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Lukas Nystrom, MD, an orthopedic surgeon at Cleveland Clinic specializing in musculoskeletal oncology, joins the Cancer Advances podcast to talk about the management of soft tissue sarcoma in adults. Listen as Dr. Nystrom talks about the misconceptions and the multidisciplinary care that is needed to treat this rare cancer.

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Management of Soft Tissue Sarcoma in Adults

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig phase one and sarcoma programs. Today I'm happy to be joined by Dr. Luke Nystrom, an orthopedic surgeon here at Cleveland Clinic specializing in musculoskeletal oncology as a member of the Cleveland Clinic Sarcoma team. He's here today to talk to us about management of soft tissue sarcoma in adults. So welcome to the podcast.

Lukas Nystrom, MD: Thanks for having me. I'm excited to be here.

Dale Shepard, MD, PhD: Absolutely. So, give us a little idea, what is your role here at Cleveland Clinic? What do you do?

Lukas Nystrom, MD: Well, I have a couple of different hats that I wear. So as an orthopedic surgeon, I do take care of many different general orthopedic problems, hip and knee replacement, fractures, infections, things of that nature. But my real passion is musculoskeletal oncology, and so that involves primarily taking care of sarcoma and metastatic disease in the arms and legs and pelvis is how I describe it.

Dale Shepard, MD, PhD: There we go. And so, I had mentioned something about soft tissue sarcoma. Tell us a little bit about soft tissue sarcoma and bone sarcoma. What are these? What is a sarcoma?

Lukas Nystrom, MD: Yeah, sarcoma is a generic term for a malignancy that happens of mesenchymal origin. So, it's oftentimes in the muscles, or the way I describe it, is the connective tissue, the fat, muscle, nerves, bone, that type of tissue, not our solid organs, not our blood. It's in these other tissues. And so soft tissue sarcoma specifically is a subset of that very generic category that happens in the muscle, or the fatty tissue separate from the bone.

Dale Shepard, MD, PhD: And so, give us an idea, how common are these? So, if you think about lung cancer, 250,000 cases a year. What about soft tissue sarcoma?

Lukas Nystrom, MD: So rare, just so you know, it's so rare. The number I quote is 12,000 to 13,000 a year in the United States. And so, it's a really small percentage of the overall cancer volume.

Dale Shepard, MD, PhD: And when you take that number and you consider that you said there's lots and lots of tissues involved, about how many subtypes do you normally describe to people?

Lukas Nystrom, MD: It depends on how fine you want to get with that subtype, and I think we're gaining more and more as we get molecular information, but I tell people about 50 to 100 depending on how you want to divide it up.

Dale Shepard, MD, PhD: Yeah. So, you take 12,000 to 13,000, split it up 50 to 100 different ways, and that's a lot of different diseases to treat.

Lukas Nystrom, MD: Now you're talking. That's right. It's extremely, extremely rare.

Dale Shepard, MD, PhD: All right. So, when we think about treatment of soft tissue sarcomas here at Cleveland Clinic, give us an idea of somebody shows up, what's an experience for a patient when they show up in your office?

Lukas Nystrom, MD: Yeah, there's a number of different ways that folks can show up. One is just with a mass of concern, something that they've noticed, or they've brought to the attention of one of their physicians, and they've been referred to us without a definitive diagnosis. So that's one way, and we start from the very beginning. That's certainly a common way that we see people. The other way is that people come in with a known diagnosis, and they see us either for a second opinion or for that first opinion, but very well established. And so most oftentimes, we find these by people detect a mass, something that's not supposed to be there. They may monitor on their own or with a local physician for a period of time, but it has some features that might be concerning. So those would be, it's growing in size as one of the big ones. It seems to be bigger than a golf ball. It's deep to the skin or deep to the fascia. It's within the muscle. Those are all things that are generally concerning.

And then we really make the diagnosis by getting an MRI scan and ultimately, a biopsy. And so, I'll meet them anywhere along that way, along that path, but wherever that happens, it doesn't really matter. We take it from there.

Dale Shepard, MD, PhD: Now, one thing you didn't mention was pain. Are sarcomas typically painful? Tell us a little bit about that.

Lukas Nystrom, MD: Yeah, typically painless. So, this is a common misconception I think a lot of people have, that is because the mass didn't hurt, it's not something that they should be concerned about. And unfortunately, that's not a reliable indicator. Most of these are painless. And so, you really have to be concerned about any mass that develops.

Dale Shepard, MD, PhD: When we think about patients that come through our clinics, what you never like to see are these oops procedures and things that somebody may have gotten into something they shouldn't have. You mentioned some characteristics of things that might be sarcomas, but those could be other things as well, and benign tumors and things. So, give us a little guidance. I mean, there's a lot of different people that listen in. Who should see a sarcoma specialist. If there's a mass like this, if there's a concern, who should say, "Well, I can go see a general surgeon. Maybe I should see a sarcoma person?"

Lukas Nystrom, MD: This is such a common issue. You hit the nail on the head there. And I don't mean to imply that all masses should come and see a sarcoma specialist. Of course, that's not feasible. However, those things, those red flag things that we mentioned, so masses that are growing, masses that are painless, firm, seem to be deep to the fascia, bigger than the size of a golf ball, those should be looked at a little bit further. So, I think a physician who's seeing a fair number of masses can reliably tell what a subcutaneous lipoma is for the most part, or a benign fatty tissue right underneath the skin.

But anything that happens outside of that very, very obvious presentation, I think should be looked at further. And the first step is getting the MRI or getting a CT scan if they can't get an MRI, so we have a little bit better idea of what we're dealing with. From that standpoint, I mean, after that, we can determine a little bit better are we really dealing with a lipoma or something a little bit more concerning? And if we don't know what we're dealing with, that person should get referred to somebody who deals with this kind of thing regularly.

Dale Shepard, MD, PhD: You mentioned biopsy. What kind of guidance could you provide? Certainly, anybody there's a concern, we're happy to see them, happy to take care of things, but if someone's going to embark on a biopsy, what recommendations would you make? Needles or excisions.

Lukas Nystrom, MD: The vast majority of soft tissue sarcomas can be diagnosed by a needle biopsy. It's a very, very good and reliable way to do it. And the biggest, I mean, this is a whole topic. We could do a whole hour-long talk on biopsy techniques and principles, but the biggest thing I think, is that it should be done by somebody who understands what the resection is going to look like. Because in an ideal world, that biopsy track would be number one, contaminating minimal tissue on the way in from the skin to the tumor. And then secondly, it in an ideal world would be able to be excised with part of the resection. So, you want to put that biopsy track very carefully oriented with relation to where you're doing your work.

Dale Shepard, MD, PhD: And I guess with that is a consideration, I guess ideal state, again, if there's concern, would you rather do the biopsy or would you rather have someone come in with a diagnosis?

Lukas Nystrom, MD: If there's a concern, I would 100 percent rather be the one that did the biopsy. Yeah, absolutely.

Dale Shepard, MD, PhD: So, somebody comes into the clinic, they have a diagnosis. What are the next steps? How do we approach here at Cleveland Clinic multidisciplinary care and get other disciplines involved?

Lukas Nystrom, MD: Yeah, yeah, absolutely. Definitely, this is a multidisciplinary diagnosis. At the bare minimum, we're involving the orthopedic oncologist or the surgical oncologist and radiation oncology in the initial evaluations. And depending on other risk factors like the size of the tumor, the grade of the tumor, and whether or not there's metastatic disease, the medical oncology team is involved to have discussions around chemotherapy. And so, if we have a diagnosis coming in that we already know about, we like to get all of these teams on board right away from the very get-go. If not, oftentimes they'll see one of the surgeon physicians first to get all of the biopsy and staging information squared away and then come back to discuss the multidisciplinary aspect of it the next time.

Dale Shepard, MD, PhD: So, being a surgeon, what are some of the important points to consider when thinking about soft tissue sarcomas? What are some of the factors that you weigh in?

Lukas Nystrom, MD: So, I think the big thing here is limb-salvage surgery or not. So as an orthopedic oncologist, I'm again mostly dealing with this in the limbs. And when can the limb safely be saved and when is it may be better that the limb isn't saved? Because at the end of the day, by far, the most important thing is that that tumor has to get out. This is a disease that if there's a chance at a cure, it's primarily surgical in combination with other modalities like radiation. But a wide surgical resection is felt to be probably the most important factor. In terms of that, it's negative margins. So, try to do everything you can to get a negative margin. If you can do that and save the limb, perfect; that's the ideal situation. But if you can't, those are tough conversations, but sometimes the limb has to go in order to have a chance of getting rid of the disease.

Dale Shepard, MD, PhD: And we think about challenges and misconceptions about sarcomas, thinking about things in the limbs. I think oftentimes people immediately think amputation. But has that changed over time? Are there changes in our abilities to treat radiation or chemo or surgical techniques that have changed that landscape?

Lukas Nystrom, MD: Yeah, I think it certainly has. And you're right, if you wind the clock back 40 years, this is primarily a disease treated with amputation. A couple things have changed our ability to do that. I think number one, MRI scans. It's not new technology anymore, but they're getting better all the time, and that is our roadmap to getting these things out safely and knowing whether it's safe to even try to get them out. So, the ability to see the tumor in three dimensions like we can with an MRI clearly makes that job a lot easier.

I think while I'm not a radiation expert, radiation techniques have certainly improved. And we now know that if we're going to be getting really close to the tumor in one spot or another to save a nerve, save a blood vessel, save bone, the addition of radiation therapy either before or after the surgery makes it safe to do that. And so, we can get close in one area and stay wide in other areas and still have a chance at saving the limb. So, you're right. I think a misconception is that a lot of people think that this is a straightaway amputation. It's not. We save the limb the majority of times, but there are still times when it's not able to be done. But if we can, we will, and I think that's the best for everybody if it's possible.

Dale Shepard, MD, PhD: And I guess just to continue along with from surgical technique, a lot of these podcasts we end up talking about minimally invasive surgeries, minimizing the extent of surgery and things like that. How has that in any way been taken into practice with sarcomas? I mean, you mentioned wide margins, the importance of making sure that you get rid of all the disease, things like that. Where are we in orthopedics standpoint from that? Because it seems like maybe a little bit different than a lot of other disciplines.

Lukas Nystrom, MD: Yeah, you're right. A lot of other, well, not only cancer disciplines, but especially orthopedic disciplines have gone the way of trying to minimize invasiveness. Unfortunately, that's not, in the limb sarcoma world, that is not a term that we frequently use. So, this is a pretty maximally invasive surgery. Of course, we do it as minimally as possible, but again, the goal at the end of the day is to get that entire tumor out. The only way to do that is to see everything that you need to see. And so, these are typically pretty big surgeries.

Dale Shepard, MD, PhD: I guess that's the reason I ask the question because it seems that if someone's trying to push for a minimally invasive procedure, then maybe someone needs to reconsider that because that's not really in play here.

Lukas Nystrom, MD: It's not. It's not exactly right. It usually just takes a little education on the part of the patient to understand why it's not because, yeah, this is far from the world of minimally invasive techniques.

Dale Shepard, MD, PhD: You mentioned before about changes in things like MRIs and imaging and things like that. How have newer imaging modalities helped out things like MRI PET? Are there other upcoming imaging things that look like they would be promising?

Lukas Nystrom, MD: Well, it seems like the magnet on MRIs is always getting stronger. So, I think that's one thing that has been helpful. I don't know if we can gain a whole lot more there. I think we're seeing the tumor pretty well at this point. Things like PET scans, either PET CT or PET fused with MRI do show a lot of promise in terms of identifying tumor activity, and also perhaps in the world of staging. I think that we're learning more and more all the time about how we can best assess the extent of their disease at presentation and also when we follow them for surveillance. So, I think that there's a lot there.

I think right now where we primarily are using those kinds of techniques is if we're wondering where the best spot to biopsy is or is there a recurrence of a tumor in an area that's been previously operated or has some other thing that's going to make interpretation of a standard modality difficult. So, you're right, we got a lot of tools, but we've obtained these tools faster than we have learned how to use them in some ways. And so, we're figuring that out right now.

Dale Shepard, MD, PhD: Yeah, makes sense. When we talk about the surgery itself, has there been a lot of change from a technique standpoint? Is there anything that looks promising? Is there anything that can improve either from a reconstruction standpoint or taking the tumor out itself? Anything that can make that surgery a little less morbid, regain function a little faster? Anything like that?

Lukas Nystrom, MD: Yeah, there's a lot of different things that we're looking at here at Cleveland Clinic, but also that other investigators around the country are doing. And I'd say if we're talking about what we're doing here, it's not so many changes to the surgery, but the change that we're delivering, the whole episode of care, if you want to use that term. And that primarily involves how we are using radiation. So, radiation we know has a lot of side effects of its own. It kills the tumor cells, which we love, but it also creates nasty effects on the normal tissue that we're leaving behind. And primarily that involves creating scar tissue and fibrosis is the term that we use for that scar tissue. And what that ultimately does is it impact the function of the joint above or below or both. And so, we're trying to find ways that we can minimize those side effects of radiation while maintaining the same effective local control.

And so that's different ways that we've done that has been to shorten the course of radiation and deliver different doses and fractions, but also use different techniques of radiation. Brachytherapy is something that we do a fair bit of here, and that really confines the side effects of radiation to one specific spot. So, when we put those two things together, I think it ultimately has been something we've been very happy with in terms of how it impacts the outcome in the end in terms of function of the limb without compromising the cancer outcome.

Dale Shepard, MD, PhD: And I guess just to interrupt really quickly, you mentioned brachytherapy. Just briefly, what is that for people might not be familiar?

Lukas Nystrom, MD: So, brachytherapy involves a very focused delivery of radiation through tubes placed in the wound at the time of the surgery. And so rather than the other form of radiation that we use, which is called external beam radiation, where we're shooting x-rays at a target in a very detailed way, but it's not nearly as focused as what you can do when you put the actual tube that the radiation source is going to go in right where you want it. And so that doesn't lend itself to all sarcomas, but many it does, and it's very effective when we can. So, we're excited about that.

Dale Shepard, MD, PhD: So, have a diagnosis. You've had surgery. You're talking about surgical technique things, radiation incorporated. How about post-op care? Are there things we're doing here at Cleveland Clinic or is it more of a trend in terms of improving post-op recovery? Things like managing wounds, or mobilization, or pain control, things like that?

Lukas Nystrom, MD: Yeah. Well, you've touched on probably one of my biggest passions, which is wound complications after sarcoma surgeries, soft tissue sarcoma surgery. It's a huge problem. I think the best study that we've seen in our literature shows that the prevalence of wound healing complications is 35 percent in patients who've had pre-op radiation. And if you're looking at just the legs, that number goes up to 45 percent. So, it's a massive problem. And unfortunately, we have to tell people up front that this is what we're going to do. We're going to do pre-op radiation. We're going to have surgery. We know that it's going to have X, Y, and Z benefits. On the downside, there's a flip of a coin whether you're going to have some kind of a wound issue or not. And you see it, and it happens, and it's terrible, and it's just miserable to watch somebody suffer with that.

And so that's an area that I'm interested in. And one of the things that we're doing is we have a study ongoing about how can we identify patients who might have a wound-healing problem, and what can we do upfront to mitigate those problems and hopefully, avoid them. So that's the ultimate goal, and we're working hard on that here.

Dale Shepard, MD, PhD: So, you are certainly a work in progress, but any early thoughts on some of those factors?

Lukas Nystrom, MD: The biggest factor is the use of pre-op radiation. So, if you have radiation before surgery, which there's a lot of good reasons to do that, and we still do it more often than not, that is going to be your biggest risk factor for having a wound-healing complication. But other things, diabetes, use of certain medications like steroids, having some immunocompromised state, and obesity, can all do it. And I didn't mention the big one, of course, smoking. So, all of these things can really impact it as well. But that radiation is certainly the biggest player.

Dale Shepard, MD, PhD: When you think about how we're going to make patients' lives better with soft tissue sarcomas in the next five or 10 years, what's going to be the big break?

Lukas Nystrom, MD: I think it's going to be something along the lines of how we can be sure that we've got the margin that we want. I'm speaking strictly from a surgical standpoint. I think if we're talking about sarcoma as a whole, I think it's going to be finding some way to systemically attack the disease and prevent it from spreading and killing it and then taking it out. But there's a lot of work being done right now in terms of margins and how can we identify during the time of surgery, how do we get that tumor out safely? And so, I think that's going to be the big surgical break. And then I think folks like yourself are going to tell us how we ultimately cure the disease.

Dale Shepard, MD, PhD: Very good. Well, you've provided some great insights today.

Lukas Nystrom, MD: Thank you. I'm happy to do it. Thanks for inviting me.

Dale Shepard, MD, PhD: Thank you. To make a direct online referral to our Taussig Cancer Institute, complete our online cancer patient referral form by visiting clevelandclinic.org/cancerpatientreferrals. You'll receive confirmation once the appointment is scheduled.

This concludes this episode of Cancer Advances. You'll find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget, you can access real time updates from Cleveland Clinic's Cancer Center experts on our Consult QD website, at consultqd.clevelandclinic.org/cancer.

Thank you for listening. Please join us again soon.

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