October 01, 2025
4 min read
Key takeaways:
- Risk for late feeding tube dependence was low and did not differ between intensity-modulated radiation therapy and proton beam therapy for oropharyngeal cancer.
- Patients who received IMRT had lower rates of significant weight loss.
Intensity-modulated radiation therapy did not increase the risk for feeding tube dependence for patients with oropharyngeal squamous cell carcinoma compared with proton therapy, according to results of a randomized phase 3 trial.
The data, presented at American Society for Radiation Oncology Annual Meeting, also showed patients had similar quality of life metrics in the long term, including taste, chewing and speech, and survival outcomes regardless of the type of radiotherapy they received.
Data derived from Thomson D, et al. LBA 02. Presented at: ASTRO Annual Meeting; Sept. 27-Oct. 1, 2025; San Francisco.
“Contemporary intensity-modulated radiation therapy performed better than anticipated, showing the importance of fully optimized contemporary radiation therapy” David Thomson, MD, consultant clinical oncologist at The Christie NHS Foundation Trust, said during a press briefing.
“IMRT represents a very good treatment for this type of cancer, physicians and patients can be reassured of no requirement to access proton beam therapy which is a specialized treatment.”.
‘Severe’ adverse events
Oropharyngeal squamous cell carcinoma is the most common HPV-related malignancy in men and second most common HPV-related cancer in women, according to a press release.
IMRT plus chemotherapy is standard of care for the disease. It has “high cure rates,” Thomson said, but it also can cause “severe long-term side effects” such as difficulty swallowing, which could result in patients needing a feeding tube.
Proton therapy is an emerging treatment option that leaves less radiation in surrounding tissue, possibly reducing toxicities.
However, proton therapy requires special equipment, is not easily accessible and can be “substantially more expensive,” Thomson said.
“What we wanted to do in this randomized control trial is to establish the place of proton beam therapy for this type of cancer to see if it does reduce toxicities and improve quality of life for patients in the long term” he added.
Thomson and colleagues enrolled 205 patients (median age, 57.1 years; 79.5% men) with locally advanced oropharyngeal squamous cell carcinoma from the United Kingdom.
They randomly assigned them 2:1 to receive intensity-modulated proton therapy (n = 136) or IMRT (n = 69).
Both groups received the same radiation dose to the tumor (70 Gy/56 Gy in 33 fractions over 6.5 weeks) and concurrent cisplatin (100 mg/m² every 3 weeks).
Feeding tube dependence and weight loss of at least 20% (grade 3) from baseline, and patient-reported quality of life, both at 1 year, served as dual primary endpoints. Researchers evaluated quality of life with the University of Washington quality of life composite score of saliva, taste, chewing, swallowing, speech and appearance.
MD Anderson Dysphagia Inventory (MDADI), locoregional recurrence and OS served as secondary endpoints.
IMRT matches proton therapy
At 1 year, both arms had low rates of feeding tube dependence (1.7% each), but patients who received radiation had a lower rate of grade 3 weight loss (5.7% vs. 18.2%).
After combining the two outcomes, the proton therapy arm did not have a significantly higher risk for events (OR = 2.8; 95% CI, 0.8-10.4).
“These data showed that proton beam therapy delivered similar results to IMRT for treating oropharyngeal cancer,” Thomson said.
The IMRT arm also had a similar mean quality of life score as the proton therapy arm (77.1 vs. 78.3) and a similar mean MDADI composite swallow function score (79.7 vs. 79.5) at 1 year.
At median follow-up of 27 months, the radiation arm had similar 2-year locoregional free survival (96.8% vs. 94.3%) and OS (95.3% vs. 94.6%).
Overall, both arms had “very good outcomes in terms of tumor control,” Thomson said.
Perspective
These results are likely to generate considerable discussion within the head and neck community and may prompt questions on the results of other existing proton trials, given the contrasting findings. While not entirely unexpected, the results were different from what many anticipated.
Several aspects of the trial stood out.
At 6 weeks post-radiation therapy, the rates of acute side effects were comparable between intensity-modulated proton therapy and IMRT. Even at the conclusion of radiation therapy, the differences were not as marked as one might expect. Organ-at-risk doses remained relatively high with IMPT, such as 36.5 Gy to the oral cavity and 38.9 Gy to the inferior constrictor. In addition, there was considerable and prolonged weight loss at 12 months on the intensity-modulated proton therapy arm.
Overall, the differences — whether clinical, dosimetric or both — were less pronounced than anticipated. This raises important questions about the specifics of radiation planning, including the extent of elective dose and volume coverage.
With modern radiation planning and comprehensive supportive care, patients treated with IMRT can achieve excellent outcomes. Ultimately, biology and individualized treatment strategies matter more than the technology itself. Technology should be viewed as a tool to be effectively integrated into a treatment approach based on the understanding of tumor biology and behavior.
To sustain high cure rates while minimizing side effects, the most logical and potentially high-yield next step would be to reduce treatment volume and dose, both in gross tumor and elective regions.
It would be valuable to incorporate on-treatment tumor response monitoring via imaging and liquid biopsy for personalization of therapy.
C. Jillian Tsai, MD, MS, PhD
Disclosures: Tsai reports no relevant financial disclosures.
Sources/Disclosures
Source:
Thomson D, et al. LBA 02. Presented at: ASTRO Annual Meeting; Sept. 27-Oct. 1, 2025; San Francisco.
Reference:
Disclosures:
Healio could not confirm relevant financial disclosures at the time of publication.
