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 neurolog ic toxicity was investigated in a series of patients with primary cere bral lymphoma (PCL) and no known cause of immunosuppression. Patients and Methods: prognostic factors for survival and treatment-induced lat e neurotoxicity were investigated in a retrospective series of 226 pat ients with PCL. Results: With a median follow-up of 76 months, the med ian overall survival was 16 months and 5-year survival was 19%. In a u nivariate 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, increa sed serum lactate dehydrogenase (LDH), but not histological subtype, w ere significantly correlated with a poor survival. Treatment with chem otherapy versus radiotherapy alone (P = .05), high-dose methotrexate ( HDMTX; P = .0007), and cytarabine (P = .04) correlated with a better s urvival in univariate analysis. Using the Cox model, age, performance status, and CSF protein were independently correlated with survival. A fter adjustment of these factors, treatment with an HDMTX containing r egimen remained the only treatment-related factor independently correl ated with survival (P = .01). The projected incidence of treatment-ind uced late neurotoxicity was 26% at 6 years in this series, with a medi an survival from the diagnosis of late neurotoxicity of 12 months. Tre atment with radiotherapy followed by chemotherapy was the only paramet er correlated with late neurotoxicity in multivariate analysis (relati ve 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 wit h other treatment modalities in this series. (C) 1998 by American Soci ety of Clinical Oncology.