High-dose methotrexate for the treatment of primary cerebral lymphomas: Analysis of survival and late neurologic toxicity in a retrospective series

Purpose: The impact of treatment options on survival and late neurologic toxicity was investigated in a series of patients with primary cerebral lymphoma (PCL) and no known cause of immunosuppression. Patients and Methods: prognostic factors for survival and treatment-induced late neurotoxicity were investigated in a retrospective series of 226 patients with PCL. Results: With a median follow-up of 76 months, the median overall survival was 16 months and 5-year survival was 19%. In a univariate analysis, age greater than 60 years, performance status, CSF protein level greater than 0.6 g/L, involvement of corpus callosum or subcortical grey structures, detectable lymphoma cells in CSF, increased serum lactate dehydrogenase (LDH), but not histological subtype, were significantly correlated with a poor survival. Treatment with chemotherapy versus radiotherapy alone (P = .05), high-dose methotrexate (HDMTX; P = .0007), and cytarabine (P = .04) correlated with a better survival in univariate analysis. Using the Cox model, age, performance status, and CSF protein were independently correlated with survival. After adjustment of these factors, treatment with an HDMTX containing regimen remained the only treatment-related factor independently correlated with survival (P = .01). The projected incidence of treatment-induced late neurotoxicity was 26% at 6 years in this series, with a median survival from the diagnosis of late neurotoxicity of 12 months. Treatment with radiotherapy followed by chemotherapy was the only parameter correlated with late neurotoxicity in multivariate analysis (relative risk, 11.5; P = .0007). Conclusion: Patients with PCL treated with regimens that included HDMTX followed by radiotherapy have an improved survival, but not a higher risk of late neurotoxicity as compared with other treatment modalities in this series. (C) 1998 by American Society of Clinical Oncology.