Extracranial Hypofractionated Radiotherapy for Advanced Melanoma in the Era of Immunotherapy

Abstract

<h3>Purpose/Objective(s)</h3> The role of radiation therapy in optimizing localcontrol continues to evolve in the era of immunotherapy which has dramatically improved outcomes for select patients with advanced melanoma. We sought to evaluate the temporal relationship between hypofractionated radiation therapy and immunotherapy delivery and its impact on outcomes. <h3>Materials/Methods</h3> On an IRB approved protocol, we evaluated patients treated from 2017-2021 with 6Gyx5 fractions for extracranial disease with cutaneous melanoma at a single institution managed with intensity modulated radiation therapy, 3D conformal radiation therapy, or electron therapy. Radiosurgery patients were excluded. Patient characteristics and IO therapy delivery schedules were extracted from the medical record and Kaplan-Meier curves were generated for progression free survival (PFS) and overall survival (OS). Patients were divided into cohorts of receiving IO therapy within three weeks of radiation therapy (concurrent) vs those that did not. Treated targets were assessed using RECIST 1.1 criteria. Chi-Square was utilized to assess relationships between response rates and sequencing of IO (concurrent vs not). <h3>Results</h3> Twenty-seven lesions were treated in 25 patients and 19 patients received IO. Fourteen (56%) patients carried BRAF mutations. Median OS for the entire cohort was 36.3 months (95% CI 15-62) and median follow up was 15.2 months. There were no significant differences between patients who received dual agent IO vs single agent IO, or between IO therapy within 3 weeks of radiation vs outside of this window. In patients with gross disease, the complete response rate was 60%, partial response was 8.7% and 21% experienced stable or locally progressive disease. Response rates did not vary by radiation therapy timing when using Chi-Square (p>0.05). Therapy was tolerated well with no acute grade 4-5 toxicities. <h3>Conclusion</h3> No temporal relationship between IO therapy and hypofractionated RT was found within the cohort. Treatment was well tolerated well with 68% obtaining a complete or partial response to hypofractionated radiation therapy for gross disease with 6Gy x 5 fractions. The short treatment duration makes this treatment schedule appealing and convenient for patients with advanced disease. The complexity of therapy for advanced melanoma with multiple prior treatment lines, limited number of patients, and uncertainty of duration of activity immunotherapy limit the extent of this analysis. Larger datasets with more granular detail are necessary to identify a potential temporal relationship between concurrent immunotherapy and hypofractionated radiation therapy.