Journal of Neuro-Oncology

, Volume 38, Issue 2–3, pp 245–252 | Cite as

Current diagnosis and treatment of leptomeningeal metastasis

  • Lisa M. DeAngelis

Abstract

Meningeal metastasis occurs in 3–8% of all cancer patients, producing neurologic morbidity and a high mortality. Diagnosis is best established by the demonstration of malignant cells in the cerebrospinal fluid. However, in patients with known cancer, MR scan with gadolinium may be diagnostic when subarachnoid nodules can be demonstrated in the head or spine. Therapy usually involves radiotherapy to symptomatic sites, often followed by intrathecal chemotherapy. Intrathecal chemotherapy is best delivered by an intraventricular reservoir system but can also be delivered by repeated lumbar puncture. Methotrexate, cytarabine and thiotepa are the most common agents instilled into the subarachnoid space. Their limited efficacy can be explained by their restricted spectrum of antitumor activity. Patients with leptomeningeal metastasis from leukemia, lymphoma or breast cancer tend to respond best and this may, in part, be attributed to the relative sensitivity of these primary tumor types to the agents administered intrathecally. Systemic chemotherapy may prove a more attractive alternative to intrathecal drugs since it can penetrate into bulky disease, reach all areas of the subarachnoid space, and not be restricted by CSF bulk flow. The prognosis for patients with leptomeningeal metastasis is poor, most individuals surviving a median of only about four months. Occasional patients do have prolonged survival and improvement of their neurologic function.

leptomeningeal metastasis radiotherapy chemotherapy cancer 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Posner JP: Neurologic Complications of Cancer. F.A. Davis Company, Philadelphia, Pa, 1995, p. 143Google Scholar
  2. 2.
    Wasserstrom WR, Glass JP, Posner JB: Diagnosis and treatment of leptomeningeal metastases from solid tumors: Experience with 90 patients. Cancer 49: 759–772, 1982Google Scholar
  3. 3.
    Balm M, Hammack J: Leptomeningeal carcinomatosis. Presenting features and prognostic factors. Arch Neurol 53: 626–632, 1996Google Scholar
  4. 4.
    Glass JP, Melamed M, Chernik NL, Posner JB: Malignant cells in cerebrospinal fluid (CFS): The meaning of a positive CSF cytology. Neurology 29: 1369–1375, 1979Google Scholar
  5. 5.
    Rogers LR, Duchesneau PM, Nunez C, Fishleder AJ, Weick JK, Bauer LJ, Boyett JM: Comparison of cisternal and lumbar CSF examination in leptomeningeal metastasis. Neurology 42: 1239–1241, 1992Google Scholar
  6. 6.
    Schold SC, Wasserstrom WR, Fleisher M, Schwartz MK, Posner JB: Cerebrospinal fluid biochemical markers of central nervous system metastases. Ann Neurol 8: 597–604, 1980Google Scholar
  7. 7.
    Fleisher M, Wasserstrom WR, Schold SC, Schwartz MK, Posner JP: Lactic dehydrogenase isoenzymes in the cerebrospinal fluid of patients with systemic cancer. Cancer 47: 2654–2659, 1981Google Scholar
  8. 8.
    Oschmann P, Kaps M, Volker J, Dorndorf W: Meningeal carcinomatosis: CSF cytology, immunocytochemistry and biochemical tumor markers. Acta Neurol Scand 89: 395–399, 1994Google Scholar
  9. 9.
    Cibas ES, Malkin MG, Posner JB, Melamed MR: Detection of DNA abnormalities by flow cytometry in cells from cerebrospinal fluid. Am J Clin Pathol 88: 570–577, 1987Google Scholar
  10. 10.
    Rhodes CH, Glantz MJ, Glantz L, Lekos A, Sorenson GD, Honsinger C, Levy NB: A comparison of polymerase chain reaction examination of cerebrospinal fluid and conventional cytology in the diagnosis of lymphomatous meningitis. Cancer 77: 543–548, 1996Google Scholar
  11. 11.
    Rodesch G, Van Bogaert P, Mavroudakis N, Parizel PM, Martin J-J, Segebarth C, Van Vyve M, Baleriaux D, Hildebrand J: Neuroradiologic findings in leptomeningeal carcinomatosis: the value interest of gadolinium-enhanced MRI. Neuroradiology 32: 26–32, 1990Google Scholar
  12. 12.
    Freilich RJ, Krol G, DeAngelis LM: Neuroimaging and cerebrospinal fluid cytology in the diagnosis of leptomeningeal metastasis. Ann Neurol 38: 51–57, 1995Google Scholar
  13. 13.
    Gorson KC, Ropper AH, Muriello MA, Blair R: Prospective evaluation of MRI lumbosacral nerve root enhancement in acute Guillain-Barre syndrome. Neurology 47: 813–817, 1996Google Scholar
  14. 14.
    Pannullo SC, Reich JB, Krol G, Deck MDF, Posner JB: MRI changes in intracranial hypotension. Neurology 43: 919–926, 1993Google Scholar
  15. 15.
    Mittl RL, Yousem DM: Frequency of unexplained meningeal enhancement in the brain after lumbar puncture. AJNR Am J Neuroradiol 15: 633–638, 1994Google Scholar
  16. 16.
    Chamberlain MC: New approaches to current treatment of leptomeningeal metastases. Curr Opin Neurol 7: 492–500, 1994Google Scholar
  17. 17.
    Gray JR, Wallner KE: Reversal of cranial nerve dysfunction with radiation therapy in adults with lymphoma and leukemia. Int J Radiat Oncol Biol Phys 19: 439, 1990Google Scholar
  18. 18.
    Larson SM, Schall GL, DiChiro G: The influence of previous lumbar puncture and pneumoencephalography on the incidence of unsuccessful radioisotope cisternography. J Nucl Med 12: 555–557, 1971Google Scholar
  19. 19.
    Shapiro WR, Young DF, Mehta BM: Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med 293: 161–166, 1975Google Scholar
  20. 20.
    Grossman SA, Trump DL, Chen DCP, Thompson G, Camargo EE: Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using 111Indium-DTPA ventriculography. Am J Med 73: 641–647, 1982Google Scholar
  21. 21.
    Chamberlain MC, Corey-Bloom J: Leptomeningeal metastases: 111Indium-DTPA CSF flow studies. Neurology 41: 1765–1769, 1991Google Scholar
  22. 22.
    Glantz MJ, Hall WA, Cole BF, Chozick BS, Shannon CM, Wahlberg L, Akerley W, Marin L, Choy H: Diagnosis, management, and survival of patients with leptomeningeal cancer based on cerebrospinal fluid-flow studies. Cancer 75: 2919–2931, 1995Google Scholar
  23. 23.
    Mason WP, DeAngelis LM, Yeh SDJ: 111Indium-DTPA cerebrospinal fluid (CSF) studies in leptomeningeal metastases (LM) predict intrathecal methotrexate (MTX) distribution and response to therapy. (Abstract) ASCO 15: 155, 1996Google Scholar
  24. 24.
    Van der Gaast A, Sonneveld P, Mans DRA, Splinter TAW: Intrathecal administration of etoposide in the treatment of malignant meningitis: feasibility and pharmacokinetic data. Cancer Chemother Pharmacol 29: 335–337, 1992Google Scholar
  25. 25.
    Champagne MA, Silver HKB: Intrathecal dacarbazine treatment of leptomeningeal malignant melanoma. J Natl Cancer Inst 84: 1203–1204, 1992Google Scholar
  26. 26.
    Berg SL, Balis FM, Zimm S, Murphy RF, Holcenberg J, Sato J, Reaman G, Steinherz P, Gillespie A, Doherty K, Poplack DG: Phase I/II trial and pharmacokinetics of intrathecal diaziquone in refractory meningeal malignancies. J Clin Oncol 10: 143–148, 1992Google Scholar
  27. 27.
    Chamberlain MC, Khatibi S, Kim JC, Howell SB, Chatelut E, Kim S: Treatment of leptomeningeal metastasis with intraventricular administration of depot cytarabine (DTC 101). A phase I study. Arch Neurol 50: 261–264, 1993Google Scholar
  28. 28.
    Jolivet J, Cowan KH, Curt GA, Clendeninn NJ, Chabner BA: The pharmacology and clinical use of methotrexate. N Engl J Med 309: 1094–1104, 1983Google Scholar
  29. 29.
    Gilchrist NL, Caldwell J, Watson ID, Cunningham D, Forrest GJ, Soukop M, Stewart M, Fitch W: Comparison of serum and cerebrospinal fluid levels of methotrexate in man during high-dose chemotherapy for aggressive non-Hodgkin’s lymphoma. Cancer Chemother Pharmacol 15: 290–294, 1985Google Scholar
  30. 30.
    Blaney SM, Balis FM, Poplack DG: Pharmacologic approaches to the treatment of meningeal malignancy. Oncology 5: 107–123, 1991Google Scholar
  31. 31.
    Grant R, Naylor B, Greenberg HS, Junck L: Clinical outcome in aggressively treated meningeal carcinomatosis. Arch Neurol 51: 457–461, 1994Google Scholar
  32. 32.
    Siegal T, Lossos A, Pfeffer MR: Leptomeningeal metastases: Analysis of 31 patients with sustained off-therapy response following combined-modality therapy. Neurology 44: 1463–1469, 1994Google Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Lisa M. DeAngelis
    • 1
  1. 1.Department of NeurologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA

Personalised recommendations