Combined-modality therapy for primary central nervous system lymphoma: long-term data from a Phase II multicenter study (Trans-Tasman Radiation Oncology Group)

Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):408-13. doi: 10.1016/j.ijrobp.2005.07.958. Epub 2005 Sep 28.


Purpose: To assess, in a multicenter setting, the long-term outcomes of a brief course of high-dose methotrexate followed by radiotherapy for patients with primary central nervous system lymphoma (PCNSL).

Methods and materials: Forty-six patients were entered in a Phase II protocol consisting of methotrexate (1 g/m(2) on Days 1 and 8), followed by whole-brain irradiation (45-50.4 Gy). The median follow-up time was 7 years, with a minimum follow-up of 5 years.

Results: The 5-year survival estimate was 37% (+/-14%, 95% confidence interval [CI]), with progression-free survival being 36% (+/-15%, 95% CI), and median survival 36 months. Of the original 46 patients, 10 were alive, all without evidence of disease recurrence. A total of 11 patients have developed neurotoxicity, with the actuarial risk being 30% (+/-18%, 95% CI) at 5 years but continuing to increase. For patients aged>60 years the risk of neurotoxicity at 7 years was 58% (+/-30%, 95% CI).

Conclusion: Combined-modality therapy, based on high-dose methotrexate, results in improved survival outcomes in PCNSL. The risk of neurotoxicity for patients aged>60 years is unacceptable with this regimen, although survival outcomes for patients aged>60 years were higher than in many other series.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Ataxia / etiology
  • Ataxia / mortality
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / mortality
  • Central Nervous System Neoplasms / radiotherapy*
  • Combined Modality Therapy
  • Cranial Irradiation / adverse effects
  • Cranial Irradiation / methods
  • Humans
  • Lymphoma / drug therapy*
  • Lymphoma / mortality
  • Lymphoma / radiotherapy*
  • Methotrexate / therapeutic use*
  • Middle Aged


  • Antimetabolites, Antineoplastic
  • Methotrexate