A phase II randomized study of proton therapy vs intensity-modulated radiation therapy in patients with unilateral head and neck cancer.

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.