The Use of Protons in the Management of Recurrent, Previously Irradiated Adenoid Cystic Carcinoma

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Introduction: Adenoid cystic carcinoma (ACC) of the head and neck is a rare malignancy with a high risk of perineural invasion, local recurrence, and distant metastasis. Recurrent ACC poses unique challenges due to its aggressive nature, resection limited by morbidity, and prior radiation. Proton therapy, with its ability to spare normal tissues via the Bragg peak, may offer a promising and safe re-irradiation approach, especially in patients not amenable to resection requiring high definitive doses. The purpose of this study was to evaluate outcomes of patients with recurrent ACC treated with proton radiation. Methods: We reviewed the records of all patients with recurrent head and neck ACC treated with proton therapy between November 2012 and December 2023. This cohort included patients with both resected and unresected disease. Standard imaging, including MRI for perineural spread and PET for distant recurrence, was used in all cases. Descriptive statistics were used to analyze patient, tumor, and treatment characteristics, and the Kaplan-Meier method and cumulative incidence curves were utilized to estimate overall survival (OS) and loco-regional recurrence (LRR), respectively. Results: A total of 19 patients were included, with 6 (32%) receiving adjuvant re-irradiation and 13 (68%) receiving definitive proton re-irradiation. Median dose in the adjuvant group was 63.36 (59.40-70.07), and 59.20 (14.80-70.00) in the primary RT group. The median OS for all patients was 62% at 24 months and 48% at 48 months. Patients receiving adjuvant therapy had an OS of 80% at 24 and 48 months, while those not receiving surgery had an OS of 52% and 31% at 24- and 48-months. LRR at 24 months was 11% for all patients. No grade 5 toxicities were observed. Conclusion: This study demonstrates the feasibility and potential benefits of proton re-irradiation for recurrent ACC, with promising local-regional control and minimal toxicity.

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