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Purpose/objective(s): In the absence of randomized prospective data, the role of postoperative radiotherapy (PORT) for localized Merkel cell carcinoma (MCC) is controversial with varying practice patterns. Although a majority of patients with resected stage I/II MCC without adverse features may be cured with surgery alone, those with adverse features including head and neck (HN) primary tumors have local recurrence rates of 20% or more without PORT (Takagishi et al. Adv Radiat Oncol, 2016). Extrapolating from our experience demonstrating high rates of local control with single fraction radiotherapy (SFRT) for metastatic MCC (Iyer et al. Cancer Med, 2015), we hypothesized that SFRT (8 Gy) may be effective as PORT to optimize local control for stage I/II MCC with adverse risk features (e.g., HN disease, immunosuppression, recurrent disease, non-oncologic resection, lymphovascular space invasion (LVSI)), especially in patients for whom a conventional RT course may not be feasible.Materials/methods: A single-institution, retrospective review of patients with clinical or pathological stage I/II MCC receiving SFRT (8 Gy) as postoperative treatment (SF-PORT) was completed from a prospectively-enrolled database.Results: Thirty patients (median age 78 years) were identified who received SFRT after wide local excision (n = 24; 80%), Mohs surgery (n = 1; 3%), shave or excisional biopsy only (n = 5; 17%) of the primary. Patients had pathological stage I (n = 15; 50%), clinical stage I (n = 10: 33%), pathological stage II (n = 3; 10%) or clinical stage II (n = 2; 7%) disease. All patients received SF-PORT (8 Gy) at a median of 43 days (range: 14-203) following resection or biopsy. Five patients (4 with HN disease) received SFRT to draining lymph nodes. The majority of patients had HN tumors (77%), LVSI was present in 23%,17% were immunosuppressed and 7% had locally recurrent disease (n = 2). At median follow-up of 11.3 months (range: 3-45.7), no local or in-field recurrences were observed. No local or distant recurrences, MCC specific deaths, or RT related toxicities grade > 1 (CTCAE v5.0) were observed. There were two out-of-field regional nodal recurrences in HN patients who did not receive elective nodal RT.Conclusion: Our early experience demonstrates a high rate of in-field local control in patients with stage I/II MCC with adverse features managed with SF-PORT. This approach warrants further study. [ABSTRACT FROM AUTHOR]