 Thank you everyone here for braving this nice North Carolina winter storm and welcome to our 2017 kidney cancer Association patient and survival Survivor Conference. This is a nice tradition that we have here and a beautiful, I think collaboration between multiple disciplines and multiple institutions. We have a really good lineup of speakers today to hopefully help everybody come away with a better understanding of kidney cancer and the journey of having kidney cancer and I think the the one thing to say is that we hope that this is a very interactive session. I think the beauty of this conference is always that we get not only our opinions out there, but everyone else's questions and thoughts and support and opinions and it works best, I think, when we have interaction back and forth and so we really encourage questions and this day is about you guys and what you want to know and so all the speakers, I think, have prepared some slides, but please feel free to interrupt to ask questions about what it is that you came to know today. A couple requests is when you do ask questions, if you could just use the microphone so everybody can hear and so that we can the KCA is video recording this so we can get the questions on recording as well. Thoughts, Ray? I just want to echo and what Tracy has said and thank everyone for coming here especially off the patients and survivors and caretakers and caregivers that are in the room and also just want to recognize the vet and Tracy who did a lot of the legwork to get this all organized so if you have any comments or feedback or, you know, please let us know so we can always make it better and hope you guys enjoy. So the other thing I wanted to do is give a shout out to the Kidney Cancer Association who is sort of supporting today. Unfortunately, they usually give sort of an introduction to their association at the beginning of this, but none of their representatives were able to come today. So I just wanted to make sure that everyone is aware about the KCA and aware of some of the things that they do. They have a great comprehensive website. This is just a screenshot. I took of one of their pages where they have sort of you can't see all the way down but a list of some of the common treatments that we use in kidney cancer with some good patient information and their website has got a lot of good information as well as a lot of links to both events like this and events outside of North Carolina. There's also a kidney cancer support group that meets at Duke that everyone here could, some of you I'm sure are maybe involved in, but could be that have the option to be a part of and they have a sort of national conference for patients. I think every year that is also an option. You know, they support a lot of our research. They give some grants for research. And so all in all are an important organization that sort of represents kidney cancer. And I encourage all of you if you haven't to sort of check out what they have to offer on their webpage. So we have a great line-up of speakers today. I think it covers a big breath of the kidney cancer journey starting from sort of some discussions of surgery, the genetics of kidney cancer, and then we get into the nitty-gritty of treatment and then how to manage some of the side effects of treatment, which I know for a fact some people in the room have dealt with personally, as well as, you know, a wrap-up of talking about palliative care and kidney cancer and sort of where the field is going with ongoing clinical trials. And so I think it's a beautiful overview. You've got some of the best kidney cancer doctors in the state and the country, I think, talking at you today. So I hope that it is very educational. And I tried to sort of go through everybody's slide. I was incredibly impressed that all the speakers managed to send me their slides in a timely fashion and have actually done a lot of preparation for today. And so I try to go through their slides and pick out terms or concepts that I thought might be confusing or that it may be to have more of a general oncology conversation at the beginning of the day so that everybody can sort of come into the same page and understand terms when the speakers use these words like overall survival and adjuvant. And so I just want to make sure that we're all starting with understanding what some of these words mean so that we have a better background of the talks that are coming. So a cancer is number two. As I'm sure you are all acutely aware of the leading causes of death in the United States, second only to heart disease, and with, you know, 600,000 people a year, which is a huge number. And as we learn more and more about cancers, you know, we get some answers and I think we get even more questions. And I think the kidney cancer world is not immune to this at all. I think that it is, the research is rapidly growing. I remember the agenda that we had and the conversations that we had last year at this conference and a lot of it, even from last year, has been thrown up in the air and is now in different places. And some of our treatments are used differently than they were even a year ago. It is so frequently changing and a lot of our cancer treatment is based on some idiosyncrasies of certain cancers and some subtleties and some of the newer clinical trials. And so I think, you know, although this number is huge, you know, it breaks down into buckets of types of cancer and then smaller buckets of types of types of cancer and the smaller buckets of types of types of cancer. And kidney cancer is no exception. And so, you know, I think that that although you're going to see all the great work that's been done, we still have a lot to do and I think, you know, as much as we're important in that, so is everyone in the room. So for renal cell carcinoma incidence, it is a relatively common cancer, although not quite as much as prostate or breast cancer, which you hear more about sort of in the media. But in men, it's number six and in women, it's number 10 with, you know, over 60,000 cases diagnosed in the U.S. every year. So not an insignificant number and clearly and clearly a cancer that's getting increasing recognition, I think in terms of research funding. We have a new Department of Defense research mechanism this year for specifically for kidney cancer. The DOD is Accepting Grants for sort of kidney cancer research, which is a great move ahead for our field. And you can see that the majority of kidney cancers are diagnosed in sort of what we call localized disease. So the kidney cancer is only in the kidney and has not spread outside of it. And so you can see somewhere, you know, definitely more than half somewhere around two-thirds to three-quarters of patients get diagnosed with localized disease and then some of those patients will will end up having recurrent disease in the future. You can see that it's slightly differs by race. I think there was a talk here a few years ago about some of those differences and but you can see black patients are slightly more likely to be diagnosed with localized disease and then distant disease. So one thing to sort of talk about very much from the beginning is sort of sometimes I use the word kidney cancer and sometimes I use the word renal cell carcinoma and then it even goes on from there. And and you know, kidney cancer is a really non-specific term and can refer to a bunch of different types of cancers. The most common by far is a type of kidney cancer called renal cell carcinoma. And those are the types of cancers that have started from the the two wheels in the kidney whose job it is to filter the the blood and turn it into urine essentially. And so most of our cases of kidney cancer are these renal cell carcinomas and that's the the talks today are really focusing on this subset of what we call renal cell carcinoma or RCC. But there's actually other types of kidney cancers or kidney tumors as well. One of the more common ones that we see is actually your athelial cancer and so some people can get tumor in their kidney that has just started from a different cell like the cell that lines the part of the kidney that collects the urine and those can turn into cancers as well. And so those aren't so you can actually have kidney cancer but not have renal cell carcinoma. And so this is just a list of other types of tumors that can happen in the kidney. You know, there's a number of different types of cells in the kidney. You know lymph cells, muscle cells and any of those can turn into cancers and we sort of name our cancers based on what cell it started from. And so you know all of our talks today are on renal cell carcinoma and what it's like to live with that. But just to have an awareness that that's not the only type of kidney cancer that exists. Some of these are even not even considered cancer like angiomyelopoma. But there are some more rare tumors like Wilms tumors for example, which mostly happen in children to be aware of that can happen in the kidney. So if you hear someone has a tumor in their kidney, it's not necessarily renal cell carcinoma, although chances are that it may be. And so this is a very famous slide from a very famous paper that was published about the spectrum of renal cell carcinomas. And so there are, it is not just one disease. And as we learn more about the genetics of cancer, we learn more and more about these different subtypes of renal cell carcinoma. The most common is clear cell renal cell carcinoma. That's the one on the far left. And they call it this, as you can see from the picture, because they're pretty large and look clear under the microscope. And a lot of our studies are done in these clear cell renal cell carcinomas. And so a lot of the times when we talk about treatment, we talk about treatment in terms of what we know about clear cell renal cell carcinoma. And sometimes we have to sort of extrapolate into the other different types of cancer. Some of the other non-clear cell, so we commonly will group them into clear cell and non-clear cell, will have their own studies. But unfortunately for the non-clear cell cases, you know, we think that these are all different actors and different types of cancer, too. There's papillary, which comes in type one or type two. There's chromophobe. And then, you know, there's this type that I rarely see called oncocytoma, which, you know, it's very slow-growing and, you know, is we don't consider, sort of, in the malignancy pathway. But the the the thing to know is that in a lot of our research and trials, we sort of group all these non-clear cells together and treat them together in studies when really they probably act like different cancers. And we're, you know, because they're more rare, it's harder to figure out exactly how to treat which one. And so because a lot of our research is in clear cell, and a lot of what you'll hear today was research in clear cell, there will be some reference to the other types, too. But just to know that, you know, even within renal cell carcinoma, all these cancers don't necessarily act the same. Papillary type one tends to be a little bit more indolent, slow-growing tumor. Papillary type two tends to be more aggressive, faster-growing. Chromophobe, similarly, seems tends to be very slow-growing. We can, we tend to watch people for years and years sometimes before they need to switch therapies. And so there's a lot of heterogeneity, a lot of differences. It's very much a spectrum. And, you know, some of this, when you hear, you know, we treat this with this kind of treatment, and this with this kind of treatment, you know, it is very patient-dependent tumor characteristics, person characteristics, how we treat some of these cancers. And so just remember, you know, it's a conversation with your providers, and everybody doesn't always fit beautifully into buckets of treatment and cancers. And, you know, I hope that you'll learn something and be able to take it back to your providers if that's what you're looking for and sort of talk in the context of some of this information. So we think that these, the reason that these different types of renal cell cancers develop from the kidney are because they started from different cells along the tubules. And so a clear cell, our most common one, we think starts in what's called the proximal convoluted tubule. And so when when your blood goes into your kidney, it gets sort of filtered into the tubule, so kind of which is eventually what you pee out. And as it goes along the tubule, different things happen to the urine. And so the, at the beginning of what we call the convoluted tubule, which is kind of the tubule that runs all around, we think that if those cells become cancer, they become a clear cell, renal cell carcinoma. We think that papillary may be more likely to come from the distal convoluted tubule, that chromophobe may be coming from the cortical collecting duct, which is sort of at the end of the pathway of urine through the kidney. And then there's another type of renal cell carcinoma called collecting duct RCC, which is a lot less common and sort of is at the very end kind of between the before the kidney cells become really these urethylial cells, which look more like bladder cells. And that cancer actually kind of acts like an intermediate kind of cancer between renal cell and bladder. And so we think that sort of where it starts from plays into what it acts like and how we treat it eventually. And so the majority of people you can see have a clear cell RCC, probably next most common is papillary and then chromophobe. And then there's a group of people who have these not specified, not otherwise specified, meaning that the pathologist look at it under a microscope and can't really tell what type of renal cell cancer it is. And you can see that these types actually vary a little bit by race. Black patients are more likely to have papillary and chromophobe than white patients. And we don't fully understand why that is. So the risk factors for kidney cancer, I really just threw this in there because I don't think it's in any of the other talks, or at least not that I saw. And we commonly get asked this. But suffice it to say that most cases of kidney cancer are sort of what we say is bad luck or just random mutations that people acquire. But we do know that there's some things that if you smoke, you're more likely to get kidney cancer than someone who doesn't smoke. Can we ever really say that things are causative? No. But the things that are associated with development of kidney cancer include smoking, high blood pressure, obesity. If you're on dialysis, there's a syndrome where you can get acquired cysts in your kidney that those people are more likely to get kidney cancer. Some occupational exposures like asbestos and cadmium, gasoline. And then there's sort of a list of things that the evidence is a little bit less strong. But we think are associated including some of pain medicine use that's called analgesics, some familial cancer syndromes which you'll hear more about from Mary in a little while, chemotherapy. And then sickle cell trade actually is associated with this very rare form of kidney cancer called renal medullary carcinoma. And so I'm not going to get too much into the weeds of genetics. There's a little bit of this in one of the later talks. But I will sort of say that because a lot of our treatment is based on some of our understanding about the genetics of kidney cancer, I will highlight it a little bit. So clear cell kidney cancer is pretty much categorized or is related to a defect in a gene called VHL. And so almost all cases of the tumors have VHL in activation. And that stands for Von Hippel-Lindau. And Mary is going to go over some of the potentially inherited causes of VHL loss. But in most cases of kidney cancer it's just within your tumor you get a mutation or an alteration in this gene which makes you lose this gene called VHL. And that essentially makes it so that your tumor can grow independently without some of the normal regulatory signals to make it stop growing. And one of the ways that it does this is through recruiting blood vessels in a term we use called angiogenesis. And so a lot of our understanding and a lot of our treatments that have emerged in the last 15 to 20 years for kidney cancer is because of VHL and the propensity for renal cell carcinomas and clear cell renal cell carcinomas to recruit these blood vessels. And so a lot of our drugs try and block this pathway. There are also we're getting a bigger and bigger understanding of the other genes that play a role. I listed just a couple of them here that we haven't figured out how to target with treatments yet but that we do want to know that can change our understanding of what people's prognosis or how well they're going to do with their cancer are. So for example if someone has a mutation in PBRM1 they tend to do better. If they have a mutation in BAP1 they tend to do worse. And all of these are important in what we call chromatin remodeling which is essentially how DNA is stored within the cells in the cancer. I think this is also very briefly in Dan's talk today but you know everybody presents with kidney cancer differently. And classically when you're a medical student and you learn about what people present with they have this sort of classic triad, flank pain, hematria which is blood in the urine, and a palpable mass in their abdomen. It is a very rare patient that we actually see present with this classic triad. And it is a very rare patient that we actually see present with this classic triad. You know usually someone will have one or none of these things. Similarly you can have some swelling in your scrotum, you can have swelling in your legs, you can have abdominal swelling, but it is a very rare patient that we actually see present with this classic triad. You know usually someone will have one or none of these things. Similarly you can have some swelling in your scrotum, you can have swelling in your legs, you can have abdominal swelling. But you know everybody is very different and it is very, it sometimes can be a very difficult cancer to diagnose. I would almost guarantee that somebody in this room had multiple tests before their diagnosis. The doctors figured out sort of what was causing their symptoms because it tends to, you know, the kidneys live in your back and can grow pretty big before you have symptoms and it is very rare for people to get sort of all of these things. And the other thing is that kidney cancer could do this thing called a perineoplastic syndrome which is cause systemic or changes to your whole body system for unclear reasons. And so people can get high blood pressure. They can get muscle weakness. They can get accumulations of some fibrils in their heart and brain and things that nobody really understands why kidney cancer can cause this. And we do know that if we treat it a lot of these things get better. High calcium is very common for people with kidney cancer. So this slide really just shows that it can, although you may just have a tumor in your kidney it can have effects to your whole body. And actually sometimes when you take out the tumor in the kidney the rest of the body gets better. And we don't fully understand why this happens. So some of the words you're going to hear today that we commonly say that I think are sometimes confusing. One is systemic treatment. So we as medical oncologists use this word systemic treatment to mean a treatment that treats your whole system. So this is different than sort of localized treatment. So if you have treatment that's what we call localized. It means just in one particular place. And typically that will be surgery or radiation. And systemic treatments are things like pills or IVs that you take that treat your whole body. And so those target sort of any cancer cells anywhere in your body as opposed to sort of localized treatment which is really just targeting a tumor or a group of tumors in one specific place. We use the term definitive meaning treatment that we want to cure somebody. And so it's the primary treatment it's intended to cure. And so typically if someone just has a mass on their kidney we will take it out surgically and we will call that sort of definitive management or definitive surgery. Palliative is sort of the opposite. We use that term to mean it's given to relieve symptoms to reduce suffering. And you know arguably in any of our cancers that we can't cure all of our chemotherapy we consider palliative because the point is to give people improve their symptoms improve their quality of life for as long as we can. And so sometimes we use this word palliative to just mean pain medicine symptom control but more often we use it in a broader in a broader scope to mean anything that we are doing to sort of improve people's palliative quality of life. So that can include chemotherapy or systemic therapy. And then salvage is a word we sort of use to mean if someone's cancer has not responded to a group of treatments we give them sort of salvage treatment to try and kind of to try and change that course. And then there's these terms neoadjuvant and adjuvant so neoadjuvant is therapy that's given prior to a primary therapy so we don't do this all that often in kidney cancer but in a lot of our cancers like breast cancer or bladder cancer we do it routinely. But if we have a planned surgery we will sometimes give treatment beforehand to try to either shrink the tumor or kill any cancer cells that have spread outside of the kidney before we take them to surgery. There's studies that are ongoing looking at neoadjuvant treatment in kidney cancer but for people that just have tumors in their kidney it's not standard of care right now. And then there's adjuvant which is treatment that's given in addition to the primary therapy so after someone has a surgery to remove their kidney cancer and we don't know if there's any cancer cells left behind it doesn't look like there is. We will talk about whether or not people will benefit from adjuvant treatment so treatment given after a surgery to decrease the chance their cancer is going to come back. And Dan George is giving a whole talk on sort of adjuvant treatment in kidney cancer today and what the current landscape looks like. And then we use these words chemotherapy targeted therapy and immunotherapy. Chemotherapy is sort of classically what we use in a lot of different cancers it's typically systemic therapy so it treats your whole system. And we really target rapidly dividing cells and sometimes cells that are sort of actively dividing but it really influences all of your cells. And so you typically the classic chemotherapy you give through IDV it makes people lose their hair and throw up and feel sick. They get side effects because of the fact that this chemo is targeting all of their cells. In general classic chemotherapy does not work very well for kidney cancer until we don't use it except in certain circumstances. And instead our treatments are typically more targeted therapy or immune therapy and so targeted therapy means that there's a specific molecule or protein or something within the cancer cells that we are trying to target. And because of that the side effect profiles can be really different than standard chemotherapy. And so a lot of the pills that we use for kidney cancer are targeted therapies against some of the signals that they use to grow blood vessels. There's also other proteins that we're learning are important in certain types of kidney cancer that we target with and these can be IVs or pills. But this tends to be the bigger group of treatment for kidney cancer. And then there's immune therapy which is essentially any treatment that revs up your immune system to attack your cancer. And so it sort of uses a person's own immune system to then recognize the cancer. Typically your immune system's job is to go around and get rid of anything that's not supposed to be there. Bacteria viruses and its job is to recognize cancer cells and get rid of it. And for some reason when people's kidney cancers grow they have figured out how to get around this. And the therapy's job is essentially to try and fix that, fix what's broken with the immune system and get it to recognize the cancer. And high-dose IL-2 has been around for many years in kidney cancer and is an example of this. And then some of our newer drugs, Nevolumab most notably and Ipilimumab which you're going to hear a lot about today because there's some kind of exciting new data are all immunotherapies. And then you're going to see this slide which is the approvals for metastatic RCC about 10 times today so I'm not going to belabor it. But I just want to spend my last minute going over to some of our survival terms. And so all of our research and our data looking at sort of success of treatments talk in these words. And so sort of the ultimate outcome that we look at in trials is what we call overall survival which is from diagnosis how long do people live if you give them one treatment versus another. And so this is sort of the pinnacle of what we consider success in a lot of trials is sort of how long do people live. Many would argue that's not always the most important thing but it is typically what the FDA considers sort of the best difference. Progression-free survival is how long until people's cancer grows. So when we start you on a treatment how long is it until the cancer grows so big that we stop the treatment. And there's actually a very it's called resist and it's a set of guidelines that you use to determine when the cancer has been considered growing big enough that it's called progression of the cancer. So if patients are on a clinical trial it's very strict sort of when this is. In real practice it's a little bit more you know we use the guidelines but occasionally we will also sort of take other things into account when we decide when to change people's treatments. And similarly disease-free survival is kind of like that it's a term used after surgery for sort of how long until someone's cancer comes back or death. Response rate is the percentage of people that's tumors shrink by a certain amount with treatment. And that's getting to be more and more important as we compare some of these sort of initial treatments for kidney cancer. And then quality of life is becoming more and more important in our clinical trials. The FDA is actually approving therapies now based on improvements in quality of life. So I think from a patients perspective this is clearly very important and I think finally becoming recognized in the oncology community that you know exact overall survival or progression-free survival is not the only thing that's important and quality of life is very important too. So I'm going to stop there and I think as Mary next I don't have the identity yet and let Mary talk a little bit about the genetics of kidney cancer. So Mary's one of our esteemed nurse practitioners at UNC.