 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 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, 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, that's a, that's a really good analogy, and is this on? Can you hear me? Okay. And I think it, it actually, it's a hundred 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, of, you know, blood vessel growth being an important target and biology of the spread of cancerous metastases. And you know, when you think about it and how metastasis happens, you know, the first step of that is, well called dissemination, cells getting out of the tumor and disseminating in the 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, 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, you know, 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, 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, it shrinks them. I, I'm not sure that biology is, is as critical, but it, you know, that could be part of it. So there's, there's still a lot we don't know, but there's good clinical data to say that, you know, when, when you've got 90%, when you get 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 chance for us to learn. My father is 80, 94 years old in Shanghai, China. Two years before, he was a relatively good health and accidentally found the left kidney have a 1.2 CM, so called a solid mass addition to the many cis. At that moment, we really think about the, the options and all the radiologist and the most urologist over there, they concern this is renal cancer, renal cancer, and they prefer to wait. And during the wait, these two years, that can, that mass grows to the 2.5 CM. And during this time, he had one stroke, but very good recovered. And this situation, I just briefly ask Dr. King, is it basically if less than 3 CM prefer to still actively monitor that? He never do the biopsy. So he, I think he don't have a chance to do any other thing without the pathologist's diagnosis. It's possible he do the radio frequency therapy and also the cry therapy. 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 that are really, you know, specific to that individual. In a case like this, you know, 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, etc. 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 persons being monitored very closely. Things like cryotherapy or radiofrequency ablation can 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 is Todd and I'm a five year survivor. This is my second time coming to the program here. And one thing that 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 U.S. 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 going to be coming to the forefront or is there certain biomarkers that you look for? I'm currently on SUTENT 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 going to be addressed in large part by Dr. Moscos, who I just walked in who's going to 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 a 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 going to 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 to 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 SUTEN 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 going to 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, and all kinds of things like that. So, so, you know, don't don't don't get anxious to get on to the next therapy. You're doing fantastic. And I always try to encourage patients when when they're doing well in therapy, you know, we really want to maximize that. It's great to look ahead, but just know that the longer you go, the better, more informed we're going to be about how to manage in the future. That's great. Any last questions? So thinking a little bit shorter term, Dr. George talked about getting on the rolling machine and it being too much. So you backed 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 when do you change your 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've been all calm. First of all, let me just say that there is a rowing machine for sale. Anybody's interested, happy to pass on the torture. No, these are these are great questions. 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 I have little 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 I can't even look at somebody and say, Gee, you're gonna 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 and when possible, doing it in person, because the phone, just this, there's 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 it's hard for you to describe that to us. And we just can't tell. But and it's a lot of it is the change, you know, how much change has there been in two weeks on a patient? You know, if if there hasn't been that much change, they weren't super functional, but they're still not that much worse, they're probably going to be okay. If they were fantastic, you know, running five miles a day. And now they're, you know, walking, you know, 200 yards in short of breath. That's a big, big difference. So I mean, 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 that frequently over time, we we will adjust the dose down a little bit. And it may not be for that horrible, you know, diarrhea or something, but it may be just sort of the chronicity of the side effect, or 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, 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 going to do that, I want to make sure, you know, they, they look like that gentleman back there and not, you know, somebody who's been worn down by the medicine. So, so that's a really important aspect of this. And it's kind of an ongoing discussion and things that that's, that's kind of how I think. If I could add to that, thank you. Is what I kind of counsel my patients is we have to think about big picture and long term to write. So I make changes to medications. Obviously, if there's significant pressure, significant progression on scans, right? 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, right? So if your liver function test gets 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, 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 my clinic, he says, I'm going to whatever city he's going to, and I really want to eat this pizza. But right now, I don't think I can, it's going to 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 the, your cancer is going to change so significantly in that two weeks period or whatever it is that you negotiate with your provider off drug. It just, it is rare that that would happen, 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 benefits, say, at this level, now we're going to increase it because we think we could get more benefits. Yeah, if we don't start you off on the maximum dose for, you know, x, y, or z reason, if you're at half dose or a 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-lido or exitinib medicine where we start low and escalate the dose up and we mention the issue of the 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 Rini, who's another doc at the Cleveland Clinic that was presented that looked at, it wasn't a large group of patients, it 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.