How I treat brain metastases of melanoma

Brain metastases are common in advanced melanoma and cause death in >50% of patients. Until recently, median survival was only ∼4 months. Improved systemic treatment including immune checkpoint inhibitors and combinations of BRAF/MEK inhibitors, however, has significantly improved intracranial tumor response and survival. In addition, advances in radiation therapy have also improved the intracranial outcomes for advanced melanoma patients with brain metastases (MBM). There has long been concern that systemic treatment of the central nervous metastases would be ineffective due to inability of active agents to cross an intact blood-brain barrier. Recent studies have shown, however, that highly active systemic therapy can have significant benefit in these patients. When determining a patient's treatment, the important factors in predicting the likelihood of benefit including the presence of neurologic symptoms, the number and size of brain metastases, performance status/status of extracranial disease, and BRAF mutation status should all be considered. In this review, we will discuss the challenges and treatment options for patients with advanced melanoma and brain metastases.