Toxicity and Oncologic Outcomes of Proton Radiotherapy for Oropharyngeal Cancer: A Systematic Review and Meta-Analysis.

Intensity-modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC) is associated with acute and late toxicities that impact patient quality of life. Proton radiotherapy (PRT) can reduce exposure to surrounding tissues, but the clinical magnitude of this advantage is unclear. A systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included studies reported toxicity or oncologic outcomes from patients treated with PRT for OPC. Pooled outcomes were estimated using random-effects models. Comparisons between PRT and IMRT were performed using log odds ratios. Primary outcomes were the pooled rates of adverse events, overall survival (OS), and progression-free survival (PFS). A total of 18 studies (16 retrospective, two prospective) consisting of 956 patients were identified. Pooled rates of acute grade 3+ toxicities were as follows: dermatitis 19%, mucositis 32%, xerostomia 1.3%, dysphagia 13%, and weight loss 1.4%. The pooled rate of acute hospitalizations was 10%. Among studies reporting late toxicities, the rates of grade 3+ xerostomia and dysphagia were 1.1% and 1.6%, respectively. Compared to IMRT, PRT was associated with lower rates of acute feeding tube use (21% versus 31%; P = 0.0012), but not long-term feeding tube use (1.4% versus 2.7%; P = 0.24). After PRT, OS at two and three years were 98% and 96%, while PFS at two and three years were 93% and 86%. PRT for patients with OPC is associated with favorable toxicity and oncologic outcomes. While randomized clinical trials are ongoing, these data provide additional evidence regarding the efficacy of PRT in the upfront treatment of OPC.