Central nervous system (CNS) metastases are the most common CNS neoplasms in adults, account for over half of all intracranial neoplasms, and are approximately 10X more common than primary brain tumors. ¹ Although diverse in their potential origin, the most common primary sources of CNS metastases in adults are lung cancer, breast cancer, melanoma, renal cell carcinoma, and colorectal cancer, all of which are associated with a poor prognosis and treatment resistance. Most often, these metastases involve the parenchyma, leptomeninges and epidural areas of the vertebral column, arising via circulating tumor cells that have travelled through the bloodstream, the brain lymphatics, or the cerebrospinal fluid. In children, the most common source of CNS metastases are leukemias and lymphomas followed by non-hematopoietic CNS neoplasms including germ cell tumors, osteosarcoma, neuroblastoma, Ewing sarcoma, and rhabdomyosarcoma. ^2,3 In adults, leukemic cells rarely metastasize to the CNS, although this may reflect an underdiagnosis of CNS involvement ^4,5.

The molecular mechanisms that facilitate and drive metastasis to the brain are poorly understood. ^6,7 Historically, the strategy of treating CNS metastases was to use the same systemic cytotoxic chemotherapy used to treat the primary tumor, but had proven largely ineffective due to delivery issues across the blood-brain-barrier and the advanced, sometimes treatment-resistant phase of disease these patients tend to be in. Modern small molecule inhibitors and/or immunotherapy have shown promise in treating CNS metastases, but further research is required. ^8-11