This, this has been like a great, I think um around the world in a minute on RGU. Um So this is your chance to ask questions. So um don't be shy. You can yell it out or maybe I don't know if there's a microphone over there. Um You can ask these folks about what they think about drugs trials, future trials. How would you treat this patient? Things like that. So who wants to go first? Don't be shy which P inhibitor is the best? I, I have a question. Um Evie Pembroke. So what, what do, what do I tell my patient? What, you know, how many times do they come in? How does it, how does it get administered? How long are they down there with you guys? What do I need to know? Um So I I'll take this one if that's ok. So the schedule for EV Pembroke, it's two weeks. So standard of care, two weeks on one week off, patients get both drugs together on uh cycle one day, one, cycle one, day eight, they come in and get ev and then they're off on week three. Um the infusions themselves are actually not, you know, compared to CISplatin based chemotherapy where we tell our patients you're gonna get labs, you'll see us, then you're gonna be in the infusion room for 56 hours. You plan for a full day. Ev pem bro is, is much shorter. Um So it's, it's nice to be able to offer our patients not only uh what seemingly is a more effective regimen um but also less labor intensive um from a time standpoint, what do you see as the biggest side effect? So I think there's two biggest side effects that I've encountered so far. Um I think probably one of the most challenging ones is rash. I think that uh Pembroke can cause rash ev can cause rash um parsing out which is causing which um sometimes I find dose reduction of the EV alone is enough to get the rash under control. Um But sometimes they need steroids and, and, and treatment breaks to really get control of that. Um I think with the duration of ev just being ongoing um as getting part of standard of care. Uh peripheral neuropathy is a big issue as well for the EV. Um I think that's what, you know, Pge's study is gonna be really important to know, can we deescalated these patients? Can we um you know, improve quality of life by, by deescalating the EV portion? Yeah, from time to time to treatment to the, from time to treatment. I mean, this is one of the big things with D DMV and, and Jem Sis, I guess from, from time, from treatment to the time that we can plan for, for, for surgery, it's shorter for the E uh EV pem bro compared to DDM back. So, so I think EV Pember is right now mostly used and approved in the metastatic setting. I think you bring up a good point, which is that EV Pembroke is gonna move towards the neoadjuvant space. There is a ready data for EV in the new adjuvant space and actually we were just talking about it. We have now patients to whom we're giving EV Pembroke in the new adjuvant setting who can't get platinum. So, um I I think, I think that's actually uh coming up and potentially would be quicker probably to surgery. Yeah, just Randall just to give some examples. Um Do we share that patient? Yeah, we do. So one patient we put on uh Pembrey is somebody who's solitary kidney, muscle, invasive bladder. Um has ureteral disease. This is a patient really needs, you know, cystectomy, he needs new chemo cystectomy and you know, distal ureterectomy does not want to lose their bladder. It's got a protracted disease, just this kind of perineurial disease. You know, we're giving him a number of see what happens. And uh I mean, if he's one of the complete responders, then it's a real game changer now just to speak a little bit about some of the work we've done is, you know, everybody's participating in these sort of trying to understand, you know, when we do give a new adrine chemo and we see nothing left in the bladder. Um, can we trust it? Can, is that, is that really, you know, complete response is that, you know, is that basically clinical T zero, is that going to be a pathologic T ZERO? And we actually did a prospective trial at Fox Chase where we scoped cystectomies, um, retard their scar at the time of cystectomy. And you know, start with my own two eyes, you know, completely clean bladders, you s you scrape the scar. 25% of patients who had completely clean endoscopic examinations had muscle invasive disease and these deeps of mucosal tumors that you just can't see, you know, intravesical. So again, this is going to be another question to be answered it, you know, is it, is it the same rate with ev you know, when you have these totally clean ureth helium from the inside, is it really, are they really clean deeper down, you know, sort of under the surface? And I think I just want to highlight this, uh for I mention it, we do have a clinical trial that doctor Vitalia is leading and maybe I don't, do you want to say a few words about it that has to do with ev I think it's for sure. Uh So we have a trial with two arms, one includes EV monotherapy and the other has EV plus pembrolizumab and essentially patients who have um a really good response initially over time, we deescalated treatment, especially the EV portion. So in the EV plus pembrolizumab arm, we uh instead of doing two weeks on one week off, if they have a, uh you know, cr pr or stable disease at 18 weeks, they uh further de escalate ev by only giving it once every three weeks with pembrolizumab. And even for the EV monotherapy arm, you know, instead of going from three weeks on one week off at the first scan, they go down if they have sta uh cr pr or stable disease, they drop their day eight and get ev every other week and then they, they continue have, continue to have cr pr or stable disease. Then they start getting treatment once every three weeks and really are the primary end point of the study is duration of clinical benefit. So how long can we keep patients uh from progressing while uh still uh preserving their quality of life and not giving evs frequently? So, we're all very excited about it. Yep. Can I ask you a question, Randall? So how do you, how do you counsel a patient? I mean, if I'm, so if I'm coming in and I have, you know, this sort of cystic renal mass, like what, what are you quoting me? Uh ho how do you take me through? Should I have surgery? Should I have a partial nephrectomy? Uh, should I just continue watching this? I'm kind of worried. Now, you've shown data that actually the cystic masses may actually be malignant. You know? How do you, how do you have that conversation with the patient? Yeah, I think, I think first, you know, it's a careful consideration of, of what we see on the radiographic imaging as well. Uh You know, Bosnia classification, like, like we had, we had discussed only takes you so far gives you the, the, the percentage of malignancy. But, you know, we're, we're really good at picking those out. It's, we're, we're, it's the ones that are uh biologically aggressive is it was that we can't predict. And, you know, I think, you know, we have been comfortable on our active surveillance protocol monitoring these patients. Um But I think it's how, how these lesions kind of progress on subsequent imaging six months later. Is there stage migration? Are these growing in size? Are there heterogeneity within the, the, the, the fluid component? I think that really drives our, our, our, our decision for for, for intervention. Uh Now that being said, I mean, you know, we look at other options as far as, you know, we don't really biopsy these lesions just because they're not accurate. We don't really uh recommend, you know, um Ira blade of therapies for these lesions. Um So, you know, it, it also takes into consideration, you know, the patient factors, the more morbidity of the patient and the uh checks at risk and benefits of, of intervention as well. All right, I got a, I got a good question for Randall, some urologists in here. This is kind of, you know, ne right nephrectomy with the left hand, left nephrectomy, the right hand kind of type of question. So, um, so walk me through, you have a cystic mass, young patient spillage isn't, is a never event, right? What, you know, you're doing it robotically, how do you make sure that you don't spill this tumor? And then, you know, you're sort of taking out this large cystic lesion and you have to extract this thing once you get in a bag, you know, what are your options? Are you decompressing it or, you know, are you just making the incision all the way? You know, what, what's, you know, there's no right answer, but how do you approach this? You know, I, I think that's one of the things that we focus on and, and I guess minimally invasive, you're, you're taking out this big, big mass. It doesn't really make sense to make these small incisions to make an extraction incision. That's, that's 10 centimeters. So, um you know, I think, you know, the focus that we, we, we placed on in doing the partial nephrectomies for the cystic renal masses is getting enough, uh you know, pal uh margin, uh, safe margin to make sure that we don't, uh, you know, uh, inadvertently get into these, uh, the, these lesions. Uh The other technique that, that, that I, I will routinely use is, is kind of pack the area with, um, you know, mini laps or something like that just in case there is an inadvertent uh, spillage there, I'll have a safety stitch available in case there is an inadvertent, uh, you know, uh scissor tip into the, into the lesion by accident. But uh your question to, to, to make sure that we keep the incision as small as possible while maintaining cancer control is that we'll, we'll bag the specimen and routinely, you know, kind of pop, pop the cysts uh within the, within the bag to make sure we keep the incision, you know, uh oncologically controlled at the same time, you know, minimizing the incision, uh size audience, questions anybody. We got lots of them but a chance. OK. I got a question for mark. So, so where are you seeing in the next 2 to 5 years? Adaptive RT being used the most? And are there prospective data to show improved oncological outcomes yet, in, in, in this uh or is that something we're doing? Uh and is this something that's taking off nationally or is this really in select places? So, I, I think it's pretty resource intensive and you know, it i it hasn't taken hold yet. I think it will be the new standard of care for most SP RT treatments. Um, you know, prostate cancer just, you know, it's a radi radi target, you know, it just kind of, the technology seems to follow prostate cancer. So that's clearly where we're using it the most. Um And it's, you know, a bulk of our patient population just by probability. But I, I think, um a lot of this, you know, the, the, the space where we're radiating patients with oligo metastatic disease is really taking off in prostate cancer and other uh other disease sites. Um And I think that's probably where most of the benefits are gonna be. It's, it's pretty early on to say that we can really uh improve the disease control. But I think that's always where radiation is headed. We have to make the step to make sure that our treatments are more precise and safe and we're at that level now, um there's a uh there's, there's a um uh the Mirage study has shown that there's probably possibly uh some improved um uh patient tolerability with this at, at, at standard doses. But I think as we try and escalate and push the envelope, we'll probably uh it will allow for that. So we're gradually doing that at Fox Chase, we have a clinical trial um uh that was uh designed written by my colleagues and I um for abdominal pelvic metastasis and this is for not, this is geo anos but of course, geo uh cancer patients are, are, are candidates and we're gradually using adaptive radiation therapy to uh escalate the dose. So it's a phase one study, um looking at dose limiting toxicity and, and hopefully that will translate into a better patient outcomes because they, the, the the small bowel is really limits your radiation dose. And, and um we oftentimes particularly when you're getting up in the upper abdomen near the pancreas and things of that nature, it's, it's very uh the stomach, it's even more uh difficult to, to get the dose in there that you want. So these new novel techniques are allowing us to do that and hopefully that will eventually translate into better control. But we're kind of uh we're, we're, we're working on that, but it will be a while. So, so um said a couple of things, one is when I get my traumatic brain injury, I'll become an anesthesiologist. But if it's less severe, I think I, all I wanna do is do space source. I mean that is like it's like the best little procedure in the clinic five minutes. Everybody's happy. So, yeah, so walk me through. So now we're doing space source with the gel, right? That you can see in your CT scan to do the sort of the adaptive, right? But we're still putting the gold seeds in sometimes, but sometimes we're not. Can you walk us all through here? And I think so the community urologists in here have that question. It's like when, when do you need one versus the other versus both? So, um you know, we, we have the fortune of having an Mr simulator in our department. And so we've always used the classic um rectal spacers without IV contrast and you can only see them on MRI, but that's not an advantage everybody has. And so the newer uh rectal spacers now have IV contrast. Um So, so that's, you know, more for accessibility of other centers that don't have the advantage of having an Mr simulator. But it's really uh helpful to use that for adaptive radiation therapy because it's CT based imaging there on the spot. And so you can actually see um you know, the delineation between the rectum and the prostate and not only is there space there, but it also helps with the alignment as well. Um That's part of it, but when we're talking about urethral sparing, uh SP RT when we're trying to actually drive the radiation dose in the urethra down below prescription, which is, you know, something you would only do if you have high precision, we are still using the gold seeds as a surrogate for that because it's more, it's more closely aligned to the urethral structures. And you can't see that on a chrome beam CT, you have to plant that on, on uh you have to actually contour that and know that where that is on the MRI. So the fiducial markers are exactly that they're fiducial for the location of the urethra. And there's some rotation that you can see. You know, that's why we use at least three gold seeds, two at the base and one at the apex. We, we put our Baker's dozen in there. So we put an extra one at the apex in case you lose one. But that really shows you some rotation that you just don't get with the, with the um the contrast to rectal spacers. And you know, it's, it's throughout the prostate. So we're using it for those applications. One of the questions to ask is, is can we get around that for patients that, that have contraindications to those? I mean, we have excellent urologists that can place in patients that are on blood thinners and things like that. But the community might not be as accessible to do that in those complicated situations. So maybe we can use adaptive radiation therapy to, to, to treat patients safely and more aggressively at the same time without those fiducial markers. So well, it remains to be seen. There's a lot of opportunities to explore that. Hello. Thank you for the excellent talks tonight and a fun evening. Um Quick prostate cancer question, the, the FDA approval for Enzalutamide monotherapy and the, the data of combination AD T and Enzalutamide seems interesting and I've been thinking about this and I'm having a hard time reconciling the the utility of this data in the PS MA era. Um Can you perhaps share some of your clinical experience with, with this? And, and what you think the the the evolution is going to be with using these therapies earlier in, in treatment and biochemically recurrent disease is the sun. You can yell there you go. Um So I agree with you. I think the biochemically recurrent setting is shrinking with PS MA scans. Um I think when I order a PS MA scan now in the biochemically recurrent setting, what I'm usually looking for um is hopefully oligo metastatic disease that I can then send to the radiation oncology colleagues because universally men do not wanna be on ad t even if it's intermittent. Um I think the side effect profile when you tell them all about the male version of menopause, the sexual dysfunction. Um If I also give the option of sparing them from that and giving, you know, radiation instead it's almost universally preferred. Um Obviously, everyone has their own preferences. So I I view PS ma pet scans as I'm more likely to pick up this oligo metastatic disease than I am to find true biochemical recurrence only. Um I think in terms of what, what is the conversation look like. Um Regarding the embarked data in my mind, I think the Enzalutamide monotherapy group to me is the most interesting. I think it's gonna be a complicated discussion to have. Um But I do think that if you tell someone their sexual function may be better in that arm and it, it, you know, that arm did better than an AD T alone. Um I think there may be more uptake with, with time. I think it's also gonna muddy the waters because now people in the biochemically recurrent space have now had a novel hormonal agent. So then when you think about in the metastatic setting, you know, high high volume disease, we think about triple therapy with either Abby or deride and and um dosa Taxol. I just think, I think the field is moving so quickly that all of these trials are stacked upon each other one by one. And I think it's gonna be hard. There's no clear flow chart of if this then that because I think the field is just moving so quickly. But I think the enzalutamide monotherapy arm to me um probably has the most interesting data rather than enzalutamide with AD T even though the numbers were better, I think you're, I, I personally think the the side effect profile is probably too great for men that are gonna do so well. Anyway. Yep. Thank you. We also have a prophylactic radiation for Gynecomasty also. So, just a little plug. Uh very interesting talk tonight. Thank you for uh I everyone's presentation. I'm Doctor Wang from nuclear medicine and uh I work some time at Fox Chase and uh as you know, we do a lot of PS MA P CD. So I have a specific question for Doctor Homan. I'm very interested in your talk about the adaptive radiation therapy. So as you know, when we give the report in PS MA City, we give the SUV value for lesions uh like uh some located at the prostate kind at the prostate itself. Some SUV value for the metastatic lymph nodes and uh or metastatic bone disease. So, do you think the SUV value can give you some indication about uh how much do for radiation? Like uh if the SUV value is high, it means more expression of the prostate cancer cells. So, uh my NA IL prediction is that you may increase the radiation dose to the location of the disease. It's a really interesting question. So you're uh just to reframe it, you know, does the higher SUV predict for better, you know, do you need a, a, do you have a better or worse radiation response? And, and, and based upon SUV from a PS MA pet, you know, I don't, I don't, I don't know. Um you know, PS MA S, you know, we're getting more and more familiar with that FDG pet. I think we've looked at um you know, that is a metabolic marker. Um We've looked at disease response and we've actually looked at that in other modalities. We have uh uh some esophagus um uh reradiation, uh cases with pulsar dose rate, radia reradiation where we've looked at using uh pet responses as a, you know, predictor of, of outcomes. And um I, I don't, I don't know if the, the, the PS MA would actually predict um whether or not you need more, more or less radiation dose for the pri you know, recurrent primary or for an oligo metastatic lesion. And in my thinking, I uh when we do SP RT type treatment techniques, they're just a blade of for generally, you know, histologist that would be radio resistant to conventional fractionation. So my hope and my belief as a radiation oncologist is that once we get to those dose per fractions sizes, um you know, pretty much any type of tumor histology is gonna be responding pretty well. So I'm not sure, but that's a very interesting question. We gotta ask Dr Myron. One question which is you asked the question of, I don't know in your role for platinum based chemotherapy with the front line. So I'm gonna ask you in your role for platinum based chemotherapy in front line. And if not a front line ever, I don't know. Um So obviously a good question. Um I think that there are some patients that can't get immune therapy. So that's an easy one to tick that box on. Um You know, I, I wish that population would shrink and we would learn more about who could get immune therapy with like a mild autoimmune disorder or something like that. But, you know, at this point, if a patient has a significant autoimmune disorder, then that's an easy one to kind of put in that category. I think one toxicity of EV Pembroke that uh or ev that I didn't really highlight was uh hyperglycemia. I haven't, I don't know how many you guys have seen but um like horribly controlled diabetics who really can't stay on top of it, that could be dangerous. So you may consider that. But um you know, generally speaking, that's not like a, a treatment selection limiting uh thing. Um As far as um you know, managing neuropathy goes, I think, you know, they, that's shared with platinum chemotherapy. I think if we learn more about how much ev to give, then maybe we could um you know, answer that question better. So I think there's a lot of considerations right now, there's not a huge population. I think that I would give platinum chemo to, I would try my best to, to figure out if they could get ev pembroke, I think second line seems like would make sense until we have a trial that proves that um you know, some other novel therapy is better. I mean, um we don't really have any of that information. That's why I didn't want to make a flow chart because I really don't think there's a flow chart to make yet. Um So that's, that's what I think. So. Chemotherapy probably has still some role, but certainly down down the line and how to sequence this is unclear, raffle time. Raffle time. All right. Well, thank you all for attending. Um, special thanks to our presenters and uh to our exhibitors um, for those who visited our exhibitors and submitted uh their raffle tickets. We're gonna picking three, correct? Ok. Three tickets. All right. Here we go. Ticket number one is 6011333. Francis Montera. Francis. No. Oh Francesca. Yeah. There you go, Francesca, you, I know you come on, it's dark in here. You're getting old. Yeah. Right. Mhm. It's on the bottom. I, I was like, where's the gift? Friendship. So Fran Francesca is our visiting student from Verona Italy who's doing research at Fox Chase and there we go. Congratulations. Was not real. Ok. Oh, I just get to read the name. Oh, fun. Let's see. I'll try to read it correctly this time. Kate Orlovsky. Kate. All right. Awesome. We get it. Mhm. Ok, Howard Altman, how we leave? I'll give it to him. Perfect. I know. I know who that is. All right. Great. Um, perfect. I'll get that for him. So, uh, have a safe drive back and uh there's gonna be a link emailed to you for evaluation, uh, and download your certificate. Please let us know your thoughts about the meetings. We value feedback and have a safe drive home. Thank you. Yep.
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