Abstract: Objective To systematically evaluate and compare the efficacy and safety profiles of proton therapy (PT)  and X⁃ray radiation therapy (XRT)  in head and neck cancer. Methods  A systematic review and meta⁃analysis were conducted, incorporating thirteen studies published between 2015 and 2024, comprising 863 cases in the PT group and 2，443 cases in the XRT group. The analysis evaluated local control (LC) rate at 1 and 2 years, disease⁃free survival/progression⁃free survival (DFS/PFS) rate at 1, 2, and 3 years,  as well as overall survival (OS) rate. Additionally, it examined the incidence of acute toxicities of grade 2 or higher. Results No statistically significant differences were observed between the PT group and the XRT group in terms of 1⁃year LC rate  OR=1.16, 95%CI: 0.19-7.25) or 2⁃year LC rate (RR=0.74, 95%CI: 0.54-1.02). Furthermore , there were no statistically significant differences in DFS/PFS rate between the two groups at 1⁃year (RR=0.93, 95%CI: 0.67-1.29), 2⁃year (RR=0.91, 95%CI: 0.67-1.22), and 3⁃year (RR=0.99, 95%CI: 0.75-1.29). However, the PT group demonstrated superior OS at 1⁃year (CI=0.47, 95%CI: 0.35-0.65), 2⁃year (RR=0.52, 95%CI: 0.40-0.67), and 3⁃year (RR=0.56, 95%CI: 0.45-0.69) compared to the XRT group. Additionally, the incidence of  ≥grade 2 dysphagia (OR=0.35, 95%CI: 0.18-0.69) and fatigue (OR=0.46, 95%CI: 0.24-0.90) was lower in the PT group than in the XRT group. Conclusions The PT group demonstrates superior survival benefits and reduced acute toxicity risks compared to the XRT group in the treatment of head and neck cancer. Further prospective studies are warranted to validate the efficacy and safety of PT.

Key words: Head and neck cancer, Proton therapy, X?ray radiation therapy, Survival ratio； Toxicity