Carcinomatous meningitis secondary to breast cancer: Predictors of response to combined modality therapy

Purpose. To identify the factors predictive of response and increased survival in patients with leptomeningeal metastases (LM) from breast cancer receiving multi-modal therapy. Background. Leptomeningeal metastases (LM) are being diagnosed with increasing frequency as anti-cancer therapies become more effective and result in prolonged patient survival. Patients and methods. 32 women (range 28 to 74 years; median 49) with LM due to metastatic breast cancer were treated. Neurologic presentation included: cranial neuropathies (10 patients); headache (10); cauda equina syndrome (6); ataxia (6); meningismus (3); radioculopathy (2); myelopathy (2); confusion (2); and seizure (1). All patients underwent radiographic evaluation of the extent of CNS disease followed by radiotherapy (21 women) and intraventricular chemotherapy: (methotrexate 32 women; cytarabine 22; thio-TEPA 11). Results. CNS imaging (cranial MR, spine MR and radionuclide ventriculography) demonstrated: interrupted CSF flow (21); subarachnoid nodules (8); parenchymal brain metastases (6); hydrocephalus (4); and epidural spinal cord compression (1). Cytologic responses were seen in 14 women to first-, 7 to second- and 3 to third-line chemotherapy. Treatment-related toxicity included 21 women with aseptic meningitis and 10 women with thrombocytopenia or neutropenia (5 related to intraventricular chemotherapy). Median survival was 7.5 months (range 1.5 to 16). 18 women died of progressive LM or combined LM and systemic disease progression. Women with persistent interruption of CSF flow fared worse than women with normal CSF flow (median survival 3 versus 10 months; p < 0.0001). Conclusion. LM in women with metastatic breast cancer may be palliated with combined modality therapy, however, success of therapy and survival is based upon pre-treatment CNS extent of disease evaluation.