Radiation Therapy for Sarcoma

[Music] Welcome to the ON target podcast. On this podcast, we discuss the ins and outs of radiation therapy. We talk with doctors and patients about what to expect during radiation treatment. Each episode will be a unique perspective of different aspects of radiation oncology and radiation treatment. For more information or to learn more about radiation treatment, please visit our website rtanswers.org. Hello everyone. Welcome to the ON target podcast. Today we're going to learn about how radiation therapy is used to treat sarcomas. I'm Dr. Malcolm Metis, a radiation oncologist at Rutgers Cancer Institute in New Jersey. Today I'm joined by Dr. Varun Choudry, who is a radiation oncologist at Roswell Park Cancer Center in Buffalo, New York. To get us started, Dr. Choudry, many people know the word cancer, but not everyone may understand the word sarcoma. What is a sarcoma? Yeah, first of all, I just wanted to thank you for giving me the opportunity to speak with you today. To dive into it, sarcomas are a rare group of cancers that arise from the zankamal tissues. The zankamal tissues, if we go back to medical school, they have different cellular organization and embryologic development is different compared to epithelial cells, which is or glandular tissues, which is where many of the cancers that we typically see. But what we need to know as radiation oncologist is that they arise from the body's connective or supporting tissues such as muscle, fat, bone, or blood vessels. So sarcomas are all, it's mainly a rare type of malignancy, they can occur anywhere in the body. And so that is what can make it challenging from sort of a care coordination standpoint and from a management standpoint, because they're not confined to a specific anatomical occasion. Okay, sounds good. And in what situations is radiation used to treat sarcomas? Yeah, so you know, in general, radiation therapy is used in patients with larger, high grade sarcomas, although there can be a lot of variation by specific histological subtypes. And that's something I've even seen since I finished residency. But I think it's sort of considering, it's kind of important sometimes to think about the historical perspective. And when we consider the treatment of sarcomas, and when I see patients for the first time, I'll review the history that, you know, going back into the 1970s, nearly half or many patients needed an amputation. And that was because there was a local excision for high grade aggressive sarcomas, ultimately did not lead to acceptable oncologic outcomes. And even despite that, many patients developed metastatic disease. And, you know, this was a similar trend that we saw in patients with breast cancer when we moved from radical mastectomy to breast-conserving surgery, followed by radiation. And ultimately through well-designed studies, clinical trials, we found that we could do a less aggressive surgery that not only resulted in a good oncologic outcome, but also allowed us to preserve function for the patients. And that's essentially an equally important goal is not just the oncologic outcome, but to result in a good function for the patient. The other situations where we yarn sort of, well, we can certainly discuss the, you know, various situations when sarcoma is used as either a preoperative or postoperative for the definitive treatment of, in addition to surgery. But we also can use radiation therapy to relieve symptoms. So palliative radiation therapy is often used. And then another emerging role that we can also discuss later is in utilizing your stereotactic body radiation or radio surgery, which can be extremely effective to either treat small areas of unresectable disease or metastatic disease, so long as, for example. And why do we use radiation in the curative management of sarcomas? Why not just take it out, search a claim? Yeah, this is a great question. And anytime I meet with a patient, I try to put myself in the patients' shoes and say that, you know, if I were a patient, I would, that would seem to make sense. Why don't we just remove the tumor and then, you know, figure out about adjuvant therapies later. And essentially, this is done through, you know, sarcomas are not particularly common diseases, so it takes a lot of time and effort to develop studies to sort of establish paradigms of care. But historically, as I mentioned, surgery alone led to unacceptable high rates of local recurrence. And what we found was that by adding postoperative radiation therapy, we're able to reduce those rates rather substantially. And then, you know, through further research, found that doing preoperative radiation therapy allowed for equivalent rates of cancer control, but as well as better function in the long term for the patient. Okay, sounds good. So it sounds like radiation does a lot for improving quality of life for patients with sarcomas. Now, sometimes as you mentioned, the radiation is given before surgery. Sometimes it's given after surgery. What are the pros and cons of each approach? And how do the orthopedic and radiation oncologist decide which approach to take? Yes, and this is a great question and often a subject of discussion during our multi-disciplinary conferences. And really, the sequencing of radiation and surgery, and even the integration of chemotherapy, it really depends on, you know, considering the biology of the tumor and the particular needs of the patient. So, you know, in general, preoperative radiation therapy is preferred. And that is because, you know, just from like a radiobiologic standpoint, tumors are better oxygenated before surgery when they're in their, you know, quote, natural environments and quote, so they tend to be more sensitive to radiation therapy. And what we have found is that while preoperative radiation therapy does lead to a slightly higher risk of short-term wound healing complications, these are ultimately reversible and through, you know, very, you know, good care in the hospital, these patients can overcome these. But in the long run, preoperative radiation therapy is associated with less side effects, such as stiffness, swelling. And this is because of the lower dose and also the smaller field size. But that's sort of the general paradigm. But in some situations, postoperative radiation therapy might make sense. For example, sometimes it's not known that the patient has a sarcoma or it perhaps it's believed thought to be a smaller low grade tumor than when the final pathology comes. It actually turns out to be something different. The other thing that's important with sarcoma is that there are sort of site-specific considerations. And for example, if you have a sarcoma in the groin or scrotum, there is a preoperative radiation therapy is associated with a much higher risk of wound healing complications. And in that situation, it's not an extremity. So the joint stiffness is not perhaps more of a secondary consideration. And sometimes, you know, even beyond that medical comorbidities of the patient, if there's any concerns about long-term wound healing. And so, I think that these decisions are not black and white and depend on, you know, the tumor, the specific anatomic and considerations of it. But also the patient, what are their goals and functional status and what risks they're willing to accept? Sounds good. So it sounds like there's a lot of factors that the oncologists need to consider when making up their mind on the approach. When do you think a patient should see a radiation oncologist for the first time after a sarcoma diagnosis? And what happens at that initial consultation with radiation oncology? Yeah. In practice, different institutions will manage these situations differently. For example, in some clinics and some institutions, you may have a multidisciplinary clinic where all new sarcoma patients are seen together. In other situations, we have a referrals. Our initial patients are often seen by either a medical oncologist or surgeon because a surgeon is required to get the diagnosis and then discussed in a tumor board. And the tumor board is often composed of similar to in other disease sites, surgeons, radiation oncologists, medical oncologists, and pathologists to come up with the best paradigm of treatment. And during these discussions, we will, you know, certainly not every patient will need radiation therapy. But if it seems that it would be part of the overall paradigm, I think it is helpful to meet with the patient early in their diagnosis, even for example, if they're going to be taking chemotherapy first. And it helps, I think, not only I think there's a help sort of for us to give time to plan the treatment, but also for the patient to have a good understanding at the onset of what to expect. And, you know, during the visit, I would certainly review like the diagnosis, imaging, and pathology and detail. And kind of as I mentioned earlier, I think one of the major questions, if I was sitting in the patient's shoes is why not to do surgery first and then do radiation and other treatments later. But I think I try to develop the paradigm with the patient that our goal is sort of not in a short term, trying to remove the cancer or shrink it, but actually trying to give the patient the best long term well-being, not only being free from cancer, but also preserving their function to the extent possible. Along with that, I think it's helpful to also set the expectations of treatment. You know, for example, when we treat certain types of cancer such as lymphomas, we might see a dramatic response during treatment. But most sarcomas will not shrink dramatically with radiation. And we often sometimes can even see some increase in size, particularly as we combine immunotherapy or pseudo progression. With the exception, there's one exception to that, which is mixtoid liposarcoma. But I think what I try to do is emphasize with the patient that the goal of the treatment is really not necessarily to reduce the size of the tumor, but ultimately give the patient the best long-term well-being. And if the patient has decided to undergo radiation therapy after that initial consultation, how does the treatment planning process work? Yeah, so once a patient decides to have treatment, you know, we certainly coordinate, you know, among the overall care the team with the surgeon and medical oncologist to make sure that, you know, we are sequencing the chemotherapy and surgery appropriately. And it's really important to kind of keep them in the loop. But once the decision is made to move forward with radiation therapy, the next step will be similar to what we do for all other types of, you know, other situations where we give radiation therapy is to do a CT simulation. And we will try to place the position, you know, position the patient in the same way that they would be treated every day. The difference, the challenge here is that our CT scanners and linear accelerators are often designed to treat either tumors of the head and neck or thorax or chest abdomen and pelvis. So it does require you to become a little bit creative with the positioning to make sure that the patient is comfortable with this for their daily treatment, but also make sure that we can develop appropriate beam angles to make sure that we can treat the patients tumor appropriately, for example, without having to have a beam go through the body, for example. And we'll also utilize any other pre-treatment imaging, MRI and PET scan to make sure that we are able to make sure we can delineate the tumor properly. And then ultimately work with our physics and dosimetry team to come up with a personalized radiation plan, which will, and one, you know, generally try to start treatment within a few days or a week after the simulation. And how many radiation treatments are usually recommended for soft tissues are coma is either before or after surgery? So we typically give about 50 gray of radiation therapy, which in the preoperative setting, which is about 25 daily treatments over five weeks. In the post operative setting, we typically give higher doses between 60 to 66 gray. Certainly, there's a lot of exceptions to this, you know, for example, patients with mixed fluid liposarcoma, there's data to reduce the dose. Ewing sarcoma, certainly a different type of has a different paradigm. And also, we have to consider like the anatomical considerations where the tumor is. And for example, tumors that are in the brain, we have to restack, have different organs at risk compared to in the extremity, et cetera. But ultimately, the overall goal is the same. We want to give the optimal dose while protecting normal tissues to the extent possible. And what are the logistics of daily treatment and what will patients experience while they're coming in for radiation? Generally, the main side effects are, you know, as with many courses of fractionated radiation therapy, we'll come on in the second to third week of treatment, peak towards the end and then improve within a few weeks later. The most common type of side effect that we see are skin reactions, like a sunburn. And certainly we walk patients through skin care both before, during, and even after treatment. Beyond that, like side effects would depend on where the, what is the nearby organs at risk? So for example, sarcoma and the head and neck may have similar side effects, such as mecositis to head and neck radiation. If you have a abdomen and pelvis sarcoma, patients can experience nausea and diarrhea. So, you know, certainly our job is focused on supportive care, you know, managing patients, skin toxicities and other toxicities to make sure that patients are, you know, tolerating the treatment well. One thing that I will add that's sort of a newer thing that I've noticed in this era where we're using more immunotherapy, that we are seeing a lot more swelling and changes in tumor anatomy. And so even being willing to, you know, being, it's much more common for now to have to, for example, do another CT simulation so that we have to, because of changes in the tumor size. So this is kind of a constant process where we're monitoring, not only the patient side effects, but certainly their anatomical considerations of the tumor to make sure that we're treating the patient appropriately. And are there other types of long-term side effects that patients can develop after radiation? So yeah, long-term side effects generally develop in the months to years after treatment. And the most common is like fibrosis or scarring of the tissues, patients can develop swelling or edema and join stiffness. The other, you know, important consideration is for tumors that wrap circumferentially around the bone, there is a risk of fracture because it's often difficult to avoid the bone completely during radiation. Now certainly we can use modern radiation techniques, whether it IMRT or V-MAD to really sculpt the dose around the bone. But I think equally importantly is I will communicate the treatment plan to the surgeon. And if we're unable to avoid a segment of the bone, making sure that the surgeon is aware that the patient could be at risk of fracture and that perhaps consider a prophylactic stabilization. How important do you think it is for patients to come back for follow-up with their radiation oncologist after completing treatment? Yeah, so this is a very much a team effort and very much, I think, certainly can be institution dependent. And often what we will do to sort of minimize the burden of care is coordinate care between the surgeon, the medical oncologist and the radiation oncologist. So for patients that have surgery, they often will be maintained with follow-up with their surgeon. And for example, when I see patients that have metastatic disease where they have us, when we're providing radio surgery, whether it's to the local area or to the lung, then often then I will take over the follow-up care as the radiation oncologist often best understands kind of the expected changes. So we really try to make this a multidisciplinary discussion to really minimize sort of the number of visits and even do virtual visits when possible. So I think ultimately it comes down to coordination with the entire care team. Sounds good. And most of what we've talked about today is management of soft tissue sarcomas and adults, but there's many types of sarcomas. What other types of sarcomas is radiation commonly involved in treating? Yeah, so certainly in the pediatric population, you know, you wing sarcoma and rabdomis sarcoma where radiation therapy is a key component of treatment. There's another unique group which is often grouped with soft tissue sarcomas called Desmoid tumors or aggressive fibromatosis. They're sort of technically not malignant, but they can be locally aggressive and cause morbidity and radiation therapy works extremely well for these. And then we're seeing less and less of a role these days in retroperitoneal sarcomas, but I think it still does have a place in selected cases. And where I'm seeing a major evolution is in patients that have small local recurrences and we're doing radio surgery for small areas of disease. Even in diseases like osteosarcoma, for example, that are thought to be less sensitive to radiation. I found that we can make a meaningful difference and improve patients' outcomes using, you know, higher doses of focused radiation therapy. Sounds good. And finally, what new innovations do you think are coming in the treatment of sarcomas? Yeah, so from, you know, from a radiation standpoint, I think we're seeing more hypofractionated and ultra hypofractionated regimens, which means shorter courses delivered in shorter treatment times. And there are studies that are showing that we can provide comparable local control and toxicity, but being more convenient for patients. Certainly for these, I work closely with the surgical team because these can play into wound healing and also there, from a logistical standpoint, the operative schedule, so making sure that everybody is coordinated. As I mentioned a few times, I think radio surgery is really a growing area in the treatment of sarcoma. And in some situations, even for example, in retroparatineal sarcomas where we don't necessarily see a benefit of radiation therapy treating large areas to lower doses, but I think where we can sort of salvage patients or help patients is really when there is a small local recurrence and you can give highly focused treatment. I also think that there's a lot of innovations in systemic therapies, which are being coordinated with radiation therapy. So agents like Pizzappanib, which can be often utilized with radiation, there's a lot more targeted therapies like NTRK inhibitors or Nirogassistat, which is a Gamma secretace inhibitor for Desmoid tumors. And sometimes we even use these concurrently and we get outcomes that we think, you know, much better than perhaps what I've been expected. And then the big area, which I also had alluded to earlier, is Pembrolyzamab, which is being used in certain soft tissue sarcomas subtypes, and again can be used concurrently with radiation. And ultimately, What I would say is that all of these innovations are sort of allowing us to provide more personalized care, not only sort of considering the biology of the tumor, but considering sort of the overall needs and well-being of the patient. So with that, we will conclude this episode about use of radiation therapy for sarcomas. If you want to learn more about how radiation is used to treat cancer, I'd recommend going online to RTanswers.com. I'd like to say a big thank you to Varun Chowdry from Roswell Park Cancer Center for speaking with me today, and the American Society for Radiation Oncology for Organizing this Podcast Series. I'm Malcolm Matis from Rutgers, and I hope you'll check out more of Astros on target podcast episodes in the future. Thank you for listening to this episode of the On target podcast. This episode has been brought to you by the American Society of Radiation Oncology and Our Care Partners. For more information about topics discussed in this episode, please visit our website RTanswers.org. [Music]