The Art and Science of Oncology: Yunan Nie '15 is a cancer researcher and physician at Mass General Hospital in Boston

[0:00]Hello, the guest today is Yunania, class of 2015. She is a cancer researcher at the Mass Gen. Hospital. So hi Yunan, what's your research on? Hey Tony, thanks for having me on this podcast. I've listened to a bunch of these, so really honored to be here. I work in Cancer Research. So specifically I'm a physician, an oncologist, and I actually just finished up fellowship and I'm starting as a faculty at Mass General working on small cell lung cancer specifically. And in particular, I'm going to be focusing on clinical trials and hopefully with a translational component, meaning that my goal is to bring new, you know, medications, new therapies to the clinic, to patients through clinical trials. And then hopefully also taking some of the information that we learned from those clinical trials and from our patients and bring it back to the lab to try to figure out, you know, what are the mechanisms that make patients develop these cancers? What are the mechanisms that either predispose someone to responding to therapy or not? Because that's something we still don't understand very well, unfortunately. And it makes a huge difference for our patients, but very excited to talk more about this very rapidly growing field and lots of new exciting things actually happening. What about small cell lung cancer? What? What about the interested? Yeah, no, that's a great question. So I think, you know, to give context, I, I started out, you know, I did a hematology oncology fellowship. So I trained in both, you know, blood, both malignant and benign and oncology. So the solid tumors. And I think I really, I, I've been drawn to lung cancer since I was a resident. I saw a lot of patients with this really terrible cancer when I was in training. I took care of them when they were in the ICU. It's an area of unmet need in general, not the small cell, but

[2:00]also non small cell because they're two different major types. Actually, you know, the the most diagnosed most lethal cancer globally. Then when I became a fellow, I met lots of patients with small cell lung cancer and met some wonderful mentors that worked with these patients. And I learned so much about both the disease, which is very aggressive, and the therapies are getting better than they were, but there's still so much unmet need in this area because of how aggressive the cancer is and how quickly it sort of gets around the 1st or even second therapy that you throw at it. And I think it's also just a very special population because I think there's a lot of medical complexity, you know, just with how aggressive cancer is. And there's also sort of some of these associated symptoms that you really have to put all of your internal medicine knowledge and get all the team members involved from all sorts of specialties to take care of these patients. So I really, I think enjoyed that part as well. So it really, and there's just a lot going on in the space as well. It's a good time. Can you give like, like to, to like to give like a more specific example, like, like if someone walks in with like who says there's like chest pain or like lung, lung pain, I go, well, what's the typical way of getting diagnosed? What's the typical next steps? And then how do you see them through the months? Yeah. Over time, yeah, that's a good question because it happens so frequently, right Where, you know, so with patients with cancer, sometimes it's completely instantial, like they're doing a CAT scan for something else, like looking at their heart to see if they have heart disease and you catch a nodule or something like that. And then at that point, hopefully they would get a biopsy. We get the tissue back and we get the diagnosis and then they come see us in the oncology. Or sometimes what can also happen is they have symptoms like chest pain, as you mentioned, or trouble breathing or they're coughing up blood, which is absolutely a reason to go see someone in the hospital. And then they get imaging that shows, you know, what looks like

[4:01]a cancer. We still need to do the biopsy and get that diagnosis. But you know, at that point, usually we can sort of get have a sense and start talking to the patient about next steps when we see that imaging. And then once we get the biopsy, that's actually, I think it's actually been it's a really interesting area because I think we've had so much development in technology for actually looking at the tissue and figuring out what kind of cancer, not just what kind of cancer it is, which is super important, but also what are some, you know, of the drivers of why this cancer happened? If it's a non small cell, sometimes we see these mutations that are very specific and are driving that cancer along, but sometimes we see the markers that tell us, OK, we think this treatment might work better for you than this other treatment, for example, immunotherapy. So we get so much information and when we see the patient, we have to put it all together in a way that makes sense for everyone, for the patient, but also for us. And then that's where we have our very long discussion about, hey, this is the diagnosis and these are the treatment options and work with the patient to figure out a plan that makes sense. So depending on what stage that could be surgery, that could be chemotherapy, immunotherapy, targeted therapies. I'm kind of throwing out all of these different terms because it's, it's sort of a reflection of how complex treatment and just diagnosis of cancer is these days, but also is a reflection of how many more options we have with all of this new information from all the research we've done. And then after that, you know, depending on the research, the treatment plan, we we might start them on the treatment or we may offer a clinical trial, which is a whole separate discussion. So like if you take the biopsy from one patient, you take the biopsy from another patient. Like how different are the two biopsies from each other? That's a good question. So every biopsy is obviously individual for that patient. And that actually that's such a good question because it gets to

[6:01]the heart of what we're trying to do in Cancer Research and cancer treatment, which is really try to understand what makes each cancer tick. You know, the biopsies can be very different from patient to patient. They can look different under the microscope. You know, the way that lung cancer, which is my area of specialty, obviously, if I mean this could be, there are so many different types of cancer that you can see under on a biopsy. But even lung cancer, you can get small cell lung cancer, you can get non small cell lung cancer. There's a, there's another type called large cell neuroendocrine sort of falls under non small cell, but not really. Then you get deeper and you can get into, OK, what are these specific markers? There are things like PDL one's a term you might hear. There are mutations you can start looking at over expression, under expression deletions. It gets so complicated. And all of this is individualized to the patient, right? And not just to the patient, but also to that specific site. Because what we also see is sometimes you get a biopsy from different parts and it's the in cancer, but they might have different mutation profiles even, which is which makes it kind of tricky, right? Sometimes to really know like how what's the best way to treat a patient If one site expresses for example high PDL one and the other expresses low, she can sometimes. In the same patient. Yeah, it can happen. You know, after someone's already gotten treatment and maybe one sites developed a little new mutation or they've figured out how to get around the treatment by over expressing a marker or some other mechanism. So it's, it's complicated and I think we're finding the more we know, the more we find out, the more complicated it gets. So there's like all the different types of cancers and there's also all the different types of treatments like like how do they map into each other? Is like some treatments good for every type and the other treatments good for some. And don't use it for this, but use it for that. You are you are speaking my language, which is it's.

[8:01]So it's so many different iterations in combinations of therapies. So I'm, you know, I'm a lung cancer specialist. So even within lung cancer, you know, which treatment maps out onto like which patient is still an area of study. You know, back in the old days, I say old days, but it's really only maybe let's say 30 years ago, it was pretty much chemotherapy for all that was really your only option. I'm in terms of things that, you know, go through your whole body. You might have radiation, you might have surgery available as options, depending on the stage. And then just within the last 10 to 15 years, we've had new treatments that are immunotherapies that harness the patient's immune system, Revs it up to actually attack the cancer, helps it recognize the cancer. We have medications that target specific mutations that, you know, if you think about a mutation that drives the cancer forward, if you block it, you've cut off that driver, the cancer dies. But knowing who should get each of those treatments or which common patients work together versus actually maybe cancel, not cancel each other out, but actually make the treatment less effective is still very much an area of research. I thought that's actually part of my what I'm interested in is figuring out, you know, who are the patients that benefit, for example, for from immunotherapy, you know, which is an amazing advancement, but it only, you know, in let's say stage 4 non small cell lung cancer. It really, you know, really it's depending on specific markers, it can be anywhere between 18 to 30% of patients who get immunotherapy may live to five years. But what about the rest of those patients? What do we do for those patients? What's the best treatment? How do we make more patients respond to immunotherapy? All these questions that we're working on right now. So that's why we need the research and you know why we're we're always working in teams because it's such a such a huge amount of work. Like, like when it comes to coming up with a good treatment, how does the skill of the doctor

[10:03]get reflected in the treatment plan is in like, is there like the best practices where like 100% of all doctors would do this? But then it's in the like the 50%, twenty percent, 10% where the best doctors are able to create a better treatment plan? Like where does the skill come in? Yeah, that's, that's a good question. I think you're getting at sort of what is the standard of care? You know, what is the treatment that, you know, you see a patient with X and they should get X treatment versus like the art of medicine in some ways, which is that, you know, you have to individualize for the patient, you have to individualize for all the circumstances surrounding the patient. So I think, you know, in terms of standard of care, we do have guidelines that are evidence based. They're based on clinical trial data, they're based on research, they're based on expert opinion. So frequently we use something called the NCCN guidelines. So you know, not that so that that's more specific for, I would say North America, but there are also European guidelines that basically it represents called the, it's an acronym for National Comprehensive Cancer Network. But essentially it has all of the different types of cancers and it has sort of like, you know, if you have X cancer at this stage, this is sort of of the standard of this is what we'd recommend as a, as a body, but it gets complicated because the field is advancing so rapidly. I mean, I can, you know, just as an example, you know, I, we went, the American Society of Clinical Oncology conference was just passed this past June. And there is, there were so many trials that were presented and so many practice changing trials that, you know, even coming out of that conference, I think what the NCCN guidelines will say will change or have already changed for many different cancers. And so, you know, I would say that oftentimes if you're specializing in a disease and you just can focus, for example, in lung cancer, even small cell, you can really stay up to date on all of that evidence as it

[12:03]comes out. And sometimes you're able to get folks on, you know, get the novel therapies either through clinical trials or something called expanded access where it's not quite, you know, like it's not quite approved yet, but maybe through passionate use program or some other way you're able to get the patient early access. And I would say, you know, that's sort of the medication part, like the, you look at the patient profile mutations, the type of cancer medication. So that's, you know, already complicated enough. But then I, I think the art of medicine comes into play, which is what does the patient look, do you know, is the patient likely to benefit from a treatment? Like, even if, you know, on paper it says, if patient has asked, they should get, you know, why maybe they have a particular medical condition that makes it so that they would be susceptible to a lot of bad side effects from the medication. Or maybe the patient themselves have preferences. Like I have had patients where they've had really bad experiences with family members getting chemotherapy. And they say, you know what, I never want to keep get chemotherapy. Even if we have better ways of controlling side effects and preventing them. I just don't want to do that. And that's sort of their, their boundary. And so we work with that and come up with tailored plans. That's all to say that I think there's there's a reason that we do so many years of training and have so many reps and seeing patients and and learning. So, so like when you go to the big conference, I like in the one in June that you went to like like how do you present the paper? Like how does the how does it work? Like the research work as are The Who are the big stakeholders in the research area? Like who are the, are their papers journals? Are they universities? Like what? How does research get pushed forward in the? Conference like that's, that's a great question. So, you know, it, there are lots of conferences, this ones one of the biggest ones, but there are also lots of other smaller

[14:03]conferences. But I think overall, you know, everyone sort of who is doing research, you know, loves to talk about their research. And so these conferences are a forum where we can share research results, research ideas, talk with other sort of, you know, state, as you said, stakeholders, but like researchers, physicians, pharmaceutical representatives, other like providers, even patients, patient advocates are such an important part of these conferences as well. And so, you know, there's sort of the research component where you submit your abstract, you know, and it's reviewed by a, a group that comes together and looks at all of them and decides, OK, these are the abstracts we want to publish online only versus a poster versus a presentation. And then, you know, oftentimes you still go to these conferences just to be able to hear a lot of the newest updates. So I guess I would say that it's sort of it's sort of just a meeting of minds because there's the research component, but also it's like an opportunity to catch up with colleagues in your specialty, outside of your specialty in academia, but also in industry, which you know is really important. I think particularly for oncology, because so many of our sort of advancements do rely on partnering with our industry partners to try to move the field forward either with a new treatment or, you know, sort of shifting who a treatment, who gets the treatment. So it's, it's a lot of fun. It's a ton of fun. And I think it's, it's so great to actually talk to get out of your bubble sometimes because like, you know, you have your colleagues that are at your same institution and you see them frequently and you sort of oftentimes there's almost like an not an institutional, you know, guideline or anything like that. But oftentimes a lot of the institutional sort of like standard of care tends to at least somewhat be in the same realm. And then you get to talk with your colleagues and they may have very different opinions, which is like so, so important actually for patient care and

[16:04]for moving the fuel forward. You always want new ideas and new ways of doing things right? Yeah. So within the research area, are there different areas where a lot of people are concentrating on? How different are the different areas of research? I think it's, I think that I mean, there's someone working in every area. I would say there's, there's more than enough work to go around in small cells specifically. I think it's, it's a really exciting time actually, you know, before like just to give sort of a little bit of a context for why I think it's such an exciting time. So prior to about 2019-2020, there had been like no approvals for new small cell therapy for give or take about 20 years. And then immunotherapy was approved for small cell in the first line. And suddenly every, it seemed like everyone, you know, got really interested in small cell. Suddenly there are other options. So now you have researchers that work on, you know, radiation for patients with small cell radiation when combined with immunotherapy for small cell immunotherapy, you know, immune redirection therapy, for example. Then there are also targeted therapies and epigenetic therapies, which are, you know, sort of my areas of interest. And there are folks that are looking at sort of what are, you know, now we know that they're actually not just not, it's not just small cell, there are subtypes of small cell. So you know, looking at the different subtypes of small cell and how those affect treatment responses and aggressiveness of the disease, there's just a lot going on. And there's, you know, also a lot of focus on how patient on survivorship and how to manage the symptoms from small cell therapies as we have more and more options as well. So it's an ever expanding field and I highly recommend that anyone that's interested, you know, come talk to talk to me, reach out or come to one of these conferences. Everyone's always super friendly

[18:04]and happy to talk about their work. Like there's like resources when company comes up in like 2019 for example, what happens to all the resources flowing in? Is it like more grants are suddenly written for it or is more like pharma companies funding research as well? Yeah, no, that's a, that's a great question. So, so, yeah, I think when, you know, when there's a breakthrough, so leading up to the breakthrough, you need the research funding. There's just no way around it. You need the grants. And so, you know, it's it's incredibly important to have those National Science Foundation NIH grants to fund the work leading up to these breakthroughs. You know, of course, pharmaceutical companies absolutely essential as well for developing drugs and funding these trials. That's sort of leading up right to like one of maybe these like these breakthroughs. And then once you're, you know, once you're, you're sort of opening up the field, you often do have more grants because there's more interest in that disease. Suddenly there's a way to treat it. Suddenly there are other iterations. So I think, I think research does beget research. And so I think, you know, once there's a, for example, a drug and immunotherapy that's worked in one disease, oftentimes you do see that there are other drugs in development as well and more funding as well in industry for that disease. Now that's sort of the way he's been paved in some ways. So I think that's really important. But I think it's, it's also, you know, I think it's also really important to, to mention the, the funding that goes into like things like basic science that goes into lab research, because that really forms like the basis for the work, right to get to that level. Because we, you know, oftentimes. So sometimes it is sort of a stroke of luck where you have a drug, for example, that you give to a bunch of people and you see a pattern and you go back around and then you're like, OK, it worked because of X. Other times it's because in maybe a. In a lab or basic science, you know, group, they figure out, OK, this is a mechanism that

[20:06]drives this cancer, so let's target it with X. And a lot of that work happens sort of very early on and is very dependent on like things like NIH grants and other sort of foundation grants as well. So it's you kind of need like a, a varied flow of of funding from different sources to actually move this research forward. So the research before 2019, that was all funded by those? I think it was a mix. I think it was still a mix. You know, I think there, there were absolutely grants, you know, grants from various sources, foundations, NIH, national grants, and there were also industry funded research as well. I think it's more just that there wasn't quite a breakthrough before 2018-2019 when sort of this data about immunotherapy and small cell was published. And this is specifically for small cell. I think it's just that before that they're just that the options were rather slim for treatment, unfortunately. And it's just AI think it's a, it's a great representation of what science and research can do for a patient. You know, it's not just we have another type of treatment, it's actually some patients are living five years or more after being diagnosed with stage 4 small cell lung cancer, which is amazing, right? Like this is just very real impact on on people coming out of this research. So you're researching at the time already in like 2019, but how did the, how did the research like breakthrough like impact you like did you like work more on it as a result? Like what? How did it impact you? So gosh, 2018-2019 So I was actually class of 2019 for, for incidentally, while Cornell Medical College, so the Med student and still in 2018-2019. So at the time I was still interested in research and I was working on neurology research actually at that time before sort of I decided actually, you know what, I'm really interested in internal medicine and I want

[22:06]to know more about area. But I think I, you know, you were hearing about the, the research actually even in the news. Not I think not so much as maybe today, I think. So I don't know if I would say social media wasn't as developed then or as, you know, you know, sort of pervasive, but you heard you heard some, you know, pops of positive news and this is a new breakthrough. And of course, like for patients who have that disease, you know, that absolutely was a big thing, but I actually don't think I, I was quite, I don't think I was quite focused on lung cancer yet at that point. And then it was sort of after through residency and fellowship that I started working a more clinical research and less sort of lab based. And I was like, Oh my God, wow. Like this is sort of the research that I want to do because you're, you're seeing patients, you know? That makes sense. So going forward you'll be working in between the clinical trials and also the the research that happens so between. Yeah, exactly. So I'm gonna be splitting my time between, of course, seeing patients because I, I think, you know, it's really important to find meaning in your work. And I think a big part of what brings me meaning and what prevents burnout is actually seeing and talking to patients. So we think patients two days a week in the clinic with a focus on lung cancer, of course, and then working on research within, you know, the clinical trial space in small cell and hopefully also doing some teaching. You know, a huge part of, I think being in medicine is being a teacher, especially in academia, you know, kind of trying to, to sort of, you know, pass it on forward. After all, I had just amazing mentors, which is where I ended up, how I ended up where I am and with my current interests. So I'd like to be that for for future researchers and and oncologists too. Nice. Yeah. And so for, for the for the like the for the research side, like how do you figure out what is like important to research based on the conversations with patients? Yeah. Oh, that's such an important point for me.

[24:07]It is, it is based on my patient, right? Like I think a lot of, you know, being a a physician researcher is, you know, my, my goal is always to bridge the clinic and the research. You know, take what I see with my patients where the need is and take that to a research question. You know, for example, as an example, like when we're seeing patients in the clinic, you know, for example, there's a certain subpopulation of patients with this specific mutation called EFR. And in general, they respond very well to these pills and and now this infusion, this SIV drug as well. And they do really well for the most part. But there are some certain patients that just don't respond for very long and we don't quite understand why yet. Work is ongoing. So that's a question like who are the patients that are resistant to these targeted therapies and why? So that's a question that comes out of seeing a patient, for example, that they didn't respond to the pill when we were like, we expect you to respond and feel a lot better within just a couple of weeks and they didn't. So once you come up with a question like that, well, what's the process of answering it? That's a great question. And sort of the $1,000,000 question, which is like, how do you get to the answer? I think once you've formulated your research question, you of course you want to refine it. You know, oftentimes that does involve a lot of looking through the literature and seeing, OK, what's work that's been done so far, what is work in progress? And sometimes that also means pulling in your colleagues and asking them like, hey, you know, have you seen this before? Like what's your sense of how prevalent this issue is, for example? And then, you know, sort of figuring out, is this a question that can be answered with looking at patient data, like retrospectively, like you gather a cohort of patients that we've already treated and see if we can find a pattern. Is this a question that we need to sort of figure out through a combination of patient data and

[26:08]maybe doing testing on biopsies more and more so or is this some something that is all of the above, Some of this work's already been done and maybe we have an idea for how to get around the problem. And maybe this is actually clinical trial in the writing. So it's, it really often times it's, it's very much a multifaceted question and a multifaceted approach. And then of course, there's a question of funding. You know, you have to often fund your research projects either via institutional funding or potentially foundation grants or national grants or sometimes industry sponsorship as well. So that's always sort of like that's a little bit of a look behind the curtain. You usually look for something that impacts like a lot of patients like how do you determine to look into right now or is it like another thing to look? At right, Yeah, because there's always, there are always more research projects and always more research questions you could answer, right. And time is finite. So are resources. I think, you know, of course, like we want to impact as many help as many patients as possible, but sometimes that also means that a lot of resources are required and sometimes it can be hard to have a huge project just start right up and be ready to go immediately. So what often happens is will a researcher will have sort of a spectrum of projects, which I think is actually really important because we also don't want to forget the patients maybe who have a rarer disease or rarer subtype or mutation. And maybe it can be hard to find those patients and it may be just a smaller number, but maybe it's like a really in depth look that might actually take a little bit less time in some ways if we're just looking retrospectively. But you also want to have those big sort of projects where you're looking at a bigger cohort of patients where you can actually see patterns because it's so hard to draw a conclusion based on one or two patients, right? And then you also want to see if

[28:08]you can have a variety of, you know, trials where you're doing something that are that's an intervention and then, you know, research where you're sort of looking and trying to understand some of the mechanisms. So a diverse profile of research is always is always preferable. I think it's about. Do you also like vary the the research in terms of like how basic the research is versus how translational the research is? Yeah, that's a great question. So I think everyone's a little different. For me personally, I I'm really interested in the translational component. You know, I have a pretty like I did sort of basic science research for years right up until and through residency and fellowship, though much less so during residency and fellowship time constraints. But I like, I really wanted to ground that with inpatient and patient care. And so I think that translational component where you're sort of going between the two was really appealing to me. But there are definitely like many researchers who focus on the clinical, on clinical research, many researchers have focused on really very lab based work. There are folks that focus on medical education research actually there, which is actually really important. Like what I mean, what's the best way to actually teach the next generation and be effective about it, which I think is, is a developing field. Very much. So that's all to say that there's something for everyone, which I think is the really fun part of medicine. You can, you can do so many different types of careers, even within a field. And you'll hear a lot of people actually, you know, talk about pivoting where at one part in their career, perhaps they were very much lab based and then they transitioned to be more clinical or more clinical investigations or more teaching or administrative. And I think that's the fun of it. You never, you never get bored because there's always something new that you could do. That makes sense. So the translational research, do you have to like translate

[30:10]the the patient outcomes into like the more science like what's that translation? What that looks like. So I think it's a little different for everyone. So for me in my new in my new positions that I will be starting in about two weeks, I'm not planning to be in the lab myself, rather I'm going to be hopefully collaborating with lab based scientists. So it may, it's, I would say it's more of a model of like, you know, I'm seeing patients so I'm able to able to recruit them for studies. I'm able to sort of get these biopsies, these very precious samples that hopefully the lab scientists can then take and do experiments on investigation sequencing, which is a huge new thing, and make models out of these, these samples that are patient derived, which I think is just so amazing because, you know, I think so like, I think mouse models are very much important, but are not, you know, they, they aren't necessarily always a good representation of the human and how a human might respond. It turns out our immune systems are pretty different. And so I think it's just it's, it's like a really fascinating field. And I think being sort of in the middle of that as the translator, so to speak, is my ideal. But I think we'll have to see what that actually looks like. You know, as I said, oftentimes there are many pivots right now. That's my goal. But who knows, you know? Super so like when you are picking like which group to join? Like how do you pick a group to join? Yeah, tricky question. So I think so when I was going through the interview process and looking at different positions, I mean, I, I really, really enjoyed meeting so many different groups. I mean, just it's a wonderful field. I mean, I'm a little biased, obviously, because I love working in cancer and you know, all of the, the oncologists that I met and you know, in these groups were just wonderful. I think a big part of my choice was also sort of life my singeth

[32:12]another who you know very well. Exactly. Bella Cornelian met in debate was in Boston. And so that was a big part of my decision to look sort of very much in the Northeast. And then I think it was just looking at sort of like the group dynamics and research support, clinical support, sort of general like just all of these factors. And I think I am really happy with my work with my with the group that I'm joining. I just loved meeting them. But I think it, it was also just like I had a sense is that I would get a lot of support and I just also had just good timing in that there was a space for me to continue to work in small cell lung cancer. And so I wanted to continue to do that. And so it was a good fit. Is support like like access to the right machines for the research or support like access to the patients that you need like the that's a? Great question. All of the above, all of the above. I think depending on the type of work that you want to do, I think mentorship is super important. Having a supportive group where like you can bounce ideas off of other of your colleagues, sometimes crazy ideas, a group that you know, is willing to sort of, for example, my case, if it's a trial, help recruit patients to the trial for my type of research, that's super important. But it's also just like having that comfort level of going to another, you know, college and say, hey, like, I'd really like to just run this patient case by you. I'd really like to just run this idea by you. And just feeling confident that, you know, you're going to get a thoughtful response and like, you know, have other brains at work with you. And I think having the infrastructure and the patients to actually, you know, continue to do research is also super important because you can't, you can't really move a clinical trial forward if you're not seeing enough patients who have

[34:12]that disease. And you can do translational work if you don't have a lab collaborator or a lab that can do sort of some of the the experiments, especially if you yourself do not necessarily want to be doing the experiments. So you need so it has both of them, the access to patients and also access to exactly. Access, Yeah, yeah. Support, mentorship, infrastructure, administrative support, it's, it's all just a, it's a, it's sort of an all around package that you need. Like how hard is it to recruit patients? Like is it just you post on clinicaltrials.gov and then people apply for it? Like what's how? How hard is it to recruit patients? Yeah. Good question. So I think it it depends if it's a clinical trial for a very specific subtype of cancer, for example, there just may not be so many patients. And so that can be slower going. Sometimes patients do come like they, they will see that a clinical trial that they're interested in is offered at hospital and they will actually come to the hospital for trials. Other times, you know, we see patients in the clinic just as you know, as they are diagnosed as part of their treatment course. And I think we're always trying to give patients the best option. And sometimes clinical trials offer that sort of novel therapy where, you know, we, you know, we would never offer a trial if we didn't think that it was going to help someone. But, you know, we, we present what a clinical trial is, you know, the idea of it to the patient and we sort of give them the information and talk about the risks, the potential benefits, the fact that it's not a guaranteed benefit. And really, you know, talk through, OK, this is a clinical trial. These are the standard of care options. If there are, if there is a standard care option and let the patient choose, you know, it's always the patient's decision and it's always a very individual decision. And I think one thing that we also really try to emphasize is like at least in oncology, you know, our trials are usually not like you get nothing or you get the treatment arm.

[36:12]Usually it's sort of is dependent, but usually it's whatever is the standard of care. So what you would get if you didn't, you know, participate in clinical trial versus, you know, novel therapy or novel therapy plus standard of care. So we try to emphasize like we are treating you, it just is a question of is it standard of care or is it something new? That, that makes sense. Yeah. So it's so how many patients do you need to get like statistical significant? Yeah. Oh, that's, you know, that is a whole, that's that could be a whole hour long statistical discussion, which I'm totally not like quite. I'm not going to say that I'm an expert in terms of the statistics. So it is actually often times it is a statistical sort of decision in many ways. So to get significance, you know, the larger, so the larger the trial in some ways like the like or the larger the number of patients, the I wouldn't say it's easier to get significance, but sort of the, the, the easy, the the fewer, I guess like what's a good way to put this? So we have phase one trials which are often very small and oftentimes the end point isn't necessarily efficacy. And then sample size is based on how many patients we need to say, let's say reach an endpoint for safety. Phase two and phase three trials are often bigger. And so the sample size is bigger based on what the endpoint is. You know, with phase three trials, you can have hundreds to thousands of patients, pretty amazing, right? Whereas with the phase one trial you might have, you know, 15 patients or 40 patients. So it really does it ranges. So being at like a hospital where there's a lot of patient flow that that helps a lot in filling out the trial over. Yeah, I think it is, it is helpful, but it's not just patients, it's also having the infrastructure to actually run these trials because trials are

[38:12]are pretty heavy in terms of how and resources. Well, you know, you, you need research coordinators, you need research nurses, you need the physicians, of course, and the Apps, the advanced practice providers. You need like a good sort of just of good infrastructure to be able to run trials smoothly because it can, you know, it's a lot of oversight, rightfully so for trials. Yeah, that makes sense. It's like all these new therapies that you have to apply. Exactly. And there's a lot of monitoring because I want to make sure that, you know, the results are accurate and that they're interpretable and scientifically sound. And all that means that there's there's a lot of moving pieces in running a good trial. Yeah. That makes sense. So, so so for the closing question, I always ask the guest, what's the kindest thing anyone's ever done for you? The kindest thing, oh God, you know, I've been the recipient of so much kindness throughout my my life and my career. But I think I think one of the one of the moments that really stands out to me actually from when I was a resident is and, and you know, I think it's, it's hard to say it's the kindest per per SE. I think it's just, it stands out because I think it's something that was just done so well. So when I was a resident, I had a very difficult patient case. I say difficult patient case in that it was a young patient with cancer and there were a lot of complications, both the cancer and of treatment. And I think it was, it was just a very sort of emotionally difficult case. And one of my attendings, you know, I, I try, I would say I try to put on a like a happy face or a brave face and, you know, try not to show when. When it's it's a difficult case, but one of the attendings that I was working with and picked up on it actually and actually took me aside and said like, Hey, like, let's just sit down. We have a little bit of quiet in

[40:16]a very busy ICU and let's just talk about this case. You know, I want you to share all of your thoughts and feelings and we're going to just reflect on what this case means for you, for the patient, for the team, for, you know, the future. And I think it was just like, I think something I didn't expect, right? It was a very busy, it was a busy rotation. And yet this attending took the time to actually, you know, check in with me. And I think that's something that I hope is something that I will do for someone in the future and without them asking, because I don't know that I would have asked for that moment or that time.