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

Purpose. To identify the factors predictive of response and increasedsurvival in patients with leptomeningeal metastases (LM) from breast cancerreceiving multi-modal therapy. Background. Leptomeningeal metastases (LM)are being diagnosed with increasing frequency as anti-cancer therapiesbecome more effective and result in prolonged patient survival. Patients andmethods. 32 women (range 28 to 74 years; median 49) with LM due tometastatic 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 radiographicevaluation 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 radionuclideventriculography) demonstrated: interrupted CSF flow (21); subarachnoidnodules (8); parenchymal brain metastases (6); hydrocephalus (4); andepidural spinal cord compression (1). Cytologic responses were seen in 14women to first-, 7 to second- and 3 to third-line chemotherapy.Treatment-related toxicity included 21 women with aseptic meningitis and 10women with thrombocytopenia or neutropenia (5 related to intraventricularchemotherapy). Median survival was 7.5 months (range 1.5 to 16). 18 womendied of progressive LM or combined LM and systemic disease progression.Women with persistent interruption of CSF flow fared worse than women withnormal CSF flow (median survival 3 versus 10 months; p < 0.0001).Conclusion. LM in women with metastatic breast cancer may be palliated withcombined modality therapy, however, success of therapy and survival is basedupon pre-treatment CNS extent of disease evaluation.