Adenoid Cystic Carcinoma of the Head and Neck: Patterns of Recurrence and Implications for Radiotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Radiotherapy (RT) plays a central role in locoregional control for adenoid cystic carcinoma of the head and neck (ACC). Guidelines on the optimal RT dose, treatment volumes, and modality are lacking in the highly conformal era. We sought to evaluate ACC patterns of recurrence to assess the efficacy of highly conformal RT and optimize target volumes and dose. <h3>Materials/Methods</h3> We identified all patients with ACC consecutively treated at our institution with curative-intent adjuvant or definitive RT from 2005 to 2021 and recorded local (LR) and distant metastasis (DM) events. RT plans were compared to diagnostic imaging to identify in-field, out-of-field, and marginal LRs. Marginal LRs were defined as those within the 50 Gy isodose line but outside of the CTV. <h3>Results</h3> Ninety-nine patients were included. Median follow-up was 5.1 years (IQR: 2.2-9.0). Eighty (80.8%) patients underwent surgery prior to RT. Dose was <60 Gy (10, 10.1%), 60 Gy (49, 49.5%), >60/<70 Gy (19, 19.2%), or 70 Gy (21, 21.2%). CTVs included at least one lymph node level in 61 (61.6%) patients. CTVs tracked along cranial nerves (CN) in 67 (67.7%) patients, with 61 (61.6%) receiving RT to CN V and 43 (43.4%) to CN VII. CN were tracked to the skull base and brainstem in 46 (46.5%) and 21 (21.2%) patients, respectively. Thirty-one (31.3%) patients received intensity modulated proton therapy, with the remainder (68, 68.7%) receiving photon-based intensity modulated radiation therapy. The 2- and 5-year LR risk was 3.6% (95% CI: 1.2-10.9) and 12.2% (6.6-22.7). Predictors of LR on univariate analysis included nasal cavity/nasopharynx location [HR 7.30 (1.17-45.66), <i>p</i>=.034] and primary tumor volume [per 10 cc, HR 1.44 (1.05-1.97), <i>p</i>=.023]. All other factors including concurrent chemotherapy and proton therapy were not associated. Although prescribed RT dose was not significant, 7 of the 10 patients with in-field LRs received ≤60 Gy [50 Gy (n=1), 54 Gy (n=1), 56 Gy (n=1), 60 Gy (n=4)]. Only 2 patients experienced a marginal LR, one with an oral cavity primary that recurred in the mandible bone, and the other with a submandibular primary that recurred in the oropharyngeal mucosa. Only 1 patient each had an out-of-field LR and regional nodal recurrence. Six of the 7 patients with a skull base recurrence (SBR) had coverage of CN to the skull base (n=3) or brainstem (n=3). Six recurred in a treated CN (in-field), and the other recurred in an untreated CN (out-of-field). DM risk was 26.9% (18.9-38.2) and 44.0% (33.8-57.3) at 2- and 5-years, respectively. Median overall survival was 9.2 years. <h3>Conclusion</h3> Modern conformal RT provides excellent locoregional control for patients with ACC. Marginal and out-of-field LRs are rare, validating the use of intensity modulated RT, including proton therapy. Given a low rate of regional nodal recurrence, elective nodal coverage may be omitted in well-selected patients. SBR, while uncommon, occurs primarily in those receiving skull base RT, suggesting a potential role for dose escalation in high-risk patients.