Durable local control with hypofractionated radiation therapy for unresectable or metastatic melanoma

•Dose-escalated hypofractionated radiation therapy (HFRT) for patients with unresectable or bulky metastatic melanoma was evaluated.•Forty-nine patients received treatment to 53 targets with 12-17 fractions of HFRT between 2015-2022.•HFRT provided durable local control and improved tumor-associated symptoms in patients with limited toxicity.•HFRT is an effective form of local control for advanced melanoma patients with limited overall disease progression not amenable to SBRT. As patients with advanced melanoma live longer in the context of systemic therapy advancements, better strategies for durable control of bulky tumors are needed. In this study, we evaluated if dose-escalated hypofractionated radiation therapy (HFRT) can provide durable local control and improve tumor-associated symptoms in patients with unresectable or bulky metastatic melanoma for whom stereotactic ablative radiotherapy (RT) approaches are not feasible due to tumor size or location. We retrospectively reviewed 49 patients with unresectable or bulky metastatic melanoma who were treated to a total of 53 tumor targets with 12–17 fractions HFRT at our institution between 2015–2022. Clinical scenarios included: unresectable, locoregional only disease (26 %); oligometastatic disease (