A phase II randomized study of proton therapy vs intensity-modulated radiation therapy in patients with unilateral head and neck cancer
In brief
Proton therapy reduces acute mouth sores by about two-thirds compared with IMRT
In a randomized phase II trial of 98 patients receiving unilateral postoperative radiotherapy, grade 2 or higher oral mucositis occurred in 7.4% of those treated with proton beams versus 22.7% with IMRT, and taste loss was also markedly lower. Local control and survival were similar, and late toxicities were rare, suggesting proton therapy may improve early quality of life without compromising efficacy.
- Journal
- Journal of the National Cancer Institute (Q1)
- Published
- 3 September 2026
- Study design
- Phase 2 randomized trial (exploratory)
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Edward Christopher Dee, Noah S Kalman, Daniel J Ma, Scott C Lester, Zhigang Zhang, Daphna Gelblum, et al.
- PMID
- 42690689
- DOI
- 10.1093/jnci/djag257
Why clinicians should know about it
- Picked for Radiation Oncology (paper of the day, 4 September 2026): Phase II RCT, practice-changing for adjuvant therapy
Abstract
Proton beam radiotherapy (PBRT) offers dosimetric advantages over intensity-modulated radiation therapy (IMRT), but prospective randomized data in the postoperative unilateral head and neck cancer setting remain limited. We conducted a multicenter, randomized phase II trial comparing PBRT and IMRT for patients with resected, well-lateralized head and neck cancers requiring unilateral adjuvant radiotherapy. Adults were randomized 1:1 to receive PBRT or IMRT to 60 Gy (relative biological effectiveness) in 30 fractions, with elective regions treated to 54 Gy. The primary endpoint was clinician-reported acute grade ≥2 oral mucositis through 3 months after radiotherapy. Ninety-eight patients were analyzable (PBRT, n = 54; IMRT, n = 44) with a median follow-up of 27.2 months. Acute grade ≥2 oral mucositis occurred less frequently with PBRT than IMRT (7.4% versus 22.7%, P = 0.03), as did acute grade ≥2 dysgeusia (9.3% versus 31.8%, P = 0.005). Rates of grade ≥3 dermatitis and grade ≥2 dysphagia were similar between groups, and late toxicities were uncommon with no grade 3 events. Patient-reported outcomes mirrored these findings, although confidence intervals were wide. Three-year local control, progression-free survival, and overall survival were high and were no different between arms. These findings indicate that PBRT reduces clinician-graded acute mucosal toxicity compared with IMRT in unilateral postoperative head and neck radiotherapy, in the context of some numerical but not statistically significant differences in patient-reported outcomes. ClinicalTrials.gov: NCT02923570.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.