Abscopal Effect in Metastatic Melanoma: Generating Clinical Insights From Radiation-Induced Immune Response

Abstract

Despite modern advancements in systemic therapies, melanoma remains a highly malignant cancer, with persistent resistance to therapies such as checkpoint inhibitors and inhibitors of mutated BRAF V600E. Current therapy for targeting metastatic melanoma remains palliative radiation therapy, particularly directly at symptomatic sites. Extraordinarily, few case studies have reported locally targeted radiation resulting in regression of distal non-targeted lesions. This rare phenomenon was coined as the abscopal effect and presents with increasing frequency due to the advancement of systemic therapy. This narrative review attempts to understand the underlying mechanisms behind the abscopal effect through clinical data from 21 melanoma patients reported in 19 case studies. Case identification focused on patients who had progressed on systemic therapy before receiving radiation. Our study observed a mean total Gy of 34 (median total 30 Gy) and mean fractionation Gy of 8 (median fractionation 7.5 Gy) with increased frequency of reported abscopal effects with incorporation of modern systemic immunotherapies. The reviewed cases suggest that combining radiation with immunotherapy may enhance systemic tumor control, though further research is required to better understand the underlying mechanisms and improve treatment outcomes.