New Clinical Trial Results: How This Changes Head and Neck Cancer Treatment
Episode Summary
In this episode, host David Raubach sits down with Dr. John Chang, Medical Director of the Oklahoma Proton Center, to unpack a landmark clinical trial just published the week of recording. The paper — Proton versus Photon Radiotherapy for Patients with Oropharyngeal Cancer in the USA: A Multicenter Randomized Open-Label Non-Inferiority Phase 3 Trial — compared proton beam therapy head-to-head against conventional photon (X-ray) radiation across 21 institutions and more than 440 patients. Dr. Steven Frank of MD Anderson Cancer Center served as lead author, and the data represent the highest tier of clinical evidence available: a Level 1, multicenter, randomized controlled trial.
Dr. Chang begins by grounding listeners in the anatomy of oropharyngeal cancer — tumors arising in the tonsils, soft palate, base of tongue, and the region just above the larynx. These structures govern swallowing, speaking, and breathing, making the area uniquely vulnerable to radiation side effects. He explains the core physics difference between the two modalities: photon beams pass completely through the body, depositing low-to-medium dose radiation in healthy tissue beyond the tumor, while proton beams can be engineered to stop precisely at the tumor margin, depositing the majority of their energy at that point and sparing downstream tissue entirely.
The trial’s side-effect data were striking. Dysphagia — difficulty swallowing — occurred in 49% of patients in the photon arm versus only 31% in the proton arm, an 18-percentage-point absolute reduction and roughly a 40% relative risk reduction. Xerostomia (chronic dry mouth from salivary gland damage) was also significantly lower with protons, with downstream consequences including reduced dental decay. Lymphopenia, the depletion of immune cells that occurs when radiation reaches bone marrow, was more common with photon therapy, compromising patients’ ability to fight both infections and the cancer itself. Gastrostomy tube dependence — requiring surgical placement of a feeding tube — dropped from roughly 40–50% in photon patients to approximately 19–20% in proton patients, a reduction Dr. Chang attributed in part to work he led at Northwestern University.
Perhaps the most unexpected finding was a difference in overall survival. At five years, patients in the proton arm achieved approximately 90% overall survival compared to roughly 80% in the photon arm — a 10-percentage-point gap that Dr. Chang called “enormous” in the context of a large, randomized, multicenter trial. He theorized that treatment completion plays a critical role: fewer severe side effects means fewer interruptions to the radiation course, and any gap in treatment gives cancer cells an opportunity to repopulate. More treatment-related deaths were reported in the photon arm, reinforcing the hypothesis that tolerability translates directly into survival outcomes.
Dr. Chang closes the episode by situating this trial within a growing body of evidence supporting proton therapy — citing recent randomized data for glioblastoma and esophageal cancer — and by urging patients diagnosed with head and neck cancer to advocate for a multidisciplinary evaluation that explicitly puts proton therapy on the table. He notes that Oklahoma Proton Center offers all modalities, including conventional and stereotactic radiation, and that his team triages 5–10 outside patient inquiries per day at no charge to help patients find the right path regardless of where they ultimately receive treatment.
What You’ll Learn in This Episode
- Oropharyngeal Cancer: Cancers arising in the tonsils, soft palate, base of tongue, and the region above the larynx — a densely functional area governing swallowing, speech, and breathing.
- Proton vs. Photon Radiation: Photon (X-ray) beams pass through the entire body, while proton beams stop at a programmable depth, concentrating dose at the tumor and sparing surrounding healthy tissue.
- Level 1 Evidence: The trial was a multicenter, randomized controlled study across 21 institutions with over 440 patients — the highest tier of scientific proof available in clinical medicine.
- Dysphagia Reduction: Swallowing difficulty dropped from 49% in the photon arm to 31% in the proton arm — an 18-point absolute reduction and approximately 40% relative risk reduction.
- Xerostomia (Dry Mouth): Proton therapy significantly reduced chronic dry mouth by better sparing the salivary glands, with downstream benefits for nutrition and long-term dental health.
- Lymphopenia and Immune Function: Photon radiation reaching bone marrow suppresses immune cell production, increasing infection risk and impairing the body's own cancer-fighting capacity — an effect significantly reduced with protons.
- Gastrostomy (Feeding) Tube Dependence: Proton therapy cut feeding tube placement rates from roughly 40–50% down to approximately 19–20%, allowing far more patients to maintain oral nutrition through treatment.
- Treatment Completion and Survival: Fewer side effects with protons meant fewer treatment interruptions; gaps in radiation let cancer cells regrow, so completing the course as planned is directly linked to cure rates.
- Overall Survival Difference: Five-year overall survival was approximately 90% in the proton arm versus 80% in the photon arm — a 10-point gap considered landmark in a trial of this scale and design.
- Expanding Proton Evidence Base: Recent randomized trials for glioblastoma and esophageal cancer have also shown meaningful benefits from proton therapy, signaling a broadening clinical case for the modality.
- Multidisciplinary Care Teams: Dr. Chang urges every head and neck cancer patient to see a team of specialists — surgical oncology, medical oncology, and radiation oncology — who communicate with each other to build a coordinated treatment plan.
- Patient Advocacy for Proton Access: Because proton centers are not universally available, patients must proactively ask their oncologist whether proton therapy is appropriate for their specific tumor, size, and location — and seek a second opinion if needed.
The publication of this Phase 3 randomized trial marks a turning point for oropharyngeal cancer treatment. For the first time, the highest level of clinical evidence directly confirms what proton physicists and early adopters long suspected: stopping radiation at the tumor boundary is not merely a theoretical advantage — it translates into fewer feeding tubes, less immune suppression, less dry mouth, better swallowing, and, most critically, more patients alive five years after treatment. Dr. Chang and David Raubach encourage every patient facing a head and neck cancer diagnosis to ask specifically about proton therapy, seek a multidisciplinary evaluation, and connect with centers like Oklahoma Proton Center that can assess all available options without bias toward any single modality.
Full Transcript
Read Full Transcript
David Raubach: I want to thank you for joining us on today's episode of The Cancer Project podcast. We are really fortunate to have Dr. John Chang, the Medical Director of Oklahoma Proton Center, back on today, and we're going to talk about some really groundbreaking clinical trial results that just got published last week. Dr. Chang, thank you so much for joining us.
Dr. John Chang: Oh, thank you for having me.
David Raubach: So I've got to ask — you've treated quite a few head and neck cancer patients. Talk a little bit about the challenge of treating head and neck cancers.
Dr. John Chang: Yeah. So head and neck cancers are located in an area that have a lot of critical structures. Your essential functions day-to-day — eating, swallowing, talking — are all processed through this one area. So these head and neck cancers, when we treat them, they cause a lot of side effects because of the irritation that we cause in there. And so we try to minimize that as best as possible with techniques that really shield out the normal parts of the body.
David Raubach: So head and neck cancer — that's a broad term. We kind of toss that around. What are head and neck cancers?
Dr. John Chang: Well, typically when we refer to head and neck cancers, we're more talking about the cancers that are in the tract from your nose to your mouth to your throat to the back of your throat and your voice box. It includes all those areas. Now, each of those cancers can be unique, but there are groupings of those types of cancers that we approach with treatment and we have different techniques for each aspect. But again the main premise is trying to minimize damage to the normal parts of the body so that you have good quality of life going forward.
David Raubach: So what are the different types of treatments that a patient who has a throat cancer, tonsil cancer, base of tongue cancer, or a cancer in the nasal cavity might get?
Dr. John Chang: Yeah. So we have a lot of times this kind of three-pronged approach which can include surgery, chemotherapy, and radiation, and all of that has to work together in a team-like fashion to give the best results — both from the standpoint of effectiveness and also minimizing toxicity. So it's different for every cancer, but the most predominant cancer that we're seeing nowadays is in the oropharynx, which includes your tonsils, the palate, the back of your throat, and also right above where your voice box is.
David Raubach: So let's talk about radiation specifically. There are really two main types of radiation that we would use to treat head and neck cancer. Talk about those two types and the difference between the two.
Dr. John Chang: Sure. So the two types of radiation basically out there for all types of cancer are the photon treatments — which is regular radiation or X-ray treatments — and proton treatments, or particle-type treatments. X-ray treatments are essentially just a beam of energy that you throw at tumors and targets in the body. And like a beam of energy, it just passes straight through. There's a little bit of efficiency decrease with those treatments because that energy as it passes through, when it heads to the target, only about maybe 15 to 30% of that beam gets to that target. So you need multiple beams aimed at that same area to create the right targeting. But that means some low and medium dose radiation gets to the other tissues.
Dr. John Chang: Now, particle radiation — like protons, which is the most prevalent form of particle radiation that we use — is basically like shooting little tiny BBs at the cancer. And so based on how hard and fast you send those BBs, they go to a certain distance inside the body and then stop — and that's where most of the damage happens. And there's nothing going beyond it. So the benefit of protons, if I could summarize, is that as a form of radiation it can be stopped at a point inside the body. You as a doctor can say, “We want to stop this radiation inside the tumor” — and you can concentrate where you want the dose to go and really minimize any dose going anywhere else.
David Raubach: Okay. So I want to talk a little bit about this paper. The title of the paper is Proton versus Photon Radiotherapy for Patients with Oropharyngeal Cancer in the USA: A Multicenter Randomized Open-Label Non-Inferiority Phase 3 Trial. That is a mouthful. Let's take that phrase by phrase. First of all, when it says proton versus photon radiotherapy, what do we mean by that?
Dr. John Chang: Yeah. So exactly what I was just talking about — just the different types of radiation used to treat head and neck cancer. Both have been successful in curing patients, but we're always trying to maximize the second priority, which is maximizing quality of life afterwards.
David Raubach: Okay. So this is proton radiation versus traditional photon radiation. And then it says “with oropharyngeal cancer.” What is oropharyngeal cancer?
Dr. John Chang: So like I talked about before, the oropharynx is really the lining of the mouth and throat that encompasses where the tonsils are, where the palate is — that flap in the back of your throat — the back part of your throat, and then the part that sits right above the voice box. It's the area that helps you swallow and processes everything that goes down your throat, and also the part of the tongue that helps direct where the food needs to go and helps with talking.
David Raubach: Okay. And then this says it was a multicenter, randomized trial. What does that mean?
Dr. John Chang: So what it's doing is not just one institution treating patients — it was 21 institutions, which makes it much more relevant because you don't have just one place doing the treatment. You have every type of institution doing this treatment. So it's much more applicable to all the cancer centers that can do this type of treatment. And with that they were able to take over 440 patients and randomize them — meaning they didn't decide ahead of time who got which treatment. There was no bias. They basically enrolled on the trial and with an electronic flip of a coin, got one treatment or the other.
David Raubach: And that randomization is really important because it takes any bias out — any preconception a physician might have about which treatment to prefer. That's really the highest level of proof we'd be looking for as clinicians.
Dr. John Chang: Yeah. So we call it Level 1 evidence. We have a direct comparison, and whatever outcomes come from that should be applicable very well — the highest form of science we have.
David Raubach: Okay. So let's talk about the results of the paper. And I do want to mention — Dr. Steven Frank, who heads up the particle therapy program at MD Anderson, was the lead author on the paper. I want to give him credit for his work. There were two things that came out of this paper that I think were really interesting. One is a reduction in side effects. Let's talk about that first. Maybe just generally talk about side effects with radiation and proton therapy versus photon therapy.
Dr. John Chang: Sure. So in general the side effects you would get in the oropharyngeal area when delivering radiation — and adding chemotherapy on top of that — would be swallowing issues, dryness of the mouth, pain and soreness inside the throat, difficulty speaking, possible aspiration of food because the tongue isn't working as well, and food might go down the wrong way. So all those things can be a factor. And so the less of the normal tissues in that area that you damage, the better you preserve quality of life. We don't hit the swallowing muscles that don't have cancer in them as hard. We minimize the areas of the tongue that don't need treatment. We also spare the salivary glands that produce saliva — damage to those causes dry mouth. We are able to spare those a little better with proton treatment.
David Raubach: So a couple of numbers here. We'll start with one side effect: dysphagia. In the photon arm — traditional radiation — 49% of patients experienced dysphagia. In the proton arm, only 31%. That's an 18% absolute difference, and the relative reduction is closer to 40%. So what is dysphagia?
Dr. John Chang: That's any swallowing difficulty — whether it's mechanical or due to pain — anything that factors into your inability to swallow normally.
David Raubach: Okay. So basically any challenges with swallowing — significant reduction with protons. The next side effect here is xerostomia. There was a significant reduction in xerostomia in the proton arm versus the photon arm. What is that?
Dr. John Chang: That's dryness in the throat — basically the salivary glands not being able to produce enough saliva for you to swallow normally. When you eat food, unless you're chasing it with water all the time, it's hard to get more solid foods down your throat. So the xerostomia or dryness in your mouth can also impact swallowing. It leaves your teeth at higher risk for decay as well — that's an indirect problem. If you minimize the xerostomia, you're able to preserve your dentition better.
David Raubach: And this is like — okay, I woke up and I had dry mouth, but it just keeps going. It never goes away.
Dr. John Chang: Yeah. And it's like the Sahara Desert and you're not able to eat. And sometimes it's so dry that it blocks your airways because the mucus plugs up your breathing passage. A severe side effect for sure.
David Raubach: Okay. So then another side effect listed where there was a very noticeable reduction was lymphopenia. Lymphopenia was more common in the traditional radiation arm than in the proton arm. What is that?
Dr. John Chang: That is basically the amount of your immune cells available — which comes from your bone marrow. The more normal bone marrow that you expose to radiation, the less production of immune cells you have, and that can lead to a higher risk for infections.
David Raubach: And I think we've talked about this on another podcast — your body's immune system is trying to perpetually fight off disease. So if you damage it going through treatment, that makes you more susceptible to other complications. But your body's immune system is also doing what it can to fight the cancer as well. So there's a dual impact when you damage the immune system during treatment.
David Raubach: Okay. So the last side effect here — and there was a pretty significant reduction as well — is gastrostomy tube dependence. What is that?
Dr. John Chang: So a gastrostomy tube is the G-tube, or what we commonly call a feeding tube. It's basically putting a tube directly into your stomach to feed you with liquid nutrition if you're not able to swallow things by mouth. That's a surgery, that's a procedure, that's something invasive that you do to your body and we'd like to avoid that if we can. It used to be that when I treated all my head and neck patients, we would just preventatively put a feeding tube in. And more than half the time they would need it to get through treatment because they weren't getting enough nutrition by mouth. Now, we've gotten to the point — and this is a study we did at Northwestern — where we were able to reduce the amount of times we needed a feeding tube by half. It was never zero, but we had it down to about 19 to 20% with protons versus 40 to 50% with patients who got regular radiation.
David Raubach: Yeah, that's amazing. A feeding tube — that's also a very severe side effect, and it can impact a patient's ability to get through treatment without interruptions. And then — maybe I didn't mention this — but later in the paper they talk about weight loss as well, and there was a big difference in weight loss for patients getting traditional radiation versus protons. And the other thing that was almost surprising that came out of this paper — but maybe it actually shouldn't be that surprising — is that there was a difference in overall survival. Talk about what you saw as a doctor from the survival component.
Dr. John Chang: Yeah, and that's a part of the paper that I think needs a deeper dive to figure out the mechanism. There were more deaths related to the treatment with regular radiation than with protons. And what we know as oncologists is that as patients go through treatment, if there are any interruptions and delays, that has the potential of worsening your cure rate — because when you do a delay due to side effects, you're giving the cancer a chance to regrow during the interval. So the fact that you cause fewer side effects during therapy means you proceed through treatment as planned, and that gives you better results. You want to complete the treatment on time, on task all the way through. When you have delays in the middle of it, it allows the cancer to kind of grow back. And that's where I think we're seeing that patients are basically doing better effectiveness-wise by getting protons — because they're getting through treatment in its entirety as planned.
David Raubach: Okay. And I think the numbers here are roughly 90% overall survival at five years in the proton arm and about 80% overall survival in the photon arm — about a 10% difference. That's huge.
Dr. John Chang: That is an enormous difference, especially in a study like this where we've collectively treated tens of thousands, probably hundreds of thousands, of patients. There are some expectations about what survival would look like. So to have this randomization and have that big of a difference — it was surprising. And truly understanding what specific things are impacting that survival or causing a lower survival for photons is really important. But what we do know is that there's a benefit with protons, at least based on this trial.
David Raubach: So talk a little bit about how we apply what we've learned here to somebody who's been diagnosed with head and neck cancer. How should they be thinking about approaching care once they get that first diagnosis?
Dr. John Chang: With any cancers, I always advocate for them to see their oncologist and then also meet with all the other specialists — and hopefully they do it in an environment where all the specialists will talk to each other and then come up with a game plan that is right for their treatment process, best efficacy, and the best chance at minimizing side effects. You need all of that. And you want to make sure that they have all the right treatments at their disposal. Proton centers are not readily available everywhere, so patients need to advocate for themselves and ask: “Do you think this is a case where proton therapy would be better than regular radiation?” Sometimes it may not be — if it's just a very small tumor on one side that can be tackled with radiation using very small beams, sometimes regular radiation could be equal. But basically advocate for yourself, make sure you see a multidisciplinary team, and have that game plan laid out and explained to you.
David Raubach: And I think this is important at Oklahoma Proton Center because — despite what the name may imply — you actually do deliver and treat with traditional radiation as well. So when you see a patient, you're really assessing multiple options for that patient.
Dr. John Chang: Exactly. We have all the tools at our disposal so that if we want to do regular radiation, we can. If we want to do stereotactic radiation, we can. If we want to do protons, we can. And we have the ability to plan all those different types of modalities to see which one is best, equivalent, or inferior. I would encourage patients to talk to a doctor who uses proton therapy on a regular basis — not to say other doctors don't understand how protons work at a high level, but to understand how to apply it to a specific patient, because every cancer is unique.
Dr. John Chang: One of the things that is really nice about our center is that we have all the modalities, and on top of that I really enjoy talking to patients even if they don't come here for treatment — to get them on the right path. We have a website where patients can put in an inquiry. The triage team will tell them what they think they should do, or they'll present the information to me and I'll review the case. I'm not going to charge them for anything like that — I'm just going to tell them whether this is the right path to come or whether they should stay locally. I do that at least five to ten times a day. Taking the fear out of the diagnosis is half the battle initially, and then getting them to the right treatment.
David Raubach: Well, I really appreciate your time. Any final thoughts on the paper, the study, or where proton therapy is headed?
Dr. John Chang: What I really want to bring up is that this is a pivotal paper and a difference of 10% on overall survival is huge — especially in the context of it being a multicenter trial. We've recently had such huge innovations in proton therapy: glioblastoma, which is a deadly cancer where we've had no traction on improving it, just showed in a large randomized international cooperative group study — through RTOG — that there was a benefit in dose escalating with proton therapy. And there's also the study for esophageal cancer that showed a dramatic benefit for patients who had concurrent chemoradiation with protons over regular radiation. The data are starting to get out there, and the more patients we see and enroll on trials — at least on a registry trial if not an actual clinical trial — that's where the science will help guide us to the right treatment. And it's really pointing the way to using protons more and more.
David Raubach: Because I think we know that the physics are better — we've always known that protons stop and traditional radiation doesn't. But then what does that mean from a clinical standpoint? What are the differences we're going to see in side effects and survival? That's what we're still learning as we treat more and more patients and do these clinical trials. And the results have looked really good for protons. Theory becomes reality.
Dr. John Chang: Yeah. Theory becomes reality.
David Raubach: Well, that's great. Thank you so much, Dr. Chang. I really appreciate you stopping by to talk about this. As you mentioned, a very pivotal paper.
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