Phase III Oropharyngeal Cancer Trial Shows Proton Therapy Improves Survival and Quality of Life
February 10, 2026
Since the mid-2000s, the incidence of oral cavity and oropharyngeal cancers has increased by about 1% per year, a rise coincident with a demographic shift to younger patients. These changes have largely been driven by an increase in cancers associated with human papillomavirus (HPV), which estimates suggest affect up to 80% of new oral cavity and oropharyngeal cancer diagnoses in the U.S.
Our goal as physicians is to both extend life and preserve its quality in these patients, a feat that can be difficult for these cancers due to the affected anatomy and nearby structures. Until recently, it wasn’t clear whether photon therapy (intensity modulated radiation therapy, IMRT) or proton therapy (intensity modulated proton therapy, IMPT) was the best choice for meeting this aim – but a new study by our group and MD Anderson Cancer Center, Massachusetts General Hospital, Memorial Sloan Kettering Cancer Center and others show that IMPT is the clear winner.
Dr. Jason Molitoris
Associate Professor of Radiation Oncology, University of Maryland School of Medicine
Intensity Modulated Radiation Therapy’s Drawbacks
Although IMRT has been considered the gold standard for oral cavity and oropharyngeal tumor radiation, the treatment field for these cancers is full of critical structures that often suffer collateral damage. For example, dose to nearby salivary glands frequently leaves patients with lasting dry mouth, which can further affect oral health and patient comfort. Muscles and anatomy critical for swallowing can also be damaged, sometimes necessitating feeding tubes and other invasive interventions.
In contrast, IMPT’s targeted nature has the potential to deliver effective radiation therapy while decreasing dose to critical structures. But how it compared to IMRT had never been tested in a definitive clinical trial.
Patient being fitted for mask in preparation for proton therapy treatment.
Significant Advantages for Intensity Modulated Proton Therapy
To address this question, the Maryland Proton Treatment Center joined colleagues at 20 other treatment sites scattered across the U.S. for a randomized, open-label, noninferiority phase 3 trial designed to compare IMRT with IMPT in 440 oropharyngeal cancer patients. Patients were assigned about 1:1 to each group and received the same radiation dose of 70 Gy in 33 fractions, along with systemic therapy determined locally at their institutions.
At a follow-up of five years, we and our colleagues found that IMPT was not only noninferior to IMRT but also held significant advantages. For example, overall survival was about 10% higher in the IMPT group compared to the IMRT group at 5 years. Although local/regional recurrences and distant metastases were about the same between the two groups, patients who received IMPT were significantly less likely to suffer from dry mouth (33% vs. 45%), have trouble swallowing (31% vs. 49%), depend on a gastronomy tube (26.8% vs. 40.2%), or experience a severe drop in lymphocytes (76% vs. 89%). It’s extraordinarily rare for a treatment modality to both extend survival and reduce side effects compared to the current gold standard.
Together, these findings demonstrate that IMPT represents a new standard-of-care treatment option for oropharyngeal cancer. Future studies in the works will build on these findings by assessing outcomes in these patients over a longer follow-up period, as well as comparing long-term healthcare costs between these two treatments.
Real-World Benefit For Our Patients
The reduced side-effects seen in this trial translate to meaningful benefits for our patients. This is exemplified by one such patient, Paul Murray, who is a gifted and passionate singer. He was enrolled in the clinical trial and treated with IMPT, which allowed him to preserve function of his vocal cords. He spoke with WBAL-TV and shared his experience with treatment.
