 So just there's some microphones in the middle if you have questions. Otherwise, I'll grow these people So Dan You're not allowed to do that Bob can I make a comment about the adjuvant trials? Of course So one thing Dr. Share was mentioning is all these adjuvant trials that are out there and they're all compared to placebos and patients are randomized potentially to a placebo containing treatment and when we talk about these in front of patients it's a challenge Oftentimes to tell patients you could be on a trial and be assigned to a placebo, which is no treatment and To make patients understand that that's an ethical treatment that the standard treatment for for early-stage high-risk disease is really no treatment but but close observation and Patients are oftentimes uncomfortable thinking they could be assigned to a placebo treatment And part of it of our job is to make them understand that that's actually The standard of care. Thank you David. So so Dan, let me ask you Just to set people's minds at ease How often when you see a pathology specimen from an outside institution that you're doing a secondary review of? Are are they different enough that it might change therapy or change the conclusions Well, you know, we probably see Maybe five or six secondary reviews a week And I would say maybe one or two of those we do have a slight difference of opinion Which would be a staging issue perhaps we would identify Intravascular invasion or invasion into a renal vein or into the renal sinus which would upstage from a t1 to a t3 essentially So yeah, so maybe 20% of the time we do see Significant changes also classification subtype classification is actually pretty common as well There's a tendency because of the commonality of clear-cell RCCs And again, I it's just you know the nature of the business a lot of Pathology that's diagnosed outside of major academic institutions is done through Either commercial labs or small private Pathology laboratories where they might see a renal cell carcinoma. Maybe once a month whereas we see on a daily basis We see two three four potentially a day. It's our bread and butter. It's we're really good at it as our UCLA and USC I mean you want somebody at your pathology reviewed at a big institution where they're very comfortable doing it So it's it's very easy for someone who only sees one a month to say well I think it probably is clear-cell because that's the most common subtype I'm just going to sort of sign it out as such and send it along and it might be something different young Let's talk a little bit more about surgical approaches in your practice how often to use the robot how often laparoscopically and and talk a little bit about Hospital stays loss of blood during out a procedure and and kind of the What the patients feel as a result of your interventions? Yeah, so those are all questions that You know that are on the very forefront of patients minds If you do an open operation, you're in the hospital typically for a week If you do laparoscopic surgery you get out in one or two days And so there is a big difference people who are having curative surgery are looking to get back to work quickly And so you know we do laparoscopy when we can The only time we have to actually make a big incision is if you have tumor growing into the Major vessels of the body like the vena cava which leads right to the heart So for when you have to open up blood vessels and major vessels We do that through a larger incision Otherwise, we can almost always do it using a minimally invasive approach whether we're taking the whole kidney or not and that leads to also a decrease in blood loss and The robot is used by Physicians who have not been formally trained in laparoscopy It allows them to do laparoscopic surgery You know we we in our hands the robot Does not add to the operation. It doesn't make it less invasive doesn't allow us to do Something we can't normally do with the laparoscope. So we don't usually use it So there's not the only time we might use it is You know if the only room we we can get to do a case is the room with the robot so So sometimes it's a more of a scheduling issue than a tech, you know, then Then than anything else But but I guess if you look at the whole field of urology the robot has allowed Many more Urologists to do minimally invasive surgery and even partial nephrectomies where Because they because they didn't have the laparoscopic training In the in the past so it's it's been an important advance But I think you'll find that you know what I what I'm saying to be the true at a lot a lot of major Academic centers So Steve and please anybody just if you have a question just step up to the microphone So so Steve one of the I want you to put on your your visionary hat and where where The intersection between radiation oncology and immune-based therapies are going to Kind of exist not just in kidney cancer But in in cancer in general and kind of elaborate a little bit upon some of the work that you do Which really starts to raise the question of whether Giving more radiation is in the best interest of the patient's immunologic response Versus giving a little bit less to control but also Stimulate an immunologic reaction that there's been a sea change in the way I think the biology of radiation which is not necessarily which is kind of just in the early stages of being translated to kind of clinical care, but we think that radiation Because of its you know It's one of the few cancer treatments that's actually Evolved with you know from single cellular organisms. So if you think about it You know, it's not as if a lot of these targeted agents, you know We're affected, you know throughout the history of evolution, but radiation has always been there to some extent And so what we find is that there are unique mechanisms for For removing things that have been irradiated and many of those mechanisms involve Things that I study in the lab which are immune things So recognition from the immune system that a cell for instance has been irradiated and it's damaged And there are also a lot of control mechanisms for that because it's a very Complicated process so you don't want to have inflammation anytime your body encounters even small radiation which happens Which permeates the environment all the time? And so it's a complicated Way that your body removes it in a way that's non-inflammatory And so one of the things that we've tried to do and I think where radiation will be going is to try and understand the mechanisms that regulate the the control of inflammation because in the setting of tumors we want to develop more Antitumor-immune responses and so how we plan to do that is we want to try and understand how the body itself Regulates it and through some of these newer agents. So there are agents that target something called PDL one that Dr. Shear mentioned there are also trials looking at high-dose IL-2 in combination with radiation and these radiation Strategies are very different. So it used to be that we use radiation As Dr. Biglin mentioned to really try and you know kind of clean up an area like you treat this wide area You're trying to get rid of you know conceptually every last cell But when you think of radiation as an immune stimulant, it's completely different where we would treat You know either a portion of a tumor if we if it's not safe to treat the entire thing or you would treat You know smaller, you know certain tumors, but not other ones and in the in the hope is to really do it in combination with an Immune therapy as a different way of thinking about it That radiation is more like a targeting agent to give you an in situ vaccine essentially So we know we're treating the tumor and we're radiating it and it allows kind of new tumor tumor antigens to be released so that your body can recognize the tumor again and then in combination with immunotherapy We think that that's a way in kidney cancer But also in maybe many other cancers in which radiation will have an evolving and changing role because it's one of the few It's a it's uniquely mechanistically driven by we think the immune Mediated systems and so some of the things I study in lab Or we look at macrophages or certain cell types like T cells and we ask you know What are the T cells that are there one of the macrophages that are there? Which are certain types of white blood cells and how do we affect their their function by targeting immune pathways? So things that traditionally, you know would have been used for you know For instance autoimmune disease or asthma or kind of any any of those different things We think can actually affect the immune system in general and we think that using radiation in combination with some of those things Will probably be a way that the future evolves quickly and differently than it kind of has in the past Time for lunch. Thanks everybody. We'll reconvene at noon