Summary
Leptomeningeal metastases (LMM) consist of diffuse involvement of the leptomeninges by infiltrating cancer cells. In solid tumors, the most frequent primary sites are lung and breast cancers, two tumors where the incidence of LMM is apparently increasing. Careful neurological examination is required to demonstrate multifocal involvement of the central nervous system (CNS), cranial nerves, and spinal roots, which constitute the clinical hallmark of the disease. Cerebro-spinal fluid (CSF) analysis is almost always abnormal but only a positive cytology or demonstration of intrathecal synthesis of tumor markers is diagnostic. T1-weighted gadolinium-enhanced sequence of the entire neuraxis (brain and spine) plays an important role in supporting the diagnosis, demonstrating the involved sites and guiding treatment. Radionuclide CSF flow studies detect CSF compartmentalization and are useful for treatment planning. Standard therapy relies mainly on focal irradiation and intrathecal or systemic chemotherapy. Studies using other therapeutic approaches such as new biological or cytotoxic compounds are ongoing. The overall prognosis remains grim and quality of life should remain the priority when deciding which treatment option to apply. However, a sub-group of patients, tentatively defined here, may benefit from an aggressive treatment.
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ME Olson NL Chernik JB. Posner (1974) ArticleTitleInfiltration of the leptomeninges by systemic cancer A clinical and pathologic study. Arch Neurol 30 122–137
JR Little AJ Dale H. Okazaki (1974) ArticleTitleMeningeal carcinomatosis Clinical manifestations. Arch Neurol 30 138–143
WR Shapiro JB Posner Y Ushio NL Chemik DF. Young (1977) ArticleTitleTreatment of meningeal neoplasms Cancer Treat Rep 61 733–743 Occurrence Handle577896
WH Theodore S. Gendelman (1981) ArticleTitleMeningeal carcinomatosis Arch Neurol 38 696–699 Occurrence Handle6975612
WR Wasserstrom JP Glass JB. Posner (1982) ArticleTitleDiagnosis and treatment of leptomeningeal metastases from solid tumors: experience with 90 patients Cancer 49 759–772 Occurrence Handle6895713
JG Kaplan TG DeSouza A Farkash B Shafran D Pack F Rehman J Fuks R. Portenoy (1990) ArticleTitleLeptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias J Neurooncol 9 225–229 Occurrence Handle2086737
MC Chamberlain J. Corey-Bloom (1991) ArticleTitleLeptomeningeal metastases: 111indium-DTPA CSF flow studies Neurology 41 1765–1769 Occurrence Handle1944906
JB Posner NL Chernik (1978) ArticleTitleIntracranial metastases from systemic cancer Adv Neurol 19 579–592 Occurrence Handle570349
Takakura K, Sano K, Hojo S. Metastatic tumors of the central nervous system. 1982
SM Monte Particlede la GW Moore GM. Hutchins (1983) ArticleTitlePatterned distribution of metastases from malignant melanoma in humans Cancer Res 43 3427–3433 Occurrence Handle6850649
J Aisner SC Aisner S Ostrow S Govindan K Mummert P. Wiernik (1979) ArticleTitleMeningeal carcinomatosis from small cell carcinoma of the lung Consequence of improved survival. Acta Cytol 23 292–299
RS Aroney DN Dalley WK Chan DR Bell JA. Levi (1981) ArticleTitleMeningeal carcinomatosis in small cell carcinoma of the lung Am J Med 71 26–32 Occurrence Handle10.1016/0002-9343(81)90254-0 Occurrence Handle6264785
HY Yap BS Yap CK Tashima A DiStefano GR. Blumenschein (1978) ArticleTitleMeningeal carcinomatosis in breast cancer Cancer 42 283–286 Occurrence Handle667799
SA Jeyapalan TT. Batchelor (2000) ArticleTitleDiagnostic evaluation of neurologic metastases Cancer Invest 18 381–394 Occurrence Handle10808374
ST Rosen J Aisner RW Makuch MJ Matthews DC Ihde M Whitacre EJ Glatstein PH Wiernik AS Lichter PA Bunn SuffixJr. (1982) ArticleTitleCarcinomatous leptomeningitis in small cell lung cancer: a clinicopathologic review of the National Cancer Institute experience Medicine (Baltimore) 61 45–53
JB. Posner (1995) Leptomeningeal Metastases, in Neurologic Complications of Cancer FA Davis Philadelphia 143–171
JC Bendell SM Domchek HJ Burstein L Harris J Younger I Kuter C Bunnell M Rue R Gelman E. Winer (2003) ArticleTitleCentral nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma Cancer 97 2972–2977 Occurrence Handle10.1002/cncr.11436 Occurrence Handle12784331
D Crivellari O Pagani A Veronesi D Lombardi F Nole B Thurlimann D Hess M Borner J Bauer G Martinelli R Graffeo C Sessa A. Goldhirsch (2001) ArticleTitleHigh incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel Ann Oncol 12 353–356 Occurrence Handle10.1023/A:1011132609055 Occurrence Handle11332148
JP Glass M Melamed NL Chernik JB. Posner (1979) ArticleTitleMalignant cells in cerebrospinal fluid (CSF): the meaning of a positive CSF cytology Neurology 29 1369–1375 Occurrence Handle573381
JC Gonzalez-Vitale R. Garcia-Bunuel (1976) ArticleTitleMeningeal carcinomatosis Cancer 37 2906–2911 Occurrence Handle949711
CP. Kokkoris (1983) ArticleTitleLeptomeningeal carcinomatosis How does cancer reach the pia-arachnoid?. Cancer 51 154–160
L Bubendorf A Schopfer U Wagner G Sauter H Moch N Willi TC Gasser MJ. Mihatsch (2000) ArticleTitleMetastatic patterns of prostate cancer: an autopsy study of 1,589 patients Hum Pathol 31 578–583 Occurrence Handle10.1053/hp.2000.6698 Occurrence Handle10836297
AA. Geldof (1997) ArticleTitleModels for cancer skeletal metastasis: a reappraisal of Batson’s plexus Anticancer Res 17 1535–1539 Occurrence Handle9179192
R Boyle M Thomas JH. Adams (1980) ArticleTitleDiffuse involvement of the leptomeninges by tumour–a clinical and pathological study of 63 cases Postgrad Med J 56 149–158 Occurrence Handle7393804
D. Koch (1996) ArticleTitleSpinal metastases of cerebral glioma Case report. Neurosurg Rev 19 201–203
LK Norris SA Grossman A. Olivi (1997) ArticleTitleNeoplastic meningitis following surgical resection of isolated cerebellar metastasis: a potentially preventable complication J Neurooncol 32 215–223 Occurrence Handle10.1023/A:1005723801479 Occurrence Handle9049883
TC Ree Particlevan der DW Dippel CJ Avezaat PA Sillevis Smitt CJ Vecht MJ. Bent Particlevan den (1999) ArticleTitleLeptomeningeal metastasis after surgical resection of brain metastases J Neurol Neurosurg Psychiatry 66 225–227 Occurrence Handle10071105
K Hoang-Xuan M Napolitano P Cornu J-Y. Delattre (1999) ArticleTitleMétastases cérébrales et leptoméningées des cancers solides Encycl Méd Chir (Elsevier, Paris), Neurologie: 17 225A–210
WR. Wasserstrom (1995) Leptomeningeal metastases RG. Wiley (Eds) Neurological Complications of Cancer. Dekker New York 45–71
P Klein EC Haley GF Wooten SR. VandenBerg (1989) ArticleTitleFocal cerebral infarctions associated with perivascular tumor infiltrates in carcinomatous leptomeningeal metastases Arch Neurol 46 1149–1152 Occurrence Handle2552969
L Madow BJ. Alpers (1951) ArticleTitleEncephalitic form of metastatic carcinoma AMA Arch Neurol Psychiatry 65 161–173 Occurrence Handle14798993
K Hansen F Gjerris PS. Sorensen (1987) ArticleTitleAbsence of hydrocephalus in spite of impaired cerebrospinal fluid absorption and severe intracranial hypertension Acta Neurochir (Wien) 86 93–97 Occurrence Handle10.1007/BF01402291
T Siegal B Mildworf D Stein E. Melamed (1985) ArticleTitleLeptomeningeal metastases: reduction in regional cerebral blood flow and cognitive impairment Ann Neurol 17 100–102 Occurrence Handle10.1002/ana.410170121 Occurrence Handle3985577
EM Hiesiger A Picco-Del Bo LE Lipschutz GA Basler HT Thaler JB Posner WR. Shapiro (1989) ArticleTitleExperimental meningeal carcinomatosis selectively depresses local cerebral glucose utilization in rat brain Neurology 39 90–95 Occurrence Handle2909919
HY Yap CK Tashima GR Blumenschein N. Eckles (1979) ArticleTitleDiabetes insipidus and breast cancer Arch Intern Med 139 1009–1011 Occurrence Handle10.1001/archinte.139.9.1009 Occurrence Handle475518
WA Houck KB Olson J. Horton (1970) ArticleTitleClinical features of tumor metastasis to the pituitary Cancer 26 656–659 Occurrence Handle5272295
FS Marcus EM Dandolos MA. Friedman (1981) ArticleTitleMeningeal carcinomatosis in breast cancer presenting as central hypoventilation: a case report with a brief review of the literature Cancer 47 982–984 Occurrence Handle6261920
JW Miller DW Klass B Mokri H. Okazaki (1986) ArticleTitleTriphasic waves in cerebral carcinomatosis Another nonmetabolic cause. Arch Neurol 43 1191–1193
JB Reuler D. Meier (1979) ArticleTitleLeptomeningeal carcinomatosis with normal CSF features Arch Intern Med 139 237–238 Occurrence Handle10.1001/archinte.139.2.237 Occurrence Handle434981
A Gajjar M Fouladi AW Walter SJ Thompson DA Reardon TE Merchant JJ Jenkins A Liu JM Boyett LE Kun RL. Heideman (1999) ArticleTitleComparison of lumbar and shunt cerebrospinal fluid specimens for cytologic detection of leptomeningeal disease in pediatric patients with brain tumors J Clin Oncol 17 1825–1828 Occurrence Handle10561221
JJ Murray FA Greco SN Wolff JD. Hainsworth (1983) ArticleTitleNeoplastic meningitis Marked variations of cerebrospinal fluid composition in the absence of extradural block. Am J Med 75 289–294
GG Klee RD Tallman JR Goellner T. Yanagihara (1986) ArticleTitleElevation of carcinoembryonic antigen in cerebrospinal fluid among patients with meningeal carcinomatosis Mayo Clin Proc 61 9–13 Occurrence Handle3510343
M Malkin JB. Posner (1986) ArticleTitlePerspectives and commentaries: cerebrospinal fluid tumor markers for the diagnosis and management of leptomeningeal metastases Eur J Cancer Clin Oncol 22 387–392 Occurrence Handle10.1016/0277-5379(86)90103-3 Occurrence Handle3525181
ES Cibas MG Malkin JB Posner MR. Melamed (1987) ArticleTitleDetection of DNA abnormalities by flow cytometry in cells from cerebrospinal fluid Am J Clin Pathol 88 570–577 Occurrence Handle3673940
S Biesterfeld B Bernhard S Bamborschke A. Bocking (1993) ArticleTitleDNA single cell cytometry in lymphocytic pleocytosis of the cerebrospinal fluid Acta Neuropathol (Berl) 86 428–432
R Dux A Kindler-Rohrborn M Annas P Faustmann K Lennartz CW. Zimmermann (1994) ArticleTitleA standardized protocol for flow cytometric analysis of cells isolated from cerebrospinal fluid J Neurol Sci 121 74–78 Occurrence Handle10.1016/0022-510X(94)90159-7 Occurrence Handle7510788
IF Granberg-Ohman BI Andersson SK Gupta UM. Lying-Tunell (1979) ArticleTitleChromosome analysis in meningeal carcinomatosis Acta Neurol Scand 60 255–259 Occurrence Handle525257
Twinstra A. (2002). Leptomeningeal metastases from solid tumors. EANO V Educational book: 111–115
DS Hoon CT Kuo RA Wascher P Fournier HJ Wang SJ. O’Day (2001) ArticleTitleMolecular detection of metastatic melanoma cells in cerebrospinal fluid in melanoma patients J Invest Dermatol 117 375–378 Occurrence Handle10.1046/j.0022-202x.2001.01417.x Occurrence Handle11511319
M Tosaka M Tamura N Oriuchi M Horikoshi T Joshita K Sugawara S Kobayashi H Kohga T Yoshida T. Sasaki (2001) ArticleTitleCerebrospinal fluid immunocytochemical analysis and neuroimaging in the diagnosis of primary leptomeningeal melanoma Case report. J Neurosurg 94 528–532
M Srodon WH. Westra (2002) ArticleTitleImmunohistochemical staining for thyroid transcription factor-1: a helpful aid in discerning primary site of tumor origin in patients with brain metastases Hum Pathol 33 642–645 Occurrence Handle10.1053/hupa.2002.124910 Occurrence Handle12152164
SC Schold WR Wasserstrom M Fleisher MK Schwartz JB. Posner (1980) ArticleTitleCerebrospinal fluid biochemical markers of central nervous system metastases Ann Neurol 8 597–604 Occurrence Handle10.1002/ana.410080609 Occurrence Handle7212647
M Fleisher WR Wasserstrom SC Schold MK Schwartz JB. Posner (1981) ArticleTitleLactic dehydrogenase isoenzymes in the cerebrospinal fluid of patients with systemic cancer Cancer 47 2654–2659 Occurrence Handle7260857
SK Singh JM Agris NE Leeds LE. Ginsberg (2000) ArticleTitleIntracranial leptomeningeal metastases: comparison of depiction at FLAIR and contrast-enhanced MR imaging Radiology 217 50–53 Occurrence Handle11012422
SK Singh NE Leeds LE. Ginsberg (2002) ArticleTitleMR imaging of leptomeningeal metastases: comparison of three sequences AJNR Am J Neuroradiol 23 817–821 Occurrence Handle12006284
MC Chamberlain AD Sandy GA. Press (1990) ArticleTitleLeptomeningeal metastasis: a comparison of gadolinium-enhanced MR and contrast-enhanced CT of the brain Neurology 40 435–438 Occurrence Handle2314584
KA Jaeckle G Krol JB. Posner (1985) ArticleTitleEvolution of computed tomographic abnormalities in leptomeningeal metastases Ann Neurol 17 85–89 Occurrence Handle10.1002/ana.410170118 Occurrence Handle3872622
YY Lee JP Glass A Geoffray S. Wallace (1984) ArticleTitleCranial computed tomographic abnormalities in leptomeningeal metastasis AJR Am J Roentgenol 143 1035–1039 Occurrence Handle6333146
GF Ascherl SuffixJr. SK Hilal R. Brisman (1981) ArticleTitleComputed tomography of disseminated meningeal and ependymal malignant neoplasms Neurology 31 567–574 Occurrence Handle7194972
G Sze S Soletsky R Bronen G. Krol (1989) ArticleTitleMR imaging of the cranial meninges with emphasis on contrast enhancement and meningeal carcinomatosis AJR Am J Roentgenol 153 1039–1049 Occurrence Handle2801423
WP Mason SD Yeh LM. DeAngelis (1998) ArticleTitle111Indium-diethylenetriamine pentaacetic acid cerebrospinal fluid flow studies predict distribution of intrathecally administered chemotherapy and outcome in patients with leptomeningeal metastases Neurology 50 438–444 Occurrence Handle9484369
KS Kim SU Ho PE Weinberg C. Lee (1982) ArticleTitleSpinal leptomeningeal infiltration by systemic cancer: myelographic features AJR Am J Roentgenol 139 361–365 Occurrence Handle6979894
G Krol G Sze M Malkin R. Walker (1988) ArticleTitleMR of cranial and spinal meningeal carcinomatosis: comparison with CT and myelography AJR Am J Roentgenol 151 583–588 Occurrence Handle3261521
ED Kramer S Rafto RJ Packer RA. Zimmerman (1991) ArticleTitleComparison of myelography with CT follow-up versus gadolinium MRI for subarachnoid metastatic disease in children Neurology 41 46–50 Occurrence Handle1985295
G Sze A Abramson G Krol D Liu J Amster RD Zimmerman MD. Deck (1988) ArticleTitleGadolinium-DTPA in the evaluation of intradural extramedullary spinal disease AJR Am J Roentgenol 150 911–921 Occurrence Handle3258107
V Lim DF Sobel J. Zyroff (1990) ArticleTitleSpinal cord pial metastases: MR imaging with gadopentetate dimeglumine AJR Am J Roentgenol 155 1077–1084 Occurrence Handle2120938
AG Pedersen OB Paulson C. Gyldensted (1985) ArticleTitleMetrizamide myelography in patients with small cell carcinoma of the lung suspected of meningeal carcinomatosis J Neurooncol 3 85–89 Occurrence Handle10.1007/BF00165176 Occurrence Handle2987430
MD Wiener OB Boyko HS Friedman B Hockenberger WJ. Oakes (1990) ArticleTitleFalse-positive spinal MR findings for subarachnoid spread of primary CNS tumor in postoperative pediatric patients AJNR Am J Neuroradiol 11 1100–1103 Occurrence Handle2124036
DJ Rippe OB Boyko HS Friedman WJ Oakes SC Schold SuffixJr. GR DeLong WJ. Meisler (1990) ArticleTitleGd-DTPA-enhanced MR imaging of leptomeningeal spread of primary intracranial CNS tumor in children AJNR Am J Neuroradiol 11 329–332 Occurrence Handle2107715
MC. Chamberlain (1995) ArticleTitleComparative spine imaging in leptomeningeal metastases J Neurooncol 23 233–238 Occurrence Handle10.1007/BF01059954 Occurrence Handle7673985
DM Yousem PM Patrone RI. Grossman (1990) ArticleTitleLeptomeningeal metastases: MR evaluation J Comput Assist Tomogr 14 255–261 Occurrence Handle2312855
RJ Freilich G Krol LM. DeAngelis (1995) ArticleTitleNeuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis Ann Neurol 38 51–57 Occurrence Handle10.1002/ana.410380111 Occurrence Handle7611725
LM. DeAngelis (1998) ArticleTitleCurrent diagnosis and treatment of leptomeningeal metastasis J Neurooncol 38 245–252 Occurrence Handle10.1023/A:1005956925637 Occurrence Handle9696379
MC. Chamberlain (2000) ArticleTitleNeoplastic meningitis: a guide to diagnosis and treatment Curr Opin Neurol 13 641–648 Occurrence Handle10.1097/00019052-200012000-00005 Occurrence Handle11148663
G Rodesch P Van Bogaert N Mavroudakis PM Parizel JJ Martin C Segebarth M Van Vyve D Baleriaux J. Hildebrand (1990) ArticleTitleNeuroradiologic findings in leptomeningeal carcinomatosis: the value interest of gadolinium-enhanced MRI Neuroradiology 32 26–32 Occurrence Handle10.1007/BF00593937 Occurrence Handle2333130
KC Gorson AH Ropper MA Muriello R. Blair (1996) ArticleTitleProspective evaluation of MRI lumbosacral nerve root enhancement in acute Guillain-Barre syndrome Neurology 47 813–817 Occurrence Handle8797486
VB Joseph L Raghuram IP Korah AG. Chacko (2003) ArticleTitleMR ventriculography for the study of CSF flow AJNR Am J Neuroradiol 24 373–381 Occurrence Handle12637285
SM Larson GS Johnston AK Ommaya AE Jones G. Di Chiro (1973) ArticleTitleThe radionuclide ventriculogram Jama 224 853–857 Occurrence Handle10.1001/jama.224.6.853 Occurrence Handle4540526
G Di Chiro M Hammock A. Bleyer (1976) ArticleTitleSpinal descent of cerebrospinal fluid in man Neurology 26 1–8 Occurrence Handle942765
MK Lyons FB. Meyer (1990) ArticleTitleCerebrospinal fluid physiology and the management of increased intracranial pressure Mayo Clin Proc 65 684–707 Occurrence Handle2190050
MC. Chamberlain (1994) ArticleTitlePediatric leptomeningeal metastasis: 111In-DTPA cerebrospinal fluid flow studies J Child Neurol 9 150–154 Occurrence Handle8006365
MC. Chamberlain (1995) ArticleTitleSpinal 111Indium-DTPA CSF flow studies in leptomeningeal metastasis J Neurooncol 25 135–141 Occurrence Handle10.1007/BF01057757 Occurrence Handle8543969
RE Latchaw TO Gabrielsen GF. Seeger (1974) ArticleTitleCerebral angiography in meningeal sarcomatosis and carcinomatosis Neuroradiology 8 131–139 Occurrence Handle10.1007/BF00341592
TM Cheng BP O’Neill BW Scheithauer DG. Piepgras (1994) ArticleTitleChronic meningitis: the role of meningeal or cortical biopsy Neurosurgery 34 590–595 Occurrence Handle8008155
Pradat PF, Delattre J-Y: Méningites chroniques. Encycl Méd Chir (Elsevier, Paris), Neurologie: 17–160-C-130, 113p, 1995
F Aichner G. Schuler (1982) ArticleTitlePrimary leptomeningeal melanoma Diagnosis by ultrastructural cytology of cerebrospinal fluid and cranial computed tomography. Cancer 50 1751–1756
MH Savitz PJ. Anderson (1974) ArticleTitlePrimary melanoma of the leptomeninges: a review Mt Sinai J Med 41 774–791 Occurrence Handle4610369
SW Silbert KR Smith SuffixJr. S. Horenstein (1978) ArticleTitlePrimary leptomeningeal melanoma: an ultrastructural study Cancer 41 519–527 Occurrence Handle630534
MT Smith VW Armbrustmacher TW. Violett (1981) ArticleTitleDiffuse meningeal rhabdomyosarcoma Cancer 47 2081–2086 Occurrence Handle7194734
M Machado M Salcman RS Kaplan E. Montgomery (1985) ArticleTitleExpanded role of the cerebrospinal fluid reservoir in neurooncology: indications, causes of revision, and complications Neurosurgery 17 600–603 Occurrence Handle4058696
EA Obbens ME Leavens JW Beal YY. Lee (1985) ArticleTitleOmmaya reservoirs in 387 cancer patients: a 15-year experience Neurology 35 1274–1278 Occurrence Handle3839573
N Sundaresan ND. Suite (1989) ArticleTitleOptimal use of the Ommaya reservoir in clinical oncology Oncology (Huntingt) 3 15–22
T. Siegal (2003) ArticleTitleToxicity of treatment for neoplastic meningitis Curr Oncol Rep 5 41–49 Occurrence Handle12493149
M. Chamberlain (1998) ArticleTitleLeptomeningeal metastases: a review of evaluation and treatment J Neurooncol 37 271–284 Occurrence Handle10.1023/A:1005976926058 Occurrence Handle9524085
PA Dinndorf WA. Bleyer (1987) ArticleTitleManagement of infectious complications of intraventricular reservoirs in cancer patientsq: low incidence and successful treatment without reservoir removal Cancer Drug Deliv 4 105–117 Occurrence Handle3480777
T Siegal MR Pfeffer I. Steiner (1988) ArticleTitleAntibiotic therapy for infected Ommaya reservoir systems Neurosurgery 22 97–100 Occurrence Handle2449629
DL Trump SA Grossman G Thompson K. Murray (1982) ArticleTitleCSF infections complicating the management of neoplastic meningitis Clinical features and results of therapy. Arch Intern Med 142 583–586
RG Blasberg C Patlak JD. Fenstermacher (1975) ArticleTitleIntrathecal chemotherapy: brain tissue profiles after ventriculocisternal perfusion J Pharmacol Exp Ther 195 73–83 Occurrence Handle810575
LJ. Novak (1989) ArticleTitleRadiotherapy of the central nervous system in acute leukemia Am J Pediatr Hematol Oncol 11 87–92 Occurrence Handle2653079
GJ D’Angio LA French EM Stadlan SA. Kieffer (1968) ArticleTitleIntrathecal radioisotopes for the treatment of brain tumors Clin Neurosurg 15 288–300 Occurrence Handle4942251
H Doge R. Hliscs (1984) ArticleTitleIntrathecal therapy with 198Au-colloid for meningosis prophylaxis Eur J Nucl Med 9 125–128 Occurrence Handle10.1007/BF00253514 Occurrence Handle6325197
O Metz W Stoll W. Plenert (1982) ArticleTitleMeningosis prophylaxis with intrathecal 198Au-colloid and methotrexate in childhood acute lymphocytic leukemia Cancer 49 224–228 Occurrence Handle6274505
JC Benjamin T Moss RP Moseley R Maxwell HB. Coakham (1989) ArticleTitleCerebral distribution of immunoconjugate after treatment for neoplastic meningitis using an intrathecal radiolabeled monoclonal antibody Neurosurgery 25 253–258 Occurrence Handle10.1097/00006123-198908000-00015 Occurrence Handle2770989
RP Moseley AG Davies RB Richardson M Zalutsky S Carrell J Fabre N Slack J Bullimore B Pizer V. Papanastassiou et al. (1990) ArticleTitleIntrathecal administration of 131I radiolabelled monoclonal antibody as a treatment for neoplastic meningitis Br J Cancer 62 637–642 Occurrence Handle2223581
K Kramer NK Cheung JL Humm E Dantis R Finn SJ Yeh NL Antunes IJ Dunkel M Souwedaine SM. Larson (2000) ArticleTitleTargeted radioimmunotherapy for leptomeningeal cancer using (131)I-3F8 Med Pediatr Oncol 35 716–718 Occurrence Handle10.1002/1096-911X(20001201)35:6<716::AID-MPO51>3.0.CO;2-0 Occurrence Handle11107154
WA Bleyer DG Poplack RM. Simon (1978) ArticleTitle“Concentration × time” methotrexate via a subcutaneous reservoir: a less toxic regimen for intraventricular chemotherapy of central nervous system neoplasms Blood 51 835–842 Occurrence Handle638249
WA Bleyer J Drake B. Chabner (1973) ArticleTitleNeurotoxicity and elevated cerebrospinal fluid methotrexate concentration in meningeal leukemia N Engl J Med 289 770–773 Occurrence Handle4517004
R Price P. Jamieson (1975) ArticleTitleThe central nervous system in chidhood leukemia Sub-acute leukoencephalopathy. Cancer 35 306–318
Poplack D, Bleyer WA, Horowitz M. Pharmacology of antineoplastic agents in cerebrospinal fluid. 1980
PA Burch SA Grossman CS. Reinhard (1988) ArticleTitleSpinal cord penetration of intrathecally administered cytarabine and methotrexate: a quantitative autoradiographic study J Natl Cancer Inst 80 1211–1216 Occurrence Handle3418727
S Blaney D Poplack K Godwin C McCully RF Murphy F. Balis (1995) ArticleTitleThe effect of body position on ventricular cerebrospinal fluid methotrexate following intralumbar administration J Clin Oncol 13 177–179 Occurrence Handle7799017
WR Shapiro DF Young BM. Mehta (1975) ArticleTitleMethotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections N Engl J Med 293 161–166 Occurrence Handle806016
MC Chamberlain S Khatibi JC Kim SB Howell E Chatelut S. Kim (1993) ArticleTitleTreatment of leptomeningeal metastasis with intraventricular administration of depot cytarabine (DTC 101) A phase I study. Arch Neurol 50 261–264
S Kim E Chatelut JC Kim SB Howell C Cates PA Kormanik MC. Chamberlain (1993) ArticleTitleExtended CSF cytarabine exposure following intrathecal administration of DTC 101 J Clin Oncol 11 2186–2193 Occurrence Handle8229133
L Ettinger D Chervinsky A Freeman PJ. Creaven (1982) ArticleTitlePharmacokinetics of methotrexate following intravenous and intraventricular administration in acute lymphocitic leukemia and non-Hodgkin’s lymphoma Cancer 50 1676–1682 Occurrence Handle6956429
DL Trump SA Grossman G Thompson K Murray M. Wharam (1982) ArticleTitleTreatment of neoplastic meningitis with intraventricular thiotepa and methotrexate Cancer Treat Rep 66 1549–1551 Occurrence Handle6807542
DR Strother A Glynn-Barnhart E Kovnar RE Gregory SB. Murphy (1989) ArticleTitleVariability in the disposition of intraventricular methotrexate: a proposal for rational dosing J Clin Oncol 7 1741–1747 Occurrence Handle2809687
AM Moser PC Adamson AJ Gillespie DGB Poplack FM. Balis (1999) ArticleTitleIntraventricular Concentration times time (CxT) methotrexate and cytarabine for patients with recurrent meningeal leukemia and lymphoma Cancer 85 511–556 Occurrence Handle10.1002/(SICI)1097-0142(19990115)85:2<511::AID-CNCR33>3.0.CO;2-H Occurrence Handle10023723
T Petit P Dufour AS Korganov F Maloisel F. Oberling (1997) ArticleTitleContinuous intrathecal perfusion of methotrexate for carcinomatous meningitis with pharmacokinetic studies: two case studies Clin Oncol 9 189–190 Occurrence Handle10.1016/S0936-6555(97)80080-5
PC Adamson FM Balis CA Arndt JS Holcenberg PK Narang RF Murphy AJ Gillespie DG. Poplack (1991) ArticleTitleIntrathecal 6-mercaptopurine: preclinical pharmacology, phase I/II trial, and pharmacokinetic study Cancer Res 51 6079–6083 Occurrence Handle1933871
S Zimm JM Collins J Miser D Chatterji D. Poplack (1984) ArticleTitleCytosine arabinoside cerebrospinal fluid kinetics Clin Pharmacol Therap 35 826–830
MJ Glantz KA Jaeckle MC Chamberlain S Phuphanich L Recht LJ Swinnen B Maria S LaFollette GB Schumann BF Cole SB. Howell (1999) ArticleTitleA randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors Clin Cancer Research 5 3394–3402
SA Grossman DM Finkelstein JC Ruckdeschel DL Trump T Moynihan DS. Ettinger (1993) ArticleTitleRandomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis Eastern Cooperative Oncology Group. J Clin Oncol 11 561–569
LB. Mellett (1977) ArticleTitlePhysicochemical considerations and pharmacokinetic behavior in delivery of drugs to the central nervous system Cancer Treat Rep 61 527–531 Occurrence Handle884690
T Siegal A Lossos MR. Pfeffer (1994) ArticleTitleLeptomeningeal metastases: analysis of 31 patients with sustained off-therapy response following combined-modality therapy Neurology 44 1463–1469 Occurrence Handle8058150
W Boogerd AA Hart JJ Sande Particlevan der E. Engelsman (1991) ArticleTitleMeningeal carcinomatosis in breast cancer Prognostic factors and influence of treatment. Cancer 67 1685–1695
R Grant B Naylor HS Greenberg L. Junck (1994) ArticleTitleClinical outcome in aggressively treated meningeal carcinomatosis Arch Neurol 51 457–461 Occurrence Handle8179494
K Fizazi B Asselain A Vincent-Salomon M Jouve V Dieras T Palangie P Beuzeboc T Dorval P. Pouillart (1996) ArticleTitleMeningeal carcinomatosis in patients with breast carcinoma Clinical features, prognostic factors, and results of a high-dose intrathecal methotrexate regimen. Cancer 77 1315–1323
F Bokstein A Lossos T. Siegal (1998) ArticleTitleLeptomeningeal metastases from solid tumors: a comparison of two prospective series treated with and without intra-cerebrospinal fluid chemotherapy Cancer 82 1756–1763 Occurrence Handle10.1002/(SICI)1097-0142(19980501)82:9<1764::AID-CNCR24>3.0.CO;2-1 Occurrence Handle9576299
F Bokstein A Lossos T. Siegal (1997) ArticleTitleLeptomeningeal metastases in solid tumors: exclusion of intra-CSF chemotherapy does not affect treatment outcome Comparison of two prospective series. Neurology 48 IssueIDSuppl 2 A35
T. Siegal (1998) ArticleTitleLeptomeningeal metastases: rationale for systemic chemotherapy or what is the role of intra-CSF-chemotherapy? J Neurooncol 38 151–157 Occurrence Handle10.1023/A:1005999228846 Occurrence Handle9696366
MC Chamberlain P. Kormanik (1998) ArticleTitleCarcinoma meningitis secondary to non-small cell lung cancer: combined modality therapy Arch Neurol 55 506–512 Occurrence Handle10.1001/archneur.55.4.506 Occurrence Handle9561978
R Donehower J Karp P. Burke (1986) ArticleTitlePharmacology and toxicity of high-dose cytarabine by 72-hour continuous infusion Cancer Treat Rep 70 1059–1065 Occurrence Handle3461882
E Morra M Lazzarino E Brusamolino G Pagnucco C Castagnola P Bernasconi E Orlandi A Corso A Santagostino C. Bernasconi (1993) ArticleTitleThe role of systemic high-dose cytarabine in the treatment of central nervous system leukemia Clinical results in 46 patients. Cancer 72 439–445 Occurrence Handle8319175
ML Slevin EM Piall GW Aherne VJ Harvey A Johnston TA. Lister (1983) ArticleTitleEffect of dose and schedule on pharmacokinetics of high-dose cytosine arabinoside in plasma and cerebrospinal fluid J Clin Oncol 1 546–551 Occurrence Handle6583325
M Ozdogan M Samur HS Bozcuk E Sagtas M Yildiz M Artac B. Savas (2003) ArticleTitleDurable remission of leptomeningeal metastasis of breast cancer with letrozole: a case report and implications of biomarkers on treatment selection Jpn J Clin Oncol 33 229–231 Occurrence Handle10.1093/jjco/hyg046 Occurrence Handle12865466
W Boogerd LD Dorresteijn JJ Sande Particlevan Der GC Gast Particlede PF. Bruning (2000) ArticleTitleResponse of leptomeningeal metastases from breast cancer to hormonal therapy Neurology 55 117–119 Occurrence Handle10891918
J Zovickian RJ. Youle (1988) ArticleTitleEfficacy of intrathecal immunotoxin therapy in an animal model of leptomeningeal neoplasia J Neurosurg 68 767–774 Occurrence Handle3258632
HS. Friedman (2000) ArticleTitleTemozolomide in early stages of newly diagnosed malignant glioma and neoplastic meningitis Semin Oncol 27 35–40 Occurrence Handle10866348
SL Berg FM Balis S Zimm RF Murphy J Holcenberg J Sato G Reaman P Steinherz A Gillespie K. Doherty et al. (1992) ArticleTitlePhase I/II trial and pharmacokinetics of intrathecal diaziquone in refractory meningeal malignancies J Clin Oncol 10 143–148 Occurrence Handle1727916
S Blaney F Balis RF Murphy CA Arndt A Gillepsie DG. Poplack (1992) ArticleTitleA phase I study of intrathecal mafosfamide (MF) in patients with refractory meningeal malignancies. (Abstract 274) Proc Am Soc Clin Oncol 11 113
VA Levin M Chamberlain P Silver L Rodriguez M. Prados (1989) ArticleTitlePhase I/II study of intraventricular and intrathecal ACNU for leptomeningeal neoplasia Cancer Chemother Pharmacol 23 301–307 Occurrence Handle10.1007/BF00292408 Occurrence Handle2706735
J List RP Moser M Steuer WG Loudon JB Blacklock EA. Grimm (1992) ArticleTitleCytokine responses to intraventricular injection of interleukin 2 into patients with leptomeningeal carcinomatosis: rapid induction of tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, gamma-interferon, and soluble interleukin 2 receptor (Mr 55,000 protein) Cancer Res 52 1123–1128 Occurrence Handle1737371
FM Balis DG. Poplack (1989) ArticleTitleCentral nervous system pharmacology of antileukemic drugs Am J Pediatr Hematol Oncol 11 74–86 Occurrence Handle2496615
JM Strong JM Collins C Lester DG. Poplack (1986) ArticleTitlePharmacokinetics of intraventricular and intravenous N,N’,N”-triethylenethiophosphoramide (thiotepa) in rhesus monkeys and humans Cancer Res 46 6101–6104 Occurrence Handle3096555
TF Witham MB Fukui CC Meltzer R Burns D Kondziolka ME. Bozik (1999) ArticleTitleSurvival of patients with high grade glioma treated with intrathecal thiotriethylenephosphoramide for ependymal or leptomeningeal gliomatosis Cancer 86 1347–1353 Occurrence Handle10.1002/(SICI)1097-0142(19991001)86:7<1347::AID-CNCR34>3.0.CO;2-M Occurrence Handle10506724
YM Chen MC Chen CM Tsai RP. Perng (2003) ArticleTitleIntrathecal gemcitabine chemotherapy for non-small cell lung cancer patients with meningeal carcinomatosis–a case report Lung Cancer 40 99–101 Occurrence Handle10.1016/S0169-5002(02)00504-4 Occurrence Handle12660014
I Cokgor AH Friedman HS. Friedman (2002) ArticleTitleCurrent options for the treatment of neoplastic meningitis J Neurooncol 60 79–88 Occurrence Handle10.1023/A:1020200317464 Occurrence Handle12416549
SM Blaney R Heideman S Berg P Adamson A Gillespie JR Geyer R Packer K Matthay K Jaeckle D Cole N Kuttesch DG Poplack FM. Balis (2003) ArticleTitlePhase I clinical trial of intrathecal topotecan in patients with neoplastic meningitis J Clin Oncol 21 143–147 Occurrence Handle10.1200/JCO.2003.04.053 Occurrence Handle12506183
EH Oldfield Z Ram Y Chiang RM. Blaese (1995) ArticleTitleIntrathecal gene therapy for the treatment of leptomeningeal carcinomatosis. GTI 0108 A phase I/II study. Hum Gene Ther 6 55–85
MR Rosenfeld I Bergman L Schramm JA Griffin MG Kaplitt PI. Meneses (1997) ArticleTitleAdeno-associated viral vector gene transfer into leptomeningeal xenografts J Neurooncol 34 139–144 Occurrence Handle10.1023/A:1005702228721 Occurrence Handle9210060
JJ Viola Z Ram S Walbridge EM Oshiro B Trapnell JH Tao-Cheng EH. Oldfield (1995) ArticleTitleAdenovirally mediated gene transfer into experimental solid brain tumors and leptomeningeal cancer cells J Neurosurg 82 70–76 Occurrence Handle7815137
MT Brown RE Coleman AH Friedman HS Friedman RE McLendon R Reiman CJ Felsberg RD Tien SH Bigner MR Zalutsky XG Zhao CJ Wikstrand CN Pegram JEn Herndon NA Vick N Paleologos RK Frederiks SCJ Schold DD. Bigner (1996) ArticleTitleIntrathecal 131 I-labeled antitenascin monoclonal antibody 81C6 treatment of patients with leptomeningeal neoplasms or primary brain tumor resection cavities with subarachnoid communication: phase I trial results Clin Cancer Res 2 963–972 Occurrence Handle9816257
I Cokgor G Akabani HS Friedman AH Friedman MR Zatusky LM Zehngebot JM Provenzale CD Guy CJ. Wikstrand (2001) ArticleTitleLong term response in a patient with neoplastic meningitis secondary to melnoma treated with (131) I-radiolabeled anti-chondroitin proteoglycan sulfate Mel-14 F(ab’) (2): a case study Cancer 91 1809–1813 Occurrence Handle10.1002/1097-0142(20010501)91:9<1809::AID-CNCR1200>3.0.CO;2-L Occurrence Handle11335907
GE Archer JH Sampson IA Lorimer RE McLendon CT Kuan AH Friedman HS Friedman IH Pastan DD. Bigner (1999) ArticleTitleRegional treatment of epidermal growth factor receptor vIII-expressing neoplastic meningitis with a single-chain immunotoxin, MR-I Clin Cancer Research 5 2646–2652
DD Bigner GE Archer RE McLendon HS Friedman HE Fuchs LH Pai JEn Herndon IH. Pastan (1995) ArticleTitleEfficacy of compartmental administration of immunotoxin LMB-1 (B3-LysPE38) in a rat model of carcinomatous meningitis Clin Cancer Res 1 1545–1555 Occurrence Handle9815955
JC Reijneveld MJ Taphoorn OA Kerckhaert TA Drixler W Boogerd EE. Voest (2003) ArticleTitleAngiostatin prolongs the survival of mice with leptomeningeal metastases Eur J Clin Invest 33 76–81 Occurrence Handle10.1046/j.1365-2362.2003.01056.x Occurrence Handle12492456
D Brandsma JC Reijneveld MJ Taphoorn HC Boer Particlede MF Gebbink LH Ulfman JJ Zwaginga EE. Voest (2002) ArticleTitleVascular cell adhesion molecule-1 is a key adhesion molecule in melanoma cell adhesion to the leptomeninges Lab Invest 82 1493–1502 Occurrence Handle12429809
LR Laufman KF. Forsthoefel (2001) ArticleTitleUse of intrathecal trastuzumab in a patient with carcinomatous meningitis Clin Breast Cancer 2 235 Occurrence Handle11899418
HI Robins G Liu L Hayes M. Mehta (2002) ArticleTitleTrastuzumab for breast cancer-related carcinomatous meningitis Clin Breast Cancer 2 316 Occurrence Handle11899365
J Renbarger A Aleksic L McGuffey R Dauser S Berg S. Blaney (2004) ArticleTitlePlasma and cerebrospinal fluid pharmacokinetics of SU5416 after intravenous administration in nonhuman primates Cancer Chemother Pharmacol 53 39–42 Occurrence Handle10.1007/s00280-003-0683-z Occurrence Handle14551735
LS Lashfford AG Davies RB Richardson SP Bourne JA Bullimore H Eckert JT Kemshead HB. Coakham (1988) ArticleTitleA pilot study of 131I monoclonal antibodies in the therapy of leptomeningeal tumors Cancer 61 857–868 Occurrence Handle3338052
RP Moseley JC Benjamin RD Ashpole NM Sulli #132;van JA Bullimore HB Coakham JT. Kemshead (1991) ArticleTitleCarcinomatous meningitis: antibody-guided therapy with I-131 HMFG1 J Neurol Neurosurg Psychiatry 54 260–265 Occurrence Handle2030355
M Hisanaga S Kawai M Maekawa Y Hattori K. Kotoh (1988) ArticleTitle[Neoplastic aneurysms due to cerebral metastasis of choriocarcinoma Report of two cases]. Neurol Med Chir (Tokyo) 28 398–403
JT Kemshead V Papanastassiou HB Coakham BL. Pizer (1992) ArticleTitleMonoclonal antibodies in the treatment of central nervous system malignancies Eur J Cancer 28 511–513 Occurrence Handle1591076
AT Myklebust A Godal O. Fodstad (1994) ArticleTitleTargeted therapy with immunotoxins in a nude rat model for leptomeningeal growth of human small cell lung cancer Cancer Res 54 2146–2150 Occurrence Handle8174121
VG Johnson C Wrobel D Wilson J Zovickian L Greenfield EH Oldfield R. Youle (1989) ArticleTitleImproved tumor-specific immunotoxins in the treatment of CNS and leptomeningeal neoplasia J Neurosurg 70 240–248 Occurrence Handle2783608
WA Hall O. Fodstad (1992) ArticleTitleImmunotoxins and central nervous system neoplasia J Neurosurg 76 1–12 Occurrence Handle1727147
RJ. Youle (1996) ArticleTitleImmunotoxins for central nervous system malignancy Semin Cancer Biol 7 65–70 Occurrence Handle10.1006/scbi.1996.0010 Occurrence Handle8740561
DW Laske KM Muraszko EH Oldfield HL Vroom Particlede C Sung RL Dedrick TR Simon J Colandrea C Copeland D Katz L Greenfield ES Groves LL Houston RJ. Youle (1997) ArticleTitleIntraventricular immunotoxin therapy for leptomeningeal neoplasia Neurosurgery 41 1039–1049 Occurrence Handle10.1097/00006123-199711000-00005 Occurrence Handle9361057
MJ Glantz S LaFollette K. Jaeckle (1999) ArticleTitleRandomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis J Clin Oncol 17 3110–3116 Occurrence Handle10506606
CC Liaw KT Ng JS Huang CH Wang MC Kiu GM. Lai (1992) ArticleTitleMeningeal carcinomatosis from solid tumors: clinical analysis of 42 cases J Formos Med Assoc 91 299–303 Occurrence Handle1354692
BW Ongerboer de Visser R Somers WH Nooyen P Heerde Particlevan AA Hart JG. McVie (1983) ArticleTitleIntraventricular methotrexate therapy of leptomeningeal metastasis from breast carcinoma Neurology 33 1565–1572 Occurrence Handle6685829
HY Yap BS Yap S Rasmussen ME Levens GN Hortobagyi GR. Blumenschein (1982) ArticleTitleTreatment for meningeal carcinomatosis in breast cancer Cancer 50 219–222 Occurrence Handle6177395
WT Sause J Crowley HJ Eyre SE Rivkin RP Pugh JM Quagliana SA Taylor B. Molnar (1988) ArticleTitleWhole brain irradiation and intrathecal methotrexate in the treatment of solid tumor leptomeningeal metastases–a Southwest Oncology Group study J Neurooncol 6 107–112 Occurrence Handle3225633
M Schabet I Kloeter T Adam E Heidemann H. Wietholter (1986) ArticleTitleDiagnosis and treatment of meningeal carcinomatosis in ten patients with breast cancer Eur Neurol 25 403–411 Occurrence Handle3792399
MR Pfeffer M Wygoda T. Siegal (1988) ArticleTitleLeptomeningeal metastases–treatment results in 98 consecutive patients Isr J Med Sci 24 611–618 Occurrence Handle3144516
H Nakagawa A Murasawa S Kubo S Nakajima Y Nakajima S Izumoto T. Hayakawa (1992) ArticleTitleDiagnosis and treatment of patients with meningeal carcinomatosis J Neurooncol 13 81–89 Occurrence Handle10.1007/BF00172949 Occurrence Handle1613540
MC Chamberlain PA. Kormanik (1996) ArticleTitlePrognostic significance of 111indium-DTPA CSF flow studies in leptomeningeal metastases Neurology 46 1674–1677 Occurrence Handle8649568
MC Chamberlain PA. Kormanik (1997) ArticleTitlePrognostic significance of coexistent bulky metastatic central nervous system disease in patients with leptomeningeal metastases Arch Neurol 54 1364–1368 Occurrence Handle9362983
SA Grossman DL Trump DC Chen G Thompson EE. Camargo (1982) ArticleTitleCerebrospinal fluid flow abnormalities in patients with neoplastic meningitis An evaluation using 111 indium-DTPA ventriculography. Am J Med 73 641–647
R Grant B Naylor L Junck HS. Greenberg (1992) ArticleTitleClinical outcome in aggressively treated meningeal gliomatosis Neurology 42 252–254 Occurrence Handle1310353
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Taillibert, S., Laigle-Donadey, F., Chodkiewicz, C. et al. Leptomeningeal metastases from solid malignancy: a review. J Neurooncol 75, 85–99 (2005). https://doi.org/10.1007/s11060-004-8101-x
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DOI: https://doi.org/10.1007/s11060-004-8101-x