Adjuvant radiation for major salivary gland adenoid cystic carcinoma in the modern era: updated patterns of care and survival from the National Cancer Database (2004-2021).

Postoperative radiation therapy (PORT) is widely recommended following surgical resection of adenoid cystic carcinoma (ACC) of the major salivary glands, yet its association with overall survival in the contemporary treatment era remains incompletely characterized. Using the National Cancer Database, we identified 2,384 patients with nonmetastatic ACC of the major salivary glands who underwent definitive surgical resection between 2004 and 2021. Of these, 1,776 (74.5%) received PORT and 608 (25.5%) underwent surgery alone. Median follow-up was 75.9 months, and follow-up was censored at 100 months to account for the indolent natural history of ACC. PORT was associated with improved 8-year overall survival compared to surgery alone (76.9% vs 70.3%), which remained significant on multivariable analysis after adjustment for age, sex, comorbidity, extent of disease, margin status, and chemotherapy receipt (HR 0.76, 95% CI 0.62-0.95, p = 0.013). This benefit extended to patients with early-stage disease (pT1-2 N0/NX: HR 0.65, 95% CI 0.51-0.85, p = 0.001), large tumors without nodal involvement (pT3-4 N0/NX: HR 0.69, 95% CI 0.48-0.99, p = 0.043), and negative surgical margins (HR 0.67, 95% CI 0.51-0.89, p = 0.006). However, among patients with pT3-4 tumors and positive surgical margins, PORT was not associated with improved overall survival (HR 0.81, 95% CI 0.48-1.37, p = 0.423), a finding that was robust on adjusted analysis (HR 0.97, 95% CI 0.56-1.68, p = 0.913). This subgroup may represent a biologically distinct and more aggressive subset of ACC in whom locoregional therapy alone is insufficient to alter survival outcomes, possibly due to a higher propensity for distant metastasis driving mortality. These findings support the broad use of PORT in nonmetastatic major salivary gland ACC while identifying a high-risk subgroup warranting further investigation into the role of systemic therapy and intensified multimodality treatment.