 مرحباً، أتمنى أنكم جميعاً يمتلكون ومجمعون هذه الصحة نحن نحضر الثلاثة الآن ونتحدث عن محاولة محاولة لذلك متاستتيك أولاً سأخبر أصدقاء أصدقاء أصدقاء أصدقاء نعلم من بعض الأشياء أن نتتخذ منك كثير من المتاستتيك والمتاستتيك والمتاستتيك ونحن نتخذ منك أكثر محاولة لذلك المستخدمين والمشاهدين فهذا هو محاولة محاولة أبداً هناك أخرى محاولة محاولة هذا why نحضر الثلاثة محاولة محاولة لكن هذا هو المعاولة محاولة عليها أن نبدأ من المحاولة هذه محاولة مخاولة المستخدمين في محاولة محاولة وإمكانه أن يكون في محاولة محاولة وابتسل على تدريق محاولة لا يوجد أي محاولة او يوجد محاولة محاولة أولاً خلال عمر أبداً فهي لديه محاولة ولكنه يوجد سلطة أنيمية الهيميغلوبن رد بلد كان is a little low 10.3 ولكن الجميع المنزل are normal لن يوجد أفضل مكتستيك ديزيس ببونسكان بايمراف ديبرين ولكنه يوجد كما سنرى في next slide بولموندرينوديوز ومأس في السلطة right لذا هذا is why he underwent أبابسي of this tumor in the right kidney وانه يظهر أفضل مكتستيك ديبرين كانسر what we call or refer to as clear cell فرمن in grade 3 as you heard from this morning this is an aggressive tumor and as you can see obviously the mass is a large one measuring approximately 14 centimeter this way and about 9 centimeter this way so a fairly large tumor other views you could see that he has in addition to the mass here the big kidney tumor this is the right kidney here what you see of it and there is an enlargement of the right adrenal gland there are two glands over each kidney and there is another adrenal gland on this side on the left side as well here and you can see there are spots in the lungs so he has evidence of metastatic disease to the adrenal glands and to the lungs so what would you offer this patient and question to my panelists and we'll start with our surgeons here Dr. Matin would you do up front site reductive nephrectomy and would you remove both adrenal glands and if so why and if not why not yeah I mean just to be clear we usually do these cases by discussing it with one another I usually walk down his hallway and find him and talk so we don't make these decisions in a vacuum you know my looking at him he's having symptoms of hematuria, blood in the urine the overwhelming majority of the cancer is in the kidney and so I would consider actually doing removal of the kidney and removing the adrenal on that side whether you remove the cancer and the opposite adrenal or not it gets to be a little complicated because sometimes there are clinical trials that they can be eligible for after removal of the kidney but not if they're on steroid replacement if you remove both the adrenal glands the patient has to go on lifelong steroid replacement and so it's just something to talk about I think most clinical trials now don't exclude that factor so it's just one of those things you want to think about just so you can set everything up for success but it's a discussion that needs to be had whether or not you remove that or not that would be my thinking is just to do surgery first at least the very least remove kidney and the adrenal on that side consider the other side Dr. Karam do you agree? yes I would agree with Dr. Matin and like he said we don't make these decisions in a vacuum we always discuss among each other like we're talking now in a less formal setting but I would choose option number one after discussion with you unless there is a clinical trial that he is eligible for and wants to enroll choice number one would be my recommendation would you remove both adrenal glands or just epsilon? if the aim is to make him disease free in the abdomen and retroperitoneum and if it doesn't interfere with any planned clinical trials I would try to render him disease free but you would remove both adrenal glands and the kidney and the lymph nodes as well okay Dr. Wood? yeah the issue here is I would recommend a pre-settler reductive surgery and the real issue about the adrenals not only clinical trials but if you take both adrenals and it takes IL-2 off the table and this patient young excellent performance status just metastatic disease to the lung and adrenal لذلك يجب أن تقوم with the adrenal glands, you would take that off the table for the patient and I'd have that discussion with him but I think at the end of the day, definitely cytroductive defect to me, definitely removal of the right adrenal and then a discussion about the left adrenal and if the medical oncologist thinks that IL2 might be a good choice for this patient then I would leave that left adrenal. Dr. Pillay, would you recommend upfront systemic therapy instead of surgery? No, I agree with my colleagues. I think the challenge also for systemic therapy, you would commit this patient to a therapy that might not need immediately. These are what we call synchronous metastasis. Meaning the patient has neurodegenerative kidney cancer and also unfortunately has small lesion in the lungs and in the adrenal but he might not need therapy right away. A different story probably for immunotherapy where we want to try to treat the patient when the tumor is rarely small so I would say I would agree removing the kidney and assess the patient where it would be candidate for high dosing to look into. Dr. Harrison, what do they do at Duke? I totally agree. I mean I think this is a great patient to get cytroductive nephrectomy and then the patient is young, sounds like it's healthy, has only a few risk factors and would otherwise be appropriate for high dosing or looking too and so we'd really be thinking about that. Okay. Alright, so now we did the surgery, we took the kidney out and we took the right adrenal gland out and as per the recommendation of our surgeons they left adrenal gland in. Now the patient recovers from surgery and is anxious to start systemic therapy. What would you pick from this menu? Dr. Piele? I think if the disease is only in the lungs and has a really too little nodal, there is nothing wrong actually for the patient to wait because we don't know how fast this tumor has been growing. If the patient is motivated I would say yes I would offer high dosing to look into. We have a trial of a Rouser and Hopkins where we combine with Antinostat. It's an agent that makes IL-2 hopefully work better. But I would also discuss even as young, just maybe doing other scans in two or three months to get a sense of how fast those lung donors are growing. Because sometimes we do see that those lung donors do not grow and why committed the patient to a therapy that unlikely will cure his cancer but will definitely make him sick. Actually I'm glad you brought that up because I was going to ask you, ask earlier, before we had the TKI's that was sort of standard practice. You know we used to do the surgery and we'd send them to you guys but then in about 30% of cases you guys wouldn't treat. Partly because the therapies weren't really that effective. But I'm glad you brought that up because it seems like the threshold to want to treat is lower now. Yeah I would not say it's lower but I think it's, I think not because we have a therapy but we have to use it right away. And I think it's a discussion that we need to do with the patients. And some patients are uncomfortable. I mean I need to disclose I'm here actually to learn today not to talk about what I do because I want to learn also from you since you are patients and it's important for us also to get some feedback so we should discuss all these things with patients that are actually involved in the care. So you know I think it's an open question especially when we don't know the natural history of this disease and we know that sometimes kidney cancer grows very slowly. As you point out that most of the tumor was in the kidney and it's really left a little bit left behind. So there were nothing wrong to watch it. Dr. Haresap, would you like to add? The patient still has pulmonary nodules six weeks post op with repeat imaging studies. The left adrenal gland was left in place. So he has metastatic disease to the lungs and to the left adrenal gland. And the patient will do what you recommend. If you recommend as Dr. Peel is recommending since he is asymptomatic to assess the behavior of this tumor after a while or would you say let's go ahead we have a window to cure you let's try to start some systemic therapy now without delay or would you observe for longer? Well I think I mean for the purposes of this we're trying to be definitive so to be definitive I don't disagree with what Dr. Pilley said and I don't disagree that it would be okay to watch the patient. I mean we have so many options nowadays I don't know that you're going to lose a lot by monitoring for a little while and perhaps talking with the patient about their wishes more but you also hate for a chance to miss a cure and so what we're talking about when we're talking about Hytocenterolucan 2 is we're talking about the only therapy that induces what we think are durable complete responses and so those are it varies depending where you look but maybe at 3 years 5 to 8% of patients have a durable complete response again again varies and you hate to miss that now I don't know that we would really miss that window if we waited for 3 months so I can't really push back that hard but this is the type of patient that I would be a little bit more directive and personally at least in trying to get them to consider and understand Hytocenterolucan 2 and understand what it could offer them and if we don't offer it to have a good reason why not okay well so the patient undergoes cytroductive nephrectomy with ipsilateral adrenalectomy the pathology is consistent with clear cell fermentically grade 4 T3A and 0M1 and he started on the standard dose and schedule and 3 months later the patient has restaging and it shows partial response in the lungs and no change in the left adrenal gland and the therapy is continued but it had to be reduced by 25% because of side effects predominantly here hand foot skin reaction and 6 months later there is evidence of progression in the lungs with new tumors as well as increase in size of the existing tumors and increase in the left adrenal gland and a new solitary liver metastasis now what would you what would your option be now Dr. Peelan you have the option of serial metastasis but first of all I would be curious why IL2 was not offered or whether it was offered to this patient and the patient declined as we know unfortunately with all the caviat and limitation and toxicity is still not offered to the majority of patients who are candidates for this approach but it looks like this patient is progressing with new lesion so this is definitely warrants change in plan I think I found that opportunity to increase the dose of sunedin to 50 and why is that we are being experiencing and also other that definitely there is a dose dependent effect what does that mean the more drug we can give it to the patient the better it is but we started also looking at that in some patients who are able to tolerate sunedin at the time of progression if we are able to dose escalate to increase the dose we see responses we have some very nice data also in animals where we observe the same things we started with sunedin at the time of Resista we increased the dose we see response but I think usually the approach if a patient experiences severe toxicity as a certain dose of sunedin we tend not to go back on higher dose of sunedin in this patient unless it's totally the 37.5 very well and we know that as also I know that you have a manuscript from your institution in term of intrapatient dose escalation different schedule of sunedin it might be helpful so maybe this patient might still be able to go to 50 but two weeks on the schedule probably is more tolerable for patients and we can still achieve a higher level of this drug so maybe consider also that long answer to a short question but alternative I would probably look for a different mechanism of action of the drug so I'm not a big fan of sequencing this drug they have the same mechanism to go with the everolimus or a clinical trials that include everolimus okay doctor Harrison since the patient did not get high dose interleukin 2 up front and received sunedin instead would you consider high dose interleukin 2 now I would not consider high dose interleukin 2 at this point I think there's definitely limited data but what data we have shows that the high dose interleukin 2 is probably more toxic when it's given so I know it has been done in some cases but I would not recommend that Doctor Wood any role for surgery here No there's no role for surgery here the disease is too extensive and I think that my recommendation to this patient would be to do everolimus or a clinical trial and I think the teaching point here also is that the window of opportunity with high docile 2 was when the patient first presented it was the ideal candidate but that bridge has been burned with getting the targeted therapy okay so we move on to another case this is a 55 year old male with history of kidney cancer in the past he had a right radical nephrectomy with IVC thrombectomy more than a decade ago and the pathology as shown clear cell T3B and 0M0 Furman Grade 3 and he underwent routine surveillance studies last was 2 years ago which was negative he has no symptoms except for history of prosthetic hypertrophy and kidney stones now by cat scan of the chest he has multiple small pulmonary nodules but no other disease elsewhere what would you offer this patient and do you see here also Chris so this is a you know many patients ask when they are getting surveilled in the clinic when can we stop this when can I stop getting cat scans now here's a guy that's 14 years out from surgery and now has a disease in his left adrenal gland the other key point here and Nizar maybe you can point it out is that when they did the right radical nephrectomy they left the right adrenal gland which is important because again putting someone on adrenal replacement therapy for the rest of their life is not a very can you point out the right adrenal putting that's there's the left but you can see see on that picture right there on the down is in there but you know making someone adrenal insufficient and having to take adrenal replacement therapy for the rest of their life is not very appealing so we have a solitary metastasis to the adrenal no other evidence of metastatic disease in my mind this patient would best be served by metastasectomy where we would go in and remove that mass with the associated left adrenal and then observe afterward what about the you know yeah I mean that's the issue that they're indeterminate they could represent metastatic disease but I would argue that if we sit and wait to see if they developed then they will be metastatic disease and so you know we'd have to counsel the patient that you do have these indeterminate nodules in the lung and that those nodules could represent metastatic disease and you might require additional systemic therapy in the future but you know 55 years old I say you know swing for the fences and and one one one one one one 5 1 5 1 1 1