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

To evaluate efficacy and toxicity (CTCAE v4.0) outcomes in patients with adenoid cystic carcinoma (ACC) treated with proton beam therapy (PBT). 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. 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. 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.