CME, a multidisciplinary team of Abramson Cancer Center sarcoma experts review a variety of recent sarcoma cases, discuss their coordinated approach to care and considerations from each discipline, and reference potential treatment options, including clinical trials. Sarcoma Management Case-Based Discussion
well then I will get started. Good morning everyone. Thank you so much for joining us today. I know that people will continue to trickle on and there will also be um people watching after the fact but um we're very glad to have you here. I wanted to um welcome you all to this uh cmI webinar on sarcoma management and this will be a case based discussion. So hopefully that will um illustrate many of the topics that we would be speaking about in a lecture format anyway with a little bit more um opportunity to engage and discuss and we really do hope that you will submit questions. I appreciate the questions that some of you already sent in and uh and we will try to address those as we go along. Please do feel free to either say something or type your message in the chat. We have sarah and Carly here who will be monitoring the chat for us and we'd love to hear your thoughts on, on whatever we're talking about and your questions next slide please. So just to introduce all of us here and we're going to go around and say a few words. I'm kara soprano over there on the left uh and I'm the Chief of orthopedic oncology here at Penn. I'm originally from the bay Area in California and moved out east for school. I went to medical school here at Penn. So I actually became interested in orthopedic oncology as a medical student then and um and then went to Chicago for my residency at Rush and did my oncology training at uh Princess Margaret University of Toronto. Um So after that I practiced seven years at Washington University in ST louis before coming back here to pen just over a year ago. So it was very excited to join the fantastic team that will be speaking here today. So lee why don't you go ahead and just say a couple words. Sure, I'm lee Hartner. I'm one of the medical oncologists here that that sees sarcoma patients have been here for about 18 years. Uh did my fellowship training at Tufts New England Medical Center up in boston uh and learned a lot of what I know about sarcoma chip statin, who was my partner here for many years until he retired. Thanks. Great. And jim I am Jim shuster, uh professor of neurosurgery here at Penn. I've been at penn since 2001. Uh I trained at the University of Washington. I have been interested in tumors that involve the spine and specifically pertinent to these cases. Sarcomas that involved the spine. Thank you. Jacob. Good morning everyone. I'm Jacob Davison, Assistant professor here at the pen and radiation oncology with a specialty in sarcoma. I've been here for seven years on staff, grew up in the region and actually did all my clinical training at Penn with a short stint at the NIH. And excited to talk to you guys this morning. Great, fantastic. Very, very diverse group of backgrounds here. You guys Carly. Please go ahead with the slides and we'd we'd love to know a bit about you um as well, who's in the audience. So if you don't mind typing into the chat, um just you know, who are you, Who you are, basically what feels you represent, I think based on the the sign up sheet. Uh we do have quite a variety, which is which is exciting, and so we'll try to tailor this to whoever whoever is here. Um We even have one of our colleagues from veterinary medicine over it, pens and people from other institutions, so really, really glad to have you again if you want to just type that in and maybe Carly you can uh copy some of that over to us um while you do that, just to briefly review the learning objectives. The point of this is that we we want to discuss sarcoma in the context of the coordinated care approach that we utilize and uh and describe the roles that each of us play in the in the care of these complicated patients. Um we'll also go over the potential treatment options and and have a discussion about how those, how those interact with one another, which basically reflects the discussion that we have weekly in our our Sarcoma board, um so that every patient who gets seen here has a multidisciplinary approach and as you'll see, there may be some some of it gets a little bit nuanced. So next slide please disclosure is nothing really to disclose, I had put something on there that's probably not relevant. Even so um just for absolute completeness sake and that within a week you'll you'll be able to obtain your credits for those who are watching after the fact unfortunately we're not able to give um see any credits for that, but but hopefully this will still be a good source of information. Next. Great, so case the first case is is an s to the correct to me. So jim why don't you talk about um talk about that one for us. Thanks. Alright, um thanks again. So this is a case of a 20 year old woman that we treated within the last year and she presented with worsening buttocks pain over time and that's a very non specific complaint and many times people early on start with otherwise would be very general sort of complaints of back pain or in this case buttocks pain. The patient was neurologically intact. The other issue is um because you know, tumors, you know, sarcoma is of the spine are very rare tumors. Uh they're very often tend to be extreme latency between onset of symptoms and when these patients are diagnosed. And so, you know, sort of in the rear view mirror there, you know, you look back and very often they're like warning signs but they're such unusual tumors that if someone presents with buttocks pain or back pain, it's not the first thing that you think of especially when they're neurologically intact. Next slide please. So this patient eventually had some imaging and that imaging initially started with the C. T. Scan which is the image on on on the far left. And you can see uh down at the bottom of the sacrum there's there's a mass uh and it's involving and destroying the sacrum. And so you know radiology is key. You know there are things that you know as part of our multidisciplinary team we're very reliant on the radiologist to help us make these diagnosis even before biopsies. And also to give us an idea of extent of humor because the the uh tissue is is the most important thing. And there there were a lot of questions in the chat about biopsy uh and you know only half kidding, I'll say I never have seen a biopsy that I didn't like. So I I'm always almost always in favor of biopsy. Um because as we'll talk about the cancer, the type of cancer is key to defining treatment and we have uh people that we utilize that pen that are very skilled at doing these biopsies. And so for instance you know there used to be this concern that a few biopsy that you would track you know cells through the biopsy side. And that would lead to uh you know uh contamination of the field but you know are the radiologist that do our biopsies use uh sort of co actual needles, one with the sheath and then a needle that goes in to give uh you know, to get us core biopsies and not to contaminate the field if there's any concern will mark the site and will ellipse it at the time of of surgery. And again, we really want to know up front what the tumor is because uh it dictates care for these sorts of tumors. The approach is very different than it would be for, say um metastasis. We know that with these tumors, extent of resection or in this case on block resection is the most important thing to dictate patient outcome and long term survival. And so it really is very important. And so again we have a low threshold for boxing. And uh my personal preference is to have someone do these biopsies that has a lot of experience and is very skilled at getting us tissue and not contaminating the field. The other important thing as we look at the radiology here is Jim Jim, I would just jump in quickly to add to what you said about the biopsy and and the importance of doing that in uh in an appropriate manner. I think that's even if anything more important in the extremities um uh where the I think there's a greater propensity to I think you have more options about how to approach something. Um And so having keeping in mind the definitive surgery so that you can, like you said, a lips out the biopsy tracked if if necessary is really critical because as someone who operates on the extremities quite a bit, or even in other areas of the pelvis, if you have the biopsy in the in the wrong spot, it really does complicate things because you're now it's telling you you have to put your incision somewhere else or it's trans verse or there's a lot of contamination. And and it can it can be the difference between um between limb salvage and amputation in some situations. So I can't stress that enough. And not that I need to certainly not. You know that I need we need to do every biopsy ourselves. But I think at least being in coordinating with or speaking with someone who will ultimately be able to take care of the patient is really critical. So, great point there. And to that same point in general were not advocates of open biopsies of of questionable lesions again, because it compounds the issues. And for us, the most sort of, you know, disappointing thing is, you know, when a lesion doesn't get biopsy undergoes an interregional decompression, then it turns out that this is a primary tumor that would have been better treated with an on block or marginal resection. So, another thing to keep in mind um there were lots of questions about biopsy. So we'll go through that also in my case next. So, okay, so in this case um can we have the next slide please? So this is a patient who underwent 22 ct guided biopsies. And then eventually an open biopsy at an outside institution. And you know, biopsies aren't perfect even in in the hands of people that do them routinely. You can get a negative biopsy. And and uh and again for many of these lesions, we would advocate re biopsy to get tissue. Uh she was seen at an outside institution and that the provisional diagnosis was Condra sarcoma. And we'll talk a little bit about that. Um uh And so she was offered a sacred resection with the sacrifice of the high um uh sacral nerve roots and then an upfront colostomy. Um You know, we uh we talked about, you know, on block three sections on block perceptions in this part of the anatomy comes at a price. And uh and that price is, the higher you go in the sacrum, the more likely that you'll have balance bladder issues after the surgery. So, uh you know, it is part of our planning in addition to trying, you know, really trying to do on block perceptions. We try to save as many of the sacral nerve roots that we can to at least give the patient a chance at at uh retain balance bladder function. Again, the the provisional diagnosis here was condo sarcoma. Uh and you know, which is certainly a tumor that we see in this part of the the the body. The other one that we see routinely in the sacrum is chordoma. And um again very often are such those cases, you know, on block resection is is our is our goal. But in the case of chordoma there are options um in addition including proton therapy. Uh and uh and so uh in the other thing that's unusual in the management of sarcoma as compared to say, metastatic diseases that we very often would do the radiation upfront. Uh you know, and um I guess I accept Jacob way in and on the you know, how for instance, if this was a chordoma, what our approach would be. Yeah, I think, yeah, I think, you know, this is obviously unique case, especially with the diagnostic uncertainty. Um and the young age complicates things. But this location. Yeah, classically, something like this would be usually thinking about chordoma. And we're often trying to treat these patients with almost like with a split course of radiation where we do up front radiation to a sufficient dose. That doesn't, you know, that also allows for a bit wound healing after the operation. And then a few weeks after After we we try to come in with a radiation boost. And there's some data behind that approach that was developed at mass general, which is very good responses. But 20 year old with uncertain diagnosis, radiation in this area has a lot of implications for, you know, future fertility, ovarian function and such. So um uh certainly, um but that would have been kind of a potentially favorite approach if we knew this was a chordoma upfront. Yeah. There's a lot of there's there's been some controversy I know about radiation in chordoma and I know that you've really scoured the literature and so um certainly rely on your your having done that for for situations like this because it does get it does get quite complicated making those decisions. Yeah. And as I said, without randomized data and a rare disease, you kind of have to make your best judgment. There's not really a clear cut right or wrong answer. Yeah, certainly conversations to have with the patient. So this patient came to us for a second opinion. And uh and we you know, we see many second opinions with regard to these tumors again because they are very difficult cases. Um and you know, that's our you know, we have a multidisciplinary sarcoma conference which involves neurosurgeon, orthopedic oncologists, medical oncologists, radiation oncologists, pathologists, radio radiologists, plastic surgeons, uh general uh surgical oncologist. And so we present these cases, we go over the uh the pathology if we have in advance, we go over the radiology and we come up with a plan. And in this case our plan was was different from the recommendation from the outside institution. Uh And in that um we did not feel the patient needed an up front close to me. And I'll be honest, that was a big uh you know, for a 20 year old girl, um 20 year old woman uh you know, she was very concerned about having a colostomy. And so that was a big issue. And and again if if that's what she needed, that's what we recommended. But we we thought, you know, based on our conversations that we could do this operation without a colostomy. And we really felt very strongly that we could save the S two new routes. And um you know, S. Two is really sort of the you know, if you take both s two nerve roots, it's it's almost it's almost completely unlikely that patient would have any chance at normal bowel and bladder function. If you can save the S two nerve roots, at least they have a chance. You know, they can be functionally continent and may not be perfect. But obviously um you know, the part of the morbidity and and and the quality of life sort of issues with these patients is trying to maintain bound bladder function. And then the thought was, you know, based on the final diagnosis that we would make recommendations with regard to radiation or chemotherapy next next. And I sort of, you know, I put this slide up there and I won't go through all the details. But you know, as you can imagine, these are very complicated cases and it involves multiple surgical teams, There's the neurosurgical team, orthopedic oncology team. We always uh have the colorectal surgeons available because the proximity to the rectum and the colon. And you know, you can imagine these are sections very often leave a big uh you know, soft tissue deficit. And so we have highly skilled plastic surgeons that are part of our team. And so this really is a multi team approach to these um to these cases. You know, we utilize every, you know, surgical adjunct that we can we use inter operative navigation, we use navigated bone scalpel so that we really know that we can make these precise cuts and stay out of the stay out of the tumor. And then this is this is the path specimen. And so uh this is a, you know an on block resection were able to get around and not violate the tumor capsule. And in the lower left you can see that we have a list the site where they did the open biopsy. And you know, so that we you know, hopefully our goal is to to not leave any potentially contaminated tissue behind. And then on the far right, you can see that's the view from the back. So this is the patient prone and that's after resection. And it shows that we've we've we've maintained the integrity of the S. Two nerve roots, which again is very important for this. This patient's long term quality of life. And this is just, you know, are again the pathologists are a big part of our team, You know, you know, they the way they handled the tissue, the way they cut it. Because what we're looking for is to make sure that we have not violated the capsule. And this in this case that the margins were negative. So very important. It's a nice specimen. I saw that we have someone in our in our one of our participants today is is a pathologist. So maybe we could um comment on the diagnosis, which I'm sure you were getting to. Yes. So, you know, as I said, is uh in this case this turned out to be a very unusual diagnosis. You know, if you if you look at the, you know, these are uncommon tumors, but you know, common things being uncommon, we would have thought most likely that this was going to be contra sarcoma and maybe a chordoma. But it actually turned out to be the next line. I guess it's one more or this is just the post op. And you can you can see where we've made the cut in the in the sacrum, right at the S. Two level and again, no evidence of residual disease by radio uh radiology. And just with in terms of the patient outcome. Um she's actually done very well. Um initially she did require a bladder catheterization and self catheterization, but she at this point is continent of um of balance bladder obviously very important uh for her quality of life. Um this turned out to be a very unusual sarcoma. In fact, uh this type of sarcoma, these 80 R. T. S. Uh would would be extremely unusual uh diagnosis uh in uh in the sacrum. Um this very often is a pediatric tumor. My pediatric colleagues will see them in the cerebellum of the brain. So very unusual. Uh and then at this point, you know, we sort of circle back with regard to, you know, what's the next step. And there were discussions of radiation and I think the the the result of that conversation is that this we would not offer her radiation, but she did go on to to get chemotherapy um uh for this particular tumor post operatively. Yeah. Jim this is like, I'll just jump in for a second. I mean, these are incredibly rare tumors and definitely incredibly rare to see them in in this part of the body in an adult. Uh They are typically treated with multi agent chemotherapy in Children and certainly makes sense to do that here. So, uh that that lead that was what led to the recommendation for chemotherapy. But like a lot of diseases that we treat because there are many, many types of sarcoma and many of those types of sarcoma are very uncommon. We don't always have a lot of data, certainly not randomized controlled trial data to guide management. So sometimes we have to make decisions based on your limited information. But in in this case with this type of tumor combination chemotherapy in my opinion was definitely indicated. Alright, great. Because that that might be it for that case. Um Certainly if there are any, I know we had some issues with the chat there, but if there are any questions, you all can type them into the Q. And A. Um And in the meantime we'll move on to the next case. Uh This is this case is a mix of fiber mix of fiber sarcoma. The patient actually presented with a 63 years old presented with a mass in his lower leg. And he said that he noticed a lump for several years but recently it increased in size and it's it's kind of a classic presentation as we all know that sarcoma czar typically painless. Um So pain is not the presenting symptom but there's a mass. And we we also know that classically things that are growing quickly are more concerning or that are very large. But there can also be small tumors or small tumors that have been indolent for a long period of time and still end up being sarcoma. Which makes things tricky. And I don't know that people talked there were questions about biopsy ng those. So we'll try to go over that as part of this case. But in any case he underwent an ultrasound and an M. R. I. And I think that's really important. I think one of the one of the ways that people run into trouble um is very well intentioned. They'll you know try to remove the mass in clinic or the operating room whatever is an exceptional biopsy without having imaging first. And I think that can that can lead to um unforeseen situations. And so just to address it um I think it's it's safe to remove cutaneous lesions. So if if there's something that's truly cutaneous I think that at least from a sarcoma perspective is okay to remove as an as an exceptional biopsy. Um Even as you get subcutaneous even though it's superficial sometimes those masses are bigger or can be more you know um And an exceptional biopsy can lead to problems if not done appropriately. So what I would recommend to everyone is at the very least get ultrasounds. So you know I think what you're dealing with um if it looks definitively like a light poma on ultrasound or like assist then those those diagnoses can be made but they really have to have a classic appearance if there's any doubt. Um I would get other imaging or or make a referral. Um And then just the general principles of biopsy you really want to make sure if your lips sing something that the orientation of your lips is longitudinal etcetera. So this does become a longer conversation but and I actually have other talks about about this very topic. So if anyone has other questions or would like to go over it in greater detail. We can certainly do that. Um In the meantime I'll leave it at this patient had an ultrasound and an M. R. I. And next slide please. And this is what they this is what the M. R. I. Showed. Um You can you know, you see the location and extent of the mass and uh next slide please. And he underwent reception of the mass elsewhere. And um it was the pathology came back as a mix of fiber sarcoma grade three as opposed to um like a like a lower grade tumor. So there's a high grade tumor with positive margins um and positive margins is is another conversation that will differ for the moment. But this this was I would say uh grossly positive in multiple locations. So really um not a clean reception. And at that point he was referred to us, which is the right thing to do. I've unfortunately seen some patients that get a sarcoma diagnosis and then aren't promptly referred and that can that can be problematic to. So, um so we saw him, we restaged him in terms of local imaging to look for residual or recurrent tumor as well as systemic stage staging where we look for metastases specifically in um you know, most commonly in the chest. We discussed that tumor board as we always do. And our considerations for this particular case were whether to do a real, you know, you could do a re excision or potentially just observe. Um There are some cases where margins might be marginal or it might be appropriate to observe. Uh I would say most cases re excision is more appropriate. And that's what we certainly decided here given several factors um including the diagnosis and the nature of the prior surgery. And then there was pre versus post operative radiation or adjuvant versus neo adjuvant versus achievement. And we'll have Jacob talked about that in a moment and then the surgical plan itself. Um I will let's see next slide please. So again, this is our restaging here. We saw that uh there you can actually see on the on the M. R. I. Of the lower leg. You can see where the tumor was. And even though you don't see an obvious recurrent mass, you can see a lot of signal change in the area and that represents um if not tumor than areas that were affected by the previous surgery and and are potentially contaminated. And that really illustrates um that illustrates how removing something can um increase the size of the subsequent surgery that's needed. And then fortunately his chest cT was free of metastatic disease. So that's in many in many ways the most important thing uh Car I'm going to just jump in for one second. One thing that one thing that often comes up in cases like this, particularly in the extremity with a high grade soft tissue sarcoma is whether or not patients should be treated with either neo adjuvant adjuvant chemotherapy uh in this case specifically, and actually in general we often don't recommend it. But in this case, specifically for mix of fiber sarcoma, that's a subtype that really tends to be less sensitive to chemotherapy than some of the other subtypes retreat. Uh So I would not have recommended any chemotherapy either up front or for that matter, uh after surgery. And in general, the benefit of chemotherapy and I'll talk about later is is relatively low. Can I just say to your point, cara related back to the first cases, it's really important to stage these people to make sure they don't have uh tumors in their lungs because obviously if it's already metastatic, you know, certainly in a case with doing, you know, large cases, it or you know, larger sections, it may change what you do. And so, you know, I didn't make that point, but it's really important to make sure that, you know, it's an isolated finding because it really does affect how you treat these patients. Thank you. And we just got a great question in the Q. And a um that if the mask were growing directly on the nerve and the imaging wasn't conclusive, which is, you know, I think even if the imaging is pretty strong? We we like the tissue sample anyway. So um would you do an open biopsy or is it still safe to do a per catania's biopsy? Given proximity to the nerve is a fantastic question. Um I I think that if it is not the nerve itself then we can typically uh we can almost always get the per catania's biopsies safely. Um And I think that's actually also a conversation that we have at tumor board because our radiologists are and are there as well. Who will the M. S. K. Radiologists who do the biopsies? So the same for actually pulmonary lesions if we want to get a biopsy, there's a discussion around whether that's feasible. Um So typically yes we will be able to. Uh And and so and so that's usually the way we'll go. But it is a conversation and sometimes they're you know, I've had especially if they're lesions, say in the back of the knee and the political space. I've had patients show up with sort of a small indeterminant lesion tucked in between between the nerves and vessels. And they say it's not safe to biopsy that just go in and take it out and then we take it out as if it were a tumor. Um So hopefully that answers the question. Otherwise please feel free to write. And again it was a really good question. Alright, next slide please. So Jacob why don't you talk about this for a minute or two and then we'll get on to the actual surgery. Yeah. And thanks carrie. Yeah. So one of the big questions um in the management of local sarcoma is the timing of radiation and I'm not going to go into the data that you know for why radiation is indicated for the majority of high grade sarcoma is um but this has been examined in randomized and randomized trial. And the real big issue here is about toxicity. Um and the local control is pretty equivalent, which is typically very good between the two modalities and most Sarcoma sits in the order of 90% or higher and overall survival also is equivalent. So it's all related to the toxicity. Um and here is really the highlighted differences and you know, just to jump to the punchline and if you could advance the slide one more because there's some other bullet points uh and one more please. Um So in Neo Adjuvant radiation um we treated to a lower dose 50 grays opposed to 60 or 66 I'm not without the outside the scope is talk but even that we're working on reducing the dose of radiation and certain sarcomas are the timing. Um We treat a smaller volume, just kind of the target with a margin as opposed to when it's a judgment it's a larger cavity kind of have to treat everywhere that's been touched during the operation, assuming it may be contaminated. And this all kind of leads to different toxicity profiles. The big toxicity for Neo Adjuvant radiation is wound complications that is definitely worse. Um It's in the order of 30% or higher. Um But that's often reversible. Where the long term complications such as fibrosis or Dema those sometimes never get better despite aggressive physical therapy. Um So often were. And this is where it's kind of a multi D approach um willing to take a little bit higher of a wound complication risk to spare the patient some of those long term toxicities. So again the really the most important thing is it's not really about local control survival, it's about how you're going to reduce toxicity. And although Neo Ottoman is often the favorite approach, there are indications where we would want to treat patients adamantly. Um I can go to next slide please. Um So actually despite this we did look at this data here and this is a data from national Cancer Database. Um Still the vast majority of patients across the country are treated with postoperative adjuvant radiation. That trend is starting to equalize a little bit and again even the status now seven years old. Um So it's ever since that trial was published that the trend is trending in the opposite direction. Um And the next slide please. So in addition to kind of preoperative versus postoperative um you know within sarcoma. The technique does matter. Um And one that we often try to use insurance permitting is a technique called intensity modulated radiation therapy. Any of the radiation oncologists on the um call or the uh the lecture will understand what that is but it's basically using more sophisticated radiation techniques with inverse planning multiple beam arrangements if not 360 degrees um to modulate the dose to where high dose where you want it and spare certain structures which a lot of these is actually the skin and some of the soft tissue. And there's just some kind of a slide of generated um where you know if you look from right to left, right is the post operative arm of that randomized trial? The second slide. Uh The second column, I'm sorry I can't point um is the preoperative arm. And then the other two are more modern trials which primarily use I. M. R. T. Really the take home point is that these late toxicities regardless go down with I. M. R. T. So that is something we often try to use. Um interestingly I. M. R. T. Does not appear to affect wound complications risks. Um I think there's some reasons for that based on these trials and hopefully practice there a little lower but really the goal is to reduce the late complications. Also thrown in here about um limited data on proton therapy. We have that as an option here at 10 but it's actually rarely used for extremity sarcoma. Um Next slide now throw it back to you, thanks and such an important topic. Um definitely like you said, we I at least we as a team prefer preoperative radiation for all the reasons you mentioned. But it's a very patient specific conversation carol. What's your what's to that point? What's your ideal timing between radiation when you do the operation? Because you know, I mean what's what's your feeling on that, You know, the data out of out of Toronto where where I trained suggests that five weeks is about the right time. And so anywhere in the 4-6 week range, I think that is based on slightly older techniques. And I will usually assess the patient around three weeks and decide and you know, take get a sense of how they're looking if the skin looks like they've recovered well. Um and and that they're doing well. I'll maybe do it a little closer to the four week uh end of that window um to avoid some of the later scarring. But if things are, if the skin looks like it needs longer, then I'll push it out to five or you know, I usually don't go beyond 5.5 6 weeks. So yeah, it's it's it's become a little bit nuanced over after having, you know, the years of having done it. I've probably adjusted that a little bit. Um So then as for the surgery itself, uh there are lots of things that we consider when we when we plan the surgery um in addition to, so, you know, to begin with the histology mix of fiber sarcoma, we know to be um, a very infiltrated tumor. So whereas some sarcoma czar more contained by structures and tissues like fashion, that we really can't trust those margins quite as well with mix of fiber sarcoma and so that's some heightened awareness about the, about the risks there. Um, and you can see what I'm looking at here is not the post operative imaging. We did re image him as we showed previously, but this is the preoperative scan. So, fortunately this was obtained, which I am very, very thankful for that. They got this imaging. Um, because this lets me see everything that the that the tumor was was touching and where the and the tissues that were involved originally. So, uh, the contamination piece, we're looking at where the, you know where the tumor was. Well look post operatively where we're seeing a demon et cetera. And you'll notice that this is the anonymous out there will know that this is um right by the fibula right where the perennial nerve is and that's a nerve that is important to foot function for dorsal flexion. Uh, and and diversion. And so, um this was this was this definitely was one of those conversations I had with with the patient. You can look at the actual cut on the far left. That's right where the nerve would be. And and we discussed, you know, should I at the time of surgery. If the nerve is typically, we can, you know, I tell patients that we can peel the nerve right off the side of the tumor. And that's what we do and what we're used to when we're familiar with the concept of a planned positive margin. Again, something published out of Toronto where um we we know that if this is a purposeful intentional marginal resection against a critical structure, such as a nerve vessel, bone, etcetera, uh, that the if, if done appropriately and treated with radiation, the local control can be is comparable to a negative margin resection, but that's different from if it's an unintended positive margin, which is what this original reception was. So long story short, we talked about everything with the patient. And uh, and when we went to do the surgery, as it turned out, the nerve was involved, like essentially encased in the tumor. And so we did respect the perennial nerve, which was his um preference anyway if things looked even close, he wanted to air on the side of removing all the cancer. So, we had talked about that before and what the functional implications would be. And that's certainly something where the musculoskeletal training um, is is helpful to talk talk with them about what that will look like and how how it can be managed with bracing, etcetera, even tissue transfers. So the next consideration is the soft tissue, as you notice there there's a lot of superficial involvement. And especially with mixed fiber sarcoma was uh there's concern about and radiation is concerned about that healing and coverage there. Uh And then lastly the knee stabilizer. So if you look a little higher up uh onto to the to the cut for this to the right, which is about the level of the knee. You see that there's all this involvement and signal increase um in the lateral knee stabilizers. And so that was something to be considered as well. And so you see how not terribly large tumor can very quickly become problematic just based on location and what's involved. Next slide please. So this is what we did. He underwent preoperative radiation and then he underwent re excision. Five weeks later we did respect the perennial nerve. I did a lateral collateral ligament reconstruction because we basically stripped the lateral side of the knee joint and reconstructed that with mesh. Um And and then did a gas truck flap with skin graft over there. Uh This is early postoperative. Next slide please. And then just to you know, we didn't didn't just bring out the perfect cases. This is one that did develop wounded distance in spite of the patient taking good care of it. Uh These things really do happen quite commonly. So this was managed with operative debridement once and a wound vac and then that healed in by secondary intention. And so in the future we can consider things like tendon transfers for him. In the meantime he's in a brace. And we're monitoring uh next slide please, just very briefly about surveillance uh for him we're getting a chest C. T. And M. R. I. Of the calf. Next slide, there's quite a bit of data on this and I just wanted to point out some references because this is a whole other conversation and a particular interest of mine. Um This is this review article that we wrote for um in the orthopedic literature a couple of years ago has a few figures and charts that might be helpful if those of you who are out there are looking for ways to you know they're different systems. Um There's the british sarcoma group and and CCN etcetera etcetera. Uh Everyone has their own slightly different recommendations. And so there are a few tables in here that summarize those in addition to giving some of the um the rationale. So if anyone needs a resource that's one you could consider another one. Next slide is this appropriate use criteria developed by the M. S. T. S. And um and I was uh really I got to be a part of this as well which was really interesting to see how it was created but basically taking whatever literature is there which is not too much. Um but creating this app where you can enter in things like what you think is the risk of metastatic disease, local recurrence etcetera, etcetera, the type of tumor how far out and and then you enter it and it spits out to you what are appropriate and recommended and inappropriate ways of following it. So I'm hopeful that they will you know, have taken this opportunity to try to publish research and publish more on this so that the next time they update this um that that there can be a bit more data driven. But those are great resources in the meantime next slide. So that's that's all for that one. I know I don't want to take the rest of the time. So we'll turn it over to lee for the last case. Can I just say yeah, it's the conversations you have with patients can be very difficult because when you're talking about taking like functional nerves and leaving people with a deficit, you know, as a neurosurgeon, I spend most of trying to preserve. So when you know, but the difference is we know that extent of resection is really the most important thing for these patients surviving and sometimes that means you know hard decisions are made about, you know taking nerves or nerve roots and but those are extremely difficult. You know, decisions and difficult conversations to have with patients. I mean it's really something sort of very unique to these sorts of surgeries. Yeah and it really does alter, you know influence how we treat them, really try to take their wishes into consideration and and educate them as much as we can. Alright, right, so next slide please. I'm gonna pivot a little bit. This is a patient who unfortunately develop more advanced disease as I'm going to go through. So this is a 43 year old woman who was initially diagnosed with the lima sarcoma of the humerus. Sarcoma is usually a soft tissue sarcoma, but it can sometimes occur as a primary tumor of bone. And it is something that we definitely see from time to time. It is typically treated with resection and radiation. She was diagnosed in 2009. She got adjuvant radiation uh after her reception. And after that, as we were just talking about was monitored with imaging surveillance, which she continued on an annual basis at this point beyond the first five years after diagnosis. So in 2017 she had a routine chest X ray and M. R. I. Of the left humerus. Uh And as you'll see on the next slide, a liver lesion was identified. This is actually on the Scout film for the M. R. I. So this was a purely incidental pick up. You can see it there in the lower left about maybe about a two centimeter lesion there. Next slide. So this was evaluated further. She had an abdominal M. R. I done about 2.5 centimeter mass. Was seen there with a smaller satellite lesion. She then had a pet ct done. That is a test that we do sometimes in staging sometimes for restaging. In this case it did not reveal any other sites of cancer. So she had a she had surgery done for the river and it was found to be metastatic landmine of sarcoma. I will say just parenthetically, many of the people that we see who have metastatic recurrence will recur within the first year or two after diagnosis, which is typical for most types of cancer. But we do see late recurrences and various types of sarcoma. So while this is uncommon, it is certainly not unheard of following that surgery, she did well for a while, so maybe about a year or a couple of years but then developed Aussies metastasis and the corporate process as well as there was a lesion in the rib that we really weren't that we weren't sure about but that we were concerned about. And so given the presence of multiple sites, we opted to treat her with chemotherapy and she got Dr Benson which I'll touch on in a little bit. Got three cycles of that and repeat imaging. Unfortunately, really didn't show much response. So there was persistent uptake in the core coid there was now evidence of uptake in the right hue mural head which wasn't there before. So, you know, with the pet ct we we saw persistence and worsening disease. We did an M. R. I. The human head which revealed findings that were consistent with metastatic disease there as well. Unfortunately next slide. Uh So based on that her chemotherapy was stopped. She was treated with radiation and we'll touch on that in just a few minutes. Further surveillance imaging showed possible lesion at the classical about this is again about another year or so after the radiation she was sent for a colonoscopy which was done and revealed a polyp biopsy was done and that biopsy did not show any evidence of cancer. But on a routine follow up M. R. I. That was done soon after the colonoscopy that lesion actually grew quite a bit up to about six centimeters. So given that she was referred for surgery and that was done and revealed metastatic lymphoma sarcoma. No treatment was given following that. But in february of the following year she was found to have a coral lesion in the left upper chest. And this also was treated with S. P. R. T. And again at that time had no other sites of disease. Next slide. So this case I think highlights a few different things. So one is the importance of post treatment surveillance the second the treatment of Oliver metastatic disease. Looking through the case. Uh it's obvious that when she rickard she rickard with one or a couple of sites at a time and did not recur with multiple sites and then that setting the treatment considerations and often how we approach the disease is very different. And then finally I want to touch on the role And also unfortunately, the significant limitations of systemic therapy in the treatment of sarcoma. Next slide. So as car summarized nicely, uh surveillance, post treatment surveillance is very, very important. Recurrences for people with sarcoma are either at the primary site or at metastatic sites. For most soft tissue sarcomas, metastatic spread is hematology anus. So the lungs where we tend to see these, there are other, there are certain subtypes where normal task disease and other sites can be seen, but that's less common Now. The, you know, value of imaging, you know, comprehensive imaging, say anything other than chest imaging uh, is unclear. But as you can see here, there are certain subtypes like I just mentioned, where we do consider doing that, you know, how often we do that and how we do that is, you know, not really well worked out. But for these subtypes we will often look at more than just the lungs. The other thing that's not entirely clear is how long should we be doing this imaging? How often should we be doing it? And as Kyra mentioned, different groups have given slightly different recommendations on this point, but I do think it is reasonable to consider at least annual imaging uh potentially of the primary site as well as the chest beyond five years as this case really illustrates Next slide. So for all of the metastatic disease, we do consider things such as where is it occurring? How many lesions are there? How big are those lesions and the timing of recurrence. So for example if there is early recurrence particularly in more than one site early being said within a few months of initial diagnosis and treatment, you know we can treat with local therapy but the risk of further recurrence goes up significantly um on the flip side if the recurrence is relatively late, say about a year or two after or even longer after the initial diagnosis and treatment would say one or maybe a couple of sites it becomes very attractive to treat those locally. Uh chemotherapy given either before or after. Local therapy for analytical metastatic site isn't typically helpful uh And isn't and I don't often recommend it next slide. So I think Jacob's going to talk a bit just about how this patient was treated in the use of particularly stereotype radiation for the treatment of metastatic disease. Thank you early. So as lead kind of highlighted, you know, these were late recurrences and Oliver metastatic cancer and radiation oncology. Our approach to metastatic cancer particularly all of the metastatic cancer has changed in the last decade or so. And so this patient was treated on that and you know 2 to 2 sites, the right humerus and the left cork oid uh to a dose of 40 gray and five fractions with this technique of S. P. R. T. Which is sort of a high dose of blade of radiation over 1 to 5 treatments. And she did wonderfully with that had a mild plane flare which is well established control with Nsaids and otherwise no toxicity even a few years out. Um And no progression at that site for you know still to this day Over three years. Next slide please. And this is just kind of a characteristic plan here where this is the humerus lesion which um to the actual tumor was treated to 40 grand. In the humerus there appeared to be two spots. So the interceding space was treated to a slightly lower dose. But just to give a sense of that we can get a high dose to these regions with minimal spillage to other tissue and minimal toxicity. Next slide and then similarly this is the left cork Oid uh metastasis similar approach. And what was tricky about this is that this was actually in her initial radiation field. So this was really a radiation 10 years later. Again with minimal minimal toxicity despite a very high dose because we can get it to a small area. Um next slide please. So you know. And then unfortunately three years after treated both of those sites, she then unfortunate develop the colonic metastasis. And then this asymptomatic metastasis in the lungs pleura which is an odd place to develop metastatic lesion. We treated that again with aggressive local therapy this time. 45 gray and five treatments with no reported toxicity, no chest wall pain. Um and really no issue. So we've really been able to take an approach for this patient to pick off her metastatic disease every year or two when when it does occur and she has very functional great performance status continues to live her life normally. Next slide, please. And here's just some data to kind of support this approach in the radiation oncology literature literature. Recently the Saber comment trial was published. It looks at the benefit of S. P. R. T. This is across all cancers for all of the metastatic disease. And sorry, in the interest of time really just showed an overall survival and progression free survival benefit. Um So I just kind of gloss over this in the interest of time and next slide. Um And you know, in addition for sarcoma specifically there is there's not randomized data but there's been a lot of single institutional studies to show that with this approach we get excellent local control table. One there on the left shows sp. R. T. For pulmonary metastases where you see, you know, the 22 year local control is 90 85 to 95%. And similarly we're doing this a lot for spine metastases or brain metastases. So the local control is in the order of 90%. So we do an excellent job of controlling that disease. Of course the bigger problem is other sites of metastatic disease. Um and next slide. All right. So, so I'm gonna talk just for a couple of minutes about chemotherapy. Um If I can go through my slides I will but I'll try to highlight important points. So as chemotherapy which really isn't directly relevant in this case but is not indicated for most patients that there is some potential benefit for high grade soft tissue sarcoma, the extremities, but that benefit is relatively small. The toxicity is significant. Certain histology is as you see listed here, however, uh do benefit and we do often offer it different types of chemotherapy for different histology is next slide. So when we're giving a chemotherapy for metastatic disease, you know, we typically reserve that for more disseminated disease. That's not amenable to local therapy. There are many drugs available. Response rates are relatively low. Front line docks, Robison, it's about 30 or 40%. That's unfortunately the best we get anything second line or later, we're looking at a response rate of 10% or less. Uh And the duration of those responses is unfortunately typically short. Next slide, there's a number of drugs that we use. I'm not gonna go through all of them. These are various chemotherapy drugs that we use basically there are some drugs that tend to be active for various histology is such as dr Robinson jump side of being other drugs that tend to be more maybe niche drugs such as a rebellion for lipo sarcoma maybe for like sarcoma and impact the tax which we use for angio sarcoma. But I think again, the theme here is that while we do use chemotherapy the potential benefits uh and most patients are limited. Next slide, there are also a number of targeted therapies that are using and I'm not going to go through all these. These are more specific in some cases for different histology is and they target different kindnesses. Uh and I think really that the idea and the point here is that while many sex sarcoma is very difficult to treat, we have many more options for the various histology ease in different patients than we did in the past. And when you consider that there are about 50 plus types of soft tissue sarcoma, really knowing what's active and what to do for different people makes a big difference. And in the the other point I'm going to highlight here just getting into the potential role of next generation sequencing. You can see here our inhibitors and then the use of N track inhibitors, You know, it does become important to do next generation sequencing to try to find some of these alterations while they don't uh impacted treatment in most patients. Occasionally we do find alterations and they can have a major impact. Next slide. And then finally, I think no medical oncology talk is complete without a plug for immunotherapy. And what I will say is that pD one and PD L one inhibitors have a limited role at this point. All right. So for undifferentiated polymorphic sarcoma mix of fiber sarcoma, there is some evidence, there's some and I'd say even less compelling evidence in angio sarcoma, but more and more trials are ongoing. Looking at this next slide and then with regard to clinical trials, that's a very important consideration. I think for any type of advanced cancer for which standard therapies are not what we want them to be. Clinical trials are something that we are always considering for our patients with advanced circle but we do have a number of trials that are available here and more that are opening for different types of sarcoma and they can have a real impact on the treatment trajectory for this population of patients. So I do think it's always important if you're treating somebody with advanced sarcoma uh to look to see if there are trials available. We are certainly happy to see patients for consideration of trials obviously also happy to see patients just to help co manage uh and provide input. I think that's the last slide. Thank you very much. Thanks thank you. Um And uh I am going to I know that we're a couple of minutes over, we started a couple minutes late so we'll call it an hour. But um I'm gonna ask carly to share my email in the, in the chat. Should anyone else have questions about things like biopsy I know that I think I speak for all of us that were very open to um to discussion of these issues even out you know outside of the webinar. Um And I personally in my practice have always been happy to consult with anyone who has a questionable lesion or a questionable X ray or something I want to be available so that um so that you can get these questions answered for patients as quickly as possible and and not cause them undue anxiety as they wait for you know to see an orthopedic oncologist. Although we do try to get them in immediately so definitely feel free to let us know if there's anything clinical or otherwise that you would like more information on. Um And I don't think I think we answered the questions as we went along so I don't think there's anything else outstanding. Does anyone else have comments? There's actually one question if we have another minute go for. That was about kind of close margins. Um Yeah after new management radiation particularly if it's kind of right along the nerve. What is the role for additional radiation? And damn potential toxicity. Um So you know there is some variability in this. There are some who will say that for close or probably not close but more positive margins would give a postoperative boost of an additional 16 to 20. That's actually in the N. C. C. N. As an option. I personally don't really believe in that. I don't know if it's a it's a close margin or that I wouldn't boost afterwards. You're giving a very low dose with a two month really delay if you say four weeks to surgery and then another few weeks to heal from surgery. Um So you're I don't see much of a benefit for that. Especially even if it's planned positive car already kind of touched upon that. If you know that with radiation on board we still there's still a very high local control rate and I'd rather hate to say this but like almost save the radiation if it then does recur rather than give a in my mind inadequate dose at the time right after. I think Jacob were very much aligned. That's basically I sent a written response so didn't show up to others. But yeah the literature we have suggests that the postoperative boost isn't really doesn't really provide any benefits. So we just try to save the toxicity exactly like you said. Um And if it's I think the post operative radiation may be attempting solution to a positive margin but it's either a planned positive margin that really doesn't need additional radiation or it's an unplanned positive margin where it's probably going to require additional surgery and just giving additional radiation is a little bit like hiding our hiding our surgical heads in the sand so sweet. Um And so anyway. Yeah. Great questions. Especially about the biopsy. We know that also just tying it back to the literature that often unplanned receptions don't lead to increased mortality, but they do lead to increased morbidity in terms of additional surgeries and procedures that need to be done even, you know, sometimes, um leading to uh, you know, where limb salvage becomes not possible. So, anyway. Great. Alright. I think that's um that's it for for now, we certainly appreciate all of you being here and and hope this was a good format for you. We welcome any feedback and of course, feel free to contact us. Thanks everyone. Thank you. Hi everyone. Thank you.