SAN FRANCISCO, September 29, 2025 — A new phase III clinical trial finds that intensity-modulated radiation therapy (IMRT) and proton beam therapy resulted in similar quality-of-life outcomes and low rates of side effects for people with locally advanced oropharyngeal cancer. The TORPEdO trial, a randomized study conducted across the United Kingdom, found no meaningful differences between the treatments in patient-reported quality of life, swallowing function or feeding tube dependence at one year.
Both advanced radiation approaches resulted in excellent tumor control and notably fewer long-term side effects than expected. Initial results of the trial will be presented today at the American Society for Radiation Oncology (ASTRO) Annual Meeting .
"We found no evidence of a difference in late patient-reported physical side effects or quality of life between proton beam therapy and IMRT, with contemporary IMRT performing better than we anticipated," said David Thomson, MD, chief investigator on the trial and a consultant clinical oncologist at The Christie NHS Foundation Trust in Manchester, England. "Our results confirm that high quality IMRT is a very good treatment for this disease."
Oropharyngeal squamous cell carcinoma (OPSCC) is a head and neck cancer affecting the middle part of the throat. Its incidence is rising in many countries due to increasing human papillomavirus (HPV) infection, a primary driver of the disease. It is the most common HPV-related cancer in men and the second most common in women. Standard treatment for locally advanced OPSCC involves IMRT combined with chemotherapy, and while this treatment is highly effective at curing and controlling cancer, it can also cause severe side effects such as difficulty with swallowing that may require the use of a feeding tube.
IMRT is an advanced photon-based technique that shapes and modulates radiation beams to precisely target tumors. Photon beams effectively eliminate cancer tumors but scatter bits of radiation along the way that can lead to side effects in the area treated. Proton therapy, a newer approach, uses proton beams that deposit less radiation along their path to the tumor, potentially sparing surrounding healthy tissue and resulting in possibly fewer side effects. This type of radiation treatment requires specialized facilities and training, however, and is thus less widely available and substantially more expensive.
"There's been interest in the use of proton beam therapy specifically for head and neck cancers because of the intricate nature of treating this area, with nearby organs for chewing, swallowing, speech, hearing and other important functions. Trying to reduce the radiation dose to these organs is important because it may result in fewer side effects and improved functioning," Dr. Thomson said.
For the TORPEdO (TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer) trial, 205 patients with locally advanced OPSCC were randomly assigned 2:1 to receive either intensity-modulated proton therapy (n=136) or IMRT (n=69) with concurrent cisplatin chemotherapy at centers across the UK between 2020 and 2023. The median age was 57.1, most patients were male (79.5%) and most had fewer than 10 pack-years of smoking history (67.8%).
The trial's co-primary endpoints combined clinical measures and patient-reported outcomes: clinicians assessed feeding tube use and severe weight loss (20% from baseline), while patients were asked to self-report side effects and quality of life via questionnaires at baseline and multiple timepoints after treatment.
One year after treatment, both groups showed very low rates of patients who were dependent on a feeding tube (1.7% each). Severe weight loss occurred more frequently in the proton arm (18.2%) compared with IMRT (5.7%). The trial's design specified that the clinical endpoint would be a composite of these measures, and no statistically significant difference was observed between the treatment arms (p=0.08).
These findings offer additional context alongside a phase III trial reported in 2024 that also compared proton therapy and IMRT for locally advanced OPSCC. That study found proton therapy reduced feeding tube dependence at the conclusion of treatment when compared to IMRT. This report of the TORPEdO trial focuses on dependence at one year.
For patient-reported outcomes, no differences were observed between the proton and IMRT arms one year after treatment on a composite functional index for saliva, taste, chewing, swallowing, speech and appearance (University of Washington Quality of Life: 78.3 for protons vs. 77.1 for IMRT) nor on a measure specifically for swallowing function (MD Anderson Dysphagia Inventory: 79.5 vs. 79.7, respectively).
"IMRT performed better than expected based on historical data involving patient reported outcomes, and long-term feeding tube dependence was much lower than reported in previous trials," said Dr. Thomson. "It's an encouraging finding that patients with this type of cancer can receive excellent care at their local treatment centers with this advanced technology."
Survival rates were similarly high for both groups. At a median follow-up of 28.3 months, two-year freedom from cancer returning at or near the original tumor site was 94.3% for protons and 96.8% for IMRT, with overall survival rates of 94.6% for protons and 95.3% for IMRT.
Dosimetric analyses showed that proton therapy was able to lower radiation exposure to nearby swallowing and salivary gland structures, Dr. Thomson said, but "these reduced doses to healthy structures did not translate into measurable differences in patient-reported outcomes, function or quality of life." He said the dosimetric effect "seems to be necessary but not sufficient" for meaningful patient benefit in OPSCC.
In addition to focusing on patient-reported, clinically relevant outcomes, Dr. Thomson said a strength of the TORPEdO trial was its rigorous quality assurance. Treatment planning and delivery in both arms met strict standards overseen by the UK's National Radiotherapy Trials Quality Assurance Group. "We wanted to be confident that both arms delivered the highest-quality care to ensure a valid comparison between these advanced techniques."
