 This is a 45-year-old lady who presented with a mass in the abdomen. She herself felt actually this mass in her belly. She presented to M.D. Anderson, had a little bit discomfort, and the blood work was normal except for that high LDH, which what we discussed earlier is an indicator of high tumor burden. And you can see here on the CAT scan, this is a huge mass with bulky lymph nodes. And this is a huge mass that's clearly not accounted for laparoscopic surgery. It's a huge mass and maybe involving surrounding structures. So Dr. Karam, assuming this patient has, we said, there is no metastatic disease to the brain or bone. And this is the, would you consider looking at this? This is a surgical candidate for nephrectomy, or would you treat her with systemic therapy? Would you do a biopsy? You were a proponent of doing a biopsy before. What would you do? I would do a biopsy or just go straight for surgery if this is resectable. I mean, the patient is 45 years old with no medical problems and good performance status and no other metastases. So if it is resectable after looking at everything else as far as the images, then I would go for that. Okay, I'll show you some more of the images. Do you think this is resectable? Dr. Matee? Well, you know, receptability is really sometimes an issue of how strongly the surgeon feels and what the patient is willing to go through. But it does, it would require very extensive surgery and, you know, potentially the risk for taking a lot of surrounding tissue out and possibly leaving cancer behind. So I think if there's a clinical trial open, you know, we had a, Chris actually had a neo-adjuvant trial for his cases that were locally advanced. Actually, I'm not sure if she would have been eligible for it or not. But this would be a good candidate for that. On physical examination, when the patient was referred to me, she had a palpable left supraglavicular lymph node. Would that change your approach? I would biopsy her. This patient has basically a large renal mass with lymph node-only disease. I would be worried about papillary renal cell. And with all this, I would probably not do surgery first. Okay. Dr. Wood, you think this patient... No, I don't think she's receptable, but can you go back one? On that first picture, you can see there's disease really, you know, right at the... Diaphragm. Yeah, right at the cruise. And I mean, I don't think you could render this patient disease-free with surgery. I think that the magnitude of the surgery would be huge even for a 45-year-old, and so she'd be significantly debilitated and deconditioned after surgery. And I think it would be a race between her recovering and the cancer taking over, and I think the cancer would win. We don't want that to happen. So, as I mentioned here, there is disease above the diaphragm, so another lymph node metastasis. This is small pulmonary nodules, so she has a vast disease with infra-diaphragmatic and supra-diaphragmatic lymph node metastasis and possibly lung metastasis. So, a patient was seen by Dr. Wood, and he felt that she has unresectable disease. We did, perhaps, as Dr. Karam suggested, and she had this rare variant, metastatic chromophore. Again, this is among 100 cases of kidney cancer. This would constitute 5%. And in patients who have metastatic disease, this is even less so. Maybe 2% of patients with advanced kidney cancer will have this histological time. Very rare, but luckily, this is a disease. Even when it is metastatic, it is slow-moving disease compared to some other tumors that we heard about this morning with some of the tumors that have sarcomatoid features with them. So, this is a disease that, even if it's advanced, it behaves in a more indolent fashion than some of the other types of kidney cancer. Dr. Peely, so she has metastatic chromophore. You saw the scans. What systemic therapy would you recommend and why? I would discuss with Dr. Wood whether this patient would still benefit from, what we call a polydenefractomy, if a patient has any symptoms. Even if this patient has a lymphoma of metastasis, but a chromophore, but it tends to be a slow-growing tumor, whether, you know, even removing the kidney would do any benefit. We're not going to cure for a disease, but we're going to just take some of the tumor out. I don't know, because systemically, we know that the drug that we have in non-clear cell carcinoma and, Niza, you have published on this, chromophoresis to work even less, you know, these drugs in this tumor. So I would discuss, but the first question, number one, whether or not the tumor from the kidney should come out. And I don't know. Dr. Harrison, you have an opinion about systemic therapy options? Yeah, I mean, I agree about thinking about debulking and whether that would benefit in having a serious conversation about that. But as far as systemic therapies, I think Dr. Pillie mentioned well that it's not really clear what the right option is. Certainly clinical trials could be an option. So your clinical trial and our clinical trial at Duke Aspen, you know, that could be a reasonable option, because we don't know if the kind of anti-VEGF approach with, say, Sunitinib is a better option than, say, Everolimus and mTOR inhibitor. So for me, I guess regardless of what we did locally, I would think about a clinical trial systemically. But suppose when none is available, what would you recommend? And then, you know, and this is just my personal bias, I would think about using Sunitinib. There is some data with Sunitinib. Again, the response rate is probably not as high as with conventional clear cell carcinoma, but there may be some benefit. Dr. Witt, do you think this is un-resectable? I think it says un-resectable if I can read. No, I don't. I did not think this. I mean, there's a couple of issues here. First of all, side reductive nephrectomy has never been shown to be beneficial in the setting of non-clear cell histology. So that's, you know, right there, kind of off the ranch. And as I said, looking at those films, I do not think that we would be able to take all of the disease out of her abdomen, but I do think it would be a major, major morbid surgery and, you know, lots of blood loss in prolonged recovery. And I think that it's very likely that the cancer would progress faster than her recovery and she'd never get treatment. These are just out of curiosity. What was biopsied? Was it the primary tumor or the metastasis? It was the nose, I think. Okay. There are some genetic studies suggesting there might be some protein called C-Kit that is overexpressed in other type of tumor like just in the gut, tumor in the gut. And in C-Kit, it does have some C-Kit inhibition. So that would be my first choice. I think what we can say also about the bulk in nephrectomy in non-clear cell carcinoma, I totally agree with Dr. Wood. But the question that we promised, these are much rare diseases than clear cell carcinoma. So we don't have the number of patients to be studied to definitely have an answer about. So in my practice, I still go case by case, even non-clear cell carcinoma, whether or not the bulking, if a patient is symptomatic, again, with the idea that we are not going to cure it. But if it can be done safely. And of course, I need to rely on the surgical expertise. So after the discussion with Dr. Wood, we felt that the surgery is not really, the disease is not receptable. We did a biopsy and we proceeded with enrollment on a clinical trial for patients with non-clear cell, the less common types. There are several of these non-clear cell subtypes. So she got enrolled on that trial and she received synitinib at full dose and tolerated it very well and had a good response actually for about one year. And we'll see, we'll show you some of the, you recall how big the mass was and how, you know, now it is definitely smaller and the bulky lymph nodes here are definitely smaller. And you could see that there is some plane now around the tumor where, you know, the surgeon can go in and resect this with less morbidity and more confidence that you're going to be able to resect the tumor and maybe all the lymph nodes in the abdomen and render her NED without evidence of disease in the abdomen. So she had a good response. Dr. Wood, would you consider now surgery? Absolutely. I would take her and do a side reductive nephrectomy and do an extensive lymph node dissection and resect the nodal disease. The patient has the same response to the lymph nodes? Yes. She had a response in the left supraclavicular lymph node as well as the retroperitoneal lymph nodes. The small lung nodules remain stable and yet, as you see, she had a good response in the primary tumor itself. Now, these are technical comments but this, I think, is potential evidence that Sunidin has a direct anti-tumor effect because if you believe a chromophobe it's not driven by VHL and it's not driven by VEGF. I think probably that Sunidin has a direct anti-tumor effect in this chromophobe patient. And I think a chromophobe... Throw the secret inhibition. Maybe other kinases that we get in the beach to me that's compelling. But it's a great response. Okay. Dr. Karam, Dr. Mateen, you agree with just going ahead do an open nephrectomy and retroperitoneal lymph node dissection? Yes. So, the patient underwent a psychoreductive nephrectomy with a resection of all the lymph nodes and the pathology is on the slides, D3A, N1, N1, chromophobe arena supracinoma with matted nodes and she had an uneventful post-operative course, was discharged five days later, but she was re-admitted 16 days after surgery with chylous acitis and that's a complication that I will ask Dr. Mateen to comment on. Dr. Mateen, would you like to briefly comment on why this happens and how we treat this? Well, it wasn't my complication, but I'll still speak to it. Just kidding. No, listen, whenever we do these extensive removal of lymph nodes, this is one of the known side effects or adverse events that can occur and basically it's the lymphatic drainage and some of it which actually comes from the intestinal area and so generally the good thing with it is that it's treatable, it just takes time sometimes. The first thing is to change the diet to a low-fat or non-fat diet or medium chain triglyceride. In a lot of my cases, that's usually sufficient. If that doesn't work, you can try a drug which is really expensive and it's questionable whether that works and then ultimately if none of those things work and they're still draining, you basically restrict any form of diet and you put the patient on IV nutrition, which obviously is kind of a big deal, but it can be done and you can send patients home with it eventually and in most cases that will suffice, but these can take time to heal and unfortunately it's one of the prices that one pays with extensive surgery such as this. So I think it's important to emphasize that we do not resume systemic therapy with these target agents for at least four weeks to allow complete recovery before we start sutent and the like because of the concern about wound dehiscence. In some instances we wait six weeks after surgery to resume these therapies. So after she recovered from this complication, synitinib was restarted and the dose was reduced and we gave it at a slightly modified schedule and despite continuing with therapy, she had disease progression again in the lymph node chains in the left supraclavicular area as well as under the diaphragm in the retrochloral space and she started complaining of some back pain and MRI of the spine showed that there was a tumor involving T7 vertebra. Dr. Harrison, what would you do now? I might consider thinking about palliative radiotherapy to the T7 and then as far as systemic therapy, again it's unknown what to do. I might favor a mechanistic switch, meaning switching from a VEGF receptor TKI like synitinib to some mTOR inhibitor probably Everolimus which is oral, but I think no one knows what to do here. Dr. Pillay, agree? Local therapy to the spine and then systemic therapy? Yes, radiation and systemic. Again, I'm compelled. I think the response to synitinib at least initially is pretty compelling and I wonder whether in this patient is young, you could even try to dose escalate the synitinib back to 50 or switching to exidinib or pass upinib, the same type of drug because maybe the 37.5 is not high enough drug. Unfortunately, this patient is not kind of immunotherapy. We don't know that the new immunotherapy is coming, the PD1 has a new role in this more rare disease, but I would probably try to dose escalate synitinib or switch to full dose pass upinib or exidinib. Because of the initial response. So this patient participated in the clinical trial as I mentioned to you and we had five patients with this rare tumor, chromophob on the trial and two of the five had a dramatic response. She was one of those two patients who had a dramatic response. So two out of five small numbers but 40%, which is what we would expect of this drug or similar drugs to achieve in patients with the most common type of renal cell carcinoma, the clear cell type. And the median, which is the average, progression-free survival, that is how long the disease stayed in partial remission or without progression was 12.7 months in that study. So in our experience or in our view, this rare subtype of kidney cancer that belongs to this non-clear cell group does respond in a similar or comparable way to the more common type clear cell to agents such as the one that she received. I think there are some retrospective analysis. My understanding was chromophob tend to respond even less than papillary to TKI's but there's something going on in this patient maybe. But I think even Senate has a case report because I think a main use patient, I mean a physician still tries on internet. We're going to know more about the ongoing clinical trial but probably you're not going to have a lot of chromochromos. So there are more trials looking at the same group of non-clear cell, the rare subtypes. As we mentioned earlier, the Aspen trial led by Duke and the ESPN trial led by M.D. Anderson and basically treating those patients with Sunetin versus Everolimus. So we elected to treat her with Everolimus, 10 milligram a day. She had stereotactic radio surgery to the T7 metastasis and her back pain resolved. She's still receiving Everolimus now past one year without any significant toxicity. She is still maintaining active lifestyle and working. But 18 months later, while she's still on therapy with Everolimus and her disease is under control, she showed up in Dr. Wood's clinic. He was happy to see her. But she said, no, not for me this time, it's for my husband. So she brought her husband and her husband was diagnosed with kidney cancer. Mass will show you the scans he had a left renal mass, a mass in his left kidney and on chest X-ray and subsequent cat scan of the chest, he has metastatic disease to the lymph nodes in the chest. The rest of his workup was negative and the blood work was normal. Now his review of system is negative except that he has hyperlipidemia and hypertension. And here is the mass in the left kidney and here you can see the lymph nodes. Dr. Karam, what would you recommend? These are the only sites of metastatic disease. His performance status is basically zero. Again, I would discuss the option but to give you a brief answer, I would go for cytoreductive nephrectomy on the left side. Is there a possibility you could do a partial here? There is a possibility but given that the patient will start targeted therapy probably after surgery, I will try to do the operation with the least possible side effects. And again, doing partial nephrectomy in the setting of metastatic disease, it's been reported in at least three studies, very small studies, it's doable but typically these have been patients who have one kidney or one functioning kidney. So if the mass is small, I would consider it but I don't see a compelling reason to do it in this patient. So you would do a laparoscopic robotic-assisted, robot-assisted left-radic nephrectomy. Just a laparoscopic left-radical nephrectomy. Okay. All right, Dr. Mati? Yeah, I agree. Okay, you agree? All right. The other thing I would tell him to do is put his house up for sale and move as far away from there as possible. All right, so the patient underwent a laparoscopic cytoreductive nephrectomy and the pathology was consistent with T3A and 0M1 clear salinoma, carcinoma, so different subtype of cancer than his wife, who had chromophob, if you recall. He had metastasis to the resected left adrenal gland. Dr. Pili, what would you recommend now? If he's a candid file, too, I would offer him the... If he was in Buffalo, I would offer the clinical trial that we have. Okay, Dr. Harrison? Yeah, I mean, I think he's young. It looks like he's a candidate. I would offer him high-dose, and I'll look into it. Okay, all right. So we did offer him that, but he elected to be treated with target therapy, and he is enrolled on the STAAR trial and was randomized to first-line therapy with Everolimus, so him and his wife are taking the same medication, both tolerating it very well, and he's shown already tumor regression response now six months since he was enrolled on the trial. We'll do one more case, and then I think we can wrap it up and open it up for questions again. This is the last case we're going to discuss. A 62-year-old male with blood in the urine, diabetes and high blood pressure, had appendectomy and knee surgery, examination under-remarkable, no tobacco or alcohol use, and imaging studies showed a locally-advanced right renal mass and spots in both lungs, so pulmonary metastasis. Here is the mass, and then here are the pulmonary nodules, here and here, here, so at least several in both lungs. In addition, he has anemia, so lohemoglobin. The brain and bone were negative. Bobsae of this lung, one of the lung lesions, confirmed the diagnosis of metastatic gliosarion sarcosinoma. I think in the case of time, we'll just move on quickly here. What he has is anemia, and he's presenting with advanced disease with primary treatment in place, so he has two risk factors, so he falls in the category of intermediate risk. He has this here by the memorial risk classification, as well as the more modern classification that has been developed in the era of target therapy. He has what we refer to as intermediate risk disease. So, Dr. Mati, would you offer this patient side-productive nephrectomy upfront? Yeah. Dr. Karam, different opinion? No, yes, I would still do the surgery. Okay, Dr. Wood, agree, okay. My medical oncologist colleagues, surgery, okay. So he undergoes surgery and it's uneventful now. What systemic therapy would you consider for this patient? Assuming he recovered completely and postoperatively has mild anemia, but his perform status is good. I would consider high-dose IL-2 first, assuming that it was available at my institution, because, again, this is a young guy, low-volume, lung-only metastases. I think he'd be a great candidate for high-dose IL-2, barring that. I think that the best evidence would suggest that he should start on either Sinitinib or Pizopinib, either one. Dr. Pili? We already heard from the medical oncologist, so I don't need to add anything. Exactly what I would say. Okay. Dr. Harrison? I agree. So we want to all be aggressive and treat him with high-dose IL-2. I agree with our three medical oncology colleagues. Really? Offer it to him. Dr. Matee? You know. Okay. All right, we can stop here. We have a few minutes to ask any questions, make any comments. And then Carrie wanted to say something. Brian, could you get Carrie in here? Any other questions related to what we talked about or any other questions outside of what we talked about? Is there anything that we didn't cover that you have questions about? Please don't hesitate to ask. So what do we think about the format? Yeah, go ahead. I guess it would be kind of outside of what we discussed. How concerned should we be as patients of the full implementation of the Affordable Care Act? Very. Any comments? It depends on whether you're going to continue having insurance or not. I mean, I think there's real concern. Yeah, I mean, you know, their concern goes both ways. I'm not sure how much we want to get into this, but, you know, the problem is, whether you realize it or not, all of you who are here probably have the luxury of being able to afford insurance. But the truth, you know, the ugly truth about medical care here is that there's two tiers. And there's a huge population of patients who get their care through the emergency room. And so, you know, to try to address that and at the same time contain costs, which everybody agrees is out of control. Some of which has contributed, I think, you know, my personal opinion is that there's a preponderance of greed across the entire medical spectrum. And it starts with patients and doctors and insurance companies and politicians and drug companies. Patients want every test done sometimes. Doctors get insecure, so we order everything. So anyway, it's across the board and nobody wants to give up anything. And so all of that adds to the issue of rising costs and care. But the ugly truth, and I don't know the solution, but the ugly truth about medical care here, as good as it is, is that there are patients who are dying from inability to afford care and from preventable conditions. We all see the possibility of the cost of, I mean, these new drugs and where we've come is wonderful and it's great. It's benefited all of us. But it comes out at very high costs, again, as we know. Do we see that being hampered as far as this future? You know, we're talking about things, we're always talking about things upcoming, you know, or those things in jeopardy. You know, the research, the research dollars, is that a hindrance? Is this going to be a hindrance on... Yeah, I mean, I think all those issues are very real. I mean, the cost of these agents that have revolutionized the outcome for patients is astronomical. And, you know, I think with Obamacare being instituted, we're going to have to make choices, and those choices are going to be very difficult ones, you know, and I think that we're going to have limited access to these agents. I think that, you know, with this comparative effectiveness, that some of these agents are going to go by the wayside because they're not better or they're not, you know, even though they're different, they're just not better, so they're not going to be used. And I think that, you know, it's going to be a real challenge. I think it's sort of a double-edged sword. On the one hand, we have these great drugs that can potentially cure cancer, but we really can't afford to use them. We're already seeing, as I mentioned earlier this morning, where we're getting really denials from insurance companies. So it's going to get worse with insurance companies, a clerk or a bureaucrat on the other side of the line, the telephone line basically dictating to us what tests we order and what treatments to give. And it may get worse. I think, you know, we have to really be prepared for this where we may not be able to give the success of what you heard. You know, we treat people sequentially, but we may get to a point where, like in Europe or Asia, where some of these drugs, we have all the drugs available to us. And in Europe, you know, they may have only two or three, and they may not be able to go back using what worked for the patient in the first line for, say, two, three years. They cannot go back to that drug again because they say you can use it only once. So it's going to impact, there's no question, it's going to impact our ability to order tests and treat the way we think is best for the patient. And I think, you know, I mean, the issue is that it's hard to have a frank, you know, what we want to really have is a good discussion, and patients need to get involved to some degree and, you know, the whole population because everybody's going to have to give up something, you know, and nobody wants to give up anything. And on top of that, you have this chaos created by extremes in both political situations where there's basically a lot of unsupported claims being made for the sake of gaining political ground. And we all stand to lose a lot from that. And, you know, when I mean everybody has to give up something, you know, in some ways it may mean physicians having to accept becoming middle-class people. Like they were back in the 50s and 60s. It may mean you all having to accept fewer choices and maybe not having the option of paying several thousands of dollars for an extra two months of life. That sounds harsh, and I don't mean it to be harsh, but that's where that discussion, you need to tell us, is that worth it from a societal perspective? Listen, my family, yeah, I'm going to say, if it's my family, I'm going to say hell yeah. But really, if we can distance ourselves and look at that from a global perspective, that's the kind of population-level decisions that, you know, these are things people talk about. But, you know, it's hard to have that discussion because there's these incredible extremes, political extremes that drown out where most of us stand, which is somewhere near the center. I find that to be a real shame right now. I'll know that Dr. Matine has totally bummed us all out. Kerry, why don't you come up and talk a bit about the kidney cancer association? Is there another question? Aren't you so glad you asked that question? Sorry, go ahead. Sorry about that. No, just that I want to know if there is any evidence that this is hereditary. Could it go down to the kids or down in the line grandkids? There are, I mean, there are genetic syndromes that are associated with kidney cancer. They're rare. Sporadic is much more common. We typically don't worry about it unless there are two first-degree relatives that have kidney cancer. We also worry about it in patients who presented a very young age with kidney cancer. Those are sort of warning signs to us that there could be a genetic syndrome. But the vast majority of cases are sporadic, not inherited. But it is tough. I mean, there is probably some familial predispositions. We saw a case earlier where there was three, you know, family members. Of course, you think Von Hippel-Lindau. But, you know, a lot of times, the tough thing also is that the family could have had the same exposure to product, whatever it was in the environment or diet that put them all at risk. And that's one of the hard things. We have a researcher here who's actually collaborates with us. And she's a molecular epidemiologist. And Chris, I don't remember the exact finding from that study, but if you remember, she was actually able to show that if you have kidney cancer in the family, it does predispose to the rest of the family, you know, being at a higher risk for developing it. Yeah, the risk is like five-fold increase risk. Yeah, so, you know, not something small. But so I think it points out the fact that there's probably some genetic predispositions that some people have that we still don't know exactly what they are. But then when you add to that something in the environment we're exposed to that could... I think that means I need to stop talking. No, I just wanted to... Nancy asked a question earlier to me during the break, but there are some red flags or some, you know, factors or variables that when we see in a patient that basically rings the bell. And for further evaluation to study if there is really an inherited syndrome. And these are three. First, you know, having kidney cancer at a young age. Secondly, having tumors in both kidneys. And thirdly, if there are multiple tumors in the kidney or in both kidneys. So if you have that, a family history, young age, both kidney tumors, tumors in both kidneys, those four things then... one would then need to consider one of these inherited syndromes. And, you know, beyond the VHL disease and the Papillary Type 1 inherited syndrome and the hereditary Lyoma, Mariana Soccassidoma syndrome, Papillary Type 2. There is a recent syndrome that has been BAP1, characterized by BAP1 mutation. So I think there are those things that we may discover more families, more inherited syndromes. But one would not think about it or worry about it if there is no family history at all and it's an occurrence at 60 years of age or older and it's just typically unilateral one lesion in the kidney.