Two major clinical trials presented at the American Society of Radiation Oncology (ASTRO) Annual Meeting have produced conflicting results regarding the comparative effectiveness of proton beam therapy versus intensity-modulated radiotherapy (IMRT) for treating head and neck cancer, highlighting the complexity of evaluating advanced radiation treatments.
UK TORPEdO Trial Finds No Advantage for Proton Therapy
The nationwide TORPEdO trial, funded by Cancer Research UK and The Taylor Family Foundation and managed by The Institute of Cancer Research, London, found no significant differences between proton beam therapy and IMRT in treating head and neck cancer patients. The multi-center study randomly assigned 205 patients to either treatment between 2020 and 2023.
"For most people with head and neck cancer, proton beam therapy did not reduce side effects compared to IMRT," said Professor Emma Hall, Professor of Oncology Trials at the Institute of Cancer Research and TORPEdO trial co-lead. One year after treatment, both groups reported similar outcomes in taste, chewing, swallowing, speech, saliva function and appearance.
Professor David Thomson, Clinical lead for head and neck cancer at the Christie NHS Foundation Trust and Chief Investigator of the TORPEdO trial, emphasized that "for most people with head and neck cancer, IMRT and proton beam therapy are equally effective treatments, giving similar results in terms of survival and quality of life afterwards."
MSK Study Shows Proton Therapy Superiority
In contrast, Memorial Sloan Kettering Cancer Center's phase 2 clinical trial (NCT02923570) demonstrated significant advantages for proton beam therapy over IMRT. The study, conducted across nine locations including seven MSK sites, enrolled 108 patients with salivary gland tumors, skin cancers, melanoma, and tonsil cancers requiring post-operative unilateral radiation.
Among 98 evaluable patients, the proton therapy group showed dramatically lower rates of acute grade 2 or higher mucositis at 7.5% compared to 22.2% in the IMRT group (p = 0.0376). Proton beam therapy also demonstrated significantly lower incidence of acute grade 2 or higher taste dysfunction at 7.7% versus 33% for IMRT (p=0.002).
"Until this study, prospective evidence comparing proton beam radiotherapy with IMRT for this patient population had been lacking," said Dr. Nancy Lee, Service Chief of Head & Neck Radiation Oncology and Proton Therapy at MSK, who designed and initiated the trial. "Importantly, our study included patient-reported outcomes as clinician grading alone tends to underestimate symptom burden."
Comparable Survival Outcomes Across Both Studies
Despite their different conclusions regarding toxicity, both trials demonstrated excellent survival outcomes. The MSK study reported three-year progression-free survival rates of 92.3% for proton therapy and 94.1% for IMRT, with three-year overall survival rates of 97.4% and 97.6%, respectively. The TORPEdO trial similarly found no differences in survival between treatment groups.
Patient Experience and Quality of Life
Patient-reported outcomes differed significantly between the studies. In the MSK trial, patients receiving proton beam therapy reported better functional and global health outcomes, with fewer complaints of mouth and throat soreness, skin burn sensitivity, and skin darkening affecting quality of life.
The TORPEdO trial included patient testimonials like Tex Leece, a 52-year-old delivery driver who received standard radiotherapy and remained cancer-free more than three years later. "I'm really well, and still super active thanks to the treatment I received," Leece said. "I'm not surprised by the results of the trial as I'd done so well with the standard radiotherapy I was given."
Treatment Methodology Differences
Both proton beam therapy and IMRT represent advanced approaches to radiation treatment. Proton beam therapy directs highly charged particles called protons onto tumors, while IMRT uses computer programs to create radiation beams that match tumor shapes, delivered through linear accelerator machines.
The MSK study focused on patients requiring unilateral radiation, with high-risk regions receiving 60 to 66 Gray and lower-risk areas receiving 50 to 54 Gray. Among the 98 evaluable patients, 60 had parotid/salivary gland tumors, 27 had skin cancers, and 11 had tonsil cancers, with squamous cell carcinoma, mucoepidermoid carcinoma, and adenoid cystic carcinoma being the most common histologies.
Infrastructure and Access Considerations
The conflicting results have implications for treatment infrastructure. Proton beam therapy is available at only two UK locations: The Christie NHS Foundation Trust in Manchester and University College London Hospital. In contrast, IMRT utilizes more widely available linear accelerator machines, though the Royal College of Radiologists estimates that many of England's approximately 340 LINAC machines require upgrading.
"These findings reinforce the importance of ensuring that high-quality IMRT is accessible to patients across the UK, which will require further investment in modern linear accelerator machines," Professor Hall noted.
Dr. Catherine Elliott, Director of Research at Cancer Research UK, emphasized the broader context: "Between now and 2040, we expect 6 million new cancer cases to be diagnosed across England, and we will need to ensure that health services are prepared for the increased capacity this will require."
