 We have a whole day of presentations but I want all of you to be vocal, please stop at any point if there are anything in the presentation that's unclear. We want your voice to be heard and we want this to be a useful day for you to take information with you. So I'm going to start just doing a brief overview of kidney cancer just to set the stage for the other presenters for this morning. So I'll start off by just saying here is a picture of the kidney and not all tumors that are in the kidney are really kidney cancer. The ones that we are going to be talking today is those that arise in the cortex. So this is the cortex and these are the ones that are the real kidney cancer that we are going to be talking about today. What are the other tumors that can happen in the kidney? You can see that this is the part where urine is made and it comes through the urinary tube called the ureters and it's a common cancer that usually happens in the bladder but you can have this type of tumors happening in the kidney as well and those are called transitional cell carcinomas they're more like bladder cancers. Then you can have Stanford is an institution with expertise that's world renowned in a disease called lymphomas they usually happen in lymph nodes all over the body but because we are an institution of referral inevitably when we see sometimes tumors in the kidney they end up being a lymphoma. There are other cancers that can happen in the kidney but our date today is going to be focused on the kidney cancer that arises in the cortex. So what is the incidence of this disease? This is a slide taken off from the American Cancer Society they put up these every year with sort of estimates what's the what is the burden of disease that we are talking about and this is a new cancers that happen in men and women and sadly kidney cancer features as the top 10 diagnosis both in men and in women. So about 40,000 cancers each diagnosed each year in men and in women about 25,000 so it's certainly not as big as diseases like prostate cancer and breast cancer but certainly it's enough for us to have our voices heard and for us to continue working on this disease to get the best that we can in terms of outcomes. So what about kidney cancer at diagnosis? You know most patients present with fortunately today we see a lot of patients coming into the emergency room for another reason maybe they have a gallstone or they have abdominal pain and incidentally kidney cancer is discovered those are good and they represent about less than 50% of the time where it's confined to the kidney. Unfortunately half a quarter and even a third spread by the time the diagnosis is made because kidney is in an anatomic location where if you don't have a symptom the tumor can continue to grow and unfortunately for a third of patients by the time the diagnosis is made it may have spread elsewhere. Here is a brief staging as you hear multiple talks today I just want to set the stage for what the different stages are. So stage one are small tumors less than seven centimeters confined to the kidney. Stage two tumors are greater than seven centimeters but they are still in the kidney and you're going to hear about the surgical management for those group of patients. Stage three we call it locally advanced disease where there is tumor that's left the kidney to either the blood vessels either the renal vein or the inferior vena cava or the fat involves the perinephric tissue and finally stage four diseases if we have distant disease so whether there's lymph nodes up in the neck or disease in the lung liver bone or brain would be considered stage four. So we now know that kidney cancer is not one disease it used to be even five years ago we would classify all of kidney cancer as one we know that this list is growing and it's just I have another slide where this list now includes 20 different types and I think that speaks to good things where we are learning more about this disease we are learning more about the biology we don't want to lump all kidney cancers as one but we want to get to subgroups where we are able to have different treatments that are directed to different subtypes but the most common kidney cancer is called clear cell and all of our drugs that we have today are really focused on this histologic subtype and that's where the drug development has been focused the most that represents 75 percent there's a less common one and all of the rest are lumped as non-clear cells so there's clear cell and the rest are considered non-clear cell what does non-clear cell mean it includes those with a papillary type and we now know again that there is type one papillary and there is type two papillary and each of these are specific mutations that drive these different tumors and I think as the what we look forward in the future are specific drugs that target each of this that we will have different drugs for each of this and then there's a less common one called chromophobe and oncocytoma we have other subtypes which I haven't actually put in but there are many more that are coming so overall just a brief slide on the background so again you know we said this is in 2012 but I already showed you it's around 40 000 patients new diagnosis per year majority a clear cell about a third of patients unfortunately have stage four at diagnosis prior to 2005 we had very little in terms of medical treatments for kidney cancer and it was all with the immunotherapy or cytokine with the drug called interferon but today things have changed remarkably and we are going to be spending the latter part talking about it so here's a slide which I'm really proud of to talk about where we headed and where we are today so these are the drugs that we have had just in the last decade you can see we have made so much progress had I done this talk in 1993 I would have stopped shot with one drug which was high dose intraleukin 2 starting in 2005 we have had remarkable success in approval of various drugs for kidney cancer and we are going to be talking about seraph anib sunitanib another class of drugs called mTOR inhibitors with temsirolimus and everolimus there's avastin or bebasisumapizopanib and acetanib I know it's 2012 and it seems like what's happened since 2012 by the end of the day I'm going to share some new drugs that we may be having even by the end of this year so what do we know a little bit just about one slide on the biology just so that we understand where things started and how drug development went on for kidney cancer to the left is a normal this is what happens in normal situations we have a protein called VHL it binds to this hydroxyproline and combines with this element called HIF 1 alpha and once this complex is bound it gets broken down by ubiquitin and proteasome and then the HIF gets degraded in our body that's the normal process that needs to happen in kidney cancer and when this VHL protein is mutated or is abnormal this is what happens here VHL is unable to bind via a hydroxyproline with HIF so HIF just accumulates in your body without getting degraded and what are the consequences when we have too much HIF in our body you get all of these proteins called VEGF and PDGF and this is what drives these tumor cells to proliferate and spread so knowing this was really important that now that we know this is what happens in kidney cancer people then started thinking about how about if we find ways to block VEGF if VEGF is what is increased let's find drugs that target VEGF and that's what the slide is and it just shows you that there are many different ways by which we can block VEGF you can block the ligand with a drug called Bevacissimab or you can block the receptor with a variety of drugs that we are going to be talking about today so these are the main two two classes of drugs that we have in kidney cancer one are called VEGF inhibitors and the second class are called mTOR inhibitors and these are names that you are going to be hearing a lot by the end of the day and so I'm just going to wrap up this by just saying this is what kidney cancer medical therapy looks like in 2015 we actually have three classes of drugs there's immunotherapy and now it includes interferon and interleukin 2 and I think by the end of this year there will be a new class of drugs called PD1 inhibitors or a drug called nivolumab we are hoping will get approval by the end of this year and there's also going to be a new drug called cabozantinib then there are VEGF inhibitors with sunitinib, soraphinib, pisopinib, acetinib and Bevacissimab and mTOR inhibitors so that's just a brief overview so that it puts in perspective and context some of the talks for today yes so immunotherapy is definitely a separate class of drugs they are not targeted drugs they sort of it's like if you get the flu you know how your whole immune system is all revved up with a variety of chemicals that the body secretes to help fight your flu it's identical to that that's what immunotherapy is when we mean for cancer therapy and we talk a little bit about that the targeted drugs the VEGF inhibitors are all the idea here was it was aimed at blocking the VEGF so it's completely different from immunotherapy so here is our agenda for today I gave a I went a little bit over on my welcome we are going to have Carrie Konoski from the kidney cancer association who's sponsoring this meeting today talk a little bit about their association and what they can do for our patients I'm then going to make a slight switch on the agenda because it makes sense to talk about local therapy first what do you do when you have tumor confined to the kidney and we are really happy to have our surgeon here today Dr. Jeff Son who's an assistant professor in urology he's going to give us an update on what can be done for local therapy so we're going to make a little bit of a switch and then it makes sense for me to talk about medical therapy and we're going to go over some of the drugs that I just spoke and then we'll take a very small break and then I would like for Sujatha Narayan who's one of our medical oncologist here at Stanford she's going to give us a little overview on clinical trials I think that's a big part of all of the progress that's happened in kidney cancer and I think as patients it's nice to understand how this process works where do you start with clinical trials what are your risks what are the benefits of Sujatha is going to give us an overview about how clinical trials work then I think one of the things that are really new is genomic testing who should we be doing it on we think a lot of this is how we are going to be headed in the years to come people are going to have their individual tumors tested and maybe that will help us drive specific therapy that's what personalized medicine is it's so confusing today as to who should get it done what do we do with the results so we have one of our fellows who's doing molecular testing Joshua Gruber he's going to come and talk to us a little bit about genomic testing and I think that would be he's going to give us some examples about some of the tests and see how we can learn from those we'll take a break for lunch and I think there's a latter part of the afternoon we are going to talk a little bit about imaging and how we can improve with some of the ways we can diagnose this early are there different modalities by which testing can be done and then I'm going to have Tommy Messner who's works with us in our research enterprise talk a little bit about what Stanford has done in terms of how we collect blood tissue and what we hope to learn from that in the future and then I want the best part of the afternoon which is really about a patient forum where Jordan Chavez who's a social worker come and engage all of us in sharing our stories and how we can help each other in this journey for this disease and then we'll wrap up so with that I'm really hoping it'll be a good day for all of us to take some information