Abstract
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.
References
Chamberlain MC: Current concepts in leptomeningeal metastasis. Curr Opin Oncol 4(3): 533–539, 1992
Chamberlain MC: New approaches to and current treatments of leptomeningeal metastases. Curr Opin Neurol 7: 492–500, 1994
Shapiro W, Posner J, Ushio Y, Chernik N, Young D: Treatment of meningeal neoplasms. Cancer Treat Rep 61: 733–743, 1977
Wasserstrom W, Glass J, Posner J: Diagnosis and treatment of leptomeningeal metastases from solid tumors: Experience with 90 patients. Cancer 49: 759–772, 1982
Grossman S, Moynihan T: Neurologic complications of systemic cancer: Neoplastic meningitis. Neurologic Clinics 9: 843–856, 1991
Lopez J, Nassif E, Vannicola P, Kirkorian J, Agarwal R: Central nervous system pharmacokinetics of high-dose cytosine arabinoside. J Neuro-Oncol 3: 119–124, 1985
Ackland S, Schilsky R: Review article: High-dose methotrexate a critical reappraisal. J Clin Oncol 5: 2017–2031, 1987
Chamberlain MC, Dirr L: Involved field radiotherapy and intra-ommaya methotrexate/ara-C in patients with AIDS-related lymphomatous meningitis. J Clin Oncol 11: 1978–1993, 1993
Balis F, Poplack D: Central nervous system pharmacology of antileukemic drugs. Amer J Pediatr Hemat/Oncol 11: 74–86, 1989
Collins J: Pharmacokinetics of intraventricular administration. J Neuro-Oncol 1: 283–291, 1983
Shapiro W, Young D, Mehta B: Methotrexate distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med 293: 161–166, 1975
Fulton D, Levin V, Gutin P, Edwards M, Seager M, Stewart J, Wilson C: Intrathecal cytosine arabinoside for the treatment of meningeal metastases from malignant brain tumors and systemic tumors. Cancer Chemother Pharmacol 8: 285–291, 1982
Gutin P, Levi J, Wiernik P, Walker M: Treatment of malignant meningeal disease with intrathecal thio-TEPA. A phase II study. Cancer Treat Rep 61: 885–887, 1977
Sze G, Abramson A, Krol G, Liu D, Amster J, Zimmerman R, Deck M: Gadolinium-DTPA in the evaluation of intradural extramedullary spinal disease. AJNR 9: 153–163, 1988
Chamberlain MC, Corey-Bloom J: Leptomeningeal metastasis: Indium-DTPA CSF flow studies. Neurology 41: 1765–1769, 1991
Chamberlain MC: Comparative spine imaging in leptomeningeal metastases. J Neuro Oncol 23: 233–238, 1995
Grossman SA, Trump DL, Chen DCP, Thompson G, Camargo EE: Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. Am J Med 73: 641–647, 1982
Chamberlain MC, Sandy A, Press GA: Leptomeningeal metastasis: A comparison of gadolinium-enhanced MR and contrast-enhanced CT of the brain. Neurology 40: 435–438, 1990
Yap HY, Yap BS, Rasmussen S, Levens ME, Hortobagyi GN, Blumenschein GR: Treatment for meningeal carcinomatosis in breast cancer. Cancer 79: 219–222, 1982
Ongerboer de Visser BW, Somers R, Nooyen WH, van Heerde P, Hart AAM, McVie JG: Intraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma. Neurology 33: 1565–1572, 1983
Boogerd W, Hart AAM, Van der Sande, Engelsman E: Meningeal carcinomatosis in breast cancer. Prognostic factors and influence of treatment. Cancer 67: 1685–1695, 1991
Fizazi K, Asselain B, Vincent-Salomon A, Jouve M, Dieras V, Palangie T, Beuzeboc P, Dorval T, Pouillart P: Meningeal carcinomatosis in patients with breast carcinoma. Cancer 77 (7): 1315–1323, 1996
Glantz M, Hall WA, Cole BF, et al.: Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow studies. Cancer 75: 2919–2931, 1995
Chamberlain MC, Kormanik PK: Prognosis significance of 111Indium-DTPA CSF flow studies. Neurology 46(6): 1674–1677, 1996
Siegal T, Lassos A, Pfeffer MR: Leptomeningeal metastases: analysis of 31 patients with sustained off-therapy response following combined-modality therapy. Neurology 44: 1463–1469, 1994
Grant R, Naylor B, Greeberg HS, Junck L: Clinical outcome in aggressively treated meningeal carcinomatosis. Arch Neurol 51: 457–461, 1994
Grossman SA, Finkelstein DM, Ruckdeschel JC, Trump DL, Moynihan T, Ettinger DS: Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. J Clin Oncol 11: 561–569, 1993
Hitchens R, Bell D, Woods R, Levi J: A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol 5: 1655–1662, 1987
White CA, Glantz M, Jaeckle KA, Phuphanich S, Recht L, Chamberlain MC: Treatment of leptomeningeal metastases with intra-CSF Depofoam encapsulated cytarabine. Proc Am Soc Clin Oncol 15: 160, 1996 (Abstract).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chamberlain, M.C., Kormanik, P.R. Carcinomatous meningitis secondary to breast cancer: Predictors of response to combined modality therapy. J Neurooncol 35, 55–64 (1997). https://doi.org/10.1023/A:1005803918194
Issue Date:
DOI: https://doi.org/10.1023/A:1005803918194