The impact of timing of immunotherapy with cranial irradiation in melanoma patients with brain metastases: intracranial progression, survival and toxicity

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Abstract
Immunotherapy (IT) is increasingly incorporated in the management of metastatic melanoma patients with brain metastases, but the impact of timing of IT with stereotactic radiosurgery (SRS) remains unclear. The aim of this study was to determine the temporal significance of IT in melanoma patients treated with cranial radiation therapy (RT) with respect to patterns of intracranial progression, overall survival (OS), and toxicity. We retrospectively reviewed consecutive melanoma patients with brain metastases undergoing cranial RT and IT between 2008 and 2015. Concurrent IT/RT was defined as IT administration within 30 days of RT. Intracranial progression, OS and radionecrosis were assessed. We identified 74 patients with 136 treated brain metastases. Median OS was 13.9 months. Performance status, pre-SRS surgery, and intracranial progression were correlated with OS. Concurrent IT/RT was used in 35 (47.3%) patients. Patients receiving concurrent IT/RT were less likely to have a BRAF mutation (p = 0.027) and more likely to be treated after 2013 (p = 0.010) compared to non-concurrently treated patients. Patients receiving concurrent IT/RT were more likely to have intracranial progression within 60-days (54.3% vs. 30.8%, p = 0.041). However, 25.7% of concurrent IT/RT patients attained ≥ 1 year intracranial progression-free survival. There were no significant differences in symptomatic radionecrosis (11.4% vs. 12.8%, p = 0.67). In conclusion, although melanoma patients with brain metastases receiving concurrent IT/RT were more likely to exhibit early intracranial disease progression, a significant proportion of non-early-progressors attained durable intracranial control. The combination of IT and cranial RT appears to be efficacious and safe. Prospective studies are required to clarify these retrospective findings.

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