Time from stereotactic radiosurgery to immunotherapy in patients with melanoma brain metastases and impact on outcome.

Abstract

The role of immunotherapy for metastatic melanoma has expanded over the past decade triggering questions regarding the combination and timing of immunotherapy and radiation for brain metastases. We used the National Cancer Database (NCDB) to see if the time from radiation to immunotherapy in patients with melanoma brain metastases had an impact on survival. We queried the NCDB from 2010 to 2015 for patients with melanoma brain metastases treated with immunotherapy and stereotactic radiosurgery (SRS). Receiver operator characteristic (ROC) curve analysis was done to determine a timepoint associated with outcome. Cox regression was used to identify predictors of survival. Propensity matching was done to account for indication bias. We identified 247 patients meeting the above criteria. The median patient age was 62years (27-90) and the vast majority were Caucasian (99%). The median SRS dose was 22Gy (18-24Gy).The median time to SRS was 39days (0-344) and the median time to immunotherapy was 56days (6-454). The ROC analysis revealed 8days from SRS to immunotherapy as associated with outcome. Fifty-six patients had immunotherapy prior to SRS, 30 patients had immunotherapy within 0-7days of SRS, and the remaining 161 had immunotherapy greater than 7days from SRS. Three year survival rates were 21%, 55%, and 35% for those timeframes, respectively (p = 0.0153). Propensity matching of the 0-7day and > 7day groups yielded 28 pairs and Kaplan Meier analysis showed 3year overall survival of 55% and 35%, in favor of immunotherapy within 7days of SRS (p = 0.0357). Multivariable Cox regression identified lack of extracranial disease, more recent year of treatment, and time from SRS to immunotherapy of 0-7days as predictors of improved survival. Immunotherapy within 7days of SRS shows a possible association with improve outcomes in patients with brain metastases from melanoma.