Advancements in Stereotactic Body Radiation Therapy for Head and Neck Cancer

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances at 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 toxic phase one and Cleveland Clinic sarcoma programs.

Today I'm happy to be joined by Dr. Shlomo Koyfman, director of Head and Neck and Skin Radiation here at Cleveland Clinic. He's here today to talk to us about stereotactic body radiation therapy for head and neck cancer. So welcome.

Shlomo Koyfman, MD: Thank you, Dale. Thanks for having me.

Dale Shepard, MD, PhD: Absolutely. Give us a little bit of an idea. What's your role here at Cleveland Clinic? What things do you do?

Shlomo Koyfman, MD: Well, one of the beautiful things about the main campus of Cleveland Clinic is we're all super sub-specialized. So that means that we get to do a small number of things a ton and get really good at it just from experience. So, I do head and neck and skin cancer radiation. Skin cancer's been a newer thing. When I was training here, I saw a handful of skin cancers in my whole four years here. Now I probably see in a week what I saw in a year back then.

So, skin cancer's a big part of what we do, but we've also managed to build a team. I have three other colleagues that do head and neck and skin with me. So, it's really a thriving program and the best part about it is how multidisciplinary it is here with our surgeons and our medical oncologists and the team. So that's really what we focus on.

Dale Shepard, MD, PhD: Excellent. So as an overview of what we're going to talk about today, we're going to talk about SBRT and head and neck cancers. We have a lot of different people that might be listening in with more or less knowledge about radiation and head and neck cancers. Give us a little bit of an idea when we talk about SBRT, what is that?

Shlomo Koyfman, MD: Yeah. No, that's a great question and I think it's important to give some overall context to appreciate why SBRT and head and neck is such an important and hard thing to do usually because we're doing it in the context of reradiation. So typically, people come in with cancer and a lot of head and neck cancer is curable, but it requires long and complex therapy. It's usually a lot of weeks of radiation Monday through Friday, five days a week for seven weeks, 30 to 35 treatments oftentimes with chemotherapy. It's a long intensive treatment with some pretty good results overall. But that's like the typical way we approach cancer. And the reason is because biologically, if you go out in the sun on the beach and you spend 20 minutes a day for two weeks, you'll get a little tan and it'll be great. If you spend one afternoon for three straight hours from 12 to three, you're going to get a blistering sunburn and it may leave a permanent scar.

It's the same thing with radiation. If you do little bits each day, your body knows how to heal the radiation damage and you tend to heal up and do okay. If you do really big doses all at once, it's much more effective. You can kill lots of cancer that way, but you can cause a lot of long-term damage. SBRT is the idea that instead of doing the normal slow and steady radiation over many weeks, you do super high doses of radiation in just a few treatments. Typically, in the head and neck we do five treatments. It's usually something like 4,000 centigrade, five treatments, which is essentially four full weeks of treatment in a week and a half.

So, by doing those super high doses of radiation in just a short period of time, a few things are important. Number one, in head and neck cancer, oftentimes we're treating a lot of tissue. We might be treating a tongue, we might be treating both necks, we might be treating other areas that we're worried about till intermediate or lower doses. In SBRT, you're just treating the tumor, you're just treating what you see. It's a much smaller area, and it's really high doses in a small amount of time. And of course, that means we're at much higher risk of causing a lot of problems.

So SBRT means you have to pick your patients. You have to be really thoughtful about how you do it, and you got to try to make sure that it's not too big, not in too crazy a place, not too close to normal things. And then if you can pull it off, especially for some of these resistant tumors, it's theoretically a better way to have a better effect.

Dale Shepard, MD, PhD: And you had briefly mentioned something about you do a lot of reradiation. Is this something that's being used more for reradiation or primary therapy?

Shlomo Koyfman, MD: It's a great question. So, it started as reradiation. The Pittsburgh group probably were the first to do a small phase one study 20 years ago. And what they did is, is that when patients have the slow and steady seven weeks of radiation and chemotherapy, and hopefully they're cured and sometimes it spreads, but sometimes often in head and neck cancer big problem is that a lot of other cancers, the cancer tends to spread to other organs. It's a whole-body problem, usually treated with chemotherapies or immune therapies.

In head and neck cancer more than half of the time, if cancer comes back, it comes back only in the head and neck, which means it hasn't spread to the lungs, the liver of the bone. Theoretically these patients are still curable. It's just that now you have to go and do surgery or radiation or chemo or a combination, but it's already a cancer that came back, which is hard. And your body doesn't forget all the treatment you had before. So, the risk of side effects goes up.

So SBRT really started in the reradiation setting where shoot, now we got a tumor, it came back, we want to give it enough radiation to get rid of it, but we don't want to cause all this damage. About 15 to 20 years ago, with all of the advent of much fancier radiation technologies like IMRT, you were able to get these beautiful plans by using seven beams or nine beams. Now we use arcs with hundreds of beams. You can modify the beam to just target the tumor you're worried about and bend the radiation beams around the carotid artery and the voice box and the swallowing muscle and the mandible and the jawbone and the tongue and all the other things so that hey, maybe we can get away with this. We can do high dose radiation to just a small area, avoid all the other stuff and maybe get away with it.

So, it started in the reradiation setting. Again, SBRT is like the mainstay, one of the mainstays of treatment for early lung cancer and people who can't get surgery or living cancer. SBRT has had such wild success in so many parts of the body. In head and neck, it was a little bit later to come because the problem in head and neck is if you take out a little bit of longer, take out a little bit of liver, it's no big deal. Your body can deal with it. So, if you give super high doses of radiation to a little bit of lung, liver and scarred up, okay. But in the head and neck, you got one tongue, you got one throat, you got one voice box, you got a carotid artery. These are called serial structures instead of parallel structures. If you damage a small piece of it's a big problem.

So that's why it started in the head and neck a little bit later after the technology got a little bit firmer in other places and the stakes are higher in head and neck, but that's why we started it in Reradiation because we were up against a rock and a hard place. What if you had a tumor, you couldn't cut it out? It wasn't going to melt away with chemo. But the patient theoretically is curable, and it hasn't spread anywhere, but the slow and steady radiation isn't working. We need something else. So that's how it started. We've been doing it for, man, probably over 10 years now and have learned a ton. For better or for worse, we've learned a ton about when it works really well, when not to do it, when it's safe, when it's not so safe. And we've built on that experience, and it's become a really important tool in our toolbox to take care of these really tough problems.

Dale Shepard, MD, PhD: So, we'll talk about a little bit more about fancy radiation techniques and things here in a few minutes. But let's touch upon the last point about what we've learned. Who are good candidates? I mean, are there people that you just know outright bad idea? Are there things you're like, this is all awesome, I have a tumor I know is going to work. What things have we learned?

Shlomo Koyfman, MD: Yeah. It's interesting you say that. I had two people in clinic yesterday and one of them was this is a perfect patient and the other one was, yeah, that's a really terrible idea. So, I have them fresh in my mind. So, I have a great privilege. Here at Cleveland Clinic, we're pretty invested in research, and we do a lot of cooperative group research. So, the NRG oncology group is the flagship for radiation oncology research in head and neck cancer. There are others also ECOG and SWOG, but NRG is probably the most fundamental. And I'm actually helping to run the first SBRT study in head and neck cancer period, the first multi-institutional prospective randomized study that we are doing in the cooperative group setting. And for that study, my job as the radiation doc, it's testing whether or not it's a randomized phase two study, whether to just do the SBRT reradiation or to add pembrolizumab, one of the immune therapies.

But my job was to try to figure out who we should do this in and who's eligible, who's ineligible. So, some of the things we've learned is when you do slow and steady radiation, the body will often heal. When you do really high dose radiation, it's almost like an ablation and that means it can leave a lot of damage in the way and make some holes. So, if you have a tumor deep in the neck and it's surrounded by lots of healthy tissue, you're probably going to be okay. If you have a tumor that's sticking out of the skin, if you do it, you might have a permanent hole. If you have a tumor that's up against the carotid artery, one of our big blood vessels that bring blood to the brain and that tumor is up by that vessel, you might end up with a hole and can lead to really life-threatening bleeding.

So, the classic reasons not to do SBRT in somebody who has lots of skin involvement, lots of carotid involvement. Also, if you have a tumor down by the voice box or the swallowing muscle and you don't have a breathing tube or a swallowing tube. If you get a lot of damage, you get a hole there, all of a sudden you can't swallow, you can't breathe, you might need a breathing tube and a swallowing tube. So, what we've learned is that this is an ablative technology. People aren't necessarily going to heal the way they normally do. And therefore, in the beginning we were very, very conservative.

I will tell you that we do SBRT in a lot of these patients because again, the real need is what happens when you have a patient that has a tumor growing in their head and neck. It has not spread. They're not going to die anytime soon. But if you don't control that tumor or you give it, When I was growing up, I was a good boy. I did little bits of five low doses or 10 low doses, 20 and five, 30 and 10, no big deal. And it was great. And that's what I did when I started. And I remember my first patient I ever did SBRT, I didn't learn it in training.

And I had a patient, and he was 82 years old and perfectly functional. And he lived near me, and he was walking to Heinen’s and taking care of himself. And he was an investor, retired, but he had a tumor growing in his cheek under his eye and he had been had radiation before. And he came to me, and he like, "Shlomo, what can we do?" I said, "Okay, we'll give it the usual week or two of lower dose radiation, we'll shrink it down, it'll be great." He came back to me five months later and he said, "Shlomo, it worked great. Three months shrank, but now it's growing again. Now what do I do?"

And I'm thinking, "Okay. Well, if tumor's growing, you must have tumor elsewhere." Got a whole-body scan, nothing else. How are you feeling? Feeling great. What am I going to do? Well, it's now creeping by his eye. And I was like, "Shoot. I'm between a rock and a hard place." And I learned from that patient, Paul, I remember him dearly. Eventually we ended up radiating him a little bit. We tried SBRT, it was my first time, it was a little too late and it didn't work. But from that time on, I've learned sometimes you got to be aggressive upfront even if you're going to cause some problems because if you're not uncontrolled, head and neck cancer is a really bad thing.

And if docs are a little bit too gun shy to say, "Well, we did it already. You've had your lifetime dose; we can't do it anymore." They're going to be back in your office in three or six or nine months and they're going to still be okay. And they're going to still be with their family, they're doing their work, they're doing their thing. They're just having a lot of really bad suffering from tumor. And it's not only about curing people, but also about preventing suffering. So sometimes being willing to put up with some moderate side effects in order to control the tumor and not let it get out of hand is my motto. So, what we've learned is that I now am very aggressive. I'll do it in the skin. I've learned that you could put a Band-Aid over a hole in this skin and they're okay. And if they do well for a while, I have surgeons that can fix holes. And we've learned a lot of lessons about if you put a feeding tube or a trachea in people and you get rid of tumor, they're okay.

So, it's a very razor's edge. It's why these conversations are so important. It's so important to have the whole team together. It's so important to talk to patients about what they want. People who are like, "Doc, I just want a few good months." I don't do SBRT for them. I give them low doses, I hook them up with a pill, think about hospice and maximize their quality of life. That's a really important approach for a lot of people. But for people who like, "Doc, I want to live, I got weddings to get to, I got grandkids to take care of. If I have to deal with a little bit of side effects, I'm in," then that's what we do. And probably the thing I've learned most is actually how to manage the side effects because they come up in their big deals and getting good at how to prevent them or treat them or deal with them has been integral to knowing how to be able to push the envelope.

Dale Shepard, MD, PhD: Well, congrats on the NRG trial. I mean, just getting that open is half the battle, and so hopefully we come up with some good answers. But related to that, you mentioned there's an arm with pembro. So how has addition of chemotherapies targeted drugs immunotherapies affected our ability to maybe use less radiation or change the outcome, change recurrence? What have we learned from that standpoint with systemic therapies?

Shlomo Koyfman, MD: Yeah. So, it's a great question. So, it turns out we're doing way more SBRT now than we were a few years ago. And I think the number one reason for that is immunotherapy. What happens is, again, the reason you need high dose radiation, and we do SBRT in head and neck cancer patients, not just to their head and neck. We'll do lung SBRT, we'll do bone SBRT, we'll do it in other places, but by and large, head and neck are one of those weird cancers that tend to come back where it started more than spreading elsewhere.

The secret sauce to why SBRT will matter is when you have patients that are going to live a long time because SBRT is a high risk, high reward proposition. You're doing super high doses of radiation often in places that they've gotten a lot of orations before. You're risking some side effects. And like I said, we've learned how to manage infections and IV antibiotics and keep people on antibiotics long term, good pain management, a lot of surgical fixes to holes we make. I have a patient who if it's too close to the carotid, ironically, a lot of the times the reason they run into trouble is because it works so well that when the tumor melts and there's a hole, all of a sudden that blood vessel that was plugged up is now unplugged and can bleed. We're now working with our neuro interventionalists to do carotid occlusion tests and stent vessels and coil them. And we're doing all kinds of stuff to avoid the problems.

But the person we need to do this in is if they're going to live a long time and this tumor in their neck or in their throat is going to grow or up by their eye or their skull base is going to grow. If we don't control that, they're going to be in a lot of trouble. But if we have the more effective systemic therapy we have, the better the chemo, the better the immune therapy. The longer these people live, the more important it is to take care of those spots that are going to cause trouble.

We have two phenomenon and head and neck that make SBRT so important. Number one, we have HPV associated disease. HPV-positive disease is exquisitely chemo sensitive. And on average, if you ever had a neck cancer patient that after chemo radiation, the cancer comes back. On average the survival's about a year. Now some people do much worse. Some people do much better. But on average for HPV unassociated, non-associated virally related tumors, they live about a year. A virally related tumor, they live two and a half years on average.

I have a patient, we gave him radiation, chemo radiation, his cancer came back, he got traditional chemotherapy before even immune therapy was a thing. His cancer disappeared after three and a half years. It came back, he got another set of chemo. The guy lived eight years and immune therapy came on board. We have other patients that with immune therapy, immune therapy is magic. I have patients with cancer all over their body. They get immune therapy; it melts away and they're cured five years later.

Interestingly, what we have noticed, and I have a growing number of these people, they have the magic immune therapy response. They're "incurable," they get their immune therapy, now they're curable, their cancer melts away. And all of a sudden, a year and a half later, a lymph node pops up in their neck and I zap it and we continue their immune therapy, giving it SBRT. A year and a half later, a lymph node comes up in their armpit. I just saw her two days ago, gave it SBRT. Two years later, another one comes up on the other side of the neck, giving it SBRT. And sometimes we do it a few times and never again. Sometimes every few years we're doing SBRT to these focal lesions. But immune therapy and chemotherapy has basically changed the natural history of the disease where now you're turning incurable cancer that people have a year to live into a chronic disease that people are living five or 10 years with, but for one reason or another, a clone escape here or there.

And then we have to manage it. And those are the perfect patients where you get them small when they're in good spots, they're not threatening the carotid in the scan and SBRT is a dream. And what's ended up happening is because we've gotten this experience, we're actually doing more and more SBRT, not in the rear radiation setting, but in the upfront curable setting for a lot of cancers that are just really hard to cut out. So, I'll give you an example, thyroid cancer. We're seeing a lot of young people who have thyroid cancer that maybe come back multiple times, spread to their lungs, but they can live 20 years and they're coming in, they've had 2, 3, 4 operations in 10 years and now they have a tumor deep in their neck sitting by their voice box, sitting by their carotid and they're 55 and healthy and they're working.

And surgery would mean taking out their voice box or threatening their carotid or doing really intense surgery. And we're learning thyroid cancer isn't the most responsive to radiation. We do the slow and steady, but it's not too big. We got the location down, we do SBRT, they've never had radiation. We do it to that one little node. We spare all the side effects that we used to get with comprehensive whole neck treatment. It's working unbelievably.

So SBRT is expanding in its indication. I just got a call yesterday from a surgeon for a person who doesn't even have cancer. They have recurrent parathyroid adenomas and they've had three operations in their neck and it's getting tough and they're going to have to take out all kinds of stuff and it's going to be very morbid. Shlomo, can you do SBRT? I answered that email yesterday. I said, "I have no idea, but send them over. Let's review. Let's think about it." SBRT has become a growing way that either they've had radiation and we need newer tech techniques, or they need surgery, but they just can't get it. And SBRT is one of these things where we can do some really neat stuff.

Dale Shepard, MD, PhD: So, we've gone a long way from traditional slow and steady radiation. Now we have SBRT, what's the next plateau? Radiation oncology is about technology and new toys. So, what's the next thing you're excited about?

Shlomo Koyfman, MD: Yeah. So, the two things I'm most excited about I just touched on before are new indications for SBRT and the other is new technologies for SBRT. So, the new indications to start off with and then we'll get into technology. The new indication is, like I said, I'm getting called to do things I've never heard of, but we're probably going to do it because it just makes so much sense. So, for example, I have treated three patients with arterial venous malformations of the head and neck. So, we have a long experience of treating. It's not cancer, it's just abnormal blood vessel collections. We have a long experience of treating them in the brain using gamma knife radiosurgery and other high dose radiation techniques. But outside of the brain, there's very limited experience.

So, when I was a resident back in 2009, I had a woman came to me, had had nine embolizations, two surgeries, had already gone blind and deaf in her left eye, had a giant crazy blood vessel collection in her tongue, in her cheek, up her deep neck, up towards her brain. And basically, she had had a couple life-threatening bleeds, lots of surgeries. She was 42 years old, and the surgeon said, "If you bleed out of your mouth because these blood vessels just rupture, just hold pressure and pray." I was a resident at the time, came to my chairman, I was on his service. He said, "Shlomo, what do you think?" I said, "Let's try SBRT." We did it together. We treated her for the first time after I graduated, stayed on his staff. I kept following her. She's now, gosh, 14 years out, has never had a bleed, did amazing, unbelievable. We wrote it up and published it.

Since then, we've treated two other people. One, somebody in her neck and recently I had a refugee from Nicaragua come to me with an arterial venous malformation of his face. Embolizations would make him go blind. He looks almost like a monster a little bit. He has a wife and three kids. Young guy in his thirties came to America. We just did SBRT and thank God he is doing amazingly well. He's coming up on a year. So, these are the kinds of things, thyroid, cancer, weird, recurrent, benign things in the neck that you don't have anything else to do. Abnormal blood vessel collection. So, one exciting thing is how can we push the envelope on using this high dose radiation in all problems we don't even know about? So that's one big thing that's really exciting. And to be continued.

The next big thing is technology. I said IMRT and VMAT, which is like the usual fancy radiation that most radiation oncologists do in the world. The other up and coming technology is proton therapy. Proton therapy is a heavy particle therapy. It used to be in a handful of centers. Now there's over 40 centers in America that are building proton facilities. And the magic of protons is that number one, it has a little bit of a higher biologic effectiveness, which is actually a double-edged sword. One of my dear friends at Sloan Kettering, Nancy Lee, has been making a lot of protons for SBRT reradiation. Said, "Shlomo, we're getting a lot of holes."

So, learning how to use that carefully is important. But the beauty of it is that with protons, that brag peak physics phenomenon is that when that radiation goes in, as soon as it deposits its dose, it just stops. So, the exit dose is much less, and you can get really beautiful sharp dose fall off. So, if you're treating near the eye, treating near the brain, treating near the skull base, treating near the jawbone, treating near the carotid artery, you can do magic in terms of getting the dose where you want it and really having it just disappear a few millimeters away, which is super exciting. And why I think Cleveland Clinic is so invested in investigating, trying to get the latest and greatest technology.

Even newer than protons are carbon ions or another heavy particle. It's really in Japan that it's taken off. It hasn't really made it to the US, but five or 10 years ago, carbon was a pipe dream. I could tell you here at Cleveland Clinic and other places, it's now on the table. It's part of our discussions. We are thinking about how to bring those really cool novel technologies to Cleveland Clinic and other incredible technologies called flash radiation. Flash radiation isn't the tool you use to deliver the radiation, but more so how quickly you deliver it. And usually radiation IMRT, when I started doing it, used to take nine beams, it would take 40 minutes on the table. Now we use hundreds of beams with arc therapy. It takes about two or three minutes on the table. Flash radiation is an idea that you can deliver all of that radiation in a second, within a second or two. It's like turning on a flashlight for a second. The whole thing is over. It's still an investigation, still under research.

But these are the kinds of incredible technologies that imagine somebody coming in with this large tumor that can't be cut out in a very dangerous place. They walk in the door, they lay down, we line them up, radiation takes a second and they go home. Maybe five treatments, maybe three, maybe one. So, these are the technologies that are coming, and I expect that the better and better we get understanding not just the physics of it, but also the biology. I'm a big biology guy. Building biomarkers, building circulating tumor DNA, who are the people that are going to benefit from it most? How do we reduce the side effects? What compounds can we add to reduce side effects? How do we use the best technologies to do it? SBRT is going to be a huge part of our practice in the future.

Dale Shepard, MD, PhD: Well, this has certainly been enlightening. It's been great technology and the future looks really bright. We'll look forward to having you back and learning more about it as things develop.

Shlomo Koyfman, MD: Awesome.

Dale Shepard, MD, PhD: Thanks for being with us.

Shlomo Koyfman, MD: Thank you so much, Dale.

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.

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