SBRT for Oligometastatic Disease

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 Sarcoma Programs. Today I'm happy to be joined by Dr. Balagamwala, a radiation oncologist here at Cleveland Clinic. He's here today to talk to us about stereotactic body radiation therapy or SBRT for oligometastatic disease. So welcome, Ehsan.

Ehsan Balagamwala, MD: Thank you, Dale. It's an honor to be here. I'm very excited to talk about this exciting space of SBRT and oligometastatic disease.

Dale Shepard, MD, PhD: Excellent. So maybe just to start, tell me a little bit about your role here at Cleveland Clinic? What do you do? What do you see?

Ehsan Balagamwala, MD: Absolutely. So I've been at the clinic for over 10 years, starting here as a medical student and doing residency here as well, and now I'm faculty. My primary role is at the intersection of gastrointestinal tumors, spine tumors, as well as SBRT and delivering specialized radiation to patients with GI and spine tumors.

Dale Shepard, MD, PhD: Excellent. Just so everyone knows what we're talking about and we have a diverse group of people perhaps listening in. Let's define a couple of terms. What is SBRT and what do you mean by oligometastatic?

Ehsan Balagamwala, MD: Absolutely. So these are two very important terms. So I'll start with SBRT because it's a radiation technique and we'll delve deeper into all of the metastasis, as well. So SBRT is a form of highly advanced, precise radiotherapy technique to target tumors in a very short period of time. It was initially developed as a non-invasive method of delivering radiation for brain metastasis patients, most commonly known as Gamma Knife radiosurgery. And as the technology has advanced over the last 20 to 30 years, we have been able to deliver ablative radiation to tumors across the disease spectrum, all the way from head neck tumors, to lung tumors, to liver tumors, and now boney tumors.

It used to be that, with conventional radiation, we would see patients over the course of 20 to 30 treatments, over the course of 5 to 6 weeks. But with SBRT, we can deliver ablative doses of radiation and as little as one dose of radiation, up to 5 treatments. In terms of oligometastases, actually, that was initially described almost 100 years ago and it was called as such, but more recently it was described in the '90s and labeled oligometastases, it's really a spectrum of disease in patients. As systemic therapy has advanced, we're seeing more and more patients with oligometastases, where it's defined, typically less than 5 extra lesions outside of the primary tumor and that definition is very gray.

Some studies define it as less than 3 tumor metastases, and up to even 10 metastases, as some of the more recent studies evaluating treatments in these patients. And the whole cornerstone of all of the metastases, is there is a thought that patients with limited metastases are potentially curable. As you're the director of the sarcoma program, you know this very well, sarcoma is one of those diseases in which, all of the metastases were initially described in and renal cell is another paradigm. And in GI tumors, colorectal metastases to the liver, has been one of those great triumphs in medicine as well, where up to 30% of patients with limited liver metastases can have a long-term survival or potentially, a cure. So it's a very exciting space and we're pushing the boundaries of what is considered oligometastases.

Dale Shepard, MD, PhD: So let's run with that. How are we pushing the boundaries? What are the things that we're leading the charge to make better?

Ehsan Balagamwala, MD: So with all oligometastases, some of the early trials included only one, say lung metastases from sarcoma or renal cell. And the most recent trials run out of Canada, that trial, actually looked at patients with 1 to 5 metastases and there was a smaller phase II, randomized trial, and that actually showed a survival benefit in those patients. And that was including primary diseases across the spectrum, including prostate cancers, liver cancers, kidney cancers, lung cancer. And so the current trials that are enrolling, are not only looking at lesions that are more than 5, so 4 to 10 lesions and seeing if we can alter the natural history of disease with advancing systemic therapies, including immunotherapy, as well.

Dale Shepard, MD, PhD: So, I guess we've been having a discussion here, about the number of tumors. What about size? How does size play into the ability to get it SBRT?

Ehsan Balagamwala, MD: Yeah. So it used to be, size was an important thing, when we first were learning about SBRT, that size was a big criteria. It was like, "Hey, if the tumor is over 3 or over 5 centimeters, SPRT is not possible." But with advancing radiation delivery and targeting, we're learning that tumors up to 7 or 8 centimeters can also be effectively ablated in a very non-invasive manner. And that requires certainly, a lot of expertise and it's not only clinical expertise. And the important point to make here, is that when we deliver SBRT, certainly a multidisciplinary team is important, surgeons, medical oncologists, radiation oncologists, and expertise in those departments.

But also, something that happens on the background of radiation oncology and they're extremely crucial, so we have PC level physicists that help with the SBRT program, dedicated machines that actually have dedicated therapists that help with the delivery of the SBRT. And so it's really a multidisciplinary team effort, even within radiation oncology to deliver such precise latent doses because it is higher risk. And so having that excellent team is crucial in delivering this treatment very safely and very effectively.

Dale Shepard, MD, PhD: So what sort of tumors have just become standard of care?

Ehsan Balagamwala, MD: So SBRT over the years, as I said, it started in the brain as non-evasive surgery and since then, for lung tumors, it's become a standard of care, for some liver tumors, it has become standard of care. There is emerging data, in primary treatment of renal cell cancers as well, prostate cancers, and bone metastases. And so we're a huge center where we do a lot of spine SBRT, as well and bone SBRT, as well. And so in the setting of spine, there's emerging data showing that the pain control with spine SBRT is significantly better, as well as local control. And so the applications are varied, but nonetheless effective across the board.

Dale Shepard, MD, PhD: What are some of the other advantages of SBRT, in terms of, for instance, toxicity or time spent getting treatment, things like that?

Ehsan Balagamwala, MD: Absolutely. So there's several advantages of SBRT over conventional radiotherapy, granted, the patient and their tumor is amenable to SBRT. Certainly convenience, like you mentioned, instead of being on treatment for 6 or 7 weeks, the patient's typically on treatment for a week, week and a half, and so the treatment time is significantly shortened. There's also a lot of data showing higher efficacy and better local control with SBRT because with SPRT, we're able to deliver ablative doses of radiation. And so the local control, for instance, in lung tumors, can approach over 90%, which is very encouraging.

And SBRT allows us to treat multiple lesions at the same time. And with advanced immobilization techniques and very precise planning techniques, the toxicity profile is also much more favorable because of reduced risk for toxicity such as radiation pneumonitis, or radiation hepatitis, or esophagitis. And so we see a lot less of those toxicities with SBRT, as well, with the primary side effect, being fatigue, which patients recover from very quickly.

Dale Shepard, MD, PhD: What sort of trials are going on right now, that you find interesting, in terms of moving the field forward?

Ehsan Balagamwala, MD: I'll start off by mentioning one of our in-house trials, which is an IIT-funded spine radiosurgery, where we're looking at a single treatment for spine metastases versus two treatments for spine metastasis and that's a really exciting trial. As some data has shown that single fraction may be slightly inferior, in terms of pain control compared to two fractions of spine radiosurgery, so that's really exciting. And there's a lot of studies going on both within the United States, as well as in Canada, looking at multiple lesions and trying to define how many lesions are going to be amenable to SBRT for all of the metastasis.

And there's several trials soon to come at the Cleveland Clinic as well, hopefully incorporating SBRT and immunotherapy, across a variety of disease sites. There is a lot of interest, especially in diseases like melanoma, where immunotherapy is extremely active and whether doing SBRT to metastases, will generate an abscopal effect, as well. And so that's a really exciting space and we'll hear a lot more about that over the next few years.

Dale Shepard, MD, PhD: So certainly a lot of interest in this abscopal effect? Maybe you can fill the listeners in on what that's all about?

Ehsan Balagamwala, MD: Yeah. So that's again, one of those effects that has been described many years ago but is gaining a lot more interest more recently, with immunotherapy. The simplest way, I guess I would describe it as, is if the patient has say, 10 metastases and we use radiation in conjunction with immunotherapy for one of those metastases, what we would notice on future scans is that those other 9 metastases also shrink. And that's very favorable because you're priming the immune system to fight the rest of the metastases and leveraging the advances that immunotherapy have brought and adding a very cost-effective way of treating these patients. And potentially getting an improvement not only in local control but also, potentially disease-free survival and overall survival.

Dale Shepard, MD, PhD: Are there currently any tumors that we cannot use SBRT? And I guess I ask that, thinking either histologies or location of tumors.

Ehsan Balagamwala, MD: Yeah. Histologies are varied and for the most part, I don't use histology as an exclusion criteria for SBRT. Certainly, location is an important one. If the tumor is very close to say, the esophagus, then SBRT, at least in 5 treatments is higher risk. Having said that, we can still deliver ablated radiation to those tumors, it might just take a few extra doses, instead of 5 treatments, it might be 8 treatments or 10 treatments. And certainly, the pattern of spread is also important. So the classic example where SPRT would be inappropriately utilized would be, say, a Stage 3 lung cancer, where you want to, as a radiation oncologist, treat involved nodes in the mediastinal, and you can't do that effectively with SBRT.

So in the metastatic setting, if the tumor is close to luminal organs, such as the abdominal tumors close to bowel, that is more challenging. Having said that, more recently we have had a lot of interest in pushing that envelope, as well. So our ability to treat, such as pancreatic metastases or primary pancreas cancers, which are very close to the duodenum, we're able to deliver ablative doses with advanced planning and immobilization. But one of the things that I've started using more recently is a breath-hold, a device that actually freezes the motion of the tumor, allowing us to deliver ablative radiation more accurately and minimizing toxicity that way, as well.

Dale Shepard, MD, PhD: So you mentioned before, certainly, this whole concept of SBRT has been around for a while. You also mentioned that a lot of this, to effectively do it, a lot of it depends on the equipment and physicists and things like that. So how widespread is use of SBRT in community settings, for instance?

Ehsan Balagamwala, MD: SBRT is becoming more and more widespread and adopted. A lot of places feel very comfortable doing lung SBRT because that's been around the longest. As the disease sites progress to abdominal or spine SBRT, fewer and fewer places are doing it. Having said that, I think even though more places are doing lung SBRT, the expertise is still necessary because there is a risk for toxicity, and advanced planning, as I mentioned, is very important. And it's not just the physician that's involved here, it's the whole team that really matters.

Dale Shepard, MD, PhD: So in many cases, unless it's a pretty routine case, you're recommending people should probably seek out an academic center to get their treatment?

Ehsan Balagamwala, MD: Right. An academic center or a place of excellence where they have done a lot of SBRT and they have reported on their outcomes, as well. So I think that's key, is places that are doing SBRT ought to report outcomes, in terms of local control, as well as toxicity. And we have been very proactive in that setting. All of our patients that are treated with SPRT, go into an institutional database and we are constantly reviewing that and learning from our experience and reporting that, at national conferences, manuscripts, as well.

Dale Shepard, MD, PhD: Excellent. So what are the biggest gaps? How do we make that leap? You talked about changes in the size of lesions, things like that. What do you think is the gap beyond that? Where do we go?

Ehsan Balagamwala, MD: I think we need to understand biology first and foremost. Because the number of lesions is important certainly, but understanding the biology of tumors is crucial. We all have had patients who have only one metastasis, we treat them, and then at their 3-month scan, the whole body is riddled with metastases. And that biology is very different from that sarcoma lung or a rectal cancer liver metastases, where you do a wedge resection of the lung or SBRT, wedge resection of the liver or SBRT and that patient is around 10 years later.

And so I think as we understand the biology better, we will be able to better leverage SBRT and other local metastatic effectively, for instance, to improve upon outcomes. And so I think that will be the next big frontier in the treatment of all of the metastasis. The other thing that's really exciting, is biological imaging. As that develops better and we have, for instance, PSMA was recently approved for prostate cancer staging. I think that that will improve our ability to detect really small lesions, that if we were to ablate wouldn't cede other metastases. And so as we get better at imaging, get a better understanding of biology of the tumors, we can really make a huge impact on these patients with early metastases.

Dale Shepard, MD, PhD: What else should we know?

Ehsan Balagamwala, MD: I think from an SBRT perspective, experience and expertise matters and a multidisciplinary evaluation of these patients is extremely crucial. So if a patient comes to me, I'm actually seeing a patient from Colorado coming up for lung metastases, and when I do that, I actually set them up with a surgeon, as well. The patient needs to hear about the different modalities that we can use to treat all of the metastases and make a collaborative decision.

So I think that's what I love about my job here at the Cleveland Clinic, is I get to work in a very multi-disciplinary manner, working with surgeons, medical oncologists, my partners in radiation oncology, and come up with a coherent overall treatment paradigm. I think that's crucial, especially in a realm in which we are rapidly learning, when it is appropriate to treat, when it is not appropriate to treat. And so that's what I would recommend patients look for, is a multidisciplinary team, wherever they might end up, but a multidisciplinary team is extremely crucial.

Dale Shepard, MD, PhD: Well, you've provided some great insight for us here today. If anyone listening would like to refer a patient for consideration for SBRT, they can call 216-444-5571, that would be 216-444-5571. Thank you again for being with us today.

Ehsan Balagamwala, MD: Thank you, Dale. This was an honor. I appreciate it.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will 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 Clinics Cancer Center experts on our Consult QD website, at consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.