title: Phase II multicenter study of brief single-agent methotrexate followed by irradiation in primary CNS lymphoma.
abstract: OBJECTIVE
  To assess, in a multi-institutional setting, the impact on relapse, survival, and toxicity of adding two cycles of intravenous methotrexate to cranial irradiation for immunocompetent patients with primary CNS lymphoma.
  
  
  METHODS
  Forty-six patients with a median age of 58 years and Eastern Cooperative Oncology Group performance status 0 to 3 were entered onto this phase II study. The protocol consisted of methotrexate 1 g/m(2) on days 1 and 8 followed by cranial irradiation on day 15. A whole-brain dose of 45 Gy was followed by a boost of 5.4 Gy. Intrathecal chemotherapy and spinal irradiation were given only to patients for whom cytologic examination of CSF was positive for CNS lymphoma. The median follow-up time was 36 months, with a minimum potential follow-up of 12 months.
  
  
  RESULTS
  Median survival was 33 months, with 2-year probability of survival 62% +/- 15% (95% confidence interval). Twenty patients have relapsed. The predominant site of relapse was the brain. Neither performance status nor age was found to influence survival. Six patients developed a dementing illness at a median of 16 months after treatment, and three of these died as a consequence.
  
  
  CONCLUSIONS
  A brief course of intravenous methotrexate before cranial irradiation is associated with 2-year and median survival rates superior to those reported for radiotherapy alone and similar to more intensive combined-modality regimens. Neurotoxicity remains an important competing risk for these patients.
authors.affiliation: Trans-Tasman Radiation Oncology Group: Department of Radiation Oncology, Newcastle Mater Hospital, Newcastle, New South Wales, Australia. mdpco@cc.newcastle.edu.au
authors.forename: P
authors.initials: P
authors.lastname: O'Brien
authors.forename: D
authors.initials: D
authors.lastname: Roos
authors.forename: G
authors.initials: G
authors.lastname: Pratt
authors.forename: K
authors.initials: K
authors.lastname: Liew
authors.forename: M
authors.initials: M
authors.lastname: Barton
authors.forename: M
authors.initials: M
authors.lastname: Poulsen
authors.forename: I
authors.initials: I
authors.lastname: Olver
authors.forename: G
authors.initials: G
authors.lastname: Trotter
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008223:Lymphoma / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010349:Patient Compliance; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate