 Thank you very much for having me. It's a delight to be here. I'm computer phobic, so that explains why people are helping me. I'm in private practice in New Jersey. To me, I try to always be the advocate for the patients for whatever disease they may have. I have the privilege to be in a large group that affords me the time to be taking care of patients with the GU. It is an evolving disease over the last few years that we've been blessed as medical oncologists to be able to offer patients treatments where we did not have that opportunity ten years ago. And kidney cancer is the prime example about how the evolution of science and research has allowed us to offer patients therapy in a disease as you heard before that offered limited amounts of options. So I'm going to give you a brief overview. I try to make it brief because to get into formal detail it becomes very, I guess, boring. But more importantly, I think it's going to lead to a lot of opportunity to ask a lot of questions which I think may be applicable to some people. So this is meant to be a small overview and hopefully you can stimulate more questions afterwards. Broadly put, there are two main opportunities to treat patients with kidney cancer. You've heard Dr. Wang speak about surgery and I think that is the integral part about when one has a malignancy that could be protected, but that is the ideal therapy that one should try. But when it comes down to systemic therapy, when the cancer has traveled outside of the kidney and requires therapy for disease that traveled to other regions like lymph nodes, lungs, even other organs, we do have therapies. So dating back to before 1992, there was really no FDA approved drug. Immunotherapy appeared to be the therapy that was studied most. Dr. Dutcher is one of the leaders when it came down to the data that was published early. And I think the immunotherapy science really is that it's able to attack cancer cells systemically throughout the body. It's an intravenous therapy. Sometimes it's subcutaneous, but it does train the immune system to recognize and target only the cancer cells. So it has this ability of really being primed that it's going to probably help kill the cancer cells. It does have some effect on other parts of the body. We'll talk about that shortly. But the main launch category in the therapies that we've evolved over the last nine years has been the targeted therapy. And these therapies actually target and interfere with the growth of cancer cells at a molecular level. It focuses on specific pathways to inhibit cell growth, replication, and ready to disrupt the blood flow supply to the cells. And when you look at the main categories that's listed, you have immunotherapies. There are two drugs. There's interferon alpha, and then there's IL-2 or Intiolucan-2. And then there's the targeted therapies, and we're going to break them down a little bit. And again, I don't want to get into details about each one specifically. And we're going to not talk about the data, how it got its FDA approval. We're going to sort of leave it very broad. But these are how, when you see a medical oncologist, this is how we think. We think about opportunities we have. What therapies are best to be used first? We try to think about the sequences of therapy, and there is sciences behind it. And there's many different conflicts, how one should think. And I think it's important to definitely hear the conversations that you hear from the physician. But this is all stemmed from a multitude of conversations and data that's been published over the course of the last eight years. When we assess patients, Dr. Wong spoke about the surgical approach about how patients are evaluated. We have two prognostic risk models that we've utilized over the course of the last few years. The second one being the one on the right by Dan Heng. The one that's been used over the last 15 years was based upon the, let's call it the MSKCC or Bob Motzer. They actually utilize this data based upon use of interferon and surgery. And they came up with how we should assess how patients should predictively be doing from when we start seeing the patients upon disease progression. So looking at Dr. Moters, I'm going to start on the bottom of Dr. Moters criteria. There actually is two parts to it. The early 1999 analysis actually looked at patients who had prior refractories, presection of their cancers. And then what we use as Karnofsky performance status is really the patient's functional performance status. And there are criteria by that. Looking at the hemoglobin, the calcium level and the LGH is a blood test. So in essence, every time we see patients and medical oncologists, we should have the category pretty much in our head by the first visit. Because a lot of these blood tests have already been done, we've assessed the patient. The Dr. Moters criteria did change a few years later and they took out the first prior nephrectomy and they actually used the criteria of the interval of time between when the patient had their surgery to when they presented to you as a need to start therapy. The difference between Dan Heng and Dr. Moters criteria is really on the last bullet point. There are times of LGH, which could be a marker for the burden of cancer. Sometimes it's normal and therefore it's sometimes an inconsistent study. So they utilize the neutrophil count, which is a white blood cell count and a platelet count, which sometimes can be elevated with inflammatory processes. Sometimes that number can reflect a true volume of cancer predictor. So you'll see a shift every time you read these articles. They talk about usually it still goes back to how we've always dealt with the MSKCC criteria. That's Bob Moter, but Dan Heng's now the criteria is being utilized a little bit more. So when we look at these risk factors, it's not just one of those. We just see the patient's data and we just see where their survival is going to be. It does actually allow us to see which therapies may be best. A lot of times if someone has a favorable risk factor, it actually would be an excellent candidate to go for surgery for cytotidinefractomy that Dr. Wayne pronounced, actually discussed. And then sometimes even for the intermediate risk, it may be a benefit to have these patients undergo cytotidinefractomy as well. But based upon these risk categorizations, we're able to sort of feel which therapies may be better for patients. We'll talk about how poor risk did come about based upon that categorization about the approval of one of the drugs that are used for kidney cancer. But for the most part, every physician should try to believe that their patients should fit a criteria before you come up with a decision about how to take care of these patients. A little broad discussion on immunotherapy. Immunotherapy really just boosts one patient's own immune system to sort of recognize and attack cancer cells. It activates and increases the number of immune cells. It activates these immune cells again to recognize and kill cancer cells. The death of the cancer cells slows or halts the tumor growth, possibly leading to tumor destruction. For the most part, for kidney cancer, we try to slow down and stop growth of disease that are times we are able to be successful that we can actually reduce them, the tumors that is, and they can go away completely. But for the most part, our goal when it comes to patient care and survival is actually slowing down this disease and sort of halting the growth. Kidney cancer as well as melanoma are one of the two therapies that actually respond quite well to immunotherapy. Specifically for interferon alpha, this interferes with the life processes within the cancer cell and it prevents the growth and making it more susceptible by other elements to be destroyed by the immune system. Typically, this is medication that's given subcutaneously. It's given several days a week. It depends on how it's administered. It's got a lot more headlines since 2009 when Vastin got FDA approved. The Vastin was FDA approved with its usage with interferon. But because of its benefit with the Vastin, the use of interferon as a single agent has gone down in regards to its usage. The over-response rates, it looks small. The problem when it was actually analyzed interferon, the criteria about how to analyze the data was different back then. The use of response criteria was a little bit different, so the rates may be smaller than actually what we see. But again, the best candidates are patients who have good performance statuses prior to nephrectomy. Dr. Wang showed the data that was published in 2001, as well as disease that's primarily in the lungs. And again, the response rates talked about not just how patients do, but just the reduction of the cancer by 50% or more. So the stability of the disease is not reflected by the data that's resented. Again, these therapies usually work by regressing the tumor slowly. It's not a therapy that's going to be initiated and start reduction of cancer within the course of weeks. Usually it's several months before the disease actually responds. There is a multitude of side effects. I always tell the patients it's like having the bad flu. A lot of times these therapies are given three days a week. So sometimes by the time you buy it gets better from the symptoms of the toxicity of the therapy, you get an injection all over again. And based upon the dose, you can actually predict the side effects. Of course, every patient for every disease, for every therapy are different. So a lot of times you have to unfortunately administer a therapy at a dose that offers a higher risk of toxicity before you find a dose that actually can be utilized and adjusted to the patient's success of tolerability as well as efficacy or efficient ways of treating the disease. Another form of immunotherapy, IL-2, proloquine, is a therapy that's been FDA approved since 1992. It's genetically engineered to a product that once body open makes, everyone has IL-2 within their own self. It does allow the stimulation of T cells and natural killer cells. This is a therapy that can be given subcutaneous as well, has a lot more success being given intravenously. There are, I think, between 50 and 70 centers in the United States that actively utilize this agent in the way of using it as a high-dose therapy. There have been studies comparing high-dose to low-dose or subcutaneous doses. Still, I believe most patients are receiving this therapy in a high-dose setting. Before these high-dose centers became more comfortable with this usage, it was just given with a low-dose in the office. It was sometimes combined with interferon, but the toxicities were vast. The most success is actually given as a high-dose. When you are in the hospital for five days of IL-2 therapy, given a dose every eight hours for 14 doses, you have a five-day rest. I'm sorry, you have around anywhere between a five to ten-day rest and then five days again back in the hospital. I learned over the course of several meetings that there must be 50 different ways how to give high-dose IL-2 as a high-dose. You find that there is a lot of variability in how people are administering it these days, but still a very successful therapy. It is the only data I think that the doctor is going to show you a slide that actually has therapies that are given to patients that can put these patients into not only complete remissions but durable remissions. These are therapies that, if given and if it works, you don't always have to have a complete remission to have a cure. You can always have a therapy that can be working partially, can stabilize the disease. The benefit of these therapies can actually be where you are postponing the inevitable next dose of therapy. If one can actually be on this therapy and being able to possibly slow down the disease that you don't need to get any further therapy, I think that's the ultimate goal when it comes down to trying to treat patients and the fact that one's able to believe that over the course of a lifetime if one's going to be exposed to many medications, then limiting the amount of therapies to patients is going to be probably the most beneficial for patients' quality of life. The side effects for high-dose IL-2, unfortunately, are difficult. I think that, again, in the trained center, and as much as I think that we know how to do it, I have to value my nurses and the nurses to have on the hospital floors, because they pretty much are beyond diligent, how to monitor these patients and avoid any worsening of the toxicities. But there is a phenomenon called capillary week syndrome with the capillary week in essence. If you remember, good old-fashioned biology between your arteries and your veins, every capillary fluid drifts out. And because of that, you have a multitude of side effects, that being lower blood pressure, you have kidney dysfunction, blood tests can be a rye, and even says good old-fashioned hallucinations. The patients go through bad rigors, I describe as good old-fashioned earthquakes from California, but they're very terrible. The great thing about this therapy, the adverse effects are predictable, they're manageable, and they completely resolve upon completion of the therapy. So, best spoken to by a person who got IL-2, but I can tell you that these therapies not only offer a therapy of benefit for the immediacy, but also possibly long-term. And then we talk on the targeted therapies. So, there are three different categories. One's called TKIs, tyrosine kinase inhibitors, and these are anti-angiogenesis agents. They inhibit vascular endothelial growth factors and platelet-derived growth factors to block the growth of new blood vessel formations in tumors. Simply put, cancers need blood supply, and so it built its own blood supply to sort of build a bridge between the tumor and an existing blood vessel. So, these therapies actually have the ability of not only inhibiting the growth of these blood vessels, but also having the ability of disrupting the blood vessels that are already formed. They do work in different pathways that were multi-kinase. It just reads that different pathways that these work by will bring them down a little bit, but they really, as I said, designed to slow down the tumor growth, possibly even shrink to the existing tumor. I do set goals with my patients when we start our discussions with therapy, is that my goal is for them to tolerate the therapy and live as long as possible. We as medical oncologists, of course, like to believe that we understand what it's like to be a patient, that we want the cancer to go away. There are times if we stop the growth of cancer, we are very happy with it. Shrinking it is a blessing, and going away completely is sometimes great hope. But we always believe in everything we do, so a lot of times when we talk to patients about that the tumors are not growing anymore, that is a success. The common side effects with tyrosine kinase inhibitors, they put them up here because we can talk about them individually with each drug, and they have some variability amongst all of them. But for the greater good fatigue type of rash, we'll talk about that. Diarrhea and high blood pressure seem to be the most. There are some that have different within each other, and we'll talk about it. Bleeding, clotting, and wound healing is part of the VEGF pathway, and I think when you have all these drugs that have part of the VEGF pathway, they're all going to have issues that way. Nexivar was the first FDA approved drug. I can't tell you why I know, but December 20th, 2005, nothing else is during the day. So with that, again, that was the first drug, and literally five weeks later, January 26th, 2006, Sutin gets FDA approved, and I think within the course of five weeks to have two drugs that worked very well was really beyond the blessing. I know we've seen articles that talks about the embarrassment of rishes, and I think that's something that applies. Nexivar got its FDA approval based upon its patients who received the prior therapy, then received this as a second option of therapy, and this did improve the median time for the tumor to grow by double, and I think that sort of got the foot in the door, and Sutin got its FDA approval based upon two phase two studies. Shortly after, they did release data on a phase three study, and Sutin pretty much became the drug of choice for kidney cancer. It definitely had the best favorable response. It reduced the disease in a third of the patients by more than 30%, and for some time, that became the go-to drug for patients who had metastatic kidney cancer. Three years later, similar pathway, Voltrient or Pizzatinib gets FDA approved, given once a day its side effect profile a little bit different, and you have to watch the web of function tests almost every two weeks for the first three months, it can affect your electrolytes. So again, monitoring with that seems to be very important. Again, something we instill into our patients, we do ask patients to sort of follow through with the way the protocols were done, and I think it's sometimes we do see patients that we have to adjust the therapies because of these side effects. In LIDA, or I said it was the one that's most recent FDA approved two and a half years ago, it too has its own set of side effects. Horseness seems to be something that we see, and actually they started utilizing, can we start predicting who should be doing well, and they started to use sort of a biomarker, even just using high blood pressure, sometimes within LIDA, and now with Sutin we're going back and sometimes recognizing that patients who have started these therapies and have high blood pressure, they sometimes can predict that they may started having a better response than others. The other target therapies, the M-tor inhibitors, these inhibit the M-tor stands for mammalian target of Rappermycin. It's a protein that controls cell division and survival. Taurus cell and Affinitor are the two drugs that fit this category back in the day, and even now if you look at the M-tor and Taurus cell and Affinitor, they actually incorporate the mechanism into the name of the product. Taurus cell is an FDA approved drug in 2007, it's an IV formulation, and it actually got its FDA approval based upon the poor risk categorization. Some patients who have Sutin and Nexobar, its first FDA approval, these were for clear cell, renal cell cancers. Taurus cell sort of fit the need of what wasn't being covered, so patients were not eligible for those studies because of their poor risk categorization if they had looking at the MSKCC criteria, or if they actually had non-clear cell patients were getting Taurus cell at that point, and its FDA approval was based upon those categories. So its FDA approval is not based upon the fact that it can be taken care of patients who have clear cell, but actually non-clear cell or patients who have clear cell at poor risk. So it gave us an opportunity to treat these patients where data was not offering us that knowledge when it came to Nexobar or Sutin. It blocks the M-tor pathway, interferes again with cell replication, angiogenesis, and Affinitor has a similar mechanism, the side effects appear to be similar. It happens to be an oral drug taken once a day, has a little bit more pathway inhibition, even angiogenesis, or again the same pathways that the VEGF incorporates. It's there again, the side effects between both agents are relatively similar. I'm not going to go through each one of them. You do find with Affinitor you do have more of a mouth infection risk and sometimes you can actually develop an inflammatory condition in the lungs that are readily reversible in steroids. Again, two agents that have actually fitted quite well to our armamentarium. The last one is the pure VEGF inhibitor, that thing, Avastin. It got its FDA approval for kidney cancer in 2009. Avastin is FDA approved in other malignancies, given intravenously once every two weeks. Again, its FDA approval is with interferon, but there are times where it actually can give Avastin by itself and it too has the common side effects of the high blood pressure that headache and the fatigue. I think it was Mike Actins back in 2009. Actually, you came up with this first roster about how we should be thinking that when it comes down to patients, and this list has grown over the course of the last five years, and when we go through experience, when we go through the NCCN guidelines, when it comes down to data, this is how medical oncologists should be thinking. This is kind of the playbook we have in our head when we see our patients. It's relatively easy and it really is important to try to incorporate our therapeutic interventions when it comes to patients, because it's not just about what the doctor feels. This is gut feeling. There's a lot of data that supports that hopefully they're gut feelings. Now, first line and second line is really the first agent they receive. Again, I still think surgery in my ideal scenario is the best thing. And sometimes, as Dr. Wang was saying, you can actually go for surgery and actually do absolutely nothing afterwards. And there's a period of time where you can just keep valuing the patients doing CAT scans or MRIs ever so often to feel that the disease is truly almost a typical kidney cancer where it is a slow-growing process. You can actually be living with cancer and do nothing for it and actually not have to be involved in any of these therapies. But when these therapies are important to be utilized, we do have pathways to think in our heads about based upon the data how we should be thinking it. And again, I'm not going to go through the list on each individual one because this also is a subject for discussion. Just because when it comes down to our oncology meetings, everyone has a reason why they use one drug for the other. The future is going to be discussed probably in the next nine minutes, but more for how the data is going to evolve over the next two years. The science has now evolved to a new pathway. The new pathway is PD-L1, which is program death of Lycan 1. These are expressed on tumor cells and tumor infiltrating immune cells where these are normal pathways that suppress the T cells. So these are inhibitors of those suppressors of the T cells. So our T cells that are normally used to incorporate to help boost our immune system, these are therapies that are now able to sort of inhibit the blockage of our normal immune system to fight cancers. These Ketruda and Urvay are FDA-approved drugs as these types of therapies for melanoma that are being studied extensively. Again, those three bold points at the bottom are active studies that are in a lot of centers across the United States, even in this region. And I'm going to leave that part of the discussion up to Dr. Dutcher. So to sum up, immunotherapy is still the mainstay of therapy for advanced kidney cancer. The FDA-approved drug Progokin or IL-2 appears to be the best drug if one wants to sort of over, I guess, to undertake a therapy that can be toxic temporarily but reversible with its toxicities but possibly be able to be on a therapy and then have a long, durable response, remission for the therapy possibly postponing inevitably maybe having to get another therapy but possibly postponing any other therapy that you may require for advanced kidney cancer. Targeted therapies for the last nine years have been a breath of fresh air for our patients in regards to options of therapy. They do have its set of toxicities and I think that when I talk to patients about therapies, it's about the tolerability of the therapy as well as the efficacy but in that order and that applies for the TKIs as well as mentors as well. As to how one approaches therapy, it really comes down to the patient's presentation, their quality of life, their extent of disease, their goals, our goals and really one always tries to apply the risk categorizations of prognosis to find out how the patients should be able to be given their therapy form. Again, the checkpoint inhibitors, again, is going to be a new science that's going to be incorporated into our practices definitely within the next five years. A new way of taking care of kidney cancer patients allowing us to do what we've done over the last nine years is give them therapies that we were not able to give them in the past. So with that in mind, I think I have five minutes. We should just go into the next one because we're going to have a question and answer period after the break and get to ask questions at that time. So I thank you for your time.