Proton Therapy for Head and Neck Adenoid Cystic Carcinoma: A Multi-institutional Review.

Purpose: To evaluate efficacy and toxicity (CTCAE v4.0) outcomes in patients with adenoid cystic carcinoma (ACC) treated with proton beam therapy (PBT). Patients and Methods: From 2012 through 2023, 79 patients with non-metastatic ACC were treated with PBT and enrolled on the Proton Collaborative Group (PCG) registry. Kaplan-Meier analyses quantified locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). ACC patients receiving reirradiation with PBT were excluded from this analysis. Results: Median follow-up was 3 years (0.01-6.72). Twenty-six patients were unable to undergo surgery and received definitive PBT versus postoperative PBT (n=53). Median postoperative PBT dose was 66 GyE and 70 GyE for definitive patients treated with conventional fractionation. Most patients had localized disease (n=75); few had nodal metastases (n=4). 62% were locally advanced (T3-T4) at the time of PBT treatment. 3-year Locoregional control (LRC) for all patients was 98% [95% CI (94.3, 100)]. Advanced T-staging, positive margins and definitive-intent PBT were not associated with worsened LRC. 3-year Progression free survival (PFS) was 80.5% (70.6, 91.7). Patients receiving definitive intent PBT had lower but nonsignificant PFS (73.3% vs. 83.8%, p-0.075). Advanced T-staging and positive margins did not have worsened PFS. Overall survival at 3 years was 89.2% (81.4, 97.8). Acute grade 3 toxicities occurred in 16 patients, the most common included the following: mucositis (n=5), oral pain (n=3), and dermatitis (n=5). Late grade 3 toxicity (n=2) included middle ear inflammation (n=1) and skin ulceration (n=1). There were no grade 4+ toxicities. Conclusion: PBT appears to be highly efficacious in providing LRC for patients with ACC including those patients treated with definitive intent. PBT toxicity was acceptable. Longer follow-up is needed.