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"Battling cancer takes place in many parts of the world and our next guest has led initiatives to do just that. In Part Two of this Oncology, Etc. Podcast episode, Professor of Cancer and Global Health at King's College London Dr Richard Sullivan shares with us his research into cancer care in conflict zones around the world (0:58), his thoughts on "colonial" cancer research (5:50), his advice to people interested in pursuing a career in global oncology field (10:08) and using "pooled procurement" as an innovative approach to cancer care (11:13). Participant Disclosures Dr. Richard Sullivan: Honoraria – Pfizer; Consulting or Advisory Role – Pfizer Dr. David Johnson: Consulting or Advisory Role – Merck, Pfizer, Aileron Therapeutics, Boston University Dr. Patrick Loehrer: Research Funding – Novartis, Lilly Foundation, Taiho Pharmaceutical If you liked this episode, please follow the podcast. To explore other episodes, as well as courses visit https://education.asco.org or contact us at education@asco.org. TRANSCRIPT The disclosures for guests on this podcast can be found in the show notes. Pat Loehrer: Hi. I'm Pat Loehrer, director of Global Oncology and Health Equity at Indiana University. I'm here with Dave Johnson, a medical oncologist at the University of Texas Southwestern in Dallas, Texas, and a friend of mine. This is the second half of our Oncology Etc. conversation with the professor of cancer and global health at King's College in London and the director of the King's Institute of Cancer Policy and the co-director of the Conflict and Health Research Group, Dr. Richard Sullivan. In part one, we chatted with Professor Sullivan about his international travels as a child to his transition from biochemistry and finally to a great career in health policy and research. Today we're going to continue our conversation with Professor Sullivan by asking him about his insight into the current state of the progress in global health care. Richard Sullivan: Conflict and fragile populations around the world are sadly growing. They're unique ecosystems for a whole variety of reasons. I think fundamentally, though, to do research in those systems requires a huge amount of sensitivity and experience and expertise because you're dealing with the most vulnerable of the most vulnerable. And then, of course, whatever research you do, you're constantly thinking in the back of your mind how you then tie this into any form of impact. There is a tendency, often with research in these populations, that the research is just done for the researcher's sake rather than actually being utilized to help improve those lives you're actually involving and studying. But I admit it's a very tricky area to work in. Cancer in conflict populations, a particular interest is a relatively new domain. It's only really been around for the last eight to ten years for a variety of very understandable reasons. Let's be honest, 30 years ago, cancer was not a significant factor in humanitarian conflict operations. You were dealing with demographically untransitioned societies, much younger. Really the group one, infectious diseases, child and maternal mortality, et cetera, were the primary foci. That still is the case. But what we're seeing now is much more transitioned populations being impacted by conflicts. And you think about in Mexico, in the Narco Wars, Syria, Iraq, even Afghanistan, and all of those have changed dramatically the nature of how care is delivered and how patients move. And we call these new therapeutic pathways, and we consider them kind of post-Westfalian. We're not talking about cancer care anymore that's boundaried within nation states. Patients moving across national lines, we have patients moving in pathways which are absolutely unique and we've never experienced or seen before in the high-income West. And that means you have to have a different paradigm for care and a different paradigm for building cancer control systems. And I guess for the last ten to fifteen years that's what we've really been interested in is this dynamic of conflict populations and how you deliver care and who delivers it. And there, of course, you're talking with a very mixed act, a bunch: humanitarian organizations, the big NGOs, the ICRCs, Medecins Sans Frontières. You're talking about the militaries in many countries. The militaries are very powerful in many countries in terms of providing care. And then finally there is, of course, the health services or systems that exist to varying degrees in the individual countries infected by conflict. So our program really tries to understand how you strengthen health systems per se in these conflict populations. And obviously, my particular interest is in cancer and palliative care. But I'm going to be honest, for that we have a very large team, some remarkable colleagues I've worked with over the years, sub-Saharan Africa, the Middle East, and increasingly, there's a lot of leadership coming out from these countries taking these sorts of programs forward. It's an important time, and I think Ukraine has taught us as well that if you don't think about, for example, cancer care within humanitarian operations, within UNHCR, you can end up in serious trouble in terms of planning, financing, sustainability. So I think Ukraine is going to be an interesting turning point in generally thinking about cancer care and conflict and humanitarian operations because it's really illuminated to everyone very clearly in Europe and the USA, what cancer and conflict really is, because I think the Middle East has felt a little bit far away, and it's been quite difficult selling all that kind of policy and work. But Ukraine is really having a dramatic impact and I think it's producing a lot of learning points. Dave Johnson: You recently published, along with colleagues, I thought, a very provocative paper in JAMA Open Network about the participation of lower and upper middle-income countries in oncology clinical trials led by high-income countries. You made the point, be sure to correct me if I'm wrong on this, that first of all, Ukraine and Russia are actually two of the top participants in these kinds of trials. Number one. Number two, the question is, is it exploitative of the higher-income countries to be conducting these trials in these two countries and then more particularly, what the recent conflict in Ukraine has done to the participation of patients? And I wonder if you might comment on those points. Richard Sullivan: I'll maybe talk to the last point first. The conflict has been devastating for recruitment. It's also important to realize a lot of these sorts of clinical trials are funded by industry and they've been the backbone of funding research and also to a greater degree also access to certain types of medicines in these countries. Is it exploitative? I think it's a very hard judgment call to make and I think if you ask my Ukrainian colleagues, the answer is no. We know exactly what we were getting into. When companies work in these places, they pay and they pay properly. The difficulty I think is, generally speaking, there is obviously this discussion now ongoing about neocolonialism and exploitation of low middle-income settings more generally. It's very hard, all the research we've been doing, it's very hard to make generalizations. There is absolutely no doubt. I want to recognize right up front that there has been some appalling exploitation and what I would consider to be colonial cancer research going on over the last 20 years. And it's blindingly obvious when you read papers, when you look at authorship, when you undo this sort of analysis, that there has been a lot of exploitation where high-income countries are parachuted in. Investigators have taken whatever they needed data, samples, interview data, made good careers on the back of it and good research funding, and not really put much back into the ecosystem they've been working with. So that's absolutely clear up front. Then we have this other problem, as well as research funding generally, because if you step back and look at the data, and this is something we've published on, actually, with Julie Gralow, and ASCO, we talk the talk about funding global cancer, that's big, high, powerful, wealthy, high-income countries. But when you actually look at the data and you ask that question, of all the cancer research publications, how many from the USA, the UK, the Frances, the Germany are actually with lower middle-income countries, you barely get above 4%. It doesn't take a rocket scientist to realize we taught the talk here, but we're not walking the walk. The money is not being provided to do genuinely equal collaborative work. We've not built capacity and capability in many countries in terms of clinical research methodologies and strengths. We failed to back up a lot of the rhetoric. We talk about global cancer with actually proper cancer research system strengthening. And I think there's that realization, and there's been that realization over the last five or six years that that's been the case. And when you take countries like India who kind of realized, you know, maybe ten to fifteen years ago this was the case, they've obviously gone themselves and driven their own agenda. So the National Cancer Grid of India, the development of Credo, the methodology workforces led by Dr. C.S. Pramesh from the Tata Memorial Centre, has been absolutely superb work. I mean, it's been amazing. A real master class in national development. But I think we do, as high-income countries have to think, look ourselves in the mirror and ask the question, is this what we mean by global cancer? Are we really putting enough money in? And are our research priorities right? You've heard me argue about this enormous amount, about how much money goes into discovery science and biopharmaceuticals. Where's the money going into implementation science, health services research, social science research, health economics, all the stuff that actually leads to direct improvements by strengthening cancer systems. It's a drop in the ocean compared to the billions and billions a year that have been spent in these other areas. So I think the agenda is unbalanced. But I think when you talk about exploitation, you have to be kind of more nuanced about that argument. Pat Loehrer: Richard, we were just at the World Cancer Congress and it was heartening to see all these wonderful young people from around the world thinking about global oncology and various different aspects of things. But I'm thinking about Brexit. I'm thinking about some of the issues going on in our country in which we are hunkered down to issues in our own country. P30 grants for the cancer centers are focused on issues in our catchment area. They have an illusion of global stuff, but it's really not a priority. What would you say to young people who are interested in pursuing a career in global oncology? Is this something that's worthwhile for them to do, and what would you advise them? Richard Sullivan: Yes, it's absolutely worthwhile to do. And I think two pieces of advice I would have is develop, first of all, your interests with friends. The work we do around the world is with friends. These are close colleagues. This is not some instrumental transactional research program of sending your samples to a genome lab for them to sequence it and send back to you. These are really long-term true friendships. That's what makes the difference, is that long-term commitment, year after year, decade after decade. So find out where it is and what it is you're really passionate about. Make those friends and then develop the suite of knowledge that you're going to require to do the kind of research. I mean, the thing with global cancer is it requires a very broad outlook. It doesn't matter what you are the master of; whether you're an epidemiologist or social scientist - mixed methods is absolutely the way to go. What you have to be able to do then is sort of think more broadly about other sorts of disciplines to bring out, because most of the really complex problems require a very transdisciplinary approach methodologically, and that takes a few years to build the insight into these other disciplines and also to make research relationships. And again, there is no substitute for experience in terms of going to places, working with people, working on projects. And of course, with that comes the advocacy. Cancer crosses borders, the advocacy for global cancer. You need people who are going to be passionate about this, who are really going to stand up and shout from the rooftops what's really needed and change, I think, the minds of both national and the philanthropic funders, which, as you said, Pat, you're spot on, are still very, very insular, very inward looking in terms of how they see the world of cancer research. And I think it needs a bit of a sea change. But the opportunities are out there. There's some, as we know, wonderful, wonderful people working all over the world on really, really different problems. Building capacity in surgery in Zambia is not the same as building capacity in surgery in one of the states in India, for example. So there's an incredible richness and diversity. It's a really, really important area. And I think younger crowds don't get put off because there's no clear pathway and there's a reason there's no clear pathway. It's so diverse, but it's absolutely worth it. And there's plenty of us, I think, out there now that can help. There's some great conferences like the Word Cancer Congress, amazing regional conferences like AORTIC, which is happening in Senegal next year, the big conferences in India. Absolutely superb. Just go immerse yourself in this. Dave Johnson: You've talked about a lot of different innovative approaches to cancer care and lower- and middle-income countries. One thing that I read that you'd written about was something that I had never thought about. I think you called it pooled procurement. Can you talk about that? Where maybe two countries can join together? It seems irrational to me that we could expect something like that to happen. Are you aware of any examples? Richard Sullivan: It's interesting because I've the pleasure of working with a lot of colleagues over the years on access to essential cancer medicines. And it's interesting because we're now getting into a domain in global health, which again is very rich for more learning, for more people coming into which is the political economy of cancer. Because this is where the disciplines of health economics, decision procurement, logistics, all kind of fuse together, as well as an understanding of power and decision making in individual countries. So, in and of itself, procurement is where groups of countries or centers within a particular country will come together to create sufficient volume to negotiate with suppliers for a particular consumable. And that drives down the prices. You become much more powerful in negotiating prices if you can all get together. One of the biggest problems, and again, there's some amazing work that's been done, for example, by Chai on this, who have really innovated in the pool procurement medicine space. But we've also seen pool procurement as well for radiotherapy. If you can come together as large groups with common needs, you've got a lot more power to negotiate prices with individual suppliers. And more importantly, one of the problems with suppliers, whether it's essential medicines or other sorts of consumables, is if the market is too small, if you're trying to negotiate on a center by center basis, it's often it's just not worthwhile for the supplier to come to attend a deal with you. They don't want to contract with you because the volumes are too small and the margins are therefore too small. So pooled procurement is one way of getting around this. But I speak very easily about something that's actually a very complicated and complex subject. There's a lot of law involved in this, there's a lot of economics in this, there's a lot of business work in this. Again, it's one of those areas of research and expertise in the cancer area that's really quite thin and really needs to be bolstered. And here we're talking about the second translational gap is you've got the Essential Cancer Medicines list - how on Earth do you deliver that in an equitable and affordable manner to population X and country Y? That is in of itself a research question, that falls under the political economy of cancer in terms of research, but again, also falls out with most research funding organizations who don't quite know how to handle supporting this sort of research and capacity building. But as you can see, absolutely crucial. Great. You've invented the drug, you've invented the new surgical technique, or the new form of radiotherapy. It delivers clinically meaningful benefits. So how on Earth do you embed that in a sustainable manner in a health system? And that is a big missing gap in the global research agenda. Pat Loehrer: You can have all the drugs and radiation equipment in the world, but if you don't have the healthcare professionals trained to give it, it's worthless. I think one statistic was that there's 176 physicians in the United States for every one in Uganda. And how do you deliver cancer care by trained oncologists? It's getting more and more complex for us, too. But this has been just a wonderful discussion. Just as a quick question, though, Richard, Dave mentioned his book. Anything you're reading right now or anything of interest? Richard Sullivan: Yeah, yes, I've just started reading a fascinating book called Dadland by Keggie Carew. And it's fascinating because this is a marvelous piece of work, actually. And this is a daughter trying to make sense of her father's life. And she really sort of spends years patiently collecting all these details of her father's life and growing up with it. And she sort of takes, juxtaposes– when she starts the book, he's got dementia. But this is a man who in his early days was in Jedburgh, was a Special Operations executive, fought behind enemy lines in France in D-Day, went to the Far East in Burma. And there's this extraordinary pathos and sensitivity in this book about watching his decline with dementia, as she puts it, as he slowly disconnects from reality and then he disconnects from himself, and trying to make sense of it with the individual he once was and the kind of individual. And through that, she gets to explore all the kind of boxes of letters and things that were all stuck in the attic. Memento mori, essentially, of his time in Burma and France. But it's very, very touching, and I would really recommend your listeners to read it because it unpacks dementia in a way I've never seen a book unpack before in terms of the impact it makes to an individual. And it asks that question about - what makes you you? And when this father, he dies, is he still the same man who jumped out of airplanes in the middle of the night in France? Is he still the same man as he was in Burma? It's very touching. It's one of the most impressive books of exploration into human nature and an identity that I've read for a long time. So, yeah, Dadland, excellent. Pat Loehrer: I'll get it. Dave Johnson: Absolutely. Sounds great. Well, that's all the time we have for today, and I want to thank Richard Sullivan so much for joining Pat and me. This has been a fascinating conversation and you're to be congratulated on all of your many accomplishments and all the things that I'm sure you'll do in the future. I want to take the opportunity to thank our listeners for tuning in to Oncology, etc. This is an ASCO Educational podcast where we'll talk about almost anything and everything. So if you have an idea for a topic or a guest you'd like to hear on our show, please email us at 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.

Diffuse Large B-Cell Lymphoma or DLBCL is the most common type of lymphoma. Much progress has been made in treatment of the disease lately, particularly with emergence of CAR T-cell therapy, but not all patients are benefiting from it. This episode of Cancer Topics features Drs. Loretta Nastoupil and Chijioke Nze exploring treatment approaches for two cases of refractory DLBCL: a 60-year-old man with no comorbidities (1:30) and a 39-year-old woman with HIV (18:35). The guests also discuss improving patient access to CAR T-cell therapy and managing its toxicities (10:35), as well as emerging therapies for DLBCL (14:30). To learn more about management of refractory DLBCL, check out the ASCO course linked bellow. Guest Disclosures:Loretta Nastoupil, MD: Honoraria – Gilead Sciences, Novartis, Bayer, Janssen Oncology, TG Therapeutics, Bristol-Myers Squibb, ADC Therapeuitcs, Morphosys, Epizyme, Genmab, Takeda, Genentech/Roche; Research Funding – Janssen Biotech, Celgene, Genentech/Roche, Epizyme, Novartis, IgM Biosciences, Caribou Biosciences, Gilead Sciences, Allogene Therapeutics, Takeda Chijioke Nze, MD, MPH: No Relationships to Disclose Resources: ASCO Course: Second-line Therapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma (Free to Full and Allied ASCO Members) ASCO Podcast: Cancer Topics - New Therapies for Lymphoma (Part 1) ASCO Guideline: Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor (CAR) T-Cell Therapy ASCO Article: Navigating the Evolving Treatment Landscape of Diffuse Large B-Cell Lymphoma If you liked this episode, please follow the show. To explore other educational content, including courses, visit education.asco.org. Contact us at education@asco.org. TRANSCRIPT The disclosures for guests on this podcast can be found in the show notes. Dr. Loretta Nastoupil: So, I do have optimism that as we have more and more treatment options entering into the treatment landscape, we'll have fewer patients that are experiencing a refractory disease, and potentially succumbing to the lymphoma. Hello, my name is Dr. Loretta Nastoupil, I'm an Associate Professor and Deputy Chair of the Department of Lymphoma and Myeloma, at the University of Texas MD Anderson Cancer Center. Welcome to this ASCO Education podcast episode. It's my pleasure to welcome Dr. Chijioke Nze. Dr. Chijioke Nze: Hello, everyone. I'm Dr. Chijioke Nze, a Hematology/Oncology fellow at MD Anderson, I'll be co-hosting this episode with Dr. Nastoupil. Dr. Loretta Nastoupil: We've seen notable advances in diffuse large B-cell lymphoma research lately, with novel treatments including CAR T-cell therapy, offering the prospect of long-term remission for some patients, yet many patients are not even receiving second-line or later therapy, and even fewer are treated beyond the second line. How do you approach a patient with refractory diffuse large B-cell lymphoma? In today's episode, we'll explore strategies for management of refractory diffuse large B-cell lymphoma through two patient cases. So, Dr. Nze, walk us through our first case. Dr. Chijioke Nze: Our first case is Frank. Frank is 60 years old and has no comorbidities. He presented with severe back pain in September 2021, and was evaluated locally. He had a CT scan that showed retroperitoneal mass, prompting further evaluation. He had a biopsy of the left retroperitoneal mass in November 2021, which was consistent with diffuse large B-cell, germinal center B-cell of phenotype Ki-67 of 90%. He had a subsequent PET-CT scan, which showed a large conglomerate, and invasive left retroperitoneal hypermetabolic mass with satellite nodularity and contiguous bulky retroperitoneal adenopathy. He had bulky, FDG-avid metastatic retrocrural and intrathoracic adenopathy as well. He was treated with R-CHOP for six cycles, and at the end, achieved complete remission. He had a PET-CT a year later that showed new and worsening intensely FDG-avid abdominal adenopathy. This was new from a PET scan he'd had in January 2022 of the same year. He had a biopsy of this retroperitoneal adenopathy, which was consistent with relapsed diffuse large B-cell germinal center phenotype, also Ki-67 of 90%. Locally, he was treated with ICE, times five cycles, and had a follow-up CT scan at the end, which showed persistent bulky nodal disease with periaortic regional nodes with double 5, consistent with persistent disease. He also was found to have new and more conspicuous nodes in other areas as well. He presented for his first visit at MD Anderson in September 2022. Dr. Nastoupil, when you see a patient like this coming into your clinic, what's your typical approach? Dr. Loretta Nastoupil: For a diffuse large B-cell lymphoma, we are always hoping for cure with frontline rituximab, containing anthracycline-based chemotherapy. And so, it's always a gross disappointment when patients experience relapse. The timing of that relapse right now informs our current approach. And the reason I mention that, is because there have been three large randomized studies conducted and reported out just in the last year demonstrating that CAR T-cell therapy is the preferred option for patients who experience either primary refractory disease, or relapse within 12 months. And that is because they resulted in better outcomes than standard salvage-based chemotherapy and high-dose therapy autotransplant in the setting of chemosensitive disease. I have to acknowledge, of the three studies that were done, two were positive trials, so that's why currently, we have axi-cel or Axicabtagene ciloleucel, or Lisocabtagene maraleucel, and not tisa-cel or Tisagenlecleucel, as CAR T-cell therapy options. And again, that's because two of the three studies were positive trials. Now, the challenge is why would we have two positive studies in one negative trial? There are a lot of caveats to how those studies were conducted, but I think one of the biggest important lessons to be gained is that if you're going to consider CAR T for these high-risk patients, you want to do it as soon as possible, because that delay from identifying CAR T as a preferred option to actually infusing cells in a disease-- in a case particularly like this, where patients may have bulky, aggressively-behaving disease - that prolonged time may actually have an impact on outcomes. Dr. Chijioke Nze: Excellent. Thank you. So, you've mentioned he had an early relapse. How would you define early relapse in this patient population? Dr. Loretta Nastoupil: Thinking back to how we've been approaching diffuse large B-cell lymphoma over the last two decades, the PARMA study, which was done prior to Rituximab, suggested that for patients who had chemosensitive disease to a platinum-based salvage chemotherapy, which generally, was at least a partial response on CT, if they went on to high-dose therapy autologous stem cell transplant, 50-60% of those patients could anticipate cure. Whereas for the folks who continued on salvage chemotherapy, 10-20% of those patients had favorable outcome. So, we generally do try salvage-based chemotherapy, and for patients with chemosensitive disease, go on to high-dose therapy autotransplant. However, in the modern era where we've approached patients who've had rituximab as part of their frontline therapy, at least two studies - the ORCHARD study, and the CORAL study suggested that only 20% of patients who relapse in the post-rituximab era, particularly within 12 months, were successfully salvaged with platinum-based chemotherapy and high-dose therapy autologous stem cell transplant. Now, fortunately for patients who fail salvage, we have had CAR T-cell therapy as an option based off of three pivotal phase II studies, demonstrating about 40% of patients could anticipate a cure with CAR T-cell therapy. So, it only made sense to try and move that therapy up into second line, and the preferred population was those that had progressed within 12 months of frontline rituximab and anthracycline-based chemo. Now, to qualify for those studies, patients had to be considered fit for the control arm, which was salvage and auto transplant. Nonetheless, I do think for a patient like this, who's 60, without any other significant comorbidities, whose biggest challenge to longevity of life is his aggressive lymphoma, CAR T-cell therapy should be considered as soon as possible for this patient. Dr. Chijioke Nze: Is there still a role for high-dose therapy and autologous transplant in the new era, given the efficacy shown with CAR T-cell therapy? Dr. Loretta Nastoupil: I think there is. And the reason why I say that is, the trials that were done really did focus on the highest-risk patients, which were those with primary refractory disease or those who progress within 12 months of frontline. Now, there are patients that will have later relapse. And so, I do think for those patients, particularly those who are young and otherwise fit, should be approached first with a platinum-based salvage chemotherapy, in the setting of chemosensitive disease, proceed onto high-dose therapy and autologous stem cell transplant. Now, what do we do for those patients who have a late relapse but are otherwise older, or who have comorbidities that would make them suboptimal candidates for the high-dose therapy preceding stem cell transplant? I have a couple other options for those patients - so, there was a trial done with liso-cel for patients who were otherwise older, or not fit for intensive therapy. It's a single-arm phase II without a randomized comparison, but also demonstrated that liso-cel in second-line, later relapsed patients who are not fit for intensive therapy, resulted in comparable outcomes to what we would anticipate on that third-line or later setting. We also have other non-CAR T-cell therapy options, such as tafasitamab, which is a naked CD19 antibody, which has been combined with lenalidomide in the L-MIND study, again, for patients without primary refractory disease and who would not be appropriate candidates for intensive therapy. So, I do think we have alternative options, it's just when we look at the totality of the data right now, my conclusion is that CAR T-cell therapy, particularly for high-risk patients, is the most likely chance to result in cure. Dr. Chijioke Nze: Excellent. In a patient who we are considering CAR T-cell therapy, what are some of the short-term and long-term consequences, or toxicities that we should worry about? Dr. Loretta Nastoupil: One of the challenges right now with CAR T, and why it's still only available in specialized centers, is the acute toxicity, which is really a derivative of its mechanism of action. We take patients' own T-cells, we use a viral vector to introduce extracellular receptor, but also a co-stimulatory molecule. So, once these cells engage their antigen, sort of prime to react to that, and that can lead to pretty rapid T-cell expansion, release of cytokines, recruitment of other inflammatory cells to that tumor bed, and as a result, a large portion of patients can anticipate to experience cytokine release syndrome, which again, is the result of the activation of these T-cells, the expansion and the recruitment of other inflammatory cells. Fortunately, for most patients, this results in fever alone that can be managed with supportive measures. Occasionally, they'll have concomitant hypoxia or hypotension, and unfortunately, few patients will have significant or severe toxicity. The other toxicity that's less easily manageable or less predictable is the neurotoxicity that can vary according to patient-specific characteristics, such as age, and the amount of tumor burden, their performance status going into CAR, but even more importantly, the construct that's utilized, with highest rates of neurotoxicity associated with axi-cel. Again, likely speaking to its construct and the CD28 costimulatory domain that is unique to axi-cel. As a result of these acute toxicities, patients are required to stay within two hours of their treating center for the first four weeks, and they're also discouraged from operating heavy machinery, such as driving, for the first eight weeks following CAR T. So, I do you think this creates some barriers to access to this therapy, particularly the patients that are treated in community settings that may reside long distances from these certified CAR centers. Dr. Chijioke Nze: So, you mentioned that obviously, given the specialized care needed for the CAR T therapy, that they're kind of localized in certain sites. What are some of these issues with access that you're noticing both in the logistics of giving CAR T, and also in patient access? Dr. Loretta Nastoupil: I'm hoping we're going to address one of those issues right now, which is, education and awareness, because we've had these three randomized studies, and two being positive readouts just in the last year. It's important to get the message out that CAR T-cell therapy for high-risk early relapsed refractory large cell lymphoma patients can result in a significant improvement in event-free survival and progression-free survival over the standard of care. And so, being aware that this therapy can result in more favorable outcomes is step one. Step two is, we have to ensure that there are minimal barriers to getting those patients into these treating centers as quickly as possible. So, recognizing who delivers the care - is it your traditional stem cell transplant physician? Is it a lymphoma doctor? What centers are certified? Some of these issues can be addressed with quick internet searches. So, for instance, in our center, we have a 1-800 number for anyone who's interested in CAR T-cell therapy that connects them directly to a CAR T coordinator who can help them understand do they meet the FDA-approved indication? Would they be interested in seeking consult? And we try and prioritize getting those patients in the door as soon as possible since time likely does have an impact on outcomes. And then, partnering with our community oncologist - you're going to be the primary oncologist for these patients leading up to CAR, and then after that four-week window, when we're keeping the patients in close proximity to our centers, we often send them back. And so, making sure that they're comfortable knowing what potential late toxicities to be on the lookout for, which include B-cell aplasia and risk for infection, or prolonged cytopenias, beyond just lymphopenia. And so again, there's a need for education and partnering with our community sites to make sure that there is successful handoff of these patients back after they've completed the monitoring for the acute toxicity. And then, really trying to explore opportunities to utilize some of the better tolerated CAR T, such as liso-cel, in your non-traditional academic centers. Those that are equipped to handle phase I studies or stem cell transplant, for instance, may not be affiliated with the university. So, I think those are all types of strategies that could be employed to try and improve access for patients. Dr. Chijioke Nze: And then, you mentioned the liso-cel, but in some of the toxicities, are there ways of predicting which patients will do better or worse? Are there ways to reduce toxicities? And is there any hope for things such as outpatient administration of CAR T? Dr. Loretta Nastoupil: So, my answer today may improve over time as we get larger numbers and more experience, but what we currently understand is that the patient performance status, their degree of tumor, how quickly that tumor is increasing, LDH and some inflammatory markers such as CRP or ferritin pretreatment can provide some insight into a higher risk of toxicity. And then obviously, the construct that's utilized. Again, axi-cel has higher rates of neurotoxicity. All will have some form of cytokine release syndrome, generally speaking, but rates of grade three or higher are quite infrequent, particularly with liso-cel and tisa-cel. So, it's multifactorial. That then raises the question, can we do anything to alter those modifiable risk factors? Can we reduce the disease burden? Can we improve the performance status? Can we do anything to reduce the inflammatory markers pre-treatment? And so, those are strategies that are being discussed, and I think in general, as we get more effective therapies that enter into the treatment landscape, it's probably some of the best ways to try and reduce some of those risk factors. Dr. Chijioke Nze: Rounding that up, are there any exciting developments or things to look out for, for exciting therapies in the relapse setting? Dr. Loretta Nastoupil: A couple of things beyond CAR T that I think we should all be aware of and anticipate to be in our toolkit relatively soon; probably, one of the most exciting, is the development of the bispecific antibodies. So, another challenge with CAR T is the requirement to collect these patients' own T-cells and send them off to a central manufacturing site, and the turnaround time can be anywhere from 3-4 weeks. And again, in a situation where you have an aggressive disease, that can be a long time to wait. And so, is there any treatments that are more readily available, that again, will be effective at reducing disease burden? And so, by specifics kind of fit those unmet needs to some extent - you have essentially two heads; one head is going to bind the endogenous T-cells that eliminates the need to leukapherese these patients and manufacture, and then the other head is going to generally engage CD20, which we know is an effective targeted antigen, particularly in B-cell lymphomas. And there are a number that are under development. We saw preliminary phase II data with glofitamab, epcoritamab, as well as combination strategies with mosunetuzumab. So, I do have optimism that the bispecific antibodies will potentially enter into the treatment landscape. I anticipate they'll probably be used first post-CAR T, but will likely move their way into earlier lines of therapy. I've already mentioned tafasitamab in combination with lenalidomide, which is an effective non-chemotherapy option. We have antibody-drug conjugates, such as Loncastuximab, which is a CD19 antibody-drug conjugate. It's essentially targeted delivery of chemotherapy, and it looks to have a pretty promising activity as a single agent in that third-line or later space, and then polatuzumab, which is a CD79b antibody drug conjugate, in the relapse setting has been combined with bendamustine and rituximab, but also demonstrated significant improvement in the frontline setting in the POLARIS study where vincristine was replaced with polatuzumab. So, I do have optimism that as we have more and more treatment options entering into the treatment landscape, we'll have fewer patients that are experiencing refractory disease, and potentially succumbing to the lymphoma. Dr. Chijioke Nze: And then, one additional question: How do you approach a patient who is not quite as fit, in thinking about what their options are for later-line therapies? You already mentioned some of these, but which of those would you prioritize in this setting? Dr. Loretta Nastoupil: Again, as we get more experience, we develop skills that help us sort of navigate all these different options. In my practice, if I'm even considering CAR T, I'm going to delay bendamustine until after I've collected those cells. I think that's one caveat that-- we do get nervous about the quality of those autologous CAR Ts if they're generated in someone who's had recent exposure to bendamustine. So, that may help me sequence that later on. We have questions right now about what's the optimal sequencing of CD19-directed therapy because we have several options beyond just CAR T-- As I mentioned, we have Lonca, we've got tafasitamab and lenalidomide. Currently, we don't have prospective data that really informs that question, and there's a number of research studies underway to try and help us understand if there is a preferred sequence, or even if it matters how we handle CD19 targeting. For my older, frailer patients where I'm really worried, they're not going to be able to tolerate something like liso-cel, or they're not going to be able to have that caregiver, and they're uncomfortable relocating to an area where CAR T might be available, my general approach right now is to consider tafasitamab and lenalidomide first in that relapse setting, followed by either Lonca or Pola-BR. Selinexor is another option. It's an oral agent, though again, in my opinion, if we look at the totality of the data, may be less effective than the other options. So, I might reserve that as a last option for someone, again, with relapsed/refractory large cell. Dr. Chijioke Nze: Excellent. Thank you. This has been very helpful. Dr. Loretta Nastoupil: All right. So, Dr. Nze, now I'm going to turn the table and ask you some questions. I'm going to change this up a little bit - she's now a 39-year-old female. She has significant comorbidities. She has HIV, and again, large cell lymphoma. So, let me walk you through her case, and then we'll discuss some of the challenges, again, in a very different scenario, albeit a similar disease. So, our female is, I mentioned 39, pre-existing HIV, she's treated frontline with six cycles of R-CHOP and intrathecal methotrexate for CNS prophylaxis. Because of her comorbidities, again, not well controlled HIV, she also has a poor functional status at the time of relapse. This was a couple years ago, and CAR T was not an option in second line, though she is someone who had a relapse that was beyond 12 months. So, for her second-line approach, because of her comorbidities, she actually receives rituximab in combination with high-dose cytarabine, dexamethasone, and oxaliplatin for three cycles, and actually achieves a chemosensitive disease and is referred to our stem cell transplant colleagues. Unfortunately, at that time, due to comorbidities, she was deemed not to be an appropriate candidate for high-dose therapy, and she's been monitored for signs of relapse. Despite being in the minority, she actually does not have a recurrence of her lymphoma but has a number of other, again, challenges in regards to her comorbidity, including multiple infections, resulting in recurrent hospitalizations. And so, it's always been a challenge for me in being intimately involved in her case, deciding when she's presenting, how alarmed to be about recurrent lymphoma versus infection, and how I might approach her in the setting of relapsed large cell lymphoma. So, what role does prior type and response to therapy play in treatment selection at your next line of treatment? Dr. Chijioke Nze: I think in this patient, it sounds like she got one adequate therapy on and the initial presentation with R-CHOP, and then with IT chemotherapy as well. She looked like she had a good response. I think the fact that she achieved a complete response and the duration of her response, lets me know that she likely has chemosensitive disease. This, in turn, helps me to pick what to do next. As you mentioned previously, we know how efficacious the CAR T therapy is, but in someone like her who had a long duration, trying salvage therapy and proceeding to autologous transplant might make sense. I'd be interested in your thoughts. Dr. Loretta Nastoupil: Yeah, I agree. And I think part of the challenge, particularly when we're facing patients with HIV, they're often excluded from prospective studies. And so, we're often in a scenario where we may not have the wealth of data to inform our treatment decision. But I do think in general, comorbidities play a major role-- we're navigating treatment options. Because again, traditionally, we've used intensive chemotherapy as our mainstay of treatment, and there are clear criteria that patients generally should meet that help us predict how likely they are to have significant or severe toxicity from high-dose therapy. And this is a prime example of even though she was young, her comorbidity made her a poor candidate for intensive therapy. I think the other sort of non-clinical factors that we sometimes take into consideration, because CAR T was approved off of single-arm phase II studies, again, none of which would've included someone like her, because of her HIV status, how do we extrapolate-- for instance, if she had relapsed in that third-line space, and suggesting that she did not have significant infection or other significant comorbidities, do we have experience to proceed with an autologous CAR in that setting? So, again, there've been a few cases where we have case reports where people have reported on their standard of care outcomes, particularly with CAR T in patients with active HIV disease, but one of the concerns I have in these scenarios is very selected. If you have active infection, that can make the acute toxicity with CAR significantly worse. And so again, we're trying to navigate a sort of limited data zone to try and help her and choose the right therapy. Again, you've met this patient with me, you helped care for her for some time, and you have a unique experience of also practicing in a county hospital where comorbidities, particularly, like HIV, can be much more common. What is your perception regarding barriers to accessing CAR T as it pertains to social factors, clinical factors, and again, this is a case that highlights some of those issues. Dr. Chijioke Nze: You mentioned at first that she had uncontrolled HIV. So, I think which, one, speaks to her treatment reference of her non-malignancy-related diseases, and trying to get that under control would be one of the first things I could think about. Thinking about how her care is managed and what kind of support she has are very important for us to think about as well. The other thing that's very important is, a lot of patients who we're seeing in the community may not have access to such specialized centers such as MD Anderson, where patients do have access to clinical trials and CAR T therapy. So, patients who are unlike her, who might qualify, may not actually be able to get these therapies as well. Part of the reason is, it can be insurance status, which is what we see in a lot of our patients. So, a barrier to get into the door. And then too barriers, lack of social support can be a big issue as well. And then there's also a big push in the community to improve the trust and awareness of these novel therapies, as you've mentioned. So, in a lot of the community practice, some of the community practitioners may not be comfortable with these, and a lot of the patients may not have heard of these new technologies, and also want to defer trying new therapies before having other people try new therapies before they consider them themselves. I think all these things present specific significant barriers to patients in the community. One, their ability to adhere to care, two, their insurance and their ability to get care and the financial toxicities associated with that. And then third, really understanding the options that are available. Dr. Loretta Nastoupil: And again, just to try and illustrate a couple other points. You know, we use a case here, which is a real case, with significant comorbidities such as HIV, which again, is something that is not frequently encountered, and will have a large impact on treatment selection. What if I just told you this patient has comorbidities, but she has moderate type-2 diabetes, and as a result, she has mild renal insufficiency, ejection fraction is actually adequate, would you have done anything different in this case? Dr. Chijioke Nze: No. I think in this particular case, I do think the fact that she did have a good response for a long duration of time, and did seem to have chemosensitive disease, I would probably still have tried a salvage therapy and autologous transplant in this patient. In the event that she was refractory, or had early relapse, and in that case, I would consider her to not be chemosensitive and would definitely have sought some more active therapies such as CAR T cell therapy through available products. Dr. Loretta Nastoupil: And then one last question for you: What if we just changed her age and we made her 79, but no other significant comorbidities, how would that have impacted your approach? Dr. Chijioke Nze: I'm going to turn that one over to you, I'm not exactly sure how I would treat with older patient with the same disease. Dr. Loretta Nastoupil: That's fair. So, if you have an older patient who has a late relapse, but not necessarily someone you would consider appropriate for salvage chemotherapy and high-dose therapy, then I think tafasitamab and lenalidomide would be probably my first choice in that setting, just based off of the L-MIND study. Dr. Chijioke Nze: Thank you, Dr. Nastoupil, for a great discussion of the management of diffuse large B-cell lymphoma. And thank you to all our listeners. We appreciate you tuning in to this episode of the ASCO Educational podcast. 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.

Battling cancer takes place in many parts of the world and our next guest has led initiatives to do just that. In Part One of this Oncology, Etc. Podcast episode, Dr. Richard Sullivan, Professor of Cancer and Global Health at King's College London, shares with us his intriguing life trajectory, encompassing a childhood in various parts of the world, aspirations for a veterinary career that turned to basic science, medicine, health policy (4:27), and even a long-term stint with the British Army Intelligence (12:22). Dr. Sullivan, who served as Director of Cancer Research UK for nearly a decade also discusses traits he looks for in a cancer investigator (19:21), and how to be happy (21:16)! Guest Disclosures Dr. Richard Sullivan: Honoraria – Pfizer; Consulting or Advisory Role – Pfizer Dr. David Johnson: Consulting or Advisory Role – Merck, Pfizer, Aileron Therapeutics, Boston University Dr. Patrick Loehrer: Research Funding – Novartis, Lilly Foundation, Taiho Pharmaceutical If you liked this episode, please follow. To explore other episodes, as well as courses visit https://education.asco.org. Contact us at education@asco.org. TRANSCRIPT Pat Loehrer: Hi, I'm Pat Loehrer. I'm director of the Center of Global Oncology and Health Equity at Indiana University Cancer Center. Dave Johnson: And I'm Dave Johnson at UT Southwestern in Dallas, Texas. Pat Loehrer: And this is Oncology, Etc. Dave, what book have you read this last month? Dave Johnson: I have one I wanted to recommend to you. It's very interesting. It's by Steven Johnson, not of the syndrome fame. It's entitled Extra Life: A Short History of Living Longer. You may have heard of this because PBS made a special documentary about this particular book. But in it, Johnson talks about the remarkable increase in human lifespan, especially over the 20th century, and the various factors that contributed to increased years of life from on average in the United States of about 48-49 in 1900 to just about 80 in the year 2000. So that beats anything in the history of mankind before. And he has a chapter about each of the factors that contribute to this, and some of which I think we all recognize. Things like antibiotics playing a role, but some of the things that I hadn't thought about were improved drug regulation and the development of randomized controlled trials, which all of us have participated in. How important that is. He also talked about, at least in the United States, the importance of automotive safety. And I'm sure some of us on this podcast are old enough to remember cars that did not have safety belts and certainly not other safety maneuvers that have really improved lifespan in that regard. So I found it a fascinating book. I think our listeners who are interested in medical history would also enjoy this text. Pat Loehrer: Did he mention this podcast? Dave Johnson: No, actually it wasn't mentioned, and I thought that was a tremendous oversight. So, I've sent him a letter and recommended that he add it. Pat Loehrer: We may not live longer, but it just seems like we're living longer. When you listen to this podcast, time stands still. Pat Loehrer: Well, it's my real great pleasure to introduce our interviewee today, Richard Sullivan. I met Richard several years ago through the late Professor Peter Boyle in Leon, and it's one of the greatest highlights of my life to be able to know Richard. Professor Richard Sullivan's Research Group studies health systems and particularly chronic disease policy and the impact of conflict on health. He's a professor of cancer and Global Health at King's College in London and director of the Institute of Cancer Policy and Co-director of Conflict and Health Research Group. As well as holding a number of visiting chairs, Richard is an NCD advisor to the WHO, a civil military advisor to the Save the Children Foundation, and a member of the National Cancer Grid of India. His research focuses on global cancer policy and planning and health system strengthening, particularly in conflict ecosystems. He's principal investigative research programs ranging from automated radiotherapy planning for low resource settings to the use of augmented or virtual reality for cancer surgery through the political economy to build affordable equitable cancer control plans around the world. Richard has led more Lancet Oncology commissions than anyone else. In fact, Lancet is talking about calling it the Sullivan Commissions. He's led five Lancet Oncology commissions and worked on four others. He's currently co-leading the Lancet Oncology Commission on the Future of Cancer Research in Europe and Cancer Care and Conflict in the conflict systems. His research teams have had major programs in capacity building in conflict regions across the Middle East and North Africa. He's done studies on the basic packages of health services in Afghanistan and worked in Pakistan, Syria, and the Democratic Republic of Congo. He's been a member of the British Army, intelligence and security, and in that capacity he's worked many years in biosecurity and counterterrorism issues. I think in some ways, this is the most interesting man in the world, and it's our pleasure today to have Richard join us. Richard, thank you for coming. Richard Sullivan: Pat, Dave, you're really too kind. Marvelous to be with you. Thank you for the invitation. Pat Loehrer: Can you tell us a little about your upbringing and early life before you became Dr. James Bond? Richard Sullivan: I'm not sure that's anywhere close to the truth, sadly. But, yeah, I have had a very interesting, eclectic life. I was born in Aden just on the cusp of where the British Aden Protectorate met a country which actually no longer exists, the People's Democratic Republic of Yemen. Because after the British left Aden, essentially the East Germans, and what was then the Soviet Union took over southern Yemen. So I was born in a very unusual part of the world, which sadly, since then has just deteriorated. I spent many years of my life with my parents, who were in the diplomatic service and doing other things, wandering around the globe, mainly in the Middle East and East Africa. We spent quite a lot of time, strangely enough, we washed up on the shores in the USA once as well. Dayton, Ohio, and eventually- Pat Loehrer: Not to interrupt you, Richard, there are no shores in Dayton, Ohio. So just correct you there. Richard Sullivan: That is so true. My memory - cornfields everywhere. I had a wonderful dog then, that's how I remember it so well. And I didn't really come back to the UK until, oh, gosh, I was nearly 10-11 years old. So, coming back to the UK was actually a bit of a culture shock for me. And then relatively classical in terms of the UK, sort of minor public school and then into medical school. In the old days when it was in the 80's. I had a fabulous childhood, going all over the place, seeing lots of things, being exposed to lots of different cultures. I think it remained with me all my life. I never really feel a foreigner in a foreign land. That's nice. That's really unique and it's been marvelous being able to tie in the passion for global health with my upbringing as well. So, yeah, I had a wonderful childhood. Dave Johnson: Would you mind expanding on your medical training, Richard? Tell us a little bit about that. Richard Sullivan: Yeah, so when I, when I went to medical school in the UK, we were still running the old system. And by the old system, I mean, you know, these small medical schools with entries of, you know, 70, 80 individuals, particularly in London, you had that St. Mary's Hospital Medical School, which is where I went, Charing Cross, Guy's, St. Thomas', and they were all individual medical schools. Now, most of these now have merged together into these super medical schools. But certainly when I went to medical school, I'll be absolutely honest with you, I wanted to be a vet to begin with, but actually discovered I wasn't bright enough to be a vet. It was harder to become a vet than it was to become a doctor. In my day going into medicine, and people listening to this, or some people who understand the A level system in the UK will recognize if you're offered a BCD, that's quite low grades to get into medical school. So I went to Mary's, to be absolutely honest with you, because I heard that they took people that played rugby, and I came from a rugby-playing school. And sure enough, 90% of the interview was based on my rugby prowess, and that was St. Mary's Hospital Medical School. So it was wonderful. And we'd already had people going there who were big rugby players. And again, it was, I remember thinking to myself, am I making the right decision here? But it was interesting, as soon as I went into medical school, I realized that was the life for me. I had done myself a favor by not going into veterinary science, which I would have been awful at. We had six years of very, very intensive pre-medicine, the classical medical rotations, and then that movement into the old schools of pre registration house officers, registrar jobs. We were quite an early stage. I kind of slightly went off-piste and started doing more academic work. Interestingly, most of my academic early days academic work was not in health policy and research. It was actually in very hard core cell signaling. So my doctorate was in biochemistry, and we worked on small GTPases, calcium-sensing proteins. There were some really extraordinary heady days, and I'm talking here about the early nineties and the mid-nineties of tremendous discovery, real innovation. I was at UCL at the time, but mixing and matching that up with a sort of surgical training, and again, surgical training in those days was pretty classical. You went into your general surgery, then sort of specialized. It was really, really interesting but it was full on. I mean, you spent your entire life working. Morning to night so these were the days of 100 hours week rotations. You were doing one in twos, one in threes. That's every other night and every other weekend on call. It was incredibly intense, but there was a lot more diversity and plasticity in those days. You could dip in and out of medicine because of the way you were chosen and how you were recruited. So it suited my personality because I liked moving around and doing different things and that sort of took me through, really until the late 1990s. Pat Loehrer: You became a urologist, right? Richard Sullivan: That's right. Exactly. So I trained up until the late 1990s, it was all pretty standard, I would say. And then I decided I was bored and moved into the pharmaceutical industry and I went to work in for Merck Damstadt at the time, which was relatively small. I was going to say family owned, but it was quite family-owned pharmaceutical company that was just moving into oncology. And because I'd done the background in cell signaling and cell signaling was really the backbone of the new era of targeted therapies, this seemed like a great move. To be absolutely blunt with you, I didn't last very long, less than a couple of years, I think, mainly because I just found the whole environment way too constraining. But what it did provide me with was a springboard to meet the wonderful late Gordon McVie, who I met at a conference. And he said to me, 'You're absolutely wasting your time and life by staying in the pharmaceutical industry. Why don't you come out, get an academic job at University College London and become my head of clinical programs?" - for what was then the Cancer Research Campaign. This Cancer Research Campaign and the Imperial Cancer Research Fund were the forerunners of Cancer Research UK. So, you know, this was an offer that was too good to be true. So I jumped ship immediately, went back into academic life and joined CRC. And really the next ten years was this extraordinary blossoming of the merger of CRC with the Imperial College Research Fund, the creation of Cancer Research UK, and that was Paul Nurse, and obviously Gordon and me, bringing that all together. And it was the heady days of that resurgence of cancer, the importance of cancer care and research in the UK. And coupled with that, of course, it was the blossoming of my interest, really then into the global health aspects of cancer, which really, Gordon, people like you mentioned already, the late, wonderful Peter Boyle, all those individuals were already engaged in and they were the ones that really kind of catapulted me into a more international scene. Dave Johnson: Did you know Dr. McVie before you met him at this conference, or was it just a chance encounter? Richard Sullivan: No, he actually met me via John Mendelson, because John had picked up a paper I'd been writing on basically the very early versions of Rituximab that we were working on and we were looking for pharmacodynamic endpoints. And of course, one of the things I noticed with the patients is they were getting all these skin rashes on their faces, and I thought, that's terrific. Just seemed to be the skin rashes seemed to be together with those individuals that had better responses. And I remember writing this paper for Signal, which was a kind of relatively minor journal, and I think it was John Mendelson who picked it up and must have mentioned something to Gordon. Gordon hunted me out down at a particular conference, said, "How on earth do you know about this, that you're not anything more than a surgeon?" He was absolutely right about, goodness sake, what do you know about pharmacodynamic endpoints, and I kind of had to sort of confess that I've gone kind of slightly off-piste by doing biochemistry and cells signaling and working with these extraordinary people. And that's how I essentially met Gordon. He was very good for spotting slightly unusual, eclectic human beings. Pat Loehrer: I'm very curious about the intersection of your work and how you got into the British Army and Intelligence with medicine and how that even may continue even today. So explain that story, that part of your life a little bit to us. Richard Sullivan: Yeah, it was very early on, as I went into medical school, one of the key concerns was making money. I looked around for ways of doing something interesting to make money, and most of the jobs on offer were bar jobs, et cetera. Then I thought, what about the Territorial Army, which, in the early days of the 1980s, was, and still is, a very large component of the UK Armed Forces. So I actually joined the Royal Army Medical Corps, as you would expect for someone going into medicine. I thought, okay, I'll join the Royal Army Medical Corps, and I was a combat Medical Training Technician, et cetera. So I went along, signed up, and I think I was about three months into training when I was at a place called Kew Barracks and some chap came up to me and handed me a little bit of paper. It said "Intelligence Security Group" and gave a phone number. He said, "This is more your line of work. Why don't you give them a ring?" It was interesting because, in those early days, they were looking for analysts who could work on lots of different areas. In those days, most of the work was domestic.. Of course, there was counterterrorism with Northern Ireland, but there was also the Soviet Union, and the fallout from the Warsaw Pact, so they were still actively recruiting into that area. There are lots of details I can't talk about, but it was relatively, to begin with, quite hard work and low level. It was a lot of learning foreign equipment recognition. It was what we consider to be standard combat intelligence. But the more time you spend in it, the more interesting it gets. One of the areas they were looking to recruit into, which I didn't realize at the time but only later, was bioweapons and biosecurity. They needed people who understood biotechnology and the language of science, and who could be taught the language of infectious disease on top of that. That is quite a difficult combination to find. It's very easy to teach people trade craft and intelligence, it's very hard to teach them subject matter expertise. And they were really missing people who specialized in that area. It was interesting because it was still a relatively open domain. There was still a lot of work going on in the counterterrorism front with biological weapons, and a lot around the Verification of the Biological Weapons and Toxin Convention. And it was an interesting, and I'd almost say parallel life. But your medical knowledge and the scientific knowledge I had already gained and was gaining was what was being looked for. So that was very early on and it has expanded over the years. More and more now we talk about health security and intelligence so that goes beyond what you would consider classic medical intelligence or Armed Forces - this is more about putting together the disciplines of intelligence with the securitized issues of, for example Ebola. That is a classic example. The big outbreaks in West Africa, the DRC, these are sort of the classic security intelligence issues - even COVID 19 for example - and mostly around the world, what we've seen is the intelligence apparatus taking front and center in that, whether you're looking at states like South Korea, et cetera. So I've moved more into that, and we do a lot of work and research into this as well. So we look at, particularly now, how to improve human intelligence in this area, the pros and cons of signal intelligence collection. And we go as far as to kind of ask sort of deep ethical and moral issues, for example, about how far should these sorts of apparatus of state be applied to public good issues like health. Because at the end of the day, when you're talking about the armed forces security sector, their primary job is for defense of the realm. So applying them in other areas obviously comes with a whole load of moral and ethical challenges. So, yes, it's been a fascinating journey, which, as I said, it extends all the way back to the late 1980s. It's been both complementary and different. Dave Johnson: So, Richard, there's so many things in your resume that warrant exploration, but you served as Clinical Director of Cancer Research UK for nearly a decade. What was that experience like, and what accomplishment are you most proud of? Richard Sullivan: It was an enormous privilege. In your life, you always look at some jobs and you think, "How lucky I was to be there at that time with those people." I think, first of all, enormous respect for the people that ran both Cancer Research Campaign, Imperial Cancer Research Fund – I mean, Paul Nurse and Gordon McVeigh, Richard Treisman – I mean, some extraordinary people who were leading both of these charities. And so to be there at that moment when they both came together, but more importantly as well, they had this most amazing global network of literally the illuminati of cancer research, spanning from basic science all the way through to epidemiology, public health, health systems. And in those days, of course, those individuals would come on site visits to the UK to look at the different units and evaluate them. So you can imagine when you're bringing those sorts of individuals across, you get a chance to go out with them, go drinking, talk to them, learn about their research, and also learn about the extraordinary breadth of research that was there in the UK. So you're condensing almost a lifetime's worth of learning into a few years. It was an absolute privilege to have been able to serve the community like that. What I'm most proud of? Gosh, I like to think I suspect that most proud of trying to help a lot of the fellows get through to where they were going to actually get the most out of their careers. When I look back, there are lots and lots of names of people who started at a very early stage with funding from Cancer Research Campaign or the Imperial College Research Fund, who are now very, very senior professors and global research leaders. And I like to think that we did a little bit to help them along that way and also help to support individual research programs actually reach their full potential. Because I think research management and planning is often overlooked. People think of this as very transactional – it's not transactional. It's an incredibly important, serious discipline. It requires very careful handling to get the very best out of your research ecosystem. You've really, really got to get under the skin and really have a clear view of how you're going to help people. So I think that's what I'm most proud of – is the individuals who made it all the way through and now these great leaders out there. But it was also, let's be honest, it was halcyon days. Great innovations, great discoveries, new networks growing, incredible expansion of funding in the UK, in Europe, in the USA. They were very, very good days. And it was, as I said, it was a real privilege to be there almost at the center for nearly a decade. Dave Johnson: Let me follow up on that, if I may, just for a moment. You have had such an incredible influence. What characteristics do you think are most desired in a cancer investigator? What sorts of things do you look for, especially when you're thinking about funding someone? Richard Sullivan: Creativity. I think creativity is really important. We talk about the word innovation a lot, and it's an interesting engineering term, but creativity is that spark that you can see it in people, the way they talk about what they're doing. They have this really creative approach. And with that, I think you have to have the passion. Research careers are long and difficult, and I'd probably suggest there's probably more downs than there are ups, and you have to have that passion for it. And I think along with that passion is the belief in what you're doing – that first of all, you have that belief that actually drives you forward, that what you know you're doing is good work, and that you're really dedicated to it. But obviously, hand on heart, when you're looking at researchers, it's that passion and that creativity. I think it's a brave person to judge how any person's career or program is going to go. I don't think any of us are prophets. Even in our own land. We might be able to see slightly into the future, but there are so many elements that make up "success". It's funny when I look back and I think those who've been successful, it's people who've also been generally happy in their lives. They've found their careers in whatever shape or form, fulfilling, and they've generally been happy human beings, and they've managed to create a life around research which has given them meaning. Pat Loehrer: Richard, you have reinvented yourself a number of times – this transition of going from like a basic scientist, a surgeon, moving into public policy and global policy. Tell me a little bit about the journey that's been in terms of academics. How do you learn? What were the transition points in each of these things to get you now to be, as I mentioned before, kind of the key person for Lancet's commissions to somebody who was a rugby player? Richard Sullivan: I suppose if you're being mean, you say, he clearly gets bored easily. But it's not that. Actually, I'm not very instrumental about life either. I mean, there are many people you will meet who have got their lives and strategies mapped out. They know they're going to do X next year, Y the following year. And for me, it's never been like that. For me, it's that excitement, that creativity of working on new and interesting things, but also knowing when you've run out of road in a particular area, where it no longer gets you out of bed in the morning, where you no longer feel happy, where you no longer feel you're contributing. All of us talking today have the great privilege of having choice about our lives, about what direction our lives should take. And it's not a privilege one should squander lightly because many people do not have choices about their lives. It's all about chance. And having that choice to be able to move into different areas is really important because I said you can stick in the same thing because you think you have to. And you can become an unhappy, miserable human being. And that makes you a miserable researcher to be around. It makes you a terrible doctor. Probably makes you a terrible person, actually, generally, if you're having a miserable life. So finding new things, that really you're passionate about how you do it, there's no shortcut in this. It's hard work. Readily admit I went back to law school of economics, retaught myself lots of things. There are no shortcuts for. Deciding if you're going to a new area is learning, learning, practice, practice, practice, and just doing the hard work. I think that's an ethos that was probably drilled into us quite early anyway in medical school, because that's how you approach medicine. That's how you approach science when I was growing up. And it was that idea of humility that you can never have enough learning, you will always learn off other people. That's probably what drove me and how I've managed to change and as I say, who knows what the future is? I don't know. Maybe one day I'll think about doing a bit of poetry. Dave Johnson: Your comments about happiness and work resonate with Pat and me. I think we both feel like humor is really important for happiness and career success. And, you know, Osler once said, "The master word of medicine is work." You can't get around that. It is what it is. And I think you just reaffirmed that. Well, this concludes part one of our interview with Richard Sullivan, professor of Cancer and Global Health at King's College, London and director of the King's Institute of Cancer Policy and co-director of the Conflict and Health Research Group. In the second part of this episode, Professor Sullivan will speak about the progress of global health, especially in conflict areas, and the need for young people to enter into the world of oncology and oncology research. Thank you to all of our listeners for tuning into Oncology, Etc. This is an ASCO educational podcast where we will talk about just about anything and everything. So if you have an idea for a topic or a guest you would like us to interview, please email us at education@asco.org. Thank you again for listening. Thank you for listening to the ASCO Education podcast. To stay up to date with the latest episodes, please click subscribe. Let us know what you think by leaving a review. For more information, visit the Comprehensive Education Center at 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. 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.

Getting into oncology requires a lot of education and training. How does one deal with the success and stress of such a journey? In Part Two of this ASCO Education Podcast, moderator Dr. Aakash Desai – fellow at the Mayo Clinic along with guests Dr. Madison Conces – fellow at Cleveland Clinic, and Hematology/Oncology fellowship program directors Dr. Lori J. Rosenstein (Gundersen Health System) and Dr. Deepa Rangachari (Beth Israel Deaconess Medical Center) explore the past, present, and future of Oncology Training. They discuss the transition from training to clinical practice (1:02), how to stay current with new treatments and guidelines (6:39) and what oncology training should look like in the future (12:12). Resources: ASCO Education Podcast: Cancer Topics - Burnout in Oncology: Trainee Perspective ASCO Education Podcast: Cancer Topics – Career Paths in Oncology (Part 1) ASCO Education Podcast: Cancer Topics – Career Paths in Oncology (Part 2) If you liked this episode, please subscribe. Learn more at education.asco.org, or email us at education@asco.org. TRANSCRIPT Dr. Deepa Rangachari: I think really this idea of what I call work-life negotiation, is present very much during training, and one continues to be very present in your ongoing clinical practice. Aakash Desai: Hello, everyone, this is Dr. Aakash Desai, I am currently a Hematology and Oncology fellow at Mayo Clinic, in Rochester, and this is part two of our discussion on the past, present, and future of Oncology training. My guests are, Dr. Madison Conces, Hematology/Oncology fellow at Cleveland Clinic, Dr. Lori Rosenstein, Hematology, and Oncology Fellowship Program Director, at Gundersen Health System, and Dr. Deepa Rangachari, Fellowship Program Director, at Fellowship Program Director, at Beth Israel Deaconess Medical Center. In part one, we gave our insight into what motivated us to get into Oncology, along with spotlighting the rewards and stresses of going through fellowship. Today, we're going to look at what the future of Oncology should look like. But first, I and my guests will explore the challenges of transitioning from training to clinical practice in Oncology. Lori, gives us her answer. Dr. Lori Rosenstein: You know, I think part of it is, you are in that final stage, this is the rest of your life. So, I think a lot of my fellows feel like when they're leaving fellowship, they have to find the perfect job, because it's where they're going to be for the rest of their life, and I think everybody who is out in practice knows that it's very unlikely you stay in the first job out of fellowship. And so, having less stress on yourself, of finding that perfect experience, I think, finding an experience that fits with your goals and aspirations, and what you see your life being like, is good enough. And then if you go there, and it turns out it's not a great situation for you, feeling free to go somewhere else, that's a different paradigm than I think fellows expect. They put so much stress on themselves. We're all type-A people, right? And you just want to make the right choice. I've now had a couple of jobs. Each of them was the right choice for me at the time, and each of them taught me really important lessons that I have carried on to my next role. When I started my first job out of fellowship, I had no idea medical education was going to be a huge part of my life and career. I like to teach - that was what I knew about myself, but as I got more involved in medical education as a career, as a research opportunity, as probably the most important part of what I do in work, it changed where I was going to go. It changed what I ended up doing. You know, I ended up as a program director, and when I talked to my fellows and I say, you know, my job is research and taking care of patients, and teaching, and then medical education. To me, medical education is at the top, and that would not have been what I said as I left fellowship. So, having that openness to say, "I'm going to take in experiences and continue to grow and develop," is huge. Aakash Desai: Madison, what challenges do you think you are going to have to face when you start clinical practice from training? Dr. Madison Conces: I think for me right now, the main things on my mind are making sure I have the support I need after I graduate. I don't think I'll be abandoned anywhere, but I just want to make sure I join a supportive practice. And I think the second kind of big stress on my mind is doing research as a staff. Obviously, have mentorship, but as a fellow, I feel like there's a little bit more of a structure maybe with that, and so again, I'm not sure how that will be as a staff, but you'll be kind of more of the PI right on the project rather than a co-PI necessarily, and kind of going with patient care, like all the details, and making sure all T's are crossed and I's are dotted, and I know I'll be ready when it's time, but I just feel like it's kind of always in the back of my mind, like that it's coming - exciting, and I think one thing I try to reflect on, is I have made it; I'm literally the 10th year of my medical training. If I've made it this far, and I have problem solved, and helped patients, and worked as a team, and been a leader when I needed t0 this far, then I have to have faith that I can figure it out as a staff as well. Aakash Desai: Deepa, can you answer next? Dr. Deepa Rangachari: Couple of recurring themes: one, appreciating the interdisciplinary nature of the care that we give, and just recognizing that the need for help, whether it's help with regard to clinical decision making, or intuition, or best practice, or the need for help just in terms of supporting the needs of your patients, those things never, ever go away. That sort of segues very nicely into this idea of consistent and ongoing rapidity of the growth and knowledge that doesn't end when you come out of fellowship. Those things continue to evolve and change well after your fellowship training. You need to know when and how, and who to ask for help. You also need to develop paradigms for lifelong learning. What will it mean to you to be a learner during career span journey, where not only will the knowledge change, but the way in which you access that knowledge will change? And I think those are important things to recognize as challenges of making us transition. I think really this idea of what I call work-life negotiation is present very much during training, and one continues to be very present in your ongoing clinical practice. And what I mean by work-life negotiation is, on any given day or any given week, or any given month, the way in which you organize these relative priorities at home and at work certainly can change dramatically. And this idea that you can be in charge of refining, and reorganizing, and defining, and turning up or down the dial at home or at work, according to what's going on in your life, is very important to recognize, and so, I think that idea of paying attention to the need to continue to negotiate those factors on a regular basis is something that is very important as you transition from training to clinical practice. I would not go so far as to say that it necessarily ever becomes easier, but I absolutely think it becomes more manageable for two main reasons; one, you have more control over your career and your life as you move from training to practice, and two-- and I think we should be open and honest about this, you have more resources to do so - whether there's financial resources, or supportive resources. But both of those things, I think, make it more manageable, even if the challenges never go away. Aakash Desai: And now we'll move on to the next question. I think this is a question I think most fellows have in mind because they realize that as and when they go out to clinical practice, the treatments you learned during fellowship and what ends up happening when you're actually interactive, there's going to be a lot of difference because of all the new updates, and the new drugs, and others that come out. But how do you stay current with new treatments and guidelines, and what would you advise current fellows and future Oncologists, the resources to use for these kinds of updates? So, Madison, I'll start with you. Dr. Madison Conces: That's a tough question, I think because some groups, the field is changing so fast. I would say if I'm dealing with something I've not seen before, or I don't know in depth as much as maybe, you know, GI malignancies, which is mostly my interest right now, we'll start out with the NCCN guidelines, and I'm well aware there are plenty of people who don't follow those verbatim and all of that, and there is some interpretation with those, but at least, it gives you a structure to work with. And so, I like to start there, and they usually have at least updated, you know, genetic mutations and some drugs that are, you know, used for those mutations, and so any targeted therapy might be listed on that guidelines. And so, I usually start there and then go beyond there. I mean, I'm obviously talking in a very general sense here, because patients with a really rare cancer, you're just going to have to read up more and look at case reports, you know, see if there's any recent trials. That's kind of where I start, and I just kind of read from there. It's almost like a trickle-down effect in a way. Dr. Lori Rosenstein: So, Madison, I think that is also where I start - NCCN guidelines, up to date, those sorts of things. I will tell you that as I have gone along, I have become much more likely to phone a friend than I used to be. I used to be, as a fellow, like, "I'm not going to call that person." I still remember, as a fellow, I called somebody at MD Anderson to ask about Mantle Cell lymphoma, and he was absolutely lovely, but I was petrified. I was like, "Oh, he's going to think I'm an idiot, and why am I calling him?" Now, I know that people are out there and they're experts for a reason, and they're experts because they want to share their expertise, and it's very rare that someone is just completely not interested in helping you. But reaching out, I think there's lots of ways on social media that you can reach out, and my fellows, they think I'm silly because I tell them, "Look what I just found on Twitter." Like, if you're following the right people on Twitter, and people who you trust their opinions, and you know they're experts in their fields, and they say, "Hey, I was just at ESMO, and here's the slide from what I think is really important." That helps guide me to like, "Hey, this is something." Now, obviously, social media is what it is, and you have to take it with a grain of salt - I try not to trust complete strangers, but at least it leads me to new articles that I wouldn't necessarily have seen. Currently, on my desk, I probably have about 30 "Bloods" because I just am so behind in looking through those, so, knowing that someone who I know in Hematology said, "Hey, this is a really great review article on X, Y, or Z," I'm texting that to my fellows at night when that comes across Twitter. And likewise, there's some really good groups on Facebook that are specifically for Hem/Onc, that provide support, you know who the experts are, they're willing to help. ASCO and ASH both have 'phone a friends' where you can present difficult cases and MedNet -- I have no financial disclosures for any of these, by the way. MedNet is a really interesting 'phone a friends' where you can put in a question around a general concept with a clinical case, and get experts in the field to reply back. So, all of those things, I'm much more likely to do now, than I was when I was a fellow, just because I'm now less concerned that people would think I don't know what I'm doing; I'm much more likely to say, "Hey, I don't know what I'm doing, and I need help in this situation." Aakash Desai: That is so great to hear because social media really has become one of the primary sources of updates that we get. It's definitely not the ideal resource, but I think in a fast-paced world, I think having a few things on updates, I think definitely has been very helpful. How about you, Deepa? What are your thoughts on this? Dr. Deepa Rangachari: Yeah, being, staying current, it's really a challenge and I think lifelong learning is often interpreted as sort of like being willing to continue to learn over time. The trickiest thing about this is learning how to adapt the ways in which you learn over time, and so, I'm a very pen-and-paper sort of a person, I've had to really learn how to be savvy with using digital resources. I keep a very brisk PDF library of key literature, not only that I like to read and save to re-review myself, but also in terms of a lot of the teaching, and presentations, and talks, that I'm invited to give. And so, I think I've gone from a very pen-and-paper modality, and I still have the notebooks that I kept during my residency and fellowship training, and I still remember at the quarter left hand of a page, I wrote something that I really wanted to remember, but I've had to move away from that because I can't be walking around with pen and notebooks all the time. And so, I've developed PDF libraries and things that are available leveraging the technological support provided by my institution to maintain things on the cloud. I've incorporated podcasts into my lengthy commute time to, and from work, to sort of have a chance to keep up. And I think the honest truth is that everybody has to develop a system, and you have to be willing to be flexible and iterative with that system, and modify it, and grow it as time goes along. So, I don't have any simple equation for this other than a willingness to recognize the importance of being organized, and a willingness to be willing to change as the ways in which we learn and get information change, and a willingness to ask - that's the most important thing, is to be willing to ask others, and have others in your realm, who you know and trust, and can get candid and accurate answers from. Aakash Desai: So, now I have a very simple question, I think, to which you'll all have to give straightforward answers: What do you think Oncology training should look like in the future? What are your thoughts, Deepa? Dr. Deepa Rangachari: I think two of the things that we really have to acknowledge are; one, it has never been possible, nor will it be possible in the future, to think that three years of clinical training can prepare you for all of the questions, and nuances, and advancements that our discipline is fortunate to witness, or that we are fortunate to be a part of, and contribute to. So, really, fellowship training then has to be about developing a very rigorous infrastructure for critical thinking, and lifelong learning, and recognizing general frameworks and scripts for illness, and wellness, and therapeutic intervention, and understanding when are moments to push, and when are moments to sort of take a step back, and sort of revisit or refine the care trajectory along with our patients. I think that's one thing - sort of really just acknowledging there's no way we're going to be able to train people to see everything and know everything, so to really make sure that our training programs provide each trainee, and the program at large, with that sort of rigorous infrastructure and framework for thinking about complex problems, and really for working in complex interdisciplinary teams. I think the second thing that conceptually, I think, training program leaders should be thinking about is, helping make connections between different disease entities so that we're not training folks to think in disease-specific silos, but really think about emphasizing concepts that are shared across disease entities; thinking about making connections between common disease biologies, and things that may be similar or different, rather than memorizing a series of therapeutic pathways in stage III non-small cell lung cancer versus locally advanced breast cancer, versus early stage pancreatic cancer, but really thinking, what are the things that these different disease entities, at the biological level, or at the care coordination level, what are the things that are similar or different? I think this serves a couple of different things. From a learning science perspective, it sort of reinforces what we know are effective strategies for knowledge acquisition and retention, but I think also part of our obligation as training program leaders, is to make sure that we're training people to be thought leaders and innovators in their respective clinical and scholarly domains, and that really requires a lot of cross pollination of ideas - what is something that we know works well in lung cancer? How might that same way of thinking or science be applied to a patient in breast cancer? And how could we use those insights to innovate across different diseases? And I think a lot of this comes down to just acknowledging that this finite amount of training time will never be enough to fully expose people to every aspect of the breadth and depth of the discipline, let alone, how we're practicing now, or even thinking about the future. And so, really thinking about making sure that training programs create paradigms of thinking and collaborating, and lifelong learning that will go the distance rather than just emphasizing very specific content. Aakash Desai: Lori, what are your thoughts on this? Dr. Lori Rosenstein: From my standpoint, I think if I could totally change fellowship-- the thing that I'm most worried about with my fellows is trying to have all the medical knowledge for Hem and Onc by the time you finish three years. ACGME is so useful, as a program director, to help me guide what I need to be helping my fellows learn during that time. But for any of you who are program directors all know, there continues to be more and more things that we need to show that we're doing - we need to show that we're teaching our fellows multidisciplinary approaches to care of patients, they need to know about patient safety and quality improvement, they need to do research, they need to have all this medical knowledge. And as more and more things kind of come on the plate of what we need to turn out in three years, and more and more knowledge is out there, it becomes this point where we're not going to be able to do that. And if I had my choice, I would drop the medical knowledge part of knowing every esoteric drug mechanism and pathway, and having testing for that, and more, can we prove that they can critically think and take care of patients who are very complex? It's hard to test on that, and it's hard to just check that box and say, "Complete." But when you're a program director, and you're working very closely with fellows during that three years, you learn that - is this someone you want to take care of your patients or not? And they may be extremely able to take tests and answer questions correctly, and still not the Hem/Onc doctor that we would want them to be. In general, I would just say, less and less emphasis on test taking, and you know, regurgitating medical knowledge, and more and more emphasis on, where can you find the knowledge, and how do you apply it? Aakash Desai: So, as currently the programs are structured, I think most programs in the country are dual Hem and Onc boarded. Some programs do allow for single boarding, but I guess I want to ask thoughts on the future. There'll be more and more programs who will opt for singular boarding Hem or Onc, rather than a dual board. Dr. Lori Rosenstein: Yeah, so this is Lori. I think that single boarding is extremely challenging with the way our healthcare structure is laid out. So, you know, we all have to be very realistic that most of our fellows are going to leave fellowship, and are going to practice both Hematology and Oncology, and they're going to take care of the broad spectrum of all of those diseases. And in order to do so, their hospital is going to require they're credentialed, and certified in both of those. So, I think if we start to either only have Hem, or only have Onc, people are going to have extended training, and it's going to become less and less attractive. It's already a really long slog to be a medical oncologist and hematologist, and making that longer, I really don't think it's the way to go. Aakash Desai: Madison? Dr. Madison Conces: I'll jump back to the prior question of where do I see fellowship training in the future. I definitely think that the critical thinking aspect will still be there. I think there'll have to be more of an emphasis on thinking through patient care, and not so much the regurgitation medical knowledge of memorization. I think, you know, core lectures, like I'm sure a lot of fellowships we do here, which I think are really important to have, maybe at the beginning of the year, just to kind of lay out the basics for first-year fellows, but I think beyond that, doing case conferences where it's not crystal clear what even the subject is going to be and walking through it, and making people answer questions even in more of an interactive manner is another way we could go about the conferences. Other than maybe some very obvious information, I think a lot of this we just need to make sure we know how to find it - like we've already mentioned the NCCN, up to date, I think probably a lot of us got used to doing some of that in residency, in terms of where to find information. We've all been-- I think most people who are in fellowship right now have trained through all their training with computer and the internet, so you know, I think a lot of us are very familiar with it. Aakash Desai: Yeah, I think completely agree. And I think, you know like Lori mentioned, fellowship should be more than just preparing for Boards. And especially, I think as we move on in our fellowships Madison, and I think I've realized that you know, to know what your blind spots are and when to ask for help is also a critical part of actually training during fellowship. And I think as I come towards the end of my fellowship journey, I think I've realized now that it's a continuation of a longer journey. You know, three years is just the tip of the iceberg, and there's obviously a whole lot of you know, things that I'm going to see in the future. So, that, to me, I think in the future, needs to be kind of emphasized for the fellows to kind of really be okay with the idea of not knowing it all at the end of three years. And as we've geared more towards-- and we talked a little bit about work-life negotiation rather than balance, I think will be also very important. Thank you. I think those are phenomenal points, and I really appreciate everyone's time today. So, that is all what we have for today. Thank you so much, Dr. Conces, Rangachari, an Dr. Rosenstein, for this candid and vivacious conversation on Oncology training. I'm sure our listeners will appreciate and be able to relate to many of the personal anecdotes that you've shared, and the insights that you have shared today. Thank you also to our listeners, we appreciate you tuning in to this episode of the ASCO Education podcast. Thank you for listening to the ASCO Education podcast. To stay up to date with the latest episodes, please click, "subscribe". Let us know what you think by leaving a review. For more information, visit the Comprehensive Education Center at: 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.

Getting into oncology requires a lot of education and training. How does one deal with the success and stress of such a journey? In Part One of this ASCO Education Podcast, moderator Dr. Aakash Desai – fellow at the Mayo Clinic along with guests Dr Madison Conces – Hem/Onc Fellow at Cleveland Clinic, Dr. Lori J. Rosenstein, Hematology and Oncology fellowship program director at Gundersen Health System and Dr. Deepa Rangachari, fellowship program director explore the past, present and future of Oncology Training. They discuss their motivation of pursuing oncology (1:55), the rewards (5:51) and the stresses (8:44) of fellowship, coping with the loss of a patient (12:52) along with methods to keep up with advances in the field (19:50). TRANSCRIPT Dr. Lori Rosenstein: What I learned in fellowship is completely different than what I know now. And I passed the Boards, I did well on the Boards, I stressed about them, but the Boards do not define who you are as a cancer doctor; they are just a step along the way. And so, really, I am much happier if a fellow has that thought process and that self-reflection and knowledge of what they do and do not know; they're going to be amazing when they're done. Dr. Aakash Desai: Hello, and welcome to the ASCO Education podcast. My name is Aakash Desai, and I'm a Hematology/Oncology fellow at Mayo Clinic in Rochester. I will moderate this episode focusing on how Oncology training has changed in the last couple of decades. Do you think today's fellows have it easier with the electronic medical records, or is it rather harder with that? Given the much bigger pool of treatments to choose from and the constant stream of information, is it more difficult for Oncology fellows in this day and age? On a personal level, what challenges persist? How might we reimagine Oncology training in the future? To discuss all these questions and more, I'm joined by current Oncology fellow Dr. Madison Conces from Cleveland Clinic and two former fellows; Dr. Lori Rosenstein, a Hematology/Oncology Fellowship Program Director at Gundersen Health Systems in La Crosse, Wisconsin, and Dr. Deepa Rangachari, a Medical Oncologist, Assistant Professor of Medicine at Harvard Medical School, and Director of Hematology/Oncology Graduate Medical Education at Beth Israel Deaconess Medical Center in Boston. As we are all colleagues, I'm going to refer to everyone by their first names, if that is okay. And so, I'm going to pose my first question to Madison. Question is, what motivated you to get into Medicine and specialize in Oncology? And then, I will have Lori and Deepa answer the same. Dr. Madison Conces: Thank you, Aakash, for having me join this conversation today. So, I'll kind of answer the Medicine and Hematology/Oncology portion at the same time. I was in college when I actually was shadowing Dr. Pat Loehrer at IU over the summer, and I worked in the lab while also doing clinic with him one day a week. And I think being able to see the science and working to improve patient care while also witnessing the patient interactions, and the relationships, and the trust between the physician and the patient, is something I really admired, and that really drew me. So, I think that's kind of when it first sparked. And then, just during residency in medical school, my recurrent interactions with Oncology patients is what kind of definitively made me go that route. Dr. Aakash Desai: Lori? Dr. Lori Rosenstein: So, I was a little bit slow to figure out what I wanted; I thought Neurology or Internal Medicine, and then I had no plans after that, and I really debated a long time. You know, ultimately, now that I'm a Hematologist-- and this totally makes sense with my personality and everything else, what I love about Hematology is the mystery and the detective work that happens. It also happens in Neurology. That's what I liked was figuring out where the lesion was based on your exam. But in Hematology, we figure out where the lesion is, and then often, we can fix it. And to me, that was really exciting. So, I joke with my fellows all the time that I'm a blood detective, and the best thing ever happened yesterday - is that one of my fellows knocked on my door, and she came in, and she said, "Today, I'm a blood detective. I figured this out." And it's super cool. I think that's a really fun part about Hematology and Oncology. Dr. Aakash Desai: How about you, Deepa? What are your thoughts on this? Dr. Deepa Rangachari: My inspirations mimic those shared by my colleagues already today. At a very young age, a very dear family friend whose mother is a Pediatric Hematologist/ Oncologist, and I think I was immediately enthralled by her demeanor. And later in life, as a medical student, I had the opportunity to shadow her and really see her in action. And I think she really embodied all of the things that I always considered in terms of being a consummate physician. And I think, on a daily basis, what inspired me to become an oncologist is, really, what to this very day holds me deeply, devotedly to this lifelong career which is the ability to exhaust and frankly apply all of my intellectual, emotional, and interpersonal skills to achieve the best possible outcome for a patient and their loved ones in what is often very challenging and/or devastating circumstance. The inspiration, in many regards, from years ago is the ongoing inspiration. Even today, I'm very much informed by early experiences, seeing such folks practice in a way that I felt was truly the art and science of Medicine. Dr. Aakash Desai: I guess the next question I would want to ask both of you is: What is the most rewarding part of the fellowship? Lori? Dr. Lori Rosenstein: I hate to say this; I'm the oldest one of the group here, so I've been here the longest since I did my fellowship. But I will say, the best part of being a Heme/Onc doctor is the longitudinal relationships that you develop with those patients over time and the difference that you make in people's lives in the really short amount of time that sometimes you're with them. I think fellowship-- we'll talk later about the stresses and difficulties of fellowship - but knowing that you're in that final stage, you know, everything up until fellowship is, "I'm doing this to do the next thing. I'm doing this to do the next thing." There is really not a next thing after fellowship. That is what you're going to do. And I think that's the most exciting part - everything you're doing is for that purpose. You know, once you pass the Boards. Dr. Madison Conces: I agree with what Lori just said, and I think as someone who's in their final-- I'm a third-year Heme/Onc fellow right now, and I would agree where you're just like, "This is it. This is what I am going to do for the rest of my life." And there's excitement with that, there is some little bit of anxiety, I guess, under it, but there's a lot of excitement with it, and I think-- like when I sit and talk with patients now, I know we keep kind of reiterating a human connection, but I feel like at least as a fellow now, I'm able to explain things or understand things in a way I didn't before. And I feel like that makes me even more connected in their care, and also in a way kind of, I wouldn't say I understand, because I'm not in their position, but I'm able to, I feel like, meet them closer to the middle than I was before. So, I really appreciate that, I guess, growth I've had during fellowship, that's allowed me to, I think, be closer with patients and their journey. Dr. Lori Rosenstein: Madison, this is Lori. So, I was just going to ask based on that; I see externally as my fellows are going through their training, there's usually just this moment where I can suddenly see that it's kind of clicking, and, you know, the hardness of first becoming a fellow all of a sudden, starts to get easier; and they really start to fly - they start to do fantastically. Do you remember if that was something that you experienced? Dr. Madison Conces: So, I was on Oncology consults August of my first year of fellowship, and I am September of my third year of fellowship. And I just noticed how quick I can be. Like in July, I was like, "Oh my gosh, I'm a third year. How am I going to be ready for next year?" But now that I'm on Oncology consults, again, seeing every type of solid tumor malignancy, specifically for solid tumors, obviously, but I see the pace I'm going compared to before; I know the depth of knowledge I have is much greater, I kind of am more aware of my deficits of knowledge. So, I would say, just even in the past week, I've noticed, like, "Wow, I've definitely gotten better." I don't know if I'd call that an aha moment, but I've definitely had that perception of myself in the past week. Dr. Aakash Desai: Yeah. I think, as a third-year fellow myself, I agree. I think that's, you know, very rewarding. Essentially, recently, I was giving a talk to our first-year fellows as a primer talk on lung cancer. And, you know, I realized like some of this comes so naturally to me now, and I remember myself being a newly-minted, first-year fellow, and just thinking like, "How am I ever going to make sense of all this data and everything that's coming out?" That's also, I think, the part of the personal growth - you grow as a fellow. I think it's also very rewarding, as the fellow that I've found. So, with that, I think one other thing that's been, you know, obviously, more recently brought out is resident burnout, fellow burnout. Just in general, position burnout has been the theme, and we are becoming very aware of this. And I think fellowship, being the training, it obviously has its own stressors. So, what are the most stressful aspects of fellowship that you've found? Tell us about the most stressful day you've had so far and how do you cope with stress and workload. And any tools or strategies that you would recommend to current fellows and other peers that would be useful. Dr. Madison Conces: I would say, probably, it's twofold in terms of what's most stressful about fellowship; one is the information which you had already mentioned, Aakash, and I think with that, is kind of the research aspect and balancing that. Like, how do we dive into research and look into spaces that are unknown, if you will, and then at the same time, know the data of the cancers we're already treating? I think the outpatient stressors are different from the inpatient stressors in a way because I think during inpatient, you're constantly engaged in these difficult situations patients are in, and there's not much of a break. And so, I think sometimes, not that we don't have difficult clinic days, but I think there can be a little bit more emotional drainage, and I think, in terms of trying to deal with that stress, like you mentioned-- I'm a distance runner. And so, even when I'm on service, I actually still make time for a run, even if it's just a quick run in the evening, or get it in before work if I'm on call that night, or something, sometimes just some light weights. That's been my crutch, if you will. I've done that all my medical training; I've been running for most of my life. And I've been very deliberate and diligent about continuing that, and I think, somehow, it kept my head above water some days. I do wonder what else I could do to help because I definitely have days where I feel like my running isn't enough. I think, as many people have felt since the COVID pandemic started, there's been a real struggle with burnout. Dr. Aakash Desai: Lori? Dr. Lori Rosenstein: Yeah. I think there's a lot that's stressful about Heme/Onc fellowship, and as a Program Director, you see the cycle. You know, first-year fellow comes in; they're brand new. That first six months, as I said previously, is just so, so hard, and you, as a program director, want to help. You know you want to get them through that. Because, you know, many people are coming in, it's a new hospital, it's a new system, it's new diseases, it's working in the clinic instead of the hospital-- most Internal Medicines are very, very hospital-focused. And then all of a sudden, you're in a clinic where it's almost all outpatients, and you don't know how that works, even though you should. You know, like people think, "I could be an internist; I could be done." And yet all of a sudden, I'm right back at the bottom of the barrel, so to speak. You know, not knowing how to do anything. And so, that first six months for sure is really stressful because you feel like you've had autonomy; when you're a third-year resident, you're ready to go out, and then boom, you don't know what you're doing again. And so, at the same time, you are a young adult who often is having families, thinking about settling down, buying homes, you know, growing up, and that just adds to all of the stress because you have the stress at work, and then potentially, stress at home. For me, I had my first child when I was a resident and then had my second as a third-year fellow. And so, I had these different stresses as I was going through my training. You know, some of my fellows have had parents die while they've been in fellowship or parents that they're helping to take care of. So, not only are us older people in kind of the sandwich generation, but I think younger people in fellowship are seeing that as well. So, yeah, I think there's a lot going on that can make it challenging. But my encouraging part of it is that it gets easier. You start to figure out where you can find the information that you need, how to make things happen, and there's just this tipping point where suddenly it becomes easier, and then I see that they're back having fun again. You know, that, "Oh, this is such a really interesting disease, and I've never seen this presentation before, and I looked in the literature, and there's only three cases." You know, that passion and that excitement for finding new things, or, you know, "I wasn't sure if this chemo was going to work, and I gave it, and they're back today, and they are so much better." Just that excitement and passion. It's so wonderful to see as a program director. Dr. Aakash Desai: The other thing is also; I feel like the stresses are different as you kind of evolve through your fellowships. So, I think, as Lori very rightly pointed out, like the first year is, you know, just getting used to the information, the flow, and everything. But what I've found particularly challenging is, as you enter the second and the third year, and when you have patients that you continue to follow, just by the nature of the disease and the field that we are in, you will end up having some patients who you lose along the way. And I think that dealing with it emotionally; I think because during the first two years of your fellowship, you know, you meet them every few weeks, you kind of get attached to them, and you know what their life is like, you share part of your life with them. How have you found your way of coping with loss of the patients that you kind of have a deep connection with? I think that's part of the stressful aspect of, like, later years of your fellowship, I feel. Any insights on that, Lori? I mean, you've obviously been doing this much longer than me and Madison. How do you deal with this kind of loss and keep going every day, even with the same enthusiasm? Dr. Lori Rosenstein: Yeah. I think that absolutely is a really challenging part of our field, but it's also part of the blessing of our field - is that we are there, and we can help negotiate people through difficult times. And if we're doing this well, we have seen this coming. We have been able to prepare people; we've been able to make sure that we're honoring the things that are important to them at the end of life, and we're working to make sure they're not in pain and that they have their family members near them. And so, for me, that's always that rainbow at the end - is that I was able to assist them in this process. We all know we can't stop death. We may, you know, fool ourselves into thinking this carbo/etoposide is going to change the world for this patient. But I think being realistic about what we can and cannot do. For me, having a great conversation with a patient and their family and knowing that I've helped them, even if the end result is not that they have another 20 years to live, is super meaningful. And I think most oncologists that can do this for a long time find the value and the meaning in that part of their job. I think if you're constantly trying to stop death and trying to, like continue chemo till the very bitter end, this could be a very draining job. Dr. Aakash Desai: You know, and more and more, we are realizing the importance of supportive care in Oncology. And I think what you just pointed out is that, you know, improving someone's quality of life, even for two months, is also very rewarding in its own way. So, thank you for saying that. The next question I have is especially geared towards you and Deepa for fellowship program directors: How has Oncology training changed since you were a fellow? And is training for current fellows harder or easier do you think? Dr. Lori Rosenstein: You know, any program director who trained a long time ago will give you the woes of, you know, 'I had to walk both ways with no boots in the snow'. I think that probably the biggest change since I was a resident is work-hour restrictions, which came sometime during my residency. So, I was a fellow when there were work-hour restrictions. But to be very honest, in fellowship, you almost never are reaching that 80-hour work week like you would've been when you were on an ICU rotation in Internal Medicine. Most of my fellows, you know, they log their hours every week, and we're somewhere around 40 to 45 hours a week, depending, you know, there's going to be times where it's busier. So, I think the work hours are less of an issue, but that doesn't mean it's easier. And I think now, the most difficult challenge is, all the new treatments, all of the options-- it used to be-- we had two choices; you could do this, or you could do this. And now, there's all these nuances, and nuances are very challenging when you're first learning. You know, you can see this study, and it was this compared to this, and option A was better. But then you would talk to your attending, and they say, "Well, option A was better unless you were from some esoteric country," and then you know you did worse. So, you start to really piece apart, and you know, you gain your basic understanding, but then start to try to apply that to your patients. And that is, I think, a very big challenge. Dr. Aakash Desai: How about you, Deepa? What are your thoughts on this? Dr. Deepa Rangachari: I think it's become harder in that it has become incredibly more nuanced than incredibly more sophisticated. Three things, in particular, come to mind; one's are the burgeoning evidence basis for what we do and the prospects for advancing our knowledge and understanding and thereby have better interventions that's certainly been a seemingly explosive growth in our knowledge and understanding, especially considering the humble origins of our field. They work daily with colleagues and friends who remember those days when Heme/Onc was sort of an esoteric field of people whose methods were considered bizarre at best, and that's absolutely not where we are anymore. It's an incredibly exciting time, so a lot of information to keep up with. Secondly, one of the things that maybe we didn't really appreciate at the time was true before but is increasingly true now is the importance of recognizing your role as the leader of a very sophisticated interdisciplinary team. Thankfully, I think this is true for all patients with any illness, but thankfully, in our disease area, care by an expert village is really the new norm, not the exception. And sort of learning how to function in those interdisciplinary teams in an incredibly collaborative and productive way across the spectrum of a patient's care and needs is incredibly nuanced, more so than ever before. And something that fellows, at the earliest instance of their training, really need to learn to be agile with. So, I think that's something that is also both a sign of progress, but also an added layer of nuance and sophistication. And I think the final thing is that there are so many diverse ways in which someone can have it truly impactful and fulfilling career within Heme/Onc, and I think this makes fellowship also that much more exciting and complicated, nuanced, really trying to understand within your career span, what is the pathway or the different pathways, honestly, that you may choose to train and prepare for and conduct yourself is really dizzying. And I think we really are expecting a lot in terms of our fellows these days to sort of be willing to understand those options and understand which options are most meaningful to them and then prepare in a very deliberate and rigorous way for those specific career interests. So, kudos to all of you. You guys are doing an incredible job; you are the future of our field. And those of us who run programs, direct such programs, we really have a continued challenge and inspiration to meet your needs. Dr. Aakash Desai: The field is moving so fast that I can say, like when I joined fellowship in first year compared to now, I think there is a lot more treatment options. And I think as fellows also, it's so difficult to keep up with this, you know, constant stream of information. So, Madison, how do you think things have changed since you joined fellowship, and how do you envision yourself, you know, resources to use to kind of keep yourself updated? Dr. Madison Conces: I would agree with both of you. It's definitely changed. It's also interesting because it's not always the addition of treatments; it's sometimes showing that adding this extra drug does nothing. And so, all of a sudden, you've now changed the paradigm again for how you treat that patient. And I think for me, what I've found during fellowship is-- and maybe Lori would enjoy this part, but the thinking of it, right? So, even Hematology, I definitely think of as the puzzle, but in general, all these patients, there's something about them, whether their tumor's genetics, or the family history, or any of their germline mutations they have. So, there's always this kind of; every patient is very specific. And so, I think what has helped me, at least during fellowship, is in clinic, to go through that, in that mindset with the staff I'm working with. And I think sometimes, at least, I've been fortunate to have staff who do a great job of making sure I'm thinking of everything, which is like, "Oh, if this doesn't work, what are you going to do next?", which makes me think about, "Well, what do we know about the patient? What do we know about their tumor? What are the other options?" I'm someone who learns by doing, which I think is many of us at this point, and so, I think the constant feedback from staff of kind of pushing us to think on our own is going to be helpful in the long term, rather than expecting us to come in remembering, you know, every part of the NCCN guidelines, because those are going to change as well. So, we've really got to be able to think through these patients' cases like puzzles, and also, you know, a lot of these patients don't read these textbooks a lot of times. Lori was talking about seeing the excitement of her fellows. Again, you know, yesterday I saw a patient who has paraneoplastic nephrotic syndrome. It's like these things; we have to be able to keep pace with essentially our patients in their pathophysiology. And the more we learn, the more kind of breath that's going to be. It's going to be wider and wider in terms of what we have to know, and I'm not sure knowing it all is going to be the way to go. And for me, I try to know the basics, and then beyond that, really look at the patient. And instead of thinking about every treatment for that whatever cancer of the patient, look at, "What do we already know about it, and what can I go from there?" Dr. Lori Rosenstein: That's so interesting, Madison. And Deepa and I had talked about this; you know, as program directors, my goal for fellows is that they learn how to think about cancer, and how to have a really regimented way of going through a new patient, and thinking through, "Do I have the diagnosis? Do I have the stage? Based on those things, what do I know about the patient and their disease to make my treatment plan?" And that's the same for every cancer. Essentially, you're going through this regimented process. If I have a fellow that I know can think through a cancer, to me, it doesn't matter if they know that Merkel cell is associated with the Merkel polyomavirus virus. They may never see a Merkel cell, or they may see it once. So, that regurgitation of information that you are so used to doing for Boards and for tests, to a program director, is really so much less important than, "Can you think through the process? Can you find the own holes in your knowledge base? And then, can you find where to fill those holes so that you can take great care of patients?" If I could tell any first-year fellow coming in, don't panic about your knowledge base because what I learned in fellowship is completely different than what I know now. And I did well on the Boards, I stressed about them, but the Boards do not define who you are as a cancer doctor. They are just a step along the way. And so, really, I am much happier if a fellow has that thought process, and that self-reflection, and knowledge of what they do and do not know; they're going to be amazing when they're done. Dr. Aakash Desai: This kind of reflects how the program directors in our field actually, you know, are thinking beyond just like, "Oh, you need to score good on the Boards," because they realize the importance of thought process, and how to come up with treatment plans. So, thank you, Lori. I think this is phenomenal, and I'm sure all the fellows listening to this podcast will be delighted to hear what you just said. Dr. Lori Rosenstein: Now, you still have to pass the Boards; that's still a key component. But I think if you polled program directors about what we think about Board passing, most of us would say it's probably sixth or seventh on the list of importance. Dr. Madison Conces: Yeah. I would actually add onto that. We've been talking about thinking through processes, and through these cases, and using, you know, the thinking process more than just memorization. And I think also in fellowship, we are trained to also have these conversations with patients, right? Because it's not always what would be the right answer when we think about it in a treatment sense, but if that doesn't match what the patient wants, then it's not the right treatment. And how do we adjust that based on what's in the patient's best interest or what the family wants, depending on what the situation is, obviously? I think fellowship is about this critical thinking, but also in the context of the fact that we're taking care of this human being in front of us. Dr. Aakash Desai: Well, this concludes part one of our discussion on the past, present, and future of Oncology training. My guests have been Dr. Madison Conces, Hematology/Oncology fellow at Cleveland Clinic, Dr. Lori Rosenstein, Hematology and Oncology Fellowship Program Director at Gundersen Health System, and Dr. Deepa Rangachari, Fellowship Program Director at Beth Israel Deaconess Medical Center. In the second part of this episode, we will explore the different ways to stay current with new treatments and guidelines, as well as our guests' insights into how Oncology training should look like in the future. Thank you to all of our listeners for tuning into this ASCO Education podcast. If you have an idea for a topic or a guest you'd like to see on the show, please email us at: education@asco.org. Thank you for listening to the ASCO Education podcast. To stay up to date with the latest episodes, please click "Subscribe." Let us know what you think by leaving a review. For more information, visit the Comprehensive Education Center at: 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. Resources: ASCO Education Podcast: Cancer Topics - Burnout in Oncology: Trainee Perspective ASCO Education Podcast: Cancer Topics – Career Paths in Oncology (Part 1) ASCO Education Podcast: Cancer Topics – Career Paths in Oncology (Part 2) If you liked this episode, please subscribe. Learn more at https://education.asco.org, or email us at education@asco.org

Vaccine development is a tremendous scientific breakthrough. In Part Two of this ASCO Education Podcast episode, Dr. Doug Lowy, Principal Deputy Director of the National Cancer Institute describes overcoming the hesitancy of taking vaccines in the era of Covid (:57), the scientific impacts of other nations like China (3:54), the importance and the standing of the NCI (5:10) and the future of oncology (10:36). If you liked this episode, please subscribe. Learn more at https://education.asco.org, or email us at education@asco.org. TRANSCRIPT Pat Loehrer: Hi, I'm Pat Loehrer, Director of Global Oncology and Health Equity, at Indiana University. I'm here with Dave Johnson, a colleague and friend, and Medical Oncologist at the University of Texas Southwestern in Dallas, Texas. This is the second half of our Oncology, Etc., conversation with Principal Deputy Director of the NCI, and Chief of the Intramural Laboratory of Cellular Oncology in the Center for Cancer Research, Dr. Doug Lowy. In part one, we chatted with Dr. Lowy about his interest in cancer, which was developed through his personal academic experiences, including that of his parents, as well as his groundbreaking work on the HPV vaccine with Dr. John Schiller. Today, we're going to continue our conversation with Dr. Lowy by asking him about overcoming the hesitancy of taking vaccines in the era of COVID. Dr. Doug Lowy: Pat, it's very difficult. There was some vaccine hesitancy when the HPV vaccine was introduced initially. My view is that the people you want to speak to and with, are the people whose minds can be changed. So, I don't try to change the minds of people who are opposed to vaccination for one reason or another, but instead, try to talk with people about evidence, but directing it towards those people whose minds potentially can be changed. A big advantage with the HPV vaccine is that this has been going on over a number of years. With COVID, everything happened in a greatly truncated way. So, the vaccine was introduced less than a year after the pandemic. But concomitant with that was a lot of vaccine hesitancy, and I think that that's going to be difficult to overcome. What I have really worried about is whether the vaccine hesitancy associated with COVID might extend to other vaccines and not just to the HPV vaccine, but to childhood vaccines, et cetera. The national data for 2020 and 2021 for HPV vaccination is almost counterintuitive and provisionally reassuring, both. Compared to 2019, the last full year without the pandemic, the number of people being vaccinated with the HPV vaccine went up between '19 and '20, and between '20 and '21, went up again. So, at least by that metric and through that time, it doesn't look as though the vaccine hesitancy associated with Covid is extending to the HPV vaccine, at least in the short term. So, what we've seen between 2019 and 2021 is that HPV vaccine uptake among teenagers actually has gone up each year. So, at least in the short term, the vaccine hesitancy associated with the Covid vaccine does not seem to have extended to the HPV vaccine. Dave Johnson: So, Doug, I'm going to shift gears just a little bit. I read recently, in Science, that China had overtaken the United States in terms of scientific publication and impact; and I'm wondering what you think about that, and what we need to do to retain our longstanding leadership in that role. Or does it really matter? Dr. Doug Lowy: If China's research, if their quality is outstanding-- I mean, there's nothing wrong with another country making important contributions to biomedical research. I don't see this, per se, as a competition. Perhaps, it's because I'm just looking at it through the lens of cancer research, and we think that cancer research is much too big to be done exclusively through support of NCI, exclusively in the United States, et cetera. So, to me, if other countries are doing high-quality research that can help people all over the world with regard to cancer- Pat Loehrer: -Let me ask you this, Doug, you've been at the NCI for 50 years. And I calculated that you've served under nine presidents, and of the NCI's 16 directors, you've served with 10 of them- Dr. Doug Lowy: Really ancient. Thank you. Pat Loehrer: -so, with all that, what do you think; one, about the importance of the NCI, and then also, we'll ask you a little bit about the reflections of the directors, and lessons learned from them, and maybe, some good stories. So, where do you think the NCI stands, and why is it important for the world, and for the country? Dr. Doug Lowy: What's really important is the funding from Congress. It is long-term and sustained. Cancer research can't be done in two or three years. It just takes a while to do really high-quality cancer research. And what really counts, from my perspective, is you can rely on the government to be strongly supporting cancer research through the NCI. In other words, private philanthropy is very important, but private philanthropy can decide, "Tomorrow we don't want to be doing what we have been doing." It's very much like pharmaceutical companies - they can decide that they're not going to be doing it. But it's almost impossible for us to say, "We are no longer going to support basic science research. Okay? We're not interested in investigator-initiated research," because, of course, we are. And that's the bedrock of development. We can't say, "We're no longer interested in doing clinical trials," because, of course, we are, because we can't make the progress that we need to make without clinical trials. We can't say, "We're not interested in doing implementation research," because it's one thing to have a new approval, it's something else to have it widely and equitably disseminated, and doing some kind of research with implementation. Science is critically important, and this applies for prevention, screening, diagnosis, treatment, survivorship, all of these areas that NCI supports, and will continue to support. The proportion may vary from one year to another, from one director to another, but all of those areas are going to continue to be supported. Dave Johnson: So, Doug, during your various tenures as the interim director, what program or programs are you most proud about? Dr. Doug Lowy: Instead of programs that I'm most proud of, I would say that working with NCI staff is what enables the achievement. The mission of the NCI is just incredible, and virtually everyone on the staff buys into the mission; which is, to help people live longer and healthier lives through research-related advances in cancer. That's what people do. And the first time when I was Acting Director, was the first Cancer Moonshot, so I was involved in that. But tremendous amount of credit needs to go to the Obama administration for wanting to do it, to the Congress for its strong bipartisan support for the initial Cancer Moonshot, and to my NCI colleagues, and then extramurally, for everybody who really got on board and tried to do things. So, this is very much a team effort, and it's not limited to NCI, you know, extramural colleagues are critically important to everything that we do. Pat Loehrer: Doug, you've alluded to the fact that you've served under so many different presidents and directors, and they all have different leadership styles. If you were gonna be a mentor on leadership, what advice would you give to the listeners as to what makes a good leader, and perhaps, what makes a not-so-good leader too? Dr. Doug Lowy: I think that there is a spectrum - there are some people who lead by intimidation, and some people who lead by example; and all of them can be effective leaders. My own view is that I like to lead by example because I really feel that that leads to very high morale. People who lead by intimidation may get a lot of work out of people, but it is nowhere near as satisfying as knowing that you are an extraordinarily, highly-valued member of a team and that the whole is greater than the sum of its parts. So, I think that having tremendous admiration and respect for the people that you work with, is absolutely number one, and number two, is listening to them. You don't always need to do what they advise, but people really thrive on being listened to, and everybody wants to make a difference. And so, help them to achieve that goal. When they look good, you'll look good. Dave Johnson: So, Doug, I'm attending on the general medical wards right now. Just got asked today by the medical students to give them some advice about the future of Oncology, and where did I think it was going. Before I go back and meet with them, I'd love to get your thoughts. Dr. Doug Lowy: Well, the future of oncology is extraordinarily bright. On the one hand, we've made tremendous progress. On the other hand, there are still 600,000 people dying every year in the United States from cancer, and worldwide, the problem is even greater. But what's going to happen in the future is, we will understand the causes of cancer better, and so, that will enable us to prevent more cancers. I think there's going to be an enormous increase in the opportunities for screening, and to reduce either the incidence of cancer or increase the outlook for people with cancer, because asymptomatic cancer will be diagnosed at a substantially earlier time point. And then when it comes to treatment, my view is, we've barely scratched the surface. With the opportunities for making drugs, immuno-oncology, and who knows what other areas lie in front of us, are almost limitless. The Biden administration has a goal for the reignited Cancer Moonshot of decreasing the mortality rate over the next 25 years by 50%. What I think we need to do is to decrease mortality over the next 25 years by even more than that, and in addition, to make progress against those cancers where progress thus far has been limited. Take pancreatic cancer as a specific example; 10 years ago, the RAS oncoproteins were thought to be undruggable targets. But last year, we had the first approval from the FDA of a RAS-specific inhibitor. The good news is, that can target about half of lung cancer that has mutant RAS. The bad news is, it targets very few people with pancreatic cancer who have mutant RAS. On the other hand, there now are G12D inhibitors where there's excellent preclinical data and hopefully, sometime next year, be starting clinical trials. G12D mutations account for about half of people with pancreatic cancer. If the success there mirrors the success that we've seen thus far with lung cancer, it means that we are potentially on the way to actually making a difference in outlook for people with pancreatic cancer. But I just see this as one of many opportunities as time goes forward. Pat Loehrer: You did, this week, something that no one has done, and that is, to turn the reins of the directorship of the Cancer Center, over to the first woman director, Monica Bertagnolli. What was in your letter that you left on the desk that you gave her? What kind of advice did you give her? Dr. Doug Lowy: My advice that I gave her was really, "How can I help you the best and the most?" Dave Johnson: That's awesome advice. No doubt about it. It's a really historical moment, and of course, we, who are members of ASCO, are particularly proud that Monica has taken the reins, as a former ASCO president. And Doug, we really appreciate you taking the time to spend with us. It's been incredibly interesting, and congratulations on an amazing career. Pat Loehrer: Absolutely. Dave Johnson: And also, thanks to our listeners for tuning in to Oncology, Etc. As you know, this is an ASCO Educational podcast, where Pat and I will talk about just about anything. If you have an idea for a topic or a guest you'd like us to interview, please by all means email us at: education@asco.org Thank you for listening to the ASCO Education Podcast. To stay up to date with the latest episodes, please click, "subscribe". Let us know what you think by leaving a review. For more information, visit the Comprehensive Education Center, at: 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.

Vaccine development is a tremendous scientific breakthrough benefitting countless human lives. In Part 1 of this ASCO Oncology, Etc. Education Podcast episode, you will hear from the pioneering co-developer of the HPV vaccine Dr. Doug Lowy who serves as Principal Deputy Director of the National Cancer Institute , He speaks about how he got into the cancer field through the influence of his parents (4:49), the path that led him to focus on HPV (8:04), and his collaborative professional partnership with fellow HPV vaccine developer Dr. John Schiller (9:31). He also discusses his ongoing trial of one-dose administration, which promises to boost HPV vaccine uptake and reduce the burden of cervical cancer globally. If you liked this episode, please subscribe. Learn more at https://education.asco.org, or email us at education@asco.org. TRANSCRIPT Pat Loehrer: Hi, I'm Pat Loehrer. I'm Director of the Center of Global Oncology and Health Equity at Indiana University. Dave Johnson: I'm Dave Johnson. I'm a Professor of Medicine at UT Southwestern Medical Center in Dallas, Texas. Pat Loehrer: And this is Oncology, Etc. Dave, what have you been reading lately? Dave Johnson: Well, you and I have talked about a couple of books, but I thought in light of our guest today, I would mention a book I actually read probably nearly 60 years ago called The Microbe Hunters by Paul de Kruif - very interesting book, written, if memory serves me correctly, in the '30s, about many of the early bacteriologists and physicians who were interested in microbes; Pasteur, for example, and others. And I don't remember all the details, but it certainly was one that was influential for my choice of Medicine as a career, much like Arrowsmith. It was a really impactful book. I doubt many of our listeners today would've read that book, but if one is interested in the history of Medicine, it's a really interesting book to read. Pat Loehrer: You said 60 years ago. Okay, when I was reading books back then, it was about Dick and Jane. Dave Johnson: It's my understanding that you're not past Dick and Jane yet. Pat Loehrer: Good, good point. Good point. Well, it's such an incredible honor today, we have Dr. Doug Lowy as our interviewee today. Doug is the Principal Deputy Director of the National Cancer Institute and Chief of the Intramural Laboratory and Cellular Oncology Program at the Center for Cancer Research. He has served as Acting Director more than any other person - he served as Acting Director between April of 2015 and October of 2017, between April of 2019 and October of 2019, and most recently, he served as an Acting Director until Monday of this week, October 3rd. I had a chance of seeing Doug, I think, about a year ago, a week after he took over, and this is great to have that bookend here. He has had this title of Principal Deputy Director since July of 2010 and he leads many of the NCI's key scientific initiatives. He graduated from Amherst College, I think in Art History, I may be wrong on that, received his medical degree from New York University School of Medicine, trained in Internal Medicine at Stanford, and did a Dermatology Residency at Yale. His focus has been on papillomavirus and the regulation of normal and neoplastic growth. The papillomavirus is in close collaboration with Dr. John Schiller with whom he's co-authored 150 papers over the last 25 years. In the 1980s, he studied the genetic organization of papillomaviruses and identified oncogenes that were encoded by the virus, and he's been integrally involved and instrumental in the development of the papillomavirus vaccine. His laboratory did work with the RAS gene family and other suppressor genes, and as you can guess, he's just one heck of a smart guy. For his body of work and together with Dr. Schiller, they received the Federal Employee of the Year Award in 2007 and the Partnership for Public Service Award, the Dorothy P. Landon American Association for Cancer Research Prize for Translational Research, the Albert B. Sabin Gold Medal in 2011. In 2007, he got the Medal of Honor for basic research from the American Cancer Society, and President Obama awarded him the National Medal of Technology and Innovation in 2014. And in 2017, he received the Lasker-DeBakey Clinical Medical Research Award, which is considered one of the most prestigious honors in biomedical research. He is listed in the Institute of Scientific Information as one of the most highly-cited authors in Microbiology, and obviously, he's a member of the National Academy of Science and the National Academy of Medicine. Although these are notable honors, I'm told that none of them match the opportunity to speak with Dave and I today, and we really thank you so much, Dr. Lowy, for joining us. Thank you. Dr. Doug Lowy: Pat, I am speechless. Pat Loehrer: I so wish that Dave Johnson was, but could you tell us a little bit about your upbringing and your early life? Dr. Doug Lowy: Sure. I grew up in The Bronx, in New York City. I'm the younger of two boys. My brother is two and a half years older than I am. Both of my parents were general practitioners. My parents were both Americans, but my father had a classic sophomore slump when he was an undergraduate and was unable to get into a medical school in the United States. And so, he actually went to medical school in Austria, in the University of Vienna, and needed to learn German in order to go to medical school. But my parents were both very successful private practitioners. They had separate practices but practiced in the same office, and I learned about medicine, in large part, through them. They would go to lectures, and from the time I was probably nine or 10 years old, they would be telling me about cancer, and I became interested in that area. And then, when I was 16, my mother developed a deep melanoma on her leg, and so, cancer literally came home. And luckily, she had very good surgical treatment and lived for almost another 40 years - she lived until she was 80 and actually died of metastatic stomach cancer. But I got involved in thinking about cancer really through my parents. They talked with me about the role of tobacco in the development of lung cancer, and I heard about the Hammond and Horn report from the mid-1950s when it came out. Pat Loehrer: That was when Dave was reading the Microbe Hunters. Dr. Doug Lowy: I was reading it at about the same time. I must say that, although I found it very interesting, it didn't really speak to me, and now that's what I need to go and do. Although, in retrospect, that's what I've ended up going and doing. Pat Loehrer: Was it because of your mother that you had an interest in dermatology? How did you swing into there? Because we think of you mostly as a translational researcher. Dr. Doug Lowy: The dermatology was really when I was at NYU. I worked in the laboratory of Jan Vilcek, who had recently come from Czechoslovakia to NYU, and in his lab was Alvin Friedman-Kien, who was a dermatologist. And Alvin subsequently was among the first people to identify the AIDS epidemic through the Kaposi sarcoma. But Alvin talked with me about dermatology, and potentially, this might be an interesting field for me to go into. And then, when I went to Stanford, I did Internal Medicine for internship and a year of Medicine, and I did a rotation in Dermatology. And I was very impressed that the people who smiled the most were the dermatologists. And they had time also to think about what was going on with patients. And since I was at Stanford, it was a tertiary care facility and so we were taking care of people who were terribly sick, largely people with lymphoma and other types of cancer. And I thought that I might be better suited to taking care of people who were less sick than that. Dave Johnson: Is that where your interest in Papillomavirus started? Dr. Doug Lowy: Well, that was indirect. I first went into dermatology and then said, "Well, I want to be doing research. What can I do in research that might be connected both with dermatology as well as with cancer?" And the closest that I was able to come was Papillomaviruses. And when I started working on them, they were not yet clearly associated with cancer the way they are today. It was known that they were associated with an uncommon condition called Epidermodysplasia Verruciformis or EV and this is a condition where people have widespread HPV infection. And on sun-exposed areas, a subset of them develop skin cancer, but it's distinctly uncommon. The real interest, if you will, came from the identification of HPV infection and cervical cancer, which is one of the more common cancers, especially on a worldwide basis. And that was really the link with cancer. Pat Loehrer: You had an incredibly long-term collaboration with John Schiller, and as I mentioned, you published more than Dave and I have written letters to our wives with this man. Tell us a little bit about that relationship, that friendship, and that professional partnership. Dr. Doug Lowy: John, actually, he was at the University of Washington in Seattle doing his PhD, and it was so long ago that he sent me a letter, and I had been doing research on retroviruses. He sent me a proposal that he was doing his PhD in bacterial genetics, but he wanted to learn about mammalian viruses and so was writing to me about doing work with retroviruses. I wrote back to him and said, "That's very interesting, but I had just started working on papillomaviruses." And I thought the room for development and learning more was even greater there than with mouse retroviruses, which is what I was working on and what he was proposing to do some post-doctoral research on. Of course, he had never heard of papillomaviruses, so he had to look them up. But he developed a project with papillomaviruses and was able to get an NIH award to come as a postdoctoral fellow to work in my lab, and he actually did the research that he proposed, and it led to our improved understanding of the genetic organization of papillomaviruses. But then, it was clear that John and I got along very well, and it looked like both of us might be able to work together. So, he ended up getting tenure after he had been at NIH for about 10 years. And it's just been an amazing collaboration for me because John knows a lot of things that I don't know, and he thinks that I know some things that he doesn't know. And working together has been terrific, really, because when one of us doesn't want to do anything about something, the other one tends to step in. And so, it's been an amazing partnership that we have had for this time. Dave Johnson: This is really important. One of the reasons we agreed to do this podcast is to provide insight to up-and-coming faculty and fellows about mentoring and partnerships. What is the most important aspect of your partnership with Dr. Schiller? Dr. Doug Lowy: I think treating him as an equal colleague from day one, that probably is important. And then, since I was senior and he was junior, trying to make sure that he got credit when discoveries were made because the default, otherwise, was going to be that it was Doug Lowy who was doing things, whereas it was very clear that John was a key part of this collaboration. Dave Johnson: Now that your relationship is a long-lasting and mature one, how do you make those decisions now? Dr. Doug Lowy: Well, we've just worked together for a long time, and we enjoy talking, and actually, over the last few years, we are collaborating less rather than more. We're still very close colleagues, and we're in the same lab. But since I've been Deputy Director, especially during the last seven and a half years, I've been Acting Director for about three and a half out of the last seven and a half years, and there just isn't enough time to devote to the lab. And it would've been inappropriate for me to have been considered a co-principal investigator with John, who has gone off and done a lot of amazing research, more or less independent of me. Like everything else in this world, it develops, it continues to evolve, but we still are very close colleagues. As Pat was mentioning, this is my first week in several months not being Acting Director, and yesterday, John and I simply reveled in the opportunity to talk informally for 30 minutes without having to look at my watch because I needed to go someplace else. Dave Johnson: I'm glad you've reviewed that. I think a lot of junior faculty and fellows think that being in a leadership position is a cush job, and I'd tell them that it defies the laws of Physics because all poop flows uphill in this setting, and you have to deal with it. Pat Loehrer: I do want to spend some time talking about the NCI and your role there, but talk a little bit about how you have seen and where you envision that vaccines, particularly, HPV and maybe hepatitis vaccine - where you see it's been, and where it's going, and the impact that this potentially has on cancer worldwide? Dr. Doug Lowy: Well, one of the areas that John and I are continuing to work on closely is more research on the HPV vaccines. We noticed, quite a number of years ago, that the HPV vaccine performance was quite different from that of other so-called subunit vaccines. So, this is not an attenuated live vaccine, but instead is a subunit - it's just made up of one protein of the papillomavirus, the protein that gives rise to the outer shell of the virus. And what we noticed in a clinical trial that we were doing with colleagues in the intramural program, but who are medical epidemiologists - they are the leaders of the research, and what was happening was that although everyone was supposed to get three doses, there were some young women who were getting either two doses or one dose, in the trial, and this is in Costa Rica, where historically, cervical cancer has been the number one cancer of women. And it turned out that there was no difference in level of protection whether the women got one dose, two doses, or three doses. And even more surprising was that the antibody levels over the first few years were remarkably stable. And this led John and me to wonder whether it might be possible to get away with just a single vaccine dose. So, a lot of the research that we have been doing with our colleagues over the last few years is to develop stronger evidence that one dose of the vaccine would be sufficient to confer strong protection that's long-lasting. We've now carried out the studies in Costa Rica, with the initial trial to more than 10 years, and the antibody levels continue to be very stable, and the protection does not seem to have waned. Because this was not a pre-specified outcome, it's not enough to change standard of care. So, we and our colleagues are conducting a non-inferiority efficacy trial that is comparing two doses versus one dose of two different FDA-approved vaccines. One, GARDASIL 9, which is the HPV vaccine that's available for sale in the United States. But also Cervarix, which is made by GlaxoSmithKline, it's approved by the FDA, but it's no longer sold in the United States. And we anticipate that the results will read out in another couple of years. And if the results show that one dose and two doses are pretty comparable, we're expecting that this will lead to a worldwide change in recommendations for the HPV vaccine. So, whether you are in a high-income country or a low or middle-income country, that one dose is what will end up being recommended. Pat Loehrer: They could almost completely eradicate this disease, the most common cancer around the world. It's huge. Dr. Doug Lowy: So, Pat, the problem is that although the vaccine was approved 15 years ago, only about 10% of eligible young women in low and middle-income countries have actually been vaccinated up to now. And we think that the logistics and the cost of one dose could really be transformative, especially for those young women. It also would save the United States a great deal of money because needing only one dose would be far less expensive, and the government actually pays for about half of the HPV vaccine that is delivered to teenagers through the Vaccines for Children program. Dave Johnson: Well, this concludes part one of our interview with Dr. Doug Lowy, Principal Deputy Director of the National Cancer Institute and Chief of the Intramural Laboratory of Cellular Oncology in the Center for Cancer Research. In the second part of this episode, Dr. Lowy will give his insight to vaccine hesitancy in the COVID era and the evolution of accomplishments over the past 50 years working at the National Cancer Institute. We want to thank all of our listeners for tuning in to Oncology, Etc. an ASCO Educational podcast, where we will talk about just about anything and everything. So, if you have an idea for a topic or a guest you would like for us to interview on the show, please email us at: education@asco.org. Thank you for listening to the ASCO Education podcast. To stay up to date with the latest episodes, please click, Subscribe. Let us know what you think by leaving a review. For more information, visit the Comprehensive Education Center, at: 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.

In Part Two of this Oncology, Etc. episode, hosts Patrick Loehrer and David Johnson continue their chat with hematologist-oncologist Dr. David Steensma. They explore his views of key opinion leaders and a lifelong passion – collecting rare stamps, including medical stamps. If you liked this episode, please subscribe. Learn more at https://education.asco.org, or email us at education@asco.org. TRANSCRIPT Pat Loehrer: Hi, I'm Pat Loehrer, Director of Global Oncology and Health Equity at Indiana University. I'm here with Dave Johnson, a Medical Oncologist from The University of Texas, Southwestern in Dallas, Texas. Welcome to the second half of our Oncology, Etc. conversation with Dr. David Steensma. He's a highly accomplished physician and scientist in the field of Hematology/Oncology. In the first part of this episode, Dr. Steensma told us about his Dutch immigrant roots, and how a single college biology course changed his career interests from astronomy into medicine. Today, we'll explore his views on Key Opinion Leaders and another passion of his, and an interest of ours - collecting rare stamps, including medical stamps. Dave Johnson: So, David, in addition to your scientific writing, you've been a prolific writer in many other sort of viewpoints and opinion pieces. There's a lot to choose from, but I know you've been interviewed in the past about your column called 'The Raven', which I won't ask you about, as an Edgar Allen Poe fan. You also wrote a wonderful piece called, 'Key Opinion Leaders', which I thought might be quite interesting to ask you about, now that you might be calling upon KOLs. Do you want to tell us a little about that? Dr. David Steensma: Yeah, that's not my favorite term. Thought Leaders is another kind of silly term, but we know what we mean when people are talking about it. Yeah, I've had a chance to write on a lot of different things over the years, and that's been great fun. And when I first heard that term, I couldn't figure out what it meant, KOL. And then, a pharmaceutical representative actually accidentally left a list of KOLs in my office and I realized that not only are KOLs cultivated very carefully, those relationships, but there's a hierarchy of KOLs. They were people who influenced the local formulary and local practice at the institution, there were those who had a regional impact, and then there were those who were on the NCCN guideline committees, and had, you know, much broader impact that they really wanted to make sure to influence the heart and minds of-- in my interactions now, this opinion piece was a sort of tongue-in-cheek about Key Opinion Leaders and Thought Leaders. And with Thought Leaders, I was reminded of Sherlock Holmes's brother Mycroft Holmes, who, by Conan Doyle's fiction, was a brilliant man, but unwilling to stir his ample backside from his Chair in the Diogenes Club to actually get out there, and do some real work, and solve mysteries. And so, it fell to his slightly less brilliant brother, Sherlock, to become the consulting detective. So, that was fun. Now, we're sort of on the receiving end of wisdom from people who are experts in the area. And it's very important what doctors think, and in different geographies about how they think their patients will be potentially treated in a year or two, five years down the road, what the issues they have with current approaches are, where they see opportunity for some of our new compounds, for some of those of other companies, and it's different in Europe versus the US versus Australia. And so, there's a lot that we gain from advisory boards. There's an arc to an advisory board. You don't want to convene an advisory board when there's no data, because then, everybody is just speculating. You don't want to do it too late after something is already on the doorstep of FDA approval because then not anything can be changed at that point. So, you know, doing it at an in-between point where there's some initial data, but where we can really be guided by academic, clinical, and other experts, is really helpful. Pat Loehrer: I'd encourage people to pull this article out. It is really, really good. 2015, I think it came out there. The end of it, I also love it. You're talking about Kanti Rai who came up with the Rai classification and he was at this Meet the Expert session at the ASH meeting, and he said at the meeting, and this is your quote from it, and I love it, he said, "I don't like the name of this session because no one's an expert in chronic lymphocytic leukemia. I've been studying this disease for decades, and still too many of my patients die. If I was truly an expert, the disease would've been cured by now." I just love it, but it's a great read. Dave Johnson: Let me ask you, very seriously, if a younger colleague were to come to you, David, what advice would you give him or her about being invited to be on an advisory board? We'll skip the term KOL or Thought Leader. What advice would you give him or her, and what should they look for, and how should they prepare for that activity should you think they should do it? Dr. David Steensma: Well, I think getting back to imposter syndrome, people should feel, if they're invited to be in such a meeting, that they're there for a reason because their opinion does matter. And sometimes, younger physicians are reluctant to speak up in this setting, especially when there maybe leaders in the field there that have been doing it for decades, and may have very strong opinions. So, not being afraid to share their perspective and realizing that they're invited for a reason. On the other hand, I found it very helpful when I was a young faculty member and, on these panels, to listen to how colleagues were assessing data, and the recommendations they were making, and their perspective. And I learned a lot from some of those advisory boards earlier on. Many of the people who are the senior leaders in leukemia and MDS, you know, Rich Stone, Peter Greenberg, you know, John Bennett, in MDS, Marty Tallman, Hagop Kantarjian, Clara Bloomfield, just people who had decades of experience. And in part, I think it's some of my comments at advisory boards that helped get me my job at Dana-Farber, because I'd been in a number of meetings with Rich Stone, and he apparently liked some of the things I'd said about approaching patients. And so, you know, when a faculty position came open, he invited me out to come visit. And so, they can have benefits that you don't anticipate. Dave Johnson: Yeah, I would definitely agree with that. And there's pros and cons to being involved in those activities, but there are an awful lot of good that comes from it. And I think you've just touched on some of those. I'm going to shift gears a little bit because Pat has been waiting anxiously to hear all about your stamps. So, out of the many, many things that you've done and written about, I would say you've got close to 100 publications on medical stamps. It's an extraordinary productivity, David. So, tell us a little about your interest in medical stamps. How did you get involved in this, and where do you find time to write about them, and how do you decide which ones you're going to write about? Dr. David Steensma: Yeah. Bob Kyle, is really the driver on that, and we continue to do these together. Bob turned 94 this year, and he continues to be intellectually engaged. He's fun to talk to, if it weren't for COVID, he'd still be traveling and coming into the office, you know, which he was doing until just a few years ago. So, I met Bob as an intern when I was at Mayo. Somebody said, "Oh, you should meet this guy, he's really fun to talk to." And we just hit it off. And when I was a boy, my grandfather and my great-grandfather had collected stamps. And my grandfather really got me interested in it, partly given our family history, those of The Netherlands and former colonies, but also just more generally. And then as often happens, I got to be a teenager and other things took over in terms of interest, and there was less time, so, I had fallen away from it a bit. But somehow in this conversation, Bob had mentioned this, and that they were looking for someone younger who had this kind of background, to help with this series that has been running. Initially, it was running in JAMA with a guy named John Mirt, beginning around 1960, and then about a decade later, moved to the Mayo Clinic proceedings when they published six stamp vignettes on medical science per year, and Bob has done over 500 of these going back decades. And so, I got involved in that, and writing about-- thus far, it's mostly focused on individuals, but I have done a few also about more general trends in Philately. I will say that there are fewer of us, certainly those under 50, who are involved in the hobby. There's so much other distractions, but I still find it interesting and fun. And I've learned a lot, putting those vignettes together. Pat Loehrer: I started collecting stamps when I was young, I still have my Scott's album down. And now it's not stored, in properly, but I remember US Number One, I could have bought for $35, but I was only like 10 years old, and that was, you know, like $500 to me. So, I still regret that. Are you collecting stamps yourself now, still that you've resumed the collection part of it? Dr. David Steensma: Yeah. I would say, only a little bit. So, my Netherlands and Colonies collection is now actually complete, except there's one elusive. There's always one, right? Can't find this thing, even at auctions and such. And I also collected coins as a kid, and you know, still have some involvement in that. It's hard to find the time because I do do so many other things, and my wife and I have children, they're now college and PhD age, so I do woodworking, I have a telescope, so I never lost the love of astronomy. It seems like there's always other things to do. But I still have my collection over there on the shelf. Pat Loehrer: Did you inherit it from your grandfather too? Dr. David Steensma: Some of it I did. Yep. The core of it, I inherited from my grandfather and my great-grandfather. And then once I paid off my substantial medical school debt to the University of Chicago with the help of, in part, from advisory boards, but also mostly from moonlighting in emergency rooms around rural Minnesota-- during fellowship, I was like a full-time ER doc who happened to be doing a Hem/Onc Fellowship on the side, and finally got it paid off and then I could start on filling in some of the gaps. Pat Loehrer: Before we change this thing, what is your most cherished stamp that you own? Dr. David Steensma: Oh, my most cherished stamp is not a Dutch one. It is a set of national park stamps from 1934, authorized by James Farley, who was the Postmaster General at that point. 10 stamps, different colors about, you know, Zion and Acadia-- and it was my grandfather's favorite, and he was a big fan of the national parks, took two big trips there back in the '50s out West. And so, at his funeral, I put together a little display of those hanging with the photographs of other things from his life. I have that display, it's very meaningful to me - it's a connection with him. He was certainly very influential in my life. I never imagined I'd be working for a Basel-based pharmaceutical company, like he did for his whole career. Never thought that that would happen, but life has some unexpected twists. He worked for Roche in Nutley, New Jersey for much of his career as a research chemist. And ironically, when my grandmother was diagnosed in the 1990s, pancreatic cancer, and she saw the oncologist and was offered a 5-FU infusion after surgical, he said, "5-FU. I worked on that in 1959, 1960, that's still the best that we have to offer?" He was shocked by that. I was a fellow at the time. I said, "We need better drugs." Dave Johnson: For sure. So, do you have a favorite medical stamp, David? Dr. David Steensma: A favorite medical stamp? Gosh, that one's I think a little bit harder. I certainly have medical stamps that have piqued my interest. One of the sort of most moving is one of the US stamps that came out in the 1950s that has the Sir Luke Fildes' 'The Doctor', on it. You know, with this concerned physician at the bedside of a young boy, and I actually wrote a vignette about the history and background there, and I think that connection with patients at the end of the day when we don't have good drugs, that connection with patients is still so meaningful, isn't it? As you guys really know. So, and as many of our listeners know, and so much of what medicine remains despite the molecular glue degraders and CAR T and gene therapy, is still that human connection, and being there for our patients. And so, I would say that that is probably one of the most meaningful. There's some real quirky ones, too. Austria's come out with some stamps in the last few years; one made of toilet paper, when the toilet paper shortage was happening, another, made of the mask material and the shape of the mask to remind people to mask up. You know, there's been a lot of creativity. And the Dutch are very good about design. They come up with just some brilliant innovations in postage stamps. Dave Johnson: I mean, stamps are really quite artful, by the way, the Fildes painting hangs on the wall of my office. You can't see it, but it's on the wall. And then behind me, you can perhaps see a couple of framed stamps that are some of my favorites. One was a gift to me from a former Group of Chief Residents, of an Osler stamp that Canada put out, and the other is one I received actually as a gift, as part of an award. It's the first cancer stamp that was produced in the United States. So, I love them both. They're quite nice. The Fildes stamp is actually my favorite of all, so I think that's a great stamp. Pat Loehrer: I have actually looked behind me. I've got a stamp collection on the frame that was given to me too that I love. It's stamps of medicine. There was one, a Dag Hammarskjöld stamp, that was famous because they printed it upside down when they put the color in, and I think it created a huge controversy from-- you know this better than I do because they decided then just to overprint them. Instead of making a few sheets that were incredibly valuable, they ended up printing out thousands of these things, which I have one now. It's only worth 7 cents, but at the time, it seemed really cool to have a misprinted stamp in your collection. Dr. David Steensma: Dag Hammarskjöld, there's an interesting connection with what I was talking about a little bit earlier with St. Elizabeth's Hospital. So, this relatively small teaching hospital had, at one point, a very strong hematology research program led by a guy named Fred Stallman. And in 1974, Fred Stallman, who was coming back from ISH, International Society Hematology, which was in Tel Aviv that year, and his plane exploded somewhere over the Aegean Sea, ultimately thought to be related to the PLO, and so he died. There was a big painting on the wall, in the hospital of him. And Dag Hammarskjöld also, at the peak of his career, you know, as the UN Secretary-General, was killed in a plane crash. But the interesting thing about Fred Stallman is, here, you have somebody who was so important in hematology. None of the fellows had any idea who he was or their connection to hematology. You know, it shows how fleeting fame is, unless you're an Einstein or Babe Ruth level. So, that was a good thing to keep in mind as well. Pat Loehrer: We could talk for another hour or two on this. Dave, we really appreciate it. But unfortunately, this is all the time we have for today. And I really want to thank you for joining us, Dave. This has been a wonderful conversation. I also want to thank all our listeners for tuning in to Oncology, Etc. This is an ASCO Education broadcast where we will talk about anything and everything, as you can imagine. If you have an idea for a topic or a guest you'd like to see on the show, just email us at: education@asco.org. Thanks, again. And, Dave, I've got a quiz for you here. Do you know why pirates don't take a shower before they walk off the plank? Dr. David Steensma: I do not. Dave Johnson: I have no idea. Pat Loehrer: It's because they wash up on shore. Dave Johnson: Oh boy. Thank you for listening to the ASCO Education podcast. To stay up-to-date with the latest episodes, please click, "Subscribe." Let us know what you think by leaving a review. For more information, visit the Comprehensive Education Center at: 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.

"What exactly is implicit racial bias? How does it manifest in physician-patient interactions and what is the potential impact of such bias on oncology patient outcomes? In this ASCO Education Podcast episode, Dr. Lauren M. Hamel (Wayne State University) and Dr. Nimish Mohile (University of Rochester) share their insights and perspectives on these topics with host Alissa A. Thomas (University of Vermont). If you liked this episode, please subscribe. Learn more at https://education.asco.org, or email us at education@asco.org. Resources: Blindspot: The Hidden Biases of Good People by Mahzarin R. R. Banaji and Anthony G. Greenwald Implicit Associations Test 21-Day Racial Equity Challenge TRANSCRIPT Dr. Nimish Mohile: We had a patient a few years ago who had presented to our clinic, who ended up having a diagnosis of primary central nervous system lymphoma, and she was a young black woman, and it took about nine months for her to get that diagnosis. She had gone into multiple emergency rooms, she was only 22, had not had prior interaction with the medical system, but based on some of her socioeconomic demographics, her skin color, she was never given the kinds of testing that any other patient I think should have gotten at that time. Dr. Alissa Thomas: Hello, and welcome to another episode of ASCO Education podcast. Today's topic is, 'Implicit racial bias and its impact on patient care.' My name is Alissa Thomas, and I'm a Neurologist and Neuro-Oncologist at the University of Vermont College of Medicine. I'm delighted to introduce our two guest speakers; Dr. Lauren Hamel, who is an Associate Professor of Communication and Behavioral Oncology at Wayne State University, and the Co-program Leader of the Population Studies and Disparities Research Program of the Karmanos Cancer Institute. Her ongoing research explores racial attitudes in non-verbal behavior of oncology patients and physicians, and how those behaviors influence treatment decisions. Dr. Nimish Mohile is a Professor of Neurology and Oncology at The University of Rochester. He also serves as the Diversity Officer, Associate Chair for Career Development and Leadership, and Neuro-Oncology Division Chief. I'll get us started with the first question, really a definition. What do we mean by the term, 'implicit racial bias'? Dr. Lauren Hamel: I'm happy to go first. I think understanding what the definition of what implicit racial bias is is really important. You know, for good or for ill, over the last few years, it's gotten a lot more attention. And I think what's important to remember about it is that it's not a cognizant or a conscious bias, and it really is implicit, and it really is more of an association than it is anything else. It's sort of like the built-up associations that we have for anything. You know, could be race, could be gender, any number of demographics, or other factors that make our lives as humans. So, you know, associating certain aspects of people with positive or negative valuations. I think when we're talking about implicit racial bias, it's kind of like the gut associations we have for members of different racial groups. So often, it's kind of paired with "white is good, black is bad." It's a very rudimentary description of it, but that's a real kind of basic association that this kind of definition is built around. Dr. Nimish Mohile: Yeah, I would agree with that. I think that's a great discussion of what this is. I think it's really important for us to remember that these are really ingrained behaviors. It's, based on, you know, how we've been socialized and conditioned. And I think it's helpful to also put it in the framework of knowing that we all have some biases, we all probably have racial biases, and age biases, and other kinds of biases, and there's no sort of good or bad about having these biases. And the important part of this is, how do we recognize some of the biases that we have so that we can be more conscious about how we might fix those or think differently about the patients that we're seeing so that it doesn't result in actions that can be harmful. Dr. Lauren Hamel: Yeah, I agree with everything that Dr. Mohile just added. It is these ingrained associations. Really, it isn't about blaming ourselves for them because it's kind of the result of how our brains are structured. But to his point, it's once we know that we have them, and you know, we have data showing how they affect our behavior, it's then on us to identify them and then work to mitigate them. Dr. Alissa Thomas: Thank you. How do racial biases in patients and physicians influence treatment decisions or ultimately, how does this affect patient outcomes in Oncology? Dr. Lauren Hamel: You know, I think the direct relationship between certain biases and outcomes is still kind of being uncovered and investigated. But there are some interesting patterns that have been uncovered in data, specifically in the Oncology context too, because as you can imagine, a variety of professional organizations and groups examine the influence of bias. But just within Oncology, we see physicians who have higher levels of implicit bias who tend to see their patients who are black as less trustworthy, less educated, and less adherent to treatment recommendations. We also know that higher levels of implicit bias may be associated with less aggressive treatment programs recommended for black patients. We see some associations between levels of implicit bias and verbal dominance. But what was I think, especially interesting, is that we also see patterns of kind of perceptions from the patients that these physicians are communicating with. So, we see some manifestations in behavior, but we also see patients kind of "picking up" on some of these, whether or not they can identify them as bias necessarily. But for example, we see that patients who are seeing a physician with higher levels of implicit bias tend to see their physicians as less patient-centered, and less trustworthy. And I think that's a really important piece to identify because these biases are by definition kind of operating outside of our own consciousness, but they're manifesting themselves in a way that the people that we're communicating with are noticing. Dr. Nimish Mohile: We had a patient a few years ago who had presented to our clinic, who ended up having a diagnosis of primary central nervous system lymphoma, and she was a young black woman, and it took about nine months for her to get that diagnosis. She had gone into multiple emergency rooms, she was only 22, had not had prior interaction with the medical system, but based on some of her socioeconomic demographics, her skin color, she was never given the kinds of testing that any other patient I think should have gotten at that time. That was a real sort of wake-up call for our clinic, because as some of you know, this is a disease that we can really treat, especially in younger patients. So, there's real consequences to these kinds of biases. And some of them are personal, the ways they're ingrained in us, but some of them are built into our systems, and it's based on; what our ERs are designed like, where our hospital systems are, what kind of relationships we have with primary care physicians in different communities, what kind of access some of our patients have to primary care physicians. This patient in particular didn't have great access to primary care, so she didn't have this other team of people to advocate for her and to say, "Hey, you know, this is something really different in this patient, and we need to take this seriously." So, I think it can get complicated as we think about biases in ourselves, in other people, in the whole health system, and then also as we get out of our health system, some of these things are so influenced by what's going on in our communities. Dr. Lauren Hamel: Yeah, I think that's a really important point. At least with my work, I examine kind of at the interpersonal level, but these biases, as Dr. Mohile points out, exist in all levels of our society, and they interact, and they're-- I don't want to say additive, it's probably much more exponential. But yeah, it's a layer, on top of layer, on top of layer problem. Dr. Alissa Thomas: So, Dr. Mohile, you commented earlier that part of it is recognizing these biases in ourselves. Can you discuss how we might approach this with the impact of an anti-racism education program has been in your department and applications for that? Dr. Nimish Mohile: So, we've worked on anti-racism in our department on a couple of levels. One of the main levels is just building awareness for individuals to understand that they have biases, that they have racial biases, and starting to understand why they have those. So, we've gone through exercises like book clubs and talks, for people to really do some of that self-reflective work to understand how they've been conditioned as they grew up. I've personally done that and have found it very revealing and understood some of the biases that I grew up with based on people I was around, and based on my schools, and based on segregation within my school systems. So, I think that that's one piece of it. I think another piece is we don't often get taught about the history of racism in the United States, and how widespread it is. It's a very small part of our curriculums, and I think we have to take it upon ourselves now in our medical systems to go through that education. Education that we probably should have had all through elementary school, high school, college, we have to do that learning now because then we can really start seeing that impact of race on our society. And I think for physicians specifically, what is that impact of racism on patient care in our medical systems and how it's been ingrained in US healthcare. Understanding that we had segregated hospitals right until the 1960s, those are all things that were in the lifetimes of still practicing Oncologists. One of the things we did for our other professional society that I belong to, The American Academy of Neurology, is we did develop an anti-racism education program that focused on understanding this history and this historical lens in healthcare, reviewing the impact that anti-racism has on our colleagues. So, what does that mean for black physicians or physicians from other underrepresented groups and how they interact with our health systems, how they're treated, what does it mean for their roles in academic departments? Then talking about how we can connect being anti-racist with the goals of health equity. So, how can we change the systems that we have control of to have healthcare that's more fair? And then finally, how do we engage trainees and physicians in really developing anti-racism action plans? One of the important things about anti-racism is that you really have to be active, it's not a passive experience. You have to take action to change all these systems around us that are embedded with racism. Dr. Alissa Thomas: Thank you. Along the same line, Dr. Hamel, you recently co-authored a study of a longitudinal implicit bias training curriculum. And can you tell us something about this project and what's come of it? Dr. Lauren Hamel: Yeah, so it came about a little more than a year ago and kind of coincided happily with an executive directive made by our state's governor requiring implicit bias training, so we were able to kind of design it so it met those requirements. But really what the goal is, is to approach implicit bias with a 360 view. So, what are all of the issues related to it? What are the scientific underpinnings? What are the measurements? What are the pros and cons of those measurements and what we've used, and what they've shown in terms of influence on our individual behavior, our decision-making, kind of how we relate to people who might be different than us. And certainly, expanding beyond racial groups — we've looked at gender, we're looking at age, things like structural racism. So, we're trying to kind of have a comprehensive view of it. And I think, you know, one thing, and it sounds like Dr. Mohile and his group have done a really nice job of tracking what happens after those. Because, you know, I think one-off sessions are better than nothing, certainly. Awareness is critical, but also, tracking like, what does this do for our attitudes, perceptions, and behavior? And that's not easy. And so really, you know, trying to invest in tracking how things change. So, we've had a full year of assessments, we've seen some improvements in people's attitudes and perceptions. But now what we really need to start doing is tracking certain behavioral aspects, and I think that's where the next step needs to be. Our next year is just about to kick off in a couple of weeks. So, I think that that's where we need to start putting our effort where it's—okay, we've gotten kind of institutional support, the leaders of both the University's School of Medicine and also the Cancer Institute have been encouraging this, which I think is really critical, because even though it's a lot of individual work if you want these changes, you really have to have the support and buy-in from the leaders of the institution. So, we've got that, we have interest, you know, we've established a really consistent and impressive participation in terms of each session. We've had upwards of 200 people attending each session, so people want this information. Now, according to the state, they also are required to have it. So, I think building up on that now, we've established a lot of good pieces of it, but now let's start doing a better job of tracking how does this affect long-term perceptions, attitudes, and behavior. Dr. Nimish Mohile: Every cancer center and department should be doing what Dr. Hamel is doing. The risk of the one-off trainings is that people come out of an implicit bias workshop and think, "Well, I'm fixed. I don't need this anymore, now I can go on and take care of patients without bias." And you really need that time to really work on those things and start to fix some of those attitudes that we have. Dr. Lauren Hamel: Yeah. Because the associations get built up over a lifetime. You know, that's not something you're going to fix in an hour. It's a campaign, it's a marathon, to be sure. Dr. Alissa Thomas: So, you've both touched on something that a lot of this is about perception, and it's not just what we say verbally, but non-verbal behavior. It plays into implicit racial bias. Dr. Hamel, can you talk a little about your study of non-verbal synchrony, and can you describe differences between non-verbal behavior with doctors and patients of the same race compared to those of different races? Dr. Lauren Hamel: Yeah, absolutely. And you know, a lot of my work focuses on nonverbal behaviors. On the study you referenced, we were looking at something a little bit more kind of in line with how implicit bias acts. It sort of manifested unconsciously. So, this whole idea of non-verbal synchrony is kind of this non-conscious coordination of movement that happens between two people. And this is a construct that's been studied for decades in a number of settings, but we were the first to be able to examine it in an oncology setting, and also comparing diads of different racial makeup. We were able to take like real video-recorded data of naturally-occurring treatment discussions. We had a set of videos that included black patients in a similar set with white patients. And we used automated software to track their behavior and determine how coordinated they were over time. We actually observed more coordinated behavior between black patients and their physicians compared to white patients and their physicians. Some literature is non-verbal synchrony is sort of seen as always good, and there's also some new data showing that maybe it could be evidence of trying to repair a relationship. We're very early phases, I'm not in a position to offer kind of a best practice with this, but I think the point is, is that we do see differences. There is a coordinated behavioral difference between dyads. We're also starting to look at how that level of coordination is influenced by attitudes including implicit bias. So, I think identifying a difference is important, but now I think it's on us to now figure it out. Like, what is that the result of? And then, what does that do for the patient in terms of short and long-term outcomes? So, does that affect their perceptions of their physician? Does it affect their perceptions of the recommended treatment? Does it affect adherence to that treatment? Dr. Alissa Thomas: How can we do better? How can doctors improve non-verbal and verbal communication methods with our patients? Dr. Nimish Mohile: I can speak a little bit about verbal communication. I think this work on non-verbal communication is fascinating. I'd love to hear where that comes out because it's something I think we're not really thinking about very much, and I'm not surprised that there's differences there. I think sometimes with communication, just having an awareness in that you might be communicating differently with someone can be helpful. In many of our institutions, we sometimes go through coaching with our communication, particularly with Oncology patients, where you have someone witnessing how you're interacting with that patient, and what kind of verbal and non-verbal cues you're giving, how you make eye contact. I think there's models there that we could really be thinking about, not just focused on some of the stuff that oncology has been focused on, like, delivering bad news or end-of-life discussions, but also on these issues of racial bias or age bias, and see what we could do differently in those areas. Dr. Lauren Hamel: Yeah, I completely agree. And I think decades of research have shown that patient-centered communication skills are something that can be taught, learned, and improved upon. Maybe not just regarding the issues related to racial bias and other racial attitudes, but you know, for helping to improve a number of outcomes for patients. So, I think, that kind of focus, I mean there are very clear, well-established frameworks and methods around that, I think that was just, you know, something we already have in our toolbox that we can use. But I think also things like building up trust within a community, I think is critical, for really any kind of medical institution that operates within a community should be, you know, trusted by the community it's in. And there's a number of strategies that can be implemented to build up that level of trust. So, you're kind of looking at like the outside going in. A lot of these the data that I'm referring to right now are coming out of the primary care setting. But I think people like us that are in an Oncology setting are certainly well poised to start testing these in Outpatient Oncology clinics. And I think just like what we're doing right now, making the topic of race, racism, implicit bias, something that we can have in a number of settings. And I think Dr. Mohile made a really good point. Like, we're not taught this like we're taught like grammar, and, you know, math. This is a part of our lives too, and you know, it's having big effects on huge swaths of our population. So, I think normalizing these conversations is a really important step, too. Dr. Nimish Mohile: In the United States, we're particularly uncomfortable talking about racism. Even within our medical teams, we don't know how to do that. So, what do you do if you're on rounds and you see another provider have some kind of verbal or non-verbal communication that, you know, might not be appropriate, or you think that there's a racial bias in the way we're treating or talking to a patient? That's not something we know how to deal with. We don't know how to bring that up. And so, I think that that's something that within health systems, we need to start working on. We have great models for this. When we think about the transitions we've made over the last 20 years in patient safety, we have elevated these conversations about patient safety. If there's a medical error by anyone on a team, it's something we're open to discussing, not blaming, and then really having a conversation about how can we fix this next time. You know, can we work towards doing that with something like racial bias? One of the things we've started doing in our department is that one of our mortality and morbidity conferences each year is focused on racism. So, a scenario where we think that there might have been differing treatment to a patient based on race, and then having an open discussion about that, going through some of the literature about that, and just practicing some of those conversations with each other as faculty, and medical providers, physicians, nurses, advanced practice providers, of being able to name racism as one of these problems. And then we really try to model that behavior on teaching rounds, so that with our medical students and residents, and fellows, we're also having these conversations about how could racism be at play in this patient's story, and how they got to their diagnosis, and in their outcomes, and an acknowledgement that racism is having some effect on this patient's ability to get screened for cancer, and potentially, their ability to have the same survival as another patient. Dr. Alissa Thomas: Thank you. That's so helpful to think about how to elevate this through departments and people who may be less aware of the issue and raising awareness. You both have touched a lot on communication between patients and providers, and there's a theme here that it's not just the doctor-patient relationship, but also the patient's community, and the medical team, that support that physician. Can you elaborate a little bit more about that, about how we communicate to the patient and the community they represent, and the provider and the team that they represent? Dr. Lauren Hamel: Having active, mature, genuine involvement of community members within a cancer hospital or cancer institute, I think is really important. I know my work has benefited from those who have come before me that established really strong connections with people who are, either survivors, care caregivers, advocates, you know, people who are very devoted to their particular neighborhood, community, that work really closely with us and provide feedback on a lot of the interventions that we design. So, one thing that I work in with all of my research is, as I'm developing an intervention that I think will improve either communication with a physician or another care provider, I certainly would never implement that without getting that thoroughly vetted by the people who it's going to affect. My clinician colleagues are always really generous with their time. It's a little bit more challenging to get community member feedback, but I do believe that it is, I mean, not just worth it for my own research success, but also for the mission and the purpose of what we're trying to do here. So, if you seek out feedback from a community group or community members who are willing to give you their honest opinion, and you know, you have to be in a position to receive that feedback with grace and professionalism, I think that's an important piece of it. Like, you want to have that connection, you don't want to just kind of have a checkbox. You know, you really want them involved in what you're doing. I'm using my own personal experience, but I'm sure there's far greater levels of, you know, system-level issues where something similar could be implemented. Dr. Nimish Mohile: I agree with that. I think this is really hard, and I think our medical systems are just starting to learn how to do some of this work. So, I'd echo what Dr. Hamel said about really getting input from members of those communities. I think many cancer centers are trying to do more outreach into communities, and that's not that easy. We have to really start by kind of building that trust, and building a philosophy where it's really about helping that community, as opposed to getting more patients from that community, or getting more trial participants from that community, or being able to check off boxes for our NIH grants from those communities. It really needs to be a genuine approach of, what does this community need? Because we don't often know that answer. And so, we have to start with that curiosity, and then determine how can we help those communities with the resources that we have. And I think cancer centers can do this optimally if the entire health system does that, that's where you can really start building some of that trust. Dr. Alissa Thomas: Thank you. For those of us that want to know more, would you be able to share some practical tools or resources that are available for healthcare professionals who want to learn more about implicit racial bias, either on an individual or institutional level? Dr. Lauren Hamel: I think one of the first things someone can do is take an Implicit Association Test, or an IAT, as it's often referred to. They're all housed at Project Implicit, at Harvard's website - google IAT, it'll take you right there. No identifiable data are collected from the individual test taker, but it gives people a sense of what's being measured. You know, it's not a character assessment, it's a measure that's designed to test your associations. And I think just having that experience makes you a much more informed consumer of this kind of science because I think it's important to keep a critical eye. You know, if we're scientists, we have to be critical. And I think this really helps people kind of get to a point where they can understand the science a little bit more effectively, but maybe also can reduce a little defensiveness that inevitably comes up when these kinds of data are discussed. So, I would do that. And then the second thing would be, there's a wonderful book called, Blindspot: Hidden Biases of Good People, it's written by Doctors Greenwald and Banaji, and they are basically credited for creating the Implicit Association Test, as we know it. It's a relatively easy read, and it can really give you a sense of how these kinds of associations affect our decision-making and communications. I would take those two, as a way to start. Dr. Nimish Mohile: I agree with both of those. I'd say that many of our health systems have implicit bias workshops and trainings, and sometimes they're online, sometimes they're in person. They do have varying sort of quality. I encourage people to just look at those trainings a little bit differently than they look at all of the other trainings that we're forced to do. To go into those with a little bit of an open mind and a learning experience, rather than one to just sort of check boxes and move on. I think you can learn some things about yourself from them. One of the things I encourage folks to do if they're interested in more information about anti-racism is to do something like the 21-day Racial Equity Challenge - you can Google that. Kind of small bite-size openings, and then there's talks about biases, but also helps you sort of understand some of the foundations of racial inequity in this country. Dr. Alissa Thomas: Thank you so much. That's all the time we have for today. I really want to say thank you to Dr. Hamel, and Dr. Mohile for sharing your perspectives on addressing implicit racial bias in oncology, and tips for improving communication with patients and providing culturally-sensitive care. And thank you to ASCO for providing this platform for us to discuss. Thank you to all of our listeners, we appreciate you turning into this episode of ASCO Education podcast. Thank you for listening to the ASCO Education podcast. To stay up to date with the latest episodes, please click," Subscribe." Let us know what you think by leaving a review. For more information, visit the Comprehensive Education Center, at: 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.

In this Oncology, Etc. episode, hosts Patrick Loehrer and David Johnson interview hematologist-oncologist and scientist Dr. David Steensma, who currently serves as Head of Global Hematology at Novartis. In Part One of the episode, Dr. Steensma shares about his career journey from astronomy to medicine, and from academia to industry. We'll also learn about the discovery and significance of a new pre-malignant condition - Clonal Hematopoiesis of Indeterminate Potential (CHIP). If you liked this episode, please subscribe. Learn more at https://education.asco.org, or email us at education@asco.org. TRANSCRIPT Dave Johnson: Hello, everyone, I'm Dave Johnson at UT Southwestern, in Dallas. Pat Loehrer: And I'm Pat Loehrer from Indiana University, in the Center of Global Oncology in Indianapolis. Dave Johnson: And this is another episode of Oncology, Etc. Pat Loehrer: Yeah. Before I get started, I'm going to ask you a quiz. Do you know what a myrmecologist is, Dave? Dave Johnson: Is that somebody who studies snails and conches, or no? Pat Loehrer: No. Not even close. Dave Johnson: Okay. Pat Loehrer: Do you know what a philatelist is? Dave Johnson: I thought it was maybe a small cardiologist. Pat Loehrer: Someone who studies mermaids - no, no. A myrmecologist, actually, is a subject of this book that I just read called, Scientist, it's a story about E.O. Wilson. It's a biography of him. And I didn't know that much about him. Dave Johnson: Oh, ants. Pat Loehrer: Yes. Yeah. Richard Rhodes wrote this book. Actually, it's a great read. I mean, he grew up in Alabama, at the age of seven, he was fishing. And fishing, the hook got caught in his eye, he kept on fishing. He didn't seek medical attention. And later on, he ended up losing his vision in that eye, and his other eye was perfect. So, he used that to focus on little things - he loved ants and butterflies, and at the age of 18, he discovered the first colony of fire ants in the United States, eventually, went to Harvard. He was instrumental in creating the Encyclopedia of Life in which they're basically doing this global database for 1.9 million species. He was a bit of a controversial, but a very proactive person with conservation. He said basically that destroying the rainforest for economic gain is like burning a Renaissance painting to cook a meal. And he's talked about the Brazilian rainforest in which less than 1% of it is now present as it was compared to 100 years ago. It's really quite amazing. His study of ants, the best quote I have from that is he said, "Karl Marx was right." He says, "Socialism works, it's just that he picked the wrong species." So, that's my book today, but I'm gonna turn it over to you, Dave, to introduce our speaker. Dave Johnson: Well, we're very fortunate today to have David Steensma on this episode of Oncology, Etc. Dr. Steensma is a highly accomplished physician-scientist, and an internationally recognized expert in the diagnosis and management of myelodysplastic syndromes. He has numerous academic accomplishments, ranging from characterization of the prevalence of JAK 617F mutations in MDS, first description of the involvement of the IR3G in human neoplasia, and more recently, the initial definition of Clonal Hematopoiesis of Indeterminate Potential, or CHIP - more about that later. Dr. Steensma is a graduate of The University of Chicago Pritzker School of Medicine. He obtained his Internal Medicine and his Hematology-Oncology fellowship training at the Mayo Clinic in Rochester. In the early 2000s, he served as a post-doctoral research fellow and visiting scholar in the molecular biology hematology laboratories of Dr. Douglas Higgs, and Richard Gibson at Oxford University. He has served the medical community in many ways, including on the FDA ODAC Committee, a fun activity if there ever was one, Educational Chair of the 2015 ASH annual meeting, and also as a member of the ABIM Hematology Examination Committee, as well as many others. He is currently the Global Hematology Head at Novartis Institute for Biological Research, where he oversees early-phase development of malignant and non-malignant hematology drugs within Novartis. Prior to moving to industry, he served as the Edward P. Evans Chair in MDS Research at Dana-Farber Cancer Institute in Boston. He's an enthusiastic philatelist. We'll talk about that a little bit more later in the podcast. So, David, welcome to Oncology, Etc, and thank you so much for joining us. Dr. David Steensma: Thank you for having me. Honored to be here. Dave Johnson: Well, why don't we start by asking you just to tell us a little about yourself. Give us a little of your background, where you grew up, about your family, and very importantly, what and who influenced you to pursue Medicine as a career. Dr. David Steensma: Yeah. So, my family is mostly in Michigan. My parents live there now, my sister, you know, extended family - my wife is from there. And when the Dutch came to the US during the great immigration wave around the turn of the 19th into the 20th century, a lot of them settled in Western Michigan- Pat Loehrer: Dave Johnson was there. Dr. David Steensma: -watching this happen? So, a lot of them settled in Western Michigan. I think it reminded them of home, you know, flat, sandy, big body of water to the left, similar kind of climate, and that's really my origin as Dutch immigrant community on both sides. I grew up in New Jersey though, partly because of the Vietnam war. And my dad getting a low number when he was drafted and having to move there, and then they stayed there for decades, and that's where I grew up. I went to college thinking I wanted to do Physics and Astronomy - was fascinated by Astronomy, Astrophysics. Thought that that was gonna be my career, had a job as an undergraduate, working as an observatory assistant, to this day, probably the best job I've ever had. And then, I finished all the courses for my major, I took a course in Cell Biology just for fun, and I thought, "Wow, this is really interesting," and started thinking about going to medical school instead, and took Organic Chemistry over the summer between my junior and senior years of college, and one thing led to another, I ended up applying to medical school instead. I don't have any doctors in my family. My grandfather worked for Roche as a chemist, his whole career. That's the closest we get to Medicine in previous generations. My father was an Aerospace engineer, my mom, a school teacher. You never know what pathways life is going to take you down. Dave Johnson: Actually, I majored in Mechanical Engineering and I love Physics, so I get it. I mean, there were answers there. Medicine has always been a little more puzzling where they create these different words that you have to memorize. But I love people who have gone through the sciences like this. Again, you've had a terrific career in academics, and now you've moved to industry. Tell us a little bit about that transition. What was the attraction, and what have you found to be the differences between the academics and your role now in Novartis? Dr. David Steensma: I love being an academic, and you know, I envisioned that I would retire as such, but you know, things changed a little bit in 2020. It was a very unsettled time, I think, a lot of us thinking about what we were going to do for the next stage of our career. I was also turning 50 at the end of that year, so, milestones like that tend to make us think about where are we going. And Jay Bradner, the head of Novartis's Research Institute, called and said, "You know, we could really use a hematologist for leading our Early Development." And I initially said, "No." I didn't think about it. Although, tremendous respect for Jay, he had been a colleague at Dana-Farber, brilliant guy. I had first met him as a medical student at The University of Chicago some decades earlier, and then he called back and said, "Well, just come out and visit and see what we're all about." And the research institute's just based in Cambridge, Ma. So, it was an easy visit, and one thing led to another, and a few months later, I was leading Hematology Development for Novartis. It really has been a fun transition. I think one of the big attractions for me was being able to do things at a different scale, and I loved Dana-Farber, but I was really getting frustrated with all of the staffing shortages. Clinical trials were really moving slowly, and so, the ability to work with a large range of centers around clinical development was very attractive. And there's a lot of great people at Novartis's Research Institute, it's like a biotech within a larger pharmaceutical company. It's been fun for me also, not just to have that narrow focus on CHIP and myelodysplasia, like I had before, but to be able to be involved in drug development, and lymphoma, and in CAR T, and in sickle cell gene therapy and all kinds of other really fun programs. So, one of the things I've been a little bit shocked by is actually how similar life as an early drug developer is compared to academia. I mean, the biggest difference is not seeing patients, although Novartis would've let me, Dana-Farber did not. So, I've stopped seeing patients, at least for now. But there's a level of emphasis on science, and on careful clinical trial development that I really appreciate. And in many ways, academia has become a little bit more corporate. You know, greater proportion of the funding comes from industry. There are companies that are spinning off all the time from academic institutions. I like to say my Conflicts of Interest declaration has gotten much easier now because there's only one company to declare compared to before. It was, you know, anyone who you'd done a trial with or an advisory board participation. So, it's more similar than it is different. I think it would be different-- People have different roles within companies, and I think if I was in late-stage development, really focused on what's gonna be the big value return for the company, that would be a different type of job, and I'd have to think more about the financial implications and the regulatory to a greater degree than I do. I get to work with scientists who are coming up with new molecular glue degraders and calling and saying, "Hey, where's the disease where this might be applicable?" And talking to the chemists about engineering out different liabilities that might be an issue for our patients, and you know, that really is energizing. Pat Loehrer: You're one of the pioneers in CHIP. Can you talk a little bit about it, and what it means to the average clinician or to the patient? Dr. David Steensma: CHIP is one of the coolest discoveries in the biology of aging, I think in the last 20 years. And we had long had the sense that as people age, the number of hematopoietic stem cells that they have is reduced. In the late '60s, early '70s, there really seems to be a bottleneck, when in childhood, in young adulthood, we have thousands of different hematopoietic stem cells contributing in our blood cell production. And then, there's like a colony collapse that happens and, you know, at age 75, it's a much smaller number, 10 to 12 in most people. In some people hematopoiesis is dominated by a single clone. But we really didn't have an understanding of the mechanism of why that happened. Until 2014, several groups, including Ben Ebert's, led by Sid Jaiswal, a young investigator who's now at Stanford, found that somatic mutations that are common in MDS and leukemia, like TET2 and DNMT3A, these are actually common in aging people with totally normal blood counts. And similar to monoclonal gammopathy of undetermined significance, there's just a portion of the older population that has these somatic mutations. And so, we kind of needed to name for it, and I feel a little bit like what my mentor, from Mayo, Bob Kyle, just one of my personal heroes, you know, he had taken an observation in plasma cell disorders that Jan Waldenström made, that was being called 'benign gammopathy', and didn't really have a good name. And he called it MGUS, Monoclonal Gammopathy of Undetermined Significance, a name that, now for more than 50 years, has been part of the medical lexicon. And so, we did that with CHIP. I wasn't the guy who discovered CHIP, clonal hematopoiesis; it was somebody else's discoveries, but we came up with a definition for it, and a term for it, and it really took off. I mean, that paper has been cited a couple of thousand times already, and it's part of the new World Health Organization classification of hematologic diseases that just debuted this summer. So, that's been a fun world to be involved with, and it has clinical implications. And so, with Irene Ghobrial, who has a special interest in MGUS and smoldering myeloma and their progression to overt myeloma, I founded a clinic at Dana-Farber for patients with CHIP and other related precursor conditions. So, the most interesting thing about CHIP, I think, is that it not only predisposes the human malignancy, but because these cells, these clonal cells, circulate, they interact with the vascular endothelium in different ways. It's a risk factor for cardiovascular events, it's a risk for death from cardiac cause, it's a risk factor for worse gout, worse COPD, but it protects, mechanisms that we don't fully understand yet against dementia. And we think that what's happening is these cells are getting in the brain and they are replacing some of the microglia that just undergo attrition with aging. So, that's fascinating. Somatic mosaicism has been described in lots of different tissues now; the esophagus, the liver, the gut, the skin. You know, these mutations that we normally think of as associated with malignancy can be found in many different tissues as we age. It's just part of life, as part of the entropy of existence. But in the blood, it's special because there's no anatomical constraints on that tissue in the way that there is with a clonal proliferation in the esophagus. And so, the circulation of the blood is what really makes that special. Dave Johnson: So, I'd like to go back just for a moment and talk about your corporate life, if I may. I think many of, if not the majority of our listeners, come from the academic world. And so, they're familiar with the day-to-day activities of an academic such as yourself, but perhaps, less so with what do you do during the day as someone who is responsible for early-phase drug development in industry, what does your day look like? Do you come in every morning and meet with the basic scientist, or is there a corporate meeting? How does your day-to-day activity go? Dr. David Steensma: That's a great question. It's one I get a lot actually, Dave, and I think, you know, because all of us train in academic medical centers, that's a life that's very familiar to us. And what happens in these other arenas - government, industry, biotech - is maybe a little bit less familiar. So, there's a lot of meeting that takes place; meeting with clinical trial teams, meeting with basic scientists, meeting with different operational experts and program managers. So that might involve, "Okay, we have a molecule that this is the safety profile of it. We have two other similar molecules that could go into the same indication, their safety profile is a little bit different. Which one is the one that is most likely to be tolerated and beneficial for patients?" It might then be submitting packages for regulatory consideration by FDA and other health authorities around the world, and then responding to their feedback when they come and say, "Hey, we're not ready to give you this investigational new drug designation and let you start on clinical trials until you do ABC, and then we have to think about how we're going to do ABC. It can involve business development, we call it, which is, "Okay, this is our portfolio, but we really need an X or we really need a Y, and biotech company A has these. Are they willing to talk?" And sometimes they come to us and say, "Hey, we've come up with this compound, we really need the power of a big company to take that forward and do a full development. Are you interested in partnering with us?" I meet with my team members quite regularly in one-on-one meetings, both to talk about specific projects, but also their career development - make sure they're happy and you know, just as in academia, people want to progress to different roles; that's true in the industry world too. You know, connecting people to others and helping them think about what's their next promotion, what's their next role going to look like. And then, there's a lot of governance meetings. So, these are meetings where we say, "Okay, this clinical trial, should we go forward with this or not? It's gonna be $100,000,000 investment, this is the data we have to this point, you know, should we do this? What are the considerations?" That's a big part of it. There is travel, you know, during the COVID pandemic era, been much less so. The one thing I always heard people in industry complain about before I made this switch was the travel. There's been a lot less of that, so it's made me happy because it's been a more balanced lifestyle, that's for sure. But there is still some of that; travel to investigative sites, travel to the big meetings like the ASCO annual meeting, EHA, the ASH annual meeting, and some smaller meetings. So, it's a real mix of things. Dave Johnson: So, let me just follow up with one further question. Do you find that your reading has changed? Dr. David Steensma: I think that my reading has changed a little bit, but mostly because of the breadth of programs that I am now responsible for. So, in the past, I was very heavily focused, at least within Medicine, on the myeloid world and trying to keep track of developments outside of that. But now, I really have to pay attention to new findings in lymphoma, and myeloma, and non-malignant hematology to a greater extent than I was. My reading of things outside of Medicine has also been a little bit broader and there's more time for it because there's not the, you know, staying three hours at night and finishing your Epic EMR inbox. One of the things I've really been impressed by is that in industry, there's not a lot of time wasting. A lot of things that we were asked to do in academic medical centers are things that doctors really don't need to be doing. So, I get to read lots of other things too. Pat Loehrer: Let me follow up on Dave's question. This is a confession on my part. There's so many things that I have done that I don't feel like I'd really qualified to do. There's this imposter syndrome that we talk about. You're now the Head of Global Hematology. Was there a sense as you're taking these steps that, "Wait a minute, this is really a job really too big for me, and I'll try it," or do you just have this innate confidence? How was that? Dr. David Steensma: I am definitely affected by that, it's a major transition. I'd never done anything like this, and even with the assurance of knowing a number of the people at the research institute that I was going to, being confident in Jay Bradner's leadership, and that of Alice Shaw, who is our Translational Clinical Oncology leader, a wonderful colleague, this was still unlike anything that I'd ever done. And so, I was anxious about it. You know, ironically, sometimes the things that we complain about become the best preparation for what's coming in life. And about six years ago, Dana-Farber affiliated with a community-based practice in the Brighton neighborhood in Boston, called St. Elizabeth's Hospital and provided hematology oncology services there, and they really needed somebody to go out for heme malignancies. And talk about taking me out of my comfort zone, instead of having a very narrow clinic where I was seeing marrow failure, and MDS, and leukemia, and MPN, and CHIP, patients with these conditions where I really had a comfort level, I was treating patients with HIV-associated lymphoma, and myeloma, and calling a lot of my colleagues back at Dana-Farber for advice. And I grumbled about being the guy that was asked to do this, but it turned out to be terrific preparation for what I'm doing now because my myeloma knowledge is not obsolete from fellowship 20 years ago. It's up-to-date, I've prescribed, you know, a lot of the newer agents and seeing what the adverse events were, and same with lymphoma, and seeing where the patients' needs were. So, I'm actually really grateful for that experience now, in retrospect. At the time it felt like a nuisance. I had to leave the site and go to the other site, and I had patients in two hospitals, which is not easy, but I'm glad it happened. Pat Loehrer: I think that's an interesting observation. I, too, was at one point in my career spending time between two facilities, with essentially a private practice that was broad and general, versus the more narrow practice I had at the university. And it was challenging, but I think, like you say, it's so rewarding in many ways, and helped me in my transition from being an oncologist to a Chair of Medicine of a major department, in my later years. Dave Johnson: Well, this will wrap up part one of our interview with hematologist, oncologist, and researcher, Dr. David Steensma. In the second part of this episode, we'll ask David about an article he wrote on key opinion leaders, published in the JCO a few years ago - very provocative paper to be sure. We'll also explore how he got into and stayed passionate about stamps; a subject about which he's written extensively. Thank you to all of our listeners for tuning in to Oncology, Etc. 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