The field of head and neck oncology is currently witnessing a paradigm shift, as the "more is better" approach to radiation is giving way to a sophisticated "precision-first" philosophy. In a recent discussion with CancerNetwork®, Jason Molitoris, MD, PhD, associate professor of Radiation Oncology and director of the Clinical Hyperthermia Program at the University of Maryland, detailed why intensity-modulated proton therapy (IMPT) has officially transitioned from an experimental alternative to a definitive standard of care for oropharyngeal squamous cell carcinoma (OPSCC). This was contextualized by a presentation he gave at the American College of Radiation Oncology (ACRO) 2026 Radiation Oncology Summit.¹

Driven by landmark phase 3 data released in 2025, Molitoris highlighted a critical evolution: looking beyond survival to consider the quality of survival. For the rising demographic of younger patients with p16-positive disease, the goal is to minimize long-term adverse effects that can persist for decades. The rationale for IMPT over traditional photon therapy lies in its unique physical properties, with Molitoris emphasizing 2 takeaways: immune preservation and functional longevity.

Molitoris also addressed geographic and socioeconomic disparities in the field. Through innovative "cost-neutral" billing systems and logistical support at the University of Maryland, his team is working to ensure that a patient's zip code doesn't determine their access to life-altering technology.

Looking ahead, the next 3 to 5 years may promise even greater refinement. Through volume de-escalation and risk-stratification—potentially guided by circulating tumor DNA (ctDNA)—the oncology community is moving toward a future where treatment is as unique as the patient’s own biology.

CancerNetwork: What was the rationale for your presentation on proton therapy for oropharyngeal cancer?

Molitoris: The rationale for the presentation was that there were some big new data that were presented in 2025, and the organizers of the meeting wanted to have a discussion about the use of proton therapy in OPSCC given these new data that we have available to us now.

What are some of the main takeaways from your presentation?

What I tried to do was highlight different areas in which we use proton therapy for oropharyngeal cancer and highlight some of these newer data that have emerged. We talked a bit about use of proton therapy in treatment of patients where you treat bilateral cervical nodal disease, and then also patients whom we treat either postoperatively or patients where we only have to treat one side of the neck.

Can you elaborate on the theory that reduced doses to the bone marrow and circulating lymphocytes preserve the immune system’s ability to monitor cancer?

This is something that is exciting and very exploratory based on the Lancet article on the University of MD Anderson Texas Cancer Center randomized clinical trial [NCT01893307] for proton therapy in oropharyngeal cancer.² We did notice through the running of that trial that there was reduced lymphopenia, meaning that the white blood cells were able to maintain higher levels throughout the course of treatment with proton therapy compared to photon therapy. It’s still exploratory as to the importance of that with respect to patients during and shortly after their treatment, as well as the ability for the body to surveil for cancer cells in the future. There are data in other disease sites, which also demonstrate that maintaining those white blood cell counts through the course of treatment and beyond does have prognostic significance for patients.

Do you see volume de-escalation and technology-based de-escalation as competing or complementary?

They’re going to be complementary. What we’re trying to do outside of proton therapy [is] decrease the toxicity for patients by either decreasing radiation doses or decreasing the volume of the neck lymph node stations that we treat. These are going to be complementary because if you can further decrease the radiation dose to both the minor and major salivary glands with multiple technologies, you’re going to drastically improve outcomes for patients.

The data indicate that there’s a substantial reduction in feeding tube requirements with protons versus photons. What have you observed in terms of the speed of functional recovery for swallowing?

The way that proton therapy helps patients is going to be more in the long-term benefits. What I see in my clinic when I treat patients with photons or protons is that patients still have difficulty with swallowing, difficulty with lack of taste, and difficulty with mucositis towards the end of their treatment. Maybe proton therapy has slightly reduced amounts of [those toxicities] overall compared with photon therapy at the end of treatment and for the short period of time afterwards.

We haven’t noticed in our patient population a difference in percutaneous endoscopic gastrostomy (PEG) tube rate between photons and protons. The ability to maintain salivary function and decrease radiation doses to the swallowing muscles [and] the pharyngeal constrictors will have long-term benefits for patients 5 and 10 years after their treatment. This is becoming more important for this patient population because oropharyngeal cancer is affecting younger patients who have [fewer] comorbidities, and they have a lot longer time to live after their treatment.

With phase 3 data emerging showing improved survival and reduced high-grade toxicity, should IMPT now be considered the preferred standard of care for p16-positive oropharyngeal cancer?

IMPT is now an additional standard of care for patients with OPSCC, and we should be discussing differences in treatment between proton therapy and photon therapy with these patients. The differences include the findings on the phase 3 randomized clinical trial demonstrating an improved overall survival benefit, but also on limitations associated with the use of proton therapy, which can be logistic in nature or insurance based.

How do clinicians address the geographic and socioeconomic disparities in access to radiotherapy that persist for these patients?

At the University of Maryland, we do a number of things to help with socioeconomic and geographic challenges associated with the delivery of proton therapy. It’s well known that there are fewer proton therapy centers throughout the country than there are photon therapies, and it can be geographically limiting to patients. Our center has a cost-neutral system where we bill insurance companies at the same rate for proton therapy and photon therapy. This has led to the highest approval ratings for proton therapy-treated patients in the country. We also provide transportation services as well as lodging near our proton therapy center so that we can give proton therapy to patients who truly benefit from that treatment.

More broadly, there are things that we can do to help with uptake of proton therapy. First, we can run clinical trials comparing proton therapy with photon therapy. We need to find the areas where proton therapy truly benefits patients. Our center has opened all the phase 3 randomized control trials comparing protons to photons because we believe strongly in generating data for patients across cancer subsites. There are more proton therapy centers being built, and data [from studies] like this phase 3 randomized controlled trial that we’ve been discussing will lead to more availability of proton therapy across the country.

Looking 3 to 5 years in the future, where do you see the broader radiation treatment landscape for oropharyngealcancer heading?

Looking 3 to 5 years from now, we’re going to continue to increase the use of proton therapy in this patient population. I also see other significant efforts made to risk-stratify patients and use that risk stratification to allow for treatment escalation and treatment de-escalation. We have [several] trials with our medical oncology colleagues where we’re adding adjuvant immunotherapy for some of these patient populations, and those data are being collected and evaluated for patients with higher-risk OPSCC. For patients with lower-risk [disease], we’re trying to de-escalate treatment. That can be volume de-escalation treatments, like we do at the University of Maryland, but that could also be dose-based de-escalations based on ctDNA or other factors.

References

1. Molitoris J. Proton therapy for oropharyngeal cancer. Presented at: American College of Radiation Oncology 2026 Radiation Oncology Summit; February 4-6, 2026; Orlando, FL.
2. Frank SJ, Busse PM, Lee JJ, et al. Proton versus photon radiotherapy for patients with oropharyngeal cancer in the USA: a multicentre, randomised, open-label, non-inferiority phase 3 trial. Lancet. 2026;407(10524):174-184. doi:10.1016/S0140-6736(25)01962-2