Send to

Choose Destination
Neuro Oncol. 2014 Sep;16(9):1176-85. doi: 10.1093/neuonc/nou089. Epub 2014 May 27.

Leptomeningeal metastasis: a Response Assessment in Neuro-Oncology critical review of endpoints and response criteria of published randomized clinical trials.

Author information

Department of Neurology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington (M.C.); Department of Neuroscience, Division of Neuro-Oncology, University Hospital, Torino, Italy (R.S., R.R.); Department of Neurology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois (J.R.); Department of Neuro-Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands (D.B., W.B.); Departments of Neuro-Oncology Mazarin and Radiation Oncology, Pitie-Salpetriere Hospital and University Pierre et Marie Curie, Paris VI, Paris, France (S.T.); Austin Brain Tumor Center, Texas Oncology/US Oncology Research, Austin, Texas (M.D.G.); Department of Neuro-Oncology, University Hospital, Lille, France (E.L.R.); Department of Neurology, Oscar Lambret Center, Lille, France (E.L.R.); Department of Neurology, University of Michigan, Ann Arbor, Michigan (L.J.); Department of Neuro-oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, Netherlands (M.v.d.B.); Department of Neurology, Dana-Farber Cancer Institute, Massachusetts General Hospital, Boston, Massachusetts (P.Y.W.); Department of Neurology and Oncology, Mayo Clinic Florida, Jacksonville, Florida (K.A.J.).



To date, response criteria and optimal methods for assessment of outcome have not been standardized in patients with leptomeningeal metastasis (LM).


A Response Assessment in Neuro-Oncology working group of experts in LM critically reviewed published literature regarding randomized clinical trials (RCTs) and trial design in patients with LM.


A literature review determined that 6 RCTs regarding the treatment of LM have been published, all of which assessed the response to intra-CSF based chemotherapy. Amongst these RCTs, only a single trial attempted to determine whether intra-CSF chemotherapy was of benefit compared with systemic therapy. Otherwise, this pragmatic question has not been formally addressed in patients with solid cancers and LM. The methodology of the 6 RCTs varied widely with respect to pretreatment evaluation, type of treatment, and response to treatment. Additionally there was little uniformity in reporting of treatment-related toxicity. One RCT suggests no advantage of combined versus single-agent intra-CSF chemotherapy in patients with LM. No specific intra-CSF regimen has shown superior efficacy in the treatment of LM, with the exception of liposomal cytarabine in patients with lymphomatous meningitis. Problematic with all RCTs is the lack of standardization with respect to response criteria. There was considerable variation in definitions of response by clinical examination, neuroimaging, and CSF analysis.


Based upon a review of published RCTs in LM, there exists a significant unmet need for guidelines for evaluating patients with LM in clinical practice as well as for response assessment in clinical trials.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center