The Association of Radiation Dose-Fractionation and Immunotherapy Use With Overall Survival in Metastatic Melanoma Patients

ObjectiveMetastatic melanoma patients often receive palliative radiotherapy (RT) and immunotherapy (IT).However, the immunological interplay between RT dose-fractionation and IT is uncertain, and the optimal treatment strategy using RT and IT in metastatic melanoma remains unclear.Our main objective was to examine the effect of RT dose-fractionation on overall survival (OS). MethodsUsing the National Cancer Database (NCDB), we classified metastatic melanoma patients who received palliative RT into two dose-fractionation groups -conventionally fractionated RT (CFRT; <5 Gy/fraction) and hypofractionated RT (HFRT: ≥5 Gy/fraction) -with or without IT.Survival analysis was performed using the Cox regression model, Kaplan-Meier method, and propensity-score matching (PSM). ResultsA total of 5,281 metastatic melanoma patients were included, with a median follow-up of 5.9 months.The three-year OS was highest in patients who received HFRT+IT [37.3% (95% CI: 31.1-43.5)]compared to those who received HFRT alone [19.0%(95% CI: 16.2-21.9)],)], or CFRT alone [8.6% (95%CI: 7.6-9.7);p<0.0001].The magnitude of OS benefit with the use of IT was greater in those who received HFRT (18.3%) compared with those who received CFRT (9.0%) (p<0.0001).The addition of IT to HFRT, compared to CFRT, was associated with greater OS benefit in patients treated with RT to the brain and soft tissue/visceral (STV) sites.On PSM analysis, HFRT+IT was associated with improved three-year OS compared to other treatments. ConclusionMetastatic melanoma patients who received HFRT+IT was associated with the greatest OS benefit.Our findings warrant further prospective evaluation as to whether higher RT dose-per-fraction improves clinical outcomes in metastatic melanoma patients receiving IT.