New ASCO Guidelines for Managing Osteoradionecrosis

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, directing the Taussig Early Cancer Therapeutics Program and Co-Director of the Cleveland Clinic Sarcoma Program.

Today, I'm happy to be joined by Dr. Shlomo Koyfman, Director of Head and Neck and Skin Radiation. He's here today to talk to us about new guidelines for osteoradionecrosis. So welcome back, Shlomo.

Shlomo Koyfman, MD: Thank you.

Dale Shepard, MD, PhD: You were here previously, and you talked about stereotactic radiation for head and neck cancers. That episode's still available to listen to, and we're going to talk about the consequences of that and that could be osteoradionecrosis. Before we start, remind us what you do here at the Cleveland Clinic.

Shlomo Koyfman, MD: Sure. So I do radiation oncology, which means giving radiation for primarily I specialize in head and neck cancer and skin cancers. And we either use radiation to try to get rid of tumors instead of surgery, or a lot of times as an adjunct to surgery we do radiation afterwards to, it's almost like the weed spray to try to get rid of all the remaining weeds.

Dale Shepard, MD, PhD: There we go. We're going to talk about osteoradionecrosis. And so a lot of different people might be listening in, may not have a clue what this is, so fill us in. What exactly is that?

Shlomo Koyfman, MD: So when we do radiation, like any cancer treatments, you can get side effects, and we think about short-term side effects and long-term side effects. So in the long-term side effect category, this is when people are hopefully cured and doing okay, when you treat near their head and their neck and their throat and their tongue and their voice box and all that stuff, the jawbone can get in the way, the mandible.

And what happens with the jawbone is if it gets too much radiation, it's at risk of having a lot of problems. Osteoradionecrosis is actually a common problem that people encounter could be many years later, five years later, 10 years later, 20 years later, 30 years later. And oftentimes the number one call I get is from dentists because a dentist will say, "Hey, this guy doesn't have a good tooth. I want to pull it. And he's like, "Whoa, whoa, whoa. My radiation doc said you can't pull my teeth."

So we get called often because if you have too much radiation to the jawbone normal, normally it's not a huge deal, but if the tooth needs to be manipulated, like pulled or something like that, the problem is because of all the radiation, those little blood vessels don't heal that well. And you can get chronic non-healing wound problems or bone breakdown.

And that is a problem because it could be really minor, like no big deal, takes a little more time, you rinse it and it gets better. Could be more significant. You need antibiotics, you're going to get recurrent infections or could be really bad, where literally the bone dies and falls apart and it's painful and chronically infected. And our surgeons, who we have amazing ones, have to go in and kind cut out all the dead bone and do a big reconstructive surgery for 10 or 12 hours. It could be a big deal.

Dale Shepard, MD, PhD: And so I guess as you described this, I guess what comes to mind is osteonecrosis of the jaw with this phosphonates, and so-

Shlomo Koyfman, MD: Exactly.

Dale Shepard, MD, PhD: ... we're thinking of a similar process. In the old days, dentists would, well-intentioned, would cut it out, and then it just got worse and worse. And that physical manipulation was a problem.

Shlomo Koyfman, MD: Exactly. It's almost like there's a bone underneath that's not so great, but it's hanging on. But the minute you stress it by pulling the tooth or whatever, and you rely on normal healing, that's when you run into trouble. So we often get called by dentists and they're like, "Hey, we got to pull a tooth."

We look at our radiation plan, it's really important. You got to look at where the radiation dose went because it is dose dependent. So if we give 45 or 50 gray or more, the chances go up. If we give less, we say, "Yeah, no big deal. You can do what you want." So, it's really important to have this dynamic interaction between the dentists and the radiation docs.

We came out with ASCO clinical practice guidelines on this, and what was cool is that it was radiation docs, head and neck surgeons, reconstructive surgeons, dentists, oral surgeons. It was like a lot of different people that normally don't get in the same room putting their heads together on how we can work better. And one of the main hallmarks of the guidelines is lots of people talking before they get their radiation, during and after the radiation, and years down the road. So it's all about getting the teams on board with one another, because the best way to manage this problem is to prevent it if you can.

Dale Shepard, MD, PhD: And so let's start there. And you mentioned guidelines, there are new guidelines. So maybe before we launch into that, so there were guidelines before and they just didn't necessarily reflect what we needed to be doing, or what drove the need for new guidelines?

Shlomo Koyfman, MD: Well, it's interesting. So I have the privilege, one of my predecessors, Dave Adelstein, had me take over. So I'm one of the co-chairs of ASCO clinical practice guidelines for head and neck cancer for a few years. It's a volunteer thing.

And what we do is we get to basically ask the experts, "Hey, what does the community of practitioners out there, what do they need help with?" And we get to say, "Hey, there's so much immune therapy. Now, we got to give them a primer on when do we do immune therapy, what do we do? How do we do it, etc."

So topics come up, thyroid cancer, there's a million new drugs. When do we give them, what do we do? How do we do it? So we meet every year and we triage what people need to know about. And this one actually came to the top because, like I said, it's a really common problem and it wasn't like we had old guidelines about it, and it wasn't like ASCO, our clinical oncology group, has never done a guidelines on it.

There were some guidelines from the Oral Medicine Society, like EmRange, and the ISOO and MASC, which are basically other organizations dealing with oral health and dentists and oral surgeons, etc. So, what we did was we joined forces with them, so it was really a joint guideline between ASCO and ISO and MASC, which are again international or national agencies dealing with oral medicine physicians.

We joined forces and ASCO has never put out a guideline. We really should give guidance. We get questions about this all the time. Nobody really knows what to do. Let's put it all in one place. So that's how the guidelines came to be. It rose to the top of the triage list.

We got a group of, like I said, 20 or so really talented people from a bunch of different specialties, putting our heads together, and we really broke it up into what you should think about to prepare before radiation to reduce risk and anticipate it. How do you kind of good teeth, health, maintenance, prevention, during and after treatment.

If people start getting radiation necrosis, how do you identify it? How do you define it? How do you catch it early and treat it early effectively? If it gets more advanced, what do you do about it? So, it was in stages of a full package of start to finish. How do we think about managing this better?

Dale Shepard, MD, PhD: And so just big picture, what were some of the takeaways? So from a prevention standpoint, how well can we predict? You mentioned radiation dose, for instance, increases risk, but are there other prevention, anticipating who might be a problem?

Shlomo Koyfman, MD: Yeah, so it's neat. One of the things that's changed is in the olden days when we did kind of old-fashioned radiation, when you would try to get rid of cancer in the head and neck, you had two big beams from the sides and you fired away and cured a lot of people caused a lot of problems as you recall.

So what's happened is with advanced radiation technologies, it's gotten to be so much better because there's so many fancy things we can do with radiation to actually draw the jawbone and avoid it. It's something we at Cleveland Clinic started doing a few years ago, really aggressively. I was actually giving a class this morning for one of the large radiation manufacturing companies that people who buy their machines want to get educated, I use them.

I was talking about this, and this was big news to people. You can really do a lot to limit the dose to the mandible, which could be a big deal. So one of the obvious things is dentists now can't just assume, "Oh, you got radiation, you must be at high risk." They have to call the radiation doc and ask for the plan, "Did you only treat the right side? Did you treat the left side? What about the top? What about the bottom?"

So, every person is unique. That's point number one is this idea of the collaboration between the dentists and the radiation docs. Point number two is the radiation docs need to send patients to dentists with some expertise in this area. Your regular dentist may not know enough about it. You got to go to a specialized dentist who gets what happens with these patients, who also knows the radiation doc and to talk, "Hey, what doses are going where?" Because prevention is the best medicine.

So what happens is if people have wonderful teeth, great, they get fitted for fluoride trays. We have some fluoride prevention after radiation, that can be great. But if their teeth aren't that great, the number one best thing you can do is extract the teeth or pull them ahead of time, let them heal for two or three weeks. You almost never run into problems after that. So thinking ahead and taking care of it ahead of time is one big takeaway.

The other big takeaway is making sure that people get seen by the right dentist with some expertise. The third one is after radiation, get people on a good fluoride regimen. Radiation causes dry mouth, and saliva really protects teeth. So if they don't have saliva long-term and they have a really dry mouth, they're much more likely to get cavities, cavities cause all kind of problems. And then the teeth start breaking down and cracking and the next thing you know have a lot of problems.

Getting them on a good fluoride regimen was also great. And then the last big chunk, which was a big chunk is, we've done all those things, but tumor was next to the jawbone. You couldn't avoid it. You had to give it high dose. Now, we're running into problems. We're starting to see radiation necrosis, what do we do? And that was the whole second set of problems that we were trying to tackle.

Dale Shepard, MD, PhD: You mentioned a couple of times about the importance of the dentist. What dentist? How does that work? I mean, patients probably don't even give a second thought. They've been going to the same dentist for years and then they're like, well, my dentist is my dentist.

So how does that work? Do you tend to have particular dentists that you tend to refer people to? Most academic centers have a dentist or two or three, and it's not necessarily their expertise. How does that work? How do you get people to the right place?

Shlomo Koyfman, MD: Yeah, so it's important because, again, it's not like it used to be in the olden days. In the olden days, it was like, "Hey, you're going for radiation. You don't have great teeth. Take out all your teeth." So full mouth extractions were pretty common.

Go to your dentist, get all the teeth out, come back when they're done. A, that could lead to a ton of delays. B, it could take three weeks to get into the dentist, then another two weeks to refer to the oral surgeon to get everything pulled. It could take a long time, and that's delaying their cancer care.

So, it's really incumbent on radiation docs who do a considerable amount of head and neck radiation to have established relationship with dentists that they work with that can, A, get their patients in quickly, and B, have some sophistication about what to do. We at the Cleveland Clinic are blessed. We have a beautiful, wonderful, robust dental practice who get our patients in. We have a lot of them. They understand radiation. We talk all the time.

We can say, "Hey, this guy has a voice box cancer. His jawbone's not going to get much. You don't have to worry about extractions, but I want his teeth tip-top just because he might get some dry mouth." Or, "Hey, he's got a tongue cancer, he's going to have a big surgery, he's got terrible teeth. I'm going to have to radiate him six weeks after surgery. Can you make sure to see him and get those lower right teeth out three weeks after surgery?" Or something like that.

So, having a collaborative relationship is really important and there are dentists that specialize in this. So I would say upfront that's really important. Again, if you know that somebody has perfect teeth and they see their dentist regularly and they do a panoramic x-ray, that's fine. If they have terrible teeth and they need them all pulled, and they have somebody to do home to do it, great. Any nuance, it pays to see somebody at least once in the beginning that has some expertise.

I think where the expertise really comes in is after the fact. If after the fact people are starting to run into trouble, their teeth are cracking, they're having issues, they're having root canals, all of a sudden you're getting a panorex, they're getting a little bit of bone thinning, a little bit of early osteoradionecrosis. That's where I think it is hugely important to go to a dentist or an oral medicine specialist that has expertise because there are... I don't even know all of it.

But in terms of how you probe, how you clean, how you determine, what you do in terms of antibiotic and really aggressive follow-up to make sure you can help those early stuff heal, you can spare extractions and save a whole lot of problems. There's real expertise there. So I do think if they've had radiation, it's years later, they're running into trouble.

If people come and see me, I will often say, "Hey, why don't you ask your dentist if it's okay if I send you to my people just to manage this," and then you can go back to your dance for all the regular stuff. So, I do think that's an important piece of this and the guidelines do reflect that.

Dale Shepard, MD, PhD: And like you said, I mean this could be a year or five years, 10 years, 20 years, and so I guess we oftentimes don't think dentistry is part of survivorship, but in this case it's essential.

Shlomo Koyfman, MD: Huge. Survivorship for head and neck cancer is a really important topic. Head and neck cancer is unique in that basically everything we do between surgery, radiation, chemotherapy, we're affecting people's head and neck and mouth and throat, which basically every time they breathe, speak and swallow. If it's not perfect, they're noticing it, which breathing, speaking and swallowing, we do very, very often.

So it's not like something like if you have a problem in your prostate or in your breast or in your leg, when you have to think about it's a big deal, but you can live life without thinking about it. A head and neck cancer survivor that has issues, they don't go a minute without thinking about it. So, that oral health is really important to chewing, to taste buds, to swallowing.

You can imagine if somebody has early osteoradionecrosis, early thinning of their jawbone and pain and infections means every time they go to chew. What kind of foods they can eat. Maybe they're getting infections affecting their taste, getting pain, needing pain meds. It could be a really morbid process. It could be a process that leads to a lot.

I remember I had a guy, young guy, working full time. It was like a persistent problem. He had to start taking Percocet every day. I remember seeing it. I'm like, "Dude, you're going to need a surgery. Just get it soon." He's like, "Well, I don't know." The surgeons were like, "Well, maybe we could..." And it took a year, but he was on pain medicine for a year, which we know, I mean, we're in an opioid epidemic.

These are the kinds of things that we really want to avoid and it could really impact people's quality of life, ability to chew. I once had one guy, he was just doing his exercises because head and neck cancer treatment can lead to trismus, which is locked jaw. It's hard to open your mouth. They're doing exercises, and he was a really young, vigorous guy. He exercised too much, snapped his jawbone, very rare, but it happens.

People doing their exercises and then they can't really open wide because the jaw hurts and it's a vicious cycle. So, I do think these are complicated problems. They need some expertise, and ultimately, like I said, the big gun of osteoradionecrosis is what's called a segmental mandibulectomy and a fibular free flap reconstruction, which means if it gets really bad and it's fractured and it's full thickness, you got to cut out that part of the bone, take a piece of the leg bone, rebuild it. Our head and neck reconstructive surgeons do this every day. They are amazing at it, and people do great.

Their pain goes away. They're eating, they're swallowing, they're fabulous. I mean, if you look in their mouth, you can tell, but you wouldn't be able to tell from the outside. It's a 12-hour operation. If you're 60 and healthy. It's one thing if you're 78 and you have a lot of problems, it's a big deal. So that's, again, early recognition of it by people who are experts and trying to do the earlier things, the antibiotics, the cleanings, those kinds of things to prevent that kind of surgery is really important.

Dale Shepard, MD, PhD: So just taking a step back to the guidelines themselves really quickly, takes us behind the scenes, multidisciplinary group, a diverse set of people, what surprises? What was the thing that surprised you most that everyone quickly agreed on, and what was the thing that surprised you that there was bickering about?

Shlomo Koyfman, MD: Excellent questions. So one of the things that comes up most often when it comes to osteoradionecrosis is hyperbaric oxygen treatment. It is super common to get this question. And the reason is there were old studies that showed that if a dentist is about to take out a tooth of a jawbone that had radiation, high dose radiation above 50 gray, there was data that showed that if you did hyperbaric oxygen, according to the Marx protocol, which was essentially they're all over town, they're in most cities.

You go into basically a trailer that is 100% oxygen. So the air we breathe only has 21% oxygen. This is a 100% oxygen, and you basically sit there on a couch for a couple hours watching TV, and you're just breathing in super high dose oxygen. You can imagine like bikers doing this before, Lance Armstrong. And so it's a way to increase the oxygen supply because one of the ways that we think the damage happens is with all that radiation, the blood vessels get scarred.

You can't get enough oxygen to the wound, and if you pull a tooth, if you don't have enough oxygen, it just won't heal. So this is a way you get a couple of weeks of high dose oxygen treatment Monday through Friday, five days a week, and this could be 5, 6, 7 weeks of treatment or longer, two hours a day. It's very expensive. Again, insurance usually covers it, but it's a pain in the butt, and people have to get a bunch of weeks before the tooth is pulled. Then the tooth is pulled, then they get another four weeks.

So it's a big deal, but you can imagine if you're a dentist doing that extraction, you either need a radiation doctor to sign off that says, "You don't need this," which I get calls about this at least three times a week, or you're going to send them for hyperbaric oxygen, because you want to cover yourself and make sure to minimize risk, which is legitimate. Well, there was one big study that showed it helped, a bunch of studies that showed it. It is such a controversial area. I thought this was going to be the biggest blow up on the calls.

You get on the calls and basically everybody's like, "There's no good data for hyperbaric. We don't routinely recommend it." Now, I will tell you, we have hyperbaric medicine in Cleveland clinic. We have wonderful docs who work there. I send people there sometimes for a variety of reasons. The guidelines are pretty unenthusiastic about putting people through all of that.

That said, I do think it is important, especially for people with serious ORN, big time issues, they're going to go have big extractions and their risk is really high. I think it's certainly reasonable to meet with a hyperbaric medicine physician, have a consultation, discuss it with them. You're going to hear a lot of things. There are a lot of opinions on this. The data's a little bit weak. I don't think it's wrong to do. It's certainly an extra precaution.

I think what really changed from these guidelines is there were dentists like, "I will not take out your tooth without hyperbaric oxygen," and I think we came out and said, "The data isn't good enough to support that." As long as you have a risk benefit, the risk is pretty low these days, except for extenuating circumstances, maybe it's five or 10%. You don't have to do that.

We almost gave permission to dentists to say, "You can extract it without having to do a hyperbaric on everybody." So that was one big thing that came out. There were a lot of new treatments, a lot of people who use, there's vitamin E, there's pentoxifylline, there's other things, which recent studies have suggested some help. They're harmless in their pills and they're easy, and I think getting that out that that's useful to try was also a good benefit to the guideline.

The other thing the guideline talks about is something called a rescue flap. Now, rescue flap. We have a colleague here, Mike Fritz. He's the head of our head and neck reconstructive surgery department here, and he started doing this years ago and has been amazing. But what happens is that when people start to have this and they need a surgery, rather than cut the entire bone out, take a big piece of the leg with the bone and replace it, which is, like I said, could be a 10-hour operation, it's a big deal. It's a very long recovery, etc.

What he's done is rescue flaps, which means as long as the bone is only half whittled away. But there's at least 20, 30% of the bone that's still intact, what they will do is they will take an anterior little lateral thigh fascia lata flap, which is a flap from the thigh, doesn't involve the bone, much easier to harvest, easier on people, quicker surgery, let's say half as big a deal, still a big deal. But half as big a deal and take that know fascia lata is this magical vascularized piece of tissue from the thigh, cut away the dead bone, wrap the existing bone you have there, and all those blood vessels that they bring feed into the bone and build a new blood supply.

He's had incredible success. He's been doing this at least, I don't know, 10 years or so, they've published their outcomes. It's quite good, and it's been a real game changer for us because what we do is, again, when you find it early, if the antibiotics are failing, etc., instead of waiting for the whole thing to die and doing the big surgery, intervene earlier, do this rescue flap, this half measure surgery, which is still big but not as big, and you get great outcomes and you spare them quite a bit of recovery time and complication time.

And you take their bone out of their leg, they're in a boot, they can't walk. It's a big deal. So, I think the big takeaways from the guideline is we need collaboration between all of these disciplines, get the disciplines involved early. So, rad onc sent to dentists ahead of time, who know this disease. Dentists, call your radiation doc before you're going to pull a tooth or before you think they need it, because they have some insight into what the planning looks like, which is unique for every patient. There are some easy things you can do.

The other thing they said was when you're dealing with lower risk radiation necrosis, when you do these antibiotics and debridements, which are before surgery, you just cut away the dead bone and hopefully it heals. The dental physician specialists we're like, "We see them every week or two for months to make sure we're following them. We're keeping it clean, we're doing a little more debridement and we're making sure it's healing. We're doing little flaps."

There's a lot you can do in that space, so that was a real benefit. If you think they might need surgery, help them see that. Let them see that reconstructive surgeon early, because they might be able to do that rescue flap if you catch them early enough as opposed to having to do the big segmental.

Dale Shepard, MD, PhD: Well, it is luckily a rare complication. Sounds like with the newer radiation techniques may be even less of an issue in the future, but fantastic work with the guidelines.

Shlomo Koyfman, MD: Thank you. I would say one thing. We started out saying last time I was here a year ago, it was about stereotactic radiation, which is super high dose radiation, sometimes rear radiation a second time. This is the consequence. So I will say that it is a rare complication when people get standard radiation the first go round.

We here specialize in doing repeat radiation of this high dose SBRT. We do a ton of it. We're running studies on it. When you do that near the jawbone, it is almost guaranteed you'll run into this problem. The cool thing about it is that if you get your surgeons involved early, again, normally we're only doing that if there's cancer that's growing, it hasn't responded to previous treatments. You don't have any other great options for it. You could potentially cure them with this.

Even if you cause a lot of problems, like this might be their one shot. Get the surgeons involved early, and we now have a motto where if it's cancer that's returned and we have to do big time reradiation or something, I have this relationship with the surgeons where I'm like, "I'm going to make a hole. You got to fix it," kind of thing. And they say, "You treat the cancer, we'll fix the hole." And that is the relationship we have.

So, I would say standard radiation, it is a much less common problem. We see we are doing more and more of repeat radiation, high dose radiation, like higher risk radiation for recurrences and repeats and all kinds of things. People we never tried to cure that now we're curing. Of course at the price of more complications, and that's why managing this upfront is really important, because we are seeing more and more of it in that higher risk population.

Dale Shepard, MD, PhD: Fantastic work. Appreciate you coming and talk about it.

Shlomo Koyfman, MD: Thank you so much.

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