title: High-dose methotrexate for the treatment of primary cerebral lymphomas: analysis of survival and late neurologic toxicity in a retrospective series.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre Léon Bérard, Lyon, France. blay@lyon.fnclcc.fr
authors.forename: J Y
authors.initials: JY
authors.lastname: Blay
authors.forename: T
authors.initials: T
authors.lastname: Conroy
authors.forename: C
authors.initials: C
authors.lastname: Chevreau
authors.forename: A
authors.initials: A
authors.lastname: Thyss
authors.forename: N
authors.initials: N
authors.lastname: Quesnel
authors.forename: H
authors.initials: H
authors.lastname: Eghbali
authors.forename: R
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: B
authors.initials: B
authors.lastname: Coiffier
authors.forename: J P
authors.initials: JP
authors.lastname: Wagner
authors.forename: A
authors.initials: A
authors.lastname: Le Mevel
authors.forename: D
authors.initials: D
authors.lastname: Dramais-Marcel
authors.forename: E
authors.initials: E
authors.lastname: Baumelou
authors.forename: F
authors.initials: F
authors.lastname: Chauvin
authors.forename: P
authors.initials: P
authors.lastname: Biron
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D002648:Child; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate