 Hey, thank you, Sandy, for allowing me to speak. This is my third KCA Patient Survivor Conference. It's a real honor to be here. The title of my talk is called Critical Observations, the Value of Patients and Their Tissue in Teaching Us about Kidney Cancer. And the purpose of this talk is to discuss observational research studies and the patients that are participating in them and how those studies are helping us learn about kidney cancer. But before I start talking about that, I want to introduce myself. So if you look up my CV, you'll find that my name is Thomas J. Metzner. But everybody calls me Tommy, my patients, my colleagues. And unlike my colleagues who have spoken today, I am not a physician. I'm a clinical research coordinator. And I'm a research assistant with the Department of Urology. So what does that mean? What do I do? Well, what I do is write protocols and maintain protocols and consent patients for research studies. So I don't treat patients. But I investigate and I research kidney cancer by observing patients. A question I always get is, well, what's your education? What do you have to do to be a research coordinator? And I have a bachelor's degree from the UC San Diego. And I'm also enrolled in a master's program at Johns Hopkins University. And I've been in the field of cancer research for five years, kidney cancer research for three years, and all in observational clinical research studies. So what's an observational clinical research study? When most people think about clinical research studies, they think about therapeutic research studies or clinical trials, kind of what's been described to you today. So the two are very, very different. And I want to outline that first. So I'll start with a therapeutic clinical research study. So those are research studies involving human subjects in which a patient receives treatment outside of the standard of care. And data is collected for as long as they are on that treatment. So some examples of those are new cancer drugs, clinical trial drugs, as well as advanced surgical techniques. And as researchers involved in therapeutic research studies and as well as physicians involved in therapeutic research studies, we hope that those studies will benefit those patients. But that's not always guaranteed. And at times, some patients can actually be harmed by those studies as well and have serious adverse events. In contrast, an observational research study is when a patient receives a standard of care treatment and data is collected in parallel with that treatment. So some examples of that are tissue collection studies, quality of life assessments and surveys, and epidemiologic data mining that can provide information on patients and their disease. And by tissue collection studies, what we're talking about there is, when we collect tissue from a patient who's undergoing a surgery or a biopsy, something that is part of their standard of care to treat their cancer. And unlike the therapeutic research studies, observational research studies have no therapeutic benefit to the patient. In no way is the information that is gleaned from those studies utilized in the patient's treatment or to steer their care in any way. But at the same time, they also typically have no risk to the patient or very little risk, because that patient is going to undergo those procedures anyway. So why are observational research studies important? If they're not going to help a patient or provide some type of therapy to a patient, why do they matter? Why should a patient be involved in an observational research study? And that answer is, well, to put it very simply, it's because they allow doctors and scientists to gather tremendous amounts of information, add very little cost to the investigators, and very little risk to the patient. So the types of information that we can gather, we're able to study and better understand the biology of cancer cells by studying patient tissues. We can observe how a disease behaves from patient to patient and why it does so. So why does one patient who has a 3-centimeter renal mass and another patient with a 3-centimeter renal mass, take the first patient, they undergo a partial nephrectomy, and they do just fine. They never recur. But you can have another patient who undergoes a partial nephrectomy for a 3-centimeter renal mass, and they will recur with very aggressive disease and metastatic disease in a very short amount of time. Why does that happen? We can also assess why some treatments work for some patients, but not for others. So if you have a patient with the same type of kidney cancer, they both have clear cell renal cell carcinoma, they have metastatic disease, you give one patient votrient and another patient votrient, one responds and one doesn't. Why does that happen? We can also assess challenges faced by patients and their families. We can gather information from them just by the physician's notes or by speaking to patients in the clinic or having them fill out surveys and mailing them in to the research staff. And we can find out what type of problems are these patients and their families having as they're on standard of care treatments. And we can also understand how to improve treatments for future patients. This all sounds really good. It's all very general. And it can apply to a lot of types of cancer. But this is a kidney cancer conference. And to really illustrate why this is important and really give some great examples of how this is being utilized at Stanford, I want to tell you guys my kidney cancer story. So to do that, I have to introduce you to patient number one. This is the very first person I ever met with kidney cancer. This is Larry. Larry was an extremely healthy 60-year-old man, very athletic, fit, never smoked, had no exposures to chemicals, no previous history of cancer. There was no history of kidney cancer in his family. He was educated. He'd gone to Stanford, was an attorney, very successful, prominent member of the Bay Area community. And of all those things that Larry was, my favorite thing about him was that he was my uncle. Larry had a case of gross hematuria or blood in his urine one day. He went into the physician. And they found an 8-centimeter renal mass, as well as some nodules in his lungs and a mass on his hip. He had a very complicated course of treatment. He had very advanced and very aggressive clear-cell renal cell carcinoma to this day, likely the most aggressive case I have seen in the many patients that I've seen. And unfortunately, he succumbed to his disease in 18 months from the time of his diagnosis. That was obviously extremely difficult for me. At the time, I was down in San Diego. And I was researching some other types of malignancies at the Scripps Research Institute. Larry was one of my best friends. He was a mentor and just a phenomenal person. So after his death, just like any other person who experiences a death from a person that they love and care about, from cancer, my healing process started. And the first thing I did was delve deep into my work. So I was at the Scripps Research Institute, and I was working on circulating tumor cells. And these are some examples of circulating tumor cells. I worked on CTCs, as we call them, in lung cancer, breast cancer, as well as prostate cancer. And while I was down there, I was very fortunate. I was able to get on some papers, and we had some publications. And it was absolutely fantastic. I loved it. I loved my work down there. I also started working on the relationships in my life. So I started getting closer to my family. I started getting closer to my friends, spending more time with the people that I loved and cared about. I started contemplating moving back up to the Bay Area so that I could be closer to my parents and my family, and things were going well. I also started volunteering. I started volunteering in a hospital, at Scripps Green Hospital, and I worked in emergency medicine. And I loved the ED. I loved ER. And one of the reasons I got involved in it was because I'd been working on cancer so long, I didn't really want to think about cancer anymore after Larry's whole bout with it. And I liked emergency medicine because I didn't see a lot of cancer patients, to be honest with you. And I saw a lot of variety in the patients that I met, that I encountered there, with a lot of different illnesses. And all of these things really helped me get through this tremendous heartache that I was experiencing. So things were going really well. And I was getting ready. I was thinking about moving back up here to the Bay Area and I was kind of deciding what I was gonna do. And I got a little piece of information. So I had a friend at the time who really helped me through Larry's death. And she and her family were absolutely phenomenal. And she had gone into the doctor one day, see a urologist. And she went into the urologist for these little guys. Does anybody know what these are? These are kidney stones. So she was 24 years old at the time she had had a horrendous bout of kidney stones. And it spent some time in the hospital the year before. So she's now 25. She goes in to see her doctor and they perform an ultrasound. And they didn't find any stones. That was the good news. Bad news is, was they found this. This is a small renal mass in a 25 year old woman. So suddenly this disease that had taken the life of someone I cared about was now reemerging in my life. And someone who I was close with who had helped me through some difficult times. And I was dumbfounded. So if you had asked me, how are you feeling today? Probably would have been something like this. Confused, lost, perplexed. I didn't understand how a 25 year old girl could be dealing with this disease. She didn't understand it either. She didn't know what this renal mass was. Was it benign? Was it malignant? She had had underlying problems, urologically with her renal function. She had impaired renal function. So one of the questions was, well, what do you do for this patient? So I asked her, well, what is it? Is it cancer? She said, I don't know. And the doctors don't know either. I said, well, can they do a biopsy? And she said, no. And I said, how come? She said biopsies are typically unreliable and the location of the mass isn't good for that. And I said, okay, well, can they get some better imaging than that ultrasound? And she said, no. And I said, why? And she said, well, my kidney function is really poor. I can't have contrast. I said, okay, well, can they take it out? Can they operate? And she said, no. They do that and I'm likely gonna go to dialysis and I'm gonna need a kidney transplant. So these were the types of questions that were racing through my mind, as well as the questions following Larry's death. Why did Larry get cancer? Why did it progress so quickly? Why wasn't he able to respond to treatment? And at the time of his death, I didn't know anything about kidney cancer. So after all these questions were raised in my mind and I found myself having more questions and answers, if you had asked me how I was feeling at that point, one emotion became very clear and it was this one. I was angry, I was frustrated, but it put it very technically I was pissed off. Right? I was angry at this disease for hurting the people that I cared about. I felt a profound sense of injustice. Why these people were dealing with this? They were good people, why Larry had got it and he'd had such a horrendous bout with this disease. Why a 25 year old girl who should be looking forward to the rest of her life is having to deal with this, potentially having her life impacted when she needs to be thinking about graduate school and getting married and having kids and her family's now dealing with this. And I was angry. And here I was, a researcher, somebody who worked in observational research studies at a renowned institution and the next question that got raised was now what are you gonna do about it? Looking in the mirror, what are you going to do about this that's hurting the people that you love and care about? And so a new journey began and I essentially went on the war path against kidney cancer. And I thought, all right, I'm gonna do something about this. I'm gonna get involved in some type of research on this disease and I'm gonna make things better for some patients. I have to go through with this. I have to play this hand in my life. And so I thought, well, where am I gonna go? Where am I gonna do this? Kidney cancer research is a small field. It makes up less than 1% of funding from the NIH. So where am I gonna go? Well, Larry graduated from Stanford. So that's a good place to start. So I Googled who's working on kidney cancer at Stanford. And I actually ranked the researchers from number one to five. And number one was the guy that was working on it the most. And number five was a person that was kind of involved in it, but it wasn't really concentrating on it. So the number one guy was this guy, Dr. Leppert. This is John Leppert. And so I wrote him an email. And I said, hey, this is my story. And I explained everything. I told him about Larry. And I said, you know, I'm a young researcher, and I don't know if you have any funding or anything, but if you do, I'd love to come work for you. And he said, is that right? So he interviewed me on the phone. And he said, well, are you willing to come to the Stanford School of Medicine and work on kidney cancer? And I said, absolutely. And I packed up all my stuff and I came up to Stanford and he hired me. And it was amazing. So one of the questions that came up during my interview with Dr. Leppert was, what was I interested in? So now I had the opportunity to sit down and think like a scientist about this disease and say, all right, what am I gonna do? What do I wanna investigate? What interests me? And what types of questions do I wanna answer that are gonna make things better for kidney cancer patients? So I thought back to my time with Larry. And when he was very sick, I was visiting him a lot. And he and I had a lot of very candid conversations. And I asked him, so Larry, what do you wanna know about kidney cancer? And he came up with a couple of questions. He said, well, what causes Cary? What causes cancer, kidney cancer? And why did he have it? Why Larry? Of all people. He was a healthy guy. He didn't smoke. He took care of himself. He wasn't obese. He didn't have diabetes. He didn't have hypertension. He was a healthy guy. Why did he get kidney cancer? And then another question that he wanna know was, is there a better way to assign drugs? Is there a better way to treat this disease? And to really quote him, he said, because there's gotta be something better than this goddamn suitent. Because that was what he was assigned for his first therapy. And he didn't tolerate it well at all. And I thought, well, those are some great questions. That's a great place to start. And then I started thinking about my friend who had this ambiguous renal mass. And it started, it got me thinking about the surgical management for kidney cancer. So if we get a CT scan with masses like this, we don't know what they are. And I started thinking, is there a way that we can improve the accuracy of renal mass biopsy? So we can perform a biopsy on these renal masses and we can know what they are. And we can know whether we have to operate or not. And how can we better determine who should have surgery and who shouldn't? How do we know who we should take to the OR? And how can we determine if that person really needs to have surgery? What if they do have cancer? Is it going to cause them a problem? Is it going to become metastatic disease and take their life? Or is it just going to sit there, kind of like a bump on a log and never really affect the course of their life? So these seemed like very good questions to me and that was exactly what I was interested in. And I was very fortunate because there was an oncologist at Stanford who was working with Dr. Lepper who was interested in the same thing. And she'd come up with utilizing this technology. She started out in lymphoma that could potentially answer those questions. So the name of the assay or the technology that she was using was nicknamed the NIA and that stands for nanomuno assay. And what it is, it's a capillary-based microfluidic instrument. So it utilizes very small amounts of liquid in very small tubes called capillaries. It separates proteins by charge and then detects those proteins utilizing the nanobody. And then it gives out luminescent or basically a light readout. So it can produce a very unique protein signature, essentially. And the great thing about it is that it can detect high resolution protein modifications. And in kidney cancer, that's very important because a lot of proteins are up-regulated and activated in kidney cancer through phosphorylation or the addition of phosphate groups, essentially, onto these proteins that allow them to do their job within these molecular pathways and when they're up-regulated and overexpressed, that's how the cancer is essentially able to be cancer. And to put this kind of in a diagram form, she had used it in lymphoma, so she'd taken a fine needle aspirate biopsy from 40 to 200 nanoleders. Is everybody familiar with the metric system? You know how much that is? That's one billionth of a liter. But what you should glean from that is that this assay was able to be run with as little as 50 cells. And that's in comparison to hundreds of thousands or potentially millions of cells that you would need to perform a clinical biopsy and still not necessarily know what that mass is or what that tissue is. So it's put into this capillary system separated by charge and it's detected with an antibody and you get a readout like this. And what you're looking for here is the area under the curve of these proteins that are detected. So in this case, they're detecting arc one and arc two as well as phosphorylated arc two. And this was an assay that was performed in a patient. So the pretreatment chart right there, the pretreatment readout is the levels of protein that were in this patient before they were exposed to any type of drug. And then they gave the patient the drug, performed another biopsy and what they saw was this. This level of protein had gone down, which indicated that this patient perhaps responded to therapy. So that could potentially answer our question of how do we select drugs? How do we assign these drugs? Can we look for these proteins and these unique protein signatures from each patient and determine which TKI or which treatment to give them based on their level of upregulation and activation. And that was pretty cool. And she'd done this in kidney cancer and gotten some interesting data. So what they were doing was taking a kidney tumor that was already resected, so a whole kidney, and biopsying it with an FNA or the needle in a few places. And this is actually one that I did. So those colored pins are where I actually took the biopsy from. And they're collecting representative tissue sampling. So from multiple places within the kidney tumor as well as the normal tissue. And she saw something like this. And they were able to find these proteins and also assess these levels of phosphorylation. And she was also able to check the level of phosphorylation of this protein of interest and compare it to the normal tissue. So could that potentially indicate how these cancers are behaving? And she also observed that at times in the normal tissue, she saw a higher percentage of the phosphorylated irk than in the tumor. So maybe that was a way of telling which tumors were going to be the bad actors, as we say, and really cause the problems, the metastatic disease that could potentially take a patient's life, and which ones were the more indolent disease or the ones that we didn't necessarily need to take to the operating room. So that was really cool. And she'd performed that in 18 patients. So they brought me on board and they said, okay, this is what we're doing. So the next 364 days, I biopsied 101 kidneys and put 101 patients on study. And I also collected blood from 40 of those patients who had locally advanced disease so that we could look for circulating tumor cells. So that we could see if at the time of surgery, these patients had cells in their blood that might cause them to have metastatic disease. And that was awesome. But then I got to thinking, well, what else can we do? Are we really utilizing these surgeries and these observational research patients who are willing to participate in these studies in the right way? And are there more questions that we can ask in their work? And some of those questions were, well, 90% of RCC patients have their cancer found incidentally. Can we find it earlier? Can we detect it or can we find something that would indicate that they need a CT scan instead of just stumbling across these tumors? Also, drug resistance is prevalent in metastatic RCC. Is there a way to combat it? Kidney cancer metastasizes to weird places like the small bowel, the head of the pancreas, the septum in a patient's nose, as well as the places that we normally find it. And the liver and the lungs and the brain are not necessarily where we normally find it, but where we normally find a lot of metastatic cancers, other types of cancer. How does it get there? Well, that was a potential question that could be found maybe with the circulating tumor cells that we were looking for, right? And then also, who gets kidney cancer? Why? What are the long-term, non-oncologic health effects from surgery if you do take somebody to the operating room? And that was more a population-based medicine question. So, we decided that we were gonna write a new protocol. So Dr. Leppert says, all right, we're gonna write this new protocol and we're gonna look at some more stuff. And by we're gonna write this, I mean, I'm gonna write this. You, Tommy, are gonna write this. I said, okay. So this was my first protocol that I was writing and we expanded it. So now what we do, when we have a patient who has a renal mass and we know that they're going for surgery, we, of course, do our blood assay looking for the circulating tumor cells and we also biopsy their tissue so that we can run it through our NIA and we can produce a protein signature from their tissue. But we also started looking at other things. So we started looking in their urine and in their blood for early detection biomarkers that may indicate that a patient needs a CT scan or that they may have an early form of RCC that we need to go looking for instead of stumbling across these things. We also started building large databases to house the type of clinical information that we could potentially see trends in from a population-based medicine standpoint or epidemiologic standpoint that would indicate what types of people are getting RCC and what are the risk factors. We also started thinking about animal models. Well, maybe we can take some tissue from these surgeries and we could put it in a mouse and we could learn some things and we could maybe test some drugs on those mice or we could just observe the cancer and see how it behaves. And that might also give us some more information. And these were all tissues that were otherwise gonna go in the garbage. And what emerged from there was kind of the resurgence of the Stanford kidney cancer research program. So the Stanford kidney cancer research program was in existence before I came to Stanford but not a whole lot was being done with it. And what we found when we expanded our protocol and we started looking for biomarkers and all these different types of tissue from all these observational research studies, we found that we needed a lot of people to investigate all these things. That there were people that had other specialties that were outside of our realm that could potentially help us with this. So some of those guys were Dean Felscher, Jeffrey Gertner and Donne Peele and they developed animal models for renal cell carcinoma. In diagnostics and in early detection, the types of people that were gonna look at our blood in urine samples, you had Megan Hitchens and Robert Hale. On the proteomics and molecular and cellular biology side, you had John Leppert, you had Jim Brooks, an Alice fan who were conducting their work. You also had Ben Chung and Sandy Srinivas as well as John Allen who had comprised the kidney cancer database of all kidney cancer patients who were treated at Stanford and the clinical information that was so critical in determining their treatments essentially and the course of their disease really told the story of what was going on with these patients. And then you had the folks that were interested in drug targeting and resistance and understanding why some patients were resistant to these treatments and failed these treatments whereas others were successful. And we needed to get these people in the same room. So that's what we did. And we started having these seminars twice a month and we exchanged information and from there, collaborations were built. And we started setting up the infrastructure that was gonna allow us to answer potentially so many questions and look in so many different aspects of this disease from one single surgery or one single patient. And at the heart of all this was the observational clinical research studies that we were performing and the protocols that we'd written and the patients who were willing to participate in these studies. And the best part was I get to work with all of them so I have the coolest job out of everybody and the whole staff. And now I wanna talk about what I'm most excited about this year and this is in line with observational research studies. I decided to found this year the Larry Lulof Memorial Kidney Cancer Research Internship. So this is a picture of Larry and my aunt Diana and there's Larry in his cardinal red tie. He was a Stanford man through and through. So with the participation of Stanford University and the School of Medicine I have developed an internship program that's going to be a six month paid undergraduate internship for Stanford students. And they are essentially going to be working with us and getting paid for it because I think the undergrads shouldn't work for free. They have enough to do, they're already studying and to ask them to just work for experience is unfair, I felt. So we're gonna fund this internship from private donations from the community and from organizations that Larry was a part of. And what it's designed to do is allow these students to observe various aspects of kidney cancer treatment. So they're gonna be able to see surgery. They're gonna spend time with Sandy and Alice and some of the oncologic fellows and urologists in the clinic meeting kidney cancer patients and finding out exactly what it's like to interact with these patients, see the treatments they receive and understand the challenges that they're facing. And they're also gonna spend some time working on a three month research rotation with one or more of the labs from the kidney cancer research program. So they're gonna get a chance to develop basic science and potentially improve treatments for kidney cancer and understand kidney cancer from many different aspects, studying animal models, understanding proteomics, potentially genomics. And it's all designed to facilitate students getting into doctoral programs and increase awareness and interest in renal cell carcinoma or kidney cancer for future physicians and scientists. And at the heart of all of this are observational research studies. They form the core. It's what's going to allow this type of program to happen so that we can get these young academics, scientists and doctors to get excited about this disease, about this field, inspire them and make them wanna work on this disease in their future when they're in a position to be impactful. So I not only learned from kidney cancer patients tissue, I also learned from kidney cancer patients themselves, just observing them. So this quote was on the t-shirt of an RCC observational research study patient. First time I met him, amazing man. And I learned from that that it takes a whole team. And I learned from Larry's disease and his struggles with his illness that it's about the relationships you form surrounding this disease that help you face those challenges. So this is my kidney cancer team and they're in the back. Many of them have traveled very far to be here. So those are my parents, Ron and Nancy. My brother, Mike is back there with his girlfriend, Talia. And then my girlfriend, Raquel, she just drove all the way here from Vegas yesterday so she could see this talk. And she's beautiful and talented and supportive, they all are in so many ways. So I owe them a huge thank you as well as my colleagues. But then the biggest thank you of all that I have to pay in this forum, giving my opportunity to speak today is to my patients and their families. The people that agree to be on these observational research studies with no benefit to themselves thinking solely about future patients, trying to alleviate the struggles that those patients are gonna face. And I get to meet them at some of the hardest times in their life and out of the goodness of their heart, they agree to participate in these studies. And I've met hundreds of patients. I've biopsied over 230 kidneys, kidney tumors, collected blood samples from, gosh, close to 150 patients. Our research is going phenomenally. It's growing every day. We're bringing more people in to help us with these studies. And this is what I do. I've given up on emergency medicine. Kidney cancer is me. And this is my passion. And I'm happy to answer any questions. Yes, ma'am. Yes, actually. So I ran into her at a concert and asked her how things are going. And she is essentially on active surveillance. So she gets an ultrasound every year to assess the growth of her tumor. She and I, we actually don't talk anymore. But the last time I saw her, she was doing okay. So I hope that if she does have a change in her renal mass that she gets the right care. Yes. That's a wonderful talk, Tommy, Thomas. Thank you. Yeah. That's a fantastic work. And your work is being deflected in the exponential growth of all the drug detection and all the healing that's going on. And I'm sorry for your uncle. I think most of the people here are, they might have or their loved ones have something going on. So I think you have the more experience in terms of seeing people who has been going through all these things. So I want to ask you like, what is the one piece of advice you want to give to the people who has some kind of cancer and to the people whose loved ones has cancer? And in general, as a responsible human being, how can a non-biological student can contribute to the development of cancer healing technologies or whatever? Okay, so I'll start with your first question. So the advice that I would give to a kidney cancer patient, I think is to reach out and develop the relationships, lean on the people around you who love you and let them into your world and let's see, what's the best way to put this? Enjoy the quality time that you have with them, I guess. And I can speak to that in terms of my uncle. My uncle Larry is my mom's oldest brother. And I also have, well, she's got, she had three brothers until Larry passed away. She has two more brothers. So her youngest brother is Bill and Larry and Bill used to not get along. And when Larry got sick, that's very unfortunate, but it happens in some families. But when Larry got sick, Bill started coming around more and Larry was receptive to Bill and they were able to have, I think really quality experiences, the two of them and their families were able to have quality experiences until Larry's death. And actually that was one thing that my uncle Bill told me was that even though Larry's sickness was horrible, the great thing about it was that they were able to get back to just being brothers. And I thought that was great. As a family member of a patient with kidney cancer, I guess I would say the same thing, be there and just spend time with them. When I would hang out with Larry, I would usually come up about every six weeks from San Diego to visit with him. And we just kind of found, we went back to the things that we had in common that we had always loved for as long as we'd known each other. And for me and Larry, that was baseball and fishing. And that was what we talked about. And we didn't talk about his cancer very much. It was, I guess, the elephant in the room, but who wants to spend all your time talking about cancer, you know? When you can talk about the Giant's Pitching Rotation or the best fly fishing places in California. And then as far as a responsible human being goes, even if you're not scientifically inclined, you have no biology background, I think that anyone can be affected by some form of adversity in their life and look around them and go, you know what, that's not right. That's, I don't agree with that and I'm not gonna let this stand. And they have the means, hopefully, or if they look hard enough, they can find the means, even if someone else is doing it, to get involved. And for me, I didn't come to Stanford going, all right, I'm gonna cure kidney cancer. I came to Stanford thinking, if I do one thing that improves treatments for kidney cancer, for future patients, then I've done a phenomenal thing. I have refused to allow a disease that I hated, that was hurting people that I loved and cared about. I refuse to just let that stand. And maybe what I do here, I don't know what the final thing that I do here will be. I hope it's cure kidney cancer, that'd be awesome. I'd love that. A Nobel Prize would look great on my wall. But if I do one thing that helps one kidney cancer patient, then I've done something great. And I think that's the whole spirit of the KCA too. On that note, a round of applause for Tommy. Thank you.