OS2.6 Cerebrospinal fluid (CSF) plays a crucial role in the pathogenesis and treatment of patients with brain metastases

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2018-09, Vol.20 (suppl_3), p.iii220-iii220
• Main Authors: Ali, A, Ouyang, T, Thamburaj, K, Zoccoli, C, Aregawi, D, Zacharia, B, Glantz, M
• Format: Article
• Language: English
• Subjects: Oral Presentations
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noy139.019

Abstract Background The assumption that metastases reach the brain by hematogenous spread informs concepts of pathogenesis and therapy in ways that may be incorrect and harmful. We suggest that the initial site of most CNS metastasis may be the CSF and that tumor cells then invade the brain parenchyma. We show that intraventricular (IT) chemotherapy can be expected to reach most brain metastases and thus has the potential to provide effective therapy. Material and Methods Two neuro-radiologists independently assessed whether brain metastases were contiguous to a CSF space in 200 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 metastases to IT chemotherapy alone. Results Mean age of the 200 patients was 64.2 (SD 13); 100 were male; 143 had lung cancer, 15 melanoma, 12 gastrointestinal, 11 breast, 9 renal, 7 bladder. The mean number of metastases was 4.63 (SD 6.26), and 85% of metastases touched a CSF space. In 67% of patients, all metastases touched a CSF space. Neither histology, number or size of brain metastases predicted contiguity with a CSF space. In our consecutive subset of patients, 44% (10/23) with one, 46% (5/11) with two, 63% (5/8) with three, and 71% (17/24) with more than three metastases had malignant cells in the CSF (R2=0.93, p=0.037). In three patients (25, 57, and 67 years old), at least 48%, 75%, and 70% of all brain tissue lay within 5 mm of a CSF space. In 5 of 7 patients with both brain and CSF metastases who received only IT chemotherapy, a substantial reduction in the size of at least some metastases was documented. Conclusion Our data suggest that brain metastases may access the CNS through the CSF rather than the bloodstream, and that the CSF acts as a protected site for tumor cells during systemic therapy. IT chemotherapy can enter this protected site and may reduce CNS relapses if used in addition to the standard of care. If corroborated by further study, we suggest that the CSF should be monitored in all patients with, or at risk for, brain metastases, and that true cures for patients with brain metastases will require treatment of the CSF s