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

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