Subscribe to RSS
DOI: 10.1055/s-0030-1255220
Leptomeningeal Metastasis
Publication History
Publication Date:
24 June 2010 (online)
ABSTRACT
Leptomeningeal metastasis occurs in ~5% of all patients with cancer and is the third most common metastatic complication of the central nervous system. Staging of leptomeningeal metastasis includes contrast-enhanced brain and spine magnetic resonance imaging and radionuclide cerebrospinal fluid (CSF) flow study. Treatment, when clinically indicated, often requires administration of involved-field radiotherapy to bulky or symptomatic disease sites as well as intra-CSF and systemic chemotherapy. The use of high-dose systemic therapy may benefit selected patients with breast- or lymphoma-related leptomeningeal metastasis and obviate the need for intra-CSF chemotherapy. Intra-CSF drug therapy primarily utilizes one of three chemotherapeutic agents (e.g., methotrexate, cytosine arabinoside, and thiotepa) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Beginning to be utilized are novel intra-CSF agents, such as the targeted monoclonal antibodies rituximab (anti-CD20 for B-cell lymphoma-related leptomeningeal metastasis) and trastuzumab (anti-Her2/neu for breast cancer-related leptomeningeal metastasis). Although treatment of leptomeningeal metastasis is palliative with median patient survival of 2 to 3 months, treatment may afford stabilization and protection from further neurologic deterioration in patients with leptomeningeal metastasis.
KEYWORDS
Leptomeningeal metastases - intra-CSF chemotherapy
REFERENCES
- 1 Jaeckle K A. Neoplastic meningitis from systemic malignancies: diagnosis, prognosis and treatment. Semin Oncol. 2006; 33(3) 312-323
- 2 Pace A, Fabi A. Chemotherapy in neoplastic meningitis. Crit Rev Oncol Hematol. 2006; 60(3) 194-200
- 3 Kaplan J G, DeSouza T G, Farkash A et al.. Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. J Neurooncol. 1990; 9(3) 225-229
- 4 Siegal T, Lossos A, Pfeffer M R. Leptomeningeal metastases: analysis of 31 patients with sustained off-therapy response following combined-modality therapy. Neurology. 1994; 44(8) 1463-1469
- 5 Blaney S M, Poplack D G. Neoplastic meningitis: diagnosis and treatment considerations. Med Oncol. 2000; 17(3) 151-162
- 6 Glass J P, Melamed M, Chernik N L, Posner J B. Malignant cells in cerebrospinal fluid (CSF): the meaning of a positive CSF cytology. Neurology. 1979; 29(10) 1369-1375
- 7 Wasserstrom W R, Glass J P, Posner J B. Diagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients. Cancer. 1982; 49(4) 759-772
- 8 Rosen S T, Aisner J, Makuch R W et al.. Carcinomatous leptomeningitis in small cell lung cancer: a clinicopathologic review of the National Cancer Institute experience. Medicine (Baltimore). 1982; 61(1) 45-53
- 9 Amer M H, Al-Sarraf M, Baker L H, Vaitkevicius V K. Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival. Cancer. 1978; 42(2) 660-668
- 10 van Oostenbrugge R J, Twijnstra A. Presenting features and value of diagnostic procedures in leptomeningeal metastases. Neurology. 1999; 53(2) 382-385
- 11 Balm M, Hammack J. Leptomeningeal carcinomatosis. Presenting features and prognostic factors. Arch Neurol. 1996; 53(7) 626-632
- 12 Sorensen S C, Eagan R T, Scott M. Meningeal carcinomatosis in patients with primary breast or lung cancer. Mayo Clin Proc. 1984; 59(2) 91-94
- 13 Gonzalez-Vitale J C, Garcia-Bunuel R. Meningeal carcinomatosis. Cancer. 1976; 37(6) 2906-2911
- 14 Gleissner B, Chamberlain M C. Neoplastic meningitis. Lancet Neurol. 2006; 5(5) 443-452
- 15 Boyle R, Thomas M, Adams J H. Diffuse involvement of the leptomeninges by tumour—a clinical and pathological study of 63 cases. Postgrad Med J. 1980; 56(653) 149-158
- 16 Wolfgang G, Marcus D, Ulrike S. Leptomeningeal carcinomatosis; clinical syndrome in different primaries. J Neurooncol. 1998; 38 103-110
- 17 Kölmel H W. Cytology of neoplastic meningosis. J Neurooncol. 1998; 38(2-3) 121-125
- 18 Murray J J, Greco F A, Wolff S N, Hainsworth J D. Neoplastic meningitis. Marked variations of cerebrospinal fluid composition in the absence of extradural block. Am J Med. 1983; 75(2) 289-294
- 19 Rogers L R, Duchesneau P M, Nunez C et al.. Comparison of cisternal and lumbar CSF examination in leptomeningeal metastasis. Neurology. 1992; 42(6) 1239-1241
- 20 Chamberlain M C, Kormanik P A, Glantz M J. A comparison between ventricular and lumbar cerebrospinal fluid cytology in adult patients with leptomeningeal metastases. Neuro-oncol. 2001; 3(1) 42-45
- 21 Glantz M J, Cole B F, Glantz L K et al.. Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results. Cancer. 1998; 82(4) 733-739
- 22 Groves M D, Hess K R, Puduvalli V K et al.. Biomarkers of disease: cerebrospinal fluid vascular endothelial growth factor (VEGF) and stromal cell derived factor (SDF)-1 levels in patients with neoplastic meningitis (NM) due to breast cancer, lung cancer and melanoma. J Neurooncol. 2009; 94(2) 229-234
- 23 Chamberlain M C. Cytologically negative carcinomatous meningitis: usefulness of CSF biochemical markers. Neurology. 1998; 50(4) 1173-1175
- 24 Hovestadt A, Henzen-Logmans S C, Vecht C J. Immunohistochemical analysis of the cerebrospinal fluid for carcinomatous and lymphomatous leptomeningitis. Br J Cancer. 1990; 62(4) 653-654
- 25 van Oostenbrugge R J, Hopman A H, Ramaekers F C, Twijnstra A. In situ hybridization: a possible diagnostic aid in leptomeningeal metastasis. J Neurooncol. 1998; 38(2-3) 127-133
- 26 Quijano S, López A, Manuel Sancho J Spanish Group for the Study of CNS Disease in NHL et al. Identification of leptomeningeal disease in aggressive B-cell non-Hodgkin's lymphoma: improved sensitivity of flow cytometry. J Clin Oncol. 2009; 27(9) 1462-1469
- 27 Bromberg J EC, Breems D A, Kraan J et al.. CSF flow cytometry greatly improves diagnostic accuracy in CNS hematologic malignancies. Neurology. 2007; 68(20) 1674-1679
- 28 Hegde U, Filie A, Little R F et al.. High incidence of occult leptomeningeal disease detected by flow cytometry in newly diagnosed aggressive B-cell lymphomas at risk for central nervous system involvement: the role of flow cytometry versus cytology. Blood. 2005; 105(2) 496-502
- 29 Cheng T M, O'Neill B P, Scheithauer B W, Piepgras D G. Chronic meningitis: the role of meningeal or cortical biopsy. Neurosurgery. 1994; 34(4) 590-595 discussion 596
- 30 Chamberlain M C, Sandy A D, Press G A. Leptomeningeal metastasis: a comparison of gadolinium-enhanced MR and contrast-enhanced CT of the brain. Neurology. 1990; 40(3 Pt 1) 435-438
- 31 Schumacher M, Orszagh M. Imaging techniques in neoplastic meningiosis. J Neurooncol. 1998; 38(2-3) 111-120
- 32 Chamberlain M C. Comparative spine imaging in leptomeningeal metastases. J Neurooncol. 1995; 23(3) 233-238
- 33 Freilich R J, Krol G, DeAngelis L M. Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis. Ann Neurol. 1995; 38(1) 51-57
- 34 Mittl Jr R L, Yousem D M. Frequency of unexplained meningeal enhancement in the brain after lumbar puncture. AJNR Am J Neuroradiol. 1994; 15(4) 633-638
- 35 Chamberlain M C. Radioisotope CSF flow studies in leptomeningeal metastases. J Neurooncol. 1998; 38(2-3) 135-140
- 36 Glantz M J, Hall W A, Cole B F et al.. Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow status. Cancer. 1995; 75(12) 2919-2931
- 37 Grossman S A, Trump C L, Chen D C, Thompson G, Camargo E E. Cerebrospinal flow abnormalities in patients with neoplastic meningitis. An evaluation using 111indium-DTPA ventriculography. Am J Med. 1982; 73 641-647
- 38 Chamberlain M C, Kormanik P A. Prognostic significance of 111indium-DTPA CSF flow studies in leptomeningeal metastases. Neurology. 1996; 46(6) 1674-1677
- 39 Mason W P, Yeh S D, DeAngelis L M. 111Indium-diethylenetriamine pentaacetic acid cerebrospinal fluid flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases. Neurology. 1998; 50(2) 438-444
- 40 Chamberlain M C, Corey-Bloom J. Leptomeningeal metastases: 111indium-DTPA CSF flow studies. Neurology. 1991; 41(11) 1765-1769
- 41 Chamberlain M C, Kormanik P, Jaeckle K A, Glantz M. 111Indium-diethylenetriamine pentaacetic acid CSF flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases. Neurology. 1999; 52(1) 216-217
- 42 Chamberlain M C, Kormanik P A. Prognostic significance of coexistent bulky metastatic central nervous system disease in patients with leptomeningeal metastases. Arch Neurol. 1997; 54(11) 1364-1368
- 43 Chamberlain M C. Neoplastic meningitis-related encephalopathy: prognostic significance. Neurology. 2004; 63 2159-2161
- 44 Chamberlain M C. Neoplastic meningitis: deciding who to treat. Expert Rev Neurother. 2004; 4 89-96
- 45 Brem S S, Bierman P J, Black P et al.. Central nervous system cancers. J Natl Compr Canc Netw. 2008; 6(5) 456-504
- 46 Shapiro W R, Young D F, Mehta B M. Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med. 1975; 293(4) 161-166
- 47 Grossman S A, Finkelstein D M, Ruckdeschel J C, Trump D L, Moynihan T, Ettinger D S. Eastern Cooperative Oncology Group . Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. J Clin Oncol. 1993; 11(3) 561-569
- 48 Glantz M J, Jaeckle K A, Chamberlain M C et al.. A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res. 1999; 5(11) 3394-3402
- 49 Glantz M J, LaFollette S, Jaeckle K A et al.. Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol. 1999; 17(10) 3110-3116
- 50 Shapiro W R, Schmid M, Glantz M, Miller J J. A randomized phase III/IV study to determine benefit and safety of cytarabine liposome injection for treatment of neoplastic meningitis. J Clin Oncol. 2006; 24(Suppl) 1528 (Abstract)
- 51 Chamberlain M C. A phase II trial of intra-cerebrospinal fluid alpha interferon in the treatment of neoplastic meningitis. Cancer. 2002; 94(10) 2675-2680
- 52 Chamberlain M C, Wei-Tsao D D, Groshen S. Phase 2 trial of intra-CSF etoposide in the treatment of neoplastic meningitis. Cancer. 2006; 106(9) 2021-2027
- 53 Groves M D, Glantz M J, Chamberlain M C et al.. A multicenter phase II trial of intrathecal topotecan in patients with meningeal malignancies. Neuro-oncol. 2008; 10(2) 208-215
- 54 Chamberlain M C, Johnston S K, Van Horn A, Glantz M J. Recurrent lymphomatous meningitis treated with intra-CSF rituximab and liposomal ara-C. J Neurooncol. 2009; 91(3) 271-277
- 55 Rubenstein J L, Fridlyand J, Abrey L et al.. Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma. J Clin Oncol. 2007; 25(11) 1350-1356
- 56 Mir O, Ropert S, Alexandre J, Lemare F, Goldwasser F. High-dose intrathecal trastuzumab for leptomeningeal metastases secondary to HER-2 overexpressing breast cancer. Ann Oncol. 2008; 19(11) 1978-1980
- 57 Allison D, Glantz M. Intra-CSF Trastuzumab in patients with neoplastic meningitis from breast cancer or primary brain tumors. Neurology. 2009; 72(11, Suppl 3) A30
- 58 Chamberlain M C. Risk of neoplastic meningitis following surgical resection of cerebellar metastases. J Neurooncol. 2008; 89(1) 105-107
- 59 Berweiler U, Krone A, Tonn J C. Reservoir systems for intraventricular chemotherapy. J Neurooncol. 1998; 38(2-3) 141-143
- 60 Sandberg D I, Bilsky M H, Souweidane M M, Bzdil J, Gutin P H. Ommaya reservoirs for the treatment of leptomeningeal metastases. Neurosurgery. 2000; 47(1) 49-54 discussion 54-55
- 61 Glantz M J, Van Horn A, Fisher R, Chamberlain M C. Route of intra-CSF chemotherapy administration and efficacy of therapy in neoplastic meningitis. Cancer. 2010; 116(8) 1947-1952
- 62 Siegal T. Leptomeningeal metastases: rationale for systemic chemotherapy or what is the role of intra-CSF-chemotherapy?. J Neurooncol. 1998; 38(2-3) 151-157
- 63 Boogerd W, van den Bent M J, Koehler P J et al.. The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study. Eur J Cancer. 2004; 40(18) 2726-2733
- 64 Hitchins R N, Bell D R, Woods R L, Levi J A. A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis. J Clin Oncol. 1987; 5(10) 1655-1662
- 65 Chamberlain M C, Kormanik P A, Barba D. Complications associated with intraventricular chemotherapy in patients with leptomeningeal metastases. J Neurosurg. 1997; 87(5) 694-699
- 66 Siegal T, Pfeffer M R, Steiner I. Antibiotic therapy for infected Ommaya reservoir systems. Neurosurgery. 1988; 22(1 Pt 1) 97-100
- 67 Kerr J Z, Berg S, Blaney S M. Intrathecal chemotherapy. Crit Rev Oncol Hematol. 2001; 37(3) 227-236
- 68 Stapleton S, Blaney S M. New agents for intrathecal administration. Cancer Invest. 2006; 24(5) 528-534
- 69 Glantz M J, Cole B F, Recht L et al.. High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: is intrathecal chemotherapy necessary?. J Clin Oncol. 1998; 16(4) 1561-1567
- 70 Bokstein F, Lossos A, Siegal T. Leptomeningeal metastases from solid tumors: a comparison of two prospective series treated with and without intra-cerebrospinal fluid chemotherapy. Cancer. 1998; 82(9) 1756-1763
- 71 Sampson J H, Archer G E, Villavicencio A T et al.. Treatment of neoplastic meningitis with intrathecal temozolomide. Clin Cancer Res. 1999; 5(5) 1183-1188
- 72 Bernardi R J, Bomgaars L, Fox E et al.. Phase I clinical trial of intrathecal gemcitabine in patients with neoplastic meningitis. Cancer Chemother Pharmacol. 2008; 62(2) 355-361
- 73 Herrlinger U, Weller M, Schabet M. New aspects of immunotherapy of leptomeningeal metastasis. J Neurooncol. 1998; 38(2-3) 233-239
- 74 Coakham H B, Kemshead J T. Treatment of neoplastic meningitis by targeted radiation using (131)I-radiolabelled monoclonal antibodies. Results of responses and long term follow-up in 40 patients. J Neurooncol. 1998; 38(2-3) 225-232
- 75 Chamberlain M C, Kormanik P R. Carcinomatous meningitis secondary to breast cancer: predictors of response to combined modality therapy. J Neurooncol. 1997; 35(1) 55-64
- 76 Chamberlain M C, Kormanik P. Carcinoma meningitis secondary to non-small cell lung cancer: combined modality therapy. Arch Neurol. 1998; 55(4) 506-512
- 77 Chamberlain M C, Johnston S K, Glantz M J. Neoplastic meningitis-related prognostic significance of the Karnofsky performance status. Arch Neurol. 2009; 66(1) 74-78
- 78 Chamberlain M C, Johnston S K. Neoplastic meningitis: survival as a function of cerebrospinal fluid cytology. Cancer. 2009; 115(9) 1941-1946
- 79 Garcia-Marco J A, Panizo C, Garcia E S et al.. Efficacy and safety of liposomal cytarabine in lymphoma patients with central nervous system involvement from lymphoma. Cancer. 2009; 115(9) 1892-1898
- 80 Jaeckle K A, Batchelor T, O'Day S J et al.. An open label trial of sustained-release cytarabine (DepoCyt) for the intrathecal treatment of solid tumor neoplastic meningitis. J Neurooncol. 2002; 57(3) 231-239
Marc C ChamberlainM.D.
Department of Neurology and Neurological Surgery, Division of Neuro-Oncology, University of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance
825 Eastlake Avenue E, POB 19023, MS G4940, Seattle, WA 98109-1023
Email: chambemc@u.washington.edu