• Diana D Shi, Omar Arnaout, Wenya L Bi, Elizabeth I Buchbinder, Daniel N Cagney, Megan L Insco, David Liu, Jonathan D Schoenfeld, and Ayal A Aizer.
• Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: dshi1@partners.org.
• World Neurosurg. 2020 Jul 1; 139: 226-231.

BackgroundThe use of targeted therapies and immune checkpoint inhibitors has drastically changed the management of patients with melanoma and brain metastases. Specifically, combination therapy with ipilimumab, a cytotoxic T-lymphocyte antigen 4 inhibitor, and nivolumab, a programmed cell death protein 1 inhibitor, has become a preferred systemic therapy option for patients with melanoma and asymptomatic brain metastases. However, the efficacy and toxicity profile of these agents in combination with brain-directed radiation therapy is not well described.Case DescriptionIn this case series, we highlight a series of patients with melanoma demonstrating severe radiation necrosis immediately refractory to surgical resection following brain-directed stereotactic radiation therapy with concurrent ipilimumab and nivolumab. Three patients described in this series each received stereotactic radiation therapy to a dose of 30 Gy in 5 fractions to a melanoma brain metastasis. These areas developed radiographic evidence of necrosis, which was managed surgically and progressed immediately and rapidly after resection. Re-resection, bevacizumab, steroids, and/or discontinuation of nivolumab was used to mitigate further necrosis with varying efficacy.ConclusionsPatients with metastatic melanoma receiving brain-directed radiation therapy with concurrent ipilimumab and nivolumab are at risk for developing severe, surgically refractory radiation necrosis and should be closely followed clinically and with imaging. The exact mechanism for such severe necrosis is unknown, and future studies are needed to better understand this pathophysiology and identify optimal treatment strategies.Copyright © 2020 Elsevier Inc. All rights reserved.

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