 Okay, welcome everybody, welcome to our second kidney cancer association, patient and survivor conference. We're really excited to have you all here and to have, I think, a really exciting program. I think we'll have people kind of coming in and out throughout the day as we did publish the agenda and I think, you know, kind of welcome people as they come in. I'm Kim Rathmell and I'm hosting this year's meeting and I'm going to start off with just a few housekeeping notes. First of all, this is our room for the day, but I think with only one exception from 12-2, we have the building, so there's lots of quiet places to sit if you meet somebody and you really want to have a conversation. You're free to use the building as you wish. Bathrooms are all over, but right outside the door, we got the good room as far as bathrooms, but they're right here. There's, you saw food outside at every break and in between, there'll be food and coffee. Lunch is going to be in the Trillium Room and I'll announce that as we get closer to lunch, which is the dining room in the back. Other, if you have questions of our speakers, we have a great panel of speakers who are all, you know, excited to engage with you. And if you have questions during the talk or at the end of the talks, somebody else probably has the same question. Feel free to ask it. There's a microphone in the back and we ask you to use that so we can hear the question. Also, because this year, the entire program is going to be broadcast on live video feed. So right now, I think it's on because it's after 9 o'clock, so I don't know, Dylan Asheville, hello, and anywhere else, the live stream video is up there on the side if you have anybody you want to send it to and have them join us. So with that, we will keep to time. Mike, can I ask you to grab Melissa and bring her in one second? So a program like this involves a fair amount of coordination and we have really, I'll wait so I can embarrass her when she comes in. One person at Limeburger who does this very, very well and maybe she's avoiding coming in here. Is she here? Oh, okay. We'll do this again in a minute. All right. We'll do this at the end. I have a couple of more things that I wanted to say. So first of all, again, welcome and thank you. We're so glad you're here. This is one of only about four of these regional kidney cancer association, patient and survivor meetings, and we're really happy to be able to bring it to the southeast region. But it's not just to bring it to us to this region, but this area is really a tremendous hotbed of research and interest in kidney cancer. UNC and Duke and I hear folks who come from Hopkins. So this area has a lot of interest in this cancer. So this cancer is not at all alone. There are dozens of doctors who really dedicate themselves to this cancer and you'll hear from a bunch of them today. So the purpose of this meeting is really threefold. First is to give you information, because if you're armed with information, that really can be the most valuable tool in some ways in navigating this whole process. The second is to bring you together, to bring you together with other caregivers and other survivors and as well with the doctors to share experiences, share ideas. I heard some of that happening already, talking about clinical trials and where is it and who gets to do it and what's coming next. We really want you to do that, really engage with other people who are experiencing the same thing and know that you're not alone. The experience that you have is shared by everyone else in this room and on the live video feed. And then to bring us all together, to bring you guys together with the doctors outside of the clinic. The clinic interaction is a very different thing than having coffee out here in the lobby. So the doctors who we've invited here are volunteering their time today. They'll be here around their sessions, so grab them when you see them if you want to talk to them. But it's a chance to share some ideas and some common interests. And you know we're not here because kidney cancer is glamorous. It's dangerous and it's an elusive enemy, but together we're at a place and a time with lots of new therapies and new ideas that we can make really big differences. It's a time to be very hopeful and that's why we put on these meetings. We'll thank her later. She probably does. But we have a common mission and that's to defeat kidney cancer and we do that by sharing what's new, telling stories and getting to know all the fellow members of your team, the doctors as well as your comrades. With that, let me know if you have any questions throughout the day. I'll be here all day and have a great day. So when you see Melissa, who runs the table, just thank her. She put an enormous amount of effort into this as she does all of her meetings. She's really, really good. Hopefully we'll get to applaud her later. Okay, so with that, I'm going to turn over to Mike Lying, who's our advocate for the Kidney Cancer Association. Thank you, Kim. It's good to be here and I appreciate all the effort that has gone into making this conference possible. And I'm glad that we're doing a live feed on this and the videos will also be available on the Kidney Cancer Association's website and probably on the UNCA website. In future as well as just the regular UNC website. We've got some people that's watching this live in Asheville, North Carolina. So I want to welcome those people that got up early and got out in those mountains and ventured forth to come and see this. I'm an 18-year survivor of kidney cancer and I won't go into much of my story, but 18 years ago there wasn't a lot of information out there that I could access. And I am so glad that we have a lot of information out there now. And it's an honor to represent and tell you about the Kidney Cancer Association. Basically, the Kidney Cancer Association is comprised of everybody. And it's an international organization, but if you look at that slide, you want to make sure you don't call it an infernal non-profit organization because there's some really good people that's involved in the Kidney Cancer Association. And it's just like the faculty here that's doing this presentation. They have all given so much of their time, their effort to bring about all kinds of knowledge and information on kidney cancer. And we appreciate that. Kidney Cancer Association was started in 1990 by Dr. Eugene Schoenfeld. Now, he was diagnosed in 1989, set in his doctor's office. The doctor told him he had kidney cancer and he says, what can we do about it? And the doctor told him, Jean, there's nothing out there. And he says, well, why not? He says, look, if you're going to give me a hard time about this, you're a professor in journalism and everything. Why don't you do something about it? If you're so concerned about this, do something about it. So Jean did just that. It wasn't long before he and that doctor in about three or four patients sat down at Jean's home around the kitchen table and they organized what is now the Kidney Cancer Association. Jean's words initially in 1990 was telling people, hey, it's like, the doctor opens his medicine bag only to find there's nothing there. That's what a kidney cancer patient is going through. Well, today there's still some atoms in the doctor's bag that's missing. And we appreciate all the research that's going on. We appreciate all the clinical trials that's being conducted to find answers for the problems of kidney cancer. And Jean encourages each one of us today, even though he passed away in 1997, he encourages each one of us today that you should understand. You can do something about this. It takes a lot of will and a lot of action. And your actions in being here this morning demonstrates that you're not only concerned about your family, your friends, and people that have kidney cancer, you're wanting to find answers and be able to share that with other people. And I thank you for networking with other people today as you talk. And the mission of the Kidney Cancer Association is basically to reduce and eliminate as much suffering from kidney cancers as we possibly can. And we appreciate the fact that there's a lot of great strides that have come forth in the last seven or eight years in some of the targeted therapies and so much promise in the future. The Kidney Cancer Association operates in three primary areas in education, research, and advocacy. We're involved even at a local level in North and South Carolina through the North Carolina Comprehensive Cancer Program and the South Carolina Cancer Alliance to bring about some changes that can be helpful. One of the things that we're working on this year with the North Carolina Comprehensive Cancer Program is to reduce the disparities on insurance coverage of oral medications versus the IV medications. Hopefully, we'll have some legislation passed that's been brought up by a lot of agencies. And we're glad to be a part of that. Hopefully, we can bring about some equality on the coverage of that. On the education component, there's a lot of doctors that see kidney cancer patients very rarely. And one of the things that we do is we try to bring about education to the doctors. There's about 100 support group meetings that are held every year in the United States. And like Kim said, there's about four regional conferences. And we're gradually building that number. And all of these are available on the Kidney Cancer Association website. If you go there, you'll get some good coverage. This year, we had a symposium in Chicago and a symposium in Dublin, Ireland. And those doctors that participated in those symposiums learned a lot on the latest processes of treating and research on kidney cancer. Next year, we'll have a symposium in Miami, Florida. Hopefully, we'll have a lot more Hispanic participation in the symposium that's going to be in Miami and will also be in France for the European symposium. There's a lot of research going on in Europe, and we want to capitalize on that as much as possible. And we help to educate oncologists during these symposium. The number one resource that you can access about the Kidney Cancer Association is a website, www.kidneycancer.org. And it's being revised right now. It's got a completely different look to that screenshot that you have now. But feel free to access that. We've also got extensive coverage on social media. I think our Facebook page, we've got somewhere over 95,000 members right now. And we've got a good following on the Twitter feed. And a lot of our videos are available on the YouTube channel. And our latest endeavor to provide information is on inspire.com. We've got a Kidney Cancer Association community support page. And this is actually a page that people can enroll in and ask questions and provide comments and link to resources that's there. And so we invite all of you to participate in that. We're very proactive about clinical trials. We try to work with pharmaceutical companies and the research and facilities and other organizations to promote the latest in clinical trials. And the sad part is that only about 5% of the people participate in clinical trials. And there are a lot of physicians that never mention the fact that there's clinical trials available. So we're working hard to alleviate that situation because we think that every kidney cancer patient, as well as other cancer patients, deserves at least the opportunity to know about clinical trials. And it's their choice whether they want to participate in one or not. We've got some publications that you can link to. If you sign up on the Kidney Cancer Association website, you can download We Have Kidney Cancer, We Have Kidney Cancer Survivor Stories, something on Wilma's Tumor. And we appreciate one of our organizations. We've got an oncology navigators group that helps to keep the We Have Kidney Cancer book updated. And this nurse advisory board really puts forth a lot of effort to keep that updated for us. And so it's constantly being revised. And we invite you to take a look at that. You can also purchase it. But the availability of accessing it online is really incredible. I want to thank you for allowing me to be here. That's my email address. If I can be of service to you, please don't hesitate to talk to me. Look forward to chatting with many of you. And remember that website, www.kidneycancer.org. Thank you for being here this morning. Thanks, Mike. All right, we thought because a lot of the talks as we get further into the morning and into the afternoon will be about new things that are coming. But we'd hear some of the historical overview. And Dr. Kim is an associate professor at the University of North Carolina. He has a research lab and sees patients with kidney cancer, runs clinical trials in kidney cancer. And he is going to give us that landscape. OK, is that a pretty good volume? Oh, I could have done that. Thank you. All right, so like Kim said, number one, I appreciate Kim inviting me to give this. I'm sure she could have easily given this. And I could be still sleeping, which would have been a much better alternative. But that's fine. In any case, so I saw that looking through the agenda today, I saw that there's quite a bit about therapy and surgery and what we essentially should be doing with patients. And so I thought I'd give a little bit of historical overview. Part of my postdoctoral career, meaning the time when I was doing research, was actually a very exciting time for kidney cancer, sort of the time where we began to understand the molecular biology in which loss of this gene, which is probably very familiar to you, the von Hippel Lindau tumor-spressor gene, gives rise to kidney cancer. So to take care of a couple of housekeeping items, number one, kidney cancer is relatively prevalent. So these are updated numbers from 2014. As you can see in men on the left in blue, it's the sixth most common cancer. And in women, it's the eighth most common. So it certainly makes this top 10 list. And we hope that it continues to, well, we hope that it drops off, but unfortunately, as I'll show you in a second, the incidence does seem to continue to rise. Now, actually I'm showing you that right now. So the incidence continues to rise over time. So this is only up to 1997, but I believe that the trends continue even into the 2000s. A lot of this may be early detection. So there is, as I'll show you in a slide much later, there's a tendency now for us to find more smaller renalesions. So as many of you know, patients go to the emergency room for many things and CTs are essentially required when you come to the emergency room. And these are often found so-called incidentally, meaning they weren't necessarily looked for, but were seen. Fortunately, kidney cancer does not cause as many deaths as it does cases. So cancers like pancreatic cancer, there's almost a one-to-one ratio. Once you're diagnosed, the likelihood of you passing away from the disease is quite high. But you can see here, it's actually the 10th most common cause of death, cancer death in males, and doesn't actually make the list in females, fortunately. And so hopefully what we'll see is this drop off, not because everybody else is doing worse, but because kidney cancer patients are hopefully doing better. So what are the risk factors? You know, none of these are actually blaring risk factors, meaning for example in lung cancer where we see smoking as being a huge risk factor, this number called the so-called relative risk, meaning your chance if you smoked, for example, of getting lung cancer over a person who did not smoke is around eight to 10, okay? So the bottom line here is that all of these so-called relative risks while they are significant when you study them, they're not like they increase your risk to the degree that we see with lung cancer or bladder cancer or other so-called smoking-related diseases. But nonetheless, if you sort of look at what is associated, it's clear that smoking is probably the biggest culprit and that's why if you, when you first get diagnosed with this, your physician will likely ask you, did you have a history of smoking? There's a number of occupational exposures that have also been associated, again, to some degree, lowly with a, I don't know why put obesity as an occupational exposure actually, I'll have to change that. But nonetheless, asbestos exposure as well as petroleum exposure has been associated with increased risk of renal cell carcinoma. Patients with kidney failure, so those who particular end up on dialysis, they are known and I don't think the mechanism of action is quite known, but dialysis and end-stage renal disease, these patients form renal cysts. And it's believed that these renal cysts are a precursor lesion to developing frank renal cell carcinoma or kidney cancer. And then there's a bunch of genetic factors now. We know that these sort of inherited familial syndromes, such as von Hippel-Lindau disease or tubal sclerosis disease or Burt-Hog-Dube syndrome are all associated with an increased risk of kidney cancer that tends to happen multifocal, meaning many places within the same kidney, or bilateral, meaning on both sides or both kidneys if you have them. So there are many histologies of kidney cancer and what that means is when a pathologist looks under the microscope at a section or a piece of the tumor, believe it or not, to the untrained eye, these may look very similar, except the color that they look, but the pathologist can actually differentiate these the majority of the time. And the frequency or the incidence of these is in this row. And you can see that the majority of kidney cancers tend to be this clear cell type. And that's because the cells look relatively clear. And this is actually an artifact of how the tissue is actually processed. Nonetheless, we shouldn't leave out the fact that there are a number of other types of kidney cancer that affect patients and are very important. So this so-called papillary type kidney cancer can be divided into these type one or type twos. And not only do they look different in the microscope, but the patients have a relatively different outcome. And then finally, chromophobe kidney cancer, which Dr. Rathmell had a, I would call seminal paper this past year, describing the genetics of that cancer, is another one that as physicians, we don't see as much, so we tend not to think about it as much, but we now know much more about the genetics of this more rare cancer because of that work. So von Hippel-Lindau disease, this is how everything really started. And it's a familial cancer syndrome, and that means that somebody at some point had a mutation in this gene, the VHL gene. And that means that you start off as an infant or as an embryo, actually having two copies of every gene. And in VHL disease, patients have a mutation or lack essentially one copy, so they only start out with one. So you can imagine that it only takes loss of the other one to really give you cancer. And that was what was seen, the pattern essentially of patients getting these clear cell type renal cell carcinomas, these blood vessel type tumors, which if they happen in your brain or your spinal cord are called heme angioblastomas. And finally, if these blood vessel tumors happen in the back of your eye or your retina, they're called heme angiomas. And so, Treacher Collins, who was an ophthalmologist, noted this back essentially, well now, 120 years ago that these patients were coming in and they had a spectrum of these two tumors in particular. He did not make the association with kidney cancer back then. But he reported this over a decade ago. And now we know that about 100 years, really for us to, not us, I should say, I was, I think like in high school when this happened. But for very impart people like Marston Linnahan, Burton Zavar, to really come up and find location of where VHL was and how it was associated with VHL disease. And we know that it exists on this chromosome, so if you take a cell and you sort of spread it out on a slide, you can see that there's all the chromosomes and they had this kind of banding pattern, so they look black and white. And we now know that the VHL gene resides on chromosome 3P. And I won't really touch on this, I don't know if others will. The interesting thing really is, is that a number of the other genes that we now know are involved in kidney cancer development are also found very close to here. So for some reason, unlucky to us, nature made it so that you could lose VHL along with other genes like PBRM1 or set D2, sort of all at once. And that likely is a part of why kidney cancer is developed in that fashion. So who cares about, not who cares, but there's not as many people with VHL disease as have kidney cancer. And so one of the things I did when I was a postdoc was to see, and this is not all my work, I just really compiled all this data from what was published, to see whether or not VHL mutations were associated with so-called sporadic kidney cancer, meaning you didn't have a family history of kidney cancer, you just sort of developed it out of the blue. And what you can or cannot see from where, depending on where you're sitting in the room, is that in the range of 50, 40, 60% of patients who have so-called sporadic kidney cancer, meaning no family history had mutations in VHL, or in the bottom panel here, you can see that they had so-called hypermethylation, meaning not a mutation, but a mechanism which just silenced the expression of the gene. And so what we then really knew was that 80% or so of patients probably had inactivation or loss of VHL, and this was clearly an important step in kidney cancer development. I won't bore you with all this, but I think it's, I'm sure many of you heard of this gene called VEGF, or the VEGF receptor, and these are drug targets for things like sunitinib, pozapinib, or votrient, seraphinib, exitinib, and bevacizumab, so we're getting many of them. And so why does that work, and how do we actually think to target that? And the bottom line is that this VHL gene that I just described sort of negatively regulates this pathway, which is so-called the HIFVEGF pathway. And so you can see under conditions of low oxygen, meaning, for example, if you have a heart attack, your heart becomes deprived of oxygen, this pathway gets upregulated and you get high levels of VEGF. And VEGF was described at first by this gentleman, Hal Dvorak, at Beth Israel Deaconess Hospital as being a pro-angiogenic protein, and so it was sort of a protein that caused growth of blood vessels. So what happens when you have loss of VHL? So either if you have VHL disease and you lose that remaining so-called wild-type allele, or if you're unlucky enough to have both of these alleles or genes, copies of this gene lost in your kidney, you basically get upregulation of this whole HIFVEGF pathway, and we believe that's why those blood vessel-type tumors that happen in the back of the brain or the eye, or kidney cancer, which is notoriously hypervascular has a lot of blood vessels is related to this gene. And HIFVEGF does a lot of bad things, so this not only does it turn on that VEGF protein that creates blood vessels, but it does a lot of other things that are important for tumors to continue to grow and proliferate and do things like metastasize or spread. And so back in the 90s, early 2000s, we actually had this model and it's really reiterating what I've been saying. And that is really that if you had VHL disease, you were born with one copy of VHL that was just gone, okay? And that you're fortunately able to prevent cancer by having one copy, but if you lost that second copy, you really upregulated this protein called HIFVEGF, which regulates VEGF, and that could cause these cysts in your kidneys that weren't frank cancer, but could easily lead to cancer. And back then when we wrote this, the other so-called hits, meaning the other genes that were involved in developing kidney cancer weren't actually known, but now thanks to efforts from the so-called cancer genome atlas amongst other individual groups, we know that these other hits are clearly things like PBRM1 or CETD2 and they actually reside on that chromosome right next to VHL. So clinically, when I was in residency, I do remember hearing that kidney cancer was the so-called internist tumor, and that's really because not a lot, but 10% of patients would present with this so-called triad, meaning these three symptoms, okay? And that was basically flank pain, meaning you had pain near where your kidney was. You had hematuria, which is a medical term for blood in your urine, and when you went to the doctor, the doctor could feel like there was a mass there, okay? So it was really called the internist tumor, and that obviously predates the advent of things like CTS and ultrasounds that we can now just sort of look for these things. But what's also interesting about kidney cancer is it's also called the great masquerader, and I think that that, what that means is that it fools us a lot because it does funny things. It acts strangely and variably, so as I'm sure many physicians can attest to, you have a really broad spectrum of kidney cancer, some that do quite well, meaning they don't grow very fast and can kind of sit there, others that do more poorly, meaning they grow quicker. But it's interesting that this cancer can actually, this is primarily the clear cell type, I don't mean to generalize, but it can really spread to weird sites, you know, like your thyroid is a pretty good one that we know does happen a low frequency pancreas. I myself have not seen testes, but it's certainly reported in the literature. And so the bottom line is that it does weird things, and I think as physicians and as patients as well, it's very important to keep this in mind when you see strange things happen in a patient with pre-existing kidney cancer. So I alluded to this earlier, fortunately even though the incidence has been increasing, if you look at some of the tumor characteristics of the kidney cancers that we're finding, they're of a favorable nature. So basically number one, the percentage of tumors that are asymptomatic, meaning that the patient didn't go to the doctor or the ER because they had flank pain has changed, you know, back in the 1970s where it was only about 10% to now 60%. So 60% of patients now don't really have a symptom. The average size has been shrinking, so it's about a centimeter different. And then finally the organ confined tumors, meaning it's only confined to the kidney. Well, back in the early, late 1980s was only about half of patients now, it's three quarters of patients. So that likely explains why despite the incidence, meaning the percentage, the number of patients in the U.S. sort of developing kidney cancer is going up. Fortunately, the majority of these are probably sort of being found earlier and we're doing better with them. There's a bunch of so-called perineoplastic syndrome. So these are syndromes that don't appear to be related to the kidney cancer at face value. But if you treat the kidney cancer, many of these can get better. And so I won't get into all these, but things like high blood pressure, high calcium, weird things going on with your liver, high red blood cell count, et cetera, are all sort of a spectrum of what we can see here. Okay, so when I was actually going through the historical thoughts about this, it really struck me that kidney cancer therapy, if you think about it, it's all about keeping the faith. And what I mean by that is that the two major, I would say, therapeutic advances in kidney cancer have come through persistence. And number one, immunotherapy, which I think all of you are probably very excited about and have heard about in the past year. If you look at this gentleman, and this is not to say that all the work has been done by this gentleman, but if you look at sort of him as a pioneer, this is Steve Rosenberg who's at the NCI surgical branch. I don't know when this was taken. But nonetheless, he was clearly younger here. Decades went by and he's much older now, okay? But the bottom line is back in the 80s, this guy believed in immunotherapy. He persisted despite what I would, I don't have facts on this, but I would assume a perceived lull in the field of immunotherapy, meaning if he applied to the, well he didn't actually have to apply because he's intramural. But if he applied to a study section at the NIH, it would probably have sort of been thought to be out of vogue or frowned upon. But he persisted for decades and now this past year or two we now know that these immune checkpoint inhibitors are quite beneficial to patients. And so if you look at a tumor, he was very focused on this lymphocyte. He didn't give up, he persisted. And so I think this is one story where sort of keeping the faith or believing in your own ideas had paid off. And then if you think about the other thing where we've made great strides in kidney cancer, it's really anti-angiogenesis. So it's basically blocking that VEGF protein. It's inhibiting that pathway, recognizing that these kidney cancers are vascular and can we modulate their tumor size by doing this. And this is Judah Folkman, who unfortunately is now deceased. In fact, I was going to the, he passed away on his way to a tumor angiogenesis meeting. And I think, I don't know if you were going, I was there at the meeting, waiting for him, he was a keynote speaker. And when I got there to check in, they unfortunately had a picture of him with the year which he passed away. And he died on the way to that meeting in the airport in Denver, unfortunately. So, but nonetheless, he spent decades. So in 1971, he sort of wrote this seminal sort of thought piece in the New England Journal, describing, and I actually have a slide of that, describing the fact that tumors require angiogenesis or growth of these blood vessels to continue to grow. And he went through some troubled times, I think scientifically as well, in which it was questioned whether this was actually a real, did anti-angiogenesis hold a real promise? He put a lot of faith in this molecule called endostatin, which when I was a fellow there, clinical trials, and it didn't look very good. But I think he again persisted through this and others joined the bandwagon and now we have drugs that do a really good job of targeting this pathway. So, Judah Folkman, he focused on these endothelial cells in the vascular. And again, I think it's really a story of keeping the faith and persisting through decades of work. And that got me to this, kidney cancer, when you think, at least as physicians, when we read these articles and journals, they give like this history of development of something. It's always linear, it's like 1971, and such and such to this, 2000, this, this, this. But you know, for kidney cancer, I would think it almost like a circle. Dr. Folkman and Dr. Rosenberg had these ideas back in the 70s and 80s, and they sort of came back around and developed them in a better manner, okay. So this is one of Dr. Rosenberg's, one of the first reports in the early 90s of IL-2, high-dose IL-2, and its efficacy and kidney and melanoma amongst another tumors. And what is the bottom line? The bottom line is, you know, there was efficacy, so some patients had a so-called partial response, meaning their tumors shrank. Some patients had a complete response. But the biggest problem was that there was a lot of toxicity. So despite being able to achieve shrinkage of some of these tumors, the toxicity was really big. And so it really became a balancing act of whether or not toxicity being on one side, much like any drug, frankly, and benefit on this side. And you can see that back then, two to five percent of patients were dying during this treatment. So you can imagine if five percent are dying and you're only really helping five percent, what does that ultimately get you? And so you're skipping really from the 1990s to 2012 when these two great articles about blocking this immune checkpoint pathway came out in the New England Journal. And what is this all about? I mean, who's here heard of PD1 or PDL1? Not everybody, okay, so that's good. So what these are, are these actually proteins that exist on tumor cells? I'm sorry, I should have made a slide of this. But essentially, there's always been this belief that tumors should be seen as foreign, meaning they're just like a bacteria or a virus and they should be eaten and sort of disposed of by your own immune system. And obviously I know that many patients come in and ask me, how can I boost my immune system? And I used to sort of disregard that, but I actually don't anymore. Not that I know the answer, but I do think about it more carefully now. So these proteins are actually things that are on the cell surface of these cancer cells amongst other cells in the tumor. And I would equate them to being so-called don't eat me signals, okay? So if this tumor is expressing PD1 or in fact PDL1 in particular, the immune cells when they come in, they'll see that and they won't eat the tumor, okay? Whereas if you're not expressing these proteins, it's not to say that the immune system will get rid of your cancer, but I think it has a bit of a better chance to do that. And so if you could block this don't eat me signal or sort of hide it or sort of erase it, then what they found was that you could actually get relatively robust responses in some patients, not every patient. And these are so-called spider plots and the middle line in all these is, well there's no middle line here, but the middle line in both of these essentially is zero, meaning the tumor size doesn't change over time. So this is time versus tumor size. And it goes from zero to 100%, meaning the thing essentially grew tremendously or it went to minus 100%, which is completely shrank and it was not visible by our imaging. In the bottom line as you can see that there are a number of patients whose tumors went below the line and did quite well, even some for quite a while. And so there's a lot of interest and excitement about this and you'll hear more about blocking these so-called immune checkpoint pathways later. So anti-angiogenesis, this is the 1971 article in New England Journal by Dr. Folkman. And he really just, you can't say it better than he did. The growth of solid neoplasms, meaning cancers, is always accompanied by neovastorization, meaning the growth of new vessels. This new capillary growth is even more vigorous and continuous than a similar outgrowth of capillary sprouts observed in fresh wounds or in inflammation. And so what's quite interesting there is that he equates cancer to sort of a wound and that's something that has also been continued to be followed up in the scientific literature. So the first drug that was used was this antibody called Bevacizumab or Avastin. And we now know that it was able to keep patients from progressing to some degree. And now we now have Sunitanib, Serafinib, Pizop, and I can't go through all of the studies. But they all seem to clearly prolong progression-free survival and overall survival, meaning we're helping patients with these drugs live longer. And I guess one would equate chemotherapy, which is, it's not like we haven't tried this in kidney care, well, it's before my day, certainly. But that's really like carpet bombing. We weren't doing a very good job of targeting tumor cells. And I would equate what we're doing with Sunitanib, Serafinib, a little bit more like a so-called targeted therapy, which is more like a drone strike, which had its own problems. I think if you get too precise, we're not doing very well either. And lastly, we've learned a lot about genetics. The past two years have been really good. So the TCGA, which is an NCI-sponsored effort to sequence tumors, a single tumor with a ton of different platforms, or meaning different omics, per se. Clear cell renal cell carcinoma, which Dr. Rathmel led the RNA expression portion of this huge group, published this article in Nature. And then, as I was referring to earlier, she took this very, I would say, orphan disease called chromophobic kidney cancer and publishes, I think, just recently in cancer cell. Again, really allowing us to begin to think about what's going on in these tumors and can we start to develop therapies that are specific to chromophobic kidney cancer. So in conclusion, kidney cancer instance, it is increasing over time, unfortunately, but at the same time, the tumors we're finding seem to be more benign and quite, not, I don't wanna say benign, but less aggressive and hopefully can still be treated quite well. Much of science and medicine is rediscovery. So as I alluded to, we're sort of going back to the 70s and 80s, immunotherapy. Dr. Rosenberg sort of put that on the map back then. Anti-angiogenesis, Dr. Folkman put that on the map back in the 70s. Immunotherapy holds great promise. I think you'll see Dr. Moshkos will talk about that later on today, and while it has its own side effects, it's not without its own problems and toxicities. So I've had a couple of my own patients have issues with these drugs. But overall, I think the future looks brighter. I think that as we learn to use immunotherapy properly and potentially combine it with other therapies, I hope is that things will continue to look brighter as we go on and make our own history, okay? All right, I think that's it for me. Thank you. All right, thanks very much. I think that sets the stage very well. The next speaker is Jen Lehman. We're gonna hear just a patient perspective. I know that each of you has a unique story to tell, but we find sometimes kind of hearing one person's story can kind of help us all be ready to talk a little bit more. So Jen Lehman, come over here. So I have known her for at least 20 years, I don't know, long time, is married to my husband's old college roommate and has been a friend for a long time. And this summer now has a new thing to share with me, which is kidney cancer. And so we were talking about it and she tells a really good story. She's a high school science teacher. She can take care of an audience and keep everybody in control and I'm running into her time, so I will give her the microphone. Thank you. It's great to be here today. And as Kim said, I'm a science teacher from Oklahoma and this summer we had an exciting experience. First off, in telling my story, I wanna show you a picture of my family because they're gonna come up a lot in the story. My husband Josh and I have been married for almost 16 years and we have four kids, ages 12, 10, seven and five. And as most doctors would agree, I don't represent a typical kidney cancer patient. When you look at the risk factors for kidney cancer, I don't have any of the typical risk factors associated with kidney cancer. I don't have advanced chronic kidney disease. I've never smoked. I don't consider myself obese. I don't have high blood pressure. In terms of family history of kidney cancer, we don't have any kidney cancer in our family history. My dad and grandmother had had kidney stones. A few years ago, my mom even had a cyst on the outside of her kidney that she had to have drained. But other than that, pretty uneventful history, medically. My story actually began last December. We had been out Christmas shopping and I came home and I observed that there was some blood in my urine. It was a weekend and I thought, well, maybe I should have this checked out by a doctor. So, given the weekend, I actually went over to urgent med. For those of you that don't know, it's kind of an after hours type clinic. They can treat everything from ear infections, bone breaks, accidents that need stitches. The convenient thing for me, being a working mother with four kids, is that they do offer evening hours and weekend hours. And so I ran over there. I told them that I didn't have any pain, no burning sensation, no frequent urination. They did a test for a bladder infection and it came back negative. And I pretty much stoned the doctor because he thought, well, maybe this could be a kidney stone but I had absolutely no pain. And at that point, I was 39 years old and he said, you know what? Maybe this is just the results of a bladder spasm. And I thought, okay, I'm about to be 40. Is this one of those I'm getting to be over the hill type things, these old people things I gotta deal with? And he said, yeah, it can just randomly happen and maybe it just irritated things and you had a little bit of blood. Great, this is gonna be fun getting old. And so I went home just thinking it was a bladder spasm. And over the next few months this happened two or three other times. They were always single incidences and being very busy with the teaching and the kids. You know, you don't always put yourself first and I'm like, I'm not in pain so I never really went to the doctor about it. And I just didn't think much of it. And then things changed in July. Once again, I observed blood in my urine and it was a Saturday. But unlike the other times, it wasn't a single incident. It continued to worsen throughout the day. And by the next day on Sunday, July 20th, it was bad enough that I thought I probably should go back to urgent med. And I remember walking through my living room, turning to my spouse and saying, hey Josh, I'm gonna run over to urgent med real quick. I have some blood in my urine. He goes, don't you think you need to go to the emergency room? I'm like, oh no, I'm sure it's no big deal. I'll be back in a little bit. Well I went to urgent med and their urinalysis could read absolutely nothing but blood, it was that bad. And they said, you need to go to the emergency room. So I went to the emergency room, they did some blood work, did another urinalysis and it came back that I had a lot of white blood cells, which to them indicated an infection. So they diagnosed me with acute hemorrhagic cystitis, which is the technical term for you have a urinary tract infection. And at that point I sat there thinking, really, you're gonna hand me some antibiotics and send me on my merry way. I mean there was no pain, no burning and I thought, you're telling me all these other times this has happened, this is a urinary tract infection? I mean I've had those before. And they said, if you wanna call your general doctor or your urologist and follow up with them in the next few weeks, feel free to do so. And my gut was just telling me, no, this is not it. And the next morning, I tried calling my local urologist and their office was pretty busy, they couldn't get me in for a couple of weeks and I said, well I've been in the emergency room and they said, we'll tell you what, we'll have the doctor look at the emergency room report and if he feels the need to see you, we'll get you in sooner. And they call me back a few minutes later, yeah, he agrees with the ER doctor, it must be just an infection. I'm going, it's not an infection. So I called my general practitioner and she got me in that afternoon. So I went to go see her and explain my symptoms and honestly I thought at this point that I was probably dealing with a kidney stone and I just had such a great pain tolerance that I just had a little bit of blood but I just don't feel the pain from a kidney stone. And she said, okay, fine, let's do a CT scan. So she scheduled a CT scan for that Tuesday, July 22nd and then on that Wednesday morning at nine o'clock I received the phone call and when I answered it and it was the doctor, you immediately know this is not going to be good news because if it's good news then the nurse makes the call. If it's a bad news, it's gonna be the doctor. And she proceeded to tell me that they had found a three inch tumor or a three inch something on my right kidney. And I said, wait, do you mean three centimeters? She goes, no, three inches. And I'm sitting there in my bedroom because I taught science and I knew that our kidney was about the size of her fist. So I'm literally holding up my fist in my bedroom going, okay, this is my kidney and she's telling me three inches, which to me is about the size of a softball. I'm going, how do you fit a softball inside my kidney? And it wasn't making sense to me. And she said, just sit by your phone. I've called the urologist. He's gonna order some more tests and the imaging center will call you and schedule some more CT scans. We wanna do the dye enhanced and all that other fancy stuff. So I sit there by my phone, scared to even take a shower that I might miss the phone call and I'm waiting all day and the kids are wanting to go swimming. I'm like, no, we gotta stay home. We need to wait for this phone call. And finally at 3 p.m., my phone rings. And it wasn't the imaging center, it was the urologist's office. And I said, hey, he has time in his schedule. Can you come on over and visit with him? And I thought, oh, this is one of those initial consultation things where he's gonna meet me for the first time and say, oh, well, here are the other tests I'm gonna be running on you. And his office was literally a mile from our house. So I turned to the kids, I said, okay, I'm gonna run over to the doctor's appointment real fast, I'll be right back. And I left the four kids at home and I sat down with him and I was totally blindsided because he proceeded to tell me, yes, you have a three inch lesion on your kidney. He said, it's a tumor. We're gonna need to remove your kidney. I'm like, wait a minute. I thought I was here just to talk about a CT scan. And he said, well, whether this is benign or cancerous, he said, your kidney's gonna need to come out, it's so large, you're having negative side effects and here are your two options. And he explained the two options available to me for surgery. And he said, well, I'm gonna step out of the office because we need to contact your insurance company to make sure that they'll pre-approve these other tests that we wanna run. And at that point, I really think I went into shock. He stepped out of the room and evidently they went round and round with my insurance company that didn't wanna approve another CT scan because I just had one. And he had to explain to them, no, we need to scan her from her neck down to her pelvis. We need to see if this tumor has spread. And the last thing you wanna deal with is an insurance company that's like, oh, she doesn't need that. And it was taken a while and honestly, I don't think I even realized how long I sat in that little room. He came in one time and said, well, we're having trouble with your insurance company, just stay here, I wanna let you know when the appointment is made. And that whole time I kept thinking, hey, don't fall to pieces, you're in a doctor's office, you're in public, keep it together. At one point I thought, maybe I should call my husband because he's at work 45 minutes away. And I thought, oh no, I can't use my phone, the sign outside says don't turn on your cell phone. I mean, I wasn't even making sense. And he finally came in and said they'd had it approved. And when I walked outside his office, that's when it hit me and I just fell to pieces. My first thought was I cannot go home to my kids because I was bawling, I was hyperventilating. I thought, I didn't even realize it had been an hour with me sitting in this office. I said, I need to have someone to go stay with my kids. And my brother and sister and parents all live in our town. So I called my brother and he could barely understand, he goes, what is wrong? And I said, it's cancer, they're taking my kidney, go stay with my kids. And he's like, okay. And I called Josh, he said, I'm coming home. And I called mom and she was out running errands. I said, go home, I need to see you now. And so she and dad met me at their house and that's when I explained to them the two options that had been presented to me. Now this is what was available to me in Oklahoma. The first option that Dr. explained was the hand assisted laparoscopic surgery. This is the diagram right there on the left. This is not what he commonly performed. He had done a handful of this type of procedure and he explained that you would have an incision around your belly button with a few other smaller incisions. He said that this tends to have a quicker recovery time and would allow me to get back to work a little faster. He was a very humble doctor, because he flat out told me, he said, if you're gonna want the hand assisted laparoscopic surgery, I want to refer you to someone that does it like that all the time. He said, I'm wonderful at the open incision, which is this one on the right, because that's what he had trained in. And giving that the new school year was about to start in a few weeks, my husband and I talked and decided we did want to go with the hand assisted laparoscopic, even if it could get me back to the classroom within a week or two earlier than the other and we might as well do that. So, Monday, July 28th, we met with a surgeon in Oklahoma City that we referred to. Tuesday, August 5th, I had surgery. On afternoon of August 6th, I was discharged from the hospital and a few weeks later on September 2nd, I returned to work. Now, my surgeon, when we met with him on July 28th, I explained I'm a science teacher. You know, I'm all about learning and educating others and one of the random questions I had was, do you mind taking pictures of this for me? Said, yeah, I teach chemistry, I teach biology and one of the things I teach them is the human body system. I said, normally, we kind of fly through the urinary system. I don't teach a whole lot about it, but this would be really applicable to those kids. And he had a wife that was a biology teacher. So he didn't think the request was totally out there and he contacted the pathology lab and they were gracious enough to take pictures. So the next two slides, if you don't wanna see pictures, then feel free to look away because I do show pictures of my kidney and tumor. This first picture is of my entire kidney. A little educational fact about it is that you can see some of the fat deposits on the outside of the kidney. That's Mother Nature's way of helping to protect our kidney and it is quite large. I mean, normally, like they said, your kidney is about the size of your fist. This next picture shows what my kidney looked like when they opened it up. In the upper left and right hand corners, this is the tumor. When my surgeon gave this picture to me, he did a nice little science lesson showing that in the middle of the tumor, the little white areas where the tumor was already starting to die because it does have a very high blood supply. This picture was actually reassuring to me at the time because I could clearly see the outline, the border of the tumor, and it did appear to be all enclosed within the kidney. My first follow-up scan is in a few weeks. We're gonna do CT scans and blood work every six months for the next few years to make sure that it hasn't metastasized, and hopefully those results will be good. Now, in terms of anyone out there that maybe hasn't had surgery yet, I do have a few pieces of advice. First of all, I highly recommend writing down any questions that you have for your surgeon to take with you. I always found that when I got face-to-face with a doctor, my mind would go blank, and I would forget what I wanted to ask, and then it would always hit me five minutes after I walked out of the office. Also, find out if the main incision site goes above the belly button or below. My local doctor who had done a handful of these surgeries when he explained it to us with the hand-assisted laparoscopic, he said that he always did an incision below the belly button. So when I was packing for the hospital, I called my husband and I'm like, oh my gosh, on the way home, can you stop at the store and get me some granny panties? It's like, I need the ones that go really high because I don't want it to affect the incision site. And come to find out, the surgeon actually went around the belly button and straight up, which was actually more irritating because it hit right where all my pants would fasten even when I went back to work, I couldn't wear normal clothes. I was wearing the drawstring pants and the comfy clothes. I also found leading up to the surgery that I was dealing with a lot of anxiety. I had trouble sleeping. I would wake up in the middle of the night and be awake for three or four hours contemplating, okay, I've done my lesson plans for these weeks, I'm gonna be gone. Do I need to make some casseroles and freeze them? And do how I bought the kids school supplies? My brain would not shut down. And lack of sleep and the stress makes you even more emotional. And I finally just called my doctor, I said, is there anything that they can give me? And she prescribed Xanax, which became my new best friend for those weeks, leading up to the surgery and it really helped things. After the surgery, I recommend having a caregiver stay with you in the hospital. Even though we had four kids and if possible, I would have preferred my husband to be able to stay home with them. I was like, no, you're mine for the night. I need you in the hospital with me. And that helped because I was dealing with a lot of nausea. Also, to get out of bed and walk as much as you can with the hand assisted laparoscopic, they inflated my abdomen with a lot of air and a lot of that gas was still trapped after the surgery. And you need to walk and move around to get those air bubbles to work out of your body. And I had intense pain even up in my shoulders. While I was walking, and even after I got home and was walking, I would have my kids or my husband pound on my back and on my shoulders to help kind of move some of that gas around. My one week follow up appointment, I still hadn't slept in my bed. I was sleeping in the recliner all week. And I expressed to my surgeon that I was concerned because I had tried laying down a few times, but every time I would roll over, I felt like all of my internal organs were just tumbling around. I'm like, is everything falling over each other and getting all twisted up? Am I ever gonna be able to go on a roller coaster again? And he looks at me and my husband says, feel free to tell her it's all in her mind. I'm like, no, I'm serious. Is everything connected? What's going on there? I've got a big empty space now. And looking back, I really think it was some of those air bubbles still moving because I didn't lay completely flat on my bed very often and it was very painful and I'd hear a lot of gurgling and tumbling. Also have drawstring pants to wear home. That was very critical for me. And I didn't have this, but if you take a pillow with you to hold against your stomach when you're in the car on the ride home, that makes things so much more comfortable. The hour and a half drive home, I was just clutching my abdomen, trying to keep it from moving and jiggling over every bump that we would go over and subsequent road trips that we would go on, I would take a pillow and just hold against it and it made things more comfortable. And then also don't laugh, cough, sneeze or do any bodily function after the surgery. There were times I was begging my husband to stop making me laugh because it just hurts your stomach so bad. And he has a great way of making me laugh about things and keeping a positive attitude and even sneezing, very painful. Now on handling kids, whether it's your own kids or maybe even your grandkids, we took the approach that we were gonna be very open and honest with our four kids. We encouraged them to ask questions and express concerns, but we had four very different reactions. My oldest, Alex, who was 12, he took the brave, you know, approach. It was, you know, he's 12. So it's kind of like pulling teeth anyway to get him to talk. And I would say, hey, do you have any questions? Oh, no, mom, everything's gonna be fine. And the night before the surgery, he got up and gave me a hug, which is, you know, not typical of a preteen anyway. And he's like, mom, you're gonna be okay. And I just brought tears to my eyes at that time and he was just putting on a brave face for everyone. And then we had Chris, the 10-year-old, who absolutely has no filter whatsoever when we got the kids together and told them that we had news and that mom had been going to the doctor. Alex said, oh, she's pregnant. Before we could even get out the truth, the girls are squealing, yay, a baby. And Chris looks at me and he goes, well, I thought mom was looking a little, and I said, don't you finish that statement. And we explained to the kids that it was cancer, but it wasn't the type that grandpa had died from, which was lung cancer. And it was a type that they could have surgery for. And Josh had to take the three younger kids to meet the teacher night before school started. And I teach in a very small district. And most of the high school teachers knew what I was going through, but the elementary teachers, I guess word hadn't gotten around much. And so they expected to see me at open house and one of the teachers asked Josh when Chris was standing there, well, where's your wife? And Chris blorts out, oh, she's got the cancer. And he just kind of walks off and Josh is going, oh, okay, let me clarify some of this. And then another teacher, she said, well, where's Jennifer tonight? And Chris said, ah, they cut open her stomach and took out a bunch of stuff, which might be how the rumor got started that I had had a hysterectomy. So he would tell anyone and everyone, oh, yeah, mom's got cancer. And I clarified afterwards, I'm like, no, we don't have the cancer anymore, they've taken it out. And then we had Paige, who was seven. She was very nurturing, asked a million questions before and after the surgery. She's the one that slept in the living room while I was in the recliner for several nights. Because in the middle of the night, there were times I had to wake up someone to help me get up out of the recliners so I could take medicine or go to the bathroom. And she loved that she could help her mama. And Maddie, who was five, she was the one that was brutally honest. I mean, I rocked her world. I couldn't give her a bath afterwards because I couldn't bend down like that. I couldn't carry her around and horse play around with her and she finally looked at me one day while I'm in the recliner. She goes, are you ever gonna get up from there? I'm like, yep, you're keeping me honest, Maddie. So I mean, we had very different reactions from all four kids. And we, again, just tried to keep a very positive attitude. We do a lot of joking around in our family with four kids, we're always laughing at something. And in terms of advice that I have for caregivers, the most important advice for caregivers or family members is to ask the patient, what can I do for you? When we found out the date of my surgery, we had several of my family members saying, well, I wanna be there for the surgery. I plan to be there to support you. And it actually became stressful and overwhelming because I really didn't care who was there for my surgery. My main concern was who can I have watch my kids that day? So I'm not having four kids sit in the waiting room with my husband while I'm in surgery. And who can bring my kids up to see me that night? And I thought, okay, I need to let my family members be there that want to be there. And it became very overwhelming trying to make everyone happy. And the best words I heard was when I called a fellow teacher, who's a good friend of mine, and I told her, I said, this is when I'm having surgery. She said, okay, how can I help? What do you need me to do? And that was such a huge relief because I have a hard time asking for help anyway. I said, they're my four kids. I said, really, can you just keep my kids that day? I'd already arranged with my brother. He could pick him up and bring him up to the hospital that night. And that meant so much to me because I was very overwhelmed. And, which also leads me to the second piece of advice as a caregiver, be prepared to deal with extended family and to deal when your spouse gets to the point where she breaks down and is bawling, saying, I can't handle it anymore. You're in charge of scheduling everything. You're in charge of the family. And my husband wants to rock through all of this. I think marriage is very stronger when you go through something like this because you're able to be there for each other in ways you've never had to be there before. And there were times, I remember one time I crawled back and bed at three in the morning because I couldn't sleep. And he wakes up and he's like, are you okay? And I go, yeah. I go, honey. I said, thank you so much for allowing me to break down and fall to pieces because I knew I could in that he would be there to support me and be the rock. And like I said, make me laugh at times. And when I said, okay, I'm done. I'm done scheduling everything. I'm tired of it. It's all on you. He said, okay. He picked up the phone called family members. Said, okay, this is what we need done. And he was just phenomenal. Also, either you or maybe a friend of the family, if you can organize a calendar for meals to be brought in, that was a huge help for me and my family. We found that we didn't necessarily need meals brought every single night. Every other night was great for us. We studied tons of food. A website that our community uses a lot is www.mealtrain.com. A lot of people in our church can sign up through this and our other teachers and they can just pick a day in which they can bring meals. That can be used for anyone that's had a baby or recovering from any surgery. It really did help alleviate some of my stress because I was putting everything on my spouse. Getting the kids to school, getting them dressed, doing everything. And as a mom, giving up some of that control was kind of hard and you feel bad. Even though you just had cancer surgery, you still kind of feel guilty. And it really made me feel like I was lightening his stress a little bit when I had some meals brought in from friends and coworkers. The only suggestion I would have for doctors is to recommend that a patient bring a family member with her to the appointment. Like I said, when I went in to meet with the urologist, I really thought we were just gonna talk about CT scans. I really was in shock when he dropped the bomb on me. Nope, this cancer, kidney's coming out. And I was crying hysterically when I left the office driving across town to my parents' house, which probably wasn't the wisest thing to do. And had I known ahead of time, he could have said, oh, bring someone with you because you may have questions and that way they can help you remember any questions or answers. I think it would have helped alleviate some of that shock that I experienced. So overall, what I learned, luckily, if you had your kidney removed, we can all live with one kidney. I also learned that it's okay to take time for yourself and to put yourself first every once in a while and to trust your gut to question when you feel something is wrong. And when they told me that it was just a urinary tract infection, I could have just taken my antibiotics and not followed up, but I just insisted that there's something more here. And then finally, I found that laughter truly is the best medicine. It helped me get through all of this. So I'm gonna leave you with some famous kidneys that you might recognize. And thank you for having me. Thank you, Jen, that was great. And our last talk before the break, we've heard a lot about CAT scans and images and that comes up over and over again. What do they mean? What are we looking at? How do we make any sense of that? And I always turn to Dr. Fielding with that question and she will enlighten us. Thank you very much for having me at this meeting. It's one of my favorite meetings that I get to go to because it's really with the patients. And that was such a great story, but you'll notice how the cancer was found. CT scan, CT scan. And that's how virtually every person who goes through the ER now gets a CT scan. It's become a really, I think, almost indispensable diagnostic test. And unfortunately, there is a serendipitous finding, but in this case, hopefully everything will go well. So I work at UNC also and I work in abdominal imaging, which I predominantly everything below the diaphragm and above the hips, I specialize in oncology and particularly gynecology and urology. So I work in that area. And so how do I try and help out the doctors? Well, the first thing you're gonna see here is our cancer board or tumor board. So almost every major hospital will have a multidisciplinary conference and this brings all the doctors together. So anyone who might be involved in patient care together. And this includes the pathologists who look at the cells and you saw from Dr. Kim. And it calls, including the radiologists who look at the cancers from that point of view. And all of these people get together, we get a consensus sort of agreement on how things are looking because we really learn from each other. And we also yell at each other sometimes because not everything has a single answer. There are often multiple ways to deal with something. Oh, I think we have a picture of Dr. Kim right here, conference. And we have to go through that. And that way also, you don't have to run around all different hospitals, right? You have one space and you get an opinion. Now, when you get the opinion, it's there, you're gonna go over it with your physician team and you're gonna decide, do I like this? Do I not like this? But this gives you one place to go. And so if I had a tumor, I wanna go someplace that has a multidisciplinary team. So the goals for this lecture are really to describe the use of radiology in screening, staging and planning therapy, treatment and followup. Because we're sort of involved in all of those areas. And you're a very, very organized audience, but whenever I do a lecture, I always like to define what we're talking about. So tumor equals mass equals cancer to me in an oncology. So we use these terms, you might see them in your radiology reports. So unless you know you have a benign disease, mass is always something to think about, right? Tumor, mass, cancer. An image, just a picture, right? Cat scans are CT scans. Those are the ones that you go through, you get the injection. And they only take like, I can do the whole body now in 19 seconds. So very, very fast. So it's a really fast thing. Regarding people sometimes say they have an allergy to the dye that we use, it's very uncommon now. And when people ask me what the death rate is from an allergy, it's the same as for penicillin. It's about one in 100,000. So you shouldn't be worried about it unless you know you've had a serious reaction in the past. Then ultrasound is I think the easiest to undergo. No dye, no nothing. You get to sit on the table and have a massage. So that's good. And then magnetic resonance imaging that has the scariest name. We call it MRI, but it's also another tube and you get to lie in the tube and it takes longer and it sounds louder. And we still usually give you dye. Okay, why would I choose CT versus MRI? And we'll go a little bit more into that. But in general, all of the literature supports that we have previously supports CT scanning. So this goes back a long way, right? And so we have many, many studies demonstrating exactly what each finding means. Now, during the last 10 years, which is as long as I think we've had good MRI imaging and it really changes almost every week practically, I think you can use similar findings with MRI. It's particularly useful for certain kinds of tumors and also of course for the occasional patient who already has renal failure. MRI is a great option because we'll still see a lot with patients with renal failure. So renal obviously equals kidney and you also always gonna want to get reformatted images. This is state of the art now. It should be everywhere. So that's when all the axial pictures, little pictures are stacked up on top of each other and then we can cut it anyway. So we can look from the front, which is a coronal or from the side, which is a sagittal. That's extremely helpful. So we get reformatted images on everyone. So this is the renal mass. So this person unfortunately had already had a kidney out because I noticed it was done for a right lower quadrant transplant. And so we take a look at the left kidney. I always tell people ultrasound, you're allowed to use the labels because it all looks kind of gray. And this ovoid thing is the kidney, this whole ovoid thing. And then there's a dark thing in the middle of it. So the dark thing doesn't look like a cyst to me. It looks like it's going to be solid. And so it's actually a nice picture of a mass. So we're saying the word mass. I think it's the most likely gonna be a cancer. And then this person ended up getting an MRI and I'll show you why in a moment. But a lot of, when we asked to say to the, when you last speaker said they wanna see you from neck to pelvis, it's because we find this kind of stuff too. One, we wanna see if there are any metastasis anywhere else, but also we wanna see if there's any other disease going on. So in this patient, here's the cancer that we were looking at before. But you see how the aorta, which is the main supply to your body is split in half. It's called an aortic dissection. So there's blood supply that comes from the front aspect to the left and from the posterior aspect to the right. So we need to be able to know where that blood is gonna come from so that when you have your surgery, we know exactly what they're gonna cut and where they're gonna go, especially when they said the laparoscopic hand assisted. Remember that when you're using that type of surgery, the surgeons are going in through little tubes, right? Little tubes and they're looking through the tubes and I gotta tell them in advance, whoa, that aorta is split. So we need to consider if it needs treatment before, after and what we're gonna do about it. And this is what the chest x-ray looked on this patient. So another thing that most people with renal cell carcinoma get at the very beginning is a chest x-ray. And this thing up here, you're looking kinda sticks out, right? This is the right shoulder and the left shoulder. This is the neck and this is where the abdomen starts. There's the heart and there's this thing. And that's the aorta. That's where the dissection or the split starts. So the aorta split in half, very high up here and went down. So looking at all the pictures together, we now have a dissection we would call it that started at the top. We need to think about whether that needs to be fixed before or after dealing with the kidney, okay? And then we have the kidney lesion and we know now which side the blood comes from. So sometimes people, we see lots and lots of pretty healthy baby boomers, but maybe they've got another disease we don't know about. And even though we get, there's a lot of discussion from Washington about imaging and Lord knows I've been on the phone trying to get imaging agreed to in many, many cases. It is absolutely essential prior to surgery. And last year, because the government does things in such a wise way, we got what's called a haircut in imaging. We got a 50% reduction in payment for all readings and all hardware costs, wham, across the board. So they're obviously careful thoughts occurred in that. And that's why we have to spend so much time on the phone. The goal of insurance companies is not to make sure you're healthy. The goal of insurance companies right now is to make sure they're making money for their stockholders. And also the government is not really a thoughtful group right now and everything is changing all the time. So I would also advise all these other things that you get an advocate for yourself in the financial realm too. And that you make sure what, how things are going to go ahead of time. And I think that there's usually a financial services person at the hospital. You may also want to network and talk with other people who've been through it because you don't want to get a $10,000 bill if it could have been handled earlier. I know you're scared. I know things are rough, but the last thing you're gonna need is a $10,000 bill when you got things to do. So make sure you know what's gonna happen. But literally we took the haircut, as we said last year, and we have not decreased our services at all. But that's, you know, that's not gonna happen forever. So we'll have to see how that works out. Okay, renal cell carcinoma. Everybody's telling you, okay, there's so many of them. What's going on? I don't know. Some of them are increasing for some reason, maybe in our environment. But a lot of it is that everybody gets a CT scan. And it turns out I find one centimeter or two centimeter tiny renal cell carcinomas all the time. And then there comes up later on, which is the whole team's decision out there, what to do about it. Some people like choose to hang out with it. Some people say, ooh, it's cancer, I want it out of me. And some people are sort of in between. They'll watch it for a little while. And there are some rules and guidelines, but this is the case where you're making the decision on this. The final call will be yours. And so it's good to know what the guidelines are. And your physicians can go over that with you. And that's why I advise having the team approach with high quality physicians who do this all the time, because they will know what the current guidelines are. So is there a screening test for kidney cancer? No, I don't have the silver bullet. And there are some that are coming up now in imaging. We're finally there where we're doing molecular imaging. And Dr. Rathmell and I have done some work combining some of the medications with some findings on there. But ultrasound or CT, we do those patients with the genetic disorders, like we talked about von Hippel-Lindau and other family syndromes. We're gonna be screening those people, so we're gonna see that. And overall, ultrasound is great for detection. So a lot of people will have that early on. Remember, we saw the black thing. Usually you can see it. But CT is good for treatment planning. So you'll probably have those along the way. How is CT done? You've all had this, okay? Every place is kind of different. But I usually obtain three sets of pictures. The first two sets are basically used to determine the cancer. How vascular is it versus how other things. And then finally, when I stack them all together, I talked about making reformats. That's when I decide on how many arteries there are. How many veins there are. Is there any complicating factor? Are there lymph nodes? Is there anything in the liver? Or is there a secondary lesion that I need to see? Can MR be used instead? Yeah, if you're at a place where people read MR all the time. So again, our hospital happens to have a very strong MR section that may not be true everywhere, but CT is a really good test. And I use only MR as a second choice test. So what about pet and kidney cancer? Dr. Rathmell and I were talking about that and it's always been like no, no, no. But now I think it's like soon, you know? And you're going to be hearing later on, I think from a speaker specifically about that. Right now we don't use it as a routine, okay? But I think pretty soon things will be changing. But this is just a patient that I've treated, not I've treated I've seen, who has vulvar cancer and metastatic disease to the left chest wall. And so we have the vulvar, we have the bladder here, actually the vulvar cancer has been removed. These are the kidneys. And you see how you're looking from the front now. So this is right, left, superior, inferior. And this would be under the arm. The axilla and the chest wall. So now the patient gets some therapy. And this looks better, but we have a new site in the spine. So PET CT or any pet relies on a snapshot of glucose in your body. So if there's someplace that's very active with blood and sugar, okay, which tends to be most cancers, it takes a snapshot of that location. And so that's really what you're looking at. So PET is a nice whole body scan. It doesn't really focus on little pieces. And you also can't measure the size of the lesion. So sometimes we have to do two things or one thing one time and the CT the other time. But PET is very useful for identifying, you can see those bright things, you could really see that. But you can't measure the size, which is also critical for making a decision. This is new technology. Dr. Rathbell and I will be publishing some work on this soon. And we happen to have a combination of a hybrid PET and MR scanner. So we're using the MR underneath in here. This is a normal kidney there. We saw some blood supply there. This kidney is obviously abnormal, much larger. This particular case has a tumor in it. And what we do is put the PET scan over it. So we always put PET scans over CT scans. That's how we started out. But you still couldn't measure things. The concept here is I can use this part of the scan to do all the accurate measurements and stuff. And then we can use this part of the scan to see which parts of the tumor are active. So we're trying now to put those two together. We have one of these machines. There's now, I don't know, 30 or something like that. I still don't know if it's going to be a clinical tool, but for certain people. For children, I use it all the time. There was a little book up there that said Wilms tumors early at the beginning. That's a special cancer of children. It's a great tool. No radiation. So you have a child that's gonna live a long, long life from a Wilms tumor. You don't want to radiate that child. So reading the scan, I try to tell your doctors what they want to know. How big the tumor is, where it is, how many there are, and sometimes patients have a familial story. The relationship to the arteries and veins and ureters, how many there are, where they come off, again for the surgeons who are going to be looking through those little tubes. The presence or absence of enlarged lymph nodes. Measure those and find them. And all distant disease. I'm gonna take a look at the liver and the bones and those kind of things. So it really is a big sort of shopping center list for that. So I just wanted to show you a couple pictures. This is one of the very first patients I saw 12 years ago when I came to UNC. 44 years old with a large mass. And we needed to do some good staging on this person and I just got the right equipment for it at that time. So this is the normal kidney here. This is the right kidney and this is the left. And that's a big tumor, right? So quite a good size, but hard to see where everything went. I knew where most of the vessels were, but I really wanted to see the pancreas and some other things over it. So here, this is when I told you I stacked them up together, all the pictures. And now we're looking from the front, okay? And I can see that actually this tumor is just in the upper half of the kidney. And I can see that this arrow points to a piece of the pancreas. If I can tell the surgeons, it's right on it. So when you're gonna go in there, watch out for the pancreatic tail. And I can say, oh here, the adrenal gland, that's that little upside down Y thing, it's not involved. So these are sort of just different things that over the years I've learned to what people wanna know. I don't use the ones from the side as much, but it's really critical for me to get the ones from the front. And how about what kind of cancer it is? Sometimes I can be helpful, sometimes. So here, I know there's something wrong. If you pick a kidney that's wrong, this looks like the good one. It looks like the abnormal kidney. Something's going on here, but it looks like there might be a little clot in there. And here's a more tumor. And I was deciding which kind of kidney cancer it was. There's certain signals that I'm looking at. But the presence of the clot was what really made the difference for me. And that's where I saw it the best. So this is the big vein coming from the bad kidney. And there is the clot inside it. And that only happens with your standard renal cell carcinoma. There's another type of cancer called transitional cell carcinoma. Also occurs in the kidney, doesn't make clots. And then also I wanted to tell where the lymph node was. Oh, here it is. Look, it's at the lower pole of the kidney. This is where the big vessel is. And it looks like we can figure that out nicely. And this one is where we learned a little bit about, again, other things. This time the kidney was here. This one's a little bit smoother and denser, but I couldn't tell what cell type it is from looking at. I don't have that magic glasses. All I can do is tell you where it is and kind of what it's gonna be. But then, this is important stuff. How many vessels? So if you're going to have your kidney removed, that surgeon wants to know how many vessels and where are they? So usually, I mean, they're supposed to be one. 25% of patients have two. And most of the time, actually, they go to the superior, inferior poles, we call it, of the kidney, but these are all right in the middle. This is gonna be a tough, if you're gonna remove a tough part of it. And then while I was there, I found out they had a kidney stone on the right. Which doesn't seem like a huge yield. That was why they came in. Pain. No, on one side. Then find this other thing on the other side. So another patient, remember, Dr. Kim was talking about dialysis patients who get cysts on their kidneys? This patient, we did a CT scan on. And we had this thing. It's kind of solid, kind of hard to tell. This is how we measure the density. 35 is about soft tissue. It was like, oh, might be. And then it needs to assess what happens to it when we add contrast material. So now, all of these dark things are cysts. But look at this thing. And when I measured it, it doubled in density. When you increase the density, it's a cancer. It's a tumor. And so I was able to find the one this that was problematic versus all the other ones. So that's also trying to help out on what to do next. And then just a couple other things that we can help out with. This is a cancer that's posteriorly high up here. We do percutaneous therapy at our hospital where what we do is put probes right here, hot probes, cold probes in, kill off the tumor. And there it is, dead. It's pretty good. It's about 90% rate of cure with this type of tumor, compared with the surgical approach. But we use this on particularly difficult cases, very obese patients. That sort of thing. And as I said with Dr. Rathmell and her colleagues, we looked at some of these drugs that Dr. Kim was talking about, ceditinib and seraphinib and those kind of things. And when the patients got this drug, it's kind of interesting. We've always used size as a very important indicator of whether the kidney's getting better or not, right? So this patient, this is their kidney with the tumor in it. And this is after they got the ceditinib. So there's all this dead tumor in there, but it's not very much decreased in size, even though there's been a really good response. So that's where radiology is changing. In this area, we have the same type of thing going on, but this guy is a non-responder, no real change in density or size, non-responder. And this patient has plenty of tissue here, complete, very good response on this patient, very dark. So even though the size is the same, the density is different, and that may eventually come into staging. And you saw this from Dr. Kim earlier. We had different types of tumors and he showed you these different types of cells. One of the things Dr. Rathmell and Dr. Kim work on is deciding which drug works for which cell type. Because not everything is everybody. So thank you so much for listening and I'll be happy to talk with you, okay? Thank you. Thanks very much. We will take a break. I think we're a little bit behind, but we have some time in the next session. So let's all come back at a quarter till. Thanks very much. This is Dr. George, I was talking to you earlier. So they're kind of familiar with your heart rate, right? Is it not working? I figure, you know, the bigger thing, it seems like it's doing well. Just the casing, it wasn't popping all the way in. Kidney, KCA, second line. Oops. That's the one file? Yep, that's it. Thanks. Any audio or video we need to check? No, no, no. And we are doing a video recording live stream, so we're gonna have you wearing the lavalier. Just clip it on right about there. And we are audio and video recording, so we're gonna have you wearing the lavalier mic. Okay, I can do that. Move around. I need to turn my pager and phone off and all that stuff. How about if I just hand it over? Yeah, you can. Can you cover me? I'm on call this weekend. It won't go off. I just got a page, so that'll be there for a while. Don't let her go. Okay, we're gonna go ahead and get started. I think people are still coming in with their coffee, but we'll get the second morning session started. But before that, she's been captured. So this is Melissa, who put all this together, organizes the food and the time and the schedule and the live video feed and everything. So thank you very much. With that, it's my pleasure. We're gonna turn this mic over to Dan George. We're gonna talk about treatments for metastatic disease. First line, second line, then how you deal with the toxicity therapy. So here you go. Fantastic. Thank you, Kim, and thank you all for coming out this morning. I really appreciate the chance to talk. And I've got 20 minutes to talk, and then we're gonna do a panel for questions. So if you can't write down your thoughts and we'll cover them in the panel in a little bit. But I'm gonna do something that I like to do, that we never get a chance to do enough of. And that's sort of give you my thoughts on kidney cancer. And this question that Dr. Rathmell has posed for us. How do we decide when we're gonna start treatment in patients with kidney cancer? What treatment are we gonna choose first? So what I thought I'd do is rather than show you a bunch of slides and data, is to talk with you a little bit about how I view patients with kidney cancer. How you all, if you come into clinic, how the physicians are seeing you. And then what we're thinking in terms of what are the distinguishing features of your cancer of you as a patient? And then how do we think about the therapies in that context? Because the data is fantastic and it's really a huge guide for us in terms of understanding which drugs work. But it's population data. You all are individuals. Every single patient, to me, is different. And it's important for people to realize how they're different. When they look at that data or you go online and you read something about kidney cancer and the survival of kidney cancer, patients get, I think, rightfully nervous. This is a scary disease. This is a lethal disease, especially when it's metastasized. But it's not the same disease in everybody. And it's really important, particularly for people who are just diagnosed with what we call metastatic disease or disease that's spread. It's no longer in the kidney. It's out of the kidney. It may be in a lymph node. It may be in the lung. It may have spread to bones or liver or even the brain. It may have spread to all kinds of places. And those are one of the important factors that I look at. When I see a patient, even before I see the patient, even before we meet, we get the records on you and we are looking. And the things I'm looking at in your records are number one, what's the diagnosis of kidney cancer? Is it based just on the scan? If someone has scan, there's a big tumor in their kidney. It's pretty diagnostic. But it doesn't tell us the type of kidney cancer. Did they have a biopsy? Has the kidney been taken out? If the kidney's been taken out, the pathology, what does it show? Is it this clear cell cancer, the most common type, but not the exclusive type? Is it have some papillary features or some sarcomatoid features? Is it one of the more rare forms of kidney cancer like chromophobe or even oncocytoma? These are technically kidney tumors, but they have a very different biology than the clear cell cancer or even the papillary cancer. So these are all factors that I look at even before I see you in clinic. Next thing I look at is, what's the extent of disease? Is it confined to the kidney? Is it something that we think we can take out? Is it something that's spread out of the kidney? Is it spread to lymph nodes? Is it spread to the lungs or other sites? How many areas? And to me, are there any sites of disease that I'm worried about a complication? I think so often people think, well, it's just stage one, two, three, or four, but there's a big difference in stage four cancer between patients who have, say, just some tiny areas that are asymptomatic and not bothering them to parts of the body where it's really symptomatic, particularly things like bone and vertebral body, metastas along the spine, or into the brain, or pressing on a vital organ, pressing on a bronchus in the lung, or pressing on a major blood vessel, or doing some other major complicating feature to it. Those are situations where, again, we're gonna individualize care because the care is gonna be focused primarily on that site of management first. It's not to say that we're not gonna use drugs and other therapies, we absolutely are. But the first thing we're gonna focus on in a patient like that is how to manage that site of disease. So that's the second thing I look at before I go in the room to see you is I'm looking at the extent of disease. And if I can, we always request, it's a little bit of pain, the CDs with your images, because the reports don't tell the story. I know you all read the reports, but I'm always surprised how many patients I go in the room and I pull it in the CD and I say, have you seen your images? And they say, no, I haven't seen them. That's really, really important to me that you know where your tumors are and just what they're doing. It gives you, one, it gives you some peace of mind one way or the other of what's happening in your body. And two, it gives you an idea of what you might wanna expect in the future for a symptom and what to look for. So reading the reports, they're not written in layman's terms, they're frequently not descriptive enough. Nobody can write in words what a picture can show you. And so it's so important to me that we go over that. So that's one of the things, and I look at that before I go in the room ahead of time so I kinda know what we're dealing with. Another thing we look out of the labs, the labs are really important. They're important because they give us some prognosis, some indication of where you are in the spectrum of things. People have really low hemoglobins, blood counts for their red blood cells. That's a very important prognostic factor. If they've got an elevated calcium level, that's something that sometimes gets missed. It's sort of slightly elevated. It's not something that people associate a lot of symptoms with, but it can be symptomatic. And it's very prognostic. So I look at labs like that. I look at kidney function. Kidney function is really critical for the tolerance of drugs for just the well-being of the patient. Kidney function is really important. I look at a protein called albumin. It's not necessarily one that shows up a lot, but it tells us, I mean a lot in our prognosis, but it tells us a lot about the health of the patient, you know, your nutritional status. And to some extent what the cancer's doing is the cancer catabolic tumor. What I mean by that, it's a medical term, but it means the cancer's breaking down your body, that you're losing weight, right? And that's one of the symptoms we can see with patients. But the reason they lose weight is because you lose appetite, you're not eating enough, but you're also hyper metabolizing. The tumor's metabolizing away a lot of nutrients. And it's starting to break down your body's nutrients. And unfortunately, they don't start with the fat. They start breaking down the muscle. And that's the most important part of your body. So to me, I mean, it's a really critical piece here, is really understanding, you know, that aspect and if that's happening. And then I look at the doctor's notes. I look at what people have read and said about the patient, what's been going on, what's been reported so far for symptoms. We have patients fill out a little symptom score thing, a little patient reported symptom profile of what we call a review of systems, of just what they might be having. And I look at that as well. So that gives me kind of a picture before I even go in the room of what's going on with patients. And then when I'm in the room, the first thing I do is size up, how functional is this patient? Are they in a wheelchair right off the start? Or are they sitting in a chair? Do they stand up when I come in the room? Are they, you know, is it hard to get up? Those kinds of things, you know, I sometimes I'm not even necessarily conscious of it, but that's what I'm thinking when I go in a room and I see a patient is, you know, how functional. I ask questions about what do you do in your daily routine? You know, are you, what's your job if you're working? If you're not working, what's your daily lifestyle? Do you walk every day? How far do you walk? What kind of, what kind of pace do you keep? And things like that. Do you, you know, do you do a lot of activities around the house who you mostly sedentary and things like that? Although that doesn't necessarily show up as a score or a number. It's a really important characteristic for us in understanding how the patient is functioning. And to me, it's probably one of my best indicators, much more so than age or gender or size or anything else of how you're gonna tolerate a medication. It's just, you know, if you're somebody that is, you know, just active. Just I like to use the term vertical because my old Hopkins hematologist William Bell used to always tell us, are you vertical? You know, that was his term. He's a little bit crass, but at the end of the day it's really true. The patients that are sitting or lying a lot don't do as well as the patients that are up. And now we have, now it's the new thing to have vertical workstations. I'm at a vertical workstation. You know, we're, you know, this is an important part. I think we're starting to realize in our everyday lifestyle, but it's been a really simple concept for a long time. So those are some of the things that I look at when I see a patient. And then the question comes down to, you know, to prognosis, how do we determine that? The other thing, and I forgot to mention, the other thing I look at before I go in the room is the timing of this story. And what I mean by that is, is this a sudden story? You know, this patient, you know, a month ago was fine, started coughing, got a scan, and now they've got metastatic kidney cancer. And it's in multiple places. Or is this a story of somebody who had a tumor removed four years ago? And then, you know, on an incidental exam was found to have a nodule somewhere. Those are very, very different scenarios. In one scenario, this patient is already symptomatic, is already spread. The disease almost, you know, from the get-go has, you know, gotten out of the kidney. And that patient has a likely course that's gonna also continue rapidly so that we will likely be thinking of one therapy onto another pretty quickly. The other case is, frankly, someone I'm probably not even gonna treat right away. Now, that may come as a surprise to you, but I'll tell you that at Duke, we just did a retrospective analysis, just got that accepted for publication, a recent paper on our retrospective analysis of over 200 kidney cancer patients managed from 2006 to 2008. In a quarter of those patients, we deferred therapy on their first visit. We did not. You know what I mean by that? It's not like it started the next week. I mean, we decided not to start a systemic therapy. Now, we may have done a local surgery. We may have done some other kind of palliative maneuver, but a chunk of those patients, and some of them may be gone right to hospice, but most of those patients that were in that group, we decided their disease wasn't aggressive enough that we had to start therapy right away. Now, that may seem a little bit defeatist, but the rationale behind that is that there is a significant percentage of patients with kidney cancer that is like that second case that I described to you, that is slow-moving, is limited metastatic disease. And what we call sometimes oligo-metastatic disease only has a couple of spots, may only be in one organ and just one, two, or three spots, or really, really small spots, less than a centimeter. And we feel that that disease is not going to change very quickly in the short term, so we'll follow it. And the reason not to start therapy right away is because we believe the therapies will decondition the patient. And again, getting back to what's the most important factor for these patients that is under their control, to some extent, is how vertical they are, how functional they are. And if I'm gonna hurt that functional status, but I'm not really gonna make an impact on the disease because it's not really moving or growing that quickly, then I may be doing that patient a disservice by starting therapy ahead of time. And it's a concept that's not very prevalent out there. It's not in our guidelines. You don't see in our guidelines a recommendation for that. But we all practice it, we all recognize this. Those of us that see a lot of kidney cancer patients recognize that this is not necessarily a scenario where everybody has to start on a drug right away. It's hard if you only treat three or four kidney cancer patients a year to feel comfortable with that, to know that. Again, the guidelines don't really support it. But we recognize that that's an okay practice. And when we looked back at our practice of these patients, they had phenomenal outcomes. They had average survivals of five years or more. And they did get therapy, the ones that progressed. But some of them still, a few of them still didn't get therapy for several years. Now, there've been a couple of prospective studies going on and some of our colleagues at other centers are looking at actually randomizing patients, to starting them right away or watching them who meet this kind of criteria. I call them the very good risk patients. But I think it's an important concept that, again, doesn't get enough recognition, something that we're comfortable in academic centers where we see a lot of these patients, but in a lot of other places we're not. So that's one end of the spectrum. What's interesting is that's also the patient population who I will talk to about Hytocentralucin-2. Now, you may say, wait a minute, you just told me you're comfortable doing nothing for that patient, or giving him an incredibly toxic inpatient therapy. And it does seem kind of incongruous that you're gonna say, you can do this, we're gonna defer therapy, or we can do this really intensive therapy. The reason for that is because the goal of the really intensive therapy is not to slowly control the cancer. It's to try to cure you. Our goal of that is nothing short of trying to get you to a complete remission, no evidence of cancer, and hopefully the cancer doesn't come back. And we've got some cases of that. I don't know if anybody's in the audience that has done that, but we do it still because we do have some cases like that, but it's not that common. But that's the population where we can afford to try that even if it only has a 5% chance of working because if it doesn't work out, yeah, we've taken on some side effects and things that are reversible, will require work to get yourself back into shape and everything, but it's reversible. But importantly, that's a population of patients that we haven't lost ground. If three months later we didn't cure them, the cancer didn't go away, but at least we didn't lose ground in that patient. So to me, that's a really important setting where we can consider that still. But this is what we call the good or the very good risk patient. Where most of our patients fall is in this intermediate or higher risk population. Patients that are like the first case I've presented, presenting with some symptoms with disease that's already spread, and we've got some really important decisions to make. And you may have already heard about debulking nephrectomy, I haven't talked about that. So one of the decisions is, do we take out the kidney in that patient? And we do a multidisciplinary clinic just like at UNC. We talk with our surgeons, we review the case together. And a lot of the factors that I mentioned to you, how functional the patient is, what symptoms they have, their laboratory values, and the sites of metastasis, and how big, how extensive is that spread of disease, all factor into that decision. So we use those decisions to decide, can we afford to put this patient through surgery? Is it a big open surgery or is it a laparoscopic surgery? That's a factor too. So all those things kind of factor into whether or not we take out that primary tumor. But we still do a lot of that. And we do it for a couple of reasons. One, we do it when that's the bulk of the disease and we can debulk most of this cancer. We still believe that's a benefit to this population of patients. And it's been shown in the past, not as much with the newer therapies that are available, but we still believe that could be beneficial. We think that could be beneficial for future immunotherapies as well, to have that primary tumor debulked. So with the new evolving therapies, we think that's gonna be important as well. And I think the last thing is that this local disease, when it's really bulky like that, eventually can cause a lot of problems locally for the patient. And it's harder to do that surgery later on in their course. So if we have a window to do that upfront, to debulk it, to get a better idea of the pathology that we're dealing with, to have a lower tumor burden for future therapies and to avoid future complications, we like to do it. But it comes at a risk and a cost and delay and a deferment of our other therapy. So it's a balance there. The second question then for that patient population is what's gonna be their systemic therapy? And I'm gonna tell you something right now that I think is really important to recognize is that we have some really good systemic therapies for patients that have intermediate or higher risk, more aggressive kidney cancer. But I believe that the way we treat kidney cancer today with a single drug at a time is not the best for everybody. And I believe in the future, we're gonna have to figure out who are the patients that really benefit from one targeted therapy. Typically these drugs that block the blood supply, that block this protein, VEGF or VEGF, this protein that helps grow blood vessels for the tumor. And drugs that target that like Sinitinib or Pozopinib, these are really effective therapies for a big percentage of patients. And we've done some biomarker work. We think there's at least a third of this population up front that really benefit and that's all they need is that therapy. But we think there's also sizable chunk of patients that may get some benefit but not enough. They still have some poor risk features and we need combination strategies. And I think right now there's a lot of clinical trials going on looking at combination strategies and we think that that's gonna be a future as well and one of the most important questions in kidney cancer today is how can we do even better in treating these frontline patients? But for the patients that we're not gonna put on a clinical trial or we don't think are that high a risk and we think that could really benefit, we start but have some of these features, these more intermediate risk features. We start our VEGF targeted therapies and typically it's one of those two pills, Sinitinib or Pazopinib. And I think they're both very active pills. I'm personally comfortable giving either one. I've probably given more Su-10 and if you follow that Duke, I probably give more of that drug because we started with that drug and we're comfortable with it. And there's one thing I do like about it and that's an intermittent dosing. So it gives patients an opportunity to kind of recover from any side effects that they see and longer term that kind of intermittent approach is I think, you know, healthier. You know, I recently started an exercise program. I don't know if this was a gift or a punishment but my wife got me a rowing machine. I don't know if you know, this is these old school kind of, you know, torture machines. There's nothing to plug in. It's a chain, it's a fan, you pull this thing, you slide on the seat, it's rough. And I was doing this. I used to row in high school. So that was I think why she got it for me. That or the house of cards show, I can't decide. But she got me this rowing machine and I was working out and I was doing about 20 minutes for about 5,000 meters and it was killing me. And then somebody at my swim team told me that there's this intermittent approach where you work really hard for 20 seconds and you go easy for 10 seconds. So you do that for four minutes and then you know what I'm talking about. Yeah, okay, so I tried this and it was faster. I and I finished and I was still tired but I finished faster and I was still able to pick up my rate and go faster for those 20 seconds by just taking that 10 second break. And it wasn't enough to totally get back to restful but it was enough to give me a break. I think to some extent, you know, that sort of suit 10 approach is kind of like that. The other approach is a constant one and for some patients that works too because their body just acclimates to what it is. I'll give you a clue on these drugs. For both these drugs, the hardest thing is the first cycle. And I don't think people necessarily realize this, particularly people in the community, but the first time you take these drugs is the worst. You know, usually we think like with chemotherapies and stuff, there's a buildup effect. And with each cycle, with each month that goes by, it gets harder and harder. That's not true with these drugs. The first time you take it, that first month is the hardest. We look at our patient reported symptom profiles, they all fatigue, all that is the worst with the first month and then it gets better. So it's so important that people know that, that we're really active in managing around that first month, that we don't put people, you know, hit them too hard with those drugs. I think more important than which drug you choose is how you administer it, how you manage the patient. You're gonna hear about side effects and symptoms and management. But to me, that is by far and away, the biggest differentiator and outcome is how you manage a patient on one of these drugs rather than which one you choose. They've done head to head studies and they look pretty equivalent and, you know, I'm not gonna argue one is better than the other. I don't think we can make that argument. But I do think that how you treat patients through these therapies, how you maximize that benefit is critical and there's not an art or a science, it's just plain old common sense on listening to patients' symptoms and just knowing, experience what the thresholds are for when you need to change or take a break or lower the dose and do things or even change that regimen from, you know, four weeks on, two weeks off to two weeks on, one week off or things like that. So those are all the things that, you know, that I think of when I'm choosing these therapies with patients, you know, do I need to treat patient at all? If I am, what's our goal? Is it cure? Is it help them live as long as possible? Disease control? Are there symptoms we need to manage up front? Is there a kidney we need to take out first? If we're gonna start therapy, is it a clinical trial? Because I think that they need that in a combination we should do or is it a standard of care? And if it's a standard of care, which of these drugs do I feel comfortable with? So that's kind of my upfront talk right now. There's one other therapy we use in rare circumstances and that's, that's TEMserolimus. That's an IVM tour inhibitor for particularly patients with poor functional status. It's an IV drug you get once a week. So we really get to control how much patients can manage. We get to see them and manage them closely every week, which I like. It's really for the particularly sick patient I don't think is gonna tolerate some of the other therapies. Fortunately at places like Duke and I suspect UNC, we don't see a lot of those folks. Those folks can't make it all the way in. And so a lot of our patients don't have to resort to something like that. It's nice to know we have a therapy even for those patients. But a lot of that are patients that are pretty sick. They need therapy right away. I counsel a lot of doctors out in the community about that and we'd still use it there and it's a good drug, but unfortunately that's a patient population. We're still, it's still not enough. But that's the last piece of this sort of upfront regimen. So I don't know if that's 20 minutes. I probably went over, Kim, but we'll save questions. Thank you all very much for coming in your attention today. Look forward to this discussion later. Thank you. Sheriff. How we can hear more about that. After the online, we have a few other choices as well and similar kinds of things make that up. And we'll hear from Dr. Matpalowski. He leads our Gen. T urinary groups here at UNC and directs our clinical trials program. Okay. Well, thanks very much, Kim, for the invitation and opportunity to come and speak today and it's great to follow Dan George who's really a leader and someone we look up to in this field of renal cell cancer. I'm gonna do this a little bit differently than Dan, but I think it'll be helpful to look at some of the data in the way that we look at it. And what I'll do is I'll speak over some of these slides. So don't worry so much about some of the details just to give you a sense of sort of the information that we look at as physicians and how we ultimately translate this information to the patients. And so after drugs like Pizopinib or Votriensinitinib or Sutent or Temserolimus, otherwise called Toracel, what happens to patients who progress on those first line therapies? And so what I'll do is I'll review some of the main studies that have been done related to second line therapy. These are acronyms for those studies. We love acronyms in medical oncology and in medicine in general. And so we'll go through the record one trial, the access trial, the intersect trial and the record three trial. We'll talk about some potential biomarkers that may be used to predict response. And then we'll talk about some proposed treatment pathways. And people in this audience like Kim Rathmael, Billy Kim, Dan George have really been instrumental in bringing to the attention of the medical community the use of potential markers, whether it be blood-based markers or other type of markers to be able to select patients who are most likely to respond to particular therapeutics. And so this is sort of the landscape when looking at second line metastatic RCC, which is renal cell carcinoma. These are a series of studies that have been done with different agents, which are listed in this column. And this is related to patients who have previously received what are referred to as cytokine therapies. So these are historically patients treated with interferon and interleukin-2. And I can tell you that when I was in training back in the early 2000s, the only agent that we had were cytokine therapies. And in fact, we use a lot of interferon in patients which can be toxic. And unfortunately the response rates were not nearly what the response rates are with the new targeted agents. And what we're seeing and looking at many of these therapies is that we're seeing responses with essentially all of these therapies. And this PFS refers to something called progression-free survival, which is an endpoint that we use in oncology which incorporates a number of things. It relates to the progression of the cancer, the growth of new tumors. And it also includes things like cancer-specific survival. So living or dying is related to the cancer or overall survival. And so we call it a sort of a composite endpoint. And we use that to measure the success of agents. This next table demonstrates, again, second-line therapies for metastatic kidney cancer. But these are looking in patients who have previously received some of the new agents. So some of the ones that Dr. George has described, like Pizopinib or Sunitinib. And so here, Avirulimus, which is also a phenotorin-accytinib, which is in LIDA, as well as a series of other agents, once again, after patients progressed on first-line therapy, what we saw is, in fact, we were seeing responses and we were seeing historic, as compared to historical series, improvements in survival is related to these agents being used after patients had already received some of these new, very exciting drugs. And so one of the most important studies that you should know about is what's referred to as the record one trial. And so this looked at the drug Avirulimus or the trade name is a phenotor versus placebo after progression on one of these VEGF receptor therapies. And so it took patients with clear-cell disease who had progression on seraphonimcininib or both, who had a good performance status, which is what Dr. George was referring to, the vertical that he mentioned, and randomized them to receive Avirulimus in best supportive care versus placebo in best supportive care. And what you could see is that patients who received the placebo were able to go on to Avirulimus if they were progressed on placebo. And what was exciting about this trial is that the Independent Data Monitoring Committee actually recommended stopping the study because of a significant benefit for the affinitor group over the placebo group. And what we're seeing, and again, these are these sort of fancy curves that we look at in oncology, but this is really the probability of survival. So 100% being very good, of course. And then these are the months. And this is for progression-free survival, that endpoint that I mentioned before. And what can be seen is that the Avirulimus curve is on top of the placebo curve. And so Avirulimus is better than placebo. And these with immediate progression-free survival are sort of the average numbers. And I always say to patients, I'm gonna give you the average numbers if you want them, but I've never met a patient who's average. And so if one looks specifically at the record one study and looks at the prior therapies that they received, you can see that the majority of the patients received that drug, Sutent, which is the drug that Dr. George referred to. And so what was particularly exciting here is that we were beginning to get a glimpse into the effectiveness of some of these new agents in patients who progressed on these first-line therapies. And this was really the first large randomized phase for each trial that demonstrated a significant benefit associated with this new mTOR inhibitor. These drugs are not without toxicity. Dr. George mentioned this. And things like mouth sores and slight increase incidence of infection. Some patients can develop some inflammation in the lungs related to the affinity of the Avirulimus drug. Rarely is it significant. Oftentimes what we'll see is some abnormalities on the CAT scan of the chest that really don't ultimately amount to much at all. And so we generally just follow those. Some patients can develop although rarely significant cough or shortness of breath associated with those symptoms. But in general, this is very manageable and we can even treat those severe cases with things like steroids. Another drug that's been very exciting is one called ExitNib or NLIDA. And this is a series of phase two trials. So phase two trials are those trials which are designed to look at the preliminary activity or efficacy of the drug. And these phase two trials of ExitNib or the trade name again NLIDA looked in patients who had previously received, here's one trial cytokines, another trial some of the drugs that we just talked about. And again demonstrated very promising response rates and survivals in patients who had previously received some of these exciting therapies. And so once again, it looked like we had a winner with respect to a drug that could work after patients progressed on these first line drugs which unfortunately don't work in the majority of patients forever. Although some patients can be on them for years and years. And so this was the trial design. Again, one of the schemas that we typically look at as physicians in oncology, so patients after disease progression, randomized to ExitNib or the Serathinib drug. And this was again looking at that end point of progression free survival. And here again without going into all of the details you can see that the ExitNib curve is above the Serathinib curve demonstrating a significant benefit with respect to this progression free survival over the drug Serathinib. And so based on this, much like in the record three trial in Lyto or ExitNib was FDA approved for the treatment of patients who progressed after first line therapy. In terms of treatment related side effects of these drugs, so they're not without side effects. I agree with Dr. George that the most substantial period of time for patients is that first cycle and getting them through that first or second cycle of therapy is really crucial. And explaining to patients that actually the symptoms get better. Again, unlike chemotherapy where we think of things becoming more cumulative over time with respect to side effects. And so diarrhea can be a side effect. Hypertension or elevation of the blood pressure and Dr. George has done work related to elevation and blood pressure and its significance in monitoring patients on these therapies. Fatigue, there are rashes that can be associated. This is a rash that's associated more commonly with Serathinib or Nexivar, which can occur on the hands and feet and can be painful and uncomfortable for patients. And in fact, there are things to do for it. And I know Mary Dunn is gonna be talking about some of the symptom management issues. The real question is now that we have these two drugs that are FDA approved for the treatment of patients who've progressed after first line therapy, which one do we use? And that's a tricky one. And so these trials are different. They were accrued, in other words, patients went on study during different times. They had different comparator arms, right? The Veralimus or record one trial at placebo, the Axis or Exitinib trial was compared to Serathinib. There were differences on how many patients received two or more therapies before, typically patients that are more heavily pretreated may have a more difficult time or potentially a lower likelihood of response to therapy. Their poor risk, and Dr. George mentioned those very good risk patients where there are poor risk patients as well who have more adverse or bad features. And so those were different. And there were a series of other things that were different as well. And so it's not completely appropriate to try to compare these trials. That being said, in an ideal world, what we'd love to do is have a randomized trial, right? Where we took patients and we randomized them in the second line setting after progression on first line therapy to a Veralimus or Affinitor versus Exitinib. Well, unfortunately we don't have that trial. And that's a nature of the design of clinical trials, the pharmaceutical companies wanting to design their trials in particular ways. But what we do have is we do have a study where we compared an mTOR therapy much like a Veralimus or Affinitor to Serathinib, which has multiple targets, but one is that VEGF pathway. And so this was a randomized trial. It was called the Intersect Trial. And again, this is perhaps ideally what we would have liked to have seen. And what was seen here in the Intersect Trial is that there was really no significant difference with respect to the progression-free survival. There was a suggestion that there may be a benefit to the use of the Serathinib drug over the Temserolimus drug with respect to survival of patients. You can see the yellow curve for Serathinib over the blue for Temserolimus. I think that this really doesn't answer the question completely about which drug is better or which class of drugs is frankly better because we didn't really use the best drugs to be able to answer this question. But at least it provides some information related to the use of these different types of therapies in the second-line setting. And finally, one of the questions that many ask are how do we sequence these drugs? What do we do? How do we put one after the other? Unfortunately, when all of these drugs came out, there was tremendous excitement about how many drugs were coming out one after the other, but it really didn't give us a great opportunity to be able to figure out how to give them. And Dr. George mentioned the issue of combination therapies and a lot of those things are being investigated. There are toxicities and side effects that we need to think about when we give combinations and some of those haven't worked, but I think there are certainly others to explore. And this was a trial that sort of looked at that question of sequencing. And it said basically, well, our standard format is to give synitinib or the sutin drug followed by the affinity drug based on the record one data. And it asked the question of, well, what if we were to give the Averilimus drug first and then follow it with the sutin drug? Would the outcomes be just as good? And what this basically showed is it didn't appear to be the case that if you gave the Averilimus drug first, that it was similar to giving the synitinib drug first or the sutin drug. In other words, sutin followed by the affinity drug appeared to be better than affinity or followed by the sutin drug. And this is important because we begin to think about how we manage patients and how we sequence these agents. At least this begins to provide a framework for some of the data that we need to look at to be able to best answer these type of questions. And so the question of biomarkers are ways that we begin to think about who do we select for which therapy? And again, there have been a lot of work in this area. There's been some information to suggest that we can use, for example, blood pressure as a biomarker or a marker of response. So we can actually escalate the dose of the exitinib or inlidid drug based on patients' blood pressure trying to obviously work toward increasing the drug, but at the same time managing the high blood pressure which can be a significant issue for patients on this therapy. And I'm sure Mary will talk more about that. And then what we've also started to do is look at certain genes within patients to try to predict those patients who are most likely to respond to a particular drug or for that matter are more likely to experience a particular toxic side effect. That's something that we're working on a lot at UNC and I'm sure it's happening at Duke as well. And so what are the guidelines? What do we use to make these sort of decisions? So as physicians, obviously we individualize, we sit down with the patient in the room and we make a decision with the person sitting in front of us. But we also like guidelines to be able to use to make these decisions. And these are often used in the community to be able to make decisions and some of the nuanced things that Dan was talking about that perhaps don't go on in the same way in all community settings. These can be extraordinarily helpful. And I think what's really exciting is what I started with today which is when I was a fellow in training, we had interferon and interleukin2 and that was it. The response rates to interferon were somewhere between about 15 to 20%. And here we have a list of the therapies that we have available for patients who progress after first line therapy with advanced kidney cancer. These are the national comprehensive cancer network guidelines. These are the guidelines that are used throughout the United States. This is another algorithm that was proposed to look at how we think about patients being treated after progression on first line therapy. And there are slight differences, but the bottom line is again, there are multiple agents that we could think about or we could think about targeted therapies that haven't been previously used. So if a patient may have progressed on the drug like Pozopinib or even Acidinib hadn't received Acidinib in the past, one could consider using those agents. And then these are the European guidelines. So these are guidelines that are used by our colleagues overseas to make decisions about second line treatment as well. And so again, you see similar names of the drugs that we've talked about. But again, I think going back to this, it really tells an extraordinarily exciting story about what's gone on over the past 10 plus years in the management of patients with kidney cancer. And I can tell you that there is a tremendous promise for what the future is gonna bring based on our enhanced understanding. And I think you heard about this about some of the genetics of patients' tumors and beginning to better understand not only the biology of the tumor, but also understanding more about the patient sitting in front of us. And so with that, I'll end. And I think we'll hear Mary and then take some questions at the end. Thanks so much. And we will round out the session with Mary Dunn. She's a nurse practitioner with the UNCGU Oncology Group. She is extraordinary in dealing with toxicities and side effects of therapy and will give us her insights. Thank you. Morning, everyone. Can I have a minute? Oh, okay. Thank you. It's such a pleasure to be here this morning. It's really difficult when I have to follow rock stars like Dr. George and Dr. Malalski. So hang in there with me. I'm not such a rock star. So I'm honored to be here. Like Dr. Rathmell said, I'm a nurse practitioner. I wear two hats. So I work in urology. So with patients who've had surgery for kidney cancer and also medical oncology. So patients who are taking medicine for kidney cancer. So I'm all over the place. That's why I have a lot of great hairs and bags underneath my eyes. Thankfully, I love what I do. And it's actually, it's a joy to see it to be here with all of you today. So the medications we're gonna focus on today are the ones that we prescribe most commonly for kidney cancer. So I'm not gonna talk about IL-2. Not gonna talk about interferon because we don't use those as much. So we're gonna talk about the targeted agents. These drugs can have pretty significant side effects. There are some that are much more common than others. So I'm only gonna touch on the common ones, okay? Because we can spend an entire day talking about all of the different side effects and how to best manage them. So in 20 minutes, we're gonna try and squeeze as much in as I can. So things I'm gonna try and touch on are why do these side effects occur? You're gonna love the slide that I have for that. It'll make a lot of sense. What are the most common side effects and then what are the treatment options for these side effects? So before I even touch on that, just as a caveat, we all, so as oncology providers, manage these side effects very differently. Even kind of within our own group, we manage stuff differently. There's no really right or wrong way to do this. It's very much like when you're picking a treatment for the cancer, how you manage the subsequent side effects is also not a perfect science. So we individualize these things based on a lot of different factors just to kind of throw that out there. All right. When the side effects of this medication kick in, you'll forget what was wrong in the first place. So that's what we try to not have happen. We don't want things to get to the point where it's so bad that you don't even know why you're coming to see us anymore. So this is just a little blurb about why these side effects happen. So to kind of break it down just a little bit. So class effects and what that basically means is when the medicine inhibits a certain receptor that we know plays a role in a specific process. So like VEGF, we know that that plays a role in making new blood vessels. So when we give you drugs that go kind of interfering and mucking around with that, that's why we can get a side effect like high blood pressure, which I'll touch on. And then off-target effects. So when we give you a medicine that inhibits unintended targets that we didn't mean to, but we can't just based on them, we can't help it just based on the mechanism of that particular drug. So I think my next slide is gonna clear all this up why these medications have all these side effects. Oh no, it's my next slide, sorry. So what, right? Some side effects are predictable and some side effects are not predictable. We do a bunch of things before we even start these medicines because of the potential toxicity. So a lot of you have probably had more blood drawn than you ever thought you'd ever have. We take a lot of tests to check for liver function and kidney function and all other kinds of stuff. Heart ultrasounds to make sure your heart's strong enough to take the medicines and we monitor blood pressure. Sometimes we have to fix stuff before we start you want a medicine to make sure we keep you safe. All right, I think my next slide explains all of this brilliantly. So that's why these medicines cause side effects, right? That clears it up brilliantly, right? Anybody have questions about this slide? No, I can move on, okay. So that's why we have side effects, okay? Brilliant, right? This is just a list of the medicines that I'm gonna go over because these are the ones that we prescribe the most. Is anyone tired? I know I am, I'm leading on the podium. It's kind of embarrassing, I'm feeling my feeling. Dr. George is tired. So fatigue is probably the number one, at least in my practice, kind of number one thing that folks tell me about as far as side effects from these medications. So that manifests itself as these are just different words that people use to describe the feeling of being tired, okay? So fatigue is the self-perception of tiredness. So feeling sluggish, slow, tired, dragged out, heavy, all those kinds of things, which is definitely not me on a Monday morning. And that's not me on a Monday morning. That's not a self-portrait. So that's how a lot of folks feel on these medicines. So different ways to manage fatigue. It's, this is tough because there's not a magic pill. For a lot of the other side effects that these medications can cause, we can try medicines to help with the side effect that the other medicines are causing. It's so important to conserve your energy. And I know that that sounds, some of these things are gonna sound really simple and kind of duh kind of moments, but a lot of folks who have cancer and who are taking cancer therapy have a difficult time asking for help and kind of scaling things back so that they want to be able to do and have things that are still everything 100% in their control. But when you're taking these medications, fatigue is definitely one of the biggest side effects. So these are just little tips on how do you conserve your energy? So setting priorities, asking for help. People want to help you, okay? A lot of caregivers and family members and neighbors and friends also feel a little bit helpless in these situations. So if by asking someone to take your dog for a walk or go to the store for you, that's good kind of for the whole caregiver circle as well. Plan activities when you're rested. So what I try and tell folks is when you wake up in the morning, if there's something that you'd really like to do, do it then. But don't try and squeeze all of your activities into this two, three hour window because you're gonna wear yourself out. So it's all about kind of timing things that are important to you. Defer non-essential tasks. So I can't tell you what those things are, but things that just don't have to be scratched off the to-do list and doing one thing at a time. So I'm a hypocrite. When I take a nap, which is rare, it usually turns into a full night's sleep from five o'clock until five the next morning. But napping, if you nap, it's kind of embarrassing. If you nap for more than an hour, it really can interfere with kind of your normal sleep-wake pattern. Also napping between five and seven at night can really mess you up for the nighttime as well. So earlier in the day and sudden alarm to kind of get you up after half an hour, 45 minutes. And I do realize these things are easier said than done. And then distractions. So there's some evidence that things like playing games or music or reading, things like that can help with fatigue. Exercise. So I now have an exercise plan for all of you. After today, we're all gonna go to Dr. George's house and get on his rolling machine. So I'm thrilled that he brought that up because now we all have somewhere to go. So exercise has absolutely the most data to support that it's the most helpful thing with fatigue. And I know that it seems counterintuitive because how in the world can you get up and exercise when you're so tired? That's why I showed you different little tips to help conserve energy first. Because if you conserve your energy, then you have a little more umph to exercise. And I'm not talking about going to run a marathon because then I would be a hypocrite. But anything that gets your heart rate up a little bit, you can go for a walk around the block. You can do, if those of you that have computers and internet at home, find some YouTube videos, do some yoga, it doesn't have to be anything extensive. But this is why. So it really in a nutshell helps your ability to function. It increases muscle strength, flexibility. It's good for your heart, which then is good in turn for all those other things. And it helps with your mood too because you can be fatigued for a lot of other reasons other than just because you're taking one of these medicines. So good sleep hygiene, I preach this a lot. So what that means is having a good nighttime routine. So going to bed at the same time every night, waking up at the same time in the morning, comfortable room temperature, making sure it's dark. Every single one of my patients laughs when I say this, but the only things you're allowed to do in the bed are sleeping and have sex, okay? So no reading, no TV, no iPad, no phone because all of those things keep your brain active long after you're asleep. So that can interfere with getting into that deep sleep that we all need so much. And avoiding stimulates. So those of us who drink caffeine have until the time we go to bed. Other things, so CBT is cognitive behavioral therapy, massage, acupuncture, some prescription sleep medicine, if it gets to the point where you need something like that, those things can help in low doses. Okay, other things, so two things that are important, especially with these medications is that there are some labs that can be abnormal because of these medicines that we as your providers need to be checking every time we see you. So every time I see a patient with advanced kidney cancer who's taking one of these medications, these are two of the things that, so of all the hundred tubes we take for a visit, these are two of the things we check. So these medicines can alter the function of your thyroid. So if your thyroid, if you become hypothyroid, that can lead to profound fatigue and it would be, it's amazing how when we correct that with a pill, how much better you actually end up feeling. So next time you see your provider, ask them if they're checking your thyroid. They might be and you might just not know because if it's normal, then we just kinda check it off our list. Anemia, so that's just one of the labs to check to see if you need a blood transfusion and things like that, because that can make you feel tired if you're anemic. Ah, these pictures are really, I don't know, I was doing this at like one o'clock this morning, so I apologize for the ridiculous cartoons, but this is someone who has a belly ache because of diarrhea. So I decided not to put in an actual picture of diarrhea because that would be a little bit, right? I mean, they exist, I Googled it, but that would be a little bit crude and it's right before lunch. So diarrhea is incredibly unpleasant and it can be a significant quality of life issue because people are afraid to leave the house. So this is something that can be modified a lot of times with some pretty easy diet changes. So low residue food, eating small, bland things that are high in protein, and this brat diet that you all may or may not have heard about at some point and that you can see what the acronym there is for, but why those things are important because they help absorb the fluid that are in your bowel to lessen the frequency and amount of diarrhea and get you back to kind of normal, pleasant bowel functioning. It's crucial that if you are having diarrhea to drink as much fluid as you possibly can because severe diarrhea can lead to dehydration, which can lead to all other kinds. These things just kind of snowball one another, as you can tell, which is why we can have a whole day talking about them. So two to three liters a day, that's a lot of fluid. So a lot of people just have them carry around your favorite water bottle and fill it up as you go. Of course, there are medications. So the easiest one is Loparamide, which is the modium, which you can grab over the counter. This is just kind of a schedule for how you do that. You start with two pills after your first liquid stool, then one after each max eight pills a day. Then if it gets severe, there are prescription diarrhea medications that your provider can prescribe for you. If it gets really severe and you're dehydrated and you're very sick from this, then we would have to bring you into the hospital to correct things like giving you fluid and giving you really powerful medicines for this. But we try and avoid getting to that point. I know I'm talking fast, I'm sorry. If anyone wants these slides, and I'll be here through lunch, if anyone wants to talk to me. This is really slow. So basically, this is kind of a duh thing, but if you're having diarrhea, stop your stool softeners and laxatives. A lot of times we forget to tell people that. And I know it seems kind of like an aha thing, but it's important to make sure that we're not giving you medicines that are actually making the problem worse. I don't know why I just splashed. Okay, so there are some unpleasant pictures that are coming up here. But these are different types of rashes that can happen with some of these medications. Ouch. So one of the most common is this acne form rash. So that is the gentleman with his back there and then the back of the legs here. If you can see that it's kind of faint. I'm actually just saw a lady a couple weeks ago who had that very appearance. Oops, wrong way. Back to diarrhea, that's not what we want to do. So that rash can appear generally it's on the face, upper chest and on the back. It kind of goes mild, moderate to severe and we don't really do anything about it until it becomes bothersome. So if it interferes with your day to day activities or you're itching all the time, then there are stuff that we can give you. So there are medications, there are creams. And then I'll kind of go through in another slide. Ah, there it is. So how to prevent this, keeping your skin kind of nice and healthy throughout all of this. Wearing sunscreen, even when it is cold if your face is gonna be exposed, if you're gonna be out, making sure you have a light sunscreen on. Good skin hygiene, so just making sure you're keeping everything nice and clean. If it gets to the point where it bothers you and you want medicines for it, there are oral and histamines to help with itchiness and then we can provide you with prescriptions for different types of creams too. So the hand-foot syndrome is, I forget how to go back, but it was those like kind of hard callus looking type pictures on the palms of the hands and soles of the feet. So these really kind of happen on areas of friction and pressure on those. So if you kind of see this table, it's a little bit difficult to see, but again kind of a grading scale. And we use that to kind of figure out how severe these things are. But tips to kind of help prevent this. So if you're taking one of the medications that can cause this, using thick kind of alcohol-free and emollient creams, avoiding things that are of extreme temperatures like very hot showers, avoiding pressure so jogging, jumping, hand tools. So if you're in the business where you make a lot of stuff and you're holding things a lot, so hand tools and things like that, don't go barefoot and wearing thick cotton kind of supportive socks. Treatment for this, if it occurs, our prescription creams, we have a lot of stuff that we kind of use, and then pain medication that you can take as pills if it gets to be severe. Ew, I know. So probably everyone in this room has had one of these. So even those of us who don't have kidney cancer take these medications. So this is kind of what we think about as a canker sore, but you can get these mouth sores. They're shallow, kind of punched out lesions. They can happen and that cracks your mouth and kind of down here in your lip and on the sides of your tongue. So to prevent these types of things, good oral hygiene, so keeping your mouth clean. For those of you who were dentures and surely no one in here is old enough to be wearing dentures yet, make sure they fit well because if they don't fit well and they're constantly moving around, that can really irritate your gum line and make you more susceptible to kind of having these problems in your mouth. And I like something that's simple and cheap, which is a warm salt water rinse after meals. As far as treatment, again, we can take out our prescription pad and write you some stuff. So there's mouth washes and there's steroid creams that you can put directly on the lesion, lidocaine, which is a numbing jelly, and then if it gets to be severe, there are pain medicines pills. I know that this seems kind of like an aha moment, but if you get these things, just make sure you stay away from this stuff because they can really exacerbate the pain and make it take longer for these things to heal. So things like very hot and very cold things, course, fried foods, and anything with citrus in it, and especially mouthwash. Over the counter, mouthwash with alcohol in it. So if you like to kind of use a mouthwash in the morning, I think there are several brands that make one that's alcohol-free and that won't hurt. Isn't that cute? So this is your heart checking its blood pressure, which doesn't make a whole lot of sense to me. So high blood pressure. So if you have high blood pressure, lots of folks have high blood pressure even before we start these medications. So it's really important that we as your providers make sure that your blood pressure is under good control before we give you a medicine that can make it even higher. What I like to do is give my patients a blood pressure log to take and keep at home. And every day for the first two weeks that they're on one of these medications is to keep a list of the time they take their blood pressure, what it is, and then to alert us if there's anything abnormal. Ideal target is 140 over 90 or less, which can be very challenging to get to. We treat this pretty aggressively and there's a whole host of blood pressure medications that we use that work differently to control blood pressure. Speed demon here. So in conclusion, everyone tolerates these medications very, very differently. Be open and honest with your provider so that we can help you. When I start someone on a new medicine, I see them back in two weeks to see how they're doing. If that's not possible, then I do it over the phone because I know folks travel, but that's to get an idea of if they're having any of these side effects kind of upfront because like other folks have alluded to, that kind of first cycle on a new drug can be the toughest. And then I see folks at least once a month, if not more often than that if necessary. If the side effects are severe, in spite of us treating them as aggressively as we can, your provider may need to decrease the dose of the medicine that you're taking or give you a treatment break, okay? Because we always have to risk the continuing to push forward with therapy while keeping you safe, okay? And good side effect management will improve your quality of life. And good palliative care should be incorporated into all of your cancer care at all stages. Thanks. He helped me. He did. He snored the whole time. Thank you. I forgot to mention, if I may, because I talk really fast and my dog distracts me, obviously, is that there are a plethora of resources as far as side effect and symptom management. My best resource are my nurse navigators, two of whom are here today. Nurses in particular oncology nurses are expert in managing these types of things. So please, please, please call them. And also on the KCA website, I mean, there's a plethora of patient information. We have a supportive care team and a symptom management team at UNC, which I'm sure there's something very similar at Duke. So when this stuff gets kind of above my level of expertise, then we consult with them as well. So sorry, I left that for him. Thanks. My name is Suzanne. First of all, I just want to say I really appreciate the opportunity to learn more about this. My brother-in-law has cancer, kidney cancer, metastasized, I don't know if I say that right all the time, but he's on his fourth round of student. They haven't taken his kidney yet. And I guess Dr. George, I think you referred to this a little bit, this question of whether you take the kidney or not. And they've heard some people talk about an analogy of the cancer being like a tree. And that if you go in and you take the root of the tree out, which is the source of the, you know, kidney cancer that's spread, that that's a very important thing to do because it can decrease the spread in the future and maybe even kill off the other parts as well. So I just wanted to see if you all had anything to say about that analogy of kidney cancer as like a tree and killing the root and the importance of that. Yeah, that's a really good analogy. And is this on? Can you hear me? Okay. And I think it actually, it's a 100 year old theory, but it got popularized in the 70s by Judah Folkman, who's a researcher up in Boston and sort of one of the pioneers of angiogenesis idea of, you know, blood vessel growth being an important target and biology of the spread of cancerous metastasis. And, you know, when you think about it and how metastasis happens, you know, the first step of that is what we'll call dissemination, cells getting out of the tumor and disseminating into bloodstream. And if you think of that big primary tumor as sort of a source of dissemination, then taking that out makes a lot of sense. Particularly if you only have a few metastases and if you have relatively small metastases then they would proportionally shed a lot less. Once patients have larger metastases or multiple organs involved, then it probably isn't as big a factor to take out that primary tumor because you're not really decreasing that dissemination, that shedding a whole lot. It still happens from, say, one site to another. So the primary source of dissemination is that primary tumor. Initially starts out that way, but at some point in time that becomes less dependent. There's also sort of these examples that they've kind of used to point to of spontaneous regression. We don't really talk about that much anymore, but there were cases where kidney cancers would just, without an intervention, sort of just shrink. And some thought was, well, we're moving the primary tumor could cause this spontaneous regression, you know. And there it's not this dissemination mechanism. There's something hormonal, something protein, like these VEGF proteins or others that are coming out of that primary tumor that's helping those other sites grow and increase and even survive, and when you take that away, then it shrinks them. I'm not sure that biology is as critical, but there could be a part of it. So there's still a lot we don't know, but there's good clinical data to say that when you've got 90%, when you've got a big chunk of your tumor that's still in the primary of your overall burden, it makes sense to take it out. Thanks, Dr. and thanks to the kidney cancer association provided a chance for us to learn. My father is 94 years old in Shanghai, China. Two years before he was relatively good at health and accidentally found the left kidney and have a 1.2 CM, so-called a solid mass addition to the many cysts. At that moment, we really think about the options and all the radiologists and most urologists over there, they concern this is renal cancer and they prefer to wait. And during the wait, these two years, the mass grows to the 2.5 CM. And during this time, he had one stroke, but very good recovered. As this situation, I just briefly ask Dr. King, is it basically if less than three CM prefer to still actively monitor that? He never do the biopsy. So I think he don't have a chance to do any chemo or anything else without the pathologist's diagnosis. It's possible he do the radio frequency therapy and also the cryotherapy. Those are available over there in the Shanghai, China. So I think this is what we've talked a bit about which is individualizing care for patients and really understanding the patient who's sitting in front of you and making decisions that are really specific to that individual. In a case like this, and I think you've already in a lot of ways illustrated what can happen. In someone who's much older who may or may not have clear medical issues, there may be medical issues that ultimately come out or become unmasked in older patients just by virtue of age leading to the accumulation of medical issues over time. And this is a story of you've got an older individual with a kidney mass. The kidney mass has really been meaningless and then he develops a stroke. And there's probably a lot more in terms of the risk of a recurrence of a stroke or some risk as related to the heart, et cetera, than as related to that kidney mass. And it sounds like what the physicians are saying are to observe closely but to not intervene is very reasonable because any type of intervention has the potential for a complication associated with it. So I think that sounds very reasonable and it sounds like a person's being monitored very closely. Things like cryotherapy or radiofrequency ablation certainly be considered as an alternative to observation or surveillance or monitoring the patient. But the plan sounds certainly reasonable in an older individual who's already had a significant event fortunately with a good recovery. Hello, my name's Todd and I'm a five year survivor. This is my second time coming to the program here. And one thing that at the last session I didn't hear you talk much about this session maybe it'll be later is the PD1 antibody that has been I believe approved now in Japan and it's under trials and has been here for a while in the US and I just didn't know if there was any when you were talking Dr. Malowski about the second line therapies. Is that something that's gonna be coming to the forefront or is there certain biomarkers that you look for? I'm currently on sous-tent and have been for four years now and I've been doing really well with it but I'm always looking at to the future what does the PD1 antibody hold in store? So I think this is gonna be addressed in large part by Dr. Moscos who I just saw walk in who's gonna talk about immunotherapy. So I'll just sort of comment briefly and I'll say there's an unbelievable amount of promise that appears to be associated with immunotherapy and cancer in general. And kidney cancer historically has been the place where immunotherapy has had a place, kidney cancer and melanoma. And so there are active clinical trials looking at PD1, PDL1 therapies and kidney cancer. There will be studies that are going to be looking at in the first line setting and actually Dr. George is currently involved in the design of a significant trial that's gonna be hopefully run through the large cooperative group network that's run by the NCI through the United States in the United States to look at these particular therapies. In terms of markers, yes, that's extraordinarily exciting too. There are markers, one is called PDL1 and there was recently a paper in the New England Journal of Medicine that suggested a way to look at patients who may be most likely to respond to those immunotherapies by virtue of understanding more about the genetics of their tumor. Yeah, and I would just add in your particular case, someone who's really done well on SU-10 for a long period of time, times on your side, we are just learning about how to use these medications now and this next generation of studies is gonna inform us further. And I think the longer you go on your current therapy the better we'll be informed about how to pick patients for this, to enrich for the therapies, who needs a PD1 alone and who needs a combination in all kinds of things like that. So don't get anxious to get on to the next therapy, you're doing fantastic and I always try to encourage patients when they're doing wallet therapy, we really wanna maximize that. It's great to look ahead, but just know that the longer you go, the better, more informed we're gonna be about how to manage you in the future. That's great, any last questions? No. So thinking a little bit shorter term, Dr. George talked about getting on the rolling machine and it being too much so you back off a little bit and it's done talked about, well, bear with the first month because it's really tough and then it gets easier or maybe. So the question I have is really to think about, do you stay at the same level, when do you change your levels of your dosage, for example, when do you decide, well, this is not the right medicine for me, I need to change to a different medicine. How long should I give it, does one give it before we make those kind of decisions? Maybe we can all comment. First of all, let me just say that there's a rolling machine for sale. Anybody's interested, I'm happy to pass on the torture. No, these are great questions and it's hard to answer that question without a context of a specific case because every case is different and this is what I mean by that. Everybody is different when they start the therapy and then how they respond to the therapy and it's not that predictable. I mean, I have little old ladies that do fantastic on these drugs and I have these big, burly, younger guys that just get brought to their knees and so I can't even look at somebody and say, gee, you're gonna do great or you're gonna struggle. So I think it's what Mary said about seeing them back quickly, talking to them, listening and when possible doing it in person because the phone just there's no substitute to sitting across from the patient and seeing all those things I talked about that we size up with people and stuff, it's hard for you to describe that to us and we just can't tell and a lot of it is the change. How much change has there been in two weeks on a patient? If there hasn't been that much change, they weren't super functional but they're still not that much worse, they're probably gonna be okay. If they were fantastic, running five miles a day and now they're walking 200 yards in short of breath, that's a big, big difference. So a lot of it is also the context of how much change. The second part of that though is kind of the chronicity. What do you do with somebody who's on a therapy for a long period of time and I think one of the things you'll find from all of us is that for our patients that are on for a year or more of these therapies that frequently over time, we will adjust the dose down a little bit and it may not be for that horrible diarrhea or something but it may be just sort of the chronicity of the side effect or a combination of two or three side effects that are sort of lower grade but they're influencing, affecting how functional you are. And that to me is really, really important because when I have somebody that's over a year on a therapy, they're doing really well. For all I know, they could be doing really well on even a lower dose. So that's the patient whose tumor hasn't quickly adjusted and rapidly progressed. They may not have an easy mechanism of resistance and we may be able to treat them for four years or more and if we're gonna do that, I wanna make sure they look like that gentleman back there and not somebody who's been worn down by the medicine. So that's a really important aspect of this and it's kind of an ongoing discussion and things. That's kind of how I think of it. If I could just add to that, thank you. What I kind of counsel my patients is we have to think about big picture in long term too. So I make changes to medications. Obviously if there's significant progression on scans. So if there's a big new tumor, one that we've been following grows significantly then we talk about making a change in the drug. If there are side effects that are life-threatening, so if your liver function tests get through the roof and you come in and you're glowing yellow, like that's a deal breaker type of thing. Or if we are aggressively managing your side effects we've tried treatment holidays, we've tried dose reduction and still your overall clinical picture and quality of life are miserable, then we make a change. But it's very, it's very, very patient dependent. I have a patient who every time this time of year he calls me, he says, and I just saw him in clinic, he says, I'm going to whatever city he's going to and I really wanna eat this pizza. But right now I don't think I can, it's gonna taste the same. Can I come off of my drug for two weeks? That's also something that we do. Because the likelihood that having a small, what we call treatment holiday, it's like we think we're giving you a gift because we torture you so much. Have this treatment holiday. The likelihood that your cancer is gonna change so significantly in that two weeks period or whatever it is that you negotiate with your provider off drug, it's just rare that that would happen, but that would change kind of the overall picture. Does that make sense? But you wouldn't ever increase the drug? I mean, if you start off at a certain level and you say, well, we've probably gotten all the benefit, say at this level, now we're gonna increase it because we think we could get more benefit. If we don't start you off on the maximum dose for X, Y, or Z reason, if you're at half dose or three quarters of the dose, if you're tolerating it well and your scans look good and you're on board with the plan, then yeah, we do that too, absolutely. Yeah, I would just add a couple of things. So the answer is yes to that question for sure. I mean, one of the medicines where we do that is the N-Lito or Exitinib medicine where we start low and escalate the dose up and we mentioned the issue of watching the blood pressure along with that and sort of making decisions related to that. The other thing that I think is really important is this issue of when do you start a patient? And Dr. George raised this question and there was a real nice report by Brian Rainey who's another doc at the Cleveland Clinic that was presented that looked at, it wasn't a large group of patients who was 60 plus patients, but basically they showed that the average time to start the patients on therapy in a very select group of patients was on the order of about 14 months, it was over a year. And I think it really tells a story of how much we need to learn about using these agents in patients with kidney cancer and about weighing this issue of benefit and risk. And there are certainly patients out there that will not require treatment for some time and can avoid any potential toxicity associated with therapy. And I thought patients come to me, started on therapy locally, very small amount of disease. For example, only a couple of less than a centimeter lung lesions and we may elect to watch those patients, some patients who may be candidates for things like high dose interleukin-2 that Dr. George mentioned, we may consider. But it's not uncommon these days to watch patients for some time to avoid any side effects related to treatment and to make sure that quality of life is maintained. Okay, let's thank our panelists again. And actually, can you stay here for a photo? So don't go anywhere. But it's lunchtime and lunch is out the doors and to the right at the end of the hall, there's a dining room. I think there was a dance last night because there's still a dance floor. So if you feel moved, we can use the dance floor, it's still there. And we'll be back here at one o'clock.