he was the president of ASCO. Even if he wasn't the president at that point, he was certainly highly integrated with ASCO, and he kind of took me under his wing. I'm not sure why, but I was very interested in breast cancer. So he would like bring me over to the Med On clinic and teach me more about chemotherapy. So I had John and I had Barbara, and then also the mammography group was very supportive of me. I would come in literally on weekends and meet with the head of mammography, who would test me on mammograms, reading mammograms. So it was just a very supportive environment. And certainly, breast cancer was the area that I wanted to focus on. It was a great group to train under. Pat Loehrer: Dave and I had the opportunity a short time ago to interview John Glick. And as you're talking, one of the wonderful things about our field of oncology is how it's a close-knit network and there's so much mentoring. And John took both Dave and I underneath his wings, and he had no really rationale for doing that. But Eli, I mean, there are so many wonderful people that we've had the opportunity of meeting. And you yourself have mentored so many other people in another generation. It's hard to explain to people outside of oncology about how special this field is, I think. Dr. Lori Pierce: It absolutely is. And it's an honor for me to serve as a mentor because once you're a mentor, you always mentor. I mean, John, I'll run things by John to this day. Once you develop that closeness and you know them and they know you, you savor that, it never goes away. Dave Johnson: What would you tell a junior faculty or fellow are the characteristics of a great leader? What do you think makes for great leadership? Dr. Lori Pierce: That's a great question. First and foremost, you listen. You need to listen and understand what your mentee, what it is they're seeking, what it is that they want to study, where they feel they are somewhat inadequate, and they want to improve. What is it that they want to accomplish with that relationship? Because as you and Pat both know, mentors come in all shapes and sizes. Mentors come in all locations. You may have someone who is at your institution where they're coming to you to help to shepherd through your institution and the policies and understand the practice of your institution. You may have those that are mentoring you from afar, or perhaps in addition to content, but also getting a sense of what the outside environment is like. So I think first rule of mentorship is to really understand why that mentee has sought you out and whether you are the right person to fill that void, whatever void that they think that they have. I think another part of mentorship is making the time for that individual. We're all very busy people. Most people aren't looking at you to mentor them two hours a day. They are going to be very judicious in what they ask, and you should make sure that what they need, you can accommodate that, and if you can't, perhaps arrange for someone else who can. But in most cases, there's a lot that we all can do for people who approach us. And then I think really understanding, kind of putting yourself in their position, where are they in their trajectory toward greatness, and how can you work with that. And I think most of us have a lot that we can share, and a lot of times we may be sharing things, we don't even realize that what we're saying is impactful to those individuals. But I really think it's starting out by listening and being honored that you are actually asked to be a mentor. Dave Johnson: You've also received numerous teaching awards. You obviously have a gift for that. Tell us, what's the secret to being a good teacher? What are the characteristics of a really great teacher, different than mentoring? Dr. Lori Pierce: Yeah. You have straightforward conversations with your residents and your fellows. I'll give you an example. We have teaching conferences. And teaching conferences have evolved over the years. I've been at Michigan for a long time, since '92. And in the old days, the morning conference, you discussed the literature and you had a discussion, and now it's evolved to slides. The residents give the slides and I'm old school. I like to go back to the old school. Some people call that the Socratic method. I think the Socratic method has gotten a bad rap because you can do the Socratic method in not a threatening way, and you can ask questions to residents and expect for them to give an answer. And it was interesting, long story short, when I few years into becoming Vice-Provost here, I'm not able to come to morning conferences very often. And I got a knock on my door here in the cancer center, and I opened up and it was the three chief residents. And I said, "Okay. Hi. Come in. What can I do for you?" And so all male, and they said, essentially, "We miss you. Our residents, we all prepare more for your conferences than anyone else. And even though you ask us questions, we don't feel threatened by your questions. We want that type of style of learning." And I was bowled over by that because I'm just a simple person, and I don't beat around the bush. I ask questions because these are the kind of questions that you have to know when you manage patients. These are the kind of questions that you have to know when you're in a tumor board and you interact with medical oncologists and surgical oncologists. You have to know the literature, and you have to be able to state it in a clear way that, obviously, physicians get it, but patients get it, and you have to be aware of your audience. And so that little vignette of when those three knocked at my door told me that, clearly, going back to the basics and just asking questions is well received. Pat Loehrer: I'm thinking about your parents who did not go to college, and here you are now a Vice-Provost at one of the most prestigious universities in the country. It's got to be, if you reflect on that really cool. Tell us a little bit about that journey and what it takes. Or was that accidental journey or was this a purposeful journey of leadership that you wanted to go to? Dr. Lori Pierce: It was absolutely not purposeful, for sure. So I can thank my dear Dr. Lichter for that. So, Allen Lichter, after he was chair of radiation oncology, as you probably know became the dean of the medical school. Well, Allen, who had brought me to Michigan, got to know me pretty well. And so, when he became dean, Allen's so strategic. He realized that it would be important to have someone from the medical school to work in the provost's office because the medical school is the largest school on campus, and we're the different ones. We approach life somewhat differently. And so to have that perspective in the provost's office would be very helpful. So he came to me and said, "Would you be interested in doing it?" I didn't know what a provost was. I'd heard about it when I was at Brown, but I was like, "No, I'm not interested." And he said, "Well, just go and talk with them. Meet with the provost of Central Campus and just see." So I went and decided not to do it. But they did ask, would you just be a special counselor to the provost? If we have questions, we can call on you. So I said, sure. So I did that for a year, and then by the end of the year, had a much better awareness, understanding of what they did in that office, and a much better understanding of who they were, and they me. So I said, "Okay, if I decide to do this, I want it so that you can fire me at any time, and I can fire you at any time, but I'm never giving up my day job in terms of seeing patients. This is always my night and weekend job." And so that's how we did it. And so I've been doing it now for a long time—since 2005, 2006. The reason I've done it so long is we do work with amazing people across campus. We have 19 schools and colleges, and I now am the Vice-Provost for Faculty Affairs for the Health Science Schools. And it allows you to not only look at the university as a whole—we tend to have silos, we tend to live in silos. And when you're the Vice-Provost, you can look beyond those silos and you can bring together people and schools for common threads of work. If I see the nursing school is focusing on certain aspects of cancer treatment XYZ, I can bring together people from the medical school, I can bring together the school of public health and put some funding to it to give them seed funds, to then synthesize something which hopefully will then translate into a larger grant. So it is very rewarding in that regard. You oversee promotions, the hiring, and promotions of the faculty, and it further opens your eyes to what can be. And so much of what we do, obviously, in cancer is multidisciplinary, interdisciplinary. We're not just radiation oncology, medical oncology surgeons. So much of what we do in medicine, we interact with public health, we interact with dentistry, we interact with the other health science schools. It has been a very interesting ride in terms of what can happen when you bring like-minded people from different disciplines and you concentrate on a certain topic. And we've started some seed funding. We've had efforts where it really has grown into very significant NIH funding. Pat Loehrer: What are you most proud of as a Vice-Provost or your leadership at the university that we wouldn't know about necessarily? Dr. Lori Pierce: Two things. One, I was one of the key worker bees in changing our policy for time to tenure. We used to have an eight-year tenure clock. And in medicine, we need longer. It's more difficult to get funding, it's more difficult to manage all of the missions that we do and still end up right where you want to be. And so we now have a tenure clock. And so I helped to make that possible. In more recent years, probably the jewel for my provost time is getting maternity leave and parental leave. Many academic institutions don't have maternity leave. Women have to take sick leave. I'm sorry, being pregnant is not sick. That's not a sickness. If you're a dad, you want to have time for bonding, you want to have time to be there when your child is born or adopted. And so I and two other people established a policy of maternity leave and parental leave that was wildly accepted. The leadership of the university could not agree more readily. And now we have a very robust policy, and this is not just for faculty, it's for staff. And I get people who thank me all the time, whether they're staff or faculty, especially the dads, for giving them the time to be with their child. So that's an easy question to answer. I think that has been a change that has been received positively throughout. And even if it's a case where when a person is gone for their parental leave or maternity leave, other people have to step up to cover for them. But people don't complain because everyone knows that that is the way it should be and that people should be given that time. So it's been one of those win-wins. You don't get win-wins very often, and that's been a win-win. Dave Johnson: Kudos to you and your colleagues for pushing that through and making that happen. That's got to be a huge recruitment advantage for Michigan. Dr. Lori Pierce: It absolutely is. And this is something where industry has done a long time ago. But academia, we have been much slower to adopt those family-friendly policies. And obviously, we are well compensated in our careers. People don't leave usually for the money. It's usually the other pieces. And it's pieces like this where people are recognized and rewarded for being a whole person. And that isn't just bringing in grants, it's also respecting their family lives and their family time. Dave Johnson: For sure. That was certainly my experience serving as chairman of a department. The things that prompted departure, there were some academic issues, of course, but the main ones were personal. And oftentimes it was family-related, particularly amongst our female faculty, but increasingly so amongst the male faculty as well. Dr. Lori Pierce: I agree on both counts. That's exactly right. And it's great to see that men want to be present for their children. Having a woman be able to take maternity leave is great, but having a man to take that parental leave is great as well. Dave Johnson: For sure. So let's pivot over to ASCO. ASCO is a huge professional organization, largely, but certainly not solely comprised of medical oncologists. You're one of the few radiation oncologists to lead that organization. What was that experience like? Dr. Lori Pierce: Being President of ASCO is without a doubt the highest point of my professional career. ASCO has always been a place where I felt at home. I always felt that ASCO wanted everyone under the tent. So yes, I know it's primarily medical oncology, but ASCO brings everyone together because in order to move the needle in cancer, we all contribute to improved outcomes. So then fast forward to becoming president. I never, ever thought I would be president of ASCO. It wasn't like something I was like, "Oh, I have to be President of ASCO." No, I just wanted to be active in ASCO and do the right thing. And so you hear you've been nominated and you're very honored, but you're never going to be president, and you find out that you've been voted president. And my time was an unusual time because it was right in the midst of COVID. And so 2021 was completely consumed with COVID. So my predecessor, Skip Burris, he had a normal year up until about March of 2020, and that's when the world shut down. So of course, that was the first ASCO meeting that was virtual. Then my year came and from start to finish, I often tell people, I hope I will be the only president in ASCO history to say that they'd never had an in-person meeting for the entire time that they were president. All my meetings, every single meeting, were via Zoom. Yeah, you're a little disappointed by that, but in some ways, it worked to my advantage because, long story short, when I was voted president and you pick a theme, this was long before COVID; long before we knew the world was going to change, and I wanted to have an equity theme, but I worried that it wouldn't resonate with people. So I said, "Okay, I'm going to do this and just hope that it works well with the membership." Well, then you fast forward, and the world changes. You have COVID and you have all these senseless murders that are on TV every night. And so even those who perhaps had their head in the sand before, they got it during COVID: there are so many inequities, and that ended up being, I think, the right theme for that time. And not being able to meet people because of COVID—yes, I missed it, but it was the reason that we missed it because of COVID and the inequities that were borne out during COVID—that really hit home that equity needs to be first and foremost in everyone's mind. So it's a long answer to your very short question. It was an amazing time. I think the organization has gotten stronger because of it. So much of work with ASCO was in equity before, but ASCO really upped its game, and equity is now one of those topics that is ingrained in every aspect of the organization, and that is what you have to have to truly affect change. I remember when I was president-elect, you go through all these interviews, these people want to interview you, and one question they ask or post is what do you want your legacy to be as president? And I was like, you can't make a legacy in a year with an orientation like ASCO. You make a legacy in a year if you have a lousy organization that you can actually make a huge difference in one year. So what you aspire to do is take a great organization and make it even better during your time as president. I think we did that. The world is inequitable. We get so many issues here and there and it all ends up with delivering inequitable care that those who have, can get the care and those who don't have it, cannot. And so I think the biggest challenge is to be able to bring the people to the table who can really make a difference and act on what needs to be done to improve equity in care. Dave Johnson: Pat has devoted a significant portion of his career to the whole issue of equity and I'm sure would agree with you. Pat Loehrer: I want to close with this thought, if you will. Dave or I usually just talk about our books that we've read. And one of the books that I mentioned that I just got through reading is entitled The Things We Make. It's by a chemical engineer and biomedical engineer from the University of Illinois, Bill Hammack. And the whole purpose of the book is really kind of defining the differences between science and engineering. He defines engineering as solving problems using rules of thumb that can cause the best change in a poorly understood situation using available resources. And he says, in a really tangible way, the scientific method creates knowledge while the engineering method creates solutions. Much of what we do in oncology really is really more engineering than it is science. We're trying to create solutions. He went on to talk about this and it ties into the last comment. He talks about the various technological explosions, eras that have great change occurred when science took a step forward and provided better rules of thumb for the engineers. So there was the Bronze Age and the quantum physics age and even the digital age. I would love for us to come up with the health equity age for which we could work together, taking the advances of science, but using these methods of engineering to make things better with the available resources that we have. And I think if we can do that, I think this would be something that I think we can all be very proud of. Dr. Lori Pierce: What an amazing summary of that book. And first of all, what amazing work that you have done, and I'm not just saying that—you are walking the walk and talking the talk. And to your point, Dave, of what is the biggest challenge for ASCO, I couldn't have answered it better than what Pat just said. That is it. That's it. That's it. ASCO can do it, but we can't do it alone. ASCO can't do it. Health can't do it alone. This is all hands on deck and it's bringing the other parts of society to the table so that we all understand the enormity of the problem and we have an action plan. Pat Loehrer: Is there a book you're reading, Lori, that you want to share? Dr. Lori Pierce: There is. I'm reading a book now called In Shock. It's by Rana Awdish, I don't know if you heard of it. I haven't gotten to the end of it, but just briefly, I met her because she's an ICU Doc at Henry Ford in Detroit and she gave the medical school graduation speech at our graduation a couple of weeks ago. So, in advance of her coming, I wanted to read through her book. It's an autobiography. In a nutshell, she had a just horrendous experience, essentially almost died when she was seven months pregnant as a fellow. And she basically bled out and I think it was related to a benign tumor in her liver, which is probably hormonally affected by her pregnancy. And she had sepsis, DIC, liver failure, adrenal failure. So, it goes through what it's like to be on the other side and to be in her own hospital. She wanted to go to her own hospital. She was in ICU in the place that she wasn't attending. Her experience though, as a book, really ends up talking about the hope of medicine because now she's thriving. She's well, she and her husband, she lost the pregnancy, then she and her husband now have a child. She's back to being an ICU attending, and she gave her medical school graduation speech two weeks ago. But in that book, you are reminded of the pitfalls in medicine. You're reminded that we as providers often forget that the patient is sitting right there, and she talks about situations where when she's on the vent, someone saying she's sitting right there, "She's circling the drain." "She's trying to die on us." "Your kidneys aren't cooperating." And one resident who came in eating food and took out his back pocket said, "Oh, I'm sorry, I just had a really bad night last night." She's dying. It's just yet another reminder that we are in this honorable profession. We have the honor of taking care of patients, and we always need to make sure that we respect every patient that we interact with. And so, it's a very interesting book. Also, there's another book that I read that's probably been out 15, 20 years, it's called The Art of Racing in the Rain. Do either of you know that? It was a New York bestseller. My husband bought this years ago, it was in our library in the house, and I happened to pull it out. It's about a dog. So, I'm a dog person. I've always had dogs. I love dogs with a passion. And this is a book written in the voice of the dog. It's about this dog named Enzo. And it's humorous, but it's also very emotional in places because it talks about what he does to help his owner, who's a wonderful man, and the wife who ends up dying of a brain tumor. As an oncologist, you could see symptoms, and you knew where that was going, and their daughter, and the things that a dog can do to uplift a human. And even when you're at your lowest point and you're about to give up, and the owner goes through just the most horrible, horrible experiences, and you realize that all of a sudden, something very small can make you then take notice of what is really important to you and can turn the tide. This is a great read. It's a quick read. I highly recommend it. It's called The Art of Racing in the Rain by Garth Stein. It really is an inspiring story about human resilience. It's a great book. Pat Loehrer: Lori, thank you so much for taking time from your incredibly busy schedule to spend a few minutes with Pat and me. We really enjoyed it. And I also want to thank the listeners to Oncology, Etc. an ASCO Educational podcast, where we will talk about oncology medicine and beyond. So, if you have an idea for a topic or a guest you would like for us to interview, by all means, email us at [email protected]. To stay up to date with the latest episodes and explore other educational ASCO content, visit education.asco.org. Thanks again. And before we go, I have a question for you, Pat. How many ants does it take to fill an apartment? Pat Loehrer: I have to cry uncle on this. Dave Johnson: Ten, tenants. Pat Loehrer: Tenants. I thought crying uncle was a pretty good response. Dave Johnson: All right. Thank you, Lori. That was wonderful. Pat Loehrer: Thanks, Lori. It's terrific. 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.