Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma

J Clin Oncol. 2006 Oct 1;24(28):4570-4. doi: 10.1200/JCO.2006.06.6910.


Purpose: We previously reported a series of patients treated with high-dose methotrexate (MTX) -based chemotherapy, with or without whole brain radiotherapy. The purpose of this report is to update the initial results and provide long-term data regarding overall survival, patterns of relapse, and the risk of treatment-related neurotoxicity.

Patients and methods: Fifty-seven patients with an average age of 65 and median Karnofsky performance score of 70 were treated; all patients have been observed longitudinally with serial magnetic resonance imaging scans and neurologic examinations.

Results: The overall median survival was 51 months with a median follow-up of 115 months for surviving patients. Twenty-five patients relapsed or developed progressive disease; median progression-free survival was 129 months. Seventeen patients developed treatment-related neurotoxicity; all but one had received whole brain radiotherapy as a component of treatment. Seventy-four percent of patients younger than 60 years who received both MTX-based chemotherapy and whole brain radiotherapy were alive at last follow-up. Median survival for patients older than 60 years was 29 months regardless of whether or not they received whole brain radiotherapy.

Conclusion: Long-term follow-up of our initial cohort confirms the observation of excellent overall survival, particularly for those patients younger than age 60 at diagnosis. For older patients, it appears to be reasonable to defer whole brain radiotherapy in an effort to minimize treatment-related neurotoxicity.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Brain / drug effects*
  • Brain / radiation effects*
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / mortality
  • Central Nervous System Neoplasms / radiotherapy*
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Humans
  • Lymphoma / drug therapy*
  • Lymphoma / mortality
  • Lymphoma / radiotherapy*
  • Male
  • Methotrexate / pharmacology*
  • Middle Aged
  • Treatment Outcome


  • Methotrexate