Proton beam therapy in the treatment of adenoid cystic carcinoma of the head and neck: a single enterprise retrospective cohort study

Background and aims Adenoid cystic carcinoma (ACC) is a rare salivary gland malignancy with high propensity for perineural invasion (PNI) and relative radioresistance. Proton beam therapy (PBT) may improve tumor control through improved target coverage, as well as higher physical and biologic dose while limiting dose to surrounding critical structures. This single-enterprise two-site study reports outcomes and toxicity in patients with ACC of the head and neck (HN) region treated with curative-intent PBT. Methods From 2015–2025, 89 patients with HN ACC were treated with curative-intent PBT. Patients with distant metastases or prior radiotherapy (RT) were excluded. Clinical outcomes were assessed retrospectively. Toxicities were recorded prospectively using CTCAE v5.0. The Kaplan–Meier method was used to estimate local tumor control (LC), distant metastasis-free survival (DMFS) and overall survival (OS). Hazard ratios, 95% confidence intervals (CIs), and test of association between tumor and treatment variables and outcomes were estimated using Cox proportional hazards regression analysis. Results Median follow-up was 3.1 years. Sixty-nine patients underwent surgery followed by postoperative PBT, while 20 received definitive PBT for unresectable disease. The 3-year LC rate was 98.3% following postoperative PBT and 82.6% following definitive PBT. Treatment approach was not significantly associated with LC. Three-year DMFS was 86.2% and 64.9%, respectively, while 3-year OS was 94.4% in both cohorts. Twenty-one patients developed distant metastases, most commonly involving the lungs. Six patients experienced acute grade 3 toxicities, including dysphagia, mucositis, and dermatitis; seven experienced late grade 3 toxicities, most commonly osteoradionecrosis (n=4). One patient had both acute and late toxicity. No grade 4 or 5 toxicities occurred. Conclusions Curative-intent PBT was associated with favorable LC and acceptable toxicity. Outcomes according to definitive versus postoperative treatment should be interpreted descriptively due to substantial baseline differences between groups and confounding by indication. Longer follow-up and larger studies are needed.