Peri-SRS Administration of Immune Checkpoint Therapy for Melanoma Metastatic to the Brain: Investigating Efficacy and the Effects of Relative Treatment Timing on Lesion Response

Abstract

Objective: To investigate the efficacy of immune checkpoint therapy (ICT) administered with stereotactic radiosurgery (SRS) and determine the effects of relative treatment timing on lesion response.

Methods: A prospective institutional database of all patients with intact brain metastases treated with SRS from 2008 to 2015 was reviewed for patients diagnosed with malignant melanoma. Lesion response was determined using a modified RECIST v1.1 criteria. Patients were grouped according to if they received ICT and the timing of ICT relative to SRS. Cox regression was used to identify predictors of lesion failure (LF) and distant brain failure (DBF). The Wilcoxon rank-sum test was used to compare median lesion regression after SRS between treatment groups.

Results: Fifty-one patients with 167 metastases were evaluated. Eighteen patients (59 lesions) were treated with peri-SRS ICT with anticytotoxic T-lymphocyte-associated protein 4 or antiprogrammed cell death protein 1 therapy. Peri-SRS ICT was a significant favorable predictor for reduced hazard of LF (hazard ratio, 0.131; confidence interval, 0.028-0.610). Concurrent ICT given with SRS (hazard ratio, 0.364; confidence interval, 0.161-0.825) significantly predicted freedom from DBF. When quantitative lesion response was examined, peri-SRS ICT resulted in a significantly greater median percent lesion regression than did SRS alone at 1.5 (-30.7% vs. -14.6%; P = 0.018), 4 (-42.3% vs. -18.8%; P = 0.031), and 5 months after SRS (-52.01 vs. -14.9%; P = 0.002).

Conclusions: ICT combined with SRS was associated with greater lesion regression of melanoma brain metastases and decreased LF. When given concurrently, combined SRS and ICT may result in improved freedom from DBF.

Keywords: Brain metastases; Immunotherapy; Lesion response; Melanoma; SRS.