Precision Healing: Stereotactic Radio Surgery for Adolescent Brain and Spine Tumors

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 here at Cleveland Clinic, directing the Taussig Early Cancer Therapeutics program and co-director of the Cleveland Clinic Sarcoma program. Today I'm very happy to be joined by Dr. Erin Murphy, Director of Pediatric Radiation Oncology here at Cleveland Clinic. She's here today to discuss stereotactic radio surgery for adolescent and young adult brain and spine tumors. So, welcome Erin.

Erin Murphy, MD: Thanks, Dale. I'm happy that we finally were able to find a time to join up together.

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

Erin Murphy, MD: So, as you just said, I'm a radiation oncologist. I do specialize in looking after adults and children with brain tumors, and I also look after any child that might need radiation treatments.

Dale Shepard, MD, PhD: Excellent. Specifically, we're going to talk about stereotactic radio surgery in this younger population. Give us an idea what exactly, we have a lot of different people listening in. What exactly is stereotactic radio surgery?

Erin Murphy, MD: Yeah, it's a great question. So, this kind of treatment, so we call it SRS, we call it SBRT, sometimes. When we talk about SRS or SBRT, what they essentially mean, is using high definition imaging to do targeting and delivering focused high dose radiation therapy, using multiple intersecting beams, which can give a high dose over one to five treatments. The intent of these treatments is to almost be an ablative tool, like a locally ablative tool. That's absolutely non-invasive.

Dale Shepard, MD, PhD: So, I guess just from a terminology standpoint, because it seems like there's an important thing. SRS, SBRT, are there differences? Or...

Erin Murphy, MD: Yeah, great question. So, there's differences that basically comes down to what area in the body you're aiming at. So, we typically think of stereotactic radio surgery or SRS, as being used when we're targeting lesions in both the brain and the spine. And then SBRT is stereotactic body radiation therapy, and that's term is used whenever we're doing these high dose focused radiation treatments, outside the brain or spine.

Dale Shepard, MD, PhD: And then I guess again, just so everyone knows what's- ... Sometimes people come in and they will mention modalities, like cyber knife or gamma knife or things like that. These are more machine based.

Erin Murphy, MD: You're right. So, we get those questions all the time. They're just different tools to deliver these treatments. So, the gamma knife radio surgery machine is actually used only to treat tumors in the head. And so, we actually have an awesome specialized gamma knife center, where we have two gamma knives running and we teach a lot of other physicians on how to use the gamma knife radio surgery machine. Other tools like cyber knife and linear accelerators, can be used to deliver radio surgery or SBRT throughout the body.

Dale Shepard, MD, PhD: So, thanks for clarifying, because I think that people get a little confused with just all the terminology. So, when we think about treating adolescents, think about young adults, what are some of the challenges that come into treating those patients with either brain or spine tumors?

Erin Murphy, MD: Yeah. So, we have a ton of data in the literature showing outcomes, prospective studies, using these tools, but it's mostly in the adult population. And so, one of my passions is to develop programs and get the word out there about using radio surgery and SBRT for our younger patients. What I find when I go give talks nationally or internationally, is that there's a big lack of comfort level, as you know these populations. So these patients are younger, so they're still growing and developing. And so, there's some concern about what's going to be the impact on the normal tissues for these patients, who are still growing and developing. And it's a really important question. And the way I actually think about it, is that when we use these tools, because it delivers such a high dose focused radiation treatment, with a really rapid dose fall off, these tools actually result in less dose to those normal structures. And so, they're really, I think, important to consider when there's an appropriate target for these younger patients.

Dale Shepard, MD, PhD: Is it the higher energy that causes people more concern or what is the primary objection, for a lack of better way to put it, for doing these techniques?

Erin Murphy, MD: It's a good way to describe the question. So it's really the higher dose, so it's the higher dose that you deliver because a typical radiation course, as you know, is delivered every day Monday through Friday, over about five to six weeks of treatment. That's when you're giving the same low dose to the same area every day. It's divided up like that, so that the normal tissues can heal or recover in between each of those doses. When you're doing these radio surgery techniques, you're giving all that dose in over just one to five sessions. So, as you can imagine, that dose is not forgiving and it's not forgiving to the normal tissues. That's why you have to be so precise and accurate how you're aiming. And so, the concern is what will these high dose treatments do for those tissues that are growing and developing? One of the questions I wanted to understand early on, was in doing sarcoma SBRTs together. We look after a lot of patients who have metastatic sarcoma.

As you know, sarcomas tend to be less sensitive to radiation treatments, and so you have to give high doses of radiation to really try to control a tumor. And using these advanced techniques where you can get in a high biologic effective dose, may even have more benefit for these tumors that are more resistant. So, a large population that I look after are these younger patients who have sarcoma that's metastasized to lung to bone, et cetera. One of the early questions was, if you're treating a weight-bearing extremity, like lower extremities or upper extremities, if you're treating a metastasis, is there a higher rate of fracture risk because you're giving that dose in such a high dose manner? And so we looked at our series and looking at patients who have been followed for up to two years now, I've not seen any increased risk in fracture in using these techniques for metastases and weight-bearing bones. But there's still a lot of questions that need to be asked around that same kind of question.

Dale Shepard, MD, PhD: When we think about treating these sort of, if we call it a spine tumor, what are the differences that you encounter if you're treating a tumor that may be say, in the spinal canal compared to the vertebrae, compared to a paraspinal mass?

Erin Murphy, MD: Yeah, that's a great question. So, whenever we're doing spine radio surgery, we always get an updated high definition MRI of the site that we're treating because with these techniques, you're able to carve and shape the dose away from more critical structures. And so, the main structure that we're trying to avoid is the spinal cord or the spine nerve roots. And so, if something is within the cord itself, you have to be very thoughtful and you may not even use radio surgery as a technique because you might want to be gentler on that normal structure. However, if you're treating something in the vertebral body or even something with some epidural disease, we can still get in these aggressive doses safely. When we look at, I know this wasn't the question, but it kind of falls into that. When we look at questions about pattern of failure for spine tumors, where we see more failures are for those patients who have large paraspinal or soft tissue extension, or for those who have epidural disease, where you're being a little bit more conservative about that dose, right up against the spinal cord.

Dale Shepard, MD, PhD: One question, I guess, you probably get frequently, would be why do SRS, why do SBRT, compared to proton therapy?

Erin Murphy, MD: Oh, yeah, I do get that question a lot. So, I think of them as very different modalities. So where I see the huge benefit for protons, as we all know, is less low dose exposure to the normal tissues. Proton technology, just like photon technology, is continuing to be improved and developed. And so to date, SBRT using proton therapy is not a common standard practice. So it's just a different machine. So, I think of proton therapy all the time when I'm looking after younger patients, but not when I'm trying to do focus high dose radiosurgery techniques.

Dale Shepard, MD, PhD: What other cases where you might opt for proton, I guess, what cases would you think about proton instead of doing SBRT or SRS?

Erin Murphy, MD: So, when I think about sending someone for protons, it's more for upfront treating like a definitive primary tumor. So, it's certainly a standard of care to consider for kids who have primary brain tumors, or if you're treating someone with a Hodgkin's lymphoma, they have an anterior mediastinal mass, you can avoid the exit dose posteriorly into the heart, into the lungs, into the spinal cord, et cetera. Or if you're treating like a primary sarcoma of the pelvis, that's unresectable, oftentimes you can get in really conformal high dose proton therapy. If you're sending them to a place that has intensity modulated proton therapy, then you can still get the conformality in the high dose region, and the conformality in keeping that low dose out of more sensitive structures as well.

Dale Shepard, MD, PhD: What kind of situation, I guess, I'm having you compare SBRT to a couple of things here. When would you choose to do conventional radiation instead? What kind of situations or locations would you say, I just need to give traditional radiation?

Erin Murphy, MD: So, a clear situation that comes up is if I'm looking after a patient who has lung metastasis from say, Ewing's sarcoma, and they have two focal lesions. Well, for me, it all depends on the safety of those normal tissues. So, if there's a lung nodule, right in the middle of the lung parenchyma, far away from the mediastinum, from the trachea, from the proximal bronchial tubes, from the esophagus, then I know it's safe to give in that high dose treatment in just one to five sessions. Whereas if tumors are located close to those critical structures, you can't get in that full dose safely. And that's when I might do more what I call a hypo-fractionated course or deliver intensity modulated radiation therapy, over two to three weeks.

Dale Shepard, MD, PhD: So if we're looking at, I guess, kind of coming back to the young adults and adolescents, I can only imagine the impact from a psychosocial standpoint of a protracted course of radiation, compared to shorter doses and treatment intervals.

Erin Murphy, MD: So, you're getting at one of the things I like to share when I'm talking about using these techniques for these younger patients, is that because they're delivered in just one to five sessions, there's certainly less impact on daily routine and recovery. They continue going to school during these treatments. If kids are young that they need anesthesia, there's less anesthesia needs. And when we get these treatments done in one to five sessions, it wears on these patients less, so the recovery is quicker. So, several reasons why it's a really good tool to consider.

Dale Shepard, MD, PhD: And I guess because these by nature are younger patients, what are the considerations from a survivorship standpoint?

Erin Murphy, MD: Unfortunately, a lot of these tools that I've been using are for patients with metastatic disease, which unfortunately, as you know, don't have as long survivorship as we would like to see. But I think, when I talk to our survivorship groups, if patients have received these focused radiation tools, there's really less dose to those normal structures. So, we're really in those survivorship clinics, we're really thinking about the radiation exposure to critical structures. And if the SBRT and SRS is done in a safe way, we really don't expect as much late toxicity, as we would from a conventional radiation course that might spread out some of that lower dose.

Dale Shepard, MD, PhD: And of course, understanding the maybe more limited life expectancy of some of these patients. But do we have any information on secondary cancers? And sometimes people ask me, I think they ask me because they ask the radiation oncologist and they're looking for another opinion, but sometimes secondary cancers are a concern. What do we know about that?

Erin Murphy, MD: Yeah. And so, we don't have great data demonstrating this, but we expect because you're delivering it in a blade of dose to a very focused area, that there may be less risk for developing a secondary cancer. So we're not spreading out that dose over a wider area of normal tissue. And so, really the risk on secondary cancer should be less.

Dale Shepard, MD, PhD: I mean, you've done a great job putting together a program that treats these younger patients. Somebody might be listening in. What recommendations do you have in terms of... what does a good program look like? You need a multidisciplinary team. What does a good program look like?

Erin Murphy, MD: Yeah, so that's really important. So, I feel really blessed because I've got colleagues that are already world's experts in delivering lung SBRT, liver SBRT, pancreas SBRT, spine radiosurgery, right. And with those physician experts, we also have teams of physicists, dosimetrists, and therapists, that have already been doing these techniques for a long period of time. So, we're able to deliver these high dose focused radiation treatments in a safe way, with a lot of rich experience, and I've really been able to take that experience from the adult population and translate it to our younger patients. And that's why I already have a comfort level in offering these tools because I know I'm already supported by a great team. You touched upon the multidisciplinary care too. And so, I think that this is where it's critical to have a team together, looking after these patients to really figure out when is the ideal timing to utilize these tools in between their course of chemotherapy. What medications? Chemotherapy targeted agents? Immunotherapy? Are safe, to be delivered during these high dose focused treatments. So, sometimes you might want to pause something where you might get a more significant reaction, just to be a little bit more thoughtful when you're delivering the treatments. The blessing is though, because the treatments are delivered in just one to five treatments, there's not a big chemotherapy delay, if you even need to hold it at all.

Dale Shepard, MD, PhD: So, as you sort of look through where we are in the field right now, what needs attention next? What's the gap? Where do we go from here?

Erin Murphy, MD: I think because it's smaller numbers, rare tumors, it's going to be hard to do a lot of prospective studies. We do have some prospective data that's been emerging in the setting of sarcoma SBRT, over the last two to three years, where we're showing that we have good efficacy. Meaning our ability to stop these tumors from growing at two years, is on the order of 85% of the time. Also, those studies, we've been able to take a nice look at toxicity and really understand and minimize toxicity. But again, they're not huge numbers. And so, actually one of the things I'm working on right now, is setting up a large sarcoma SBRT consortium. Where I've reached out to a lot of other institutions that have larger experiences as well of doing sarcoma SBRT, and really combining data, so that we can look at how outcomes are, to try to understand who's the ideal patient population to benefit from these tools. To understand toxicity, so that we can try to avoid or reduce toxicity in the future, and to really try to improve quality of delivery of these high dose focused tools.

Dale Shepard, MD, PhD: What would you describe as an ideal patient that should come to a specialized center? Who can be sort of treated in a community? Who should come to a specialized center?

Erin Murphy, MD: Yeah. And I think that's a great question. We do treat a lot of patients who are from out of town because either there's a lack of comfort level locally in delivering these tools for younger patients, or they just don't have access to them. And fortunately, since it's done in just one week, it's not a lot of time away from home. One thing that's interesting about these younger patients, in general, is that actually there's an additional indication to treat them. So, when we think about doing these focused high dose radio surgery tools in the adult population, we really consider it in the oligo metastatic setting or in limited metastases. Actually very different in the pediatric population. So, many of our standard pediatric diagnoses, whether it's Wilms tumor, rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma, when patients present with metastatic disease, we have always been aggressive with all of their initially involved metastatic sites. And so, now we can use these tools to really deliver treatment to two or three metastasis at a time, just get it done in one week. And a lot of the data emerging, which is pretty awesome, is showing that if you consolidate all sites of initially involved metastatic disease, these younger patients, there's a survival benefit. So, that's why we're really aggressive in using these tools and we can treat many areas in the body, and it seems like it's been safe and really, really well tolerated.

Dale Shepard, MD, PhD: That's fantastic. It's a challenging set of tumors, and you're doing a great job with a program that's helping out, and I appreciate your insights and being with us today.

Erin Murphy, MD: Thanks for your awesome questions.

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