 So what I've heard is that people are getting a little bit of case fatigue, so maybe we'll just pause for a minute, and do people have questions that they want specifically answered? Aside, you know, this isn't a mini clinic. We can't do individual consultations, but if you have some general questions that you'd like answered that we haven't touched on, by all means ask. Use the microphone. We have heard about disease of the body in several forms, except the heart, heart stroke and etc. Can cancer grow in the heart, or it has to be contributed from another organ to the heart? Can it grow, develop in the heart? Can cancer develop in the heart? Is that your question? Yes, sir. Yeah, there are primary tumors of the heart, they're extremely rare, it wouldn't be related to kidney cancer, it would be, you know, probably a sarcoma because the heart is made of muscle, but tumors can occur primarily in the heart, what does I say, they're very, very, very rare. So the most common tumors found in the heart are metastasis to the heart, and the commonest one would be lung, going to the heart, lung cancer. Melanoma, which is a rarer, I mean rarer than lung cancer and breast cancer, has high propensity to metastasize to the heart, melanoma. Kidney cancer, rarely, we've seen a few patients develop metastasis to the sac and sometimes in the heart muscle occasionally, but it's rare, it's one of the rarest sites, it's more common to go, as we discussed throughout the day, to lungs, lymph nodes, bone, liver and brain, but much, much less frequently to go into the heart. Any other questions? When you just mentioned something about the brain, how often does kidney cancer advance to the brain? Because that hasn't been mentioned on any of the case presentations, and there hasn't been a lot of stuff listed as far as liver disease, you know, advanced liver disease to the, you know, metastasis. The question is about... Do you have some case presentations where you have some better metastases? Shall we say with more advancement, like to the brain, what are you going to do? What do you advise the patient to do? Sure. I don't think we have any of the cases, brain, but we certainly can, you know, answer or discuss any particular situation. You know, if there is one with the brain metastasis. Well, I know when we get in support groups and everything, and there is metastasis from renal cancer to the brain. Could you please go to the microphone? This one's not working. I have to talk closer. I don't like these things. Okay. Okay. What I'm asking is, you know, when you go online to the kidney cancer support groups, when you go to the other support groups and people there have metastases to the brain, very little is ever talked about. And of all of the presentations that you've had here, you know, we're not addressing some of the rare things, and I'm sure some of the things that we all worry about is, you know, you hear the term scan ziety, everybody loves to go for the CAT scans because what's the doctor going to tell me, you know? And so how do I know when it's affecting my brain? What's going to happen to me? Which of these medications are going to work for me? Can you answer that? Sure. These are good questions. I think the brain is not an uncommon sight for it to go to the brain. As we were just saying earlier, it is not a very common sight. So lungs, lymph nodes, adrenal glands, bone, liver. In this ranking order, brain will be the least it goes to. But you're right. There are complications or there are challenges when it goes to the brain. But I think the brain should not be looked at as, you know, a death sentence because it is not. There are patients who develop metastasis to the brain who are treated. I mean, obviously it depends on whether we're dealing with one spot, two, three spots, or 10, 15, 20 spots. I think obviously if there is that many, you know, used typically more than five, the recommendation would be to, depending on the size and the location, to treat with radiation or surgery. If one is particularly large, causing symptoms, headache or dizziness, and it looks like on MRI or CAT scans causing bleeding, is to resect it. And then the smaller ones being treated with gamma knife or stereotactic radio surgery. Sometimes if there are many, they're all small, or they're in particular locations where surgery would not be possible, then we do a whole brain radiation if there are multiple. But systemic therapy, again, this is contrary to what some people think, that the medicine doesn't get to the brain. On the contrary, some of the medicines we use to treat the metastasis in the lungs, liver, bone, et cetera, does cross the blood brain barrier. And we reported on patients, a series from Amy Anderson, seven patients that had disease in the brain where we treated with a suit and some of these patients responded. In fact, you know, two of them responded completely without surgery, without radiation to the brain. But it has to be an individual case-by-case discussion. I'm not suggesting that every patient that has spread of the cancer to the brain to not get radiation or surgery. Obviously, you have to discuss this. This is a consultation that we have with the neurosurgeon, with the radiation doctor, and the medical oncologist. But it is not a death sentence. There are patients who are alive doing well, even though they had metastasis to the brain. There are some patients who don't have metastasis to the brain, have metastasis just in the lungs, or just tumor in the kidney. But it's unresectable and continues to grow and invade surrounding structures, surrounding organs where the prognosis is worse than if the patient had their kidney removed and now they have one or two or three spots in the brain. I have many patients who have brain metastasis or alive and well for two, three, four and five years and beyond. So it's not a death sentence. There are treatment options. And it's an integration of local therapies with surgery in some patients where surgery helps radiation with gamma knife or whole brain radiation, as well as systemic therapy with drugs. Now, in terms of how do you know, the only way to find out is doing an MRI of the brain. Now, the problem is recently has been insurance companies are pushing back, they are denying. Every time we put an MRI of the brain request, they say denied. Why are you ordering an MRI? And we tell them what the patient has, cancer of the kidney and it's spread already to say lungs or other organs. We need to make sure it's not spread to the brain. We don't want to wait until the patient has seizures or is falling a toxic to then get the MRI of the brain. And sometimes when we talk peer-to-peer with the insurance companies and try to convince them they see it and they say, okay, you can do the MRI of the brain. But unfortunately, sometimes this is found or discovered when the patient develops a symptom or a sign. They may either have some abnormality, difficulty speaking or double vision or weakness in the arm or leg or numbness. And then you get the MRI of the brain and you find there is tumor there. But whenever we find this in the brain, we treat it in consultation with the neurosurgeon and the radiation therapist and the medical oncologist. Does one of you, she also asked about liver metastases. I wonder if either you or one of the other medical oncologists wants to talk about that and why we maybe haven't really covered that very much. Roberto, you want to, or Michael, you want to? Well, there is the notion that a liver metastasis carries a proven prognosis and probably that's true. There are, you know, some papers on IL-2 and the patient that have liver metastasis may respond less. But on that hand, I have a patient who has all the liver metastasis and maybe solidar liver metastasis and they're still doing okay on treatment. So I think the organ specificity tell us some about the biology of this cancer. But one thing that we didn't discuss much about the tumor that are generated today. What does it mean? And even though we're talking about kidney cancer, but there have been some very elegant studies now suggesting showing that, you know, we're dealing with several type of cancer within the kidney cancer and maybe the disease goes to the liver is different from the disease that goes to the lungs, but not necessarily all the time. Unfortunately, we still don't have the barcode to characterize this tumor. When is the kidney? When is the bone? So when is the lymph nodes? Go back on the issue about liver metastasis, you know, I totally agree with you, Nizari, about how we approach that. But I think what the message that I want to tell you, and as I was saying, is that for a patient with the disease in the brain, they do much better than they used to be. And what is because we have a better gamma knife, more experienced radio neurosurgeons, or this therapy do help, but, you know, even I agree, my practice of several patients with ester or brometastasis still alive years after. So I think probably kidney cancer is more favorable disease than other type of cancer. We didn't touch much about the radiation. We don't have a radiation oncologist here, but there is some compelling role for radiation even to treat localized kidney tumors. And probably the notion that the kidney cancer is radio-resistant, that's not totally true. I would like to ask a question here at MD Anderson. Do you use surf spheres to treat the liver cancers? I know at Stanford they do, because liver is liver when it comes to surf spheres. Do you use surf spheres treatment here? I think we have a surgeon. It's an inter-radiologist, the interventional radiologist that do it, because the medication comes from Australia. No, we're not using that, but we're using nanoparticles, the one of the... You're using the theraspers? No, they're using, you know, different chemicals, gold and others, with nanoparticles in the liver. One of the surgeons who does this is Dr. Steven Curley, but he's a surgeon. So I think maybe what she means, and I'm certainly not an expert on hepatocellular carcinoma or colorectal cancer, but there's chemoembolization that they're doing through interventional radiology. And I think maybe that's what you're talking about. Is the chemoembolization... As far as I know, it's not used for kidney cancer that's metastasized. No, it's not FDA approved, but it is for colon cancer and breast cancer. And I just wondered if they've attempted to do it here for kidney cancer for tumors, massive tumors in the liver. So I guess my response to that is that even though, in general, it's a cancer that's in the liver, it still retains the characteristics of kidney cancer, which is notoriously resistant to standard regimens of chemotherapy. So I might be best being quiet now because I'm going outside my realm and letting my colleagues in medical oncology pick up, pick that up. But the biology of the colorectal cancers that go to the liver and the liver cancers is much different than a kidney cancer that goes. So unfortunately, because that therapy might work for that patient population, it does not translate to the same for kidney. I have two questions, a little bit more general. One, if you could bring us up to date on if there is any progress on immunotherapy. He's smiling. And the second is the most recent Time Magazine front page article dealt with how we're going about our cancer research and focused specifically on trying to tear down the silos between institutions, certainly between different researchers, et cetera, and get everybody sort on one big macro team. We've got three institutions here. So I thought maybe you could speak a little bit to how, if anything's changed in terms of collaborating and seeing that as a mechanism to propel us a little bit faster and perhaps further to finding some answers. Thanks for your two good questions. Dr. Harrison, you want to address the first one on some of the new immunotherapeutic approaches to treating kidney cancer? Sure, yeah. I mean, I think it's an interesting question because there are some new immunotherapeutic approaches in kidney cancer. Certainly the one that's gained the most press is targeting the PD1 ligand or kind of anti-PD1 or anti-PDL1 antibody. So let me kind of explain what that is. So Hytocentralucin 2 is something that kind of revs up the immune system, we think, to try to attack the cancer. And so this is a little bit more specific. It's known that there are certain features of kidney cancer that make the immune system kind of immune to the immune system. And so with these inhibitors, we can kind of release that or block these checkpoints and maybe target the kidney tumors better. I don't know if that's making a lot of sense because it's kind of an inhibition of an inhibition. But at any rate, there are some interesting drugs now in phase three studies. There's one compound by BMS, there are others. So there's a study, for example, in patients who've had one line of treatment already with metastatic disease, and it's randomizing them to either Everolimus, which is a finitor, or this new checkpoint inhibitor, and seeing if that will benefit patients. And what's been really interesting is that in the earlier study, so phase two studies in smaller numbers of patients, we've seen some benefits where patients seem to have similar kinds of stable disease or kind of remission type features. And so that's been very interesting. Now, there are other interesting immunotherapy approaches. There's an autologous vaccine approach that I know Dr. Wood is involved with. This is the so-called ADAPT study. This is taking patients who present with metastatic kidney cancer and who need their kidney tumor taken out. And what it's doing is it's creating a kind of a personalized vaccine from the patient's own kidney tumor and giving that to the patient. We probably be on this to talk about all the specifics of that right now. But either giving that with Sunitinib in the first line or giving Sunitinib alone and seeing if that has a benefit. There are some other immunotherapy options, but I think to me those are kind of the most compelling ones. The checkpoint inhibitors, anti-PDL one or PD one. And then the ADAPT study of the autologous vaccine. Roberto may have some others that he's interested in. These are not FDA approved yet. These are investigational therapies. And you can only get them by participating in a clinical trial, depending on your situation. So some of these trials, the one that Dr. Harrison just mentioned is for Peso had two or one prior therapy. And they should not have received prior mTOR inhibitors such as Tori cell or Afinitor. And they get randomized, meaning randomly allocated to receive the experimental therapies in new immune checkpoint drug, anti-PD one, versus the mTOR inhibitor everolimus. But there are some phase one trials, meaning early stage of development where they are looking at giving also the anti-PD one in combination with other agents for Peso had multiple prior therapies. So you have to check and see, go online or contact your oncologist if your oncologist can find out for you whether you are eligible to participate in some of these trials. We have these trials available for patients who are interested. The other important question is about collaboration. I think this is a very important question. Every institution is different. Obviously, I'll let Dr. Pillay speak about what collaborations their institution, which is Roswell Park in Buffalo, New York, they're doing. But I'm going to understand we are collaborating with other institutions to, and we're going to submit a sport grant application to the National Cancer Institute. And in collaboration with University of North Carolina and Charlotte and Stanford and Baylor, we are putting together a grant to study different aspects of kidney cancer. This is mostly research, but that is translational, meaning we hope that whatever discovery or basic science in the lab, in the laboratory we find, we bring it to a clinical trial to patients. And so that's that mechanism, that collaborative mechanism is called SPOR, Specialized Program of Research Excellence. So it's a multimillion dollar grant. It's competitive, so not every institution or collaboration of multiple institutions will get it because you're competing not only against other grant applications about kidney cancer, but also about other types of cancer. But that's one way of institutions coming together and trying to advance science, advance research to try to find better therapies for the patients and hopefully cure. So, Robert, do you want to speak about your institution and what collaborative efforts you have or initiatives? Well, first of all, I want to commend you for the question and the comments, because I think it's very, you know, speaks about your knowledge and your interest in this. And I think you touched a very important point. There is no way that we're going to advance research who help a patient with kidney cancer unless we work together. And, you know, it's not always easy to get together and to work together. And I think the SPOR mechanism that Tamira has mentioned is one, we don't have many of these grants available right now for kidney cancer, like another disease like breast, prostate, colon, ovarian cancer, as a matter of fact. There's only one right now in the country. So we need more of this team of institution work together. And hopefully we're going to have more in the future. You know, depending also the financial support that, as you know, NIH has trouble to get. But one thing I would like to mention is what I think we're missing potentially is a network of institution to run clinical trials. So to have a kidney cancer clinical trial consortium. And I think, in case you had a kidney cancer association, and it would be a perfect organization to help the community of scientists actually to get things that together. You know, there is a similar effort in other diseases like pancreatic cancer, prostate cancer, where patient advocate groups will have been pivotal to get the funding to get this network. Because, you know, there are some institutions, some investigators have a clever idea, but they don't have the means to run this clinical trial. So I think they have an infrastructure that of course costs a lot of money. But I think if there is a resources out there and they write people to get, to make it happen. To me, you know, this poor application, these grants, absolutely we need those, but we need to also have an infrastructure to translate these in the clinic. And again, that's something that, as this comes from the patients and their family, it will help us to make it happen. Chris, I would just make one other point. I think actually one of the greatest collaborations that is ongoing that holds the most promise for kidney cancer specifically, but cancer in general is called the TGCA, stands for the Cancer Genome Atlas. And basically what this involved were numerous institutions throughout the country sending in specimens to the NCI. We actually, I think, contributed something like 70 kidney cancer specimens. And at the NCI, these specimens are being, you know, basically studied six ways from Sunday. You know, back in the old days, for the human genome project, when they were trying to sequence the human genome, took them, you know, years and years and years and hundreds of millions of dollars, now we can sequence a genome in afternoon and for a thousand bucks. So the technology has really tremendously improved and actually there is a database online that any of us, even you, could go to and study and if there was a gene of interest that you thought might be involved in kidney cancer, you could evaluate, you know, 500 patients whose tumors have been evaluated to see if it is and then develop a drug for it. So, you know, there is increased collaboration. There are still challenges with intellectual property and those sorts of issues, but, you know, ventures such as the TCGA, I think, will promise for really curing cancer in our lifetime. Any other questions from the audience? Twitter followers who are watching online that it's the sibling of a patient who was treated with high dose IL-2 and had a partial response and now is on Votrient and was curious on your thoughts with that therapy. So this is a patient who had high dose into IL-2 and presumably either didn't respond or it was intolerant to therapy, the patient had a partial response and then had progressive disease and now the patient is receiving Votrient. I think that's an acceptable therapy. There are other alternatives, but I think this is an acceptable therapy outside the context of a clinical trial. Now, if, you know, or when the patient stops responding to this agent, the patient would be a candidate for this anti-PD-1, Dr. Harrison talked about, so that there is that trial. It's in phase three and it's looking at patients who had prior immunotherapy with, say, interleukin-2 and received target therapy with agents such as Votrient or Suthent and the like. And they can, in the future, participate in that trial with anti-PD-1 versus Evrolimus. But that's an appropriate therapy. Okay, any other questions? Two couple more trials. All right.