ASCO Education

In this episode of ASCO Educational podcasts, we'll explore how we interpret and integrate recently reported clinical research into practice. The first scenario involves a 72-year old man with high-risk, localized prostate cancer progressing to hormone-sensitive metastatic disease. Our guests are Dr. Kriti Mittal (UMass Chan Medical School) and Dr. Jorge Garcia (Case Western Reserve University School of Medicine). Together they present the patient scenario (1:12), review research evidence regarding systemic and radiation therapy for high-risk localized disease (5:45), and reflect on the importance of genetic testing and (10:57) and considerations for treatment approaches at progression to metastatic disease (16:13). Speaker Disclosures Dr. Kriti Mittal: Honoraria – IntrinsiQ; Targeted Oncology; Medpage; Aptitude Health; Cardinal Health Consulting or Advisory Role – Bayer; Aveo; Dendreon; Myovant; Fletcher; Curio Science; AVEO; Janssen; Dedham Group Research Funding - Pfizer Dr. Jorge Garcia: Honoraria - MJH Associates: Aptitude Health; Janssen Consulting or Advisor – Eisai; Targeted Oncology Research Funding – Merck; Pfizer; Orion Pharma GmbH; Janssen Oncology; Genentech/Roche; Lilly Other Relationship - FDA Resources ASCO Article: Implementation of Germline Testing for Prostate Cancer: Philadelphia Prostate Cancer Consensus Conference 2019 ASCO Course: How Do I Integrate Metastasis-directed Therapy in Patients with Oligometastatic Prostate Cancer? (Free to Full and Allied ASCO Members) 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 Dr. Kriti Mittal: Hello and welcome to this episode of the ASCO Education Podcast. Today we'll explore how we interpret and integrate recently reported clinical research into practice, focusing on two clinical scenarios: localized prostate cancer progressing to hormone-sensitive metastatic disease; and a case of de novo metastatic hormone-sensitive prostate cancer progressing to castration-resistant disease. My name is Kriti Mittal and I am the Medical Director of GU Oncology at the University of Massachusetts. I am delighted to co-host today's discussion with my colleague, Dr. Jorge Garcia. Dr. Garcia is a Professor of Medicine and Urology at Case Western Reserve University School of Medicine. He is also the George and Edith Richmond Distinguished Scientist chair and the current chair of the Solid Tumor Oncology Division at University Hospital's Seidman Cancer Center. Let me begin by presenting the first patient scenario. Case 1: A 72-year-old male was referred to urology for evaluation of hematuria. A rectal exam revealed an enlarged prostate without any nodules. A CT urogram was performed that revealed an enlarged prostate with bladder trabeculations. A cystoscopy revealed no stones or tumors in the bladder, but the prostatic urethra appeared to be abnormal looking. Transurethral resection of the prostate was performed. The pathology revealed Gleason score 4+5=9 prostate cancer, involving 90% of the submitted tissue. PSA was performed one week later and was elevated at 50. Patient declined the option of radical prostatectomy and was referred to radiation and medical oncology. So I guess the question at this point is, Dr. Garcia, in 2023, how do you stage patients with high-risk localized prostate cancer and how would you approach this case? Dr. Jorge Garcia: That's a great question and a great case, by the way, sort of what you and I in our practice will call 'bread and butter'. Patients like this type of case that you just presented come from different places to our practice. So either they come through urology or oftentimes they may come through radiation oncology. And certainly, it depends where you practice in the United States, at 'X', US, they may come through medical oncology. So I think that the first question that I have is in whatever role I'm playing in this case, where the patient has seen a urologist or a rad onc or me first, I think it's important for us in medical oncology, at least in the prostate cancer space, to talk about how do we think of their case and put those comments into context for the patient. It's very simple for you to tell a patient you can probably have surgery, radiation therapy, but at the end of the day, how do you counsel that patient as to the implications of the features of his disease is going to be really important. I use very simple examples that I relate to my patients, but really this patient is a patient that has very high-risk prostate cancer based upon the NCCN guidelines and how we actually stratify patients into what we call low-risk, intermediate-, and high-risk, and between those very low and very high risk. So his PSA is high, very high, I would argue. His Gleason score, now, what we call group grading is high. He has high-volume disease. So the first question that I would have is, what are the choices for treatment for a patient like this? But even before you and I may talk about treatment options, we really want to understand the volume of their disease and whether or not they have localized prostate cancer with high-risk features or whether or not they have locally advanced or hopefully not metastatic disease. So back in the days prior to the FDA approval for PSMA PET imaging, we probably will have a Technetium-99 whole-body bone scan, and/or we probably will actually use CT scanning. Most people in the past, we used to do just a CT of the abdomen and pelvic region. As you know, with the movement of oral agents in the advanced setting, I think most of us will do a chest CT, abdomen and pelvic region, and certainly we also probably will have a Technetium-99 bone scan. Now, with the utility and the use of PET imaging, I think most people like him will probably undergo PET PSMA, where you use F-18 PSMA or Gallium-68 PSMA. I think the importance depends on how you look at the approval of these two technologies. I think that PET PSMA imaging is here to stay. It's probably what most of us will use. And based upon that, we will define yet the truest stage of this patient. So right now, what we know is he has high-risk features. Hopefully, their disease is localized. We'll probably put the patient through an imaging technology. If you don't have access to a PET, then obviously CT and a bone scan will do. But if you do, the PET will actually help us define if the patient has disease outside of the prostate region, in the pelvic area, or even if they have distant metastases. Dr. Kriti Mittal: I would agree with that approach, Dr. Garcia. I think in the United States, we've been late adopters of PSMA scans. I think this patient with high-risk localized disease, if insurance allows at our institution, would get a PSMA for staging. There are still some patients where insurance companies, despite peer-to-peer evaluations, are not approving PSMAs. And in those situations, the patient would benefit from conventional CTs and a bone scan. So let's say this patient had a PSMA and was found not to have any regional or distant metastases. He decided against surgery, and he is seeing you as his medical oncologist together with radiation. What would your recommendations be? Dr. Jorge Garcia: I think the bigger question is, do we have any data to suggest or to demonstrate that if in the absence of metastatic disease with conventional imaging or with emerging technologies such as PSMA PET, there is no evidence of distant disease, which I think you probably agree with me, that would be sort of unlikely with a patient with these features not to have some form of PSMA uptake somewhere in their body. But let's assume that indeed then the PSMA PET was negative, so we're really talking about high-risk localized prostate cancer. So I don't think we can tell a patient that radical prostatectomy would not be a standard of care. We never had a randomized trial comparing surgery against radiation therapy. This patient has already made that decision and surgery is not an option for him. If he, indeed, had elected radiotherapy, the three bigger questions that I ask myself are where are you going to aim the beam of that radiation therapy? What technology, dose, and fractionation are you going to use? And lastly, what sort of systemic therapy do you need, if any, for that matter? Where we do have some data maybe less controversial today in 2023 compared to the past? But I think the question is, do we do radiation to the prostate only or do we expand the field of that radiation to include the pelvic nodes? Secondly, do we use IMRT? Do you use proton beam or not? Again, that's a big question that I think that opens up significant discussions. But more important, in my opinion, is the term of hypofractionation. I think the field of radiation oncology has shifted away from the old standard, five, seven weeks of radiation therapy to more hypofractionation, which in simple terms means a higher dose over a short period of time. And there was a concern in the past that when you give more radiation on a short period of time, toxicities or side effects would increase. And I think that there is plenty of data right now, very elegant data, demonstrated that hypofractionation is not worse with regards to side effects. I think most of us will be doing or supporting hypofractionation. And perhaps even to stretch that, the question now is of SBRT. Can we offer SBRT to a selected group of patients with high-risk prostate cancer? And again, those are discussions that we will naturally, I assume, in your practice, in your group, you probably also have along with radiation oncology. Now, the bigger question, which in my mind is really not debatable today in the United States, is the need for systemic therapy. And I think we all will go back to the old data from the European EORTC data looking at the duration of androgen deprivation therapy. And I think most of us would suggest that at the very least, 24 months of androgen deprivation therapy is the standard of care for men with high-risk prostate cancer who elect to have local definitive radiation therapy as their modality of treatment. I think that whether or not it's 24 or 36, I think that the Canadian data looking at 18 months didn't hit the mark. But I think the radiation oncology community in the prostate cancer space probably has agreed that 24 months clinically is the right sort of the sweetest spot. What I think is a bit different right now is whether or not these patients need treatment intensification. And we have now very elegant data from the British group and also from the French group, suggesting, in fact, that patients with very high-risk prostate cancer who don't have evidence of objective metastasis may, in fact, benefit from ADT plus one of the novel hormonal agents, in this case, the use of an adrenal biosynthesis inhibitor such as abiraterone acetate. So I think in my practice, what I would counsel this patient is to probably embark on radiotherapy as local definitive therapy and also to consider 24 months of androgen deprivation therapy. But I would, based upon his Gleason score of group grading, his high-volume disease in the prostate gland, and his PSA, to probably consider the use of the addition of abiraterone in that context. Dr. Kriti Mittal: That is in fact how this patient was offered treatment. The patient decided to proceed with radiation therapy with two years of androgen deprivation. And based on data from the multi-arm STAMPEDE platform, the patient met two of the following three high-risk features Gleason score >8, PSA >40, and clinical >T3 disease. He was offered two years of abiraterone therapy. Unfortunately, the patient chose to decline upfront intensification of therapy. In addition, given the diagnosis of high-risk localized prostate cancer, the patient was also referred to genetic counseling based on the current Philadelphia Consensus Conference guidelines. Germline testing should be considered in patients with high-risk localized node-positive or metastatic prostate cancer, regardless of their family history. In addition, patients with intermediate-risk prostate cancer who have cribriform histology should also consider germline genetic testing. Access to genetic counseling remains a challenge at several sites across the US, including ours. There is a growing need to educate urologists and medical oncologists to make them feel comfortable administering pretest counseling themselves and potentially ordering the test while waiting for the results and then referring patients who are found to have abnormalities for a formal genetics evaluation. In fact, the Philadelphia Consensus Conference Guideline offers a very elegant framework to help implement this workflow paradigm in clinical practice. And at our site, one of our fellows is actually using this as a research project so that patients don't have to wait months to be seen by genetics. This will have implications, as we will see later in this podcast, not only for this individual patient as we talk about the role of PARP inhibitors but also has implications for cascade testing and preventative cancer screening in the next of kin. Dr. Jorge Garcia: Dr. Mittal, I think that we cannot stress enough the importance of genetic testing for these patients. Oftentimes I think one of the challenges that our patients are facing is how they come into the system. If you come through urology, especially in the community side, what I have heard is that there are challenges trying to get to that genetic counsel. Not so much because you cannot do the test, but rather the interpretation of the testing and the downstream effect as you're describing the consequences of having a positive test and how you're going to counsel that patient. If you disregard the potential of you having an active agent based upon your genomic alteration, is the downstream of how your family may be impacted by a finding such as the DNA repair deficiency or something of that nature. So for us at major academic institutions because the flow how those patients come through us, and certainly the bigger utilization of multi-disciplinary clinics where we actually have more proximity with radiation oncology urology, and we actually maybe finesse those cases through the three teams more often than not, at least discuss them, then I think that's less likely to occur. But I think the bigger question is the timing of when we do testing and how we do it. So there are two ways -- and I'd love to hear how you do it at your institution -- because there are two ways that I can think one can do that. The low-hanging fruit is you have tissue material from the biopsy specimen. So what you do, you actually use any of the commercial platforms to do genomic or next-generation sequencing or you can do in-house sequencing if your facility has an in-house lab that can do testing. And that only gets you to what we call 'somatic testing', which is really epigenetic changes over time that are only found in abnormal cells. It may not tell you the entire story of that patient because you may be missing the potential of identifying a germline finding. So when you do that, did you do germline testing at the same time that you do somatic testing or did you start with one and then you send to genetic counseling and then they define who gets germline testing? Dr. Kriti Mittal: So at our site, we start with germline genetic testing. We use either blood testing or a cheek swab assay and we send the full 84-gene multigene panel. Dr. Jorge Garcia: Yeah, and I think for our audience, Dr. Mittal, that's great. I don't think you and I will be too draconian deciding which platform one uses. It's just that we want to make sure that at least you test those patients. And I think the importance of this is if you look at the New England Journal paper from many years ago, from the Pritchard data looking at the incidence of DNA repair deficiency in men with prostate cancer in North America, that was about what, around 10% or so, take it or leave it. So if you were to look only for germline testing, you only will, in theory, capture around 10% of patients. But if you add somatic changes that are also impacting the DNA pathway, then you may add around 23%, 25% of patients. So we really are talking that if we only do one type of testing, we may be missing a significant proportion of patients who still may be candidates, maybe not for family counseling if you had a somatic change, rather than germline testing, the positivity, but if you do have somatic, then you can add into that equation the potential for that patient to embark on PARP inhibitors down the road as you stated earlier. It may not change how we think of the patient today, or the treatment for that matter. But you may allow to counsel that patient differently and may allow to sequence your treatments in a different way based upon the findings that you have. So I could not stress the importance of the NCCN guidelines and the importance of doing genetic testing for pretty much the vast majority of our patients with prostate cancer. Dr. Kriti Mittal: Going back to our patient, three years after completion of his therapy, the patient was noted to have a rising PSA. On surveillance testing, his PSA rose from 0.05 a few months prior to 12.2 at the time of his medical oncology appointment. He was also noted to have worsening low back pain. A PSMA scan was performed that was noteworthy for innumerable intensely PSMA avid osseous lesions throughout his axial and appendicular skeleton. The largest lesion involved the right acetabulum and the right ischium. Multiple additional sizable lesions were seen throughout the pelvis and spine without any evidence of pathologic fractures. So the question is, what do we do next? Dr. Jorge Garcia: The first question that I would have is, the patient completed ADT, right? So the patient did not have treatment intensification, but at the very least he got at least systemic therapy based upon the EORTC data. And therefore, one would predict that his outcome will have been improved compared to those patients who receive either no ADT or less time on ADT. But what I'm interested in understanding is his nadir PSA matters to me while he was on radiation and ADT. I would like to know if his nadir PSA was undetectable, that's one thing. If he was unable to achieve an undetectable PSA nadir, that would be a different thought process for me. And secondly, before I can comment, I would like to know if you have access to his testosterone level. Because notably, what happens to patients like this maybe is that you will drive down testosterone while you get ADT, PSAs become undetectable. Any of us could assume that the undetectability is the result of the radiation therapy. But the true benefit of the combination of radiation and ADT in that context really comes to be seen when the patient has got off the ADT, has recovered testosterone, and only when your testosterone has normalized or is not castrated, then we'll know what happens with your serologic changes. If you rise your PSA while you recover testosterone, that is one makeup of patient. But if you rise your PSA while you have a testosterone at the castrated level, that would be a different makeup of a patient. So do we have a sense as to when the patient recovered testosterone and whether or not if his PSA rose after recovery? Dr. Kriti Mittal: At the time his PSA rose to 12, his testosterone was 275. Dr. Jorge Garcia: Okay, perfect. You and I would call this patient castration-naive or castration-sensitive. I know that it's semantics. A lot of people struggle with the castration-naive and castration-sensitive state. What that means really to me, castration-naive is not necessarily that you have not seen ADT before. It's just that your cancer progression is dependent on the primary fuel that is feeding prostate cancer, in this case, testosterone or dihydrotestosterone, which is the active metabolite of testosterone. So in this case, recognizing the patient had a testosterone recovery and his biochemical recurrence, which is the rising of his PSA occur when you have recovery of testosterone, makes this patient castration-sensitive. Now the PET scan demonstrates now progression of his disease. So clearly he has a serologic progression, he has radiographic progression. I assume that the patient may have no symptoms, right, from his disease? Dr. Kriti Mittal: This patient had some low back pain at the time of this visit. So I think we can conclude he has clinical progression as well. Dr. Jorge Garcia: Okay, so he had the triple progression, serologic, clinical, and radiographic progression. The first order of business for me would be to understand the volume of his disease and whether we use the US CHAARTED definition of high volume or low volume, or whether we use the French definition for high volume from Latitude, or whether we use STAMPEDE variation for definition, it does appear to me that this patient does have high-volume disease. Why? If you follow the French, it's a Gleason score of >8, more than three bone metastases, and the presence of visceral disease, and you need to have two out of the three. If you follow CHAARTED definition, we did not use Gleason scoring, the US definition. We only use either the presence of visceral metastases or the presence of more than four bone lesions, two of which had to be outside the appendicular skeleton. So if we were to follow either/or, this patient would be high-volume in nature. So the standard of care for someone with metastatic disease, regardless of volume, is treatment intensification, is you suppress testosterone with androgen deprivation therapy. And in this case, I'd love to hear how you do it in Massachusetts, but here, for the most part, I would actually use a GnRH agonist-based approach, any of the agents that we have. Having said that, I think there is a role to do GnRH antagonist-based therapy. In this case, degarelix, or the oral GnRH antagonist, relugolix, is easier to get patients on a three-month injection or six-month injection with GnRH agonist than what it is on a monthly basis. But I think it's also fair for our audience to realize that there is data suggesting that perhaps degarelix can render testosterone at a lower level, meaning that you can castrate even further or have very low levels of testosterone contrary to GnRH agonist-based approaches. And also for patients maybe like this patient that you're describing, you can minimize the flare that possibly you could get with a GnRH agonist by transiently raising the DHT before the hypothalamic-pituitary axis would shut it down. So either/or would be fine with me. Relugolix, as you know, the attraction of relugolix for us right now, based upon the HERO data, is that you may have possibly less cardiovascular side effects. My rationale not to use a lot of relugolix when I need treatment intensification is quite simple. I'm not aware, I don't know if you can mitigate or minimize that potential cardiovascular benefit by adding abiraterone or adding one of the ARIs, because ARIs and abiraterone by themselves also have cardiovascular side effects. But either/or would be fine with me. The goal of the game is to suppress your male hormone. But very important is that regardless of volume, high or low, every patient with metastatic disease requires treatment intensification. You can do an adrenal biosynthesis inhibitor such as abiraterone acetate. You can pick an androgen receptor inhibitor such as apalutamide or enzalutamide if that's the case. The subtleties in how people feel comfortable using these agents, I think, none of us – as you know, Dr. Mittal - can comment that one oral agent is better than the other one. Independently, each of these three oral agents have randomized level 1, phase III data demonstrating survival improvement when you do treatment intensification with each respective agent. But we don't have, obviously, head-to-head data looking at this. What I think is different right now, as you know, is the data with the ARASENS data, which was a randomized phase III trial, an international effort looking at triple therapy, and that is male hormone suppression plus docetaxel-based chemotherapy against testosterone suppression plus docetaxel-based chemotherapy plus the novel androgen receptor inhibitor known as darolutamide. This trial demonstrated an outcome survival improvement when you do triple therapy for those high-volume patients. And therefore, what I can tell you in my personal opinion and when I define a patient of mine who is in need of chemotherapy, then the standard of care in my practice will be triple therapy. So if I know you are a candidate for chemotherapy, however, I make that decision that I want you to get on docetaxel upfront. If you have high-volume features, then the standard of care would not be ADT and chemo alone, it would be ADT, chemo, and darolutamide. What I don't know, and what we don't know, as you know, is whether or not triple therapy for a high-volume patient is better, the same, equivalent, or less than giving someone ADT plus a novel hormonal agent. That is the data that we don't have. There are some meta-analyses looking at the data, but I can tell you that at the very least, if you prefer chemo, it should be triple therapy. If you prefer an oral agent, it certainly should be either apalutamide, abiraterone acetate, and/or enzalutamide. But either/or, patients do need treatment intensification, and what is perplexing to me, and I know for you as well, is that a significant proportion of our patients in North America are still not getting treatment intensification, which is really sub-optimal and sub-standard for our practice. Dr. Kriti Mittal: Thank you, Dr. Garcia, for a terrific discussion on the application of recent advances in prostate cancer to clinical practice. In an upcoming podcast, we will continue that discussion exploring management of de novo metastatic prostate cancer. The ASCO Education Podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncologists' well-being and professional development. If you have an idea for a topic or a guest you'd like to see on the ASCO Education Podcast, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

The early 1970's saw the start of the medical specialty we now know as oncology. How does one create standards and practices for patient care during that time? Dr. John Glick is a pioneer during the dawn of oncology. He says that early work involved humanity, optimism, and compassion, all of which were the foundation of his career. Dr Glick describes the clinical experiences that drove him to oncology (4:28), his rapport with patients, which was portrayed in Stewart Alsop's book Stay of Execution (9:21), and his groundbreaking work developing the medical oncology program at the University of Pennsylvania (12:22). Speaker Disclosures Dr. David Johnson: Consulting or Advisory Role – Merck, Pfizer, Aileron Therapeutics, Boston University Dr. Patrick Loehrer: Research Funding – Novartis, Lilly Foundation, Taiho Pharmaceutical Dr. John Glick: None More Podcasts with Oncology Leaders Oncology, Etc. – In Conversation with Dr. Richard Pazdur (Part 1) Oncology, Etc. – HPV Vaccine Pioneer Dr. Douglas Lowy (Part 1) Oncology, Etc. – Rediscovering the Joy in Medicine with Dr. Deborah Schrag (Part 1) 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 Disclosures for this podcast are listed in the podcast page. Pat Loehrer: Welcome to Oncology, Etc. This is an ASCO education podcast. I'm Pat Loehrer, Director of Global Oncology and Health Equity at Indiana University. Dave Johnson: And I'm Dave Johnson, a medical oncologist at the University of Texas Southwestern in Dallas, Texas. If you're a regular listener to our podcast, welcome back. If you're new to Oncology, Etc., the purpose of our podcast is to introduce listeners to interesting people and topics in and outside the world of oncology. Today's guest is someone well-known to the oncology community. Dr. John Glick is undoubtedly one of oncology's most highly respected clinicians, researchers, and mentors. I've always viewed John as the quintessential role model. I will add that for me, he proved to be a role model even before I met him, which hopefully we'll talk about a little bit later. To attempt to summarize John's career in a paragraph or two is really impossible. Suffice it to say, he is to the University of Pennsylvania Cancer Center what water is to Niagara Falls. You can't have one without the other. After completing his fellowship at NCI in Stanford, John joined the Penn faculty in 1974 as the Ann B. Young Assistant Professor. Some five decades later, he retired as the director of one of the most highly respected comprehensive cancer centers in the nation. Among his many notable accomplishments, I will comment on just a few. He established the Medical Oncology program at Penn and subsequently directed the Abramson Cancer Center from 1985 to 2006. Interestingly, he established the Penn Medicine Academy of Master Clinicians to promote clinical excellence in all subspecialties across the health system. He's been a driving force in philanthropy at Penn Medicine, culminating in his role as Vice President Associate Dean for Resource Development. Over the past several decades, he has helped raise over half a billion dollars for Penn Med. We need you on our team, John. As a clinician scholar, John's research has helped shape standards of care for both breast cancer and lymphomas. For example, he pioneered the integration of adjuvant chemotherapy and definitive breast irradiation for early-stage breast cancer. In 1985, he chaired the pivotal NCI Consensus Conference on adjuvant chemotherapy for breast cancer. He also was a driving force in a clinical landmark study published in The New England Journal some 20 or so years ago about the role of bone marrow transplant for advanced breast cancer. Most impressive of all, in my opinion, is John's legacy as a mentor to multiple generations of medical students, residents, and fellows. So, John, we want to thank you for joining us and welcome. Thought we might start by having you tell us a little about your early life, your family, your parents, where you grew up, and how you got into medicine. Dr. John Glick: Well, thank you for having me on the podcast, Pat and David, it's always a pleasure to be with you and with ASCO. I grew up in New York City in Manhattan. My father was a well-known dermatologist. He was my role model. And from the age of eight, I knew I wanted to be a doctor. Nothing else ever crossed my mind. But having seen my father's many interests outside of medicine, I realized from very early that there was much more to medicine than just science. And that really induced me, when I went to college, to major in the humanities, in history, art history, and I actually took the minimum number of science courses to get into medical school. That probably wouldn't work today, but it was the start of my interest in humanism, humanities, and dealing with people outside of the quantitative sciences. Dave Johnson: So that's reflected in how we all view you, John. You're one of the most humanistic physicians that I know personally. I wonder if you could tell us about your interest in medical oncology, and in particular, as one of the pioneers in the field. I mean, there wasn't really even a specialty of medical oncology until the early 1970s. So, how in the world did you get interested in oncology and what drew you to that specialty? Dr. John Glick: Well, I had two clinical experiences that drove me into oncology. The first, when I was a third year medical student at Columbia PNS, my first clinical rotation in internal medicine, I was assigned a 20-year-old who had acute leukemia, except he was not told his diagnosis. He was told he had aplastic anemia, receiving blood and platelets, and some form of chemotherapy. And I spent a lot of time just talking to him as an individual, not just taking care of him. And we became friends. And he was then discharged, only to be readmitted about two weeks later. And in the elevator, the medical assistant had his admission sheet, and unfortunately, it was facing the patient, and it had his diagnosis, acute leukemia. So he came into the ward and he confronted me. "Why didn't you tell me I had acute leukemia?" Well, I couldn't say the attendees forbade me to do that. So I took what today we would call 'the hit', and apologized. But it stimulated me to reflect that honesty with patients was extremely important, and that oncology was just in its infancy. We knew nothing about it. It was not considered even a specialty. I don't think we used the word "oncology." But that inspired me to take an elective in my fourth year at PNS, at an indigent cancer hospital called the Francis Delafield Hospital. It only took care of indigent cancer patients, and there were wards, twelve patients in a ward, six on each side, and nobody would go see the patients. It was almost as if they were afraid that if they were to touch the patient, they would get cancer. And I started talking to the patients, and they were human beings, but nobody had told them their diagnosis. Nobody had told them if they were terminal. And there were a few patients who were getting a new drug at that time for multiple myeloma called melphalan, and they actually had relief of some of the symptoms, of their bone pain. But I realized that there was a huge void in medicine that I could possibly help to fill. And that was the era of Vietnam, and so I applied to the National Cancer Institute to become a commissioned officer in the Public Health Service to avoid the draft, to be on a service with, at that time, some very notable oncologists Vince DeVita, Ed Henderson, Paul Carbone. I had read some of their papers, and I was lucky to be accepted. And I was a clinical associate at the National Cancer Institute. And that was life-changing because there every patient was considered to be potentially curable. The advances at that time using MOPP for Hodgkin's disease, C-MOPP for lymphoma, some treatments for leukemia. George Canellos pioneered the use of CMF for metastatic breast cancer. It was an amazing, amazing experience. That was in 1971 to '73. Oncology did not become a true specialty till '73, but my two years at NCI were formative. However, I realized that there was something missing in my training. Everybody was considered curable, but I had never seen a patient with metastatic colon cancer, metastatic lung cancer. The radiotherapists there did not like to teach clinical associates, and I knew that there was a place called Stanford. And Stanford had Saul Rosenberg in medical oncology for lymphomas and Henry Kaplan in radiotherapy. So, everybody was going to California, and my wife and I packed up and went to California and spent a year at Stanford, which, combined with my training at the NCI, led me to the principles that guided my career in oncology; humanity, optimism, reality, compassion, and a love for clinical trials. I was very, very fortunate to be there at the dawn of medical oncology shortly after I decided to go to Penn, which at that time did not have a medical oncologist. In fact, I was the only medical oncologist at Penn for four years and did every consult in the hospital for four years, much to the chagrin of my wife. But I was fortunate to have great mentors in my career: Paul Carbone, Vince DeVita, Saul Rosenberg, Henry Kaplan, among many, many others. And that impressed me about the importance of mentorship because my career would never have been where it was or is without these mentors. Pat Loehrer: John, just to echo what Dave said, you've been such a tremendous mentor for us. Dave and I particularly, you took us under your wings when you didn't know who we were. We were people in the Midwest. We weren't from any place shiny, but we really appreciate that. Dave Johnson: So, John, I mentioned at the very beginning that I met you before I met you, and the way I met you was through Stewart Alsop's book, Stay of Execution. He portrayed you as an extraordinarily caring individual, and it tremendously impacted me. It was one of the reasons why I chose oncology as a specialty. I realize it's been 50 or more years ago and most of our listeners will have no idea who Stewart Alsop was. And I wonder if you might share with us a little bit of that experience interacting with someone who was particularly well-known in that time as a columnist for The New York Times. Dr. John Glick: His brother Joe Alsop and Stu Alsop were two of the most famous columnists at that time. Joe Alsop was a hawk right-winger who lived in the Vietnam War. Stewart was charming, was a centrist Democrat, wrote the back page for Newsweek for years. He and I had very similar educational backgrounds and interests. And we functioned on two different levels—one as a physician-patient, and then we became friends. And he and his wife adopted us into the Georgetown set. And I received a lot of criticism for socializing with a patient. But over the years, I've been able to become friends with many of my patients, and I've been able to compartmentalize their medical care from our friendship. And I use the analogy if I was a doctor in a small town and I was the only doctor, I'd be friends with people in town, with the pastor and likely the mayor. But I have always believed that patients can become your friends if they want it and if they initiated it. Taking care of Stewart Alsop was an amazing, amazing experience. We didn't know what he had. People initially thought he had acute leukemia. In reality, he had myelodysplastic syndrome, but that hadn't been described yet. He had a spontaneous remission, which I rarely see, probably due to interferon released from a febrile episode, all his blasts went away in his marrow. One of my children's middle name is Stewart. But professionally and personally, it was an incredible experience. It taught me the importance of being available to patients. They had my home phone number. We didn't have cell phone numbers in those days. We had beepers, but they didn't work. And from that point on, I gave my home phone number to patients, and I actually trained my children how to answer the phone. "This is Katie Glick. How can I help you? My father's not home. You need my father? Can I have your phone number? I'll find him and he'll call you back." Patients still remember my children and their way of answering the phone. Pat Loehrer: One of the things you did do is create this medical oncology program at Penn, which has graduated some incredible fellows that have become outstanding leaders in our field. But can you reflect a little bit about the process of creating something that was never created before, like a medical oncology program? Dr. John Glick: Well, I came to Penn, my first day. Person who recruited me was on sabbatical. I asked where my office was and there was no office. There was an exam room. There was a clinic for indigent patients which we scrubbed by hand. There was another office for patients who paid. Within two months, I had abolished that. We had one– I hate to use the word clinic, people still use the word clinic today, but one office that took care of all patients, irregardless of means. I saw every oncology consult in the hospital for four years. But I had a mentor, not only Buz Cooper, but fortunately, Jonathan Rhoads was Chairman of Surgery, and he was also Chairman of the President's Cancer panel. And what he said at Penn in surgery became the law. And then when we introduced lumpectomy for breast cancer and radiotherapy, he endorsed it immediately. All the other surgeons followed suit. I don't think there's any hospital in the country that adopted lumpectomy and radiotherapy for breast cancer as quickly. And the surgeons were instrumental in my career. Now, I was taking care of gliomas, head and neck cancers, and it was difficult. If I had a colorectal patient, I'd call Charles Moertel at Mayo Clinic and say, "What do I do?" I was there when Larry Einhorn in 1975 presented his data on testicular cancer with the platinum. Unbelievably inspiring, transformational. It also showed the importance of single-arm studies. You didn't have to do randomized studies because the results were so outstanding. And so in my career, I did both single-arm studies, proof of principle studies, and then many randomized trials through the cooperative groups. But the first four years were very difficult. I didn't know what the word 'work-life balance' meant in those days. If somebody was sick, I stayed and saw them. It was difficult introducing new principles. When I first mentioned platinum after Larry's presentation, I was laughed out of the room because this was a heavy metal. When patients were dying, they died in the hospital, and I wanted to hang up morphine to assist them. The nurses reported me to the administration. I had to fight to get the vending machines for cigarettes out of the hospital. So there were a lot of victories along the way and a lot of setbacks. It took me several years to have an oncology unit of six beds, and now I think we have 150 or 160 beds and need more. So it was an interesting and, in retrospective, a wonderful experience, but I didn't know any better. Fortunately, I had a great wife who was working at Penn and then at Medical College of Pennsylvania, and she was incredibly understanding, never complained. And I think my kids knew that on Tuesdays and Thursdays, don't bring up anything difficult with dad because he's had a really tough day in clinic. Dave Johnson: We were not in that era, but we were very close. And many of the struggles that you had were beginning to dissipate by the time we were completing our training. But it was still a challenge. I mean, all those things. I gave my own chemotherapy for the first few years I was in practice. I don't know that our colleagues today who have trained in the last, say, 10 or 15 years, actually realize that that was what we did. Most of the chemo was given in the hospital. It was not uncommon in the early days to have 20, 30, 40 inpatients that you would round on because there just wasn't an outpatient facility. But the corporate mind made a big difference, allowing us to give drugs like platinum in the outpatient arena. You span all of that era, and so you've seen the whole panoply of change that has taken place. John, the other thing you did that has impressed me, in part because of my time as a Chair of Medicine, is you created this Academy of Master Clinicians. Can you tell us a bit about that and what was the motivation behind that? Dr. John Glick: Ben had a strategic plan, and one of the pillars was talking about valuing clinical medicine and clinical excellence. But there was no implementation plan. It was sort of just words and left in the air. And I was no longer director of the cancer center, and I realized we had a lot of awards for research, awards for education, and no awards for clinical excellence. So I created the idea of having an academy and master clinician spend six months talking to all constituencies, chairs of various departments, directors of centers to get a buy-in. Wrote a three-page white paper for the dean, who approved it immediately. And then, as typical at Penn, I raised all the money for it. I went to one of my patients who was an executive at Blue Cross. I said I need $500,000 to start this program. And then subsequently, I raised $4 million to endow it. Today, it is the highest honor that a Penn clinician can receive. You could be on any one of our multiple tracks. You have to see patients at least 60% of the time. You not only have to be a great doctor, you have to be a humanist. So the world's best thoracic surgeon who has a demeanor in the operating room that is not conducive to working with a nurse as a team doesn't get in. We emphasize professionalism, mentorship, citizenship, teaching, national reputation, local reputation, and clinical excellence. And so we've elected over 100 people, maybe 3% of the Penn faculty. We give an honorarium. We have monthly meetings now by Zoom. We have monthly meetings on various topics. We never have a problem getting any dean or CEO to come talk to us. We were the first to do Penn's professionalism statement. The school subsequently adopted, and it's become the highest honor for a Penn clinician. It's very competitive. It's peer-reviewed. The dean has no influence. And we're very proud that 40% of the members of the academy are women. We have a high percentage of diversity compared to the numbers on our faculty, but you really have to be elected on merit, and some people that you might expected to be members of the academy aren't. It's one of the things I'm proudest of. It will go on in perpetuity because of the money we've raised. I think many of my accomplishments as a researcher will fade, as they typically do, but I'm very proud of the Academy, and I'm very proud of the people that I've mentored. Dave Johnson: It speaks to your values, John, and I think it's one of the reasons why you're so widely admired. Thank you for creating that. It proved to be a model for other institutions. I know that for a fact. One would think that valuing clinical care would be preeminent in medical schools, but in fact, it's often ignored. So again, I know that your colleagues at Penn appreciate your efforts in that regard. Tell us a little about your term as ASCO president. What are you most proud about and what were your most difficult challenges? Dr. John Glick: Well, the most difficult challenge was that ASCO was in transition. I had to fire the company that ran the meeting. We had to decide that ASCO was going to hire a CEO. We hired John Durant, made a small headquarters, tiny staff, and did a lot of the work as being chief operating officer myself. It was the year that email was just getting started, and ASCO wasn't using it. So every Saturday from 8:00 to 6:00, I came into the office and my secretary wrote letters inviting people to be on the program committee or various committees. But it was a society in transition. The growth of membership was huge. The meeting sites had to be changed. We emphasized science. Some of the things that we did are still in existence today. We formed the ASCO ACR Clinical Research Methods course. It's still given. That's one of our real highlights. We forged relationships with other societies, the National Coalition for Survivorship. We made the ASCO guidelines much more prominent. And I remember that we were going to publish the first guidelines on genetic testing for breast cancer, and the MCI went up in absolute arms, so I arranged a meeting. I was at the head of the table. On my right were Francis Collins, Richard Klausner, Bob Wittes, and a few other people. Then the ASCO people who wrote the guideline were on the left, and they didn't want us to publish it. They thought it was premature to have a guideline about genetic testing. And what I learned from that meeting is that you can agree to disagree with even the most prominent people in oncology and still maintain those relationships. But we did what's right, and we published a guideline on the JCO. There were so many wonderful things that happened at ASCO that I can hardly restate all that happened I guess 27 years later. It was exciting. ASCO was still young. There was a lot we had to do, and we could do it. You could just go ahead and do it. It was exciting. It was gratifying. It was one of the most fun years of my life. Dave Johnson: I mean, that transition from an outside company in many respects, controlling the premier activity of ASCO, its annual meeting to ASCO, taking that on, that defined ASCO, and that's what I remember most about your time as president. It was a bold move, and the hiring of John Durant was brilliant. I mean, he was such an incredible individual, and it was great that you guys were able to pull that off. Pat Loehrer: Thank you for what you've done. You've had a number of your mentees if you will, and colleagues that have gone on to prominent positions, including, I think, at least three directors of NCI Cancer Centers. Can you just talk briefly how you would describe your mentoring style because you've been so successful? Dr. John Glick: First, there are two aspects. One is when people come to you, and then when you go to people, you sense they're in need. The key aspect of mentoring is listening. Not talking, listening. Looking for the hidden meanings behind what they're saying, not telling them what to do, presenting options, perhaps giving them clues on how to weigh those options in pros and cons, being available for follow-up. Mentoring is never a one-time exercise. Not criticizing their decisions. You may disagree with their decision, but it's their decision, especially if they've considered it. Being proud of the mentee, being proud of their accomplishments, following them over the years. And when they've gotten in trouble or failed to get the job that they wanted, always be there for them, not just in the good times, but in the times that are difficult for them professionally. I think that's one of the most important things. Even today, I mentor three or four clinical department chairmen, and people ranging from full professors to newly appointed assistant professors. Now that I'm retired, mentoring is the one activity that I've really retained. It's extraordinarily satisfying, and I'm proud of the people that I've mentored. But it's their accomplishments, and the key aspect of mentoring is never to take credit. Dave Johnson: I'll give you credit for mentoring me, and I appreciate it. You were very instrumental at a very decisive point in my career when the old Southeast Cancer Group disbanded, and we were looking for a new cooperative group home. And you were instrumental in helping my institution come into the ECOG fold, and not just as a very junior member, but really as a player. And I'll never forget that, and we'll always appreciate that very much. Pat Loehrer: Ditto on my side, too. Dave Johnson: John, you mentioned that you're retired. What do you like to do in your "free time" if you're not mentoring? Dr. John Glick: Life is good. My daughter says I have a disease, O-L-D. My grandson says, "He's not old; he's almost 80. Look how well he's done." "Here's $20." I'm having fun. We are fortunate to have homes in different places. We spend the summer up in the Thousand Islands on the St. Lawrence River, spring and fall down in Charleston, then lots of time in Philadelphia. We travel. I play golf poorly. I'm getting a chance to read history again, go back to one of my great loves. I'm with my children and grandchildren more. I lost my first wife. I've been remarried for about twelve years, and I'm enjoying every moment of that. I'm not bored, but I do wake up in the morning with no anxiety, no realization that I have to herd sheep or herd cats. I have no metrics, I have no RVUs, not behind of the EMR. Dave Johnson: You're making it sound too good, John. Dr. John Glick: We're having fun. And I have not been bored. I've not been down in the dumps. Each day brings a different aspect. We see a lot more of our friends. I exercise. I deal with the health problems that people get when they get older, and I have plenty of those. Seeing doctors takes a lot of time, but I'm grateful that I'm having these few years of retirement. I'm one of the people who is most fortunate to have attained everything they wanted to do in their professional life, and now I'm trying to do some of the same in my personal life. Dave Johnson: John, Pat and I both love to read. We love history. You mentioned that you're reading some history. Is there a book that you've read recently that you might recommend to us? Dr. John Glick: "the Last of the Breed" {With the Old Breed} It's about a private in the Pacific campaign who was not a commissioned officer; it's just a grunt on the ground. It brings the horrors of the Pacific island campaigns to life. But there's a huge number of books, some historical fiction. I'm a great fan of Bernard Cornwell, who's written about the Medieval times, Azincourt, 1356. I'll read two or three books a week. I'm devoted to my Kindle. Dave Johnson: If you could go back in time and give your younger self a piece of advice, what would that advice be? Dr. John Glick: Try and achieve more of a work-life balance. I didn't have any choice. If I didn't do the consult, it didn't get done. That's not the situation today. But I have a second piece of advice, don't treat medicine as a 9 to 5 job. If a patient is sick, stay with the patient. Give the patient your home or cell phone number. Remember, medicine is not just a profession, but it can be a calling. Too few of our physicians today regard medicine as a calling. And even if you're employed, as most of us are by an academic or other institution, do what's right for the patient, not just what's right for your timesheet or the EMR. Remember that the patient is at the center of all we do and that medicine is a calling for some people, as it was for me. Dave Johnson: Great advice, John. Great advice. Well, I want to thank Dr. Glick for joining Pat and me. This has been a delight. You're one of our role models and heroes. I want to thank all of our listeners of Oncology, Etc., which is an ASCO educational podcast where we will talk about oncology medicine and other topics. If you have an idea for a topic or a guest you'd like us to interview, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content of ASCO, please visit education.asco.org. Thanks again. Pat, before we go, I've got an important question for you. I've been trying to school you recently, and you've failed miserably. So I'm going to ask you, why is it that McDonald's doesn't serve escargot? Pat Loehrer: I can't do it. I don't know. I give up. Dave Johnson: It's not fast food. Pat Loehrer: I like that. It's good. 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, experiences, 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.

Oncology is a rapidly evolving medical field. So how do you keep up with all the advances and updates that are delivered through publications, conferences, and social media? This ASCO Education podcast explores how three oncologists in various settings and stages of their career manage this issue. Our moderator Dr. Adriana Alvarez, a medical oncologist at Cleveland Clinic in Ohio is joined by Dr. Sharad Goyal, a professor and division chief of Radiation Oncology at George Washington University in Washington, DC; Dr. Shruti Patel, an oncology fellow at Stanford University in California; and Dr. Banu Symington, a medical oncologist at Memorial Hospital of Sweetwater County in Wyoming, and adjunct professor in the University of Utah College of Nursing. Each will describe what they do to keep up to date on research advances and guidelines (3:25), how they find time to stay current in their field (7:25) and how they follow developments outside of their area of concentration (13:57). The speakers have no relevant disclosures. Resources: Podcast: Cancer Topics - Burned Out? Here's What You Can Do About It (Part 1) Podcast: Cancer Topics - Burned Out? Here's What You Can Do About It (Part 2) Podcast: Cancer Topics - Burnout in Oncology: Trainee Perspective 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 Disclosures for this podcast are listed on the podcast page. Dr. Adriana Alvarez: An oncologist recently described that while sitting on a couch to write an article, by the time he finished his first paragraph, he received six notifications on his iPhone from WhatsApp, Twitter, and other messages. He knows what the dilemma is; you can shut down your phone, but you become worried about missing an urgent call or important update. The oncologist knows that social media is a place to follow friends and colleagues, to discover new presentations, and even debate about them. However, he understands the overload of information that is part of the rapidly evolving field of oncology. On any given day or week, there are research advances and updates in the management of cancer being shared through journal publications, conference presentations, newsletters, social media, and other methods. How does one keep up to date with these advances in oncology? I'm Dr. Adriana Alvarez, a medical oncologist at Cleveland Clinic in Ohio. In this ASCO Education Podcast, we will examine what various oncology professionals at different stages in their careers and working in different practice settings, namely academic versus community and urban versus rural, are doing to manage the large amount of information influx regarding advances in oncology. Joining me are Dr. Sharad Goyal, a professor and division chief of radiation oncology at George Washington University in Washington, DC; Dr. Shruti Patel, an oncology fellow at Stanford University; and Dr. Banu Symington, a medical oncologist at Memorial Hospital of Sweetwater County in Wyoming, and adjunct professor in the University of Utah College of Nursing. Let's start. One of the first questions I have here is how you can describe your current field of focus in oncology. Dr. Patel? Dr. Shruti Patel: My current clinical focus in oncology is in thoracic and gastrointestinal malignancies, while my research interests include clinical trials, liquid biopsy, and diversity, and equity and inclusion. Dr. Sharad Goyal: My current clinical and research focus is on breast cancer, radiation therapy, as well as radiation therapy with respect to neuro-oncology in the neuro-oncology space. Dr. Adriana Alvarez: What about you, Dr. Symington? Dr. Banu Symington: I'm a general oncologist, medical oncologist, in an extreme rural, I'm considered a frontier practice. I have a special interest in eliminating the social disparity that is represented by rurality, and I'm interested in clinical trials. We are the only Wyoming Cancer Center that opened clinical trials. Dr. Adriana Alvarez: Well, it's all wonderful to hear about you and know a little bit about what your focus of work is, and we come from a variety of backgrounds. How do you feel like you keep up to date with the clinical practice, the research parts with new drugs approval in oncology? You are still in training Dr. Patel. How do you do that? Dr. Shruti Patel: As a millennial, it may come as no surprise that I primarily stay up to date on clinical practice guidelines via Twitter on my phone. I find Twitter to be the best place to learn new information. Just because you don't just get information about the new approvals, but typically experts in the field will weigh in on the trial design, their thoughts on whether it truly will replace the current standard of care or what situations they might use the new approval for, which can really be helpful, especially as a fellow in training. It's helpful context beyond just the information that you get from the approval itself. And then, I also learn about the applications of these new guidelines in the clinic with my mentors, because I am, of course, lucky enough to still be in training where I can gather that information from my attendings. Dr. Adriana Alvarez: Dr. Goyal, what is your preferred method of keeping up to date and learning more about the new treatments and research in your area of interest? Dr. Sharad Goyal: As opposed to Dr. Patel, I am not part of social media in medicine. Actually, I'm not a part of any social media, whether it's personal or work-related. So I tend to be a little more "old school" with respect to how I ingest information. So, in terms of clinical practice guidelines and new drug approvals, which is somewhat peripheral to my field in radiation oncology, I tend to rely on NCCN guidelines and attendance at tumor boards to receive that information from my colleagues in medical oncology. I believe that with any patient that I see with a malignancy, I do tend to refer to the NCCN guidelines on a regular basis. And if it's a malignancy that I do not see, I have to reference PubMed, UpToDate, and the NCCN guidelines to determine the best course of treatment for that patient. Dr. Adriana Alvarez: What about you, Dr. Symington? Being in the rural area, I can see that you have a variety of situations. How do you keep up to date? Dr. Banu Symington: I guess I'm midway between Doctors Patel and Goyal. I do not follow Twitter, but I belong to a 5000-member online hematology/oncology support group, and we post questions, and local thought leaders will reply. I am in such an isolated location. I don't get the stimulation or the benefit of walking down the hall to a colleague to say 'What would you do?' So I am affiliated with the Huntsman and the University of Utah. I've made an effort to join every organ-specific tumor board so that I can hear discussions by disease thought leaders about how they're going to take care of each type of cancer and hearing that week after week, I do absorb it. Medical oncology is a challenging field because things move so rapidly. I took an 18-month, mostly Sabbatical, as I functioned as a chief of staff at a larger hospital. And in that 18-month period, where I volunteered in a clinic, immune checkpoint therapy arose, and targeted therapies for lung cancer arose and I felt like Sleeping Beauty. I went to sleep in one world, and I woke up in a completely different world of oncology. And it was hard to get back into the drift until I connected with colleagues. I'm an avid reader. I don't sleep much. So I am a member of AMA, ASCO, and ACP, so I get all the print journals. And I have a disorder, an obsessive-compulsive disorder, that makes me have to look through every single journal I get. So print and tumor boards and colleagues. Dr. Adriana Alvarez: So we are very busy, and the work that we do, the clinical work, trying to keep up to date and training and all that, how do you schedule time to do this, to learn about the research advances and to keep going? Dr. Goyal, how do you find the time? Dr. Sharad Goyal: In general, I do think that in my realm, in my head, I think that there are three processes that have to occur when I incorporate research into my practice. So number one, I have to learn about it. Number two, I have to determine if that's going to help change my practice. And then number three, if I do end up changing practice, I have to implement it. And that involves dealing with my staff. So I'm going to delve into each of those in a little bit more detail. So learning about the advance typically, I learn about things through CME activities. So in one of my roles in our cancer center, I help organize our grand rounds and some oncology-specific courses. Being involved in the organization, helping find speakers really keeps me engaged not only in the organization process, but also in the learning process because I have a vested interest in making sure that the trainees and other faculty that attend my courses are learning and are happy. Dr. Adriana Alvarez: To organize all these, do you schedule time during your job, outside work hours? Dr. Sharad Goyal: Yes, that is part of my job, which extends outside of work hours. Dr. Adriana Alvarez: Sounds good. Dr. Symington, well, you mentioned that you don't sleep much, you keep up to date, looks more at night. But do you find the time in between patients or during your workday to keep up to date, or is more like a solitude type of time? Dr. Banu Symington: I forgot to mention a resource that I feel like people should know about, MedNet, which is presented daily with three clinical cases and thought leaders mentioning what they would do. They often introduce research ideas that are not adopted into practice. Since I read, I read about new innovative treatments, but I am not an early adopter, so I wait until they become an NCCN guideline before I would adopt it. So that might be different from Dr. Goyal, who's in an academic center. But I see patients five days a week, 10 hours a day, so it has to be all scheduled outside of those hours. It's fortunate that my kids are grown, and I don't sleep much. Dr. Adriana Alvarez: What about you, Dr. Patel? On the go, I can imagine. I remember not long ago, being fellow and a millennial, so I guess on your iPhone. Dr. Shruti Patel: Even though I'm a fellow, I do like sleep. And now that I'm in my research years, I actually get sleep, which is lovely. I can't say that I schedule time to learn about research advances, but rather it's– Usually, I take the train to work, and so I'm scrolling on my Twitter on the Caltrain down to Palo Alto, monitoring for medical news or updates. Really, that's how I gather information. I also partake in CME activity, creating CME educational materials on Twitter as well. And so that's another way in which I learn because if I'm creating the information, then I have to go through the trials and go through all of these things, side effects. And so it's a really great way, additionally, for me to learn. But none of that stuff is really scheduled. It's kind of really when I have time, on my to-do list, usually outside of business hours. Part of the job is staying up to date with things outside of business hours. And I think we all knew that when we signed up for the job. And it's only gotten more as all of these advances are kind of coming out at us like drinking out of a fire hydrant. Dr. Adriana Alvarez: The most recent moment that you found new information related to your practice, how did you learn about it? Not about everything that you do, but the last time, the most recent one that you did that. Dr. Goyal? Dr. Sharad Goyal: I recently referenced the NCCN guidelines. I was treating a gentleman with male breast cancer, and he told me he had some half-brothers and that they were going to get tested, but he was inquiring about the screening guidelines for men with BRCA mutations, and I had to look that up. I knew what they were for women, but I actually did not know what they were for men. Dr. Adriana Alvarez: What about you, Dr. Symington? Dr. Banu Symington: So last Thursday morning at 7:00, I joined the Huntsman Tumor Board for Breast. And one of the breast-specific oncologists actually said something that defies the NCCN guidelines, but it sounded like it made sense. He said he regularly gets PET scans for staging lymph node-positive HER2-positive breast cancer because he finds, and apparently the breast cancer community finds, that other scans can give you a false-negative result. And there are enough patients with metastatic disease in the lymph node-positive setting that he recommended PET scans for staging of HER2-positive breast cancer patients but not for ER-positive breast cancer patients. So that was just five days ago. Dr. Adriana Alvarez: Wow. And what about you, Dr. Patel? When was the most recent time that you found something that was good information for your practice? Dr. Shruti Patel: Yeah, as a fellow, I love learning about new information when I'm able to learn how to integrate it into the practice with someone that's more experienced than I am. So, of course, I've already mentioned that Twitter can be a great place. But also a few weeks ago, I was attending GI ASCO up in San Francisco, and they presented the latest results from NAPOLI-3, which was a phase 3 study looking at first-line liposomal irinotecan 5FU and oxaliplatin versus gem-Abraxane. And they presented that it was shown to improve overall survival compared to gem-Abraxane in first-line metastatic pancreatic cancer. And I was actually sitting next to my clinic mentor at the time, and during the break, I got to hear about his thoughts on whether this is going to be integrated into clinical practice, given that the control arm was gem-Abraxane, and not FOLFOXIRI. And we ended up discussing it again during our weekly GI trials meetings, just when we're thinking about opening new trials and what the control arm should be. And so I just thought that was like a new piece of information. Thought about it in the clinic, thought about it in the trial meeting, and it was pretty cool. Dr. Adriana Alvarez: Great. So different settings, different ways to gain information. So, Dr. Symington, you have to see a little bit of everything. So you have to be an expert in everything. And I wonder how you, Dr. Goyal, and Dr. Patel, that you are kind of more subspecialized. How do you usually follow advances in other cancers that are not in your particular area of interest or just focus on your disease group? I'm going to let Dr. Goyal go first. Dr. Sharad Goyal: Thank you. So I find that I tend to go to conferences to learn about advances outside of my disease focus. I prefer going to the educational sessions at major conferences like ASTRO or ASCO to keep up on things. On a more local level, I do find when I cover tumor boards for my colleagues that I do have to prep their patients and learn about different treatment paradigms within those disease sites. And in doing so, I feel like I'm able to gain really a deeper understanding about oncology in general, and I do very much appreciate that. Dr. Adriana Alvarez: And Dr. Patel, well, you're in training, so you have to see a little bit of everything, even though you have the focus of your specialty that you are looking forward to do. But do you follow those too, as well? Other areas that might not take your interest right away but you want to be updated? Dr. Shruti Patel: That's exactly it. I have to have a working knowledge of all the areas of oncology that are not my focus area. But really, for the most up-to-date information, the reality is that there are so many new advances in all of these disease types that I find myself leaning on my colleagues. If I come across a lymphoma patient on consults, I'll usually reach out to my lymphoma specialized colleagues, whether that's my co-fellows or attendings, just to kind of run the patient by them, get their insight, get their input, because they're just a lot more up to date on those things than I am. But really, regardless of the subspecialty within oncology, I do think that understanding the basics of all the oncology subspecialties is important in medical oncology. Because most of us will, or are, will for me because I'm a fellow, will be spending time on the inpatient service, which is not tumor type specific, and you really do have to make decisions for patients. And while, of course, you always have your colleagues to rely on and call on, some of those decisions are being made in the middle of the night. And so having a working knowledge of all of them, I think, is important. Dr. Adriana Alvarez: We are lucky to live in a time that we have so many options, right? As a practicing oncologist myself, I rely also on all the resources that you're mentioning. The fear I have sometimes is, okay, I'm relying on the NCCN guidelines, but what if I'm missing something? The fear of missing something, right? It's like if I'm not on Twitter or in another social media; I'm missing the most recent data, that may affect my patient care or things like that. But if I have to ask one of you, if you have to pick one, what would be your preferred method or format of receiving updated information if you have to decide where you could go for it? What about you, Dr. Symington? Dr. Banu Symington: So, although I have made the case that I love reading, I actually absorb information better if someone is talking to me. So if I had the freedom to take time off, I would prefer to hear it at one-day specialty seminars where a thought leader is describing their work. That is not what I do in practice, but that would be my preferred way of getting new information. Dr. Adriana Alvarez: Dr. Goyal? Dr. Sharad Goyal: I'm very much aligned with Dr. Symington in that. I prefer a less active role in the learning process, and I prefer to be spoken to. My preferred method is via podcast, but I also do prefer the in-person or virtual learning through a conference as well. Dr. Adriana Alvarez: What about you, Dr. Patel? Dr. Shruti Patel: I promise you that Elon Musk is not paying me to say all of this because I've probably mentioned Twitter in every single answer. But my preferred method, as you guys probably can guess, is Twitter. It doesn't require too much dedicated time. Information is delivered in small doses. Like I said, I do it on my commute, so it makes me feel like my commute is actually part of my work, which is just wonderful. I do like to attend these smaller meetings to be kind of, like both Dr. Symington and Dr. Goyal said, to be spoken to and really learn additional information. I would say that I don't necessarily always get that experience at the bigger meetings where the focus is more networking. But 'Best of ASCO', those are kind of some types of meetings where the information is kind of told to you. It's distilled down into bite-sized pieces and really understandable. Dr. Adriana Alvarez: Well, all amazing experiences. And I'm glad that we have different points of view, different settings, different career paths. Someone mentioned before is that we're always learning. I feel like here; everybody's very humble to recognize that we're on the learning curve all the time and that we have a real interest in our patient care. Because we are trying to catch the moment, try to make sure that we deliver the best care to our patients, like keeping up to date and listening to the new information. Dr. Goyal, any advice for your colleagues in terms of how to best keep up to date? Dr. Sharad Goyal: My personal philosophy is that as a physician, the learning never stops. And if you do stop learning, maybe you should find a different field. During the pandemic, I started scheduling time with colleagues, friends in my field, and I would set up a meeting with them via our assistants every two or three months. And we would not only socialize but we would kind of catch up on the current state of affairs in our field. And it was an opportunity to also network, and it was very helpful, especially during COVID. It really helped me gain some normalcy and kind of keep me attached to the field of radiation oncology during that time. Dr. Adriana Alvarez: How do you navigate clinic work, keeping up to date, and work-life balance? Dr. Goyal? Dr. Sharad Goyal: Like Dr. Symington, I probably work about 50 hours a week in the office, so I tend to work from 7:00 to 5:00, and I'm out of the office at 5:00 on the dot. I have two small children at home, and I want to see them at least for two hours in the evening before they go to bed. As a radiation oncologist, we take HomeCall, and there are very few emergencies, so I have the weekends to not only spend time with my family but also catch up on any work that needs to be done. Dr. Adriana Alvarez: I'm so glad to hear that. Congratulations on your family. Dr. Symington? Dr. Banu Symington: Well, I rescue small dogs, so at the moment, I have five small dogs, and they get a walk a day when weather permits. We're in the middle of a blizzard in Wyoming, so weather hasn't been permitting for the past four days, so the love and attention of those dogs keep me grounded. I also regularly go to the gym. I dread it every time I go, but I go at least four times a week, and I leave the gym and leave some of my problems behind. When I was younger, people would comment on the fact that I was slender and didn't need to go to the gym and would ask me why I did it, and I would say it's so I don't beat my children. That was obviously a joke, but I could shed the problems of the day by running on the treadmill or using the StairMaster. So I guess that's how I keep work-life balance. Dr. Adriana Alvarez: What about you, Dr. Patel? Dr. Shruti Patel: I would say that my work-life balance has improved greatly in the last eight months since I started the research portion of my fellowship. I'm not writing papers at 2:00 a.m. anymore, so that's like a huge upgrade. But really, I think, prioritizing when you're at work, you're at work, but then when you're at home, really trying to prioritize the things that are important to you. I am currently in my parents' home, while I'm recording this podcast, I get to spend time with them. I get to spend time with my family, my friends. I like to make time for those things because they provide me joy. I think a huge part of our work is being there for people in really, really tough times in their life, and that can be extremely emotionally draining, even though it's exactly what we want to do. And I think making sure that you have things outside of work that really provide you a lot of joy is extremely important. And so I think now that I have the time to do it, I really am trying to capitalize on it. Dr. Adriana Alvarez: Well, I really want to thank you, all of you, Dr. Goyal, Dr. Patel, and Dr. Symington, for a lively discussion. I learned a lot from you and a little bit about your personal life. Thank you for sharing that and sharing how you navigate to be a physician in oncology. So this ASCO Education Podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncology well-being and professional development. If you have an idea for a topic or guest you would like to see on the show, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, visit education.asco.org. Thank you very much. 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, experiences, 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.

The availability and quality of cancer care varies in different parts of the globe. Some locations find it difficult to have proper equipment, access to medications or even trained staff on hand. In this ASCO Education podcast we look how a group of doctors are sharing their skills and experience to set up training programs to help improve outcomes for patients with cancer in Kenya. Our guests will explore the creation of a pediatric oncology fellowship program in Kenya (11:48), how a young doctor found herself interested in improving global health (14:30), and discuss lessons learned that are applicable to health care in the United States (21:07). Speaker Disclosures Dr. David Johnson: Consulting or Advisory Role – Merck, Pfizer, Aileron Therapeutics, Boston University Dr. Patrick Loehrer: Research Funding – Novartis, Lilly Foundation, Taiho Pharmaceutical Dr. Terry Vik: Research Funding Takeda, Bristol Myers Squibb Foundation Dr. Jennifer Morgan: None Resources: Podcast: Oncology, Etc. - Dr. Miriam Mutebi on Improving Cancer Care in Africa Podcast: Oncology, Etc. – Global Cancer Policy Leader Dr. Richard Sullivan (Part 1) Podcast: Oncology, Etc. – Global Cancer Policy Leader Dr. Richard Sullivan Part 2 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 Disclosures for this podcast are listed in the podcast page. Dave Johnson: Welcome, everyone, to a special edition of Oncology, Etc., an oncology educational podcast designed to introduce our listeners to interesting people and topics in and outside the world of Oncology. Today's guest is my co-host, Dr. Pat Loehrer, who is the Joseph and Jackie Cusick Professor of Oncology and Distinguished Professor of Medicine at Indiana University, where he serves as the Director of Global Health and Health Equity. Pat is the Director Emeritus of the Indiana University Simon Comprehensive Cancer Center. Pat has many different accomplishments, and I could spend the next hour listing all of those, but I just want to point out, as many of you know, he is the founder of what formerly was known as the Hoosier Oncology Group, one of the prototypes of community-academic partnerships which have been hugely successful over the years. He's also the founding director of the Academic Model for Providing Access to Healthcare Oncology Program, which has grown rather dramatically over the last 17 years. This includes the establishment of fellowship programs in GYN oncology, pediatric oncology, and medical oncology through the Moi University School of Medicine in Kenya. Through its partnership with the Moi Teaching and Referral Hospital, over 8000 cancer patients a year are seen, and over 120,000 women from western Kenya have been screened for breast and cervical cancer in the past five years. Pat is also the co-PI of the U-54 grant that focuses on longitudinal HPV screening of women in East Africa. He currently serves as a Senior Consultant of the NCI Cancer for Global Health. So, Pat, welcome. We have with us today two special guests as well that I will ask Pat to introduce to you. Pat Loehrer: Dave, thanks for the very kind introduction. I'm so pleased today to have my colleagues who are working diligently with us in Kenya. The first is Terry Vik, who is Professor of Pediatrics here at Indiana University and at Riley Hospital. He's been the Director of the Fellowship Program and the Pediatric Hematology-Oncology Program and Director of the Childhood Cancer Survivor Program. He got his medical degree at Johns Hopkins and did his residency at UCLA and his fellowship at Dana-Farber. And he's been, for the last 10 to 15 years, been one of my co-partners in terms of developing our work in Kenya, focusing on the pediatric population, where he helps spearhead the first pediatric oncology fellowship in the country. And then joining us also is Dr. Jennifer Morgan. Jenny is a new faculty member with us at Indiana University as an Assistant Professor. She, I think, has 16 state championship medals for track and field in high school. I've never met an athlete like that in the past. She ended up going to Northwestern Medical School. She spent time in Rwanda with Partners in Health, and through that, eventually got interested in oncology, where she completed her fellowship at University of North Carolina and has spent a lot of her time in Malawi doing breast cancer research. I don't know of anyone who has spent as much time at such a young age in global oncology. Dave Johnson: So Pat, obviously, you and I have talked a lot over the years about your work in Kenya, but our listeners may not know about Eldoret. Maybe you can tell us a little bit about the history of the relationship between your institution and that in Kenya. Pat Loehrer: It's really a remarkable story. About 30 some odd years ago, Joe Mamlin and Bob Einterz, and Charlie Kelly decided they wanted to do a partnership in Global Health. And they looked around the world and looked at Nepal and looked at Mexico, and they fell upon Eldoret, which was in Western Kenya. They had the birth of a brand new medical school there, and this partnership developed. In the midst of this came the HIV/AIDS pandemic. And these gentlemen worked with their colleagues in Kenya to develop one of the most impressive programs in the world focused on population health and dealing with the AIDS pandemic. They called it the Academic Model for Prevention and Treatment of HIV/AIDS or AMPATH, and their success has been modeled in many other places. They have many different institutions from North America and Europe that have gone there to serve Western Kenya, which has a catchment area of about 25 million people. About 15 to 20 years ago, I visited AMPATH, and what they had done with HIV/AIDS was extraordinary. But what we were seeing there in cancer was heartbreaking. It reminded us, Dave, as you remember back in the '60s and '70s with people coming in with advanced cancers of the head and neck and breast cancers that were untreated. And in addition, we saw these young kids with Burkitt's Lymphomas with huge masses out of their jaws. And seeing that and knowing what was possible, what we saw in the States and what seemed to be impossible in Kenya, spurred me on, as well as a number of other people, to get involved. And so, we have built up this program over the last 15 and 20 years, and I think it's one of the most successful models of global oncology that's in existence. Dave Johnson: That's awesome. Terry, tell us a little bit about your involvement with the program at Moi University. Terry Vik: Sure. So, I took an unusual path to get to Eldoret because I started off in work in signal transduction and protein kinases, then morphed into phase I studies of kinase inhibitors that was happening in the early 2000s. But by the end of the decade, Pat was beginning to establish oncology programs in Kenya. And because half the population is children and there were lots of childhood cancers, and many of them can be curable, he mildly twisted my arm to go with him to set up pediatric oncology in Kenya. And through his help and Matt Strother, who is a faculty member on the ground, establishing that, I first went in 2010 just to see how things were running and to see all the things that Pat had recognized as far as things that needed to be done to make Eldoret a center for cancer care. And so, the last 13 years now, I've been working, going anywhere from one to four times a year to Kenya, mainly helping the Kenyans to develop their medical care system. Not so much seeing patients or taking care of patients, other than talking about best practices and how we do things in the US that can be readily translated to what's going on in Kenya. And so, we've been able to establish a database, keep track of our patients in pediatric oncology, recognize that lots of kids are not coming into care, not being diagnosed. There's a huge gap between numbers who you would expect to have childhood cancer versus the numbers actually coming to the hospital. As the only pediatric treatment center for a catchment area of 25 million, half of whom are under the age of 20, we should be seeing a lot of kids with cancer, but we are probably only seeing 10% of what we would expect. So, myself, many of my colleagues from Indiana University, as well as colleagues from the Netherlands Princess Maxima Hospital for Pediatric Cancer, we've been partnering for these past 13 years to train Kenyans to recognize cancer, to have treatment protocols that are adapted for the capabilities in Kenya, and now finally starting to show real progress in survival for childhood cancer in Kenya, both in leukemias, lymphomas, and solid tumors, with a fair number of publications in Wilms tumor and Burkitt lymphoma and acute lymphoblastic leukemia. So, it's been really heartening, I think. I tell people that the reason I go to Kenya studying signal transduction and protein kinase inhibitors in pediatric cancer, I can maybe save a couple of kids over a career by that kind of work. But going to Kenya to show people how to find and treat kids with leukemia, I'm literally seeing the impact of hundreds of kids who are alive today that wouldn't be alive otherwise. So, that's really been the success of pediatric oncology there. Dave Johnson: Is the spectrum of childhood cancer in Kenya reflective of what we see in the States, or are there some differences? Pat Loehrer: It really is surprisingly similar. I think the only thing that– Well, two things that are more common in Kenya because of the so-called 'malaria belt' and the association with Burkitt Lymphoma, there's a fair number of kids with Burkitt's Lymphoma there. Although, as mosquito control and malaria control has improved, actually, the numbers of cases of Burkitt's have been dropping, and a lot of cancers were sort of hidden, not recognized as leukemia or not recognized as other lymphomas. Just because if Burkitt's is endemic, then every swelling is Burkitt's. And I think that's been shown by looking at pathology retrospectively to say a lot of what they thought was Burkitt's was maybe not necessarily Burkitt's. And then nasopharyngeal carcinoma with Epstein-Barr virus prevalence also is a little bit more common than I'm used to seeing, but otherwise, the spectrum of cancers are pretty similar. So, it's heartening to know that we've been treating childhood cancers with simple medicines, generic medicines, for 50 years in the US. And so I like to tell people, I just want to get us up to the '90s, maybe the 2000s in Kenya, and that will really improve the survival quite a bit. Dave Johnson: You mentioned that there were adjustments that you were making in the therapies. Could you give us some examples of what you're talking about? Terry Vik: The biggest adjustments are that the ability to give blood product support, transfusions of platelets is somewhat limited. So, for instance, our ability to treat acute myeloid leukemia, which is heavily dependent on intensive myelosuppressive chemotherapy, we're not so good at that yet because we don't have the support for blood products. Similarly, the recognition and treatment of infections in patients is somewhat limited. Yet, just the cost of doing blood cultures, getting results, we actually have the antibiotics to treat them, but figuring out that there actually is an infection, and we're just beginning to look at resistance patterns in bacteria in Kenya because I think that's an indiscriminate use of antibiotics. In Kenya, there are a lot of resistant organisms that are being identified, and so figuring out how best to manage those are the two biggest things. But now, in Eldoret, we have two linear accelerators that can give contemporary radiation therapy to kids who need it. We have pediatric surgeons who can resect large abdominal tumors. We have orthopedic surgeons and neurosurgeons to assist. All those things are in place in the last three to five years. So, really, the ability to support patients through intensive chemotherapy is still one of the last things that we're working diligently on improving. Dave Johnson: So one thing that I've read that you've done is you're involved heavily in the creation of a pediatric oncology fellowship program. If I read it correctly, it's a faculty of one; is that correct? Terry Vik: Well, now that two have just graduated, it's a faculty of three, plus some guest lecturers. So I feel quite good about that. Dave Johnson: So tell us about that. That must have been quite the challenge. I mean, that's remarkable. Terry Vik: That goes back to one of my longtime colleagues in Kenya, Festus Njuguna, who is Kenyan. He did his medical school training at Moi University and then did pediatric residency there. They call it a registrar program there. And then he was, since 2009, 2010, he's been the primary pediatric oncologist. Although he always felt he did not have the formal training. He'd spent time in the US and in Amsterdam to get some added training for caring for kids. But it was his vision to create this fellowship program. So Jodi Skiles, one of my colleagues who had spent some time in Kenya and myself and he worked on creating the fellowship document that needs to go through the university to get approved. That finally got approved in 2019. And so the first two fellows…I was on a Fulbright Scholar Award to start that fellowship program for a year right in the middle of the pandemic, but we were able to get it started, and I was able to continue to go back and forth to Kenya quite a bit in the last two years to get through all of the training that was laid out in our curriculum. And two fellows, Festus and another long-standing colleague of mine, Gilbert Olbara, both completed the fellowship and then sat for their final exams at the end of last year and graduated in December. So it really was heartwarming for me to see these guys want to build up the workforce capacity from within Kenya, and being able to support them to do that was a good thing. Pat Loehrer: Parenthetically, Dave, we had the first Gynecology Oncology program in the country, too, led by Barry Rosen from Princess Margaret, and they have 14 graduates, and two of them now are department chairs in Kenya. Jenny's spearheading a medical oncology curriculum now so that we have that opened up this year for the first time. Dave Johnson: It's uncommon to find a junior faculty as accomplished as Jenny. Jenny, tell us a little about your background and how you got interested in global health, and your previous work before moving to IU. Jennifer Morgan: I was an anthropology major at undergrad at Michigan, and I think I really always liked studying other cultures, understanding different points of view. And so I think part of that spirit when you study anthropology, it really sticks with you, and you become a pretty good observer of people and situations, I think, or the goal is that you become good at it. I think my interest in medicine and science, combined with that desire to learn about different cultures really fueled a lot of my interests, even from undergrad and medical school. I really felt strongly that access to health is a human right, and I wanted to work for Partners in Health when I graduated from residency. I had heard a lot about that organization and really believed in the mission around it. And so I went to work in Butaro in Rwanda, and I really didn't have any plans to do cancer care, but then I just kind of got thrown into cancer care, and I really loved it. It was a task-shifting model that really where you use internists to deliver oncology care under the supervision of oncologists from North America. So, most of them were from Dana-Farber or a variety of different universities. And so it made me feel like this high-resource field of Oncology was feasible, even when resources and health systems are strained. Because I think a lot of people who are interested in Oncology but also kind of this field of global health or working in underserved settings really struggle to find the way that the two fit sometimes because it can feel impossible with the hyper-expensive drugs, the small PFS benefits that drive the field sometimes. And so I think, Butaro for me, and Partners in Health, and DFCI, that whole group of people and the team there, I think, really showed me that it's feasible, it's possible, and that you can cure people of cancer even in small rural settings. And so that drove me to go to fellowship, to work with Satish Gopal and UNC. And because of COVID, my time in Malawi was a bit limited, but I still went and did mainly projects focused on breast cancer care and implementation science, and they just really have a really nice group of people. And I worked with Tamiwe Tomoka, Shakinah Elmore, Matthew Painschab, really just some great people there, and I learned a lot. And so, when I was looking for a job after fellowship, I really wanted to focus on building health systems. And to me, that was really congruent with the mission of AMPATH, which is the tripartite mission of advancing education and research and clinical care. And I knew from Pat that the fellowship program would be starting off, and I think to me, having been in Rwanda and Malawi and realizing how essential building an oncology workforce is, being a part of helping build a fellowship as part of an academic partnership was really exciting. And then also doing very necessary clinical outcomes research and trying to do trials and trying to bring access to care in many systems that are very resource constrained. So that's kind of how I ended up here. Pat Loehrer: That's awesome. So tell us a little bit about your breast cancer work. What exactly are you doing at the moment? Jennifer Morgan: In Malawi, during my fellowship, we looked at the outcomes of women with breast cancer and really looking at late-stage presentations and the fact that in Malawi, we were only equipped with surgery, chemotherapy, and hormone therapy, but not radiation. You see a lot of stage four disease, but you also see a lot of stage three disease that you actually have trouble curing because it's so locally advanced, really bulky disease. And so that first study showed us the challenge of trying to cure patients– They may not have metastatic disease, but it can be really hard to locally even treat the disease, especially without radiation. And so that's kind of what we learned. And then, using an implementation science framework, we were looking at what are the barriers to accessing care. And I think it was really interesting some of the things that we found. In Malawi, that has a high HIV rate, is that the stigma around cancer can be far more powerful than the stigma around HIV. And so, we are seeing a lot of women who are ostracized by their communities when they were diagnosed with cancer. And really, they had been on, many HIV-positive women, on ARVs for a long time living in their communities with no problem, and so HIV had kind of been destigmatized, but we're seeing the stigma of cancer and the idea that kids are as a death sentence was a really prominent theme that we saw in Malawi. So some of these themes, not all of them, but some of them are very similar in Kenya, and so what I'm helping work on now is there's been this huge effort with AMPATH called the Breast and Cervical Cancer Screening Program, where around 180,000 women have been screened for breast cancer in a decentralized setting which is so important - so in counties and in communities. We're looking at who showed up to this screening and why did women only get breast cancer screening and why did some of them only get cervical, and why did some get what was intended - both. Because I think many people on the continent and then other LMICs are trying to do breast and cervical cancer co-screening to really reduce the mortality of both of those cancers. And the question is, I think: is mammography a viable screening mechanism in this setting or not? That's a real question in Kenya right now. And so we're going to be looking to do some studies around mammography use and training as well. Dave Johnson: So, I have a question for all three of you. What lessons have you learned in your work in Kenya or Malawi that you've brought back to the States to improve care in the United States? Pat Loehrer: One is that the cost of care is ever present there. And so one of the things that we need to think about here is how can we deliver care more cheaply and more efficiently. It goes against the drug trials that are going on by industry where they want to use therapy for as long as they can and for greater times. And there are a lot of common things like access to care is a big issue there, and it's a big issue in our country. So we have used in IU some community healthcare workers in rural parts of our state as well as in the urban centers so that they can go to people's houses to deliver care. Terry was involved with a wonderful project. It was a supplement from the NCI, which looked at barriers to care and abandonment of therapy. And just by giving patients and their families a small stipend that would cover for their travel and their food, the abandonment rate went down substantially, and they were able to improve the cure rate of Burkitt's Lymphoma. It's probably about 60% now. And so those are issues that I think we see here in our state, where people can't come to IU because of the cost of parking, that's $20 a visit. The lesson there is that we really need to get down to the patients and to their families and find out what their obstacles are. Terry Vik: My favorite example, since I deal with kids and parents, is how striking parents are the same worldwide. They all want the best for their child. They all want anything that can be done to potentially cure them, treatment, they do anything they could. And I think the hardest thing, as Pat said, is the financial burden of that care. And the other thing that I bring back to my fellows in the US is that you don't have to do Q4-hour or Q6-hour labs to follow somebody when they start their therapy. Once a day, every 3 days, works quite well also. And just the realization that things can be done with a lot less stress in the US if you only decide to do it. Dave Johnson: Jenny, any thoughts from you on that? Jennifer Morgan: I think for me, decentralized cancer care is so important. Even being back on the oncology wards in Indiana in December, I saw a couple of really advanced patients who were really unfortunate, and they had tried to go through the system of referrals and getting to cancer care. And unfortunately, I think there are disparities in the US health system, just like in Kenya, and maybe on different scales. But cancer care that's accessible is so important, and accessible versus available, I think we a lot of time talk about therapies that may be available, but they're not accessible to patients. And that's really what we see in Kenya, what we see in rural Indiana. There are a number of grants that talk about reciprocal innovation because some of these things that we do in Kenya to minimize burden on the system are things that can be done in rural Indiana as well. And so, partnership on these issues of trying to improve decentralized care is important everywhere. Pat Loehrer: And again, from the perspective as a medical oncologist, we see patients with late-stage diseases. We could eradicate the number one cause of cancer in Sub-Saharan Africa, cervical cancer, from the face of the earth just by doing prevention. We don't do enough in our country about prevention. The other dimension I guess I wanted to bring up as far as multidisciplinary care - when we think about that in our country, it's radiation therapy, surgery, medical oncology, but one of the lessons learned there is that the fourth pillar is policy. It's really about cancer policy and working with the government, Ministry of Health to affect better insurance cover and better care and to work with a different discipline in terms of primary care, much more strongly than we do in our country. Dave Johnson: Are you encountering similar levels of vaccine hesitancy in Kenya as you might see in the States, or is that something that's less of an issue? Pat Loehrer: I'll let Terry and Jenny answer that. Terry Vik: I think there is some degree of vaccine hesitancy, and not so much that it's fear of the vaccine, but it's fear of the people pushing the vaccine. If it's coming from the government or if it's coming from outside drug companies or outside physician recommendations, it's less likely to be taken up. And if it's coming from within their own community or if it's their chiefs and their community leaders they respected, then I think there is less vaccine hesitancy certainly in a lot of things we do in pediatrics. So I think there is hesitancy, but it's coming from a different source than what we see in the US. Jennifer Morgan: I would agree, and I think also COVID has changed the game on vaccine perceptions everywhere, and I don't think Kenya is spared from that either. So it may take a few years to see really what's going on with that. Pat Loehrer: Jenny and I were at this conference, it's a Cancer Summit in Nairobi a couple of weeks ago, and we saw this little documentary there. And this notion of misinformation, as we've seen in our country, is also common over there. They were interviewing a number of men and women from Northern Kenya about prostate cancer, which is a very serious problem in Kenya. The notion was that even doing PSA screening caused infertility, and so the men and women didn't want their husbands to get screened for prostate cancer because they would become less fertile by doing that. So, again, there are lessons that we– as Jenny mentioned from the top about anthropology, I think we're all connected, we all have different ways of viewing communications in health, but I do think that we can learn from each other substantially. Dave Johnson: I mean, it's remarkable work. How is it funded? Pat Loehrer: Well, I've been fortunate to be able to work with some friends who are philanthropists. We've had strong support as we've told our story with various different foundations. And we've been very grateful to Pfizer, who are very helpful to us in the early stages of this - Lilly Foundation, Takeda, Celgene. And I think as we basically share our vision of what we're trying to accomplish, we've been very humbled by the support that we have gotten for us. The U54 helps support some of the research. We have D43 we're doing through Brown University. So we plan to increase our research funding as best as we can. But this is active generosity by some wonderful people. We have a $5.5 million cancer and chronic care building in which a large sum of it came from Indiana University and the Department of Radiation Oncology. Dr. Peter Johnstone helped lead that. There was a Lilly heir that gave us quite a bit of money. An Indian Kenyan named Chandaria also donated money. So it's a matter of presenting the vision and then looking for people that want to invest in this vision. Well, I just want to say, from my perspective, I am more of a cheerleader than on the field. But Terry, I know you spent a tremendous amount of time on the ground in Kenya, and Jenny, you're living there. I just wanted to say publicly that you guys are my heroes. Dave Johnson: Yeah. I think all of our listeners will be impressed by what they heard today, and we very much appreciate you both taking time to chat with us. So at this point, I want to thank our listeners of Oncology, Etc., an ASCO Educational Podcast. This is where we'll talk about oncology medicine and beyond. So if you have an idea for a topic or a guest you'd like us to interview, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org. Pat, before we go, I have an important question to ask you. Pat Loehrer: I can't wait. Dave Johnson: Do you know how snails travel by ship? Pat Loehrer: As cargo! Dave Johnson: Awesome. You got it. All right. Well, Terry and Jenny, thank you so much for taking time to chat with us. It's been great. I'm very impressed with the work you guys are doing. Really appreciate your efforts. Terry Vik: Great. Thank you. Jennifer Morgan: Thank you. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Clinical trials are essential to progress in medicine, but racial and ethnic minorities are frequently underrepresented in such studies. In this ASCO Education podcast episode, we will examine this issue with Dr. Carol Brown, gynecologic cancer surgeon and Chief Health Equity Officer at Memorial Sloan Kettering Cancer Center, Dr. Ana Maria Lopez, Professor and Vice Chair of Medical Oncology at Sidney Kimmel Medical College and former Chair of ASCO's Health Equity Committee and Mr. Ted Bebi, Innovation Manager at Medidata Solutions. They discuss how diversification of clinical trials contributes to health equity (4:03), barriers to participating in clinical trials (14:37), and what clinicians and trial sponsors can do to improve participant diversity in clinical trials (20:25). Speaker Disclosures Dr. Carol Brown – None Ted Bebi: Employment – Medidata (a Dassault Systèmes company); Stock and Other Ownership Interest – Pfizer, Eli Lily, Abbvie, Merck, BMY Dr. Ana Lopez - None Resources ASCO-ACCC Initiative to Increase Racial & Ethnic Diversity in Clinical Trials Journal Article: Increasing racial and ethnic diversity in cancer clinical trials Journal Article: Representation of minorities and women in oncology clinical trials Podcast: Impact of Implicit Racial Bias on Oncology Patient Care and Outcomes ASCO-ACCC JustASK Training Program 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 Dr. Carol Brown: Welcome to the ASCO Education podcast. I'm Dr. Carol Brown, a gynecologic cancer surgeon and the Chief Health Equity Officer at Memorial Sloan Kettering Cancer Center. Our guests and I will be exploring the problems and solutions with regards to racial disparities in clinical trials. A necessary element for conducting clinical trials is, obviously, the enrollees or participants. Racial and ethnic diverse groups are frequently underrepresented in clinical trials, despite having a disproportionate burden for certain cancers. In addition, there is increasing evidence that a person's individual genetic makeup may determine the level of toxicity or efficacy of a new cancer drug specifically. Therefore, when we don't have enough diversity in our cancer clinical trials, it can really undermine the generalizability of our results. And so, to address this gap, in its recent updated guidance to industry, the US Food and Drug Administration stated that enrollment in clinical trials should reflect the diversity of the population who ultimately use a treatment. In 2022, ASCO and the Association of Community Cancer Centers issued a joint statement recommending that anyone designing or conducting trials should complete recurring education, training, and evaluation to demonstrate and maintain cross-cultural competencies, mitigation of bias, effective communication, and a commitment to achieving equity, diversity, and inclusion. Joining me to discuss this important topic today is Dr. Ana Maria Lopez, who's the Professor and Vice Chair of Medical Oncology at the Sidney Kimmel Medical College. And she's the former Chair of ASCO's Health Equity Committee. Our second guest is Mr. Ted Bebi, Innovation Manager at Medidata Solutions. His research explores underrepresentation of black patients at clinical trials and how diversity impacts clinical trials. Participant disclosures for this episode are listed on the podcast page. So why should we care about improving diversity in clinical trials? Dr. Lopez? Dr. Ana Maria Lopez: We are clinicians. We are wanting to take care of our patients as best as possible, and we can only do that if our studies include everyone. An example that I often think about is the concept of airbags began in 1953, and in 2008, the National Highway Traffic Safety Administration came out and said, "You know what? We should be testing airbags on small female crash test dummies because otherwise, we don't know that these airbags will be safe." And in fact, there were data that the airbags that existed put women and children at a much higher risk for injury or death. So, we want to be ahead of that curve, and we want to allow the best possible treatment. Dr. Carol Brown: So, Mr. Bebi, what would you say about how we could improve diversity in clinical trials? Ted Bebi: So I really like the example of the airbags that Dr. Lopez brought up because it makes it clear when building a product it's important to test the product in a representative sample of the population that will ultimately end up using it. It's the same with products like medications. If you want an efficacious drug, you should test it in the appropriate population. It's what constitutes good science. Additionally, adequate diversity in clinical trials is also important because it's ultimately an issue of health equity and providing fair access. Dr. Carol Brown: Could you kind of go on from there and talk about, specifically, how does diversifying the group of people that participate in clinical trials actually translate into increasing health equity? Ted Bebi: Well, participating in a clinical trial is a form of receiving health care. Often, we are talking about patients for which a clinical trial might be their last resort. And even if not, participating in a clinical trial means gaining early access to potentially life-changing drugs that could become the new industry standard and doing so at no cost. So, you're receiving care and follow-up from some of the best specialists in the field. So having fair access to this opportunity for all patients is definitely a health equity issue. Dr. Carol Brown: Great. Dr. Lopez, how would you answer that question about how does diversifying clinical trials contribute to health equity? Dr. Ana Maria Lopez: Yeah, no, I think I agree with everything that Mr. Bebi said. In addition, I think we have to remember that diversity is more than race. Race is truly a social construct. We need to think about gender. We need to think about age, the whole lifespan, and people are living longer. How we metabolize medications at different time points in our life may vary. So, lots of different factors that we can consider when we think of diversity. But the gold standard is really: Are folks getting the best outcome possible? And as long as that metric is not being reached, we need to be thinking of how can we facilitate that. Dr. Carol Brown: So, Dr. Lopez, you brought up this concept that health equity is really the best outcome possible. Could you comment a little bit about how do we know, particularly in cancer, what is the best outcome possible? So how do we determine what the reference is for that, so we can figure out whether our patients are actually getting health equity? Dr. Ana Maria Lopez: Sure. So, we use different time points. We can look at relapse rates, survival rates, and of course, part of that may be comorbidities. Certain comorbidities that people have may impact their cancer treatment outcomes. So, it is complex, but it is important for us to take a look contextually at what the patient's risk is and what the patient's outcome would be. Dr. Carol Brown: We can kind of all agree that when we're talking about equity, it's getting the best outcome for everybody, no matter what they're bringing to it. And I really like your comment, Dr. Lopez, about race being not only the only factor but remembering that it is a social construct. If you could add to that, Mr. Bebi. Ted Bebi: We're talking a lot about diversity in clinical trials in terms of race and ethnicity, and that is something that is ultimately very important. But we're talking about diversity in all sorts of aspects. We're talking about diversity with age. We're talking about diversity with sex, with socioeconomic aspects because we often use race as a proxy for other things that might be going on in patients' lives. And we need to consider all of this part of diversity in clinical trials because once the drug is out in the market, it will be an intersection of potentially all of those identities and many things going on in their life that might affect how they respond. So, when we're thinking about race as a diversity point, we might be using it as a proxy for a specific type of individual, a specific patient journey that we want to make sure to include. It's not necessarily that race is the end-all, be-all measure of diversity; it's that we want to capture the true patient experience for that disease. Dr. Ana Maria Lopez: What I think is also really interesting is how we collect the data. And some of what the last couple of years have taught us is that folks may not trust our healthcare systems, and so folks may not be willing to say, 'I am X, Y, or Z,' which certainly puts us a little bit in the void. So how important it is for us as clinicians, as researchers, to be part of creating an environment where patients can feel that 'Yes, I can trust and I can share, and I can say, this is who I am,' because that could impact clinical care. Dr. Carol Brown: So, acknowledging that race is a social construct and that it really is used as a surrogate for other social determinants of health and other factors that affect health, and again, really acknowledging what you said, Dr. Lopez, that even asking people to identify their race is extremely problematic. But given what we do know and what our experience has been in the clinical trial world, first, Mr. Bebi, could you comment about what has been your experience and your research with the current state of participation by diverse racial and ethnic groups in clinical trials in the United States? What have you found in your research? Ted Bebi: Recently, at Metidata, we published a paper where we looked at the state of black participation in clinical trials. We found the level at which you look at the data really matters. For example, when we looked at racial diversity across all US trials, black representation actually matched the proportion of black people represented in the 2020 US National Census, which is about 14%. But looking deeper, there were actually huge differences by therapeutic and disease area. And specifically, we saw that in oncology, black participation was only at around 8.5%, so far below the representation of black people in the United States. Another interesting story is that when we were looking at the central nervous system therapeutic area, overall, we saw a pretty high rate of black participation at around 20%. But when we looked at one of the largest central nervous system indications, Alzheimer's, we saw only 5% black participation, so much, much lower. What we discovered is that within this therapeutic area, there were actually a lot of psychiatric trials that were driving the rate up. So, the main takeaway from this research is that you cannot take a general level of diversity as adequate for all diseases. You really have to zoom in on the specific indication to understand what constitutes good diversity or representative diversity for that disease. Dr. Carol Brown: I'd like to ask both of you what do you think about that - what the bar should be. Because Mr. Bebi, you mentioned using the census distribution of races in the population, but I think a lot of us in the cancer field feel like that maybe isn't the right bar. Maybe the bar should really be what is the cancer burden distributed according to self-identified race, ethnicity, or other categories. And when you look at that, I think you find some different statistics. So, Dr. Lopez, could you comment about what your work has shown you about the current state of representation of diverse people affected by cancer in cancer clinical trials, and maybe get a little bit more into what you were saying earlier about the definition of race and the challenge of determining race, etc. Dr. Ana Maria Lopez: We really need to look closely at the data, and that looking at therapeutic trials and at specific populations can be really important. Now, we're a big country, so there can be - what is the catchment area that you serve? And in that catchment area, what are the cancers you're treating, and in which populations are at greatest risk? But right, sometimes it may not be - let's say the population is 10%x, but if that population is at higher risk for a certain disease, to really get granular about the understanding, I need to recruit more people that are from that greater-risk population. So that's where I think it's so important to know the population, to have connections with the community. And actually, the community can say, "Hey, this is what you may want to be studying because this is what impacts us." Ted Bebi: If I can speak on the research side as well, the best way to ensure representative diversity is to have a very solid understanding of the natural prevalence of a disease. We need to be able to understand what the risk populations are and, even further, what does the mortality look like? Are there differences in how different patients are experiencing the disease further on, not just how they're getting the disease and how often they're getting the disease? So it needs to look different for every single indication. And even with the oncology, for example, the two largest indications in clinical trials for oncology, lung cancer and breast cancer, they also look slightly different. With lung cancer, and our research showing at 8% black participation and breast cancer being a little bit higher at around 11%. So, we always need to take into consideration that incidents include prevalence, include mortality. And yes, the golden standard should be can we build a clinical trial that reflects the actual representative diversity of the disease in the real world? That is what we're striving for. Dr. Carol Brown: I would agree with that. I would also add, though, that there may be some specific cancers for which you want to have an even greater representation of a particular group because it might be directly related to the question you're trying to answer. So, for example, you mentioned breast cancer, so I think most of the audience is probably aware that young women who self-identify as black tend to have a higher mortality from breast cancer. And this is believed to be because they are more likely to get triple-negative breast cancer. And so one of the strategies we've looked at at our cancer center is for trials specifically for triple-negative breast cancer, trying to overrepresent women who self-identify as black or have African ancestry in those trials because we're specifically trying to make sure that we do something to narrow that gap in survival from breast cancer that they experience. So, I think that, as you all mentioned, I think what we can take from this is it's really important to look closely that there are different layers and subtleties that we have to take into account. So, I think we've clearly established that there is underrepresentation of diverse groups. But let's talk about why. So why do we think that different self-identified races and ethnicities or age groups or socioeconomic status background people are underrepresented in clinical trials? What are some of the reasons in your experience for this, Dr. Lopez? Is it funding outreach? What are the main barriers that you've experienced in terms of getting diverse populations to participate in clinical trials? Dr. Ana Maria Lopez: Maybe all of the above. But one of the things, and one of the things that we're working on, is when a person comes in and you have the trauma of the diagnosis. And they're offered a study, and there may be suspicion of the health care system, that may not be the best time to really talk and educate around a clinical trial. So, if people receive the education, learn about clinical trials before that acute event, then they can come in more prepared. So, one is just the concepts of randomization, double blind in the setting where there may be distrust of the healthcare system may be difficult. Also, some of the clinical trials, and I'm sure everyone has studies where the person needs to be at the clinic for about 12 hours getting blood draws. And people have other responsibilities, and they may not have the support mechanisms for transportation, for childcare, for elder care. And if you're taking two to three buses and, you know, here I am in Center City, Philadelphia, and you need to take two to three buses to get home at 07:00, that could be a deterrent to getting on a clinical trial. So, there are lots of clinical factors, social factors, experience with the studies, and also how we design the studies. Can we design studies so that we are more inclusive in the criteria? So, I think lots of questions, and then certainly there are clinician factors. There could be bias that we all have that maybe we don't offer studies to certain people, so something for us to be very introspective about as well. Dr. Carol Brown: So, Mr. Bebi, could you comment specifically on, with the research that you've done, are there some barriers on the side of the sponsors of the trials or in terms of industry that you found and that you found in your work at Medidata, maybe really affecting the ability of diverse people to participate in clinical trials? Ted Bebi: Dr. Lopez did a really good job at presenting what we consider patient-level barriers, such as mistrust in the healthcare system. Logistical issues such as taking time off from work, transportation, or feeling that the investigators running the trials don't fully represent the patient. But the industry-level barriers are just as important. A lot of companies are making decisions on what good diversity should look like and where they can find more diverse patients based on incomplete data sources such as disconnected external data, or they might be limited to data from the companies. Dr. Carol Brown: Great. So, Dr. Lopez, what do you think individual physicians can do, or individual investigators can do to improve the diversity of representation in cancer clinical trials? Dr. Ana Maria Lopez: Certainly, being circumspect, being aware of our own biases, our own approaches. But as a health system, I think we need to think about: How can we make it easy to enroll people into trials? So are there ways, if this is, for example, a study for people at this stage of cancer, that all of those patients could be screened in the electronic record? Let's have our electronic tools work for us so that we identify patients that are meeting the study criteria and then connecting the patients, the study, and the investigators together. So, this way, by having our systems identify potential participants, there's a less chance of there being that personal bias. The research team can come to the doctor, to the oncologist, let's say, and say these are folks that are eligible. What do you think? So, in a way, setting up systems to help with the recruitment would be very helpful. Dr. Carol Brown: Mr. Bebi, can you comment from the standpoint of specifically– because you focus on this– the importance of data, the data, how to capture the data about race or ethnicity or whatever the demographic diversity variable is, what can individual investigators do to really address the challenges around collecting this data and sharing it? Ted Bebi: Often, race and ethnicity data is not even captured at all. So, if we want to understand this issue better and improve upon it, we need better data inputs in order to produce this large-scale research that will help us ultimately advance the issue and not just rely on anecdotal information. Dr. Carol Brown: Are there any technologies or things that you came across in your specific work that can help with this ability to capture this type of data and to share it? Ted Bebi: I think it has more to do with the awareness and the clinician relationship with the patient. And I also think it has to do with sponsors and the way that they design the trial, to begin with, whether or not the race and ethnicity entry is something that they're asking in their electronic health forms. Because if that is not included in the clinical trial, to begin with, then there won't be any incentive to capture that information. Dr. Carol Brown: Dr. Lopez, do you have any specific tips that you would recommend to clinicians who want to improve recruitment of underrepresented groups in their clinical trials? Dr. Ana Maria Lopez: I think one thing that's really important is to be able to have the time. Now, that may not mean that it's all the clinicians' time. It may mean that you have a research coordinator. It may mean that you have a research nurse. It may mean that you give the patient a video that explains the study that they can take home. There can be different ways. Something that I often ask a patient is, "How do you make decisions?" People tell me, "You know, I always go over this with my wife," let's say, or, "I always discuss this in our family, and then we come to a conclusion." Because that really helps me to think about how should I best deliver the information so that the patient can really feel I made a good decision and I made a value-congruent decision. So, I think time is critical and to set up our patient experience to really facilitate that type of experience for the patient. Also, as a reference, I would urge people to take a look at the recent recommendations put out by ASCO and ACCC that talk specifically about increasing racial and ethnic diversity in cancer clinical trials. So, there are lots more strategies, a lot more ideas, and ways to really support clinicians and researchers. Dr. Carol Brown: Mr. Bebi, do you have any specific tips, particularly for trial sponsors, about how they can improve diversity in their clinical trials? Ted Bebi: In terms of companies and sponsors, what they can do if they want to improve diversity in their trials is they need to find and include the right sites that serve the populations that they are looking for. We published research that shows that there is high variability of diverse recruitment based on which sites you are looking at, with some sites providing the highest concentration of diverse patients. So, if diversity is not woven into trial design off the bat and you're not selecting the right sites, you run the risk of not reaching these populations. Companies also need to be willing to put in work to educate and develop sites into clinical trial sites. A clinical trial site is about building trust and relationships and knowing how to be culturally adept at talking to diverse communities. Dr. Carol Brown: Great. Thank you so much. Well, I want to thank both of you, Dr. Lopez and Mr. Bebi, for a lively discussion on this ASCO Education podcast about diversity in clinical trials. The ASCO Podcast is where we explore topics ranging from implementing new cancer treatments and improving patient care to oncologist well-being and professional development. If you have an idea for a topic or a guest you'd like to see on the ASCO Education Podcast, please email us at education@asco.org. To stay up to date with the latest episodes and explore other educational content, please visit education.asco.org. Speaker Disclosures Dr. Carol Brown – None Ted Bebi: Employment – Medidata (a Dassault Systèmes company); Stock and Other Ownership Interest – Pfizer, Eli Lily, Abbvie, Merck, BMY Dr. Ana Lopez – None The purpose of this Podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this Podcast express their own opinions, experience, and conclusions. Guest statements on the Podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Dr. Lisa Rosenbaum, a cardiologist and writer, discusses her family legacy in medicine, love for writing, and prompts for specific topics. She shares challenges in discussing controversial subjects, the emotional impact of books on physicians, and advice for young physicians on incorporating writing into their careers.

Advanced practice providers (APPs) are a key component to effective team-based care, but what is it that our APP team-members can do in an oncology practice? Join the Co-hosts of the APP podcast series, Todd Pickard (MD Anderson Cancer Center) and Stephanie Williams (Northwestern University Feinberg School of Medicine), along with guests Wendy Vogel (BroadcastMed/APSHO)) and Tammy Triglianos (University of North Carolina Basnight Cancer Hospital), as they highlight the services and examples of what APPs in oncology can do, their role as an APP in team-based care, if and how they bill for their services, and how they are reimbursed. Speaker Disclosures: Stephanie Williams: Consultant or Advisory Role – CVS Caremark Tammy Triglianos: Consulting or Advisory Role – Pfizer Todd Pickard: No relationships to disclose Wendy Vogel: No relationships to disclose Resources: Podcast: Advanced Practice Providers - APPs 101: What and Who Are Advanced Practice Providers (APPs)? Podcast: Advanced Practice Providers – An APP's Scope of Practice Advanced Practice Providers - APPs 101: Physicians Assistants (PAs) and Advanced Practice Registered Nurses (APRNS) in Oncology 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. Stephanie Williams: Hello, everyone, and welcome back to the ASCO Education podcast, and our fourth episode of the Advanced Practice Providers series. I'm Dr. Stephanie Williams, a medical oncologist, and your co-host for the series, along with physician assistant Todd Pickard. We'd also like to introduce you to our guest panelists today. Returning guest, Wendy Vogel, along with Tammy Triglianos. We'll take a moment to let them introduce themselves, starting with Wendy. Wendy Vogel: Hi. Thanks so much for having me today. I'm Wendy Vogel. I'm an oncology nurse practitioner by trade, and I am the Executive Director of APSHO, the Advanced Practitioner Society for Hematology and Oncology. And thanks for having me here today. I'm really excited to be here. Dr. Stephanie Williams: Tammy. Tammy Triglianos: Hi, everyone. Thank you for having me. And I'm excited to join this group for our conversation today. I'm Tammy Triglianos. I am a certified oncology nurse practitioner practicing in North Carolina. My career has been dedicated to caring for oncology patients, even starting out as a nursing assistant and then as a registered nurse practicing in a variety of settings. I've been a nurse practitioner for almost 20 years now, with the past 15 specializing in GI medical oncology. Dr. Stephanie Williams: Thank you. Todd Pickard: Thanks, everybody, for being here today. Dr. Stephanie Williams: In today's episode, we will be highlighting the services and examples of what advanced practice providers in oncology can do and describing if and how they bill for their services and how they are reimbursed. So let's get started. Wendy and Tammy, I'm starting in my clinic, 8:30 in the morning. We have a full panel of patients, patients who just need reassessment, chemotherapy prescribed, reevaluation, bone marrow biopsies, test results. How do we work together to see, as a team, these particular patients, or in other words, what can you do to help me through my days as an oncology practitioner? Wendy Vogel: Wow, that's a great question to just jump right in and start with. I'm excited to talk about that. Well, I think that, you know, as we always are talking about our team approach, we would look at that schedule. And hopefully, the AP and you have their own schedule so that we're able to divide and conquer and be able to accomplish that schedule, see all the patients in the most efficient manner possible. Hopefully, I've looked at all my patients beforehand and see if there's anything that I need to collaborate with you on. Looking at our labs, you know, maybe scans, talking about any changes in plans that we might anticipate together, and so on. Tammy, would you do the same? Tammy Triglianos: Yeah, I'd like to echo your point, Wendy. Having independent schedules, I think, makes for a more efficient workflow in the clinic. And in my practice we have a team meeting with our clinical pharmacist, physician, myself, and our nurse navigator, and review last week's and even prep for the upcoming week, trying to anticipate and make sure people are set up and orders are in, and we're prepared for the week to come. Day of, as you know, can get pretty hectic. But since we've done a lot of that prep work, I think it makes for the unknowns that pop up in clinic easier to connect with each other, with my physician and other team members. Todd Pickard: I agree. I think the great thing about how physicians and APPs work in teams is that the team can decide what's best. I have done everything from having my own independent template so that I have patients that I'm responsible for to a general template where the physician and I just divide and conquer at the beginning of clinic, and we say, "Okay, you see these patients, I'll see these patients, and we'll back each other up if we need to." All the way to seeing every single patient along with the physician when we are seeing a lot of news and consults, very complex, very acutely ill patients. And we basically just work as a team the entire day on everything. So it's really interesting about the conversation that I think we'll end up doing today is the "what" versus "how." What APPs do is– really, honestly, APPs can do anything and everything unless a state scope of practice or an institution's policy specifically says they can't. That's the good news is that we pretty much can do everything but the "how," that's a really interesting question because a lot of different things come into play. Position preferences, which could be influenced by their own personal experience or their own personal preferences of style versus, you know, having a misunderstanding of what APPs can and can't do. Then there's the institutional policies and the state scope of practices that come into play. So I think this where we'll end up spending some time today. And, you know, Stephanie, maybe we could start the conversation with you a little bit around physician preferences and what your experience has been, and some of the things that you've noted around the physicians as part of this team. Dr. Stephanie Williams: I've worked with APPs, both inpatient and outpatient, and I think it is very important to have that team-based approach. Patients really appreciate that, knowing that there is always a provider, someone there that they can turn to. And I think that's one of the great things about APPs is they always seem to be there for patients to turn to and for our nurses to turn to, to get help too. Both our clinic nurses, our infusion nurses, and our inpatient nurses really appreciate having that extra clinical provider available to them. I think as a physician, during my day, what I would like to see is us getting through our panels of patients, whether we're together, which is not as efficient as if we're independently seeing patients, but also help with things like procedures that need to be done on patients, phone calls at the end of the day, peer-to-peer reviews in order to get either medications or tests done for our particular patients. Filling out forms, no one likes doing that. No one likes filling out disability forms or other insurance forms, but those are all things that we all need help with in terms of doing. Ordering consults, seeing new patients together. I work in the transplant field, so they're complicated patients, so it actually is very helpful to have, to see a patient with your advanced practice provider so that you can come up with a treatment plan together that you know you can then follow throughout the course of hopefully that patient's treatment and recovery. Chemotherapy orders is another place that we need, that can be very valuable, whether it's the initial chemotherapy order, which were usually the physician or pharmacist initiated, but those follow-up chemotherapy appointments or problems in the infusion clinic are also helpful areas. There are some physicians, though, who want to have an APP simply as their scribe, to follow them around in clinic and to then begin whatever orders they feel is appropriate for that particular patient. That is not the most efficient way to see patients, particularly when you have a large panel of patients that you have to see. Wendy Vogel: Exactly. It really isn't. I will just tag off something you said about the AP being the scribe. That's probably one of the most expensive scribes that a physician could employ, and what a better use of our time is to not be a scribe. You know, there are other people who could really efficiently be a scribe better than the AP, and the AP could actually be seeing patients and gaining reimbursement for the practice. Tammy Triglianos: An additional comment on team-based care. I work with a physician where we alternate visits, and I think that has really worked well in establishing a relationship with patients. We both have very high touch points with the patients, very involved, and patients feel like there's that team that's always available because always one of us is usually available. Dr. Stephanie Williams: How long did it take you all, all three of you, to develop that relationship with your physician colleagues to work tightly in a team? Todd Pickard: That's really a great question, Stephanie, because I think one of the strengths of the relationship is that level of trust and comfort and not really to view it as a hierarchical relationship, but really a team. We're there for each other. And you know, that depends, you know, there's personalities involved, people's previous experience, you know. If you've only had great experiences with APPs, probably trust them right away. If you've had difficult relationships with APPs or teams that didn't work well, it may take longer. I'd say the best approach is for both the APP and the physician to really look at this as, "How can we accomplish our work together that provides the best quality and the highest level of safety for our patients?" And really just set the expectations of 'this is a trusting relationship where we work together, we support each other, and we're willing to talk about where the limits of our knowledge are. And for both of us, that's when we get consultations with other folks, and so we just approach it from this perspective.' And of course, you know,over time, that just strengthens and grows. And when you have a really good, strong, trusting relationship, that's where the real power of the team comes into play. Wendy Vogel: I like what you said about trusting. You know, the AP has to trust in the physician to be able to go and ask questions and to be mentored, and vice versa, too. I think we play to each other's strengths. If my strength is talking about hospice to a patient that needs to change trajectory of course, then maybe that's what I do better. And there are other things that another team member would do better, but feeling comfortable and saying, "You know, this is what I do good," or, "Hey, I need help with this. I don't do this as well as I would like to." Dr. Stephanie Williams: Tammy, anything? You said you work with one physician. How did that develop? Tammy Triglianos: Right now, that's my current setup because of volumes, but I have worked with a team of physicians as well, which, when you're an APP working with a team of three, four plus physicians, that can kind of get a little bit tricky, people fighting for your time. I think being in parallel clinics has helped establish our trusting relationship because all day long, you're with that person navigating care together. We've been together probably 14 years, so that's really dipping back into my memory bank of the beginning of our time together. But I think it's what Wendy was talking about is just approaching each other with questions or, "Hey, why did you do that?" Or "Help me understand this." And I think our approach to each other wasn't, "Why did you do that?" But, "Help me understand your thoughts on this." Or "Can I talk through this with you to make sure I'm on the right page." And how that response came back, then I think that has helped develop a trusting relationship. Dr. Stephanie Williams: You both bring up excellent points because there still exists that power gradient between the physician, the advanced practice provider, and a staff nurse or an infusion nurse. And it's really important to overcome that so that people are comfortable in terms of taking care of the patient, to give the patient the best possible care that there is. Todd Pickard: Yeah, I mean, I think this is a great time to really just highlight the fact that there's a lot of misinformation and misunderstanding out there around APPs, what they can, what they can't do, what they will, what they won't do. In some corners, there's this fear that APPs will go rogue, and that will harm patients. And really, that is an irrational fear because when we are trained, we are trained very clearly about when you reach your own limits, that you are required and obligated as part of your professional practice to find that support, find those resources, get consultations, work with your team to understand so that you serve the patient. And I think it's really important that folks remember that with this respect and trust and accountability, because asking for help is not a failure. Asking for help shows a successful dynamic within a team so that the entirety of the team brings to bear their expertise, their knowledge, their skills, and their judgment. And when the team doesn't know what to do, that's when you've got to reach out to your consults and your other resources. So I think that's an important thing to remind everybody is that we're all here trying to do the same work, and it doesn't do any good if you spend a lot of time wondering, "What's Todd up to today?" So I think it's important to realize and for us to kind of dispel those kinds of myths. Wendy Vogel: I think, despite a social media post by one of our well-known medical associations that will remain unnamed, we don't think that healthcare is a game. We are absolutely serious about this, and we love taking care of our oncology patients. This is something that we're trained to do and that we want to work together as a team. Great thoughts, Todd. Dr. Stephanie Williams: In terms of actual practice in the states that you're at, are there any restrictions, either statewide, institution-wise, on what you can and can't do? Tammy Triglianos: I think a big topic that comes up a lot is signing treatment plans or antineoplastic treatment plans. And I don't know across the states, but in my state, that is not a state restriction. But not allowing APPs to sign antineoplastic treatment plans is more of an institutional restriction, and that varies. Recently, I was able to work with a team of people to update our policy to allow APPs to sign antineoplastic treatment plans and how it works at my institution, they go through a privileging process, so essentially it's an opt-in privilege. So, APPs can obtain approval to sign treatment plans, and it is restricted to cycle two and after. So the treatment plan initiation and signing the first cycle is done by the physician, and APP can place the treatment plan and get it teed up. But it actually is signed by a physician for cycle one, and then an APP is now allowed to sign beyond cycle one. We have a few guidelines like they have to be in their subspecialty practice and be manipulating treatment plans that are cosigned by the physician initially and have certain subspecialty training. So, yeah, I'm excited about this update to allow APPs to practice to the top of their license. Todd Pickard: Stephanie, this is such an important concept and one that we have hit upon in all of our podcasts. And really, the limits of APPs outside of physician preferences are really state laws and institutional policies. And so, the answer to your question is 'yes, and it depends on where you are'. So, for example– Tammy gave an example of what's going on in her institution. In my institution, all chemotherapy plans must have a double signature, whether it's initiated by a physician or a pharmacist, or an APP, and that's a safety and quality check. And so everybody just needs to understand, again, limits generally are only in state laws and institutional policies rather than what APPs are trained to do or what folks will reimburse for. And so, really, that's where you have to do the most detailed examination is: what state are you in and what does your institution or your practice say? Generally speaking, most states allow teams at the local level to kind of figure out what they want to do. Sometimes they'll limit a certain medication, like a schedule II drug or a certain other medication. Institutions sometimes do the same thing. But the good news is, if it's not explicit in state law, you can change institutional policy and physician preference all day long. Wendy, what's your experience been? Wendy Vogel: Oh, I totally agree. I think it's important for APs to know who's setting the institutional policies and for physicians to know this as well because it may be someone who is not familiar with what the AP role could really be. What do they know about the advanced practitioner? We mentioned that earlier. But I think it also brings up a very important gap that we've seen in oncology, is what's the training of the AP to be able to write anti-cancer therapy orders, and it's a wide variety. There are very few, for instance, nurse practitioner oncology certification or graduate programs. Most of us are trained in a generalist level as a family nurse practitioner. PAs, as you said before on this podcast, you are trained at a generalist level, and we get a lot of our specialty education on the job or through other advanced education. So we're coming into this at all different levels: brand new APs, brand new to oncology APs, and we've seen a gap at the educational level across the US is not the same. One of the things that APSHO has done to relieve this, and I'm so excited to be able to share with you guys, is we've just recently launched the APSHO Cancer Therapy Prescribing Course. This, I think, will set the benchmark that we've just talked about and bridge this gap, and allow APs to really practice to the top of their licensure, as Tammy mentioned earlier. It's a very comprehensive online, self-paced course providing that advanced education to prescribe cancer therapies and to manage that hem/onc patient throughout the treatment trajectory. It does not just include the cancer therapies but other things we need to know as APs, like: what kind of drugs do we give with the cancer therapies, what are the standards of care, what do we do in clinical trials? And so just all this that we need to know, and I hope this will bridge that gap, if you will, for this education. Dr. Stephanie Williams: Excellent points. I think it also requires physician education to know and understand what advanced practice providers can do. And I think an advantage to our younger generation physicians is that they are now growing up in institutions where APPs are normal, as opposed to older physicians like myself, where we really do have to learn what can be done and what can't be done so that we can trust what everyone is doing there. Todd Pickard: Are we normal? Yes. But what you really mean is that we're present. It's really about interprofessional education, and I think there's a lot of importance of that concept. If we're going to be delivering care in teams, we should be trained in teams so that you grow up side by side and so that way it does seem normal. I'm working in a team; where's the social worker? Where's the APP? You know, where's the pharmacist? Because that's how you trained, and that's how we really deliver care. That's the honest truth. No man or no woman is an island in medicine. We all work in teams, whether we recognize that or not. And so I think it's great when you hear about folks that are actually training side by side because it just dispels some of this anxiety, some of these misconceptions, and you're just used to the team being around, and it's like, "Okay, where's my team?" And then it doesn't become unusual. It's just normal. Wendy Vogel: Yeah, we're all sitting here nodding our heads together. You all can't see us, but we're all nodding. So, Stephanie, I really want to know, how do you educate your colleagues who might not be as receptive to the idea of an advanced practitioner writing cancer therapy orders? Dr. Stephanie Williams: I have to tell you, it's difficult sometimes, Wendy, or it has been difficult in the past. The problem becomes not so much a "do you know what you're doing," problem is how does the reimbursement - I hate to say this – how does reimbursement figure into all this? If I let an APP see half of my patients, who gets that money? And then the other thing is just how do I efficiently use an APP? And we are trying, and ASCO through the Clinical Practice Committee, to try to get out there and reach out to practices, particularly rural practices, to help them understand the role and the value of advanced practice providers. And I think it's going to be a reach-out effort, leading by example, showing people that this is the way we can do it and we have to do it this way because we need practitioners out there to take care of patients. Todd Pickard: I want us to all pause here because what you just talked about is critically important. And we all know this is part of medicine, whether we like it or not. But reimbursement, how we get paid, and productivity, how we are recognized for what we do, are concepts that sometimes get mixed up. So when you're talking about reimbursement, APPs are reimbursed just like physicians for everything that we do. Depending on who's paying the bill, they may reduce that reimbursement. So CMS reduces generally to 85% of the physician fees. Medicaid is all over the place, depending on your state and the third-party payers, like the commercial insurance, that's based on whatever you've negotiated in your contract. Sometimes it's a little, and sometimes it's the same. So APPs get reimbursed, period. What level they get reimbursed compared to the physician's reimbursement is really up to a lot of different factors. But productivity, I think that's the thing that we really get hung up on is, well,who's going to get credit for this work? And guess what? The beauty of that is you get to decide. Every practice, every institution makes up those rules. And so, you know, the take-home message here is, don't confuse reimbursement with productivity. Reimbursement is a lot of external factors that are either statutory, or they're contractually negotiated. But productivity is an internal accounting, and you can use team-based metrics. Who's to stop you from saying 'we reward and recognize both the physician and the APP in these teams.' They both get credit, and they both get productivity measurements and recognition. And so I think that's where we really need to drive home the message is it's not about setting each other up as competitors. It's redesigning our internal productivity measures so that it's collaborative and that all the work that's being done by the entire team is being recognized and rewarded. Wendy Vogel: A lot of what we do, as Stephanie referred to earlier, is not reimbursable. All those peer-to-peer reviews, we don't get paid for that. None of us do. Calling patients back, liaisoning with the nursing staff, and answering their questions through the triage line, so much of that is vital to supporting a practice, and you can't do it without all that, but it doesn't appear on the bean counter's metric sheet. So how do we do that? I don't have the answer to that. Tammy Triglianos: Yeah, and I think in oncology/hematology, there's a lot of frequent touch points in between provider visits, and that doesn't equate to money, but equates to high-quality care, to have access to skilled providers to help manage all the complications, and, you know,in between stuff that happens between provider visits. Dr. Stephanie Williams: Wendy, there have been changes now in terms of who can enroll and write treatment orders for patients on cancer clinical trials. Could you go over those changes with us and how APPs can now fully participate in this process? Wendy Vogel: So there were some recent changes to CTEP and then now allowing APs to sign clinical trial orders. This is huge because it really makes the process of getting patients their drugs in the infusion suite much quicker. We don't have to track down a physician to sign those clinical trial orders. The AP can do that. And so this process is made much smoother. I think we'll see a lot of other cooperative groups and institutions follow suit with this. And I think this was a real demonstration of the AP's quality of care and the safety of AP prescribing and being able to have this privilege. Todd Pickard: Well, this has been a fascinating conversation today, and I would like everybody to have a final say. What's your take-home message today about what APPs can and can't do. And Tammy, we'll start with you. Tammy Triglianos: Thank you. This was a great conversation today. Happy to be a part of it. Know that APPs with supportive, appropriate training, and, you know, I just have to shout out to Wendy and APSHO for the chemo prescribing course. I think this is huge for bridging a gap. Lots of education programs don't have oncology subspecialty, and this is such a comprehensive course that bridges a gap that I think will be huge. And I hope every oncology cancer center adopts, incorporating this to elevate the education and offer some subspecialty education to our oncology APPs. Kudos for all the team-based care and physician and APP teams out there that are really working hard to care for our cancer patients. Todd Pickard: Wendy, what are some of your final thoughts? Wendy Vogel: I have to agree with Tammy. I'm really excited about the APSHO Cancer Therapy Prescribing Course. I think that we can, together as a team, really make a difference in cancer care, playing to each other's strengths, and I think that would be my takeaway is: how can we better play to each other's strengths? Todd Pickard: Stephanie, what about some of your final thoughts? Dr. Stephanie Williams: I think working with APPs is critical to the success of any medical practice and to any physician who takes care of patients. Todd Pickard: Well, I appreciate all the insights. And just as a reminder, APPs and physicians, generally speaking, can decide whatever they want that is best for the practice, best for their patients, and delivers high-quality and safe care. Just be aware of your state regulations and find those institutional policies that are holding you back. Good news on the institutional policies - you can change them just like you can change your productivity metrics and models. So the good word is APPs and physicians can work in amazing teams, and we have all the power at our disposal to do so. Well, I want to thank you to my co-host, Dr. Williams, along with Wendy and Tammy, for joining our discussion today and sharing all of your experience and highlights into the services that APPs can deliver. It's clear that APPs and physicians working together in teams are vital to a strong and efficient delivery of our team-based care. Well, until our next episode, thanks, everybody, and take care. 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.

"Various places on the globe lack the proper knowledge, infrastructure and workforce to adequately treat cancer. In Africa, one doctor is focusing her efforts to change all that. This ASCO Education podcast spotlights Dr. Miriam Mutebi, the first female breast surgeon in Kenya. One of Dr. Mutebi's goals is to improve women's health and cancer care in Africa and includes attaining her pilot's license to reach remote areas of the continent. Dr. Mutebi reflects on her life growing up in Kenya (1:21) and her inspiration for getting into medicine and pursuing what was at the time a male-dominated specialty (5:07). She also details how cancer care has improved in Kenya in the last decade (12:49) while there are ongoing challenges of working in low-resource settings (23:25). Speaker Disclosures Dr. Miriam Mutebi: None Dr. David Johnson: Consulting or Advisory Role – Merck, Pfizer, Aileron Therapeutics, Boston University Dr. Patrick Loehrer: Research Funding – Novartis, Lilly Foundation, Taiho Pharmaceutical Resources: ASCO Podcast: Oncology, Etc. – Global Cancer Policy Leader Dr. Richard Sullivan (Part 1) ASCO Podcast: Oncology, Etc. – Global Cancer Policy Leader Dr. Richard Sullivan (Part 2) 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 Pat Loehrer: Welcome to Oncology, Etc. an ASCO Education Podcast. I'm Pat Loehrer, Director of Global Oncology and Health Equity at Indiana University. Dave Johnson: And I'm Dave Johnson, a medical oncologist at the University of Texas Southwestern in Dallas, Texas. Pat, we have a terrific guest today that ties in very nicely with your interest in global health. I'd love for you to introduce her. Pat Loehrer: Thanks, Dave. Battling cancer is truly a global effort, both in research and in treatment. However, there are various degrees of quality in these fields, depending on the economic health of a particular region. Our next guest is trying to optimize cancer care in Africa. We're very excited to talk to her. Dr. Miriam Mutebi is one of the most prominent cancer doctors in Africa. Dr. Mutebi is the first female breast surgeon in Kenya, and she's currently assistant professor in the Department of Surgery at the Aga Khan University in Nairobi, Kenya. She's on the board of directors for the Union of the International Cancer Control. She has trained and studied at top hospitals in New York and South Africa. Dr. Mutebi is so focused on increasing women's health in Africa that she's trained to be an airplane pilot in order to connect with hard-to-reach areas. Disclosures for this podcast are listed on the podcast page. Thank you so much, Dr. Mutebi, for joining us from Kenya. Can you start off by telling us a little bit about what it was like growing up there? Dr. Miriam Mutebi: I grew up in Nairobi, which is a pretty urban setting to grow up in. So, most of my childhood was spent…I think it was probably a much simpler time where, you know, you would play in the street, go off to somebody's house, spend the rest of the day there and come back at the end of the day. But in terms of growing up, I think I was one of those super nerdy kids, for want of a better word. One of the sorts of things that got me interested in reading and learning and challenging myself was actually my dad. Because what would happen was we had to go to school, I would say almost about 30 kilometers bus ride, and my dad would be like, "Well, if you're on the bus for that long, you can as well, you know, carry a book and made it nice and exciting." So I remember sort of discovering the library at my primary school and going like, "My word!" Because you get access to all these different experiences and worlds. I mean, you're going in and reading, you know, The Chronicles of Narnia, you're reading about Enid Blyton and different experiences, you're reading all these different worlds and getting to, you know, identify to some extent with the core values that exist. It doesn't matter where the books were centered. And so that for me was an almost, I would say, idyllic growing up, because for me it was like, "Yes, books, check; running around, check." That's, I think, what I remember most about my childhood. Dave Johnson: It sounds like your father was a powerful influence in your youth. Can you tell us more about your father? Dr. Miriam Mutebi: Sure. My dad, how old is he now? He's going to turn 74. One of the things that he always says, "It costs you nothing to be kind." And so he would generally– Sorry, I'm just going to stop a little bit. I'm getting weepy. Dave Johnson: I'm sorry. Dr. Miriam Mutebi: It's okay, it's okay. Shame. Dave, you pushed the button. Dave Johnson: It's not our intent to push a button. It sounds like your dad's a wonderful person. Dr. Miriam Mutebi: No, it's fine. Pat Loehrer: Both Dave and I have daughters, and we feel the same way. So as weepy as you're getting, I can guarantee you that he's going to feel the same way on the other end. Dr. Miriam Mutebi: No, it's just that he hasn't been well recently, so it's just– Dave Johnson: Oh, I'm sorry. Dr. Miriam Mutebi: Yeah. Okay, cool. Let me see if I can stop getting a little weepy. Yeah. So one of the things that he frequently says is that it costs you nothing to be kind, and I think that's one of the things that he sort of instilled in us that you need to think beyond yourself. You always need to sort of think about what is the other person going through and how can I help to make it better. Now, my dad, he has a really interesting sense of humor. I think it's where I get my cheesy humor from as well. But he always talks about what we call the 11th commandment, which is, don't take yourself too seriously. And so I think that was part of the grounding steps that he sort of helped to instill in us because he was working– I mean, sort of looking back, our parents, I would say, got married at a very young age and had several kids that they were raising. And sort of looking back, you're thinking they were probably just doing the best that they can, right? But I think he did a fairly decent job, I hope. Dave Johnson: So, Miriam, when did your interest in medicine begin, and who was the inspiration for that? Or if there was someone that inspired that? Dr. Miriam Mutebi: At the end of high school, I remember I wanted to do five or, rather, was it six different things. And so I wanted to do medicine, I wanted to write, I wanted to do architecture, I wanted to do law, I even forget what the other things were. There was like two other things on my to-do list. And I think part of the genesis of that was because, as part of the high school training that we go through, we had to do the international sort of baccalaureate, and what that entails is we have to do components of creativity, action, and service. And so at the end, I'm like holding back to father dearest, and I'm like, "Dad, I have six different things I want to do, and I don't really know about." And he was like, "So why don't you spend a bit of time, sort of just going through each of those, like shadowing these different specialties?" And so we managed to track down his lawyer friend, spent time in the hospital, spent time in the pharmacy, just shadowing the pharmacist. I actually went to work briefly for a publication house. Eventually– Oh, yes, in architecture as well. So then I managed to narrow it down to, "Yes, okay, I want to do medicine, and I want to write." And so I went back to my dad and said, "Dad, okay, I have two things I want to do." And my dad was like, "Well, if you do medicine, you can write. But if you write, then you might not necessarily be able to do medicine." So that's how I sort of wandered into medicine. Although I still say there's still the great African novel waiting to get out. But again, with medicine, I think I'm guilty of what we call 'end of rotationitis', where at the end of the day, you finish a rotation, and you're like, "I can do this. I can do this." So I think going through different rotations– I think for me, the drive– Well, the slow narrowing down to surgery was really around, unfortunately, the time when we were doing our rotations, and this was just really at the start of the 2000s in Kenya. And the challenge around that time was we're really just at the tail end of the HIV epidemic, and not everyone had access to antiretrovirals. And it was an incredibly harrowing time, I would say, for the healthcare profession, just because there was still a lot of stigma around HIV. And what was happening was that we would go to the wards and find patients had been abandoned. And there was a general sort of pervasive sense of hopelessness because people didn't have access to the medication, they'd been abandoned, and unfortunately, not much was being done in terms of active management to patients. Whereas then that was like on the 7th floor, and then you would go four floors down to the surgical ward where patients come in, they're bleeding; you take them to OR, they get better, you send them home. And so, for me, the timing was like, "I need to do this. At least I could see where I was making an impact." And so that's sort of how I wandered into surgery. And I'm sure, as I said, with, of course, the developments now, the experience, of course, for medical rotations, they're entirely different, but that's how I sort of ended up in surgery. But then, how I sort of found myself in breast surgery was actually because– for me, what stood out about my breast rotation was really looking at what we were reading in the textbooks, which was breast cancers, the disease of the sixth and seventh decade and a "poster child" for this is the elderly nun who's never had any children, who's had this prolonged [inaudible]. And I'm sitting there and looking at the clinic, and I'm like, "These patients are in their 30's and 40's. All of these traditionally protected factors, like having multiple children, having breastfed, ticking all the boxes, but they're still coming in with these kinds of cancers." And so just thinking this is totally different from what the textbook is saying, and somebody needs to get to the bottom of this, and that's how I found myself going in along breast cancer surgery and also research into women's cancers and things. Pat Loehrer: My sense is that Kenya and many African nations were male-dominated. I don't know what it was like for you going to medical school, but particularly in surgery, it tends to be a male-dominated field. What was that like as a woman? In many ways, I think you were breaking some glass ceilings. I'm sure other women are doing similar things, but tell me a little bit about that experience. Dr. Miriam Mutebi: I would say bewildering for both parties. Because we had to do several interviews just in different institutions before getting into a surgical residency, and I remember these senior professors sort of peering down their glasses and looking frankly bewildered and asking the most bizarre of questions, which I don't think anyone would sort of get away with in this day and age. I remember somebody asked me, and this one always stands out in my mind because somebody asked me on the interview route, "So what happens if you get a patient in ICU and you start to cry?" I'm like, "Well, first of all, I'm guessing that I am crying because I'm having a bit of empathy for the patient. And I think that actually probably makes me a better clinician because I am really truly seeing the patient rather than bed X with diagnosis Z. This is like Mary, mother of one, two, three, and whatever." But it was really bizarre. Then somebody asked me as well, "Okay, so what happens when you're on call, and you have to breastfeed?" And I'm like, "Well, let's see. This is a tough one." You could tell as well that they were really out of their depth. So, eventually I settled on the Aga Khan just because, in terms of the faculty and the interviews, I got a sense that they were a little more open to the idea. And that's because I think one of my earlier mentors, Prof. Raja, who is our former chair of surgery, had come in from the Aga Khan in Pakistan. And for him, it wasn't anything unusual to see women in surgery. So, like, "Yeah, come along. We'll train you and stuff." And he was also pretty inspiring in terms of the decision to get into surgery because, for him, their approach to at least surgical training– and we always tease him and say, we all drunk the Kool-Aid because we kind of came back. Because it wasn't about just training surgeons for surgery's sake, it's about how do we become leaders, how do you impact care in your region. And so it was never about just learning surgery; it's how do you use the tools that you have in order to improve the health of those around you. In the Aga Khan, you're sort of, one would say, in a position of privilege. Just the backstory to those listening who might not know about the Aga Khan, it's a private university hospital. But I mean, as a private center, then, of course, I would say there isn't any difference, one would say, between the Aga Khan and most of the international hospitals anywhere in the world. But it was always sort of driven into us that this is a privilege that you're having. And how do you use this privilege to elevate the communities around you? Pat Loehrer: Let's talk about breast cancer, if you will, in Kenya. You mentioned it that when you first went into it, patients were coming in with advanced disease, they still do. But how has the field of medicine changed in Kenya during your professional lifetime as it pertains to breast cancer? Dr. Miriam Mutebi: While we still have the majority of patients diagnosed with advanced disease, the scenario ten years ago was that patients would get diagnosed with advanced disease and frequently would not complete their care. And if we did a deeper dive into the reasons behind this, we saw a constellation of factors. One being the fact that patients were having to pay out of pocket, resulting in financial toxicity, catastrophic health expenditure. And then the other major barrier was the health system itself. And again, to some extent, that still exists where we know, at least on average in sub-Saharan Africa, patients are going to see 4 to 6 healthcare providers before a definitive diagnosis of their cancer is made, which of course, again, translates into delays in ultimate treatment. Another area that we frequently don't necessarily talk about as much are the social-cultural barriers that exist and, to some extent, are still pervasive in some communities. What we see is, one, there's a lot of use of alternative therapies. There is still quite a bit of stigma around cancers. There is what we call collectivism, where we always say in Africa, 'our community is our strength'. But sometimes, that sense of community is a double-edged sword because then, if the patient is losing agency, then that becomes a real concern. Because what we find, for instance– I'll give you an example, I'll have a patient come in and discuss, and maybe she has early cancer, and discuss the options of having breast conservation versus a mastectomy. And then you will find maybe she goes home to have a think, and then a couple of days or whatever later, there's a community gathering, and the clan elder is saying, "We have decided." And I'm like, "Who's we? That's not your breast coming off. Like, what right do you have to decide on patient decision-making?" But you see, as much as we would like to sort of say have the patients have autonomy over the decision-making, it's really a question of equity and access to care. Because even if you're giving the patient autonomy, and she's saying at the end of the day, "Well, they're the ones paying for the treatment so let them decide what it is I'm going to have", then we haven't really adequately empowered our women. And so those are some of the challenges that existed, I would say, about ten years ago. We're definitely seeing an improvement. One in the patient's ability to pay, and this, I think, has been a concerted effort by the government to come up with a National Health Insurance Fund, which initially wasn't covering cancer care but has definitely helped to ensure that the number of patients who actually complete their care or going through their entire cancer journey are probably more. I remember when I was doing my internship, there were like truly heartbreaking because, as interns, we would have the medical internists sometimes– and because there weren't that many medical oncologists– prescribe the chemotherapy and as interns, we were the ones who would administer the chemotherapy. And so, you would have a patient come in and it involves– Basically, we give the prescriptions like chemotherapy, but they'll also have to buy their own saline, the IV line, and everything else,,, and then they get the first cycle, and they just disappear. And then those were the times when mobile phones weren't that common. They literally just disappear. But then they come back six months later, and they're like super excited, and they're like, "Doc, we've raised enough money for the next cycle." And we're like, "Well, it doesn't quite work like that." So, with the National Hospital Insurance Fund, it's not perfect, but we definitely see more patients going through the entire care continuum, which is gratifying. I'm sort of putting on my [inadudible] hat as the chair of Kenya Society for Hematology and Oncology, and we've been working closely with the National Cancer Control Program, really to advise the National Hospital Insurance Fund on maybe getting more comprehensive covers. Because what was happening initially was, for instance, they would cover maybe four cycles of chemotherapy. Then the patient has to come up with the remaining four, for instance, and sometimes if they're not able to afford that, then you're sort of giving them the side effects without the therapeutic benefits of some of these. So they are currently in the process of really looking more at treatment plans, and that's also been, at least, a truly– And the fact that they are willing to listen has also at least been a huge stride. And then, of course, in terms of the real efforts, I would say by the National Cancer Control Program to ensure some of the decentralization of cancer services. Initially, we had only one radiotherapy center at the tertiary referral hospital in Nairobi that was having patients traveling from across the country, 400 kilometers or more, coming in. And you come in from a rural area, you come into Kenyatta and somebody tells you have to live there for a month, you have no family, nowhere to stay. People say, "You know what? I don't need to have this stage or rather have this additional treatment." And so with the deliberate development of or decentralization of the radiotherapy services, we now have at least regional centers in planning and so really looking at how do we bring the services closer to people. And so, we now have, in addition to the tertiary referral centers, we now have two regional centers in Mombasa and in– Pat Loehrer: Eldoret. Dr. Miriam Mutebi: Yes. I think beyond Nairobi, Eldoret, we now have a comprehensive center in Mombasa. Nakuru's just launched a comprehensive center and Garissa as well, so really looking at enhancing our capability to bring these services closer. And there has also been the development of the chemotherapy units across the country that have at least tried to ensure that these services are more readily accessible to populations. And really just underpinning that with the support from the National Hospital Insurance Fund has helped to basically have more patients completing their care. One of the other things that I think deserves particular mention is really the grassroots advocacy that has really tried to increase awareness around cancers. And as a result, we definitely are seeing, as much as we are saying the majority of patients are still diagnosed with advanced disease, we are definitely seeing the entire continuum all the way from screen-detected tumors, early stage I, stage II cancers to more advanced tumors. So with that, it also really shows that there is a continuing consciousness that's really sort of driving these education efforts and awareness in the community. Of course, we definitely do need to do more because we still see that the advocacy's efforts sometimes tend to center largely around urban areas. And also, the question is how do we then sort of percolate that down to more rural areas? It's definitely something that's improved in the last ten years. And then, of course, we've also seen an expansion in the cancer workforce. And that, I think, has also been largely driven by the fact that we're having in-country training for clinical oncology, medical oncology, gyne-oncology, so we're really thinking about how to expand the workforce but– Of course, we are still looking at the patient-to-population ratios, those are still pretty low and we still recognize that there are deficits along the care continuum. But we're now having pharmaco-oncologists, we are having psycho-oncologists, increase in palliative care specialists. So there's definitely been an exponential growth of all the cadres of healthcare providers, whether it's oncology nurses and things. We've had an oncology nursing chapter now that's been developed. We really see the rise of the professional societies like the Kenya Society of Hematology and Oncology, and there is a lot of crosstalk between the academic institutions that are running the oncology training programs. So it's really a positive move in the right direction, but I think what needs to happen is, as I would say, more deliberate investment in the workforce. Because, again, even as we increase the spectrum of the oncology workforce, there's really a need to carry along the primary care providers because they invariably are the gatekeepers to access. And so unless the primary care providers are empowered and knowledgeable to facilitate early and timely diagnosis and referrals to the appropriate pathways, then it doesn't matter how many people or how much of a workforce you have on top of the pyramid. It just means you're invariably going to be still getting patients diagnosed at later stages. And so there's also been efforts around that to come up with, from healthcare provider courses to educating common signs and symptoms. This is something that the Kenya Society of Hematology and Oncology has been doing in collaboration with the National Cancer Control Program. There's a deliberate effort to come up with an online platform that are actually able to give real-time information to primary care providers. And so, I would say there are definitely steps in the right direction, but there definitely needs to be more investment in the entire spectrum of care. Dave Johnson: Miriam, what you've done is astonishing. What you've just described is an amazing infrastructure in a relatively short period of time. What you're talking about took us in the United States half a century. You're trying to do that in a matter of five to ten years. You've trained in both Kenya and in the United States. I wonder if you might just take a few moments to compare and contrast those experiences. Dr. Miriam Mutebi: In terms of working in different spaces and sort of working in the US, working in South Africa, working in Kenya, what you realize is perhaps a very different patient profile. Whereas in countries like the US, where you have vibrant screening programs, and you're definitely having a lot more discussions around 4-millimeter, 5-millimeter tumors that you are doing an MRI-guided biopsy for and maybe a lot more screen-detected tumors. Whereas working in settings, especially when you get out of the urban areas, whether it's in Kenya or South Africa, you find that you tend to have a lot more diagnoses of patients coming in with fungating tumors and advanced disease, and so it's really that spectrum. And that's what I'm saying in terms of the current state of flux that we're in. We're now, as clinicians, at least working in Nairobi, you're sort of seeing the entire spectrum and much less and less of the sort of fungating tumors. So I think in terms of the principles, and the good thing is that irrespective of where you are, principles do not change. But I think you sort of have to rapidly innovate and iterate in settings where you may not necessarily have a say, MRI to do an MRI-guided biopsy, but you also sort of look at what makes sense for the patient. Working in lower-resource settings, I think, is actually a good thing because it challenges you to constantly think about value-based care. People talk about value-based care as a concept, but you're doing it on a day-to-day basis, even between different patients in clinic, because you have to think about the cost and you have to think about how do I deliver care that's still of good quality, that's not necessarily going to break the bank. And so these are some of, I think, more challenging or at least questions that we have to think about deliberately. Whereas in the US, if you have insurance, then it's pretty much carte blanche, for want of a better word. Which we did realize, especially with COVID - and I'm sure Pat and Dave you can bear testament to this - these disparities exist globally. And so you'll find that in your patients who have no insurance or are underinsured, they're still coming in with the same, sort of, challenges. I was talking to my colleague at NYU who works at Bellevue. When she was giving me the profile of her patients, it was interesting to see that there wasn't really– and these are patients who don't necessarily have insurance, there really wasn't any difference in the images we are seeing from patient they're seeing and the patients we're seeing. So really it's an opportunity for us to sort of rethink collectively our approach to care and really thinking about how do we provide quality care. Pat Loehrer: I was in Washington this week, and President Biden had a three-day African US summit, and at the end of this, he basically pledged to spend $55 billion in Africa to help relations with them. We also had a discussion about the Moonshot 2.0, in which President Biden wants to end cancer as we know it, with a particular emphasis, I think, and now, in linking with LMICs. Briefly, what would you tell President Biden in terms of what would be very helpful for the United States to help with the cancer problem in sub-Saharan Africa? What would you say in a sentence or two? Dr. Miriam Mutebi: As we say, perhaps have the Moonshot, but stay grounded in the sense that– even before we think about complex molecules, we are still struggling as a continent with the basics of care. And so, investing in health systems and the basics will ultimately give more or improve outcomes rather than sort of focusing on specific molecules. So if we have the basics in place to deliver the basics of care, then that would go a long way toward shifting outcomes. The other bit that does need to happen is, again, with research because there is a paucity of cancer research. We did a recent bibliometric analysis and found that as a continent, we are only contributing to less than 8% of all sort of cancer research globally. And we do know that one, we have, I would say, the breadth of diversity in terms of genetic diversity. We do know that the responses to care and treatments are different. We do know that we do need to think about implementation science and what structures we can put into place, and what strategies. What works in different settings might not necessarily work in ours, and it does need to be backed by evidence. So there are opportunities to expand care and strengthen systems, but really do this in an evidence-based, pragmatic way that ultimately [inaudible] its own outcomes and outputs for the patient. Dave Johnson: Thank you for that, Miriam. Pat Loehrer: Well said. Thank you. Dave Johnson: Great advice. I hope the President is listening. Pat Loehrer: Dr. Mutebi, what was the first book that you remember that you really loved? Dr. Miriam Mutebi: I think it was actually The Lion, the Witch, and the Wardrobe. It was just the whole sort of just stepping into a different world. And then, of course, we all had crushes on Aslan, the lion, but it was more because he was like this sort of guy who would swoop in and was morally just and get to mediate the world. And so I went through the whole series, I just gobbled it down, and I think that's one of the things that really stands out for me as one of the books that I sort of remember early on. Pat Loehrer: It's such a great pleasure today. I'm really excited. We're typically talking about books. And here's a book, Dave, I know that you have not read; it's entitled 101 Things I've Learned in Engineering School. It was an interesting book. As you know, I'm an engineer background, but there were a few quotes in here that I– Dave Johnson: Pat, I live on Purdue Avenue, so I have some engineering background. Pat Loehrer: Oh, that's true. Good for you. So you might like this one, Dave. One of the quotes I have is: "Inventing is a mixing of brains and materials. The more brains you use, the less materials you need." And another one - do you know the difference between accuracy and precision? They're really different things. And so, the best example that came from the book, which I thought was interesting, was pi, so pi is what? Dave Johnson: Round. Pat Loehrer: Okay, this is going to be painful. Pi is 3.14. Right? So that's accurate. But if you say pi is 3.1415926535, that's accurate and precise. And if you said pi is 3.98, that's just inaccurate and imprecise. As I think about engineering as we move forward, I'm thinking about the Lung Pragmatic trial that has just been announced, where we're trying to do trials a lot more simply in which I think we can be accurate, but perhaps not as precise as we always deem to be important. And I think we're really excited about that and that project. Dave Johnson: Well, that's really all the time we have for today. And we really want to thank you, Miriam, for a wonderful interview. And knowing that you're up very late at home makes it all the more special. We also want to thank our listeners to Oncology, Etc. 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 email us at education@asco.org. Thanks again. Pat, I have an important question for you before we leave. What do you call a snail that's not moving? Pat Loehrer: You got me, man. Dave Johnson: Escarstay. Pat Loehrer: I love it. Miriam, Asante sana. Dr. Miriam Mutebi: Nime Shukuru. 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 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.