Overview of metastatic disease of the central nervous system

Abstract

In 2016, the American Society of Clinical Oncology reported that 1.7 million Americans were diagnosed with cancer; this number will rise to 2.3 million in the United States and 22 million worldwide in 2030. This rising need is being met by an explosion of new cancer therapies, including: immune checkpoint inhibitors, T-cell therapies, tumor vaccines, antiangiogenic therapies, and various targeted therapies. This armamentarium of targeted therapies has led to better systemic control of disease and longer patient overall survival (OS). The incidence of metastatic disease to the central nervous system (CNS) is rising as patients are living longer with these more effective systemic therapies. Prolonged OS allows increased time to develop CNS metastases. The CNS is also a sanctuary for metastatic tumor cells that are protected from full exposure to therapeutic concentrations of most anticancer agents by the blood-brain barrier, the tumor microenvironment, and immune system. In addition, CNS metastases often develop late in the course of the disease, so patients are frequently heavily pretreated, resulting in drug resistance. Although genomic profiling has led to more effective therapies for systemic disease, the same therapy may not be effective in treating CNS disease, not only due to failure of blood-brain barrier penetration, but from discordance between the molecular profile in systemic and CNS tumor.

Keywords: brain metastases; genomic profiling; leptomeningeal metastases; sanctuary; targeted therapy.