Abstract
Leptomeningeal metastases (LM) is a common problem in neuro-oncology occurring in approximately 5% of all patients with cancer. Notwithstanding frequent focal signs and symptoms in LM, LM is a disease affecting the entire neuraxis and therefore staging and treatment need encompass all cerebrospinal fluid (CSF) compartments. Central nervous system (CNS) staging of LM includes contrast enhanced cranial computerized tomography (CE-CT) or magnetic resonance imaging (MR-Gd), contrast enhanced spine magnetic resonance imaging (MR-S) or computerized tomographic myelography (CT-M) and radionuclide CSF flow study (FS). Treatment of LM involves involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy may benefit patients with LM and may obviate the need for intra-CSF chemotherapy. At present, intra CSF drug therapy is confined to three chemotherapeutic agents (i.e. methotrexate, cytosine arabinoside and thio-TEPA) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of LM is palliative with an expected median patient survival of 6 months, it often affords stabilization and protection from further neurologic deterioration in patients with LM.
Similar content being viewed by others
References
Olson M, Chernik N, Posner J: Infiltration of the leptomeninges by systemic cancer. A clinical and pathologic study. Arch Neurol 30: 122–137, 1974
Little J, Dale A, Okazaki H: Meningeal carcinomatosis. Clinical manifestations. Arch Neurol 30: 138–143, 1974
Shapiro W, Posner J, Ushio Y, Chernik N, Young D: Treatment of meningeal neoplasms. Cancer Treat Rep 61: 733–743, 1977
Theodore WH, Gendelman S: Meningeal carcinomatosis. Arch Neurol 38: 696–699, 1981
Wasserstrom W, Glass J, Posner J: Diagnosis and treatment of leptomeningeal metastases from solid tumors experience with 90 patients. Cancer 49: 759–772, 1982
Kaplan J, DeSouza T, Farkash A, Shafran B, Pack D, Rehman F, Fuks J, Portenoy R: Leptomeningeal metastases comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. J Neuro-Oncol 92: 25–229, 1990
Chamberlain M, Corey-Bloom J: Leptomeningeal metastases 111Indium-DTPA CSF flow studies. Neurology 41: 1765– 1769, 1991
Posner J, Chernik N: Intracranial metastases from systemic cancer. Adv Neurol 19: 579–591, 1978
Packer R, Siegel K, Sutton L, Litmann P, Bruce D, Schut L: Leptomeningeal dissemination of primary central nervous system tumors of childhood. Ann Neurol 18: 217–221, 1985
Yung W, Horten B, Shapiro W: Meningeal gliomatosis. A review of 12 cases. Ann Neurol 8: 605–608, 1980
Awad I, Bay J, Rogers L: Leptomeningeal metastasis from supratentorial malignant gliomas. Neurosurgery 19: 247–251, 1986
Civitello L, Packer R, Rorke L, Siegel K, Sutton L, Schut L: Leptomeningeal dissemination of low-grade gliomas in childhood. Neurology 38: 562–566, 1988
Chamberlain M, Dirr L: Involved field radiotherapy and intra-Ommaya methotrexate/ara-C in patients with AIDS-related lymphomatous meningitis. J Clin Oncol 11: 1978–1984, 1993
Rosen S, Aisner J, Makuch R, Matthews M, Ihde D, Whitacre M, Glatstein E, Wiernik P, Lichter A, Bunn Jr P: Carcinomatous leptomeningitis in small cell lung cancer. A clinicopathologic review of the National Cancer Institute experience. A J Med 61: 45–53, 1982
Glass J, Melamed M, Chernik N, Posner J: Malignant cells in cerebrospinal fluid (CSF). The meaning of a positive CSF cytology. Neurology 29: 1369–1375, 1979
Murray J, Greco F, Wolff S, Hainsworth J: Neoplastic meningitis. Marked variations of cerebrospinal fluid composition in the absence of extradural block. Am J Med 75: 289–294, 1983
Schold S, Wasserstrom W, Fleisher M, Schwartz M, Posner J: Cerebrospinal fluid biochemical markers of central nervous system metastases. Ann Neurol 85: 97–604, 1980
Ernerudh J, Olsson T, Berlin G, von Schenck H: Cerebrospinal fluid immunoglobulins and 8[IN]2-microglobulin in lymphoproliferative and other neoplastic diseases of the central nervous system. Arch Neurol 44: 915–920, 1987
Klee G, Tallman R, Goellner J, Yanagihara T: Elevation of carcinoembryonic antigen in cerebrospinal fluid among patients with meningeal carcinomatosis. Mayo Clin Proc 6: 19–13, 1986
Schipper H, Bardosi A, Jacobi C, Felgenhauer K: Meningeal carcinomatosis origin of local IgG production in the CSF. Neurology 38: 413–416, 1988
Newton H, Fleisher M, Schwartz M, Malkin M: Glucosephosphate isomerase as a CSF marker for leptomeningeal metastasis. Neurology 41: 395–398, 1991
Malkin M, Posner J: Perspectives and commentaries: Cerebrospinal fluid tumor markers for the diagnosis and management of leptomeningeal metastases. Eur J Cancer Clin Oncol 22: 387–392, 1986
Cibas E, Malkin M, Posner J, Melamed M: Detection of DNA abnormalities by flow cytometry in cells from cerebrospinal fluid. Am J Clin Pathol 88: 570–577, 1987
Grossman S, Moynihan T: Neurologic complications of systemic cancer: Neoplastic meningitis. Neurol Clin 9: 843–856, 1991
Recht L: Neurologic complications of systemic cancer: Neurologic complications of systemic lymphoma. Neurol Clin 9: 1001–1015, 1991
Walker R: Neurologic complications of systemic cancer: Neurologic complications of leukemia. Neurol Clin 9: 989–999, 1991
Chamberlain M, Sandy A, Press G: Leptomeningeal metastasis. A comparison of gadolinium-enhanced MR and contrast-enhanced CT of the brain. Neurology 40: 435–438, 1990
Jaeckle K, Krol G, Posner J: Evolution of computed tomographic abnormalities in leptomeningeal metastases. Ann Neurol 17: 85–89, 1985
Lee Y, Glass J, Geoffray A, Wallace S: Cranial computed tomographic abnormalities in leptomeningeal metastasis. AJR 143: 1035–1039, 1984
Ascherl Jr G, Hilal S, Brisman R: Computed tomography of disseminated meningeal and ependymal malignant neoplasms. Neurology 31: 567–574, 1981
Sze G, Soletsky S, Bronen R, Krol G: MR imaging of the cranial meninges with emphasis on contrast enhancements and meningeal carcinomatosis. AJNR 10: 965–975, 1989
Kim K, Ho S, Weinberg P, Lee C: Spinal leptomeningeal infiltration by systemic cancer myelographic features. AJR 139: 361–365, 1982
Krol G, Sze G, Malkin M, Walker R: MR of cranial and spinal meningeal carcinomatosis comparison with CT and myelography. AJNR 9: 709–714, 1988
Kramer E, Rafto S, Packer R, Zimmerman R: Comparison of myelography with CT follow-up versus gadolinium MRI for subarachnoid metastatic disease in children. Neurology 41: 46–50, 1991
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
Lim V, Sobel D, Zyroff J: Spinal cord pial metastases MR imaging with gadopentetate dimeglumine. AJNR 11: 975–982, 1990
Pedersen A, Paulsen O, Gyldensted C: Metrizamide myelography in patients with small cell carcinoma of the lung suspected of meningeal carcinomatosis. J Neurol Oncol 3: 85–89, 1985
Wiener M, Boyko O, Friedman H, Hockenberger B, Oakes W: False-positive spinal MR findings for subarachnoid spread of primary CNS tumor in postoperative pediatric patients. AJNR 11: 1100–1103, 1990
Rippe D, Boyko O, Friedman H et al.: Gd-DTPA-enhanced MR imaging of leptomeningeal spread of primary CNS tumor in children. AJNR 11: 329–332, 1990
Chamberlain MC: Comparative spine imaging in leptomeningeal metastases. J Neuro-Oncol 23: 233–238, 1995
Larson S, Johnston G, Ommaya A, Jones E, Di Chiro G: The radionuclide ventriculogram. JAMA 224: 853–857, 1973
Di Chiro G, Hammock M, Bleyer A: Spinal descent of cerebrospinal fluid in man. Neurology 26: 1–8, 1976
Lyons M, Meyer F: Subject review: Cerebrospinal fluid physiology and the management of increased intracranial pressure. Mayo Clin Proc 65: 684–707, 1990
Chamberlain M: Pediatric leptomeningeal metastasis 111Indium-DTPA CSF flow studies. J Child Neurol 9: 150–154, 1994
Chamberlain M: Spinal 111Indium-DTPA CSF flow studies in leptomeningeal metastasis. J Neuro-Oncol 25: 135–141, 1995
Kokkoris C: Leptomeningeal carcinomatosis: How does cancer reach the pia-arachnoid? Cancer 51: 154–160, 1983
Gonzalez-Vitale J, Garcia-Bunuel R: Meningeal carcinomatosis. Cancer 37: 2906–2911, 1976
Blasberg R, Patlak C, Fenstermacher J: Intrathecal chemotherapy brain tissue profiles after ventriculo-cisternal perfusion. Pharm Exp Ther 195: 73–83, 1975
Slevin M, Piall E, Aherne G, Harvey V, Johnston A, Lister T: Effect of dose and schedule on pharmacokinetics of highdose cytosine arabinoside in plasma and cerebrospinal fluid. J Clin Oncol 1: 546–551, 1983
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
Balis F, Poplack D: Central nervous system pharmacology of antileukemic drugs. Am J Pediat 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
Bleyer W: Current status of intrathecal chemotherapy for human meningeal neoplasms. NCI Monogr 46: 171–178, 1977
Gutin P, Weiss H, Wiernik P, Walker M: Intrathecal N, N′, N″-triethylenethiophosphoramide [thio-TEPA (NSC 6369)] in the treatment of malignant meningeal disease; Phase I-II study. Cancer 38: 1471–1475, 1976
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
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
Strong J, Collins J, Lester C, Poplack D: Pharmacokinetics of intraventricular and intravenous N, N′, N″-triethylenethiophosphoramide (Thiotepa) in Rhesus monkeys and humans. Cancer Res 46: 6101–6104, 1986
Jaeckle K, Lukes S, Krown S, Krim M, Oettgen H, Nielsen S, Posner J: Phase I study of intraventricularly administered human interferon in patients with leptomeningeal tumor. Ann Neurol 14: 138–139, 1983
Blacklock J, Grimm E, Loudon W, Moser R, Rutledge M, Katz R: CNS tumors: 362 intraventricular interleukin-2 in the treatment of leptomeningeal melanomatosis, phase I clinical trial and kinetic study. Proc ASCO 8: 93, 1989
Lashford L, Davies G, Richardson R, Bourne S, Bullimore J, Eckert H, Kemshead J, Coakham H: A pilot study of 131I monoclonal antibodies in the therapy of leptomeningeal tumors. Cancer 61: 857–868, 1988
Berg S, Ballis F, Zimm S, Murphy R, Holcenberg J, Sato J, Reaman G, Steinherz P, Gillespie A, Doherty K, Poplack D: Phase I/II trial and pharmacokinetics of intrathecal diaziquone in refractory meningeal malignancies. J Clin Oncol 10: 143–148, 1992
Arndt C, Colvin O, Balis F, Lester C, Johnson G, Poplack D: Intrathecal administration of 4-hydroperoxycyclophosphamide in Rhesus monkeys. Cancer Res 47: 5932–5934, 1987
Chamberlain M, Khatibi S, Kim J, Howell S, Chatelut E, Kim S: Leptomeningeal metastasis with intraventricular Depo/ara-C: a phase I study. Arch Neurol 50: 261–264, 1993
Kim S, Chatelut E, Kim J, Howell S, Cates C, Kormanik P, Chamberlain M: Extended CSF cytarabine exposure following intrathecal administration of DTC 101. J Clin Oncol 11: 2186–2193, 1993
Giannone L, Greco F, Hainsworth J: Combination intraventricular chemotherapy for meningeal neoplasia. J Clin Oncol 4: 68–73, 1986
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
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
Chamberlain MC, Kormanik PA: Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases. J Neuro-surgery 87: 694–699, 1997
Lishner M, Perrin R, Feld R, Messner H, Tuffnell P, Path FRC, Elhakim T, Matlow A, Curtis J: Complications associated with Ommaya reservoirs in patients with cancer. Arch Intern Med 150: 173–176, 1990
Chamberlain MC, Kormanik P: Leptomeningeal metastases due to melanoma: combined modality therapy. Intern J Oncol 9: 505–510, 1996
Chamberlain MC, Kormanik PA: Cardinomatous meningitis secondary to breast cancer: Combined modality therapy. J Neuro-Oncol 35: 55–64, 1997
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
Grant R, Naylor B, Greeberg HS, Junck L: Clinical outcome in aggressively treated meningeal carcinomatosis. Arch Neurol 51: 457–461, 1994
Balm M, Hammack J: Leptomeningeal carcinomatosis. Arch Neurol 53: 626–632, 1996
Chamberlain MC, Kormanik P: Prognostic significance of 111Indium-DTPA CSF flow studies. Neurology 46(6): 1674–1677, 1996
Chamberlain MC, Kormanik PA: Prognostic significance of co-existent bulky metastatic CNS disease in patients with leptomeningeal metastases. Arch Neurol, in press
Freilich RJ, Krol G, DeAngelis LM: Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis. Ann Neurol 38: 51–57, 1995
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
Boogerd W, Hart AAM, Van der Sande JJ, 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
Dedrick R, Zaharko D, Bender R, Bleyer W, Lutz R: Pharmacokinetic considerations on resistance to anticancer drugs. Cancer Chemother Rep 59: 795–804, 1975
Grossman S, Trump D, Chen D, Thompson G, Camargo E: Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. Am J Med 73: 641–647, 1982
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chamberlain, M.C. Leptomeningeal metastases: A review of evaluation and treatment. J Neurooncol 37, 271–284 (1998). https://doi.org/10.1023/A:1005976926058
Issue Date:
DOI: https://doi.org/10.1023/A:1005976926058