Melanie Cole, MS (Host): [00:00:00] Welcome to the podcast series from the specialists at Penn Medicine. I'm Melanie Cole. And today, we have the second part of a panel discussion with two Penn Medicine specialists on deintensification therapy for head and neck squamous cell carcinoma. In this part, we’ll be discussing relevant clinical trials involving intensity-modulated radiation therapy and proton therapy.

Joining me in this panel today are Dr. Karthik Rajasekaran. He's an Associate Professor of Otolaryngology, Head and Neck Surgery, and fellowship-trained in Head and Neck Oncologic and Microvascular Reconstructive Surgery; Dr. Michelle Gentile, she is an Associate Professor of Clinical Radiation Oncology.

Doctors, as we think about deintensification therapy, it's been researched for many years in HPV-positive head and neck cancers in a range of modalities, including radiation therapy. There are two trials that are of particular interest because both involve intensity-modulated radiation therapy and proton therapy.

Dr. Rajasekaran, you took part in the AVOID trial, which investigates the effect of avoiding radiation therapy due to the site of surgery in individuals with HPV-positive head and neck cancers. Tell us a little bit about this. Because, as I understand it, the trial involved IMRT and proton, but didn't compare the two. Can you briefly review the trial for us and its outcomes?

Dr. Karthik Rajasekaran: Absolutely. So, this was very exciting, and this goes back to that we've noticed that these cancers behave much better than HPV-negative cancers. So, we found that if we remove the cancer surgically, like we use a robot to do so, whether the cancer's in the tonsil or on the back part of the tongue, if we have negative margins, we found that we can avoid radiating that area.

So, that limits some of the toxicities from treatment. So, this we did several years ago, and I don't think proton therapy was there at that time. But the whole idea was if you can get negative margins or no bad features, then we can just simply avoid radiating that. And we've been doing that at Penn now, I don't know, Michelle, 10 years? Is that right?

Dr. Michelle Gentile: That sounds about right. Yeah. It's been a while.

Dr. Karthik Rajasekaran: And patients do really, really well. So now, that's been our standard of care. It's pretty unique to Penn. I don't really know if too many other centers do that, but we feel very comfortable doing that. And it’s also, there's a mutual trust of not only, like, when we look at these tumors, if the surgeon feels like they can truly get negative margins, and our radiation oncologist believe that that's true, then we can move forward with that.

If there's a question of there being a positive margin, things like that, then those patients do require radiation with additional chemotherapy. But the best are for patients where the tumors are small, we get negative margins. And the cure rate again, last time we looked, about 94%.

Dr. Michelle Gentile: Yeah, I agree with Karthik. It's a really unique strategy that to my knowledge is only really used at Penn. We do a lot of avoidance of this primary site for patients that still require radiation. The chance of them failing or recurring in that local area is extremely low.

It's probably close to 0% on our long-term data. So, it's a very safe approach, and it allows them to probably have better swallowing outcomes long-term than somebody who would require radiation to that primary site that was already resected. So, very cool data and something that's very unique to Penn.

Host: And Dr. Gentile, one of your colleagues at Penn Medicine, Dr. Lin, took part in an important study recently published in The Lancet, and it should be noted that Dr. Lin was the first author on the AVOID trial report. The Lancet study was the first to compare intensity-modulated proton therapy, or IMPT, with IMRT. And so, can you tell us a little bit about the findings, discuss what they suggest for proton therapy in HPV-positive SCC individuals? Tell us a little bit about that.

Dr. Michelle Gentile: This is a really interesting trial. It accrued patients over a 10-year period. And basically, the results show that there's no difference in recurrence rates between the two groups.

So, whether someone got photon or proton treatment, there was no difference in local, regional, or distant recurrences. But there was a surprising 10% survival benefit in favor of proton therapy at five years. So, this was a really interesting result that is hard to understand. And in addition, protons were shown to have less side effects that included things like decreased blood counts and dryness in the mouth and rates of feeding tube placement.

And so, there's been a lot of discussion about why there is a survival benefit when there was no difference in recurrence rates between the two groups. And so, some people have hypothesized that perhaps the proton group had less severe treatment toxicity that led to less treatment-related deaths, or perhaps there was just better survival for the patients who had protons after recurrence. So, we don't really know.

I would say we're still very interested in protons as a research topic. And at Penn, we do use a lot of proton therapy for patients with HPV-positive cancers. And then, also most of the time, we are trying to gather objective data on both plans, both a photon plan and a proton plan, to make sure that we're choosing protons appropriately for these patients.

Host: This is really an interesting topic, and I'd love to give you each a chance for a final thought here. And so Dr. Gentile, as, cancers of the head and neck can really have these devastating effects on the quality of life, appearance, function of the patient. Tell us how you work with your multidisciplinary team and the patients and their families as they go through all of these therapies we're discussing here today.

Dr. Michelle Gentile: It's a team effort with, our physicians, and I think Karthik and I and, Lee and, all of us work really well together, as well as with other members of the head and neck team. But it also requires patients' families to be highly supportive.

These patients need transportation daily for many weeks. They need help with meal planning and supporting their nutrition and making sure they're taking their medications on time. So, there's a lot of discussions, there's a lot of TLC with patients and their families. And at least for the patients that are getting radiation, we are meeting with them regularly, weekly, maybe even more regularly than weekly, to go over expectations and what to expect from week to week.

Dr. Karthik Rajasekaran: All cancers are rough. But in the head and neck, it's challenging because it affects so many things, your ability to talk, eat, drink. There's not a time where you're not reminded of you having cancer, because you're just miserable. It affects your ability to work or can. So, Michelle is right. It takes a village and a lot of TLC. And it's hard for patients to see the light at the end of the tunnel. And it's several months of a rough time, but everyone gets through it. And when they're through it, they are happy. But that initial time, it's very tough.

But we got an excellent team here, not only the physicians, but we have an excellent nurse navigator, supportive services. We even have something called Rehab 360, where we have patients see a nutritionist, physical therapist, massage therapist. There's multiple resources available while patients are going through treatment, where they help them through the whole process. And so, it doesn't seem so daunting, and patients get through this very well. So, we're fortunate we have multiple resources available to us, and patients are able to use them during the entirety of their treatment and beyond.

Host: Thank you both so much for sharing your incredible expertise for other providers and giving us so much to think about today. To refer your patient to Dr. Rajasekaran or Dr. Gentile at Penn Medicine, please call our 24/7 provider-only line at 877-937-PENN, or you can submit your referral via our secure online referral form by visiting our website at pennmedicine.org/refer. That concludes this episode from the specialists at Penn Medicine. I'm Melanie Cole.