Melanoma central nervous system metastases: current approaches, challenges, and opportunities

Abstract

Summary Melanoma central nervous system metastases are increasing, and the challenges presented by this patient population remain complex. In December 2015, the Melanoma Research Foundation and the Wistar Institute hosted the First Summit on Melanoma Central Nervous System (CNS) Metastases in Philadelphia, Pennsylvania. Here, we provide a review of the current status of the field of melanoma brain metastasis research; identify key challenges and opportunities for improving the outcomes in patients with melanoma brain metastases; and set a framework to optimize future research in this critical area.

Anti–PD-1/anti–CTLA-4 efficacy in melanoma brain metastases depends on extracranial disease and augmentation of CD8+T cell trafficking

“…To validate the relevance of extracranial disease in the context of anti-PD-1/anti-CTLA-4 therapy for BrM, we compared therapeutic efficacy between mice bearing intracranial tumors only (representing a conventional intracranial tumor transplantation model (17,27)), and mice bearing tumors at both sites. Strikingly, in the absence of extracranial disease, the anti-PD-1/anti-CTLA-4 combination failed to extend the survival or to reduce the intracranial tumor burden (Fig.…”

“…Preclinical studies in BrM are hampered by the lack of melanoma models that can recapitulate clinically observed metastatic patterns and coexistence of metastases in different organs. Spontaneous metastasis to the brain in preclinical models is a rare event and macroscopic BrM are usually not observed (17). Only two immunocompetent preclinical melanoma models of spontaneous BrM have been reported (18,19), but analysis of BrMspecific survival in therapeutic studies remains a challenge due to a faster development of extracranial as compared to intracranial metastases.…”

Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial

“…1,2 The development of brain metastases in patients with melanoma has been observed at an incidence of up to 43% and 75% in clinical and autopsy studies, respectively. 2,3 Historically, brain metastases in patients with metastatic melanoma have been associated with poor overall survival (median 4–5 months), and the poorest outcomes are observed in those presenting with neurological symptoms and leptomeningeal involvement.…”

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis

“…After lung and breast cancer, melanoma is the most common cancer that metastasizes to the brain [2]. Approximately 10% of patients with a history of invasive melanoma will ultimately develop brain metastasis (BM) [2], which contributes significantly to melanoma-related morbidity and mortality [3,4]. Treatment of BM is difficult, and historically such patients have had an overall survival in the range of 3-6 months [4-7].…”

“…Treatment of BM is difficult, and historically such patients have had an overall survival in the range of 3-6 months [4-7]. Although average survival for these patients has improved in the current era of targeted and immune therapies [2] and with advances in radiotherapy, there remains a need to enhance our understanding of the tumor- and patient-related factors that may be associated with BM development and survival.…”