The Use of Proton Radiation in the Management of Adenoid Cystic Carcinoma.

Purpose/Objectives: Adenoid cystic carcinoma (ACC) of the head and neck is a rare malignancy with a prolonged but infiltrative course, marked by perineural invasion and high risk of local recurrence and distant metastases. The standard of care for head/neck ACC is surgery and postoperative radiation. Definitive radiation is reserved for those with definitive disease. Given the advantage of proton beam to tailor its dose around the tumor while sparing critical tissues, we sought to report our proton experience in the treatment of head/neck ACC. Materials/Methods: We retrospectively analyzed 106 patients treated with definitive or adjuvant proton therapy for ACC from 2012 to 2023. All patients were staged with computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) and were evaluated by a multidisciplinary team. Radiation doses were ≥66 Gy(RBE) adjuvantly and ≥70 Gy(RBE) definitively. Patients were treated using either uniform scanning or pencil beam scanning (PBS) proton therapy. Primary endpoints included overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LRR), assessed using Kaplan-Meier and cumulative incidence methods. Results: Of 106 patients, 76 were treated postoperatively and 30 definitively. The 5-year OS was 75% overall, 86% for the adjuvant group, and 45% for the definitive group. Five-year PFS was 47% overall, 54% (adjuvant) vs 29% (definitive). Locoregional control at 5 years was 89% overall, with 93% for adjuvant vs 74% for definitive treatment. Toxicities were generally mild, with acute grade ≤2 dermatitis (53%) and mucositis (33%) most common. Chronic toxicities included xerostomia (38%) and temporal lobe necrosis (4%). Conclusion: Proton therapy for ACC of the head and neck yields excellent locoregional control, particularly in the adjuvant setting, with manageable toxicity. For patients with unresectable disease or those seeking organ preservation, definitive proton therapy remains a viable, durable treatment option. These findings support proton therapy as a preferred modality in head and neck ACC.