Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10

J Clin Oncol. 2002 Dec 15;20(24):4643-8. doi: 10.1200/JCO.2002.11.013.


Purpose: Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long-term disease control or prolonged survival. We prospectively studied the use of combination chemotherapy plus cranial irradiation in newly diagnosed patients with PCNSL.

Patients and methods: We enrolled 102 newly diagnosed, immunocompetent patients with PCNSL; 98 were assessable. Patients first received five cycles of methotrexate 2.5 g/m(2), vincristine, procarbazine, and intraventricular methotrexate (12 mg). Whole-brain radiotherapy (RT) was administered to a total dose of 45 Gy and all patients received high-dose cytarabine after RT.

Results: Fifty-eight percent of patients with measurable disease had a complete response to preirradiation chemotherapy and 36% had a partial (> 50%) response, for a 94% response rate. Median progression-free survival was 24.0 months and overall survival was 36.9 months. Age was an important prognostic factor; median survival was 50.4 months in patients younger than 60 and only 21.8 months in those aged 60 or older (P <.001). Fifty-three percent of patients had grade 3 or 4 toxicity during induction chemotherapy, half of which was hematologic. However, 12 patients (15%) experienced severe delayed neurologic toxicity, eight of whom died.

Conclusion: This is the first multicenter trial demonstrating improved survival with the combination of chemotherapy plus RT compared with previous reports of RT alone. A high-dose methotrexate-based regimen produced a high response rate before RT was administered. High-dose methotrexate combined with cranial irradiation is an effective therapeutic approach to PCNSL, but neurotoxicity is a delayed risk of this approach.

Publication types

  • Multicenter Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antimetabolites, Antineoplastic / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols
  • Brain Neoplasms / mortality
  • Brain Neoplasms / radiotherapy
  • Brain Neoplasms / therapy*
  • Combined Modality Therapy
  • Cytarabine / administration & dosage
  • Humans
  • Lymphoma / mortality
  • Lymphoma / radiotherapy
  • Lymphoma / therapy*
  • Methotrexate / administration & dosage
  • Procarbazine / administration & dosage
  • Survival Rate
  • Vincristine / administration & dosage


  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Cytarabine
  • Procarbazine
  • Vincristine
  • Methotrexate