In part one of a two-part conversation, Oncology, Etc. hosts Patrick Loehrer (Indiana University) and David Johnson (University of Texas) have a blast speaking with two physician astronauts. Hear the incredible stories of Drs. Robert L. Satcher (MD Anderson), Ellen Baker (MD Anderson), and their lives on and off this planet.

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TRANSCRIPT

Patrick Loehrer: 

Hi, I'm Patrick Loehrer. I'm Director of Global Oncology and Health Equities at Indiana University.

Dave Johnson:

My name's Dave Johnson. I'm at UT Southwestern in Dallas. Patrick, we're excited to be back for another segment of ASCO's Educational Podcast, Oncology, Etc. We have two very special guests today, Drs. Ellen Baker and Robert Satcher, oncologist and former astronauts. So I predict this will be an out of this world segment.

Patrick Loehrer:

It's starting out pretty slow right now, with that one. Thank you though. 

Dave Johnson: 

Well, listen, this should be a great segment. But before we get started, do you have a favorite astronaut book? 

Patrick Loehrer: 

Well, the one I read this summer was called American Moonshot by Douglas Brinkley, and it basically took the story of John F. Kennedy and how the space race happened from 1960 and actually earlier than that, into getting onto the moon. It was really, I thought very extraordinary. 

Dave Johnson: 

So, I haven't read that yet. My favorite would be Rocket Boys by Homer Hickam. I thought that was a fantastic book about his life growing up in West Virginia and ultimately, becoming a NASA engineer and rocket scientist. So that was really great.

Patrick Loehrer: 

I read that several years ago after you recommended it. They made a movie out of that. 

Dave Johnson: 

Yeah, I think October Sky was the name of the movie. Yeah.

>Patrick Loehrer:

Yeah, it's a terrific book.

Dave Johnson:

Well, why don't we introduce our guests? You want to start with Dr. Baker? 

Patrick Loehrer:

Oh, sure. It's my pleasure to introduce Dr. Ellen Baker. I have known Ellen over the years through interactions in global oncology. She was born in Fayetteville, North Carolina, graduated from Bayside High School in New York, got a bachelor of arts degree in geology from the State University at Buffalo. A doctorate in medicine for Cornell, masters in public health at UT Public Health, and then trained in internal medicine at UT San Antonio.

And during her residency, she decided to join in the NASA program as a medical officer. And it was actually, she did a residency around the same time I did, and I remember the space call for astronauts at that time. She was selected as an astronaut in may of 1984, had a variety of jobs. She's logged more than 680 hours in space and has been a mission specialist. She retired from NASA in 2011 and is Director of the MD Anderson project, Echo Program in which he does projects in rural Texas, as well as Zambia, Mozambique, in Central and South America. It's such a great pleasure to have you here today, Ellen. 

Dr. Ellen Baker: 

Thank you, Patrick. 

Dave Johnson: 

Our other guest is Dr. Robert Satcher, currently an Associate Professor in the Department of Orthopedic Oncology Division of Surgery at MD Anderson, as well. Dr. Satcher grew up in Hampton, Virginia. He's the son of a university professor and English teacher, so I'm sure they made him do all of his homework. He received a bachelor degree, as well as a PhD in chemical engineering from the Massachusetts Institute of Technology and received his MD degree from Harvard. By the way Patrick, Dr. Satcher enrolled at MIT at age 16 and graduated at the top of his class. Later, we'll find out what you were doing at age 16?

Patrick Loehrer:

I do have to interject that I was a mechanical engineer at Purdue, and it's like being in high school compared to chemical engineers.

Dave Johnson:

Yeah, there's a hierarchy in the engineering world for sure. Dr. Satcher's medical degree was followed by internship and residency in orthopedic surgery at the University of California, San Francisco. In addition, he did a post doc research fellowship again at MIT and University of California, Berkeley. And completed a fellowship in muscular skeletal oncology at the University of Florida, before joining the faculty at Northwestern in Chicago. You guys have a lot of connections it seems? Not satisfied with that massive amount of education and training, Dr. Satcher went on to NASA to train as an astronaut, culminating in a flight aboard the space shuttle Atlantis in November of 2009.

Apparently, he got a little bored cooped up in the shuttle because he took a couple of space walks, which I'd like to know more about. In fact, I read on NASA's website that he did some lubricating on one of his walks. I'm not sure what that's about, but I assume there's not a lot of gas stations in space. I also read that he repaired one of the robotic arms, which seems perfect appropriate for an orthopedic surgeon. You'll have to tell us more. Anyway, while these achievements would be enough for most people, it only begins to scratch the surface of the many accomplishments of Dr. Satcher's career to date. 

I really can't cover it all, but our audience should know that Dr. Satcher's has been involved in a number of community activities, as well, ranging from his involvement in Big Brother for Youths at Risk, counseling program, to serving as a lay minister in his church. He's also undertaken a number of medical mission trips to underserved areas in countries, such as Nicaragua, Venezuela, Nigeria, and Gabon, where he once served as a Schweitzer fellow at the Albert Schweitzer Hospital in Lambaréné. Dr. Satcher, welcome to Oncology, Etc., we very much appreciate your joining us.

Dr. Robert Satcher:

Thanks Dave. Glad to be here.

Dave Johnson:

Perhaps I'll start by asking the two of you, if you could give us just a little bit about your background, other than what we've stated and what got you interested in medicine and how you got interested in space? Dr. Baker, maybe we'll start with you?

Dr. Ellen Baker:

I've always been interested in space. I was a child of the '60s, and I think one of the very memorable parts of the '60s was the US Space Program. It was a fairly tumultuous decade in the US, I think otherwise, and the space program was really literally a shining star. However, there were no girls in the space program at that time. Right? There were no girl astronauts and so I thought about it, but it didn't seem like it was even possible. I come from a family of medical people. My mother was a nurse, my father was a doctor, my brother is a doctor, and so that had a lot of influence, I think, in my choosing to go into medicine. And in fact, my brother is an oncologist and though I am actually not an oncologist, I've been hanging around with him long enough that some people think I'm an oncologist. So I think that's what got me pointed in that direction.

Dave Johnson:

Your brother is Larry Schulman, by the way, right? Humanitarian of the Year Award from ASCO, a couple years ago.

Dr. Ellen Baker:

It is, yes, and he is a great humanitarian. I was actually at my last year of medical school when I saw a little article in the New York Times that NASA was selecting new astronauts and women and minorities were urged to apply. And I kind of filed that away and went off to do my medicine residency and at the end of my residency, I applied to work for NASA as a physician. And that's how I got to Houston and to Johnson Space Center.

Dave Johnson:

Dr. Satcher, what about yourself?

Dr. Robert Satcher:

I got interested in space and being an astronaut when I was a kid too, and I was watching astronauts land on the moon. And I was sitting there listening what Ellen was saying and yeah, it was a time where all the astronauts were of course, white males and I didn't see myself there walking on the moon, but I knew it was something that I would really like to do, but didn't really see a way either, at the time. So it really was with the shuttle era that women, people from underrepresented groups finally had the opportunity to become astronauts.

And right around the same time too, was when I was starting as an undergraduate at MIT and had the good fortune of meeting Ron McNair, who got his PhD from MIT. And that was the first time I ever saw someone who looked like me, who was an astronaut and that planted the seed that maybe I could do that one day. I also come from, as you mentioned, a family that values education and we've got a number of physicians in our family. Most famously my uncle, Dr. David Satcher, who was Surgeon General of the Clinton Administration. And I always remember, this is a funny story I like to tell if he's listening.

When I was going around getting advice on whether or not I should stick with medicine or think about applying to become an astronaut, he advised me just to stick with medicine. So didn't take his advice, this is the one time I didn't, but I did take his advice, in terms of going to medical school. And I wound up applying to become an astronaut, right actually, before the Columbia accident and so they actually paused taking astronauts for a number of years. And in those years, actually that's when I went to Northwestern and was on faculty there. So they opened it up again and that's when I submitted my application and I was in Chicago and was selected from there.

Dave Johnson:

There's a number of questions that spill off from that. You guys may know David Wolf, who's an astronaut, who's from Indiana University. I had him in my clinic when he was a medical student and as I always do, I basically say, "What do you want to do when you grow up?" And he said, "I want to be an astronaut." And I just smiled and I don't think I ever went back in the room with him, I just figured, "This guy is a flake, what's going on with him?" And I think he's logged more space miles than just about anybody, he's an incredible human being. And again, if he's listening, you're terrific. David.

Patrick Loehrer:

I just have to ask this as a boyhood thing, because I did contemplate being an astronaut because I was an engineer and MD just like you were Ellen and so were you Bobby. But it hit me, one is, you have not to be afraid of heights, I think. And then, you have to be willing to go around in a circle a thousand times a minute and not throw up. But in the training there, did any of that stuff bother you or was this no big deal?

Dr. Ellen Baker:

That sounds a little like Hollywood and not so much like the real thing, actually. In the early days of the space program, they did put astronauts in rotating chairs. I'm not exactly sure why? But we don't do that anymore. I would say that the training is rigorous, but it's not unreasonable. I don't know what you think, Bobby? It's fairly predictable. And I will put a little shout out for Purdue, which maybe has one of the highest number of astronauts of any university outside the military academies. I don't know if that's true now, but 10 or 15 years ago, we just had a large number of engineers from Purdue who were in the astronaut office.

Dr. Robert Satcher:

I agree, the training is not quite how it's portrayed sometimes in the media. The question I get asked from my doctor friends a lot, "I guess you can't be claustrophobic going into space because you're in the space capsule." And that really does deter a significant number of people, probably more than myself or Ellen appreciate because I'm always surprised when I get that question.

Dave Johnson:

But I'm 100% sure I couldn't be an astronaut if claustrophobia is an issue because I can't stand to be in an elevator.

Dr. Ellen Baker:

Let me step back a little, I don't want anybody to get discouraged. But you'd be surprised at how many pilots have a fear of heights if they're not encased in an airplane. So fear of heights is not necessarily something that you might worry about if you're an astronaut. And I disagree with you Bobby, I don't think space vehicles are claustrophobic. It's not like being in a submarine, which I would find very claustrophobic. Particularly in the shuttle because we actually had great windows and great views and we didn't feel confined. I don't know what you think Bobby, but I didn't think it was like being in a cave or closet or a submarine.

Dr. Robert Satcher:

Yeah, I definitely agree with that, the views are spectacular.

Patrick Loehrer:

So William Shatner just went up and had a brief stint in space and is now considered an astronaut, but he came back with such a sense of awe. Can you describe a little bit what it's like, the view from up there and how does it leave you, particularly your first time up in space?

Dr. Robert Satcher:

The words don't completely capture it. The colors are so vivid, the view is so breathtaking. It's really impressive seeing the Earth, not only at daytime, but at nighttime and it goes beyond. It's one of a few things I always tell people, that really exceeded my expectation, in terms of what my preconceived notion of what it would be. And ever since going, that's what's so addictive about going into space, it makes you want to go back just to see that again and experience it again. The closest that I've come to seeing anything like that is, they have these new virtual reality experiences, where they actually got footage that they shot in high-def on the space station, outside the space station. It comes close, in terms of the look but it still doesn't fully capture it because the colors and everything, aren't as clear and crisp as it is when you're there. Because you're in the vacuum of space and there's nothing interfering with it and it's just spectacular.

Dr. Ellen Baker:

Yeah. I'll jump in here too and I absolutely agree with Bobby. And the other thing is, you orbit the Earth every 90 minutes, so you cover a lot of ground and you see a lot of the planet and in that one orbit, you get a sunrise and a sunset. So you orbit the Earth 16 times a day and get 16 sunrises and sunsets, so every 45 minutes the sun is either coming up or going down. It's really hard to know what time of day it is, in terms of your work day in orbit, but it's just magnificent. And it did give me a sense that we're all from the same planet and of course, it makes me wonder why we can't all get along better?

Patrick Loehrer:

I think people our age remember a few things, we remember the day Kennedy was shot. We remember the landing on the moon with Neil Armstrong. We also sadly, also remember the Challenger disaster and where we all were at that point in time. Ellen, you were an astronaut at that time.

Dr. Ellen Baker:

I was.

Patrick Loehrer:>

Can you reflect a little bit about that, if you can? I'm not sure I could do it without getting emotional, if I was there.

Dr. Ellen Baker:

Yeah, I was actually at work of course, and watching the launch and it was just devastating. Obviously, I knew everybody on board, I knew their families very well. And I have to say, we knew flying in space was risky, but we were still pretty unprepared for Challenger and for Columbia. It is something that I still think about. As weird as it might sound, I actually rescued the plant from Dick Scobee's office. He was the Commander of Challenger and I still have it growing. So it's a reminder that he was a good friend and a good colleague, it was a terrible blow, as was the Columbia accident. In that same tradition, I have African violets by my sink that were in Laurel Clark's office and Laurel was a physician who was aboard the Columbia, as well as Dave Brown, who was also a physician on the Columbia.

Dave Johnson:

That's an amazing tribute to both of your colleagues. It's very touching to hear that. I wonder if the two of you could share with us, what you actually did on your missions scientifically? How did you use your medical knowledge, if at all? And Robert, what about your oncologic knowledge, was that useful at all?

Dr. Robert Satcher:

Fortunately, no use for the oncology training in space. I got to use the orthopedic training. One of the most common problems is back pain the first few days when you're in space. We attribute it to, you're going into weightlessness and all of a sudden, there's these fluid shifts, you get more fluid in your inner discs, everybody gets taller.

Dave Johnson:

Well, let's send Patrick to space.

Patrick Loehrer:

We need to get up there soon, Dave.

Dr. Robert Satcher:

Yeah. Actually, during our visit, we measured everybody's height just so that we know what that change was and we did do a experiment actually, that my background came very useful for. We were looking at the effects of bisphosphonate on bone loss. So bisphosphonates, well, everybody knows, this is ASCO, a class of drugs, anti-absorptives, used in patients with bone metastasis. It was actually being tested in rats, thinking about countermeasures for keeping people from losing bone in long duration, space trips. Unfortunately, bisphosphonates come with a lot of effects.

But it did seem to work, in terms of the bone mass, which is induced by weightlessness in rats. And then finally, I was the crew medical officer for my group because I was the only MD up there in our crew. Ellen probably was the same in hers. So, what that involves is, NASA was one of the first places to pioneer use of telemedicine. So, you're basically, communicating with the flight surgeons on the ground every day, talking about what sort of medical issues there are with the crew and getting their recommendations for dealing with whatever it is. So yeah, being a doctor actually came very much handy.

Dave Johnson:

I was going to ask both of you. During your flights, did you encounter any medical emergencies without violating HIPAA? I mean, did you have to do an appendectomy?

Dr. Ellen Baker:

No appendectomies and fortunately, no emergencies, astronauts are pretty well scrutinized and examined before flights. And I think the best insurance against a medical problem in space is to send crews that are really fit and really healthy. And of course, there's always the risk of things like trauma, but the risk is actually fairly low. So no emergencies on my flight.

Patrick Loehrer:

There's no RVUs up there are there, that you have to worry about billing or no?

Dr. Robert Satcher:

No, we didn't have to deal with third-party payers.

Patrick Loehrer:

This is looking more and more like a job I want to pursue here, I'm going to be taller and there's no billing. This is great.

Dave Johnson:

I want to hear from Ellen, what sort of experiments she was involved in and how her medical background helped her assist with that?

Dr. Ellen Baker:

Yeah. People think, "Gee, if you're a doctor and you're an astronaut, they selected you to be a doctor in space." But in fact, astronauts are selected sort of generically. So once you come into the office, you're trained as an astronaut and Bobby and I were both mission specialists, as opposed to astronaut pilots. And so we received training on all sorts of different things. Bobby did a space walk. I trained for space walks, but never did one. We trained on the remote arm. We trained how to fix things when they were broken. I was actually a flight engineer on one of my flights.

But that aside, I was also the crew medical officer and on every flight astronauts participate in medical experiments, because we are trying to gather lots of information from very few people on the physiologic effects of space flight, particularly looking towards longer flights, perhaps back to the moon or to Mars. So I did participate as a subject, I was an operator in a few medical experiments, but the bulk of my responsibilities actually were not medical. And I think Bobby, maybe you would agree with that? We did have some flights that were designated as what I would call, space life sciences flights, but there was only a handful of them and I was not a crew member on any of those flights.

Patrick Loehrer:

Boy, I could spend another three hours on this and would love to hear more stories.

Dave Johnson:

This concludes part one of our interview with former NASA astronauts, Drs. Ellen Baker and Robert Satcher. Please be sure to tune in to part two of the interview, where we will learn more about the incredible work they're doing in their post NASA careers. Thank you for tuning in to Oncology, Etc., an ASCO Educational Podcast. If you have an idea for a topic or guest you would like us to interview, please email your suggestion to [email protected]. Thank you for making Oncology, Etc. a part of your day.

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In part one of this two-part ASCO Education Podcast episode, Drs. Stephen Berns (University of Vermont), Tyler Johnson (Stanford Medicine) and Katie Stowers (Oregon Health & Science University) chat candidly about what it takes to deliver serious news to people with cancer effectively and compassionately.

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Air Date: 2/16/22

TRANSCRIPT

Steve Burns (Dr. Burns):  Hello. My name is Steve Burns. And I am a Hospice and Palliative Care Specialist and Associate Professor of Medicine at the Larner College of Medicine in Vermont. I’m pleased to moderate this episode of the ASCO Education Podcast focused on clinician patient communication in the context of delivering serious news to patients and family.

I am joined Katie Stowers, a Hospice and Palliative Care Physician and Assistant Professor of Medicine at Oregon Health & Science University and Tyler Johnson, a Medical Oncologist and Clinical Assistant Professor of Medicine at Stanford University.

Well, this is a serious discussion on delivering difficult news to patients and families. It is an extremely important one that I’m glad to be having. Let’s first start with our question, what is bad news?

I’m delighted to answer the question first mostly because I have an issue with calling it bad news. It really comes down to some of the training that I had as a palliative care physician when one of my attending said, don’t assume it’s bad. And I remember an example that I had for one of my first couple of patients, where the patient, when we were explaining that she had metastatic cancer and that she was likely going to die from this illness, she said, “Oh my gosh. I’m so relieved because I’ve been looking for an answer for months.”

So what made me realize during that moment and also what my palliative care attending reminded me of is don’t assume. And this is consistent with a study that came out, I think, by Anthony Balkin like 2011 where they did a qualitative review of patients encounters with serious news and bad news. And patients actually gave feedback that said, “We don’t want the physicians to judge our news.”  Again, sort of reframing that, it’s better to call it serious news rather than bad news.

Dr. Tyler Johnson (Dr. Johnson):   I’ll build off of that and just say that I think it’s also important that we recognize that sometimes when we call something bad news, what that’s actually reflecting is what our experience is going to be or what we anticipate that our experience is potentially going to be, which is totally fair. It’s absolutely valid to say having to share this news is going to be a difficult part of my day. And therefore, I think of this as sharing bad news. In fact, I think that recognition is important and can lead to important reflection and even to self-compassion. We should be candid about the fact that this is a hard part of our jobs. I mean, who likes to share life-changing, sometimes devasting news with patients?  Nobody wants to do that. That’s never going to be a fun part of your day.

I think, though, that it is important to recognize that that’s a different question from how the news is going to land to the patient.  Sometimes those things will match up and sometimes they won’t. And it’s important for us to be circumspect and careful in the way that we think about both how the news is going to impact us and how the interaction is going to impact us and also how it’s going to impact the patient.

Dr. Burns:  I’ll move to the second question, which is what is the ideal circumstance or modality, in person or video call or telehealth, to deliver serious news to patients?

Dr. Katie Stowers (Dr. Stowers):  I was actually struck on reflecting on that question about the ideal modality. I think COVID has actually really changed the way that I think about that question. Pre-COVID, I would have said hands down, everybody sitting in the same room being able to reach out and touch someone or be able to see them. But COVID has actually changed that. The people who need to be there aren’t always able to be there because of hospital visiting restrictions. And being in the same room often means three layers of PPE between you and the people you’re trying to talk to when they can actually see your face.

I found some really meaningful encounters of delivering serious news that’s been able to happen virtually in a way that I think I would have really surprised about pre-pandemic. I just had a patient in clinic with me a couple weeks ago who we were sitting there face-to-face, but visitor restrictions in our cancer center still wish she couldn’t have anyone with her in the clinic.

And so we were sitting there together and she wanted information. She wanted to review information that her oncologist had given her about prognosis. And so we were going to start to talk about that, and immediately she became overwhelmed and well, let’s get my family on the phone. And I would really like somebody else to hear this information. And ultimately we realized after trying to get people on and not being able to contact them that actually the best way to do this was going to be a virtual visit where she was home with her sister, with her dog in her lap, her aunt in New Mexico and her uncle in Alaska were all able to come on. We were all able to share this information together. And it was this really lovely moment where she had all of the things that she needed, and it had nothing to do with being in clinic.

In fact, clinic brought a whole different set of stressors. And so I think the way I’ve looked at this really is different and it’s what does this person actually need? Do they need me to be able to physically touch them or do they need their support system? Do they need to be able to see my face without a mask? What is it that this individual needs? And I think that’s more of how I go in and approach thinking about the ideal circumstance now.

Dr. Johnson: Yeah. I think that there is a lot of truth to that and because we are so constrained and clinic often now.  The one thing that I will mention as a practicing oncologist that I have recognized is really important, though, if you’re going to try to leverage the advantages that can come with technology is that it’s really, really important to make sure that the patient is tuned in to the kind of conversation that you’re going to be having before you launch into a discussion where you’re going to be talking about serious news. Because what we have found is that often when people are coming to see us, it’s part of a multi-hour half day or even a full day. They come in and see us. Then they get their labs drawn. They go to the waiting room. Then they go to get their chemo. Then they have to sit for a minute and be monitored afterwards. And sometimes it can be six or seven or eight hours.

The reason I mentioned that is to say that what we have found is that many of our patients, for instance, are now having video visits with us, where we can tell them. They’re like in the car driving in to get their labs done. And they love that because they’re able to save an hour or two of time instead of sitting in our waiting room, they’re doing the visit in the car. But as wonderful as that is for efficiency for somebody who’s riding the chemo train, that’s not the place that you want to be having this kind of serious discussion.

And so I think that if you know that you’re going to be having a visit that is going to involve sharing serious news, it’s really important to say, “Hey, I just want to let you know that this is going to be a particularly important discussion. Can you make sure that you’re in a quiet place where you can really focus here and have whatever family members or friends or whatever, your support that you want there so that they’re keyed in a little bit?” Because if they’re in clinic, we talk about preparing the right space. It’s better to do this in a private room in the hospital than in an Emergency Department with 27 things going on you. So by the same token, I think we have to give them the opportunity to sort of prepare the environment to allow them to have the best experience.

Dr. Burns:  I agree with both you Katie and Tyler. I think about most of my work’s done in the inpatient setting and just thinking about even in the inpatient setting, making sure that even though a patient has their own private room, sometimes they don’t and they have a neighbor that they’re sharing it with and thinking about how do we create that privacy for them? How do we incorporate their loved ones, whether that’s actually using now a iPad that rolls in where you can now have a Zoom conference with their loved ones across the country or across the globe.

But the other piece is really thinking about not tacking it on to the end of your rounds, but really setting aside some time to do that. And that’s even physically having someone hold your pager, silencing your phone so that you can be present for that conversation, just like how Tyler described that in the outpatient setting.

Dr. Johnson: Yep. Totally agree.

Dr. Burns: Well, thinking about who should be involved in the conversations, do you discuss as a team, which member of the cancer care team will deliver bad news to the patient and family?

Dr. Johnson: I can maybe address this one first and then you guys can add on. I think I come at this with a slightly different perspective because I’m actually a practicing medical oncologist. I’m not a palliative care doctor. I actually think that there are important points to be made on two ends of a spectrum here. What I mean by that is that one thing that I is important is to recognize that there is more kinds of healthcare providers can be involved in these discussions than we sometimes may think.

So for instance, Manali Patel, who’s a health services researcher here at Stanford, has done a lot of really interesting work lately with lay health workers being able to help have the first parts of these discussions in terms of exploring the values and priorities and needs of the patients.  And basically what she’s shown is that while there was initially a lot of skepticism, how can a layperson be involved in those discussions. After some training, these people actually do wonderfully well. I think by the same token, there are many members of the healthcare team that can help with that part.

Having said that, I do think that there is also then a part of it that most patients appreciate coming from one of their primary healthcare workers. I think that as oncologists, we’re here talking to the American Society of Clinical Oncology audience, I think it’s important that oncologists recognize that there are certain things that patients really want to hear directly from you.

And I think that in particular, some of the harder things to say, like we really don’t have other meaningful treatment options left, that phrase I don’t think land in quite the same way if it comes anywhere but from the treating oncologist because there’s always going to be this thought in the back of the patient’s mind that maybe my oncologist has something else in line or I need to talk to them later or what have you.

I think that while on the one hand, we should broaden the spectrum of people who can be involved in these discussions, I do think on the other hand that it’s important to recognize that there are some parts of this that really are most effective when coming from the treating oncologist.

Dr. Burns:  Tyler, I think you hit on the importance of the relationship of the oncologist and the oncologist team with the patient and their loved ones. I often think of out this tide of care cartoon. I think it’s almost like a far side cartoon where it’s a physician who’s sharing news to a patient and says I have some really bad news. So I’m going to get someone else to say it for me. I often feel like, as a palliative care physician, I sometimes am thrown into the mix. Am I the one delivering this news? What I really enjoy is partnering with the oncologist and even joining together when we can or for me to check in with a patient after the news is delivered, just because of how important that relationship is between the patient and their oncologist.

The only other thing that I would add is I love having a team with me during those meetings. And so if I can in the outpatient center or inpatient setting, having a nurse or a social worker or a chaplain join me because sometimes I misstep and I say more than I should or I don’t notice emotion. And I think having the other interprofessional lens there to watch and observe can interrupt me, give some feedback in the moment and/or take a step back so that we make sure that patients understand on what’s going on.

Dr. Stowers: I think, Steve, the part that I love about delivering news with the team is all the things you said. And when I notice my own emotions or I feel stuck on what to say, there’s somebody there who can kick the ball and run with it for a bit so I’m able to catch back up.

I wanted to add on to something else that you were saying, Tyler, about this relationship between patient and oncologist. And I see that a lot where patients will come to me and they’re not ready to talk about things until they’ve heard it from the oncologist first. I just have got this morning this guy who got discharged from the hospital and hospice had been brought up in his visit, but he sees his oncologist on Friday and there was no way he was going there with me and how he’s able to talk to his oncologist rightly so.

I also see the flip side of it not too infrequently where the relationship that the patient has with their oncologist is they’re the gatekeepers to life prolonging treatments. And they see any discussion of worries or fears as a weakness that maybe will make it less likely for them to get those treatments. And so I also see that patient population where they see me as the place as a palliative care provider where they can talk about some of those things that they’re not ready to talk about with the oncologist. They need the oncologist to be positive treatment focused and they need another place that’s not the oncologist to talk about those things.

Dr. Burns:  Yeah, Katie, I just actually had a case like this last week where a patient says that she is really tired of the chemotherapy she was getting. She has a head and neck cancer, but she was afraid to bring it up with her oncologist because, she says, “I need to be brave in front of her.” And I just thought how interesting that was. And so every time she’s in the room with the oncologist, everything’s fine, everything’s great. And then when she’s speaking to me, she’s like not everything’s fine and not everything’s great. And so I just think that the illustration of, yes, it would be great as a team, sometimes when we individually approach it, people do feel comfortable saying something differently outside of their oncology visit.

Dr. Johnson: I think that one thing that this all gets to that I think is what all of us are saying, but it’s worth articulating is that, Steve alluded to that cartoon at the beginning of this part of the discussion. The sort of underlying message from that is this idea that we as medical oncologists involve palliative care doctors if we don’t know how to do something or we’re not interested in doing it. And of course there may be times when the patient is better off with a skilled palliative care doctor doing the conversation that maybe a less skilled oncologist doesn’t know how to do so well. But that’s certainly not the optimal outcome.

The optimal outcome is that there is teamwork and a partnership between medical oncology and palliative care. I think that teamwork creates a synergy where, because you’re right, that the patient may have one face that they put on for the oncologist and a different face that they put on for their palliative care doctor. And I know there are times when I can sense as the oncologist that there is something just below the surface that they’re not quite ready to bring up to me.

And sometimes in those cases, I will say at the end of the visit, “I think this would be a really good time to touch base with the palliative care team.” And what I’m really thinking is because there’s clearly something else you need to talk about that’s not going to come out right here. So I want it to come out when you get to meet with them. Then of course, especially in those kinds of cases, having a little bit of back channels communication after the visit with me so that I can prep the palliative care doctors and let them know that I feel that there is something else there to be addressed, I think is really important.

Dr. Burns:  One question to think about is how do we prepare? How do you prepare for delivering serious news? I think I will say that the first thing I like to do is do my biopsy of the situation. I know that’s quite medical to use as analogy, but I like to know who are the players? What is the prognosis? And what I need to do is do a really thorough check-in with the specialist. So oncologist or if there’s a radiation oncologist involved to check in with them and to actually check in with the patient about information preferences and/or who would like to be in the room or who they would want to be in the room. I think all of that helps prepare it.

I always use the analogy with my trainees, like a good, serious illness discussion or a good delivering of serious news is a lot of preparation, just like how we learn to put in central lines. A lot of it’s the prep and then the central line when you place it is pretty quick. And so I certainly think about delivering serious news in the same way.

Dr. Stowers: I think the part of preparing for serious news that we probably don’t think about as much is the part about preparing ourselves for giving this serious news. And Tyler, you alluded to that earlier on in the conversation of what am I bringing to this conversation? I, through a series of tough experiences when I was a new palliative care physician in a busy outpatient practice, really found myself losing the empathy that I really prided myself on having in my clinical encounters. And I walk in and be like looking at the clock, like tapping my foot as this person’s crying in front of me and like, holy smokes, what’s going on here? And I realized that I was not prepared to give this kind of news.

And so really started instituting before I knock on the door and go into the office or click the virtual visit now as it, I’m making sure how am I? Have I gone to the bathroom? Have I eaten? Am I hot? Am I cold? Like how does this patient make me feel. What are the emotions that I’m bringing up? What are the biases that I’m bringing to this about what outcomes do I really want from this conversation and doing this little mini-checklist of how am I and what am I bringing to this conversation has really helped me get a lot more centered before I walk into their room. And so I think that that should absolutely be on that checklist that we do as we’re preparing for these conversations.

Dr. Johnson: I’ll say two things building off of those great points. One is that I think, to Katie’s point, I think it’s important that we put a plug in here for a holistic evaluation of your own wellness as a doctor in the big picture perspective. And obviously, I have my own bags under my own eyes after the last two years of the pandemic. You can choose if I’m the pot or the kettle, but I recognize that I struggle with this just as much as anybody.  But it’s just to say that if you’re not eating well and you’re not sleeping well and you’re not getting some exercise and you’re not taking time for yourself and you don’t have a sense of self compassion, it’s very difficult to fake empathy. It’s very difficult to pretend to be present.

And if you try, it usually just doesn’t really work. I mean, you kind of either are present or you’re not. But the issue is that you can’t summon self-care in the moment that you need it. You can maybe try to do that for a couple of days. I think that largely is what burnout is. It’s trying to magically materialize self-care as if you can do that the moment before you walk into a room and that’s just not how the human psyche works. So that’s thing number one.

The other point that I would make is that, and I feel like this is one of those things that I just have to learn a thousand times over the course of being a clinician, because no matter how many times I learn it, then I forget it and it blows up in my face and I think, oh, well, yeah, I forgot that lesson again is how important it is that the first thing I do when I get in with a patient and I’m preparing to have one of these discussions is to talk with them about what they already understand about what’s going on. Because you have some patients who you’re surprised to find that you know that they’re on end of line chemotherapy and they have overwhelming disease burden, etc., and then you ask them what’s going on. And they say, “Well, I’m just really excited for the next chemo because doc, you said that the next chemo was going to be the one that was going to make the difference.” when of course you probably think you didn’t say that.

But the point is just to say, that’s very different than if you ask the patient and they say, “You know, Doc, I so much appreciate everything you’ve done. If I’m really honest, I kind of feel like I’m dying. I think that’s where I am.” Well, those are two totally different discussions. And if you come in assuming either of those things and it’s actually the other one, then you’re either going to waste a phenomenal amount of time or it’s just going to be a terrible encounter. And I’ve made mistakes on both ends of that spectrum, which just reemphasizes for me the importance of figuring out where the patient is before I start saying anything.

Dr. Burns:  And Tyler, I also think about the efficiency of these conversations. Often we are so worried it’s going to take so much time. And when you start with, what have you been told or what do you understand or what’s been going on with the big picture of your cancer, it does save time. So you don’t actually have to repeat from the top. And I will say I’ve also watched people still and I caught myself a couple times where we still ask, what do you understand? And then we still repeat the whole story.

And so I certainly encourage all of us to think like if they heard it, totally fine to move forward, but the other efficiency piece and I know all of us have been vital talk trained thinking about a headline in like a big picture. What is the big message? I always think about a headline is what is sort of the summary of the medical information and what is the impact on the future of this person’s health?   Knowing that we often are pretty good with the summary of the medical information but a little less good at the impact. I always find that that helps them better understand their big picture and be able to then share the same information with their loved ones. They could easily have that catchphrase or a two-liner that they can say, guess what? The oncologist has shared this with me. I think that’s so helpful when they’re thinking about their overall care and helps them inform their goals and priorities and helps us better understand their goals and priorities. 

That concludes part one of our conversation on delivering serious news. In part two, we will continue the conversation on how the care team can prepare for delivering serious news. Useful resources and more. Thank you so much to all of our listeners for tuning into this episode of the ASCO Education Podcast.

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In this Oncology, Etc. episode, Drs. Patrick Loehrer and David Johnson Speak with Drs. Lecia Sequist (Massachusetts General Hospital) and Melissa Dillmon (Harbin Clinic) on how ASCO’s Leadership Development Program (LDP) has taken them down varying paths, as well as the ways it has influenced their lives, careers, and the lives of those around them.

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Air Date: 2/1/22

TRANSCRIPT

[MUSIC PLAYING]

PAT LOEHRER: Hi, I'm Pat Loehrer. I'm director of the Center of Global Oncology here at Indiana University.

DAVID JOHNSON: And hello. My name is David Johnson. I'm at UT Southwestern in Dallas, Texas. So Pat, we've got a couple of really great guests today.

PAT LOEHRER: Yeah. I'm really excited. I've been looking forward to this.

DAVID JOHNSON: So have I. Listen. Before we get started, I have a book I want to recommend to you. This one I got over the holidays and just finished it recently. It's called The Doctors Blackwell by Janice Nimura. So as many of our listeners know, Elizabeth Blackwell was the first female physician in America. Her sister Emily also followed her into the medical profession.

Nimura really writes, I think, a fascinating biography about both ladies, particularly Elizabeth. And one point she made, and I think it's interesting, it's not really clear why Elizabeth went into medicine.

Certainly at the point that she did in the mid-1800s wasn't a profession of great reputation at that time. And, in fact, Nimura describes Elizabeth as, quote, "lacking a caring instinct," which I thought was an interesting characterization of the first female physician.

And she indicated that she was hardly a feminist. She was actually opposed to Women's Suffrage, for example. According to Nimura, she became a doctor largely just to show that she could. And then, really, the rest of her career I won't give away. The subplot is really quite interesting. I think you would find it most interesting to recommend to you and our listeners who have a particular interest in medical history.

PAT LOEHRER: Actually, I've ordered the book. I can't wait to read it.

DAVID JOHNSON: Excellent.

PAT LOEHRER: I got a book for Christmas, Lyrics by Paul McCartney. And I read through that. That's fascinating, actually. So 158 of his songs were detailed and the backgrounds for it. So that was kind of fun.

We're excited today because we're going to talk to a couple of graduates of our Leadership Development Program. That was a program of ASCO that was conceived a little over a decade ago. It's been, to my mind, one of the best programs that ASCO has done.

It has taken younger faculty and oncologists from around the country, and Dave and I were among the first leaders of the program as mentors. I think that was one of the bigger mistakes ASCO has ever done. But despite that, we have a lot of fun. There were 12 graduates each year. They all had projects they presented to the board of directors.

There were, if you will, classes and lectures throughout the year on leadership. And they all had projects. And for me, it was the best three years of my life, I think, through ASCO. It was just a lot of fun. And part of it was getting to know a lot of people, including Melissa and Lecia, who are with us today.

Lecia is a Professor of Medicine at Harvard and Mass General Hospital. She did her medical school at Harvard, residency at Brigham and Women's Hospital, fellowship at Dana-Farber.

She is currently the co-leader of the Cancer Risk Prevention and Early Detection Program at Dana-Farber and director-- I think I want to hear more about this-- she's the director of the Center for Innovation in Early Cancer Detection at MGH.

Melissa, she went to Converse College in Spartanburg, South Carolina, went to medical school at Wake Forest. Then did her internship and residency at UAB. She did her fellowship at UAB. And she now serves as the Chairman of the Department of Oncology and the Board of Directors at the Harbin Clinic. And we're so excited to have both of you here.

DAVID JOHNSON: Yeah. Very much so. And why don't we get started by just getting a little background information. Melissa, let's start with you. Can you tell us a little bit about how you got into medicine and, more specifically, why did you choose oncology?

MELISSA DILLMON: That's a great question. I was a political science major at a women's college in South Carolina and was destined for the State Department. And we used to have January terms.

And I mistakenly got put with-- and I don't think it's a mistake-- former graduate of Emigre Medical School, who is a medical oncologist in Greenville, South Carolina, for a six-week term and fell in love with medicine, fell in love with the ministry that he provided to his patients, and followed him to Bowman Gray and went back years later and told him thank you for changing my life. So that's how I got interested in medicine. I come from a long line of accountants and engineers. There is no person in my family in medicine.

PAT LOEHRER: I was an engineer. Some of the best people in life are engineers.

DAVID JOHNSON: I didn't know you drove a train.

[CHUCKLES]

PAT LOEHRER: Eat your heart out.

DAVID JOHNSON: So Melissa, before you leave, I actually grew up very close to where you practice. How did you end up in Rome, Georgia?

MELISSA DILLMON: Well, my dad and his twin are proud graduates of Georgia Tech. So he found me a job. And I said, well, I'm grown up. I was going to stay on faculty at UAB but came to Rome, Georgia and really was excited about the multispecialty group that I ended up joining. There's about 250 of us now. And kind of had the feeling of a university but in a small town. Kind of best of both worlds.

Neither of my two daughters have gone to Georgia Tech. One of them is at Georgia. Just won that national championship. But my third one, we're hoping maybe she'll be the one that goes to Georgia Tech.

PAT LOEHRER: So you stayed up and watched the game. I have to ask this, right?

MELISSA DILLMON: I did. I stayed up to the very end.

PAT LOEHRER: And so who are cheering for? Alabama or Georgia?

MELISSA DILLMON: Definitely Georgia.

PAT LOEHRER: Interesting. Good. Good.

DAVID JOHNSON: And Lecia, why don't you tell us about your background and how you got interested in oncology. And let us know if MGH has a football team.

[CHUCKLES]

LECIA SEQUIST: Oh, sure. Thanks for having me here. This is going to be a fun conversation. So I grew up in the Midwest, in Michigan. But I've been on the East Coast now for the majority of my life. And when I was a resident, I was actually in a primary care track residency program, because I thought I wanted to be a primary care physician.

And I really liked the idea of sticking with people, getting to know them over long periods of time, and kind of standing by them through the highs and the lows of their lives. Well, I was finding out in residency that primary care wasn't really like that. That was for television shows.

People change primary care doctors and move around so much, it's rare that you actually do get to take care of people for a long time, at least in a big city. And I also found that, for me, primary care was a lot of asking people to do things they didn't want to do-- exercise, lose weight, stop smoking, do this, do that.

And I always felt that I was at odds with my patients or nagging them. And then, when I would be in the hospital on oncology rotations, trying that out, I really felt like I was allied with my patients and not nagging them or pushing them, but really here we were together against this fight against cancer.

And cancer was what we were fighting together. And I just fell in love with that. So much to the disappointment of the residency program that was really trying to get people to go into primary care, I said, I've got to be a specialist. And here I am.

PAT LOEHRER: It's interesting, though, that you do risk reduction and prevention. So you're back to telling patients to lose weight and exercise again, you know?

[CHUCKLES]

LECIA SEQUIST: Yeah. I guess, in some ways that's true, although I'm not really taking care of primary care patients. But after spending a lot of years doing a more traditional medical oncology track of drug development and targeted therapies, the last five years I have switched my research over, kind of a midlife crisis situation, where I said I've got to do something different. I'm in a rut. And I started looking at new technologies for early detection. And I really enjoyed it because it's something different.

For one thing, I just felt like I was in a rut. But it's really a way to be a lot more proactive with the community and to work on issues of social justice, thinking about cancer screening, and who has access and who doesn't, and what can we do better. So I'm really enjoying that in this phase of my career.

PAT LOEHRER: Terrific. The four of us are linked because of this Leadership Development Program that the American Society of Clinical Oncology put together. And I think Dave and I are really curious whether, here it is many years later now. It's been almost 9 or 10 years later now. As you reflect on the LDP, what are some of the highlights? What did you learn about yourselves and was the program worthwhile for you?

MELISSA DILLMON: Well, I'll start. I was part of the class, 2010-2011, best class ever. And it was the second class in the Leadership Development Program. I applied for the first year's class and didn't get it. And one of my friends and partners, a radiation oncologist, who was very involved in ASCO, encouraged me strongly. Said, don't give up. Try again. And I did.

And it was instrumental in developing both my career within ASCO as well as pushing me to leadership positions in my own clinic and in my own state. And helped develop a lot of skills that have made me successful in pushing state legislative efforts. My political science background did not go away, just like her primary care roots. And so I think that the program also made friends with Pat and with Dave and with my co-classmates.

And as the years have gone by, and I've gone to ASCO, when you see that LDP ribbon on somebody's tag, you immediately have a connection with them and know that you've been through a similar experience. So I think it's been really instrumental in developing my career. And I'm currently serving as a mentor for the leadership program. So I'm living your life 10 years ago, Pat and Dave, and it's great.

DAVID JOHNSON: Oh, I'm sorry.

PAT LOEHRER: Terrific.

DAVID JOHNSON: [INAUDIBLE]

LECIA SEQUIST: I would echo what Missy was saying about how much it's influenced my career. I was in the 2011 class. So I think the year after she was. And I also applied multiple times, and I always tell people who are thinking of applying that it often does take multiple attempts to get in and not to lose faith. The selection committee does like to see that persistence. So definitely apply more than once.

I learned so much about what leadership is. I thought it was about being the best in a group of people. So then, being selected to have a certain title. And I just really learned so much during that year, that it doesn't really have anything to do with a title, although that can be a part of it for some people.

But it's just more about a style, an approach to your profession, and that you can be a leader if you are the designated head or chief of something, but you can also be a leader if you don't have that designation.

And there are many different styles and ways to lead and to help people to ultimately get a group to do the very best that they all can together. And the friends that I made that year from my co-classmates as well as you guys and Jamie, who are our leaders, are just lifelong friends and mentors.

And you know, I think it really got me thinking seriously about my choices in my career too and not to just kind of cruise through a career and see what happened and where life took you, but to really plan and to chart your own course and to make sure to reevaluate. And if it's not going the way you want it to, to rechart and replan.

DAVID JOHNSON: We had a bunch of different lectures on different topics. Was there one of the lectures or areas that was particularly beneficial to you?

PAT LOEHRER: I can think of one. I'll start out by doing this. We threw this in the second year, just for the heck of it. We did this personality testing. And I thought it was fascinating because, in my group, there was a little bit of conflict going on with one of the people in my group.

And I realized that we were both acting out our personalities. I like to look at the big picture, and he liked to just zoom in the middle one. And the other thing that I do remember is that we showed the profiles, and it turned out Dave and I were exactly opposite. And then we both said at the same time, we should be married.

[CHUCKLES]

MELISSA DILLMON: One lesson that stands out in my mind was the press preparation lesson that we received from Press Relations group at ASCO. And I think that was essential for developing skills with regards to preparing for difficult conversations and being able to redirect questions that were difficult. I use that as leader of the Government Relations Committee oftentimes.

I will also say that the other lesson that stands out in my mind is conflict resolution because, at the time, I was not chair of my department and was having significant conflicts with the current chair of my department. And that lesson helped me to go back week after week and more constructively work towards a solution and then eventually became chair of that department. So I think those two lessons gave me lifelong skills that I've used in all my leadership roles.

LECIA SEQUIST: Yes, it's amazing how 10 years later, we can still remember the specific lectures and specific comments that people made. I remember those that you were talking about Melissa, but yeah, before you had said yours, Pat, I was going to say the same thing, that personality test was extremely helpful.

And I certainly don't remember all of the different initials of the personality types. But just to understand that concept that people have different emotional skills and blind spots that very much influence how they deal with others in the workplace.

And to be able to think about that when you're having conflict with someone and think about how to take that into a strategy where you can kind of play to their strengths and understand where they're coming from, that was extremely helpful.

And then, I also think that talking in small groups with our teams about specific problems we were having or obstacles that we were facing and getting advice from others on how to overcome them, that really started me on a recurrent mission to find friends who I could share that with outside of my institution, over the course of my career.

I think that was a real exercise in how valuable that could be. It's so critical to have peer mentors that you can talk to and strategize with and get advice about how to handle something that you're struggling with at work and have people that aren't in the same room full of people or aren't living in it. So they're a little bit more objective.

DAVID JOHNSON: Let me ask a question of the two of you. Do you think your home institutions in your case, Lecia, MGH and in your case, Missy, Harbin Clinic, valued that training that you received? Did they recognize it as something that was worth the time that you spent or do you think it just something that happened and they didn't really take notice?

MELISSA DILLMON: I learned in LDP that institutions don't love you back.

PAT LOEHRER: They don't love you to begin with. Joe Simone. Joe Simone.

DAVID JOHNSON: So I take that as a no. Your institution really said, eh, OK, great. We're glad you did it, but so what?

LECIA SEQUIST: I wouldn't say that. I don't know that they said, so what? I just, I'm not sure that they-- there was no rolling out the red carpet, thank goodness you did this. But I do think it's had an institutional impact in that I have since encouraged other people to apply from my institution. And I think that only strengthens the institution, to have multiple people going through that program.

MELISSA DILLMON: So my clinic, being private practice, when I take time out, it is just a cut from my salary. There's no support given from the institution. But in order to be in positions of leadership, department chair or on the board of directors, which I later was elected to of the clinic, you have to have completed a leadership development program. And the clinic will pay for you to go do those things.

But my participation in Leadership Development Program met all those criteria. So my clinic highly values professional development classes or meetings or programs and encourages that. Even if there's no financial support necessarily, it is encouraged, if you want to assume positions of leadership within our clinic.

And so I think that it's important for institutions, whether they're private practice or university, to recognize the benefits that come from participation in a program like this.

And it was interesting as a mentor this year, we did a personality test, but this time they did an interesting look at what our priorities, our top five priorities or values are. I think it was values.

And it was a list of 300 things basically you go through. And you listed your top five values. And then you listed the values of your institution or employer. And then you wanted to look at, did they match? And did your university value what you value?

And that was a really interesting exercise to go through because a lot of these young leaders who are taking their time out to do this program did not feel that support necessarily for them seeking out this program.

PAT LOEHRER: It's no coincidence that Dave and I asked both of you to join because you both come from different places, if you will. And I think, Melissa, you've just been a rock star in terms of the community practices and so many things that you have done in the leadership roles. And Melissa's, you can't get any more prestigious in being in one of the Boston medical schools and particularly at Mass General.

But the other reason we wanted to have you come in is to talk a little bit about your perspective as women and women in leadership roles. And if you could maybe share a little bit about your thoughts and perspectives of gender leadership and what you have noticed in men in leadership roles and women and what lessons you might give to other people, particularly other women in this capacity.

MELISSA DILLMON: Well, I think we both were trained in a day. And I might be speaking for you, but when there were, at least here at the institutions where I trained, not that many women in internal medicine. Medical school was probably 45% female by the time I was in medical school.

But when you look at the faculty of those medical schools that I went to and trained at, there were very few women in positions of leadership. And so there weren't very many role models. My dean of students at Wake Forest was a female nephrologist. And so she was a huge role model for me.

And then I went to UAB, and I remember being asked in my interview, are you OK with being in a male-dominated program? Because you will be in a male-dominated program. I think there were 45 of us in my intern class, and eight of us were female. And I said, that's fine. But I had gone to a women's college, where obviously there were only women leading.

So it was a big change for me to go back into a situation where I had to assert my unique female leadership qualities, which are different, and still use those in an effective way to lead. Right now, I'm serving as a mentor also for a small liberal arts college, primarily those interested in going into medicine or nursing, and usually most of those have been female.

And so it's been a really great opportunity, because I've had very few mentors who were female, who were positive role models for me. So I think Leadership Development Program, one of the things they taught me was to go back and say thank you to your leaders and to be a leader for others. And specifically, as a female leader, I think that has been an important call for me.

After leaving Leadership Development Program, I went back and ran for the board of my clinic as the first female to be on my board. My clinic was started in the 1860s, I think right after the Civil War, and I'm still the only female on that board.

And I feel that it's important for me to stay there or to promote up more females within my clinic to be on that board because I think that having a diverse board helps in bringing different skill sets to the table. So I think Leadership Development Program gave me that courage to step up.

LECIA SEQUIST: That's inspiring. Congratulations on being the first woman and may there be more soon. Yeah. I don't know that I've felt that I was in as much of a male-dominated field up in Boston.

But certainly, leadership in my hospital and in my cancer center has been more male-dominated. And I think as I'm getting older now, I definitely appreciate-- of course, every individual has different leadership style.

So you can't just paint a broad brush and say men are this type of leader and women are that type of leader. Everyone's a little bit different. But in general, I think women do tend to have a different leadership style and one that is maybe, present company not included, one that's less talking and more listening.

And I think, when I was younger and trying to become a leader, I really felt out of peer pressure that I needed to talk more and sort of demonstrate more what a good leader I could be or what great thoughts I had.

And I've really come to embrace a more listening type of leadership, which I have been happy to say that younger women that I work with have come up to me privately and thanked me for.

And so I do think it's important to have all different types of role models for our junior faculty and all different types of styles, sort of on display and doing their best so that people can find something that matches with their own unique style to emulate.

PAT LOEHRER: One of the lessons I learned a long time ago from someone, and I loved it, a great leader is one that changes the conversation. And to your point of listening, but it's really changing the conversation, deflecting it around it so that other people are talking. But you have a little role in moving that around. And I always liked that.

MELISSA DILLMON: Today, I was listening to the National Press Conference, and I heard a definition of leadership that disturbed me. And I thought, I don't think that's my definition of leadership. So I think that defining what your type of leadership style is, is something that leadership development helped me with.

And then, once I knew what my leadership style was, then using those skills to pull together a team and achieve a goal, a common goal, not the description of leadership today, which was pushing something up a mountain and rolling over boulders and doing whatever you had to do to get your way.

I thought, well, that's not leadership, not my leadership. So I think that that was something that Leadership Development Program help me do is identify what my leadership style is and what kind of leader I want to be.

DAVID JOHNSON: So I want to follow up on a point that both of you are making in a slightly different way. And that is, who are your role models? I mean, apart from Pat and me, but who are your role models?

[CHUCKLES]

LECIA SEQUIST: I've had lots of role models over the years, and I think at the beginning, my role models were really people that I wanted to emulate and be just like them. And that probably started with Tom Lynch, who was my initial research mentor when I started in lung cancer.

And a lot of it was just the way he was with patients. I wanted to have that ability to make a patient feel just right at home from the first minute they walked in the door, which Tom is a master at.

But over time, I think my mentors or my heroes have more become people that are different than me. And I'm not trying to be like them. But I appreciate the ways in which they lead or in which they conduct something, like balancing their home life and their professional life in a way that's just different but I appreciate. And that, in lung cancer,

I would say another real big influence on my career has been Heather Wakely. She really has been my main female role model in my career. And she's given so much of her time to me and to so many to kind of sit and have personal talks and pep talks and strategies about what we're doing in our home institutions.

DAVID JOHNSON: Missy, what about you?

MELISSA DILLMON: So I would say from a professional standpoint, someone I respect and see as a mentor is actually now the female CEO of my clinic, who has been with my clinic for 20 years and worked her way up.

And I think that's because she has retained her femininity, but she is recognized as a tiger that no hospital or other clinic wants to make mad. So she has a way of leading and listening that is unique. And I have learned a lot from her over the years and watched her rise in her leadership skills as I have alongside of her.

And then, I will say from a personal perspective, one of the books I have enjoyed reading recently really talks a lot about servant leadership. And so I've really tried to identify servant leaders in my community and why it is that they're able to weather the storms of the last couple of years, for instance, and why their teams rally behind them and support them. And they're successful.

And my husband is a restaurant owner times three, opening two of those, one right before COVID and one during COVID and yet has been able to mobilize a team. And that's because he's a servant leader that will get back in the kitchen and make pastry cream if that's what needs to be done or make reservations.

And so I think during the last two years, what I have learned from that is to be a servant leader in the tough times has really helped rally my team and my clinic to be better and to continue to work, despite the challenges for our patients, for the bigger goal.

PAT LOEHRER: Love it. We recently had a guy give a talk here at IU, and the lecture was on being a visionary leader. And to be honest, it was fine. It was good, but being a servant leader and being part of a group is more important than being the one right up in front. And it's good to be a follower too as a leader.

So I really appreciate those comments. Just in a couple of sentences, I don't know if you guys could do this and reflect a little bit about your younger self. Say you're 21, and you could give yourself some advice now, what would those pieces of advice be?

LECIA SEQUIST: I think one thing, and that's the common thread I've heard among a lot of more senior people in medicine, or in any profession probably, is that the things that you think are disappointments at the time often turn out to be some of the greatest opportunities that you're faced with. You plan and you think things are going to go a certain way, and then something doesn't work out, and you're very disappointed.

But it's usually that process of how you deal with that disappointment that actually brings so much opportunity back to you. You can't see it at the moment. All you see is the disappointment. But I think that's a big lesson.

PAT LOEHRER: Terrific.

MELISSA DILLMON: So kind of similar to that, Lecia, doing our personality test this time, I wish I had done that same exact test 10 years ago, because I'd like to see what my leadership personality was 10 years ago versus now. I would not have scored as high in certain areas that I think I do now.

And I think that one of the biggest things I have learned is, I'm very much a person of tradition. And I like things to continue the way I expect them, and I like things to be planned and done in medical school in four years, done with fellowship. So I like a regimen and a routine. And I have learned over the years to be comfortable with change. And I wish I had learned that earlier and to be open to change and listening to new ideas.

I think that probably for the first few years of my practice and training, I was very much, this is the way it's done. And I think that that expressive part of my leadership had not developed yet. And I think that being open to change and looking at things in new ways, I wish I had learned that earlier.

DAVID JOHNSON: So we only have a few minutes left. And what we have done in previous episodes, we like to ask our guests to tell us the book they've read recently or maybe a documentary or something they've watched recently that they would recommend to our listeners.

LECIA SEQUIST: I really enjoyed the book The Four Winds by Kristin Hannah. That is a historical fiction about the Great Depression and the Dust Bowl and the migration of farmers from the Central Plains out to the West. And it was a really captivating book with a female protagonist. I enjoyed it quite a bit.

MELISSA DILLMON: It's funny. I read that one just a few months ago. I love historical fiction, but I would say recently, and I know it's not a new book, Andre Agassi's Open, his autobiography, I found fascinating.

I love sports, but it was very interesting to me to see how someone who's thrown into the limelight at a very early age and the pressure put on him by his parents and how that affected the course of his life.

I found it a fascinating book and very insightful. And I like to play tennis, but I'm not a tennis player. But I found it interesting as a parent, who's got several sports-minded children, it gave me some lessons about parenting and how to just raise your children and where the focus should be.

DAVID JOHNSON: Both my wife and daughter had been tennis players. I'm sure they would both love reading that book. Thanks for that recommendation.

LECIA SEQUIST: It's a great book.

DAVID JOHNSON: Well, that's really all the time we have for today. And Pat and I want to thank both of you, Missy and Lecia, for joining us. It's been a terrific conversation. Thank you so much for what you do. You're both, in our minds, fantastic leaders. You were when you arrived, and you certainly have been ever since. So thanks so much for that.

I want to thank all of our listeners for tuning in. This is Oncology, Et Cetera an ASCO Educational Podcast. And we really have talked about anything and everything. And we'd like to continue to do so. So if you have an idea for a topic or a guest, please email us at [email protected].

Thanks again for tuning in. And Pat, I just wanted you know I've ordered a chicken and an egg from Amazon.

[CHUCKLES]

PAT LOEHRER: It's because you couldn't quite make up your mind which was going to come first. I love it. I love it. You're the best. Thanks for doing this. And Dave, it's good to see you, as always. Take care.

DAVID JOHNSON: Thank you so much. We really, really appreciate it.

LECIA SEQUIST: Thank you.

MELISSA DILLMON: Great to speak with you. Bye.

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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.

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How do you talk to patients about medicinal cannabis? Dr. Ashley Glode (University of Colorado) moderates a discussion on effectiveness and safety, misconceptions and more. Featuring Drs. Ilana Braun (Dana-Farber Cancer Institute), Daniel Bowles (University of Colorado), and Kent Hutchison (University of Colorado).

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Air Date: 1/19/22

TRANSCRIPT

ASHLEY GLODE: Hello, and welcome to ASCO Education's podcast on medical cannabis, also referred to as medical marijuana. My name is Ashley Glode, and I am an associate professor with the University of Colorado School of Pharmacy.

It's my pleasure to introduce our three guest speakers Dr. Ilana Braun is chief of the division of adult psychosocial oncology at Dana-Farber Cancer Institute, and an assistant professor of psychiatry at Harvard Medical School. Dr. Daniel Bowles is an associate professor of Medical Oncology at the University of Colorado. We're also joined by Dr. Kent Hutchison, a professor of psychology and neuroscience at the University of Colorado Institute of Cognitive Science.

Let's start with a simple but fundamental question. What is medical cannabis or medical marijuana?

ILANA BRAUN: So Ashley, I think that's such a great first question. I think of medicinal cannabis as herbal nonpharmaceutical cannabis products that patients use for medicinal purposes. And typically they're recommended by a physician in compliance with state law.

DANIEL BOWLES: Dr. Braun makes a really good point. And I think it's important to know when patients are referring to medical cannabis, there's a wide variety of different things they could be referring to. Sometimes they would be referring to smoked herbal products, but there are also edibles, tinctures, ointments, creams, all sorts of herbal-based products that people use and call medical cannabis.

And then there are also the components that make up medical cannabis-- largely, the cannabinoids. And I think the big ones people think about are THC and CBD. And sometimes those are used in their own special way. So I think that it's important for us as providers to be able to ask our patients, what is it that you mean when you say, I'm using medical cannabis?

ILANA BRAUN: I think that's such a great point. And I will add I think it's also important to remember that when you offer a medicinal cannabis card to a patient, you're giving them license in most states to access any number of products. It's not an insurmountable challenge, but it's a whole new world for traditional prescribers who are used to writing a prescription and defining what is the active ingredient, how often a patient will take the medicine, by what means.

DANIEL BOWLES: I think the other thing we need to be very aware of, as hopefully people are listening to this across the country and elsewhere, is the laws vary wildly from jurisdiction to jurisdiction about what consists of medical cannabis, who is allowed to use it, and in what quantities. So I think it's really important that as we learn about these and we think about these, we think about how they apply to any of our specific situations in which we live in practice.

KENT HUTCHISON: So it's interesting-- just follow up on what Dr. Braun and Dr. Bowles, what they're saying, those two words-- right-- medical and cannabis. I think the medical part is somewhat easier because it can refer to the reason the person is using. Are they using for medical reasons are they using for recreational reasons, even though that's a blur?

But the cannabis part I think is what's really complicated. And this is what Dan was getting at. All the different products, all the different cannabinoids, I mean all the different bioactive terpenes and everything else in the material, all different forms of administration. That is where it gets super complicated to really define what that is. And then of course, there's so little research we don't really know what all those constituents do.

ASHLEY GLODE: Now that we kind of have a little bit of familiarity with medical cannabis, can you comment on adult use cannabis and what that might mean for a patient?

ILANA BRAUN: Ashley, I think it's a really good question. And in some of the early research I did to try to understand where medicinal ended and adult use began, or adult use ended and medicinal began, I began to discover a theme that emerged, which is they sort of blend into each other often.

In other words, some of the oncologists that I spoke to believed that it was not such a bad thing for a patient with serious illness, and pain, and many other symptoms to have a sense of high or well-being. And conversely, when I spoke to patients using cannabis, sometimes a cancer patient used medicinal cannabis for enjoyment, and sometimes they used it for symptom management, and sometimes they used it for both. And so I think it is somewhat of a slippery slope between the two. Would you agree?

DANIEL BOWLES: I think there are definitely blurred lines between the two. I think that the advantages of what most states would recognize as medicinal cannabis is usually they're less expensive, patients can use them in larger quantities. There are certain advantages. But there's also paperwork that goes along with medicinal cannabis that some patients don't feel comfortable with.

Or particularly I think when you have a patient who's interested in trying cannabis or a cannabinoid for the first time, they might not want to go through all the extra steps required getting that medical marijuana card, whereas adult use, I think people feel more comfortable, at least in my state, sometimes walking into a dispensary to discuss the options with people who work at the dispensary and then get it from more of an adult use or recreational cannabis initially. And then if that's something that they find helpful for their symptom management, to then take those extra steps and try to get a medicinal card.

ILANA BRAUN: I agree with Dr. Bowles that the target symptoms or the target effect is often similar and access can differ.

KENT HUTCHISON: Yeah. Just to chime in, I agree. I agree also. It's definitely-- the lines get blurred. The recreational user might also appreciate-- for example, college students, I hear them say a lot of times that they appreciate some of the anxiety-reducing aspects-- right-- even though they're not necessarily a person who has an anxiety disorder.

And then of course, patients appreciate a slight increase in euphoria or positive affect, and what does that mean? Is I mean they're also using for recreational reasons? Or is that completely, I guess, legitimate?

On the other hand, there are sometimes I feel like when-- especially on the recreational side-- when people are using for the more psychological effects, the sort of psychotropic effects, I know sometimes the medical patients refer to that as being a little bit loopy as a side effect. So I feel like there's definitely some blurred lines. And maybe there are some places where we can think about in perhaps in a less blurred kind of way.

ASHLEY GLODE: How often do you guys have a patient ask you about medical cannabis? And what are the most common questions they might have for you?

ILANA BRAUN: In my psycho-oncology practice, patients frequently tell me they're using cannabis, often with good effect and minimal side effects for polysymptom management-- for instance to address nausea, or pain, or poor appetite, or sleep, or mood, or quality of life. But they don't ask me a lot of questions.

For instance, one of my longest-standing patients. A man with metastatic cancer and gastroparesis. Vaporizes cannabis before meals to keep his weight up. And many of my patients also use cannabis as cancer-directed therapy. And for these patients, side effects can sometimes be more pronounced.

For instance, I have a lovely patient with metastatic cancer who follows a Rick Simpson protocol. So what is that? That's an online recipe marketed with an antineoplastic claim. And so this patient targets hundreds milligrams of cannabinoids daily. And with such high cannabinoid doses, she sometimes feels spicy, or out of it, as she describes it.

And then I had another patient who targeted high daily doses and developed a debilitating nausea and vomiting that was initially diagnosed as chemotherapy-induced nausea vomiting because it was so hard to tease out in the setting of so many medicinal agents, what was what. But the symptoms resolved completely within weeks of the cannabinoids being halted.

And so as I mentioned, what's notable about all three of these patients, and many of the others I see, is that they are quite open with their oncology teams and me about their medicinal cannabis use. But they don't seem to rely me or other members of their oncology team for their therapeutic advice . We insert ourselves when we see potential harm, but much of the decision-making seems to be made-- I don't know in the naturopath's office, at the dispensary counter, or by trial and error.

And this anecdotal experience in my practice is borne out in my research findings as well. Patients are just not getting the bulk of their cannabis therapeutics information from their medical teams.

DANIEL BOWLES: In my clinical practice, I am asked about cannabis or cannabinoids a fair, amount often in the context that Dr. Braun is describing, where a patient is coming in and they're already using a cannabinoid or they are planning on doing it and they just want my opinion.

And I think unlike talking about more conventional cancer-directed therapies where they really rely, I think, on their medical team for information and guidance, we are often more a supplement I think in terms of information. In terms of the patients who come to ask me about cannabis or let me know that they're using cannabis, it's a very wide selection of people.

I see young people, old people talking about it, men, women, a variety of different malignancies. So there really is a lot of usage or are thought about usage of cannabis or cannabinoids amongst our cancer patients. I think if you look at the studies, they'll tell us that depending on where we're working, anywhere between 20% to 60% of patients have used cannabis in the last year to help manage some sort of cancer-related symptoms.

And I think the other thing that is notable is you'll find people asking about cannabis or cannabinoids who I think we might not have otherwise expected. So for instance, Just this past week, I had a patient with anaplastic thyroid cancer in his 70s, and his daughter was wondering whether he could try CBD to help with his sleep and anxiety.

She wanted to make sure that it wasn't going to interact with this cancer therapies. And I appreciated her bringing it up, and we could have a frank discussion about the pluses and minuses of it, just like we might any other therapeutic intervention. So I think that particularly as the laws have changed across the country, more and more people are willing to tell us that they're trying cannabinoids and cannabis than maybe would have even 10 or 15 years ago.

KENT HUTCHISON: I think in an ideal world, patients would be talking a lot more with their physicians about this topic. And I think unfortunately that a lot of people do get their information from dispensaries. From the media, from social media, from their kids, and from whoever. And I think that's something that I hope will change in the future.

DANIEL BOWLES: In terms of questions that I'm often asked, I'll be asked if it's going to interact with their cancer treatments, in terms of making their medications more or less effective. I do get questions about how I think their cannabis use might affect some of their symptoms. I get questions about other drug-drug interactions-- let's say, interactions with opiates, or benzodiazepines, or some of these other medications that a lot of our patients are on.

ASHLEY GLODE: In a recent survey 80% of medical oncologists who discussed medical cannabis with their patients, 50% recommended it in the past year, but only 30% felt knowledgeable enough to make recommendations. What do you guys think needs to be done to address this knowledge gap? And what resources do clinicians have to get and stay informed?

DANIEL BOWLES: So I'm a big fan of the NCI's PDQ as a great resource. It has a fairly objective information about cannabis and cancer specifically. So I think that's a nice reference for people who are interested in getting an initial overview on the topic.

I think there are also a number of different educational programs. I know the University of Colorado, for instance, has a Cannabis Science Master's and also a certificate program. So there are courses available for people who want to educate themselves more on this topic.

ILANA BRAUN: Yeah. I guess when I think about what needs to be done, I think that cannabis needs to become a routine part of medical training curricula and CME programs. I think that a federal funding for high-quality clinical trials and a loosening of federal restrictions on accessing study drug were to occur, that would be really a big boon for the medical community.

And my colleagues on this podcast I know are doing some very creative pragmatic clinical trials naturalistic studying what is happening in the field. And I am doing clinical trials using an FDA-approved version of cannabinoids. But it's still very hard to study whole-plant cannabis in a form that is sort of a standardized trial drug in a cancer patient.

And then when I think about where I would begin to read, I don't think there is a single source, unfortunately. But a great place to start reading is actually a project that Dr. Hutchinson was a part of, which was an expert panel that was assembled by the National Institute of Science Engineering and Medicine in 2017.

And they produced a monograph on the health effects of cannabis and cannabinoids. And it's several hundred pages long, including sections devoted just to oncology. So in other words, there is scientific evidence to evaluate, and it's sizable.

DANIEL BOWLES: The Austrian Center for Cannabinoid Clinical and Research Excellence also is a helpful resource. One of the nice things about that is they actually give some dosing suggestions or ideas for people who really don't quite know where to start.

Right now, there aren't a lot of people in that position to say, here's how it should be done. Here's how it gets dosed. Here are the data to support those decisions. And so the folks in the next level of training don't learn it in the same way that we have learned how to prescribe other medications. And they can't then lay it down.

So because the data are scant, in some respects, and particularly for herbal products that So. Many of our patients are using, I think it falls outside the medical model that we've all become so used to using to learn how to take care of patients. And I think that's one reason that so many oncology providers feel interested in learning more about this topic, but don't feel comfortable giving patients guidance on how to use them.

KENT HUTCHISON: So both Dr. Braun and Dr. Bowles identified some of the key resources out there. And certainly the training issues that Dr. Bowles just talked about are important. And I do want to emphasize the one thing that Dr. Braun mentioned, which is basically that we do-- we lack research and we lack data on some key important issues, like dosing, for example. What dose is effective?

So cannabidiol has been out there for a long time, but what dose is effective for what? We don't know, right? So we definitely lack research. And there are definitely obstacles to doing that research.

ASHLEY GLODE: So you guys brought up some good points about there being a lack of data, but also there is some evidence. So what is the current research and evidence on the efficacy of medical cannabis for management of cancer symptoms and cancer pain, specifically?

DANIEL BOWLES: So there was a really nice review article that just came out in the BMJ looking at cannabis and cannabinoids, not specific to cancer pain, but including cancer pain. And what they found-- they looked at different preparations from herbal products-- smoked herbal products, oral agents-- cannabinoids, more specifically.

They found there is a modest, but a real improvement in pain in patients or research subjects treated with cannabinoids versus those usually typically treated with placebo. In particular, the data are supported in neuropathic pain, I'd say more so than the other pains. I think the data are less compelling with regards to many of the other symptoms that people often use cannabinoids for, such as sleep, anxiety, appetite, things along those lines.

ILANA BRAUN: So I'll tell you a little bit about how I think about the evidence base in oncology for cannabis use. So I'll preface this with two points. The first is that, as I mentioned, cannabis products tend not to be one active ingredient, but hundreds of active ingredients-- cannabinoids, phenols, terpenes, they all have bioactivity.

And they don't work individually, they work through complicated synergistic and inhibitory interactions that have been termed entourage effects. So I don't think one can easily extrapolate from clinical trials of, say, purified THC, to understand whole-plant cannabis' activity in the body and how it might perform in humans.

And then the other point I'll make is that when I think about the types of clinical evidence that we as clinicians hold dearest, it's clinical trials of our agent of interest in our population of interest. So cancer patients using whole-plant full-spectrum cannabis that they would access at a dispensary or grow in their own home. With this in mind, I believe the strongest evidence, randomized double-blind placebo controlled trials of whole-plant cannabis and oncology populations begins to support its utility for chemotherapy-induced nausea and vomiting.

So there have been a few studies that have looked at this. But just in 2020, the most recent is a study by Grimison, et al. It was a multicenter randomized double-blind placebo controlled crossover trial comparing cannabis extract. And I think the extract they use was a 1 to 1 THC to CBD ratio versus a placebo in patients with refractory chemotherapy-induced nausea and vomiting.

And what they found was that with active drug, there was a complete response in 25% of participants versus only 14% with the placebo. And although a third of participants experienced additional side effects with the active drug-- so remember, this was a crossover trial, so they saw both arms-- 80% preferred cannabis to the placebo medication.

So that's clinical trials of cannabis and cancer. But if we expand the base of the pyramid of acceptable evidence to include high-quality clinical trials for health conditions other than cancer and extrapolate back, then I agree fully with Dr. Bowles that there's a growing body of evidence that cannabis may be beneficial in pain management. And there have been many clinical trials done in this arena, and they span myriad pain syndromes, including diabetic neuropathy, post-surgical pain, MS pain, sickle cell pain.

And so it does seem like cannabis works for pain management in several other illness models, so we could extrapolate back and hope that it works in cancer pain. And then there is a small body of evidence with nabiximols, which is a pharmaceutical that has a 1 to 1 THC to CBD ratio. And it's a sublingual metered dose spray.

And it has been trialed for opioid-resistant cancer pain. And this is not as a single agent, but as an adjuvant to opioids. In early trials, two times as many participants in the active arm as compared to the placebo arm demonstrated a 30% pain reduction. And for the pain specialists who are listening, they will know that is a substantial pain reduction.

But then, additional studies fail to meet primary endpoints. I think there were three clinical trials that followed. Nabiximols was found to be safe and effective by some secondary measures, but the FDA opted not to approve nabiximols for cancer pain. So I think there's some suggestion of effect, but there's some smoke, but no fire-- no pun intended.

DANIEL BOWLES: I think many of the studies that have been done looking at cannabis-- or cannabinoids-- have been compared to placebo or they've been crossover. And I would say fairly consistently, there is some improvement in pain scores with the cannabis products versus placebo kind of across a wide variety of disease spectrums with regards to pain.

I think one of the other questions that a lot of people have asked is, can you decrease people's opiate usage using cannabis? As we know, there's a huge epidemic of opiate misuse in the United States of America right now. And I think many people are looking for ways to decrease opiate usage.

There was a nice study done from Minnesota in conjunction with the Minnesota dispensaries-- or state marijuana program-- where some researchers randomized people to starting kind of herbal cannabis products early in their study or three months into their study. So it was kind of a built-in control.

And they looked at opiate usage rates, pain scores, quality of life scores, et cetera. What they found is there, again, was some improvement in pain control overall in the cannabis users. However, it did not equate to a decrease in opiate usage. So I think that it's an open question that I think a lot of people want to know the answers to before they start recommending or incorporating cannabis or cannabinoids more widely into their practice.

KENT HUTCHISON: It's certainly a complicated issue, in some ways, right? Because the research which is summarized very nicely by both Dr. Braun and Dr. Bowles, it is suggested, but not overwhelming, by any stretch, right? It's not clear-cut.

And I think that one of the big issues here we talked about the very beginning is how complicated this cannabis thing is. and Dr. Braun alluded to this also, that there are obviously many different formulations, many potentially active constituents in cannabis. And so what has mostly been studied so far is either synthetic versions of THC or nabiximols, which is probably the closest thing to what some people are using.

So I think the jury's still out, for sure. And I think hopefully at some point, what will happen is that some of the products that are actually being used by people-- because most people aren't using nabiximols, most people are not using THC only, hopefully there'll be some trials of the things that people are actually using out there in the real world that will tell us something more about whether it's effective or not. And maybe even more specifically, which constituents-- which parts, together are most effective with respect to pain.

DANIEL BOWLES: I think one of the other topics that some of my colleagues have alluded to already is not just cannabis' role in symptom management. I think pain is often what people think of, and people are using it for chemo-induced nausea and vomiting, anxiety, sleep, appetite, but a fair number of patients are also using cannabis or cannabinoids with the hopes that it is going to treat their cancer like a chemotherapy or an immunotherapy may.

And oftentimes, patients will point to preclinical studies looking at oftentimes very high doses of THC or CBD that might show tumor cell death or tumor reduction in test tubes. And I spent a fair amount of time-- and I know some of my colleagues spent a fair amount of time-- talking with patients about how it's a big step between cannabis or cannabinoids working to slow cancer growth in a test tube, to working in an animal system, to working in people.

ASHLEY GLODE: So what are the most important considerations clinicians should keep in mind before recommending medical cannabis to patients with cancer?

DANIEL BOWLES: We should be asking why they want to use cannabinoids. I think just like we might any other medication that people are thinking about trying-- or herbal product that people are thinking about trying-- I think we need to ask why they're interested in using these products. So is it for symptom management? Is it for some of the ancillary side effects of cannabinoids or cannabis? Why are they wanting to use it?

And I think trying to incorporate that more than into the medical model, I ask my patients, hey, if you're using this particular product, do you feel like it's doing what you intended it for it to do? If it is and it's legal in your state, great. Do it as you feel fit. If it's not meeting your goals, if it's not helping with the pain, or if it's not helping with the anxiety, or it's not helping with the nausea and vomiting, maybe we should rethink whether we would use it. Just as if I was prescribing more conventional anti-nausea medication and you didn't think it was working, we wouldn't keep using it.

So I think that's a really important thing to keep in mind. I think the other thing to know from a safety standpoint is, who else is in the household? We have a psychiatrist on the call with us today. I think there is an ample amount of data that cannabis is not safe for young people. It's not safe for growing brains.

And I think we need to make sure, just as we would want people's opiates to be secured, that their cannabinoids and cannabis products are secured as well, from those who do not want to use them.

ILANA BRAUN: And the thing I would keep in mind is that in most states, giving patients a medicinal cannabis card is allowing them to access any number of products with different ratios of active ingredients, delivery mechanisms, onset of action, potencies. And if you don't discuss all of these issues with your patients, these are things that they will decide at the dispensary counter, or by discussing with friends and family, or by trial and error. And I think it's really important that we clinicians guide this narrative.

ASHLEY GLODE: So what kinds of patients are not good candidates for medical cannabis?

DANIEL BOWLES: I would not recommend medical cannabis for people who can't meet some of the criteria we already discussed. So people who can't keep it safe in their households or have concerns about diversion in their own households. Those are people who I think would not be great candidates for medicinal cannabis or cannabinoids.

ILANA BRAUN: As the psychiatrist on the call, I would add that I worry for people with a strong history of psychosis, or currently psychotic, or with a strong family history of psychosis. And perhaps those severely immunocompromised, since there is evidence of fungal and mold contamination in some cannabis products.

DANIEL BOWLES: The other group of people I discussed this with are patients on immunotherapies. One of the ways that cannabis may be effective in some of the symptoms we discussed is it's an anti-inflammatory agent. One of the ways it could be detrimental for patients on immunotherapies is that it's an anti-inflammatory agent.

There is one small study that suggested that patients might have worse responses to immunotherapy who are cannabis users versus those who are not. So that is a conversation I like to have, just so patients feel like they can be informed. I think lastly, cannabis even for people with medical cards, is not free. So there can be a financial burden for people who are using it. So that's something that I'll often bring up with people as well.

KENT HUTCHISON: One thing I would add to this would be history of a substance use disorder might also be a consideration here as well. Mainly because you don't know what the person is going to get, and it could be something that lends itself to relapse or encourages a problem. So I would add that to list.

ILANA BRAUN: And I would second what Dr. Bowles said about the financial challenges of using cannabis regularly medicinally. It's not something that's covered by insurance, either. So these are out-of-pocket expenses, and they can add up fast, particularly for patients in the oncology space using it for antineoplastic therapy.

ASHLEY GLODE: So is there a concern about drug-drug interactions for patients currently undergoing active cancer treatment?

DANIEL BOWLES: There are some data that there can be drug-drug interactions with cannabis and certain agents. In particular, cannabidiol, or CBD, is a CYP3A4 inhibitor. And there are a lot of drugs that are metabolized through that particular system. So I think that that's the clinical relevance of those interactions, I think, is sometimes unknown. But that is another topic that I do think we need to make sure we bring up with our patients.

ASHLEY GLODE: Thank you. Yeah. So a lot of what we'll do is from a drug interaction perspective, use the FDA-approved products that we have available to run through a drug interaction checker, like Dr. Bowles mentioned. So we'll use dronabinol as the THC-based product and epidiolex as the CBD-based product. There's also some resources, such as natural Medicines Database.

And some of the pharmacy programs that we use, you can actually put in marijuana or cannabis as a drug and run drug interaction checks. So there's multiple potential interactions, like he mentioned, through the immune system. But through the cytochrome P450 pathway, cannabis has been shown in some instances to be an inhibitor, sometimes an inducer of certain enzymes, as well as a substrate. So it's really important to work with your pharmacy colleagues to run through different potential interactions that may be present.

ILANA BRAUN: I'll just add one thing, just in case that's helpful. I mentioned earlier in the episode that I had a patient who used cannabis as an antineoplastic drug, and targeted very high doses and developed a terrible nausea and vomiting. And when she stopped, so did the nausea and vomiting, even though her chemotherapeutic continued.

And I, to this day, don't know if that was a cyclic nausea and vomiting syndrome, which has been known to plague some heavy cannabis users, or whether drug-drug interactions led to her high-dose cannabis triggering high blood concentrations of her cancer-directed therapy at the time. And so I think that drug-drug interactions do need to be carefully weighed.

ASHLEY GLODE: So wrapping up, has the medical community stance on medical marijuana shifted in recent years with legalization in many states?

ILANA BRAUN: I don't think we know the answer to this, about how sentiment has shifted because there aren't longitudinal studies that I know of examining this question. But we need some. And one could imagine that as medicinal cannabis becomes are commonplace, providers are increasingly confronted with questions about how to guide care and the desire for high-quality clinical trials and in-depth cannabis therapeutics trainings increases-- and as one piece of evidence for this, at the end of 2020 the National Cancer Institute held a first-in-kind four-day conference at the intersection of cannabis and cancer. And so I'm hopeful that grant opportunities will follow from that.

DANIEL BOWLES: I think overall there has been more willingness to discuss cannabis in the context of patient care in the last decade. A couple of ways that I see this is I much more frequently see cannabis use described not necessarily in the drug history, or in the social history, but in the medical history, or in their medications, if they're using it for medical or therapeutic purposes.

I think the other place that I've noticed cannabis usage become a bit more mainstream is in the clinical trial setting-- not in clinical trials of cannabis, but one of the things that many of us do is clinical trials of new drugs. And very frequently, 10 years ago we ran into trouble trying to get our patients who were using cannabis products for cancer symptom control onto these clinical trials because of potential drug-drug interactions, or just the fear of the unknown. And I feel like we run into that less commonly now.

KENT HUTCHISON: I think it's also worth pointing out that there have been more and more podcasts like this one, right? So to the credit of this organization, I think we are seeing some change. I just wanted to highlight that. And I compliment everyone here for putting us together and putting it out there.

ASHLEY GLODE: All right. Well, thank you. That is all we have for today. And thank you very much Drs. Braun, Bowles, and Hutchison for a delightful conversation. Thank you so much to all the listeners tuning into this episode of the ASCO Education Podcast.

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SPEAKER: Thank you for listening to this week's episode to make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit elearning.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.

This episode features Dr. Quyen Chu, Chief of the Division of Surgical Oncology at Louisiana State University. A prominent surgeon, humanitarian and writer, Dr. Chu shares his life stories, from fleeing Vietnam as a young child, to finding his calling, and giving back through work in impoverished U.S. communities and war-torn regions, including Iraq, Kurdistan and Vietnam.

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Air Date: 01/04/22

TRANSCRIPT

[MUSIC PLAYING]

SPEAKER: 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.

[MUSIC PLAYING]

PAT LOEHRER: Hi. I'm Pat Loehrer and director of the Center for Global Oncology and Health Equity, Indiana University. And welcome to another episode of Oncology Etc.

DAVE JOHNSON: And hello. I'm Dave Johnson at University of Texas Southwestern in Dallas. Pat, great to have another session today.

PAT LOEHRER: It's good to see you again, Dave. I'm really excited about our guest today. And I think both of you and I were talking about this book that came to mind when we thought about having Quyen here. But it's a book by Abraham Verghese entitled My Own Country. And we hope to have Abraham on in another session of ours. You know, Abraham's story of growing up in Africa, and moving to the United States, and moving to the South in Tennessee in a time of HIV was really an extraordinary journey for him.

DAVE JOHNSON: Yeah, an amazing story, settling in East Tennessee in the Appalachian Mountains, and then going to the Northeast to do additional training, and then returning to that part of the country during the height of the AIDS epidemic-- really a remarkable story. For those who have not read it, we both recommend it very highly.

Today's guests we're incredibly excited about both. Dave and I met Quyen Chu in the Leadership Development program for ASCO. He was in the first class. He's currently the professor of Surgery and chief of the Division of Surgical Oncology and holds the Edward and Frieda Green Professorship in Surgical Oncology at LSU in Shreveport.

He earned his MB degree at Brown Medical School in Providence, trained in general surgery in Massachusetts at Springfield and at St. Elizabeth's Medical Center, and then did his fellowship training at Brown University under the mentorship of Dr. Hal Wanebo, who was a wonderful surgeon and very active in ECOG in the Southeast group. Dave and I knew him. He's authored-- or co-authored more than 178 publications, a number of book chapters, a couple of books, including translating one of the surgical textbooks into Vietnamese.

He has been an extraordinary human being. And one of the things we want to explore is his journey from childhood until now. In 2013, he was appointed by President Barack Obama to the board of Vietnam Education Foundation.

He has worked in impoverished areas in Louisiana but also in the war-ravaged parts of the world, including Iraq, Kurdistan, Vietnam. He is truly a special breed of humanists who-- I think he looks back at his roots. he sees the bright possibilities of the future and reflects on what he can do to make a difference. It's just a great pleasure to have you, Quyen, to join us today.

QUYEN CHU: Thank you very much, Pat, for that great introduction. It is very heartwarming, and I look forward to this podcast.

DAVE JOHNSON: So Quyen, why don't we start a little bit-- I mean, Pat's mentioned your background. Tell us a little about how you got here and about your family and their journey from Vietnam to the United States.

QUYEN CHU: Sure. I immigrated to the United States in 1975 right after the fall of Saigon at the end of the Vietnam War. My father was a South Vietnamese officer in the army, which means that he fought alongside with the Americans so that when the Americans pulled out, South Vietnam fell. And so because he was an officer, we were-- basically had no choice but to leave the country. Otherwise, he would be in a re-education camp, which might mean that we would never see him again.

So we left Vietnam in '75. I was seven. We left on a ship, and then we also left-- then we transitioned to boats, and then we went to the Philippines for several months. And then we finally got sponsored by a church in Florida. So then we stayed at Eglin Air Force Base for several months before we actually went to our home in Florida.

I grew up there and basically was-- grew up in a very impoverished area. It was-- basically it's a rat-infested home that we lived in. My father was an officer. He was a captain. But coming over to the United States, you have to learn English. You have to try to get a better education.

And he finally realized that he had to support a family of six, and he took on being a barber. So he was a barber for most of his-- the rest of his career, really, raising a family of six. And I was there just to do the very best that we could.

Throughout it at all, we knew that we were in the right place. And we knew that America doesn't give everything out for free, but we also know that it's a great, great land of opportunity. The philosophy is that if you apply yourself, do the very best, follow the rules and regulations or laws, you know, abide by their laws, that you can do great things. And that is a great opportunity. So that was embedded in me and my sisters, and those philosophies have stood the test of time thus far.

PAT LOEHRER: You know, I read a little piece when-- you told a story about arriving here in Florida and a police car pulling up to your house. Can you relate that story?

QUYEN CHU: It's the memory that I will never forget. And in fact, I remember it every Thanksgiving. So it was around Thanksgiving. We really didn't know what it was. We just moved into a new house.

And it's funny because when we drove by the new house, we saw the garage. And we felt, oh, my god, we're going to live in that garage. This is great. This garage is going to be our house. This is great. There's so much space. And I remember when we asked the driver, the driver goes no, no, no, no, that's where you park your car. The whole house is yours. And we were just amazed.

But anyway, so around Thanksgiving, we saw-- a police car drove up to our parkway. And I saw, and I was scared. And then I called out my dad. And I said, Dad, there's a police car here. What did we do wrong? And he was so scared. And he said, Son, you know, I will take care of this.

So the police came and knocked on the door. And when my dad opened the door, he claps his hand, and he just bow, just like this, several times to the policemen and say, we're-- in broken English, we're sorry. We know English. We did not mean to break any laws. Forgive us.

And the police just smiled. And he says, no, no, no, no. We're here to greet you as a new neighbor. And it's Thanksgiving, and we want to give you a turkey.

Then he waved to the other police to come over, and then the other police came out with a big old turkey. And they hand it to us, and they said, welcome to the neighborhood. And we were so happy. My mom-- just about to cry. And we felt that, hey, this is now our new home, and we felt that this is not going to be a strange land, that we're going to create a life for ourselves here.

DAVE JOHNSON: It's a remarkable story, Quyen. That type of story just makes it even more special. You mentioned that you had several siblings. Where do you fall in the hierarchy? And what are your siblings doing?

QUYEN CHU: So I'm a second-oldest. So my oldest sister-- she went to Cornell, and she is now a full professor of biochemistry at Union College. My younger sister, who's a year younger than me-- she graduated from Dartmouth, and she is now working at industry and also, in the medical field. She holds a PhD from Columbia. And then my youngest sister graduated from Oberlin College, and she is now working in the hotel business.

So we're very blessed. We feel very excited about the opportunities. And we look back at our lives every Christmas when we get together as a family, and we reflect back at the lives that we've gotten. And we also feel bad about family members who couldn't make it over here and wonder what their lives would have been like had they come over here. And then we also wonder what life for us would have been like had we not come over here. And through it all, we felt that we really, really hit the jackpot in life and that all of us were very, very lucky to have this life that we have.

PAT LOEHRER: I can't imagine the pride that your parents have of all of you and how much pride you have for him. I mean, it's extraordinary. Can you just because I've never-- none of us have been through this, what you've been through. But what was it like being seven years old in the middle of this war in Vietnam? What memories do you have of that?

QUYEN CHU: Yeah. I remember when I was playing with my cousins. And of course, in Vietnam, we live under a house full of cousins, aunts, and the extended family. I remember leaving them, and I felt very lonely in America. Of course, each family has its own separate family. And I just felt like it was not-- it was very lonely.

But we did have very nice neighbors. We did have great people that really was very supportive. Of course, as a young seven-year-old, the neighbor's daughter was around my age. She was cute, so, of course, I'd find every reason to visit them and say hi to them.

But other than that, it was a very nice place to grow up. They have their challenges, obviously. What I remember as a second grader-- I saw all the boys. To me, I thought they were all brothers because they were all Caucasian. They all have blond hair. I couldn't tell the difference who's who, but I thought they were all related. But they were very nice, of course.

There were curiosity between us. I've never seen African-Americans until I came over here. And I befriended a Hispanic guy, as well as an African-American, as well as my best friend. To this day his name I still remember. It's Jeff. He was very friendly.

Of course, I experienced some racism, but I think that's expected because I look very different. There were a lot of mixed messages coming out of the Vietnam War. But I think that through it all, the challenges, I realized, that there are more good people than there are bad people and that people who were bad-- probably because they were insecure, or they just didn't know me.

And then there were those who did finally get to know me. They turned out to be great people. I've learned throughout my 53 years on this earth that people have so many things in common that when we do have conflict, it's probably stemmed from insecurities rather than pure hatred.

DAVE JOHNSON: Yeah. You went to undergraduate at Dartmouth. Is that right?

QUYEN CHU: Yes. sir.

DAVE JOHNSON: So I seem to recall-- maybe you told us this in the LDP program, but you had an interesting experience when you showed up on campus at Dartmouth.

QUYEN CHU: Yeah.

DAVE JOHNSON: Can you relate a little bit of that to us, as well?

QUYEN CHU: Sure. So, again, coming from a family where your dad is a barber, I had limited means. So I basically had, I think, one tote bag that I packed together. I took a Greyhound two day's trip to Dartmouth.

And I got there on the campus. It was a beautiful green campus. And I was a little bit hesitant, a little bit reserved because there were a lot of Caucasians and whatnot. And I was a little bit, you know, introvert somewhat.

And when I got there, I saw a Frisbee flew by me. And I grab it, and then the guy goes, hey, you want to come and play with us? And I'm like, well, sure. And next thing you know, we hit it off like a bunch of 18-year-old kids-- no worries in our mind, just glad to be on campus. And we hit it off.

And I realized that, hey, you know, my reservations were basically based on my own biases rather than the reality. And then I've realized that the reality is that a lot of the kids there are just like me-- just want to find friends, just want to hang out, just want to have a good education. And they weren't being judgmental about anything, and that made me really-- it felt really good.

DAVE JOHNSON: Frisbee diplomacy, I guess, is we should call it. Maybe we should throw a Frisbee to Putin. I don't know.

QUYEN CHU: That's right.

PAT LOEHRER: Tell us a little bit about your journey to become a surgeon.

QUYEN CHU: OK. So my dad and mom instilled with me the importance of education. They told me, now listen, you have a choice-- either be in the same rut as us now, or get a good education and get out of this rut. So I really didn't have any choice but to study hard.

And I studied hard, and I got an opportunity to go to Dartmouth. I felt very, very lucky with that. They gave me a full scholarship. They believed in me. They saw something in me that I was very happy that they saw.

And then I applied to medical school at my sophomore year at Dartmouth, and I got in. I was very excited about that. And I started off wanting to be a pediatrician, but then I realized that what I had to turn in my sheet of the patients that I saw, everything had to do with procedures and techniques. I wrote down there I did a spinal tap, I did a chest tube, I helped intubate, I did all of that.

And it was really my pediatric mentor who says, it sounds like you should be a surgeon, not a pediatrician. And that kind of got me thinking about it. And then I rotated a service with Dr. Wanebo and really fell in love with surgery. It was tough. It was rough. But I felt that this is my calling.

I felt very fortunate looking back at only the number-- maybe they admitted 100 students. And I felt very fortunate that I was among those. And I knew that it was an opportunity that I did not want to waste, that I did not want to take for granted. I wanted to do everything I can to make sure that I learn as much as I can and hoping that in the future, I would give back to the country, the community that gave me a life.

DAVE JOHNSON: Yeah, my mentors suggested that I should be a forest ranger as opposed to a physician. [LAUGHS]

PAT LOEHRER: Yeah I think I shared before I got, on one of my medical-school applications, they not only rejected me, but they said, good luck in whatever career you decide to go into.

[LAUGHTER]

I was going to be a pediatrician, too, but I envisioned all these kids just laughing and having a great time. But they were all crying, and the parents didn't like me either. And so I decided to find a different life.

You have had this extraordinary journey of giving back, as I mentioned at the onset, and not only going back to Vietnam but also, going to Iraq and going to many other countries here. And about five years ago, you received the ASCO Humanitarian Award, which was so deserving for you.

DAVE JOHNSON: Very deserving.

PAT LOEHRER: But tell us a little bit about these efforts. What has pulled you or driven you to do so much of your humanitarian efforts around the world?

QUYEN CHU: Well, first of all, I want to credit my wife Trina, who's been there for me. She's basically the backbone of my life, allowing me the opportunity to pursue my passion. She's a lawyer. She put her career in the back seat so that I can have a successful career. So I want to make sure that I acknowledge her sacrifice and her love.

Because of her love and her understanding, I was able to pursue my passion, which is giving back. My colleague, Dr. Gazi Zibari is from Kurdistan. And one day, he showed me pictures of the Kurds, and he gave me the history of the struggle the Kurds. And it was reminiscent of the struggles of the Vietnamese, so it resonates with me.

And I said to him one day, hey, listen, when you do go, I would love to join you. And so I did. And from that point on, I returned, I think, four or five additional times. We did not return last year or so because of COVID, but we're planning to return again to Kurdistan and Iraq.

But it was an opportunity for me to really give back what I wanted to do all along, which is to render care to the less-fortunate individuals of our lives. I also went to Vietnam, Nicaragua, Honduras, and also on those different mission trips. And, you know, Dr. Zibari and I have gone together for many of these trips. And we come to realize, you know, what-- the great thing to do is capacity building. In other words, we should visit these countries not just once but several times to make sure that the surgeons there feel comfortable with the procedures that we taught them and that, hopefully, that they will also teach the other surgeons the procedures, the techniques that we taught them.

And we were very pleased when we went back to see that these surgeons were very adept in what they were doing-- Whipples, liver resection. They were doing phenomenal things. In fact, I think the greatest sense of pride in me was to see a young surgeon in Kurdistan who did a laparoscopic right-liver resection bloodless.

We felt very proud because-- I was looking at Dr. Zibari, and I said, you know what-- I can't even do that. And it's amazing to see how they have not only learned our skills, but they exceeded us. And isn't that what we all want, that our mentees to be better than us? And so to me, that was a great sense of pride.

At the end, the young man came up to me and says, mentor, I hope I did it right. Did I make any mistake? And I chuckled. And I said, no. I could not have done what you've done. You have done amazingly.

And he was so happy. He was so proud. He says, I'm so glad that I make you proud of me, Dr. Chu. So to me, that's probably the greatest thing is to see your mentee better than you and still see that respect that you got from them.

DAVE JOHNSON: We're really happy you mentioned that because one of the themes of our podcast has been mentor and mentor relationships. And you had a remarkable relationship with Dr. Wanebo. Would you like to expand on that somewhat or tell us about that relationship?

QUYEN CHU: Sure. Dr. Wanebo-- I always joke around. I said, Dr. Wanebo, you're a gifted surgeon with an internal-medicine demeanor. He is just so nice. He never loses his cool.

And the great thing about him is that every time I have an idea, he would always push me to pursue it. There's never been a, no, it can't be done. No, that's not how-- you will never get it done-- never like that. It's always, this is a great idea, Quyen. Why don't you pursue it. And in fact, he would give me deadlines and say, why don't you get back to me in two weeks and see where we go with that.

I remember visiting him in his very busy clinic. And his PA would always trying to brush me aside because they were so busy. And he would always say, no, no, no, come on, Quyen. What do you have for me? What do you need?

He would always make time, even in this busy clinic, to help mentor me. And then whenever I'd write a paper or abstracts, he would look at it. He would fix it, and he would send it back to me and ask me to work on it. So he's been a great mentor, just a great person all around.

PAT LOEHRER: Quyen, if you could think about a young professional or young student right now and give them some advice, what would it be?

QUYEN CHU: I think the best advice is that you pursue your passion. I know it sounds so trite, but pursue your passion. Seek out mentors who believe in you, and avoid those naysayers because I think that young people have so many insecurities. And they're great people. They're so naive, and they're so fresh. They're not tainted with all of the flaws of the world.

And I always worry that when they encounter negative people, it fills their mind with negativity. And that, to me, is not very constructive. So I would advise young people to seek out optimistic, idealistic people to be mentors. And then I think the rest will follow.

And they will learn what can be done, what can't be done. Obviously, you need a mentor to advise them so that they don't fall into your trappings of making major mistakes. But I think that mentors should be someone who is inspiring, who is positive, who can tell them that, hey, you can do it. And if you fail somewhat, it's not the end of the world. Seek out your passion, and never give up.

DAVE JOHNSON: That's great advice, Quyen. I have just one more question I wanted to ask and perhaps should have asked a bit earlier. How did you end up in Louisiana?

QUYEN CHU: That's a great question. So at the end of my fellowship, I had opportunities to stay up north. Then I got a call from my previous partner to say, hey, listen, I'm in Shreveport. Why don't you come by.

In fact, it's funny because when I heard the word "Shreveport," it sounds, to me, Chinese. And I said, why would I want to go to China to practice? I didn't know where it was.

And then they said, no, no, this is in Louisiana. And I really thought about, nah, I don't want to go. But my wife said, listen, why don't you just go down there and take a look so that at least you won't offend the person who asked you to come down.

So I went down there for an interview. And it really resonates with me about the needs, that patients there did not have, in my opinion, good surgical oncology care. There was a huge need. I saw the mortality for esophagus, gastric cancer. They were high. I saw a lot of cancers that were neglected.

And the chair there, Dr. Turnage, was wonderful. And he said, listen, Quyen. Nobody's going to compete against you. We just got a huge need. I think that you would find a niche here, that you can really, really develop a practice here, and then I can mentor you for the academic part.

So I thought about it. And then I talked to Trina, my wife. And I said, this is what I wanted to do. I wanted to give back. I didn't want to be just another spoke on the wheel. I wanted to make a difference. I think I can do this here. And so we took a chance, and I think that we're very happy with that decision we made.

PAT LOEHRER: Well, Quyen, I just, as I reflect on this and think about that leadership-development program, there are many different kinds of leaders, but I can't think of a person who serves as a better example as a servant leader than you. You have given of yourself in so many ways. In this particular past few years. Where there's been so much angst and polarization in this country, and even consideration of isolationism and not having immigrants come into the country, I hope people listen to this, the podcast, and realize what the impact was of a man and a woman who decided to bring their kids over here.

And he became a barber, which is not that prestigious of a job, if you will. But his impact on this country is huge. Mark Twain had a little quote. He said, "The two most important days of your life are the day that you were born and the day you find out why."

And when you guys were born in Vietnam, you had no clue what was going on, but you are one of the fortunate people who know why you're here, and that's to make a difference. And I just want to tell you that you have. Thank you so much for your time with us today.

DAVE JOHNSON: Yeah, it's been great.

QUYEN CHU: Thank you very much.

DAVE JOHNSON: Quyen, this has been marvelous, and we're both great admirers of yours. And I could not agree more with Pat about the impact that you've had.

One thing we like to do with our guest at the end is ask you if there's something you've read recently, or a documentary, or something, a movie or something you've seen that you would recommend to us and to our listeners. Is there something special that you've read recently or maybe seen that you'd like to recommend?

QUYEN CHU: Yes. So there's a book by Mr. David Epstein called Range. It's a phenomenal book. It's a book that contrasts Malcolm Gladwell's philosophy about 10,000 hours to be an expert. Mr Epstein took a different approach. He took the approach that you have to be a generalist. In other words, you have to do many things in life before you can hone in on one particular skill set to become an expert in that.

So to me, that book, Range, is a fascinating book. I'm midway through. And it's just-- it's a beautifully written book, and it just gives a different perspective of life.

I've always loved books that give a different perspective for a particular topic. And I would highly recommend our readership to read Range by David Epstein.

DAVE JOHNSON: Yeah. I also read that, and it is a fabulous book. I couldn't agree more.

QUYEN CHU: Yeah.

DAVE JOHNSON: Well, we've come to the end of our session. And I really want to take this opportunity to thank our listeners and thank Quyen for joining us. It's been a marvelous session.

QUYEN CHU: I appreciate it. Thank you, David, and thank you, Pat.

DAVE JOHNSON: Thanks for tuning in. This is an ASCO educational podcast, where we will talk about anything and everything, really. We really will. So if our listeners have any ideas for our topic or guests that you'd like to hear, please email us at [email protected].

Thanks, again, and remember that November 9 is National Louisianan Day. And Pat, just so you know, November 16 is National Indiana Day. I'm sure you already knew that.

PAT LOEHRER: I love it. Every day's Indiana Day.

DAVE JOHNSON: No, every day is Texas Day.

PAT LOEHRER: Thanks, guys.

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SPEAKER: Thank you for listening to this week's episode. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.

Adjuvant immunotherapy is a game-changer for early lung cancer, but it is not the best choice for every patient. Hosted by Dr. Rami Manochakian (Mayo Clinic), Drs. Karen Kelly (University of California Davis) and Howard West (City of Hope Cancer Center) explore considerations in shared decision making and personalizing therapy through patient cases. 

Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us

Air Date: 12/15/21

TRANSCRIPT

[MUSIC PLAYING]

SPEAKER 1: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

RAMI MANOCHAKIAN: Hello, and welcome to ASCO Education Podcast on new therapies for lung cancer. My name is Dr. Rami Manochakian. I'm a thoracic medical oncologist at Mayo Clinic Florida.

Today, I have the pleasure to speak with two very well known, nationally and internationally, thoracic medical oncologists specializing in the fields of lung cancer. I have Dr. Karen Kelly, who is a professor of medicine and associate director for clinical research at the University of California Davis Comprehensive Cancer Center. And I am also joined by Dr. Jack West, who's a medical oncologist as well as associate clinical professor in medical oncology at the City of Hope Comprehensive Cancer Center.

In October of this year, the FDA approved atezolizumab for adjuvant treatment of stage II to IIIA non-small cell lung cancer following a resection and platinum-based chemotherapy. This is the first adjuvant immunotherapy approved for lung cancer and has the potential to improve cure rates. In this podcast episode, we'll discuss how to implement this new therapy in the care of real-world patients.

We're going to start the conversation today with a patient case. We have a 64-year-old woman who is a 15-pack-year smoking history, quit several years ago in the 1980s, and was found on a screening CT to have lung adenocarcinoma. She underwent a full workup that included a negative EBUS and ultimately underwent a surgical resection with right upper lobectomy.

Surgical pathology showed a 3.2-centimeter invasive adenocarcinoma with some additional lepidic noninvasive AIS, and two out of eight N1 nodes were positive. The final staging was a pT2aN1 stage IIB disease. She had a molecular testing that included NGS that showed an EGFR activating mutation in exon-- 21-L858R substitution with no other driver mutation. And PD-L1 was checked, and it was 2%.

And we'll start with the first questions. And I'll start with Dr. Kelly, and then we'll ask Dr. West also to give his opinion. Given the currently available treatment and the new approvals, all the research evidence and guidelines that we have as of now, 2021, how would you manage this patient?

KAREN KELLY: Well, I think that that is a great question. And of course, for this patient, who does have that EGFR L858R mutation, that is a very important finding to have. And I applaud the ability to get the NGS sequencing, because that is important here, for patients today, based upon ADAURA results, which was the randomized trial after resection for patients with early-stage disease who got chemo or not, randomized to osimertinib versus placebo.

And so I think for this patient with that EGFR mutation, my driver in my treatment plan after adjuvant chemotherapy-- and I do want to make that important distinction here that, even though ADAURA did allow patients to not have chemotherapy, we are strong believers in evidence-based medicine that has shown that adjuvant chemotherapy has improved survivals and cure rates in this patient population. So after, I would begin with giving adjuvant chemotherapy for four cycles, cisplatinum-based. And then, based upon ADAURA, offer this patient osimertinib.

I do not believe that this is a patient that would benefit from a immunotherapy regimen. And I'm going to let Dr. West talk about that component of this case-- that immunotherapy, I believe, would be contraindicated.

RAMI MANOCHAKIAN: Excellent. Dr. West?

JACK WEST: I would say that some in the audience may know that I've had some issues with the design of ADAURA and had been critical of it at the time of its release. And I think it is always a little challenging when we have disease-free survival results, but not overall survival in a curative setting, because I believe our goal here should be to improve survival. And it's not clear, particularly with a treatment that is still ongoing, whether this is really just forestalling progression and going to translate to a survival benefit. So that comes up with ADAURA.

But that said, we are now in a situation where we have a remarkable improvement in disease-free survival with ADAURA that gave the adjuvant osimertinib for patients with a tumor harboring an EGFR mutation. And we don't yet have mature data for overall survival. I think we need to work with what we have, and that is giving the patient the benefit of the doubt and presume, until we see otherwise, that the remarkable improvement in disease-free survival will, we hope, translate to an improvement in overall survival.

So certainly, for patients with node-positive disease, I would definitely favor at least offering, if not clearly recommending, osimertinib. I would talk about the caveats that we don't yet have overall survival, but I would say that, based on what we know, with the limitations, I would be encouraged and would favor that.

And the important challenge, I would say, is what to do when you have potentially competing options, like adjuvant immunotherapy, specifically-- now in FDA approval for adjuvant-- atezolizumab, based on IMpower010 results that we first saw at ASCO in 2021 and have learned more about. And the results are also very impressive for at least a subset of patients, specifically those with stage II to IIIA disease and who have PD-L1-positive disease.

I would note that, when looking at subset analysis of IMpower010, the benefit is much more impressive in the subset of patients whose tumor has PD-L1 expression in the high range, 50% or higher, where the hazard ratio for disease-free survival is 0.43. And in contrast, for the patients with low PD-L1, that hazard ratio for DFS is 0.87. And of course, we don't yet have overall survival for this trial either.

So I would say that there is, arguably, a question of what you would do if someone has PD-L1-positive disease and an EGFR mutation. But I would note that we have seen in advanced disease that patients with a driver mutation-- say, particularly, EGFR-- are overwhelmingly more likely to benefit from targeted therapy against EGFR than immunotherapy. And if anything, it seems that PD-L1 expression for patients with an EGFR mutation or an ALK rearrangement doesn't necessarily mean the same thing as it would for someone with wild-type disease. It just is not nearly as strongly predictive of benefit, and the benefit with targeted therapy is far greater.

RAMI MANOCHAKIAN: Thank you to both of you. Really, I think you brought both a great point. I like what Dr. West said about we need to give the benefit of the doubt. We need to deal with what we have, because right now we don't have the OS benefit, talking about, obviously, the ADAURA, or even the IMpower.

And discuss with patients. Discuss what we're doing. Include them in the treatment decision and plan, and tell them this is why we're considering this and not. It appears that everyone feels that this patient, obviously, would not be the best candidate for adjuvant atezolizumab. Rather, very possibly get an adjuvant targeted-therapy osimertinib.

Speaking about adjuvant atezolizumab, I want to ask, who else you would not recommend, maybe, adjuvant atezolizumab to? And I'll start with Dr. Kelly again.

KAREN KELLY: So I think that we have learned a lot about other driver mutations based upon what we know about EGFR. And EGFR really has been the prototype for all the other mutations. And pretty much, they align with the findings with EGFR, particularly those of ALK, ROS1, and then we get into RET. And we can also talk about HER2.

And I think the difference here, between that category and that group of oncogenic drivers, is that they're characterized by being in patients who are never smokers. And so in my opinion, this group of patients that have those additional mutations-- either ALK, RET, ROS1. I would say, also, HER2-- those never-smoking, oncogenic-driven aberrations, really, would probably fall, in my opinion, into the same category that I don't think that they would be the best for atezolizumab.

I also base that on retrospective data from the IMMUNOTARGET data that came out in advanced disease, with monotherapy looking at a retrospective large series, multi-institutional, that showed that there really wasn't a benefit for mono-immunotherapy.

Now, I will say that, of course, we do have oncogenes that are smoking-related-- that being KRAS G12C, now, remembering that not all KRAS are smoking-related. But something like KRAS G12C. BRAF, typically, as well. Half of the MET oncogenes are in patients who are smokers. So I think if you're a smoker and you have an oncogene, then I think that it would be reasonable.

Again, based upon retrospective data-- I would say even based upon my own data from California-- we have found similar results. Even when you give immunotherapy with chemotherapy in patients with oncogenic drivers, they just don't have a benefit from immunotherapy. And I think we can logically make sense of that. They are more simplistic tumors. They don't have high tumor mutational burden. They don't have high PD-L1, for the most part. They're typically more characterized as being cold.

So I think it does make sense that this group of oncogenic-driven cancers, particularly those in never-smokers are really more cold tumors and don't respond. So I would add these others to the list that we do have data on, and that, of course, is EGFR.

RAMI MANOCHAKIAN: Dr. West, your thought? Especially, it looks like we're heading one way or the other to say that every patient with early-stage needs NGS testing.

JACK WEST: I think that we are in a challenging place where the principles are ahead of the actual data that we have. I think that we have been struggling with this for a few years now with things like the PACIFIC trial, where we've had very impressive data for not just disease-free survival, but now overall survival. But that was a pretty broad, inclusive population. It included patients with an EGFR mutation, ALK rearrangement, and didn't really specify otherwise.

And so the question is, do we broadly interpret that, well, if they were eligible for the trial and the trial is positive, they should be treated this way? Or do we make, I think, very logical inferences from stage IV disease that not only do these patients often not seem to benefit at all from immunotherapy, but that we could put ourselves in the challenging situation of giving immunotherapy and then having their cancer progress, and needing to give them a targeted therapy where there could be a harmful interaction between the osimertinib that we want to start and the immunotherapy that is still in their bloodstream?

And so that's a real challenge. So I think that we need to, now, do some extrapolation. And because of that, it does make sense to want to have this information to individualize the recommendations for the patient. And it's not a big leap, based on what we know about ALK, to presume that these patients are not going to be big beneficiaries or, likely, beneficiaries at all from immunotherapy.

I agree with Dr. Kelly about ROS1 and some of the other never-smoking-related driver mutations. I think it is important to say that we shouldn't paint all driver mutations with the same brush. We have seen from IMMUNOTARGET that KRAS and BRAF are not in the same category, and so we need to think of these individually. But I do believe that this information is going to be really helpful to make an informed, thoughtful decision for the individual patient in the exam room with us about whether they personally are likely to be beneficiaries of immunotherapy, targeted therapy, or whether they should withhold all of those.

KAREN KELLY: Can I make one additional statement? I just want to add to what Dr. West said, particularly raising awareness about the harm factor. I think, as physicians, we're very focused on wanting to help the patients in terms of, when we look at these biomarkers, let's look at them and give you what works for them. But we have to remember now, with the oncogenic drivers, that we can potentially harm them if we give them immunotherapy.

So I think we have to remember, now, the harm factor really comes to the forefront when we talk about immunotherapy and oncogenic drivers and the critical importance of knowing. Yes, we want to know if we can give osimertinib to those patients who are EGFR-positive. But in the same breath, we want to say, oh, immunotherapy would be harmful. So I think that's a little bit of a switch that we have to, as physicians, remember to have that really important conversation about why we don't want to give them immunotherapy.

I will say, many of my patients with EGFR or ALK or ROS-- they come in, and they want immunotherapy. And you really have to spend time explaining to them why they are not the best candidates for immunotherapy.

RAMI MANOCHAKIAN: Great point, great point.

And just one very quick question before I move two Case 2. Are you both testing for NGS for every early-stage cancer patient that comes to your clinic?

JACK WEST: I'll say that I would be most inclined to do that for a patient where it's likely to have an impact in the more immediate future. I would not say that I feel that this is a mandate for someone with a less-than-2-centimeter nodule, node-negative disease. You can argue that it would be nice to have this information at the time of relapse. But I think that, in general, you'd want to biopsy to confirm progression, relapse, disease, and the most important biology is what it is at the time of relapse and not what was resected two years earlier.

So to me, if it is potentially going to have ramifications for immediate management, so certainly for a node-positive cancer, I would say so. I think it's debatable about whether to do this in someone who has a significant smoking history and a squamous cancer, because the pre-test probability is not high. So I don't want to be too heavy-handed about that, but I would say it makes a lot of sense to think and act beyond the narrow indications that we have now just for looking at EGFR as well as PD-L1.

KAREN KELLY: Yes, I think to the point of harm. I think that we do need to be doing NGS testing in these patients that, I would say, meet the eligibility criteria from the 010 trial, in terms of adenocarcinoma.

I do agree with Jack that a small 2-centimeter tumor-- I wouldn't be checking that. But if you meet the eligibility requirements, and you're thinking along those lines for that patient, then I definitely would do the NGS, not only-- as I said, because you don't really want to harm a patient. If you don't know that they have RET or ROS, you could potentially harm them if you gave them immunotherapy. So I think that is my point. We've got to remember. Now we have to think about helping our patients, but also not harming the patients.

RAMI MANOCHAKIAN: Excellent. Thank you.

I'm going to move on to Case 2 briefly. This is more of a case of a patient that is a good representative of a patient who meet the eligibility for the IMpower trial that led to the approval of atezo. 71-year-old male who presented with chest pain. Workup showed a mass, a 4-centimeter left-lower-lung mass. A full workup, including PET and EBUS showed that lymph nodes were negative.

Also underwent left-lower lobectomy, and his staging was stage IIB, T2b, N1, with two hilar lymph node were positive. So again, very similar to the first case. A little just different size. NGS testing here did not reveal an actionable mutation, and PD-L1 was high, at a 60%.

So simple question, Dr. Kelly. Is this patient a candidate for adjuvant atezo? What benefit would you expect to see? I know we touched base on it a little bit in the first case. And then, how would you talk to your patient about potential side effects?

KAREN KELLY: So I think that this is the ideal patient for adjuvant atezolizumab, based, of course, on that very high PD-L1 of greater than 50%. That's where the data and the driver of the positive results really came from with that hazard ratio of 0.43. Remember that, in the subset analysis of the 1 to 49, the hazard ratio was 0.8 or higher. So it was really driven by the high PD-L1 status. So I think that this is a perfect patient to receive the adjuvant atezolizumab.

When I talk to patients about side effects, I begin always with saying that we now have enormous data points about the side effects of all of the immunotherapy drugs, based upon stage III disease and stage IV disease and other diseases. And these agents are, overall, well tolerated, but they do have some risk of serious side effects that are related to inflammatory signs and symptoms.

And so I do think that it's important to have a discussion about what I just group as "itises" that patients can really have. Any "itis" can occur. But the seriousness is, really, anywhere between 3% and 10% of that.

And the other thing that I'm very vigilant about with the patients is that-- I remind them that these side effects can occur at any point in time while you are on the drug, and then through several months after you've stopped the drug. So I think that that's really important to be very vigilant. It's a very different approach than chemotherapy, where we really have a great understanding of exactly when those nadirs are. So I spend time making sure-- and every time I see the patient, going over that whole list again to make sure-- that they are doing well.

So that's really how I approach a patient. And of course, make sure that they have a good understanding of those side effects.

RAMI MANOCHAKIAN: Thank you, Dr. Kelly.

Dr. West, do you agree that this patient is the ideal candidate for atezolizumab and you would offer that?

JACK WEST: I would. And I would say that it's a slightly different situation from why ADAURA is compelling to me. And I would say that ADAURA is most compelling despite the limitations in DFS being assessed in the middle of ongoing EGFR-inhibitor therapy. Here, we don't have a hazard ratio of 0.12 or 0.17 or something like we did in ADAURA.

But it is certainly impressive, certainly for the high-PD-L1 subgroup. And this is in patients who have completed their therapy in the past, and the benefit is sustained.

We also know from the mechanism of action over years of treating patients with advanced disease with targeted therapies and immunotherapy that immunotherapy can have remarkably sustained benefit, even after patients stop it. And so it's not hard to envision that patients will have a time-limited course of immunotherapy and still have very sustained, potentially permanent benefit from it. So I am impressed by the improvement in disease-free survival, even if it isn't of the same magnitude as what we saw with ADAURA, because it is being measured after patients have completed that therapy, and in particular for the patients with high PD-L1.

I do think that we need to be very thoughtful about whether patients in the 1% to 49% group are likely to benefit, in terms of overall survival, because we don't yet have overall survival data. The hazard ratio for disease-free survival is 0.87 here. And we've talked about the risks with immunotherapy are not generally catastrophic, but a lot of patients will have somewhat modest but sustained issues with thyroid problems, et cetera.

And this is the adjuvant setting. Patients may already be cured, and you're talking about an additional year of coming into the clinic for therapy. That is very costly and can have toxicities that I wouldn't want to minimize. So for me, personally, I would say it is quite compelling for those with high PD-L1. It's something to discuss for somebody with low PD-L1 in the 1% to 49% range, but not something that I would consider nearly as striking a benefit.

It does seem to me, from the subset analysis, that much more of the benefit of immunotherapy is limited to those with high PD-L1.

RAMI MANOCHAKIAN: Thank you.

So in conclusion, if I ask each one of you, please, to give a word of advice for oncology providers regarding the implementation of adjuvant atezolizumab into routine care today-- and also, of course, we know this field is evolving in a very great and promising way. What are you envisioning in the near future will bring for patients with early-stage lung cancer and, of course, could change what we're talking about today?

Dr. Kelly?

KAREN KELLY: So first of all, I think adjuvant atezolizumab is a significant advance in the field of adjuvant therapy for lung cancer. Remember, we have not had an advance in many, many, many years. And in the subset of patients, particularly those with high PD-L1, I think the data is impressive.

To Dr. West's point about the 1 to 49, I do agree that we have to be careful, but we need more data. And I think that is where having the results of the other trials will be very, very helpful.

Now, we all know that PD-L1 is really a gradient. And so I do want to say that we can't just focus on one parameter from these trials. We do that, particularly, I think-- the PD-L1s greater than 50% with a hazard ratio of 0.43, a solid number there-- that works. But when you're at 45 or 40 or 30, you really need to take into consideration other patient characteristics and other factors in making those decisions. And of course, that's a shared decision with the patient as well.

So I think it's important to remember there are other factors that we all synthesize when we're talking to a patient and trying to make the best recommendation. So that's the art of medicine, is taking the science and putting it together to really help that patient that is sitting in front of you.

So nonetheless, this is an advance. And remember, this is how we started with stage IV disease. So I really do think, to Dr. West's point about the fact that these patients, after a year, are having this really impressive disease-free survival, we're very optimistic that that will translate into cures.

Now, I want to be clear here that overall survival doesn't mean cure. But again, if we look at cure fraction, I think we will see that with immunotherapy, because we are seeing that. And I know Dr. West and you also probably have cases where you're pretty confident that you've probably cured those patients with stage IV disease. We see that in a very silent way.

[LAUGHTER]

JACK WEST: I really agree. I have been commenting recently, reflecting that we have been pretty reluctant to say the C word, say "cure" for patients who have phenomenal unprecedented results with immunotherapy for stage IV disease, I think, based on our tenets that it's categorically not curable. But I think that immunotherapy has changed everything, and the rules are different.

I would say that the IMpowere010 trial is very important, does change practice, should change practice, and is just the beginning for introducing immunotherapy into the early-stage setting. There are many other trials coming, looking at immunotherapy.

In the adjuvant setting, we have seen very provocative data for neoadjuvant, which I think is also quite compelling and has the advantage of giving you more feedback about how your treatment actually worked. You're not treating blind. I think that in the next three to five years, we will have multiple different strategies, options to choose and that it's going to be a real quantum leap in how we translate some of the benefits that we have enjoyed in stage IV disease into earlier-stage disease to translate to better overall survival.

I think that we will begin to see that for some of these earlier trials, and so we will be able to talk not just about disease-free survival, but overall survival. We will be talking about this for immunotherapy and targeted therapies. And so just like it's been about 15 years since everything changed in the adjuvant setting with chemotherapy, this is the next iteration of that, where we are working on how best to refine our strategies in a more individualized way than chemo for everybody, but to personalize the optimal perioperative treatment strategy for the patient's individual cancer characteristics.

RAMI MANOCHAKIAN: Thank you. Thank you very much to both of you. I don't think we could have ended on a better note. It's definitely a hopeful era for patients with lung cancer. With all the recent advancements and research, I think our patients are living longer, living better. We still have a long way to go and, hopefully, more to happen in this field where we're able to offer our patients some personalized treatment depending on so many different factors.

This is all we have for today. I'd like to thank very deeply Drs. Kelly and West for a great conversation and for sharing their insight and expertise. Thank you to all our listeners. Thank you to our wonderful ASCO staff, and hopefully, for more ASCO Education Podcast to keep covering this topic of lung cancer.

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Thank you all.

JACK WEST: Thanks for the opportunity.

RAMI MANOCHAKIAN: Thank you.

SPEAKER 1: Thank you for listening to this week's episode. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive eLearning center at elearning.asco.org.

In this episode, oncologist Bryan Schneider and infectious disease expert Adrian Gardner from Indiana University, share what it has been like to get knocked down with COVID-19 twice, care for patients during the pandemic, lead the University’s COVID response, and even a supreme court case on vaccination.

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Air Date: 12/7/21

TRANSCRIPT

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SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

PAT LOEHRER: Hi. I'm Pat Loehrer. I'm a director of the Centers for Global Health and Health Equity at Indiana University Simon Cancer Center.

DAVE JOHNSON: And I'm Dave Johnson. I'm a medical oncologist at UT Southwestern in Dallas, Texas.

PAT LOEHRER: Well, welcome back to ASCO's education new podcast series entitled Oncology, Etc. Today, we'll be joined by two outstanding guests, Dr. Bryan Schneider and Dr. Adrian Gardner. We're going to do a deep dive about COVID-19. And Dave, I was thinking-- I was reflecting on my life. The thing in medicine is when new diseases come out. So in our earlier lives, when we started there, was no such thing as Lyme disease, HIV/AIDS-- tumors didn't exist. And then just in the last couple of years now, we have COVID-19, the SARS CoV 2. And I think as physicians, it's kind of exciting. What's your experience been with the COVID-19 in the wards at Parkland?

DAVE JOHNSON: Well, it's been really, very challenging. You know, I don't know that the public yet has fully grasped the magnitude of this disease. I mean, 700,000-plus Americans have died of this disease. That's an astonishing number when you think about it. And I was just on the general medical wards just a couple of weeks ago with a wonderful team of residents and students. Patients with this disease are very sick. We often downplay it, but I'm telling you, these people are really quite ill and can get ill and symptomatic rapidly, within hours.

So this is a serious illness. But I agree with you. One of the things I told the residents a year ago was to keep a journal, that there are a few times during the course of your training and career where a new disease emerges, and you can be part and parcel of that. And keeping a diary of what happened is something that I wish I had done when AIDS emerged back in the '80s, or other disease processes, like Lyme, as you mentioned.

PAT LOEHRER: And syphilis for you, wasn't it?

DAVE JOHNSON: Well, that was sort of the [LAUGHS] Hippocratic oath days, but yeah, no. I think that was-- I think-- I can't remember. We were hanging out together at the time, so I don't remember exactly.

Yeah, no, it's been really remarkable. The thing that's been interesting to me is the response of individuals and their families to the disease, particularly once the vaccines came available. So maybe we can delve into that a little bit today, because I know one of our guests has actually experienced that himself, so we'll know more about that later.

PAT LOEHRER: I don't think, to be honest, that we could have a better collective wisdom than we have today with Dr. Schneider and Dr. Gardner, who will talk about their personal and professional and I think the global impact of COVID. I don't think there's any two people better than that. The only thing we could do better is if Anthony Fauci was here by himself. But these guys are tremendous people.

Dr. Gardner went to medical school at Brown, did his fellowship and infectious disease at Beth Israel, and then did his MPH at Harvard, and joined the faculty in Indiana University in 2012. When he was a student, he spent time in Kenya, with Joe Mamlin from Indiana University as part of the AMPATH program. And he came back to become the field director there. And he is just an outstanding person. He's now the director of the Center of Global Health for Indiana University and the Associate Dean for Global Health and has led the contact tracing for Indiana University. And he's going to give us some input from this.

Bryan, again, I've known forever. He's just an outstanding medical oncologist. He is now a Professor of Medicine and Medical and Molecular Genetics here at IU. He's a Vera Bradley chair of oncology. He is the founding chair of our precision genomics program and just a superstar in breast cancer as well as pharmacogenomics and was one of the first to describe the unique neuropathy associated with the taxanes in breast cancer. So it's just a pleasure to have both of you here.

DAVE JOHNSON: You know, Pat, it's great to have that talent there. It balances out the negativity of other faculty members. But that's great. Welcome, both of you.

PAT LOEHRER: I loved you a minute ago. I've turned mute on from a distance here. Adrian, tell me a little bit about yourself, growing up and how you got to where you were.

ADRIAN GARDNER: Sure, thanks. And thanks so much for the invitation and for being part of this and for the generous introduction. So as you said, Pat, I'm a product of an international environment. That's an important part of my upbringing, actually. I was born in Scotland to two parents that-- born and bred in Scotland and grew up in Scotland. I spent the first six years of my life really living in France and then moved to Lawrence, Kansas, which was quite a cultural shift, but spent four years there. And it was great, actually, time in my life to be there, before moving to the East Coast, where I went to school and did all my medical training.

So I'd had international experiences before, and I think that was an important part of my upbringing and something I sought for my kids, in the sense that it just immediately resets your sense of the world and makes you feel like a global citizen as opposed to just sort of more limited-- the community you're surrounded by.

But it really wasn't until my experience as a fourth-year medical student at Brown that I had the opportunity to see health care in a low-resource setting and see that. And that was a very powerful experience professionally and personally. And as you said, it was the time when Joe Mamlin was really just dreaming up what the HIV response was going to look like, this nice institutional partnership that we'd set up in Western Kenya.

But we set it up in the middle of the global pandemic. And true to our mission of responding and leading with care, felt a need to respond to the HIV pandemic. And that started really by-- was motivated by personal interactions that Joe had with some individuals who he saw firsthand come back to life, the Lazarus effect that has been reported. And that really spawned this whole response, changed my career and certainly my life, and had profound effects on my life.

So that's a bit of who I am as an individual and how I got to where I am today.

PAT LOEHRER: And we're going to touch on some of the work that you're doing now. But before I do, Bryan, tell us a little bit about and your background, where you grew up and how you got to where you are today.

BRYAN SCHNEIDER: Thanks to you, and Dave as well, for having me on. And this will be an interesting perspective, because I think I'm coming on here as the patient this time, so it'll be a different view.

But in contradistinction to Adrian, I am a pure Hoosier. I was born in the southern part of the state and raised there and then drove three hours north to Indianapolis, where I've set up for the last 25 years, and just been really lucky to be here at Indiana University. And Pat, you may not even remember this-- about 25 years ago, you were my formal mentor for med school, and so one of the influences and sticking around here along with some other real greats along the way. So have done, as you mentioned, breast medical oncology here in genomics and have had an absolute blast. So thanks for having me on.

PAT LOEHRER: Oh, we love having you. And just as an aside, Bryan-- one is I think the world of you, and so proud of what you've accomplished. But Bryan's backyard actually was the home of Henry Lynch, and where he first described Lynch syndrome down in southern Indiana. And I think no greater tribute in his legacy than what you have done with precision genomics. It's really terrific.

DAVE JOHNSON: Yeah. Maybe we'll have some time to delve into that. But actually, I'm curious, Bryan-- you mentioned that you've come on as the patient. My understanding is you've had firsthand experience with COVID, not just as a physician, but as the recipient of that wonderful new virus. Maybe you could tell us a little about that?

BRYAN SCHNEIDER: Yeah, an interesting experience to be sure. So about 2 and 1/2 months ago, I tested positive for COVID and got really sick. Yeah, my three-year-old son had brought it home from his preschool and infected his older brother, who's almost 12, and then my wife and myself. And so was a really fascinating experience, I guess, and brought about some aspects to the virus that I had never really thought about.

PAT LOEHRER: Now, Bryan, you also had COVID before, too.

BRYAN SCHNEIDER: Yes. And the first time-- I was probably one of the very, very early cases and got really sick with it and lost my sense of taste and smell. I actually got one of the purple fingers, which I went to the ER for. I thought I was having a or something. And at the time, those weren't well-recognized symptoms. And that loss of taste and smell went months for me. So, yeah, I think I have frankly had the infection twice. The second time, though, was documented and certainly got really sick with the second one.

DAVE JOHNSON: Can you elaborate on your second case? When you say you got really sick, was it a respiratory illness or were there other symptoms?

BRYAN SCHNEIDER: Yeah, there were two aspects to it that were interesting. I think the first was physical. I got a sense of fatigue that I don't know that I have ever experienced before. It was one that I literally just could not get out of bed. And you know, I lost about 10 to 15 pounds from just being anorectic. And I'm not an overly thick human to begin with.

But the big one was shortness of breath. And we had a pulse ox at home. My wife's a pediatrician, and I was sating in the high 80s. And I work out five or six times a week, so keep in pretty good shape, and I was stopping midway up the stairs to sit down, because I felt really tachycardic and just lightheaded. And so that degree of physical punishment is something like I have never expected or felt before.

But the psychological part of it was really something I did not expect. And one part of that was an odd sense of guilt. I was getting texts and calls from a lot of friends checking on me, and many were baffled and asking, hey, did you not get vaccinated? Or what was going on with that? And so that-- it was a very odd sensation to me, because I, of course, had been vaccinated and I mask and all those sort of things.

The other was one of real fear. I worried-- you know, luckily, I guess, our family all got infected around the same time, so we didn't have to think about quarantine. But I started wondering, could I have infected a patient? I take care of immunosuppressed breast cancer patients, before I was symptomatic. And then even after I came back to work, I had quarantined for quite some time, but I was really fearful. I would find myself double masking, washing my hands incessantly, and even holding my breath when I was trying to listen to heart and lungs during examination. So that sort of psychology was something I don't think I really expected with this infection.

DAVE JOHNSON: How long did it take you to get beyond that, or are you beyond that part?

BRYAN SCHNEIDER: Yeah. You know, I feel back to my baseline now. And I certainly don't worry about it on a day-to-day basis now. But my first clinic or two back was really hard for me, psychologically and emotionally. And part of me even wondered, should I profess to all my patients that I've had COVID? Or what things can I do to help protect them? And again, it was that mental aspect that I just didn't really anticipate prior to heading back to my clinic.

DAVE JOHNSON: You know, this is eerily reminiscent of the physician who's had cancer who experiences extreme fatigue for the first time, chemotherapy-induced fatigue, after having described it many, many times before--

BRYAN SCHNEIDER: Right.

DAVE JOHNSON: --and who has a guilt sensation in many respects as well. So quite the experience, for sure.

PAT LOEHRER: Dave was talking about himself, by the way.

BRYAN SCHNEIDER: No, I can only imagine. And you're right. We do try to paint a picture to patients about how things are going to feel, and it's amazing. When it's internalized or when you're feeling, it's-- it can often bring about a sense of, wow, I don't know that I-- I may have underplayed this to some of my patients in the past. And it really does provide some degree of empathy that's hard to capture if you haven't felt it.

DAVE JOHNSON: So when I was on the wards, Bryan, I must confess, there were times when we walked into a patient's room with COVID who, of course, had not been vaccinated long after the vaccines were approved. Our professionalism prevents us from doing anything other than taking care of those people, but I'm wondering how you feel about caring for patients who have not been vaccinated or refuse to be vaccinated.

BRYAN SCHNEIDER: Yeah. I mean, I think probably similar to a lot of people listening here today, it's a bit frustrating. And I think we all take care of patients who have a really tough diagnosis. And we're in the interesting field of giving patients medications that really immunosuppresses them, so we spend time counseling on the fact that you may get really sick or hospitalized or even die from neutropenic sepsis. And I think that is something that rests really hard with patients who are already dealing with a life-threatening diagnosis.

And so now, trying to do that counseling in the face of a global pandemic like we haven't seen for a hundred years has really brought around a sense of duress and distress in my patients like I've never seen before. You know, I even had a patient who moved away from her family to be quarantined during adjuvant therapy, which I, of course, recommended against. But it really impressed upon me how big a deal this was.

And so to see their frustration, and then in contradistinction, understanding that some people didn't want to pitch in to help-- it was very frustrating and honestly just made me very sad for people who I know were really struggling with this.

DAVE JOHNSON: Actually, I had one more question to ask you. You mentioned coming back-- did you, in fact, share your diagnosis with your patients? I mean, I-- when I had cancer and came back, I made a pact with myself that I wasn't going to do that. But then I learned that the nurses were telling patients that I had cancer, and I found that it actually was helpful to share that diagnosis with many of my patients so that they could ask questions and feel that they had someone who really had experienced what they were either going through or about to go through. So I'm wondering how you've shared your diagnosis of COVID with patients, if at all.

BRYAN SCHNEIDER: No, that's a great question. And I may have followed a similar pattern. At first I didn't. I didn't know what to do, to be frank. I didn't know if my saying that would make that patient, in that moment, more stressed out or worried, and I certainly didn't want to add to that. So I took it upon myself to try to make myself as safe to them as possible.

But now that I've had a little chance to reflect on it, I have shared it. And I think for some of my patients, it's been good for them to hear what that experience was like. I think it's also-- Dave, as you probably know, I think it also reminds them we're human, too, and we experience some difficulty with physical health and I think in some ways it allows us to bond in a little bit deeper way.

DAVE JOHNSON: I agree.

PAT LOEHRER: I want to turn the attention over to Adrian now. Adrian, you're in a unique position, obviously one because of your experience in Kenya, and we want to hear about that, but also your responsibility for Indiana University. What some of the listeners may recall is that there was a decision made that you were part of that actually mandated that students in Indiana University be required to have vaccination before they came to school.

We were in Kenya at the time when we heard that there was some consideration about that from the state legislature in terms of how-- mandating that. And eventually, this was a case that in which eight students took this case to cohort that eventually reached to Amy Coney Barrett, who decided to find in favor of Indiana University. It was a landmark decision here.

But tell us a little bit about your experience on the leadership role of COVID and the impact that you see in terms of yourself personally and from the field of the university.

ADRIAN GARDNER: Yeah. Thanks, Pat. I think it's really two different worlds in my mind, in some ways, although clearly linked by this global pandemic. You know, I was just finishing my eight-year stint, essentially, in Kenya in March of 2020 when we got the news that the entire world was about to be declared a level 4 by the State Department. And well, that-- I remember actually talking to Joe Scodro on the phone. And he's like, what the heck does that mean? That's not in our playbook of what we do when things happen and we need to bring trainees home and sort of--

PAT LOEHRER: Scodro being the lead counsel for Indiana University here.

ADRIAN GARDNER: Thank you. Yeah, yeah. So for me-- I mean, obviously I was making a transition back to a US-based career in this position as the Director for the Center for Global Health. But you know, I had a dramatic change in my position, right? I mean, who is going to do global health operations in the middle of a pandemic? Well, nobody, because nobody was traveling.

So we had really shifted all of our Kenya operations to a virtual support. We pulled all our trainees and long-term faculty back, initially. And my own position here is-- got pulled into a leadership role in Indiana University's response to the pandemic, along with three other physician leaders. And we all took on a different component of the response.

So I was involved in the contact tracing, in part because we had some experience with contact tracing and global settings and tuberculosis and HIV. And while the transmission dynamics are obviously quite dramatically different and has different implications, but some of the principles around contact tracing were similar in the sense that contact tracing is not about really a stick, but it's more about extending a carrot and extending the support that allows you then to create an enabling environment-- and a quick phone call, in this case-- to allow people to identify what it is to quarantine and isolate effectively.

To get to the Supreme Court issues and around mandates-- I think it was fairly obvious-- we were part of a restart committee that had been put together by the Dean of the School of Medicine, Jay Hess, and it was fairly noncontroversial among that group that we were going to need vaccine as we marched through this. And we immediately set up a lot of testing infrastructure and what we called mitigation testing at that point of asymptomatic individuals in addition to creating systems that enabled people to-- with symptoms, to enable testing very quickly and to get results back and to get that whole infrastructure in place.

But it was pretty obvious to us-- it was a group of medical, public health, and ethics and legal folks-- that we were going to need a high level of immunity to get back to anything normal, right? And as we began planning for the summer and the fall of 2021, it was like-- it's a no-brainer. I mean, the only way you're going to get high levels of immunity, if you want to bring people back into the same classroom, if you want to have people living in dormitories, if you want to have them engage in the normal activities that college kids want to engage in, then you've got to have a very high level of immunity. And the only way to really achieve that is going to be through vaccine mandates.

And again, it wasn't-- it didn't feel unprecedented, because you have to get a whole bunch of vaccines when you go off to college or when you go to elementary school. And that's really the only way to achieve that high level of coverage that allows us to not have a bunch of measles in our environment. And we still have mumps, despite high levels of coverage.

But yeah, it felt weirdly noncontroversial. But of course, the whole politicization, I think, of the whole response to the pandemic made this more controversial. And clearly, there are people that feel very strongly about it. But I think this-- framing it in a context of personal freedom versus public good has not been particularly healthy for us as a country. I guess I'm not terribly surprised that the Supreme Court ultimately ruled against the preliminary injunction. I think the formal case is still pending, but it's maybe been overtaken by events, because now there are government mandates that are requiring vaccine or regular testing of just about-- lots of different industries and government employees and things.

So I think it was important that we took a stand on this. And I think it has set a precedent, I think, for other universities. There were initially some hospital systems doing the same. But I think it's made it a lot easier to keep moving through industries and health systems with this kind of decision.

PAT LOEHRER: Parenthetically, there's-- this week, they announced the-- we've reached over a million cases of COVID in Indiana. But the lowest county for infectious rate is actually Monroe County, which is where Bloomington is, where Indiana University is. And it's less than half of the rate of the state. And so I think kudos to you and the staff that have done this.

Just maybe briefly, could you reflect on your experiences in Kenya, here in the United States-- lessons learned by you or by the university or by public officials about the contrast? I am reflecting now about a patient I saw today, that-- we were talking about the booster vaccine. And unfortunately, in Kenya, most people haven't gotten their first vaccine, either. So reflect a little bit about the global impact as you've seen personally.

ADRIAN GARDNER: Yeah. So again, I think it's felt like two different worlds, but obviously struggling with the same thing, right? So I think on a global perspective-- so Kenya has-- Kenya got off to a pretty good start because they were kind of late to the game when it came to COVID, and they were able to jump on and learn from some of the lessons about physical distancing and shutting things down that actually enabled them to escape in the beginning.

Of course, there was probably transmission going on behind the scenes that we weren't detecting, and even till now, the numbers that are officially reported are really just the tip of the iceberg. I think know that. Kenya has only reported 250,000 cases and just over 5,000 fatalities nationwide since the beginning of the pandemic. But there are serology studies that suggest that 50%, 60% of the population may have actually been infected-- at least, right? And that's based on blood donor studies and things.

So I mean, I think some of the initial challenges, obviously, around access to PPE-- as we think about health care settings there, which are-- our partnership is based in, as you know. It's just the lack of infection control and the ability to even think about infection control because you're lacking space. As you know, Pat, in many of these wards in low-resource settings, there are two patients in every bed. And one might have active pulmonary TB and one might be getting chemotherapy for breast cancer. And it's less than ideal.

But as you think about how to respond to that, it's pretty hard when you don't have any space, right? I mean, we did a lot here in terms of retooling space and utilizing space that was not being used and putting in negative pressure rooms where they were needed and this kind of thing that just weren't options in Kenya.

One good news was that I think in Kenya, in particular, the testing capacity was able to get an early jump because the HIV infrastructure, PEPFAR, the President's Emergency Plan for AIDS Relief, had established seven regional laboratories that were obviously running HIV viral loads and so had PCR platforms. And they were able to rapidly retool those and convert them into COVID testing laboratories for PCR.

So that was good, but then never really got to the same point where we need to get to, which is that it's readily accessible to everyone in rural regions and rapid testing in order to inform triage protocols [INAUDIBLE] patients and try to figure out how to develop that. So there's been testing available, but just not in the quantities that were sufficient.

You know, I think we've been able to work across virtual platforms to share knowledge about management and clinical protocol development. That's been another success story. Certainly our partnership is longstanding and so has allowed those relationships that have withstood the test of nonpersonal interaction.

And of course, the biggest elephant in the room now is this issue of vaccine equity, as you pointed out. So about 5% of the population in Kenya has been vaccinated. Part of that is vaccine access. Part of it is probability distribution infrastructure. Think about low resource settings-- many of them do quite well with vaccine delivery, but they're early childhood vaccines, right? So they have whole infrastructure around maternal child health that's set up to do this.

There's not a lot of infrastructure for rapidly mobilizing 50 million adults to try and get them in for a two-shot series. So how do you do that? I mean, yes there are some community assets in terms of community health workers and things, but so far, at least, the vaccine quantities available have not been sufficient to allow that kind of infrastructure to really take over, at least in Kenya. But it holds promise, I think.

But then they also are up against the same, I think-- some of the same challenges that we face here in terms of vaccine misinformation and lack of trust. This is an area where I think trust is really key ingredient in health systems, and I think we've seen it in our own inequalities that have been made very, very obvious in our own country and really, the issue globally. And it's not a new lesson. We knew it from Ebola and other very obvious infectious diseases that have resulted in high degrees of death because of lack of trust.

When I have taken care of patients here and I've had those same experiences that Dave was talking about earlier, where you want to just ask the patient, so why didn't you get vaccinated? As an infectious disease provider, we've been called in to a lot of these cases, and I've taken the opportunity to ask a couple of times-- not in a judgmental way, but trying to set the stage and just-- what is it about the system? And a lot of-- some of it is misinformation. Some of it is this politicization and political bias.

But some of it is just a very subtle mistrust and this notion that you don't feel completely welcomed or resected within the health care setting. And that's enough to just turn it off to this point where, eh, I'm just not ready to do that. And I think that's sometimes more subtle than we appreciate, but it has a huge impact.

DAVE JOHNSON: We're getting close to the end of our time. I want to pivot back, if I may, just for a quick moment to Bryan. This may be an out of-- from left field type of question, but we learned a lot about early chemotherapy from the infectious disease world. We took some of the infectious disease principles and applied them in the early years of chemotherapy.

Do you think there's much to be learned from a precision medicine standpoint from the COVID pandemic? What are you taking away from not just your personal experience but the larger experience, if anything? Or is that just-- is it just too early to say?

BRYAN SCHNEIDER: No, I mean-- I think I've always admired the speed and efficiency with which breakthroughs have happened in infectious disease. And I mean, the idea of a brand new virus coming on board a couple of years ago and coming to the point where we are today shows, I think, real innovation, but the ability to get behind a question and, as a community, answer it well. And I think from that standpoint, that's something that all disciplines, including oncology, can learn.

I certainly think we're seeing more and more intersection, too, with the way we think about treating cancer and its impact on immunity. And so certainly in that way I think there's real connections. But I do think some of the innovations that were brought about from the NCI with the vaccines are going to really also herald in things that will be game-changers in the world of oncology and therapeutics as well.

DAVE JOHNSON: That's great.

PAT LOEHRER: If I can throw in something, too-- I think, Dave, particularly as we talk about global health, many of the cancers that we see in the low-to-middle income countries are caused by viruses. One of the number one causes of cancer in sub-Saharan Africa is cervical cancer. We could eradicate that by getting vaccines out there.

In terms of the lessons learned, I think the lessons learned in oncology is that we need to deal more with population health and with prevention than we do with the treatment towards the end of the life. And hopefully that will be a lesson that we can take home with us around the world.

ADRIAN GARDNER: Yeah, and Pat, I think we do need to do better as a global community in terms of sharing vaccine and getting manufacturing up, and not just for vaccines but PPE and therapeutics. It's just not fair, the world we live in now. And at least we all know that and we take it for granted in some ways. But it shouldn't be this unfair, right? And that's been part of the problem globally, and it's part of the problem in the United States.

DAVE JOHNSON: Yeah.

PAT LOEHRER: But the tail end also is access to drugs for chemotherapy, too, and to have radiation available for all these patients. So it is-- this access is an important part of health equity globally. And I think it behooves all of us to be involved with this mission.

DAVE JOHNSON: Well, again, we've come to the end of our time. And we want to thank all of our listeners, but most of all, we really want to thank Bryan and Adrian for a wonderful interview. We really appreciate your time and you sharing your experiences with us.

Thanks again to the listeners for tuning in to Oncology Etc. This is an ASCO educational podcast. We want to talk really about anything and everything, so if you have an idea for a topic or a guest, we invite you to share that with us and email us at [email protected]. So thanks again. And remember, Pat, I before E except after C.

PAT LOEHRER: [LAUGHS] Well, I'll see you later, then.

DAVE JOHNSON: No, wait a minute. Wait a minute. Eight, leisure, sovereign, weight, weird, foreign, vein, neighbor-- apparently it doesn't work.

[LAUGHTER]

My second-grade teacher taught me that rule, and it's just wrong.

[MUSIC PLAYING]

SPEAKER: Thank you for listening to this week's episode. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

In the second part of this Oncology, Etc. episode Drs. Patrick Loehrer (Indiana University) and David Johnson (University of Texas) continue their conversation with Dr. Susan Desmond-Hellmann, exploring the prominent leadership roles she held, from first female Chancellor at UCSF to CEO of the Bill and Melinda Gates Foundation and member of Facebook’s Board of Directors.

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Air Date: 11/18/21

TRANSCRIPT

SPEAKER 1: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

PAT LOEHRER: Hi, Everybody. I'm Pat Loehrer. I'm director of the Centers of Global Health at Indiana University, Melvin and Bren Simon Comprehensive Cancer Center.

DAVE JOHNSON: And I'm Dave Johnson. I'm Professor of Medicine here at UT Southwestern Medical School in Dallas, Texas. So Pat, we're back for another episode of the award winning "Oncology Et Cetera."

PAT LOEHRER: Just seems like last month we were here time, you know? Time just flies.

DAVE JOHNSON: Exactly. Before we get started, you were telling me about an interesting book you were reading-- something about friends or something. Can you elaborate?

PAT LOEHRER: Sure, sure, yeah. This book I picked up-- actually, my wife picked it up. It's called First Friends.

It's written by Gary Ginsburg. It's a really interesting book. It was-- basically talks about-- it probably has about eight or nine presidents but the importance of having a friend that guides him.

And these were people that were, in many ways, unelected people that were close to the presidents that helped change the face of what we see today, and some of them are stories of really good friends and some of them are, I think, opportunistic friends. But it gives you a background of people like Madison and Lincoln and Roosevelt and Woodrow Wilson. It's actually a fun read.

DAVE JOHNSON: I'll definitely put it on my reading list. It sounds like a pretty exciting one. Well, speaking of influential people, we're really excited to jump back into our interview with Dr. Helman.

In our last episode, we covered her early life and career, her work in Uganda, her views on global oncology, and her experiences in private practice and industry. In the next half of our interview, we'll learn more about her incredible career and her multiple leadership roles. Let's start by hearing about her time as chancellor of UCSF.

PAT LOEHRER: Let me transition a little bit. What I'd like to do is talk a little bit about your leadership. One Of the next big roles you had, you became chancellor at UCSF, correct?

SPEAKER 2: Mm-hm.

PAT LOEHRER: And so as Dave said, I think you were the first woman in that role.

SPEAKER 2: I was.

PAT LOEHRER: You were a groundbreaker from that capacity. So now instead of working for people-- obviously, I understand that there's people you work for when you're chancellor too, but tell a little bit about that transition from industry back into academics and how that felt in the role of being a leader and then maybe the responsibility of being the first female chancellor.

SPEAKER 2: There were parts of being the chancellor at UCSF, I would say most parts of it, that I just thought were fantastic. I loved being back at a hospital and clinics. Just the way the hospital and clinical enterprise at UCSF works, the chancellor is the board.

And so once a month, you'd have neurology or cardiology come and tell you about what had happened, quality control, things that had gone on and I would have done that all day long. I mean, it was just so interesting. It was so important to run a great clinical enterprise that getting back closer to patients and medicine I thought was fantastic.

The other thing was the educational enterprise, and UCSF, as you know, has medicine, pharmacy, dentistry, nursing. I always tell people, no undergraduates, no English majors, no marching band. And the other chancellors reminded me, no athletic director, which apparently is a very good thing.

So UCSF is a very special and unusual place. And I loved the science. I would show up at research seminars and things like that as often as I could. So there were so many parts of being at UCSF that I thought were just off the charts great.

The hardest thing about being at UCSF-- being the first female chancellor, I think, was challenging but not in ways that you might expect. I was used to being a woman leader in medicine and biotech, which was unusual. So being the only woman in the room, being the first, wasn't new to me.

But the thing that was hard on our family was there are roles for the spouse of the chancellor that fit more neatly into more of a classic female role, hosting things. There was a tea party for the wives of the faculty that the wife of the chancellor typically had. And for some reason, Nick didn't think that that suited him. We sort of laughed about that.

DAVE JOHNSON: He can't make tea?

SPEAKER 2: He can't make tea to save his life. And he's a strong introvert, which made it worse. I will tell you, some of the under-recognized, underreported people in life are spouses of chancellors and presidents of universities.

And talk about unpaid labor-- my goodness! And so we sort of struggled with how did Nick show up, what did that look like. Because we didn't have any role models for what that looked like. I still laugh that Bill Clinton said he would be First Laddie.

So when you have a pattern recognition, life is easier. And then being one of 10 chancellors at the UC system, I struggled a little bit with the UC Regents just because it felt-- I became chancellor in 2009, and we had some fiscal realities that we were dealing with. And the pace of the UC Regents and the format of the UC Regents, I actually made a proposal for UCSF to kind of break off from the other 9.

And that was not well-received, got me in the newspaper. And I did not do that again. People saw it as disloyal and not very smart. But all in all, I thought then and think now that our public universities are absolutely-- they're treasures in America. And I was really proud to be a part of it and hope that I had made a contribution.

DAVE JOHNSON: Speaking of leadership, what was it like to be CEO of the Bill and Melinda Gates Foundation? What caused you to step away from chancellor to philanthropy?

PAT LOEHRER: It's not a step down. It's not a step down, basically.

DAVE JOHNSON: It is not a step down.

SPEAKER 2: So I would say a couple of things. First of all, Bill and Melinda pushed me hard to take the job. I was not looking to change.

My husband worked at the Gates Foundation for a couple of years on HIV. So they knew us, and they knew Nick better than me. But they knew both of us.

We awarded Melinda the University medal at UCSF. And to my great surprise and happiness, she accepted and came. I later think that she was using that as a reason to talk to me about the CEO job, but she got a twofer.

And I was really compelled by the mission. Who wouldn't be? I was really compelled by the mission and the chance to get back into global health after the experience I had had in Uganda.

But I'll tell you, it is the ambition of the Gate Foundation, the scope of the Gates Foundation, the resources, and the need to get something done. I tell you, it is hard work. It is really hard work-- from China to India to all of the continent of Africa and then US education.

Throw that in on top of things. So I was thrilled to be a part of driving the agenda and the mission. Some really talented people who are working very hard at the Gates Foundation-- I was surprised, especially on US education, with the amount of pushback. And I worked really hard to be successful at working with Bill, who's known as a tough character and lived up to that mutation.

DAVE JOHNSON: Good to know, just in case he calls Pat or me.

PAT LOEHRER: Yeah, yeah, I'm not going to get a medal at UCSF either. So that's a--

DAVE JOHNSON: You never know, Pat.

PAT LOEHRER: It's a non-starter. And this may not apply to you, but there's a lot of maybe disproportionate number of women who feel they suffer from this imposter syndrome. To be honest, Dave and I have talked about that.

We both feel in that syndrome too. But along the way, I mean, if you think about growing up in Reno, Nevada, and suddenly now being a chancellor and head of the Gates Foundation, the National Academy of Science, was there ever this sense of the, wait a minute, you know, what's going on? Is this real?

SPEAKER 2: For me, there has always been that sense. There has always been that sense, and I look at it as I hope there always will be that sense-- that the kind of need to demonstrate your value. And there's a part of the imposter syndrome that is humility and not overestimating what you can do.

And so on my best days, I think that leads me to say I've got to work with really terrific people. My job is to bring out the best in others. If I lead, it's because there's a great thing we're going to accomplish, and I can help people see where we're going together.

And so I definitely have had imposter syndrome. But the one thing that I probably overused and kind of grew to like too much was the thing of people underestimating me and then proving them wrong. That gets a little wearying after a while.

It's like, OK, we're going to waste some time while you decide whether I'm worthy or whether I can do this. And let's not waste that time. Why don't you assign to me-- give me some confidence, and I'll live up to that.

And I mentioned Art Levinson was my boss for most of the time I was at Genentech. And he had no time for imposter syndrome. He was like, look, how many promotions do you have to get before you think, OK, I can get this done?

He thought that was sort of-- he just didn't have time for it. We have things to do, and he had jobs to get done. And one of the things I loved about him is he would constantly push me to say, you're capable of more than you think you are, which I think is the sign of a fantastic manager, which he was and is.

And so I've tried to push myself to do that. And the thing is, like, you can do this. Come to me for help.

We'll make sure you succeed, but don't underestimate yourself. And I think that's a consequence of imposter syndrome is both wasting time proving yourself and not taking on something that you think, actually, let me give that a try and stack the deck in favor of succeeding. And so I think that's the thing that-- there's a certain fierceness that I've always had that I like about myself that, like, of course we will succeed.

Failure is not an option. Of course we will succeed. And I think that comes from working on things that I value a lot and care about a lot.

PAT LOEHRER: You have been on a number of different boards, including Pfizer as well as Facebook. And in that capacity, you've seen a lot of leaders. Can you talk a little bit about the strengths and the weakness of various leaders as well as serving on the boards and the capacities of the different companies?

SPEAKER 2: Yeah, well, first, let me say I know ASCO is actually a really good about being careful about conflicts of interest and things like that, and I am too. So when I became chancellor at UCSF and then CEO at the Gates Foundation, I avoided being on life sciences boards. And so I got asked a lot by Biotech and pharma boards to be on their boards.

Initially, I joined Procter Gamble's board, where I served for, I think, about six years. And then I joined Facebook's board. And those were both fantastic experiences.

And I actually joined the boards for two very different reasons. One, P&G's board, I wanted to learn about branding and consumers. And I felt like in medicine, I didn't really learn about consumers or branding as much as I needed to or might.

And then Facebook's board I joined because as Dave mentioned, I was with Charles Sawyers. We wrote the precision medicine report for the National Academy. And I really love-- to this day, I love the concept of using the social network to connect people.

There was sort of an infamous story or famous story-- it's actually a good story-- of patients with a certain form of myeloma who found each other on Facebook and went to Genentech and said, make a new medicine for those of us with this genetic abnormality. And we'll all enroll in a trial. And so these connections to me felt really powerful on precision medicine.

And so getting to work with CEOs at Procter and Gamble, the CEO Mark Zuckerberg at Facebook, I do see the really different attributes of leaders. But when you're a board member, you see those attributes of leaders with a very different lens. What's the return to shareholders?

How does the community think about them? What's the impact-- and increasingly for Facebook, what's the impact on the world? What's the impact on our social discourse and our ability to have a free and fair election? A lot of those things became much more operative on the Facebook board while I was on the board and really tough social issues that continue to this day.

DAVE JOHNSON: Yeah, so we could go on for another hour, hour and a half, but I have one question to ask you which may seem a little bit silly in retrospect. But if you could look back on your youthful self at 21 or 22 knowing what you know now, with all the things that you've done during the course of your career, what advice would you give yourself? And perhaps I'll addend that by saying what advice would you give particularly to young women in the medical profession who are trying to balance that work-life balance that everyone talks about and worries about and struggles with, quite frankly.

SPEAKER 2: I'll give you one thing I should have done better and one thing that I think I did well. So the advice on the one thing I should have done better, I think slow down a little bit and take a bit more time for fun and enjoyment. I was extremely worried about money when I was in college, and being number two of seven-- every summer, I worked.

I remember at one point in medical school, I had three weeks off, and I got a job for those three weeks at a deli making sandwiches. And I went to college for three years, crammed it into three years so I wouldn't have to pay for the fourth year. So I just think that I could have taken on more loans.

I could have done some things to just dial it down a bit because you don't get those years back. And that's such a great time of your life when you're 21, 22, something like that. So I wish I'd have just slowed down a bit and not been so driven for those seven years of university and medical school that I really just either worked or studied all the time.

The thing that I feel like I did well, and I would say this to anybody who's going into medicine, is there's so many opportunities. There's so many wonderful things to do. But whoever your spouse is, whoever your partner in life is, take the time and energy to make sure that's the right person for you.

I feel so blessed. Actually, my husband, who I've mentioned several times in this discussion, Nick, was my roommate in San Francisco when I was an intern, like real roommate. And we've been roommates ever since.

And we're very compatible. He's one of seven kids too. It's another Catholic school kid.

And we just have fun together and support each other. And there's no way I could have taken these crazy jobs or done the kinds of things I've done without Nick. So having a wonderful, supportive partner makes everything better.

DAVE JOHNSON: That definitely resonates with Pat and me. We're both very blessed to have wives and spouses of, for me, it's 52 years. I can't remember, Pat. Yours is close.

PAT LOEHRER: I had my first date with my wife 50 years ago, yeah.

DAVE JOHNSON: Yeah.

SPEAKER 2: OK, so you guys know what I'm talking about.

PAT LOEHRER: Absolutely.

DAVE JOHNSON: Yeah.

PAT LOEHRER: Yeah.

DAVE JOHNSON: Go ahead, Pat.

PAT LOEHRER: I was going to ask a question that you probably may have already answered there, but Bob Woodward just came out of an interview with Colin Powell. One of the last questions he asked him was if he could reflect on that one person that was a moral compass for him. And so for you, that one person, alive or dead, that has been not the most powerful person you've met but the one that's really influenced you the most in terms of giving you direction, who would that be for you?

SPEAKER 2: Probably, if I look at through line the entire time I've been alive, it would be my dad. He had the ability to look at a room and find the person who was struggling and go over to them. And I really loved that about my dad.

PAT LOEHRER: I love it.

DAVE JOHNSON: One last question. So we're at the top of the hour, and I know you're a very busy person. Pat and I love to read, but we're also documentary fiends and whatnot.

We're interested. What have you read recently that really resonated with you? Do you have a recommendation for us?

SPEAKER 2: I will say during the pandemic, I've gotten back into reading biographies, which I love.

DAVE JOHNSON: Yeah.

SPEAKER 2: So I did the Caro, Lyndon Baines Johnson, which, Master of the Senate is really good. But my favorite book of the last two years is The Code Breaker, Walter Isaacson's book about Jennifer Doudna.

DAVE JOHNSON: Yeah.

SPEAKER 2: One of the things I love about Walter Isaacson is he teaches you science through his biographies. Like, I think I understand relativity based on his Einstein biography, which is great. But The Code Breaker is really super good.

DAVE JOHNSON: Yeah, we both read it. We couldn't agree with you more.

PAT LOEHRER: Love it. Love it.

DAVE JOHNSON: So Sue, again, it's been a real honor to have you as our guest, and we really appreciate the time you've taken. Thank you so much, and we hope you enjoy the beautiful weather in Alamo California, and I hope it does turn green and the rain continues for you.

SPEAKER 2: Thank you so much. It's been my pleasure. Thank you both.

DAVE JOHNSON: Take care.

SPEAKER 2: Bye.

DAVE JOHNSON: I want to take the moment to thank our listeners for tuning in to "Oncology Et Cetera," an ASCO educational podcast where Pat and I really will talk about anything and everything. So if you have an idea or a topic you'd like to share with us and like for us to pursue, please email us at [email protected]. Thanks again, and keep in mind that Pat is a giant in oncology, but he's a short instructor. Thanks, everybody.

SPEAKER 1: Thank you for listening to this week's-- to make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

In the second part of this ASCO Education Podcast episode, Dr. Sonali Smith (University of Chicago Medicine) and Dr. Paolo Strati (MD Anderson Cancer Center) discuss the application of new therapies for mantle cell lymphoma and follicular lymphoma through examination of challenging patient cases.

Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us

Air Date: 11/15/21

TRANSCRIPT

[MUSIC PLAYING]

SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

[MUSIC PLAYING]

SONALI SMITH: Hello, and welcome to part 2 of ASCO Education Podcast on New Therapies for Lymphoma. My name is Dr. Sonali Smith, and I'm a hematologist and medical oncologist specializing in lymphoma and clinical trials for lymphoma. I am also the Elwood V. Jensen professor and chief of the Hematology and Oncology section at the University of Chicago.

PAOLO STRATI: Hello to everybody. I'm Dr. Paolo Strati. I'm a hematologist, and medical oncologist, and assistant professor in the Department of Lymphoma and Myeloma and in the Department of Translational and Molecular Pathology at the University of Texas MD Anderson Cancer Center in Houston, Texas. In part one of this podcast episode, we discuss recently approved therapies for diffuse large B-cell lymphoma. And today, we will be exploring instead new therapies for follicular lymphoma and new therapies for mantle cell lymphoma.

SONALI SMITH: Wonderful. So we are going to start off today with a discussion about a patient case. The individual is a 55-year-old woman with previously untreated follicular lymphoma, low-grade advanced stage, and low tumor burden, and low FLIPI. She was diagnosed three years ago and had observation but more recently developed a 7-centimeter retroperitoneal mass with impending ureteral compression and no PET/C concern for transformation, specifically with an SUVmax of 5.3.

Despite this radiological finding, the patient had a performance status of 0, no symptoms, no significant comorbid health conditions, and was given R-CHOP time six cycles, followed by achievement of a CR. She was then observed, but, unfortunately, 18 months later, the PET/C showed diffuse low FDG-uptake adenopathy, and a lymph-node biopsy was repeated. This showed a follicular-lymphoma relapse.

So Dr. Strati, tell us a little bit about your approach to follicular lymphoma in the initial setting. Do you consider GELF criteria? And how do you select second-line therapy in this patient? Does the early progression of disease within 18 months-- she falls into the category of POD24, or the Progression Of Disease 24 months-- how does this affect your treatment choice going forward?

PAOLO STRATI: Thank you, Dr. Smith. Those are all very good questions. So going to your first question-- we typically use GELF criteria, as you know, developed in France now many years ago, most of the time of initial diagnosis. And that's to determine whether a follicular-lymphoma patient does, indeed, have an indication for treatment.

And this criteria, as you know, are based on lymph node size and number, oragnomegaly, cytopenia. However, it's still debated whether this should also be applied at time of relapse. And in this particular case, the patient, as you said, had what we call a POD24, or progression of disease within 24 months from initiation of chemoimmunotherapy.

Given the suboptimal outcome of these patients, I think that it will not be unreasonable to treat these patients even if they don't formally meet GELF criteria-- so even if they don't have formal indication for treatment at time of relapse. Once the decision is made, standard second-line options for patients with follicular lymphoma currently include chemoimmunotherapy

So if the patient received R-CHOP in frontline, it would be BR. But if they receive BR in frontline, of course, R-CHOP, but also, immunotherapy with R-squared-- so Rituximab, Revlimid-- or lenalidomide, a single-agent anti-CD20 monoclonal antibody, obinutuzumab, which is specifically approved by the FDA in the United States for rituximab-refractory follicular-lymphoma patients, and in very selected cases-- and this is still open for debate-- a high-dose chemo with a platinum-based agent followed by autologous stem-cell transplant.

We don't know at this time what's the ideal second-line strategy for patients like the one that you described in your case-- so a follicular-lymphoma patient with POD24. And to this regard, all are very eagerly awaiting the results of an ongoing SWOG trial, 1608, which is a randomized phase II study comparing in second-line chemoimmunotherapy, immunotherapy, and also, [INAUDIBLE] kinase inhibitor for this patient with POD24.

Finally, one thing which I think is important to consider is that even if R-squared is not currently approved by the FDA in the frontline setting in the United States and, actually, is not approved at all in Canada, in Europe as a frontline treatment, in the United States, it's possible to use it in frontline thanks to existing guidelines. And over the last few years, its frontline use in our country has actually meaningfully increased.

This is creating a new clinical scenario that we never met before. And there are no standard second-line options currently established for these patients, patients who receive frontline R-squared, emphasizing the need of translational research to understand more of the biology of patients who relapse after frontline R-squared but also, emphasizing the need to mostly look into clinical trials when these patients, unfortunately, experience a relapse.

SONALI SMITH: Yes, thank you, Dr. Strati. I agree. I think that it is the way that frontline follicular lymphoma and in the relapsed setting exists is that we have a toolbox and no real clear data on how to personalize the therapy. So your comment about needing some better translational work to fine-tune the clinical trials is really important.

So for this patient, though, she did receive R-squared for 12 cycles and achieved a complete remission after six cycles. 12 months later, a PET/CT showed diffuse, low-level adenopathy, "low level" meaning low uptake on a PET scan. And she had another lymph-node biopsy. This showed persistent follicular lymphoma. So now how do you select your third-line option knowing that we have biologic therapy, as well as cellular therapy, available to this patient?

PAOLO STRATI: So going back to the metaphor that I used before, we have a very nice toolbox, often third-line. But also, in third-line, there's really no strong, robust translational data to drive us when it comes to treatment selection. Agents currently approved by the FDA in the United States as a third-line standard option for patients with relapsed/refractory follicular lymphoma include, as you alluded, [INAUDIBLE] kinase inhibitors, currently three-- copanlisib, duvelisib, and idelalisib, and an EZH2 inhibitor called tazemetostat.

The three [INAUDIBLE] kinase inhibitors currently approved in third line have very similar efficacy with a response rate of 50% and a median progression-free survival of about 10 months. And the selection among the three is typically based on toxicity profile, which is more on the autoimmune side for duvelisib and idelalisib and more on the metabolic side with hyperglycemia and hypertension for copanlisib.

Also, one element that, in my experience, is typically used to select one of these three is the route and the frequency of administration because we have to remember that idelalisib and duvelisib are both given orally twice a day, whereas copanlisib is given intravenously three times a month. And so, of course, different patients may have different preferences.

As a matter of fact, though, the use of [INAUDIBLE] kinase inhibitors for relapsed follicular lymphoma in the United States and I would say, also, in other countries, is quite limited, mostly due to toxicity and relatively limited efficacy. Tazemetostat, the EZH2 H2 inhibitor that I mentioned previously, has a response rate that can vary between 30% and up to 70%, significantly higher in patients who do have a documented EZH2 mutation. But the median progression-free survival is about a year, no matter whether the mutation is present-- so not that different from [INAUDIBLE] kinase inhibitors in the same setting.

Of interest, given the short duration of response, we may consider these agents as a bridging therapy for follicular-lymphoma patients. We [INAUDIBLE] proceed with CAR T-cell therapy because, as you mentioned in your question, CAR T-cell therapy, and specifically, Axi-cel, has been recently approved by the FDA as a third-line option for patients with relapsed/refractory follicular lymphoma based on results from the ZUMA-5 study.

It's important, however, to emphasize that Axi-cel has shown better efficacy and safety data in follicular-lymphoma patients as compared to large B-cell lymphoma patients than we discussed in the previous episode of this podcast. And, as such, Axi-cel may potentially represent a curative option for patients with follicular lymphoma, a condition that, historically, has been considered incurable.

Tisa-cel and other CAR T-cell products targeting CD19 currently approved by the FDA for large B-cell lymphoma but not yet for follicular lymphoma, may also be soon approved by the FDA for patients with follicular lymphoma based on the ELARA study. And we're all eagerly awaiting the results of this study and, potentially, its approval in the next few months.

SONALI SMITH: That's great to hear. And, hopefully, we will continue to have more options, including more cellular-therapy options for patients. So this particular patient proceeded with the standard of care Axi-cel. That went quite well.

There was only grade 1 cytokine release syndrome, no neurotoxicity. And the patient achieved a complete remission on both the day-30 and the day-90 PET/CT. Unfortunately, there was relapsed six months later. So what standard options are there at this time? And would you consider an allogeneic stem-cell transplant at this point?

PAOLO STRATI: So I have to say that, based on some of my data, I'm not surprised this patient did quite well in terms of safety, and I'm very sorry to hear that was one of those few patients who relapsed after an initial complete remission after Axi-cel. In fourth line, our options are a little bit more limited. The FDA has recently approved in fourth line, for patients with relapsed/refractory follicular lymphoma, a new [INAUDIBLE] kinase inhibitor called umbralisib.

[INAUDIBLE] umbralisib response rate is quite similar to other [INAUDIBLE] kinase inhibitors, about 50%. However, the median progression-free survival that, as I mentioned before, is about 10 months for the [INAUDIBLE] kinase inhibitors currently improving third line instead has not be reached yet two years for umbralisib. And also, the toxicity profile seems to be more limited, similarly to idelalisib and duvelisib, more on the autoimmune side. Therefore, definitely umbralisib would be an interesting option for the patient case that you described.

As for your second question, the possibility to use allogeneic stem-cell transplant for patients with relapsed/refractory follicular lymphoma, retrospective studies have shown the allogeneic transplant is effective in follicular-lymphoma patients, particularly those with POD24, like the patient you described in the scenario.

But the transfer-related mortality is significant and needs to be taken into consideration. But most important of all, as CAR T-cell therapy has been approved for follicular lymphoma very recently, we really have no data regarding the use of allogeneic stem-cell transplant in follicular-lymphoma patients who relapse or progress after Axi-cel and CAR T-cell therapy in general.

This last statement really applies to any approach as, again, Axi-cel has been approved for follicular lymphoma only within the last 12 months. And this, once again, emphasizes the importance of translational research and clinical trials for these patients. And as such, I think that, along with umbralisib, there is a standard option. Clinical trial's definitely the best option for patients with follicular lymphoma whose disease is either refractory or relapses after CAR T-cell therapy.

SONALI SMITH: Yes. Thank you for these insights, Dr. Strati. I agree. The post cellular therapy, or the post CAR-T space is a very challenging situation, and I appreciate your perspectives. So as an update, this patient received umbralisib for six months and had an initial response with a partial remission but eventually progressed and then proceeded to a clinical trial, now on a novel oral-immunomodulatory agent and has been in a complete remission for four months.

PAOLO STRATI: That's great to hear. And I hope that this remission will be durable, emphasizing, again, the importance of clinical trials for patients with lymphoma in general, and particularly, those who relapse or are refractory to standard treatments. It was very interesting to listen to this case. Thank you for asking your question, Dr. Smith.

I'm going to ask your opinion now about a second case. This is a 67-year-old man with diabetes that has a long-lasting history of rectal bleeding, for which he underwent a colonoscopy in 2016 that revealed hemorrhoids and scattered polyps that were not malignant on biopsy. However, as part of routine follow-up, a colonoscopy was repeated five years later, and this, unfortunately, showed diffuse nodularity of the colon with several areas of ulceration. Biopsy of the nodules showed a mature B-cell lymphoma, CD20 positive, CD5 positive, BCL2 positive, SOX11 positive, but negative for CD10.

FISH testing confirmed a translocation 11;14. There was no evidence of TP53 mutation, and Ki-67 was 40%. So Dr. Smith, what do you think about the overall potential histological diagnosis? And how do you approach this patient in terms of staging and prognosis discussion?

SONALI SMITH: Yes, so this poor patient, with long-standing rectal bleeding-- I mean, this can happen. It's not a very common presentation for mantle cell lymphoma, but we know that mantle cell lymphoma is very likely to involve the GI tract and can often be extranodal.

In terms of the histology itself, this is very classic. The co-expression of CD20 along with CD5 is only seen in CLL and mantle cell lymphoma. And in this case, the mantle cell lymphoma's confirmed by SOX11 positivity, CD10 negativity, and then, also, of course, the FISH [INAUDIBLE] translocation of 11;14 with a cyclin-D1 overexpression.

When it comes to prognosis in mantle cell lymphoma, there's a number of different prognostic indices, but the two biologic features that I think are most important are P53 status, as well as the proliferation rate. Patients who have a TP53 mutation typically have chemo-resistant disease. And we have no really good approach in terms of how to treat these patients the best.

PAOLO STRATI: Thank you, Dr. Smith, for outlining the diagnostic and prognostic approach to patients with mantle cell lymphoma. You alluded in your answer about the regenerative treatments, so I wanted to ask you, how do you, in general, treat patients with mantle cell lymphoma and, more specifically, this case. And also, we keep dividing patients with mantle cell lymphoma in transplant-eligible and ineligible, but the big question is, do all patients who are transplant-eligible need transplant? And what's year overall approach to this major dilemma?

SONALI SMITH: Yes. That's a really good question. The general approach to treatment for mantle cell lymphoma is based on the concept of fitness and age. So we end up dichotomozing patients into one of two groups. They are either young and fit, or they are older and unfit.

And, of course, this is somewhat controversial because age itself is just a number, and there is significant variability based on function and other medical conditions. Complicating that further is that many clinical trials have used 65 as the arbitrary cutoff between young and old, whereas some transplant studies have actually gone all the way up to age 70. So if I focus on the fact that this is a 67-year-old man who has no real significant history and clearly has a disease that needs treatment, my general approach has been to follow the younger-and-fit approach.

And as you mentioned, the historical approach to this has been to think of treatment in three phases. There is induction, there's consolidation with a high-dose chemotherapy and autologous stem-cell transplant, and then there is maintenance rituximab for three years, which has been shown to have a survival advantage. But your question-- I think there are many unanswered areas when it comes to approaching a patient who is going to be treated with an aggressive multimodality approach.

So first, in terms of the induction itself, there is data that cytarabine-based regimens likely achieve a deeper minimal residual disease state than aklylator-based therapy. And so cytarabine-containing regimens have really become the standard of care against which other regimens are compared. That being said, there was at least a SWOG study that randomized patients between BR and hyper-CVAD and found that BR was a sufficient type of induction.

And some of this controversy led to an ongoing Intergroup trial, which is EA4181, that takes patients with newly diagnosed mantle cell lymphoma, previously untreated, like our patient, and randomizes them to bendamustine, rituximab with or without cytarabine and with or without a BTK inhibitor, in this case, acalabrutinib. So outside of a clinical trial, I would use a h based induction regimen, but I have preferred to put most patients onto that.

But your second question, which is, do all patients need high-dose chemotherapy and autologous stem-cell transplant, is really important. This is associated with a need for inpatient admission, high-dose chemotherapy with subsequent late toxicity. And remembering that mantle cell lymphoma remains an incurable disease, the question is whether or not all patients should get this.

So to address this, there is the EA4151 trial, which is also being done through the United States Intergroup. And this is using a very unique minimal residual-disease assay to randomize patients to either transplant plus maintenance or maintenance alone. And so this is a next-generation sequencing test. And if patients have a negative MRD status at a very deep level, then patients will get randomized to one of those two arms, whereas if they have minimal residual disease that is detectable, then they will go ahead and get the standard of care.

So for this patient, he opted to be on the clinical trial and was randomized to BR, plus cytarabine, plus acalabrutinib. But outside of a trial, I really would have considered intensive induction, including the Nordic regimen that includes high-dose cytarabine, followed by transplant and maintenance rituximab.

Now some may argue with me that this person is 67 years old, and the Nordic regimen is quite intense. And I think this is where some of the art of medicine may come in. And, hopefully, we can have some type of assessment tools to better predict who can tolerate intensive induction. But I'm quite impressed by some of the transplant data that do lead to seven- and 10-year remissions in some cases. Of course, this new trial will tell us whether or not we're overtreating many of the patients, particularly based on their MRD status.

PAOLO STRATI: Thank you, Dr. Smith. It was very helpful. I think you outlined really well how challenging it can be to treat patients with mantle cell lymphoma and how important it is to tailor treatment based on biological but also, patient-related data.

This is all that we have for today. Thank you, Dr. Smith, for a very delightful conversation. It's been very helpful to review together today the treatment of patients with follicular lymphoma, and mantle-cell lymphoma, and safety and efficacy of novel therapies for these patients.

Thanks, everybody. And, particularly, thank you to all the listeners who tune in to this episode of the ASCO Education Podcast. And thank you, Dr. Smith, for your time.

SONALI SMITH: Thank you. It was such a pleasure to have this conversation today.

[MUSIC PLAYING]

SPEAKER: Thank you for listening to this week's episode. To make us part of your weekly routine, click Subscribe. Let us know what you think by leaving a review. For more information, visit the comprehensive e-learning center at elearning.asco.org.

Part one of this two-part Oncology, Etc. episode features an inside look at the amazing career of Dr. Susan Desmond-Hellmann (spanning from early AIDS research in Kenya and drug development at Genentech, to serving as UCSF Chancellor and CEO of the Bill and Melinda Gates Foundation). Hosted by Drs. Patrick Loehrer (Indiana University) and David Johnson (University of Texas).

Subscribe: Apple Podcasts, Google Podcasts | Additional resources: education.asco.org | Contact Us

Air Date: 11/04/21

TRANSCRIPT

[MUSIC PLAYING]

SPEAKER: The purpose of this podcast is to educate and inform. This is not a substitute for medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

DAVE JOHNSON: I'm Dave Johnson. I'm a Professor of Medicine here at UT Southwestern Medical School in Dallas, Texas.

PAT LOEHRER: I'm Pat Loehrer. I'm Director of the Centers of Global Health at Indiana University Melvin and Bren Simon Comprehensive Cancer Center.

DAVE JOHNSON: We have a remarkable guest today, Dr. Susan Desmond-Hellmann. She's like the Wonder Woman of oncology who's done many amazing things during the course of her career. It would take us more than an hour or more just to read off her CV.

But very briefly, Dr. Hellmann is a graduate of the University of Nevada, Reno where she got both her Bachelor and her medical degrees. She received her medical training at the University of California, San Francisco. And then after that, did something really interesting. She went to Uganda for a couple of years and worked at the Ugandan Cancer Institute where-- maybe we can delve into that a little bit later during the course of this discussion to find out what she did while she was there.

After which, she also did a couple of years of private practice and then joined industry, first at Bristol Myers, where she was instrumental in the development of a very important drug for a lot of different diseases-- paclitaxel And then in the mid-90s, she joined this little biotech company called Genentech, first, I think, as a clinical scientist. But over the course of a few years, she rose to the level of president of product development and really was instrumental in developing many drugs, including trastuzumab and bevacizumab.

In fact, I think it was Forbes magazine that named her as one of the world's seven most powerful innovators, which we have to ask her more about that later, about being a powerful innovator. After really a stellar career in the industry, she then went back into academics. She became the chancellor of the University of California, San Francisco, and I believe the first woman to hold that position, if I'm not mistaken.

During her tenure, many remarkable things happened at UCSF, including growth of their campus in the Mission Bay. She was responsible, with a committee put together by the National Academy of Sciences, of producing the report entitled Toward Precision Medicine, Building the Knowledge Network for Biomedical Research and a New Taxonomy of Disease.

In March of 2014, I believe it was, she took yet another position, this time in the world of philanthropy, where she became the chief executive officer of the Bill and Melinda Gates Foundation, a position she held until December of 2019. And that's certainly something we want to ask her about. Dr. Hellmann has many, many accolades. I can't list them all, but she's a member of the Biotech Hall of Fame, the American Academy of Arts and Sciences, the National Academy of Medicine, and she's even received an honorary science degree from Princeton University.

They won't even invite us to the campus, Pats. I'm not sure what it takes to get an honorary degree, but Sue, welcome to Oncology, Etc. And thank you so much for agreeing to this interview.

SUSAN DESMOND-HELLMANN: Well, thank you for having me. I'm really glad to be here and look forward to our conversation.

DAVE JOHNSON: Pat, why don't you ask the first question.

PAT LOEHRER: So Sue, if you could tell us a little bit about yourself from birth until your early career and what shaped your early directions.

SUSAN DESMOND-HELLMANN: Well, I'm actually a California native and grew up in Reno, Nevada, thus the University of Nevada connection. I'm one of seven children. I'm number two. And my affinity for science and medicine and all things regarding patients came from my dad, who was a retail pharmacist. And that's how we moved from California to Nevada.

My dad and his partner Jim opened up one of those Rexall Owl drugstores-- if you ever remember those with the owl picture-- and were partners for many years, ran a pharmacy in Reno, Nevada which, when we got there, was a really small town. And I often chuckle when people say, oh, there's something sort of funny about growing up in Reno, Nevada. Did you go to casinos all the time?

The fact of the matter is that my parents were very strict disciplinarians. We weren't allowed to work in the casinos as summer jobs, much less go to the casinos. I went to Catholic school for 12 years. Going to college was the first time I didn't wear a uniform to school, which was funny. But both my values and my passions came from worshiping my dad and the contributions he made to people feeling better.

PAT LOEHRER: Love it. Love it.

DAVE JOHNSON: It's fantastic. May I ask-- I presume you chose to go to UCSF for your medicine training because of your California connection. Is that right? Or was there other reasons?

SUSAN DESMOND-HELLMANN: There were two main reasons. One is UCSF was far and beyond my number one choice because of its reputation. And when I interviewed there, I just was so astounded that I recognized the names of my medical textbooks among the faculty. That was a big deal for me. Holly Smith was a chair of medicine. I mean, it was the dream to go to UCSF.

My dad was born and raised down the street from UCSF. And my grandma still lived there. And so, for me, it was also-- being the first time I had been away from home-- it was close enough to Reno that it wasn't crazy to drive back for the weekend. So a little bit more close to home and much more importantly, for me, the mecca where I would just get to be around so many talented people.

PAT LOEHRER: When you were there, it was really at the early times of the AIDS pandemic. And there is some wonderful people there that I'm sure you interacted with, included Paul Volberding and the other group. So tell me a little bit about that influence. And that probably led, in part, to the transition to Uganda. But tell us a little bit about that part of your story.

SUSAN DESMOND-HELLMANN: So my time at UCSF, first of all, I think it's, especially being in the midst of COVID-19, it made so many of us recall what it was like to be in San Francisco in 1982. It was really exhausting and terrifying to be a health care provider when so many of your patients-- first of all, they died quickly before antiretrovirals. But there was such a lack of understanding of what was going on initially.

And so the medical program at UCSF, like a lot of programs of its nature, in New York, LA, led to Paul Volberding, Don Abrams, Laurie Kaplan, a lot of colleagues-- the oncologists became AIDS doctors and oncologists, because of Kaposi sarcoma and lymphoma and other maladies. And I remember I did an additional year as chief resident. And one of our concerns was whether or not the medical residents were overweight HIV and underweight kidney disease and hypertension.

And there was a concern that people might not come for the residency because they were worried about catching AIDS. I mean, we were part of a study to test us. And happily, unless you had a needle stick, you really weren't at great risk. But the residency was very much influenced by that. I was very much influenced by that I had a lot of passion for caring for the patients. I think I had a lot of empathy for what they were going through.

And think about this, go home and tell your parents you have HIV. And by the way, they didn't know you were gay, because a lot more people were closeted in those days. That's a really tough set of circumstances. So by the time I was an oncology fellow and then a faculty member, I saw, really, all the patients at UCSF at the University Hospital who had AIDS-related cancers. That became my specialty.

And I was funded by the California State Task Force on AIDS to study Kaposi sarcoma. But when the Rockefeller Foundation came to UCSF to ask them to study heterosexual transmission of HIV, the late Merle Sande and Dick Root asked my husband, who's an infectious disease doc, and I to move to Uganda and accept this Rockefeller grant and study heterosexual transmission of HIV and Kaposi sarcoma.

And I actually think it's a bit of a funny story. But it was less funny then, because I was so uncertain. I had never been east of Chicago at that point in my life. But we flew and moved to Uganda. So I became a global citizen quite quickly. And it was both the most important experience that my husband and I had had in medicine and life.

And to say it was challenging would be an understatement. I mean, we did not have consistent electricity or running water. And we had this multi-page grant where we were supposed to do ELISAs and Western blots. It was a little crazy, but we got some things done and that was the important thing.

DAVE JOHNSON: So Pat's never been further between Indianapolis and Chicago. So he resonates with him.

[LAUGHTER]

DAVE JOHNSON: So you were there how many years? You were there two years, I think.

SUSAN DESMOND-HELLMANN: Two years.

DAVE JOHNSON: And did you accomplish the things that you set out to do while you were there? Or how did that go?

SUSAN DESMOND-HELLMANN: We worked with our Ugandan colleagues and really transformed what you could do at Uganda Cancer Institute at the TB clinic in collaboration with folks from Case Western Reserve and for the AIDS program. So by the time we left, things just were dramatically better and different. We also did a lot of teaching, a lot of patient care. And so there was a service element to what we did, which was really essential that that be part of it.

I had the opportunity, when I was at Gates Foundation in 2019, to return to Uganda. And the one thing you got at Cancer Institute, which was founded by NCI-- our National Cancer Institute, they are excellent at record keeping, all paper. And they dutifully pulled out some of the notes I wrote on my patients with Kaposi sarcoma with the references and citations. So this sort of nerdiness that we had at UCSF did transport to Kampala Uganda.

DAVE JOHNSON: I hope they gave you some copies of those, with the name struck out of course, for your private collection. That's cool.

SUSAN DESMOND-HELLMANN: It was actually pretty astounding to return. And now Fred Hutch has a collaboration with Uganda Cancer Institute and has done a lot of renovations and new science on the virology of Kaposi sarcoma.

PAT LOEHRER: So before we skip from this and move to something else, if you could reflect a little bit about what you currently think the importance of global oncology is. It obviously had an influence on you. And how do you think it should fit in or does fit in now? UCSF has got its fingerprints around the globe now. I'm on their EAB.

SUSAN DESMOND-HELLMANN: Well, let me just say from-- I'll speak to this sort of personally and then in a more big-picture way. Personally, I felt that the slogan of the Gates Foundation and every place can be too "slogan-y," so you always have to be careful about this. But the slogan that I just so had an affinity for is "all lives have equal value." All lives have equal value, for me, says that someone struggling or suffering, no matter where they are in the world, is worthy of our care and attention. And global oncology, I think, reflects that.

So one of the things that I learned when I was there-- and I felt really good about this. I was glad that I learned from colleagues in Uganda and they learned from me. And so there was a real collaboration on figuring out-- I'll give you a real example. As you know, Kaposi sarcoma causes a lot of edema and lymphedema in the lower extremities. Well, if you've got lymphedema in your lower extremities, you can't farm, you can't dig, you can't feed your family.

And we had bleomycin and vincristine. And with a combination of those two, in relatively small amounts to avoid toxicity, I could get someone back on their feet literally. And well, that's a great thing. And so the practical nature of symptom improvement, the avoidance of side effects, the attention to quality of life was amplified by my experience there. So I think those kinds of things-- I always like, in life, you give and you get.

I gave. I contributed. I worked hard. And I got a lot of new knowledge and understanding. In addition, the deep understanding of pathophysiology that came from thinking about African Kaposi sarcoma, Mediterranean Kaposi sarcoma, age-related Kaposi sarcoma. There's just a lot of science, just a lot to learn if you were paying attention and probing what was going on. So I think global oncology is extremely important. And it's important that it be sustainable and appropriate and with, always, service and training as a component, not only research.

PAT LOEHRER: Agreed. I agree.

DAVE JOHNSON: We have so much to cover, I don't want to spoil everything. But I'm really curious when you left Uganda, you went into private practice, right?

SUSAN DESMOND-HELLMANN: Mm-hmm.

DAVE JOHNSON: How did that happen?

SUSAN DESMOND-HELLMANN: We had to pay the rent.

DAVE JOHNSON: There you go.

SUSAN DESMOND-HELLMANN: Yeah. Yeah, when we came back, there was no global health. There was no place for us at UCSF. So we had one of those surreal academic experiences of sitting down with the new chief of medicine and him saying, there's no money for you. So you'll need to do a lot more clinical care and earn your salary.

And Nick, you're going to-- my husband-- you'll need to write at least two R01 grants. And so you better get moving. And we were disappointed that there really wasn't a place or mentorship or anything for us at UCSF. But we didn't have time to lick our wounds. So Nick is from Kentucky. And we moved back to Lexington, Kentucky and went into private practice.

DAVE JOHNSON: Yeah, economic necessity has changed.

SUSAN DESMOND-HELLMANN: I mean, I can make it a little more romantic and interesting, but it was economic necessity. And honestly, I love patients, I love oncology, and I thought that was fine. One of the learnings from that was how deeply I missed research and R&D. And I'm very academically oriented. And so both Nick and I realized, when we were there, that we did very well. People liked seeing us as clinicians. And we were well-trained and could take good care of people. But it wasn't the right fit.

DAVE JOHNSON: So from there, if I remember correctly, you transition to industry.

SUSAN DESMOND-HELLMANN: Yeah, actually it's a good story. So Nick got called up about from Bristol Myers Squibb, did he want to come and join their infectious disease group up in Connecticut at Wallingford. And he said, of course, I would love that. But I won't come unless you take my wife too.

And they said, no, we have a nepotism rule. We won't take your wife. And he said, well, you haven't met her yet. They said, why do we want a private practice oncologist at Bristol Myers Squibb. We need serious clinical trials people. And so Nick was somewhat persistent. And he just said, I won't come. He's a good husband. That's it.

PAT LOEHRER: Sounds like it.

SUSAN DESMOND-HELLMANN: He still is. And so they hired me as a consultant. And they were really busy on Taxol. It had gotten approved for ovarian cancer but not yet for breast cancer. And so I like to say they stuck me doing drug safety. And saying, she's like an LMD, she's a clinician. We'll have her do drug safety. She can't cause too much harm over there.

And I tell you, the opposite of going into private practice, which was just, like I said, not a great fit. I felt like I had died and gone to heaven. First of all, it is probably embarrassing and says something about me, I loved drug safety-- loved, loved, loved drugs-- it's like thinking like an epidemiologist, a clinician, a good physician.

You know, I love statistics and epi. I had gotten an MPH at Berkeley while I was an oncology fellow. And I just love analytics and inference and all of that stuff.

And so after a couple of months they had changed me-- they got a dispensation from the CEO so I could be a real employee. And I became the project team leader for Taxol, which was fantastic. It was such a great experience. I loved the colleagues at BMS. And we were making one of the first new oncology drugs in a while.

DAVE JOHNSON: Yeah, I think, if memory serves me correctly, that's about the time we first met.

SUSAN DESMOND-HELLMANN: Yes.

DAVE JOHNSON: And paclitaxel was being investigated in lung cancer. And that really is our connection. But those were heady times. We thought we were on top of the world.

SUSAN DESMOND-HELLMANN: Well, you know, it had been a while since there had been new active chemotherapies in oncology. And they were heady times. It was also just so interesting and hard to remember now how much the toxicity of paclitaxel had put it on the shelf, this hypersensitivity reactions and the collaboration with the National Cancer Institute.

There was a lot about the product development of paclitaxel that I remember and learn from. And I was just really grateful to be with Renzo Canetta and people like that, who it felt like going to UCSF where I thought, OK, Floyd Rector in nephrology. Now I get all these folks who I was using bleomycin and platinums. And they had written those package inserts.

DAVE JOHNSON: Yeah.

PAT LOEHRER: Yeah Bristol Myers basically owned oncology. I mean, all the products were going on there. And at that time, as you guys know, there's only one or two drugs a year that got approved for oncology. And today it is vastly different where each week there's a new drug or a new indication for oncology. The world has just changed tremendously.

SUSAN DESMOND-HELLMANN: Yes.

PAT LOEHRER: Yeah, it's been incredible. So Dave, where do you want to go next on this one?

DAVE JOHNSON: Well, I think one of the things that I think our listeners might want to learn about is Sue's transition to Genentech. I mean, it wasn't like the powerhouse organization it is today when you went there. I mean, not that it was a hole in the wall, but it wasn't the biomedical powerhouse that it is. What attracted you? I'd love to hear from you, what brought you to Genentech?

SUSAN DESMOND-HELLMANN: So I would say three things. The first thing was Art and his ambition. And so Art--

DAVE JOHNSON: You might want to tell people who Art is.

SUSAN DESMOND-HELLMANN: So Art Levinson, who then was the head of R&D and later became the CEO of Genentech, so Art Levinson worked in Mike Bishop's lab at UCSF. And so he, in many ways, showed up as a molecular oncologist as the head of R&D at Genentech. And his ambition was that Genentech would be an oncology company.

When I talked to Genentech, they had precisely zero oncology drugs. The furthest along was gamma interferon in their pipeline. So it didn't actually look very promising at the time. But Art was very compelling to talk to, and his dream.

The second thing was research. Bristol Myers Squibb was fantastic. But especially being in Connecticut, where you were sort of removed from the research enterprise, I saw BMS as fantastic clinical development organization and sales organization. They did a lot of licensing deals. That was their claim to fame was they were really good at licensing. And I respected that a lot.

But the ability to sit down with the research folks and think about what you would do with an anti-HER2 or an anti-VEGF-- and I just really respected Genetech's research capabilities and organization. And the third thing was we made the decision-- which wasn't an easy decision to make.

We had built a house in Connecticut. We were happy there. I don't know if you remember the winter of '94 was huge blizzards in Connecticut. Before we moved to Connecticut, I didn't even own a winter coat. So it was rough to experience winter in the Northeast. And my family was in Reno and San Francisco. And so moving back here was compelling.

PAT LOEHRER: Not the romance that you had in Christmas in Connecticut with Bing Crosby. It just wasn't the same, was it?

SUSAN DESMOND-HELLMANN: Well, I did love fall. I'll tell you, nothing like autumn in Connecticut. There's a lot to like about Connecticut. So it wasn't an easy move. But coming back West was a good thing.

DAVE JOHNSON: Well, what was the first really successful product that you worked on with Genentech? I should know, but I don't remember.

SUSAN DESMOND-HELLMANN: Oh, the first successful product that I worked on with Genentech was a collaboration with IDEC on Rituxan. And rituximab was really interesting because there's some real heroes at Genentech, including a business development guy, David Ebersman, who heard that maybe an antibody could work, even a chimeric antibody could work for lymphoma.

And so with Antonio Grillo-Lopez and the rest of the folks at IDEC, we got the first antibody approved in 1997. And that made a massive difference. I don't think people recognize how important rituximab was for trastuzumab, which was really only a year later-- less than a year later-- approved for HER2 positive breast cancer. But for me, that opened the era of antibodies and made people believe you could repetitively give a patient with cancer an antibody and they would tolerate it.

DAVE JOHNSON: How confident are you that would work?

SUSAN DESMOND-HELLMANN: I was very confident that rituximab would work. There was a lot of information. I wasn't sure we could make it. That required a lot of biotech manufacturing expertise that Genentech had, which was great. But I felt good about that. But there was a myth, at the time, that you could treat a liquid tumor, you could do heme, lymphoma or leukemia with an antibody. But there was this big worry you couldn't get into the tumor with a solid tumor. So I was not at all confident about Herceptin. Trastuzumab was not a give-me. But rituximab I was confident about.

PAT LOEHRER: This concludes part one 2-part interview with Dr. Susan Desmond-Hellmann. It was a wonderful discussion. In part 2, we'll talk a little bit more about Dr. Desmond-Hellmann's incredible leadership roles, including her time as chancellor at UCSF and the CEO of the Bill and Melinda Gates Foundation.

Thank you to all our listeners for tuning into Oncology, Etc. an ASCO Education Podcast where we'll talk about anything and everything. If you have an idea for a topic or a guest you'd like to see on the show, please email us at [email protected]. Thanks again. And just remember anything, because Dave doesn't.

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