Role of cerebrospinal fluid (CSF) in the pathogenesis and treatment of patients with brain metastases.

e14006Background: The assumption that metastases reach the brain by hematogenous spread informs concepts of pathogenesis and therapy in ways that may be incorrect. We suggest that the initial site of most CNS metastasis may be the CSF, that tumor cells then reach the brain parenchyma, possibly by way of the choroid plexus, that intraventricular (IT) chemotherapy can be expected to reach most brain metastases, and that such therapy may be effective. Methods: Two neuro-radiologists independently assessed whether brain metastases were adjacent to a CSF space in 108 consecutive patients using pre-treatment MRI scans. CSF was examined for malignant cells in 66 consecutive patients with brain metastases. We contoured the normal brain MRIs of 3 individuals to calculate the percentage of brain within 5 mm of a CSF space. Finally, we queried an international neoplastic meningitis registry for patients with both brain metastases and neoplastic meningitis to see whether we could document responses of brain metastase...