Prognostic Factors and Outcomes in Patients with Leptomeningeal Melanomatosis

¹ Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
² Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas

^* To whom correspondence should be addressed. E-mail: mgroves{at}mdanderson.org.

	Abstract

Purpose: To describe a cohort of patients with leptomeningeal melanomatosis (LM) and to determine prognostic factors for outcomes in these patients. The primary hypothesis was that more extensive burden of CNS metastasis at the time of diagnosis of LM (as evidenced by imaging of the CNS parenchyma and meninges, and CSF cytology status (positive versus negative) correlates poorer outcomes. Patients and Methods: The records of all patients with LM treated at M.D. Anderson Cancer Center between 1944 and 2002 were reviewed. Information on clinical course and outcomes was gathered. Univariate and multivariate analyses were performed on 110 patients using Cox proportional hazards regression analysis to examine the effects of possible predictive factors on survival. Results: The overall median survival from LM diagnosis was 10 weeks with 95% confidence interval from 8 weeks to 14 weeks. Eighty-six (78.2%) patients had cutaneous primary lesions, and 23 (20.9%) had melanoma of unknown primary site. The primary hypothesis was not proven. Neither the presence of parenchymal CNS metastases nor greater imaging evidence of LM nor positive CSF cytology at diagnosis correlated with survival outcomes. Univariate analyses revealed possible predictors of longer survival, including: the presence of supratentorial or spinal LM on imaging at diagnosis versus not, or any treatment of LM; while an elevated serum LDH at the time of LM diagnosis predicted shorter survival. Multivariate analysis revealed that a history of a primary melanoma lesion originating on the trunk predicted shorter survival after LM diagnosis (HR=2.0(1.0, 3.8), p = 0.035) and treatment with intrathecal chemotherapy predicted longer survival (HR=0.5(0.4, 0.8), p = 0.0036). The positive result with respect to treatment is unreliable due to the inability to remove treatment selection bias from the analysis. Conclusions: This retrospective analysis confirmed the dismal prognosis associated with LM. The amount of CNS tumor burden at the time of diagnosis of LM did not inversely correlate with survival outcomes, as hypothesized.

Key Words: leptomeningeal metastases, leptomeningeal melanomatosis, melanoma, neoplastic meningitis, prognostic factors, retrospective review

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