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Zachary D. Burke, MD, an orthopedic oncologist specializing in pediatric sarcomas, joins the Cancer Advances Podcast to talk about limb sparing surgical techniques for pediatric sarcoma. Listen as Dr. Burke explains the unique challenges posed by pediatric cases, the advancements being made in the field, and research efforts aimed at improving sarcoma treatments.

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Surgical Insight: Limb Sparing Techniques for Pediatric Sarcoma Patients

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 I and Cleveland Clinic sarcoma programs. Today, I'm happy to be joined by Dr. Zach Burke, an orthopedic oncologist in the sarcoma program here at Cleveland Clinic. He's here today to talk to us about limb sparing surgical techniques for pediatric sarcomas. So welcome, Zach.

Zachary D. Burke, MD: Yeah, thanks, Dr. Shepard. Thanks for having me. It's a pleasure to be here.

Dale Shepard, MD, PHD: So maybe start off, give us a little idea, what's your role here at Cleveland Clinic? What do you do?

Zachary D. Burke, MD: Yeah, I have sort of two hats that I wear here. I am a surgeon in the sarcoma program, so I'm an orthopedic surgeon by training with a specialty in musculoskeletal oncology, also called orthopedic oncology. So clinically, I take care of patients with tumors of the bones and connective tissues. That includes benign tumors, cancerous tumors, soft tissues, bones, kids to adults. On the other side of the spectrum, I also have a lab here, and developed some of my time to researching both the treatment of cancers of the bones and soft tissues, and also the complications that arise from that and how we can better take care of folks who have these diseases.

Dale Shepard, MD, PHD: All right. And maybe we'll touch on some of that here in a little bit. But the primary topic we were going to talk about was limb sparing surgical techniques in pediatric cancers. So, give us an overview, just a big picture, what exactly is a limb sparing surgical procedure?

Zachary D. Burke, MD: So, it's helpful to kind of define what the common problems are and maybe take a brief step back into where we've been historically and where we are now. So typically, in a pediatric patient, when you're talking about limb salvage, sarcoma is the cancer that we're talking about. So, sarcomas are a broad group of cancers, and there's many different types. The common ones that we deal with, particularly in children, are osteosarcoma and Ewing sarcoma. And those are both cancers that arise in the bone in relatively young patients typically. So historically, 40, 50 years ago, when kids or really any patients were diagnosed with a sarcoma in the limbs, the treatment was amputation.

We didn't have good chemotherapies, like you're involved with good treatments to treat them systemically, and we didn't have good imaging to look at that tumor in a detailed anatomic sense to understand what we could do with it. So historically, amputation was the answer, and somewhere, in the last 30 to 40 years, we had significant advancements in chemotherapy delivery, to save these patients' lives, in imaging in terms of CT and MRI to specifically define these tumors in the anatomical structures in relation to the tumors. And so, that was the advent of limb salvage. And the idea there is you take the tumor out, and you preserve the limb, and you preserve the function of the limb.

Dale Shepard, MD, PHD: So, we think about that shift, and it's kind of incredible we've had such a shift. What percentage of patients do you think still undergo amputation? Because I have got to tell you, I think that's the first thing people think of still. And so, despite the changes, everyone still thinks of amputation. So, what percentage do you think still have amputation?

Zachary D. Burke, MD: Yeah, absolutely. So, to illustrate how far we've come in a short period of time, most sort of literature that looks at this and clinically in my practice and the practices that I've been around, 80 to 90 percent of pediatric patients are candidates for limb salvage surgery. So, it's quite high.

Dale Shepard, MD, PHD: So that's impressive. So, what are some of the things that make pediatric cases unique to adult cases? So, you see both. What are some of the unique features of pediatric cases?

Zachary D. Burke, MD: Yeah, absolutely. So regardless of the limb salvage potential, pediatric cases are always a challenge, because there are unique social situations and there's a unique challenge to a child with cancer. And so, that always presents a challenge. And the social support network and the challenges of dealing with childhood cancer are sort of inherent in that. Beyond the general aspect of things, in terms of limb salvage, there are some unique aspects to pediatric cases, and one is that kids are still growing. So that's a primary challenge when we address limb salvages. How do you save a limb and account for growth changes that may result from that? So, kids grow through their bones, through their physis, their growth plates, and in some resections, you may be able to not involve those, but in many resections for a tumor, you have to compromise the growth of the limb. And so, an area of pediatric limb salvage surgery that is constantly evolving and has continued to grow is, how do we account for differences in leg length that result from limb salvage?

A couple of other areas that are important to consider when you're talking about pediatric limb salvage are the activity level of kids and the expected duration of whatever you do. So, both of those things lead to a need for more durability in what we do for pediatric limb salvage. So, if you're replacing a part of a bone that's taken out in a 70- or 80-year-old with cancer, their activity level may be relatively low, and they may not need that implant for another 30 years. The hope is that, with our pediatric limb salvage patients, that we can retain for them a high level of activity and that they're going to be using this implant or this reconstruction for 50, 60, 70 years down the road. And so, that, you can imagine, presents its own unique challenges.

Dale Shepard, MD, PHD: And I guess, as we've moved toward these procedures, what sort of work has been going on to maximize mobility and things like reconstructive techniques or surgical techniques? What has made, you mentioned, imaging and chemo, in terms of keeping people alive and being able to determine, but what kind of advances have been made in terms of surgical techniques and reconstructive techniques to make that possible?

Zachary D. Burke, MD: Yeah, so there are quite a few, and frankly, it's an actively evolving field. Pediatric limb salvage is not a one size fits all field, and there is a need. And the norm is creative solutions to difficult problems. So, where we've been, historically, there are two sorts of means, broadly speaking, by which you can reconstruct a limb that's had a big segment of bone and muscle and other tissues taken out. And those would be, broadly speaking, metal or an endoprosthesis, which is a very large joint replacement and bone replacement, and bulk donor bone. So, things like allograft, allograft, that maybe just bone, osteoarticular allograft, that includes joint surface, they can include tendons and soft tissue attachments. So those are the two primary means, historically, where we've been with limb salvage surgery, and those still have use. In particular, endoprosthesis are still very commonly used, and those have advanced tremendously over the last couple of decades.

More recently, there's been quite a bit of interest in what we sort of broadly call biologic techniques. And the idea there is that there's nothing quite as durable as native bone, so a kid's bone healing to bone, that is living bone and viable bone. And so, biologic techniques can sort of run a spectrum of reconstructive techniques. So, one that's been in use for a long time, and I think gaining popularity, is a free vascularized fibula. And what that means is we actually take, in collaboration with our plastic surgery colleagues, typically, a piece of the fibula bone from the child's leg, and it can be the opposite leg, it can be the same leg. Or if we're doing a reconstruction in the arm, obviously, it can be leg to arm. And that's removed with its blood supply, its blood vessel, and it's plugged in to a bone defect in the reconstruction area. And the blood vessels are sewn back together.

So that is a viable living piece of bone, and that's something that's been around for a while, but is gaining popularity, particularly in the pediatric limb salvage circles, as a very durable means of reconstructing bone defects. Some other sort of more biologic techniques are things like a bone transport technique. That is really sort of on the cutting edge and not widely used, but that basically means you use the healing potential of bones, which is particularly robust in children, to slowly heal that segment of bone in over time. And there's a very technical way that this is done, and it requires sort of fixation of that area and immobilization for a long period of time. But you use the body's regenerative potential to grow that area over time, and that's also potentially a very durable technique.

Dale Shepard, MD, PHD: And does that help out with things like the things you mentioned earlier about growth of bones over time, things like that?

Zachary D. Burke, MD: It can. So, the growth issue is not resolved, in and of itself, by either of those techniques. So, you can account for growth in different ways. There is even a version of the fibula technique that I described, where the fibula is transported and plugged in for being viable bone, where there's a technique called physeal transfer, where you actually take the fibula with the top growth plate, and you can put it in, oftentimes, you might see it in the shoulder. And you can actually get growth from the growth plate that was in the fibula in the shoulder. None of these solutions are perfect. So, there's a tradeoff for all of these. When you take a big piece of bone out of a kid's leg, they do have repercussions and, potentially, complications from that.

So that's a big thing that, I think, is critical when you're talking to a family and a child about limb salvage surgery is you have to really get to know a kid and a family. You have to bring your expertise and your team's expertise to bear and say, "Here's what you can expect with these different techniques. Here's the upside, but here's the downside." And complications and returns to the operating room are a reality, particularly when you have patients that you're following for 10, 20, 30 years after reconstruction. There is an expectation that there are going to be bumps in the road and that you have to overcome those.

Dale Shepard, MD, PHD: You mentioned involving the team. Tell us a little bit about how this is kind of a multidisciplinary effort.

Zachary D. Burke, MD: Yeah, absolutely. So, sarcoma surgery is a team sport, through and through, and something that I really love about the field, it sort of attracts people who are intellectually humble and interested in bringing all minds together to take care of a patient. So as pertains to pediatric limb salvage, you routinely have people like yourself in the sarcoma, hematology, oncology setting, who are administering chemotherapy and systemic treatments for patients with bone sarcoma. You have somebody like me or my partners here, who does limb salvage surgery. Radiation oncologists may or may not be in play with a pediatric limb salvage patient. There are times we do use radiation. In your standard bone sarcoma treatment, you may not use it, but they are certainly a part of the multidisciplinary team for pediatric patients. And then, you have things like plastic surgeons, pediatric surgeons. There are a number of experts that we have involved in these cases, and the list can grow quite long. And here, at the clinic, we're fortunate to have real experts, in all of those areas, who are eager and willing to help out with these complex cases.

Dale Shepard, MD, PHD: And I guess, related to that, I'm guessing most patients, most kids that get these tumors come to areas that specialize in this. How does somebody pick a place to go?

Zachary D. Burke, MD: Yeah, no, it's a great question. And I think getting these kids to the right places at the right times is an important part of this process. So just to sort of start at the beginning of this question, there is good data to suggest that adults and kids who have sarcomas have better outcomes in a number of ways when they're treated at centers who are used to taking care of sarcomas. And that doesn't mean that's the only place they get care, but that means that that's the place that manages their care overall. So ideally, that happens from the moment there's a suspicion on initial workup for a sarcoma, and not after a biopsy and maybe an index procedure, where somebody didn't know there was a sarcoma and it turned out that there was a sarcoma. So ideally, once there's a suspicion, once a clinician does an initial workup and there's a suspicion for sarcoma, that's when the call goes out to a sarcoma center, like we have here at the Cleveland Clinic.

And from there, we are always happy to talk with folks and see if it makes sense to bring kids over versus managing somewhere else. But if there's a true concern for sarcoma, we like to be involved from the beginning, from the biopsy to prove that there is a sarcoma to chemotherapy, with folks like yourself, and then, to surgery and beyond. And the process of getting to a center like this, I think, can be daunting for somebody out in the community, who maybe doesn't have a tie to a center that has sarcoma specialists. There are not many sarcoma centers in the country. So, I think the first step is to recognize that there is a potential for cancer and to pump the brakes a little bit and reach out to a center, so that they can help guide the next steps.

Dale Shepard, MD, PHD: And then, of course, there's also the components that you've kind of touched on before, like social help and physical therapy and all those other services as well. So that helps.

Zachary D. Burke, MD: Absolutely, absolutely.

Dale Shepard, MD, PHD: So, let's shift gears a little bit. Tell us a little bit about the kinds of research you're involved in and how that might relate to some of these surgeries.

Zachary D. Burke, MD: Yeah, so like I said, I spend about half my time in the Lerner Research Institute, working in a lab that looks into a couple different things related to pediatric sarcoma and limb salvage. So one is, how can we better treat the sarcoma itself? And the other is, how do we deal with these complications that arise down the line? So, we've gotten better, in the last 30 to 40 years, in preserving limbs and increasing the chance of long-term survival in patients who have sarcoma. But really, compared to 30 or 40 years ago, we haven't made much advance past that spot. So, we dramatically made a shift with chemotherapy. We dramatically made a shift with limb salvage. And since then, the shifts have been incremental. So, the questions that are looming large in this field are, how do we make the complications less and the function higher when we do perform limb salvage on a young kid? And how do we make sure that the tumor goes away and stays away?

And if it spreads, how do we treat that? And how do we increase lifespan for patients who have metastatic disease or locally recurrent disease? And so, in my lab, one of the things we do is, whenever we do surgery on a sarcoma patient, we talk to them about potentially donating some of that tissue, after it's out of the body, for study in the lab. And so, there's different ways we look at that tumor. We look sort of in terms of a deep dive, in terms of the genetics and epigenetics and transcriptomics and the things that make up the tumor on a cellular and molecular level. And we look at what therapies might work, that haven't been used before for sarcomas, and see if there is a next treatment laying out there somewhere that may help these patients. And then, the other sort of pillar of my research lab, I look at one of the dreaded complications in these patients, which is infection.

So, when prosthesis or piece of donor bone gets infected, it is a significant challenge to treat that without taking it out. And you can imagine that, if you take out a child's a majority of their femur or even their whole femur, and that gets infected and you can't retain that prosthesis, that presents significant challenge. And that's a limb threatening situation. So, it's frustrating for people in this line of work to get a patient, and particularly for patients, it's frustrating, to get a patient through their cancer, get them through limb salvage surgery, only to have an infection be the cause of amputation years down the line. So, I do some translational research, outcomes research, clinical research, that aims to mitigate and better treat infections when they arise in these patients. And the hope is that we bring our arsenal of weapons in our toolbox for infection from antibiotics, that are 20, 30, 40, 50 years old, into the modern molecular area or rather molecular era and immune era of medicine and treatment.

Dale Shepard, MD, PHD: So, infections certainly are a big problem. In terms of other complications, what are the other ones that are probably looming largest at risk? Is it a local recurrence? Is it wound healing? Poor functional ability? What would be the next thing as well that needs fixed to make a big impact?

Zachary D. Burke, MD: Yeah, it's a great question, and I alluded to it a little bit earlier. So, one of the big problems that is not oncological, but again, gets back to the durability of whatever we do for a kid to save their leg is a failure of the implant in some way. And so, that may be failure of the implant itself, like the metal or the moving pieces, or if it's bone, a fracture of the bone, or it may be loosening of that. And so, loosening, meaning where the implant meets the bone or where the graft meets the patient's host bone, if that junction isn't strong, that will fail eventually. And that would necessitate a revision. And the more revisions you have, meaning repeat surgeries, exchange of parts, the higher there is a risk of infection, the function starts to go down a little bit. And so, we try to minimize that.

One big area is what we call aseptic loosening, where the implant that goes in loosens and comes out. And so, biological fixation, like I talked about earlier, is one way to address that, where you have bone healing to bone. Another area that has become increasingly used, and this is typically in a little bit older kid, is by getting bone to grow into an implant, so that you have bone that is ingrown and on grown into an implant. And that provides a really durable long-term solution. And so, there's new implant design techniques that are aimed at inducing bone to grow into metal. And so, one is called a compress osteointegration technique that uses a physical property of bone to load across bone and induce growth into the implant. And that's shown good long-term results. And the other is really fitting an implant in, quite tightly, into the bone called a press fit to induce growth between the implant and the bone.

And those have been areas of active research and active advancement in pediatric limb salvage surgery. An important advancement with reference to the growth issue in pediatric limb salvage is growing implants. So, their implants, and they've been around for a few decades now, that can essentially telescope and expand and grow as the patient would physiologically grow. And so, historically, that was done in a very sort of simple mechanical way, where you would insert a new piece or you would open the patient up in the operating room, and you would ratchet and extend the prosthesis.

But more recently, there has been expanding use of what are called non-invasive growing implants, where an implant is implanted, that has that potential and has a magnetic coil. And so, the patient can come back to the office or even at home, be put into this small portable magnetic coil, and it slowly increases the length of the implant by the order of millimeters or up to a centimeter or so at a time. And that can allow for growth of that implant with the child, with the patient, and minimize the leg length differences that are expected to result down the line.

Dale Shepard, MD, PHD: Impressive. Early on, you said that one of the things that led to the ability to spare patients from amputations included imaging. Are there any exciting updates, in terms of upcoming imaging, that might continue to shift toward the ability to do limb salvage?

Zachary D. Burke, MD: Yeah, I think there are a few areas that are relevant to touch on here. And so, one is using advanced imaging to design and utilize patient-specific custom implants and instrumentation. So, imaging has come far enough. And things like 3D printing, based off of imaging, have allowed us, in conjunction with some of the companies who make these implants, to design tools and implants that are based off of CT scans and MRI scans of the patient's anatomy and the patient's tumor. And so, these are really coming into play in the orthopedic oncology field the last five to 10 years.

And really, I think, orthopedics oncology is leading this charge in a way, where we are able to work with these companies to design tools that allow us to use custom cutting jigs, where we can really, in a precise manner, put this cutting jig on a patient's anatomy, where it fits like a glove, and then, cut out an area of tumor with a degree of precision that we previously wouldn't have been able to use and potentially, spare the need for a bigger reconstruction, spare function, and then, put in a custom implant that is designed specifically for that patient.

And that is a big advancement in the field. Additionally, with imaging, there are emerging technologies where the hope is that we can use imaging intraoperatively. So that's not only for navigation of our instruments that we use to cut our instruments, we use to reconstruct, but also, potentially, using markers and probes and antibodies that can tag tumor cells or tag nerves and fluorescently give off light and guide us to have a more precise resection in ways that we previously wouldn't, where you use your eyes and your hands to determine tumor tissue from not tumor tissue or nerve tissue from not nerve tissue. And can we do that in a better way by actually having these structures be tagged with something and light up in the operating room for precision resection?

Dale Shepard, MD, PHD: Wow, field's come a long way.

Zachary D. Burke, MD: Field's come a long way.

Dale Shepard, MD, PHD: And it's doing some great work, and you've given us some great insights today.

Zachary D. Burke, MD: And I'm excited to see where it goes in the next 30 to 40 years.

Dale Shepard, MD, PHD: Fantastic. We'll watch it together. All right. Thanks for being with us.

Zachary D. Burke, MD: Yep. No problem. Thank you for having me.

Dale Shepard, MD, PHD: 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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