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Published online: 7 February 2018
© The Author(s) 2018. This article is an open access publication
Abstract Recent phase II trials have shown that BRAF/MEK inhibitors and immune checkpoint inhibitors are active in patients with melanoma brain metastases (MBM), reporting intracranial disease control rates of 50-75%. Furthermore, retrospective analyses suggest that combining stereotactic radiosurgery with immune checkpoint inhibitors or BRAF/MEK inhibitors prolongs overall survival. These data stress the need for inter- and multidisciplinary cooperation that takes into account the individual prognostic factors in order to establish the best treatment for each patient. Although the management of MBM has dramatically improved, a substantial number of patients still progress and die from brain metastases. Therefore, there is an urgent need for prospective studies in patients with MBM that focus on treatment combinations and sequences, new treatment strategies, and biomarkers of treatment response. Moreover, further research is needed to decipher brain-specific mechanisms of therapy resistance.
1Introduction
Melanomas are the third most common source of cerebral metastases, preceded only by non-small-cell lung cancer (NSCLC) and breast carcinomas [1]. The propensity of malignant melanomas to metastasize into the central nervous system (CNS) becomes clear considering that the incidence of malignant melanoma is far lower than that of NSCLC or breast cancer. Therefore, melanoma has the highest tendency to metastasize to the brain. The risk of brain metastases in metastatic melanoma increases with disease duration. Melanoma brain metastases (MBM) have been identified in up to 75% of metastasized melanoma patients at autopsy [2].
Prognostic factors are important not only for the choice of treatment, but also for assessing and comparing research results. Retrospective studies have demonstrated that the survival rates of patients with MBM are correlated to the number of cerebral metastases, the presence of neurological symptoms, the serum level of LDH (lactate dehydrogenase), the patient's age, the simultaneous presence of extracerebral metastases, the BRAF status (with positive BRAF mutation status being associated with a good prognosis) and the patient's physical condition [3-6].
The spectrum of available treatments for metastatic melanoma has increased substantially over the last 6 years due to the approval of effective immunotherapies and targeted treatments. However, until recently, patients with brain metastases have been excluded from most clinical studies, and prognoses remained poor, with survival typically...