Background: High-grade histology, T stage, N stage, margin status, lymphovascular invasion (LVI), and perineural invasion (PNI) predict recurrence after resection of major salivary gland tumors (MSGTs). Consequently, they are often indications for postoperative radiation therapy (RT). However, predictors for recurrence after RT are not as clear. We analyzed our institutional experience with MSGTs to identify predictors of radiation outcomes. Methods: Ninety-one MSGT patients treated with adjuvant photon RT at Memorial Sloan Kettering Cancer Center from 2010 to 2018 were retrospectively reviewed. The Kaplan-Meier method was used to estimate local relapse free survival (LRFS), regional relapse free survival (RRFS), distant metastasis free survival (DMFS), and overall survival (OS). Median follow up was 44 months (2-114) and median dose delivered was 66 Gy (50.4-70). Results: The most common site was the parotid (74%) and the most common histology was adenoid cystic carcinoma (23%). Most patients had close or positive margins (84%), 14% had recurrent disease after prior surgery, and 27% received concurrent chemotherapy. Multiple risk factors (MRF) were defined as two or more of the following: T3/T4 stage, high-grade, LVI, PNI, or close/positive margins. The 5-year LRFS, RRFS, DMFS, and OS were 96.4% [92.4-100], 97.5% [94.1-100], 86.9% [79.9-94.5], and 73.9% [64.6-84.6]. Table 1 summarizes results. Five-year LRFS and RRFS were inferior with recurrent disease, LVI, high-grade, and metastatic disease. T stage, node-positive (N+), margins, and PNI did not impact LRFS or RRFS. Five-year DMFS was inferior with LVI, high-grade, T3/T4, N+, and metastatic disease. Five-year OS was inferior with LVI, high-grade, MRF, T3/T4, N+, and gender. One patient experienced acute Grade 3 toxicity (hospitalization for nausea/vomiting) and two patients experienced late Grade 3 toxicity (osteoradionecrosis of the temporal bone and osteoradionecrosis of the mandible, both requiring surgical interventions). No early or late grade 4 or 5 toxicities were observed. Conclusion: Adjuvant RT offers excellent locoregional control and neutralizes risk factors of T3/T4 stage, N+, margin status, and PNI. Recurrent disease, and LVI predict locoregional progression after adjuvant RT and could be investigated as possible indications for dose-escalation. LVI, grade, T3/T4, N+, PNI, ECE, and MRF predict metastasis after adjuvant RT and may warrant consideration of concurrent chemotherapy.

