 Good afternoon. My mom had a total radical nephrectomy in 2007, stage two. What are the chances of reoccurrence or is there any time period where there's this many years after a total nephrectomy that you're labeled cancer-free? So you said surgery was 2007. So a new diagnosis of stage two, I usually quote my patients the risk of occurrence of around 30% or so lifetime risk. Certainly as you move through time and the cancer hasn't come back, that risk is getting smaller and smaller. But data tables are always calculated or drawn out based on time zero at the time of diagnosis. So it's hard to give somebody a numerical estimate of relative risk at year two or three or five. So at this point seven years removed, you'd like to think the risk of occurrence is very small. There was a very interesting paper that came out a few months ago. The Mayo Clinic looked backwards at their entire experience of kidney cancer going back to something like 1976, 3,000-some total patients. And apparently their internal algorithm was to follow patients. It appears to be indefinitely with body scans. The current guidelines would say five-year period of observation with imaging surveillance and beyond five years you should stop. So they were able to say, okay, how many recurrences did we find within the five years that are our guideline-based interval for recurrence? But we watched everybody forever so we can say when did they recur was after five years. And only about two-thirds of recurrences were identified within that five years. So fully a third recurred between year five and up to year 11 or 12 post nephrectomy, which I thought was interesting. I don't know of another data set that really gives you that flavor of what's the true timeline of disease recurrence. The lower the stage, the stage one in two patients had a longer scatter of late recurrences at years 10, 11, 12, 14. So that hasn't changed guideline standard practice. I would still say any body like the American Neurological Association or the NCCN guidelines would say a five-year window. So I wouldn't strongly advocate ongoing observation. The risk is small, but that Mayo data proves that the risk really isn't zero. There's this tiny chance of a late recurrence, but really hard to give you a hard number on that. Question is about proton radiation therapy. I know that recently there is a proton facility open up, I believe, out in Redmond or Woodinville. With Evergreen Hospital. Where does that fit in with like pain management or with brain metastasis treatments? Any comments on that? Well, so SCCA has a proton therapy suite up at Northwest Hospital. And I don't directly intercede in making decisions about the style of radiation therapy. But in broad strokes my understanding is proton therapy is more expensive. Third-party payers will deny it unless you can prove there's a study that says it's better than standard external beam radiation therapy. And there's no data for kidney cancer and most other cancers. The one disease where it's done a lot is prostate cancer where there is data arguing that it's better, at least by toxicity. So that would be in the domain of your radiation oncology provider if they had a mechanism to recommend protons and gain your insurance approval. But it's not being commonly done. Thank you. One is just a term ejection fraction someone removed mentioned that and I don't know what that means. So that's just a measure of how well your heart is pumping or squeezing. And with synitinib there can be a slight decrease in how well the heart functions. So it's the muscle function of the heart. Okay, thank you. And the other question was for the last speaker. There were two questions. The nivolum on whatever study. Was it studied on papillary cancer at all or was it just clear cell? So good question. The study I showed you was strictly clear cell. The MPDL 3280A antibody in its first clinical study allowed papillary renal tumors and my recollection is they treated I think six tumors and had I think one response. That's as far as I know the entire world experience with these drugs and non clear cell tumors. The phase four trial that's supposed to be coming for nivolumab is not going to restrict by the tumor histology. So it would allow any kidney cancer diagnosis to receive the drug. Chromophobes, papillaries, you'd come into it not really knowing what the likelihood of responses, but you would be eligible to participate. Great, thank you. My last question was when you had that one slide up that talked about the complete response with these different ones were like one percent or two percent or whatever. How does that compare with just a spontaneous response in the general untreated population? It's really hard to put a number on the likelihood of spontaneous remission. In my entire practice, I can really only think of one patient that had true spontaneous regression was incomplete. It didn't go to complete response, but had fairly large lung findings that shrunk down dramatically over a couple years time. Sadly, then develop brain lesions. So the brain lesion is able to grow larger despite the body lesions getting smaller. I would guess something in the range of one in 10,000 to one in a thousand patients at most. It's a rare phenomenon, rare enough that if you ever see it, you write a little paper and describe it in the medical literature because you're like holy smoke. This is unbelievable, but it's not really a therapeutic maneuver. You wouldn't say tell somebody to wait, hoping that your tumor is going to shrink down on its own. That almost never happens. Okay, general question. As a kidney cancer doctor, other than in a trial, do you guys keep records of your patient's history and what works and what doesn't? And does it go to a national database somewhere? So that's a really interesting question. And the bottom line is really no. We obviously can go back to a patient's own medical chart. It's available to us. Our center and Dr. Kamal could talk about Virginia Mason does not have good bioinformatics tools built in to our medical chart that you could in some capacity say, well, let's see what happens to the last 100 kidney cancer patients. Let's see what happened to kidney cancer patients in our center from 2000 to 2014. That just isn't possible. This idea of national registries has gained a lot of attention because this is a real dilemma in the field. Investigators would like to know what happens not to 50 or 100 patients, but 2000 and 5,000 and 10,000. You'll see statistical findings that you just can't tease out with smaller numbers. So there has been a drive to try and collect patients into larger registries. There is an interest in doing it for targeted therapies. I know Dana-Farber Group is really big on building a large national registry. There's an investigator at Duke that's tried to launch a similar effort. We're actually participating in that IL-2 data registry, but we're not a participant in the other targeted therapy registries. So there could be the possibility down the road of more patients having their data compiled into that kind of catchment mechanism. But for most practices, I don't think that's happening. Okay. And then another question is how often can a kidney cancer patient ask for a scan? Actually, I'd like to go back to the first one, the registry. I think the limitations are manpower, woman power and money. So like the HENG criteria that I showed you that was really driven by the fact that there was money available to develop a consortium and collect all the data. And a single institution, you know, when you have a medical student or a student come by and they're interested in something, that's what the impetus is to look at something specifically. But other than that, we don't keep the data. How often can somebody ask for scans? I mean, I guess they're guidelines as to how often one should do scans. So it kind of depends on what the situation is. Is it somebody who's six years out and we're just doing a follow-up? Should we be doing a scan, not a scan? So the guidelines would say no. I guess personally, if somebody came to me and was adamant, I'd probably do it once. I'm interested in that, like whenever my husband gets on a new pill, I want to see in three or four months if it's working. Yeah, so that's actually reasonable, right? So anytime you change treatment, prior to that, you'd image and then after reasonable interval, I think three months is reasonable, you know, you would see what happens. Okay, thank you. Oh, so I guess if you talk about kidney cancer, you know, it could be chest, abdomen, pelvis, the BSET scan. My question is on the oral medications. Did I understand your presentation in the arrangement, you know, the mixtures and all that? There's none of those that if you start one regimen of that that it doesn't work, that precludes another one. So let me understand. Your question is if I'm taking one oral medication, that doesn't work. Does that mean I, because I've taken that, I cannot take, you know, oral medication X, Y and Z. So I guess that's partly true, but not completely true. So let's say if you were on an anti-veget, and that stops working or the disease progresses while, you know, someone's on sunitinib. And if one's never been on an mTOR, which would be a vrolomus, you know, that would be approved and that would be the next logical thing to do. At least so we thought till very recently, but then there was another one, anti-veget, which is actually used in second line now. So I think if you've tried a couple in one class and another one in another class, I think beyond that approval does become a little tricky. So combinations, there are no combinations that are approved because they've not been shown to work. In fact, you get more side effects, you know, without any benefit. So that is very clear, but you can definitely switch around from one class to the other. I think there is a limit to how many times you can do that because A, it's not going to work and B, one also runs into insurance approval. So yeah, there's no safety reason that you couldn't use any drug after any other drug. So there's no sort of absolute barriers. Scientifically, the two mTOR inhibitors are thought to hit the same target. So I don't think I've ever treated somebody with Temsir Limus and then at some later point Everlimus, thinking that you're giving them the same drug that didn't work previously. But the tyrosine kinase inhibitors are all thought to be subtly different from each other and every time you look at applying one after another, there's always a subset of patients that have some degree of tumor response. So a lot of patients wind up getting two, three, four tyrosine kinase inhibitors over the course of their therapy. And that's not irrational. I had a follow-up question on the scan thing because with the CAT scans, if you haven't too often, they say that you have an increased risk of leukemia and things like that. And with the MRIs, if they do the contrast and you have kidney function problems, then you risk NFS. And so I was wondering if you were trying to avoid too many CAT scans and you couldn't have contrast with your MRI. Is a non-contrast MRI or a sonogram ultrasound, are those effective at all if all you're trying to do is see if the drug is working? So you know that's a good question and I'm not sure I have a straight answer for you. So it kind of depends on the situation. So a lot of the patients already have impaired kidney function because one kidney is out. And so I think I very often will use a non-contrast CT. It just depends on what information you're trying to get. And if we do do the contrast, then I may actually go down the road of an MRI because a CT with contrast is more harmful to the kidney than an MRI with contrast. And then again, within contrast, you can do things to be able to get the scans. You can hydrate patients. So it just depends on what one is looking for. But let's take somebody who has one kidney out. They have mildly impaired kidney function. So I will very often use a non-contrast unless you're specifically trying to look for something which would be... I mean, I think you can get enough information from a non-contrast CT in most of the times. Right. So as far as the radiation goes, now the only data I'm familiar with is because actually long time ago, I used to be with the VA as well. You know, when we did protocols, you had to quantify the risk of a CT scan. And I think if you do one every three to four to six months, it's probably okay. The last time I looked at the data from what I remember is, you know, if you do a CT of the chest, the amount of radiation you're going to get is probably the same as 10 roundtrip. So that's one of the two flights between Seattle and New York. So at least that's one way of quantifying risk. My brother has stage four translocation, Reno South, and not having the full picture because I'm not right there with him. I want to try to help find a study which is incredibly hard so far. What information... Could you recommend to me what information would I need to have at the moment? You know, if I'm trying to get him into something, something that I don't understand a lot of the information. Like you can't do this, you have to do this, you know. Is it... You need the whole medical record, just a snapshot? What's the best bit of information I can have handy all the time? I think if you were just calling institutions, they're going to want to know the diagnosis, the stage, maybe some pertinent past medical history. To formally enroll, they would have to have your brother come out, do an evaluation, get the complete chart to make sure there weren't any issues for past medical problems or they'd need to see up-to-date lab data. So to enroll would be more complicated but just to find out if a study makes sense and if it's a good fit, you should be able to do that with a phone call. The translocation renal cell carcinoma for the rest of the audience, it's a rare kidney cancer subtype, has a very discreet chromosomal rearrangement that can be tested for. That's the hallmark of that disease. I can guarantee, I bet there's not a single study nationwide that is a study specific to translocation renal cell carcinoma. There aren't enough patients, you'd never complete a study. So it really boxes you in to kidney cancer studies that don't care about the histologic type, which are uncommon. They almost always say it needs to be clear cell. Something like the phase four nevolumab study that would be open to any histologic type would be lovely. Or there's a lot of studies, early clinical trials, often phase one studies that are open to any advanced cancer, doesn't care, wouldn't even be kidney, it would just be any cancer process. So those are going to be available hit or miss at different cancer centers. But then the question is, well, what's the new drug? And is there any reason to think it's a clever, smart choice for kidney cancer? And that's where I think you really need your physician to guide you. Is it something that doesn't seem like it likely would work at all, or is it something that might be quite interesting to look at? I think we'll take one more question here. And then I know Dr. Taikoti is staying around for the afternoon. I don't know about Dr. Chattis, but I am going to volunteer you gentlemen to just come ask your questions. And if you're not comfortable asking in front of the group, that'll be a nice time for you to do that. So we'll take maybe two more questions. We have time for a lunch break until about 12.15 when we are due to start again. So we'll work on these last two questions and then try to come back here at about quarter after 12. I'd like to focus on spontaneous regression. In order to know that that's occurred, you have to be following the patient, presumably, without any other treatment. Today, with the treatments available, how often does that happen? And can you distinguish between spontaneous regression and a response to therapy? So if you look for these case reports in the literature on spontaneous regression, most of it is written in the 1950s, 60s, 70s. And that was a time when there were no established therapies for kidney cancer. So many patients, the doctor would say there's no treatment for this. But if you're pretty healthy and you felt well, maybe they come back and they do a scan in six months or something just to see how things were going. So it's data collected in an era where patients very often were not in any kind of active cancer therapy, but were pretty physically fit and doing okay. And they thought, well, a scan might help us to give you a sense of where you're at, how fast things are progressing. So that's where most of the literature comes from. It's pretty old. I just happened to know a patient that did a couple of months of SU-10, didn't like it. And I actually wasn't seeing the patient, but a colleague saw him over the next couple of years off of therapy. He was quite adamant. He was just going to focus on quality of life. And I believe it was for neurological symptoms. They did full assessment and unfortunately found brain lesions. But when they look back at his body where they knew he had pretty substantial disease in the lungs, it was almost completely gone. So it was fascinating that that tumor had shrunk down with no, you know, for two years, no any kind of active cancer therapy. But unfortunately it was discordant with other parts of his body. Okay, last question. Is it real drugs or fake drugs? So if a study was done with a placebo, they would tell you you're not blinded to the fact that there could be placebo. For stage four metastatic disease, that would never happen. It would be considered unethical to withhold active therapy from patients. It does happen for stage three disease. So patients without any findings of cancer, there have been several large trials where they applied one of the targeted drugs versus a placebo. So everyone got a pill bottle and they didn't know if it was a true drug or if it was a fake. Where patients didn't have active cancer by their scans and you want to find out does applying a drug help or not, the comparison is no drug at all. But the thought is you get a truer sense of everyone's behaving in the same way, believing they're taking a pill. Then if you just tell half the people take the pill, the other half you're not doing anything, you're the control group. But that's considered to be an ethically appropriate approach where the people getting placebo aren't suffering any kind of harm. Okay, thanks everyone for your attention. There is a light lunch over here in this area. Why don't we all try to come back here about quarter after and feel free to bring your lunch in here with you.