Exploring Stereotactic Body Radiation Therapy (SBRT) for Recurrent Osteosarcoma

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 Shepherd, a Medical Oncologist, Director of International Programs for the Cancer Institute at Cleveland Clinic, and Co-Director of the Cleveland Clinic Sarcoma Program. Today I'm happy to be joined by doctors Erin Murphy and Jenna Kocsis. Erin is the Director of Pediatric Radiation Oncology, and Jenna is a Resident Physician in the Department of Radiation Oncology. Dr. Murphy was previously here on this podcast to discuss stereotactic radiosurgery for adolescent brain and spine tumors, and that episode is still available. They're here today to discuss SBRT for recurrent osteosarcoma. So welcome.

Jenna Kocsis, MD: Thank you.

Erin Murphy, MD: Thank you.

Dale Shepard, MD, PhD: So, give us a little bit of an idea what you do here. So Erin, we'll start with you.

Erin Murphy, MD: Typically, for osteosarcoma, radiation therapy is not even mentioned as an upfront tool, and so we have now been meeting a lot of folks who have metastatic osteosarcoma, and we're actually able to help them. What we can do is get in really high doses of radiation, very focused doses of radiation. We're just limited by the normal tissues. And so we've been able to help children, adolescent young adults with osteosarcoma who come with metastatic disease that's not resectable, and we have this awesome tool, this SBRT, that delivers this focused high dose radiation and can almost ablate the tumor right where it's sitting.

Dale Shepard, MD, PhD: And I know you've been here and talked about SBRT in the past and so a lot of different people might be listening in. So stereotactic body radiation therapy. Jenna, maybe give us an idea of what is that?

Jenna Kocsis, MD: Yes, good question. How I like to describe it is it's high dose focused radiation intended to deliver a high dose of radiation per fraction or per treatment essentially to ablate the target, ablate the tissue. It's better than conventional radiation where they give a lower dose of radiation per fraction, or better in this case, when they give a lower dose of radiation per fraction because you're giving the high dose to kill the tumor and then you also have the ability to shape and conform the radiation so that you can better spare the adjacent normal tissues which, like Dr. Murphy said, is very important in our pediatric population to consider.

Dale Shepard, MD, PhD: You mentioned before that we don't typically think about radiation upfront when we think about managing osteosarcoma, and I guess the first question a lot of people as they heard that would say, why not?

Erin Murphy, MD: So oftentimes when folks present with very large tumors, so with SBRT we are often limited in size, so a size cutoff is typically a max diameter of five centimeters or less. So if someone presents with a very large primary site, we really rely on chemotherapy and surgery as the first tools, so that's where we really come into play more if they have metastatic disease.

Dale Shepard, MD, PhD: All right, so you guys have sort of said, you've already given us an idea of why it might be an advantage to use SBRT, about the limitations up front. Give us a little bit of an idea of what did you do to study this in terms of what we've done in the past?

Jenna Kocsis, MD: Yeah, so Dr. Mervier has done a lot of work on SBRT for the pediatric sarcoma population in general, and then we actually got hooked up with a great organization called the MIB Factor, and it's a nonprofit organization for osteosarcoma patients and their families, and we wanted to kind of share our experience utilizing SBRT in this population and see how we can advance the treatments for these patients moving forward.

So we looked at our database of SBRT in the pediatric and adolescent young adult population, looked through how many patients we had with osteosarcoma. We found over the last around eight years that we had 24 patients and then around 70 lesions that were actually treated with this. So then we retrospectively reviewed those cases, seeing where was the tumor, how big was the tumor, the dose that was given, did they get concurrent treatment? And then looked at the toxicity and our local control outcomes.

Dale Shepard, MD, PhD: And give us an idea from, I guess we'll start with the benefits, the efficacy. What are some of the primary findings?

Erin Murphy, MD: And just one more thing to point out. So even though the numbers don't sound small, we actually probably have published the largest series of looking at just osteosarcoma SBRT. We have some more SBRT sarcoma data, but it mostly groups all these tumors together, and they're quite a heterogeneous group of tumors, so that's why we wanted to pull out specifically osteosarcoma, which is known to be more radio resistant than other around blue cell sarcomas. And so far local control outcomes are still early, so we have data about one to two years out, and we're showing good local control about up to 80 to 90% of the time. And that's if you get enough of the SBRT dose safely.

Dale Shepard, MD, PhD: You talked about failure rates. So again, people may not be familiar with the radiation oncology world and how you think about failure. Give us an idea, how do you define what failure is and what are the categories you think about?

Jenna Kocsis, MD: Yeah, so patients are often getting follow-up imaging every three months, most likely about up to a few years after treatment. And then we're looking at on the MRI, on the PET scans, is the tumor growing? Is it becoming more PET-avid? And then in this case we kind of looked at a dosimetric failure rate, whereas if they fail, we overlaid those new imaging with the failure with our radiation plan, and we could see did the failure, did the tumor growth come back within our high dose volume? Did it come out on the margin as a marginal failure or was it outside of our field of radiation? And that can kind of better guide us, was the dose inadequate and the tumor just grew back right in the field? Was it right on the margin where we should have had a bigger planning margin around the tumor and things like that to help us guide and improve the treatment in the future.

Dale Shepard, MD, PhD: And I guess based on those sort of three categories, what did you learn about osteosarcomas and how we currently treat those in the spine with SBRT?

Jenna Kocsis, MD: Yeah, there was actually an even spread between the infield marginal and out-of-field failures in the whole database. A predictor of failure was actually radiation to the spine itself, so those patients did have a higher failure rate than others, and likely that's because the spinal cord is right there and so it's hard to give that same ablative dose. You can get that ablative dose to the tumor, but it's hard to get a margin on it with that spinal cord. So a lot of the failures, there are seven failures in the spine area, and a lot of them were in the epidural space. A lot of them had symptoms and then a lot of them were marginal or out of field just because we clearly couldn't get the dose there.

Dale Shepard, MD, PhD: And I guess you mentioned the epidural involvement. Can you expand on that a little bit in terms of the importance of the involvement of the-

Erin Murphy, MD: Yeah, so that's when tumor is invading into the canal where the space where the spinal cord and the cerebral spinal fluid sits, and obviously folks who have epidural disease and if that progresses are more likely to have and develop neurologic symptoms, so it's a pretty challenging area to fail within, and so it really makes us think, although we're conservative up front, we want to cause no harm for folks who have true oligo metastatic disease with osteosarcoma, you really might need to air on being more aggressive to really get after this tumor because if it fails, it's much harder to treat and much harder to salvage.

Dale Shepard, MD, PhD: And so, I guess the question would be if you have these tumors that have developed along the spine, epidural involvement, where is the decision process between surgery and radiation?

Erin Murphy, MD: Yeah, well, we're at an institution where we have a really great multidisciplinary spine tumor group, and we've really set the precedent for doing minimally invasive surgery followed by radio surgery, so certainly in a patient who presents with a component of epidural disease, you might want to do that approach where you do surgery first, kind of debulk the tumor at least away from the spinal cord, which allows more space for us to safely deliver our radio surgery, so that's kind of one way to think about it. We also certainly would loop in our medical oncology colleagues as chemotherapy can respond in these folks as well, so if you want to try to reduce or shrink the tumor before doing radio surgery, that's kind of one thing to consider.

Dale Shepard, MD, PhD: And I guess something that people listening in might also wonder about would be proton therapy.

Erin Murphy, MD: So with proton therapy, it's a newer tool in the setting of SBRT and radio surgery, so not all centers with protons are even able to do that, but with a tumor right up against the spinal cord, it's actually something where protons may be less safe because there's a lot of unknowns at the edge of the beam of radiation, so if there's a tumor right up against the spinal cord, there's just still a lot of unknowns in how to use proton therapy for something like that.

Dale Shepard, MD, PhD: When we think about other techniques, other radiation techniques, how does this data lead you to think about how you might make those changes? You mentioned before about maybe volume you're treating or the amount of radiation you're given to particular areas. What do you think are some of the big takeaways?

Jenna Kocsis, MD: Yeah, good question. So like I said before, I think it's interesting to consider allowing a little bit higher dose of the spinal cord, increasing your margins on your volumes that you're treating, but nowadays too where you can do brachytherapy, where you're giving a different way of radiation, you can do grid radiation therapy, which Dr. Murphy is doing a lot of now, so kind of different ways to increase the dose to the treated area if you want to touch more on those.

Erin Murphy, MD: And yeah, one thing, thank you for that segue. One thing to mention about grid radiotherapy-

Dale Shepard, MD, PhD: Grid, which we'd love to hear about grid.

Erin Murphy, MD: It's awesome. And so what I think about this tool is a safe way to increase your biologic dose in larger tumors. So just as I said, size cutoff is kind of a barrier for SBRT. When you have larger tumors, you can do this grid or lattice therapy where you're literally dropping two centimeters spheres of very high dose radiation in a single fraction, so anywhere between 16 to 20 gray, right within the tumor, and you're creating peaks and valleys of dose, high dose and low dose, within that tumor. And you can give it either as an upfront boost or at the end of fractionated therapy, and you might also be revving up the patient's own immune system to kind of help fight that tumor as well with using this grid therapy.

And one other thing to say is we often, when we're doing SBRT, we utilize high definition imaging, and we usually are just targeting what we see, but for tumors, even across the SBRT sarcoma literature, you see that tumors that have soft tissue component do not do as well, meaning local control is not as good. And it might be that we actually need to be thoughtful about treating where did that tumor initially sit as far as a soft tissue component rather than treating just where the tumor is at now, which just goes back to our classic understanding of how we look after a pediatric cancer diagnoses and think about radiation local control. You're usually targeting the pre-chemo, pre-surgical volume to get after a new kind of residual microscopic disease.

Dale Shepard, MD, PhD: When we think about treating pediatric patients, adolescent patients, that was kind of the patient population you looked at, what are some of the unique challenges from treatment itself, even survivorship issues, what makes this population a little bit different?

Jenna Kocsis, MD: So a lot of these patients, especially if they presented with local disease up front, a lot of them have amputations or different physical limitations. So kind of down the road, they're more hesitant about treatment going forward and that effect on their quality of life just because of the things they've gone through in the past, which is always interesting to think about and get the patient's perspective. Depending on the age, you do have to think about anesthesia when you're talking about radiation. These patients are often more in their teenage years, so it can be a little bit easier on us, but for younger patients, we do often have to consider anesthesia.

But then like you said, survivorship, how does the treatments in the past affect how the patient will choose in the future? And do they have the, as a teenager, can they choose the treatments that they want and how does the parent influence their decision as well? So it's a unique population that is helpful to learn from.

Dale Shepard, MD, PhD: I'm guessing that being, considering it's SBRT and limited fractions, that probably helps with the sort of how palatable it is to patients.

Jenna Kocsis, MD: They don't have to skip school or extracurriculars.

Erin Murphy, MD: Yeah, there's many advantages, I believe, to using these high-dose-focused radiation tools for our younger patients. Certainly the blessing is so far we've seen minimal impact on quality of life. They tolerate these treatments really well as long as we're thoughtful about the concurrent therapies that they're getting because the treatments are delivered in just one to five sessions. As we said, it's less break from school and those kinds of things, less break from chemotherapy, which is a big deal. Typically, if someone has to have a surgical resection, they need to pause chemotherapy for enough time for healing, and we don't really need to do that.

And because this is such focused radiation, there's more dose away from the normal tissues, which is important for those who are growing and developing. Obviously we don't have a lot of late effects data yet from doing SBRT for these younger patients. It's one of the reasons why I know folks are not doing it because there's just a lot of unknowns, and that's why I feel like this is one of the reasons why we try to get this research out there to show folks that hey, this is a really good tool, and it's really relatively well tolerated for folks. So ideally, we look after so many patients who are from out of town, ideally we can help form guidelines and really transform the way this tool is being offered to these younger patients.

Dale Shepard, MD, PhD: And I guess you kind of alluded to it in terms of how widely available is SBRT for children with these sorts of tumors?

Erin Murphy, MD: So, it's available, right? We can do it in adults at most cancer centers. So it's more just comes down to a comfort level. So we're actually starting an international task force of sarcoma SBRT, where in folks that I know who are looking after many patients like we are, we're going to gather that data and try to ask more questions and really develop tools that we can help others use these tools for their own patients.

Dale Shepard, MD, PhD: Well, it sounds like you're doing important work, getting some good outcomes. Appreciate you coming to share some insights.

Erin Murphy, MD: Thanks for having us.

Jenna Kocsis, MD: Thank you.

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