First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)--a systematic review and individual patient data meta-analysis

Ann Oncol. 2015 Jul;26(7):1305-13. doi: 10.1093/annonc/mdv076. Epub 2015 Feb 20.


Background: To investigate prognosis and effects of first-line therapy in elderly primary central nervous system lymphoma (PCNSL) patients.

Patients and methods: A systematic review of studies about first-line therapy in immunocompetent patients ≥60 years with PCNSL until 2014 and a meta-analysis of individual patient data from eligible studies and international collaborators were carried out.

Results: We identified 20 eligible studies; from 13 studies, we obtained individual data of 405 patients, which were pooled with data of 378 additional patients (N = 783). Median age and Karnofsky Performance Score (KPS) was 68 years (range: 60-90 years) and 60% (range: 10%-100%), respectively. Treatments varied greatly, 573 (73%) patients received high-dose methotrexate (HD-MTX)-based therapy. A total of 276 patients received whole-brain radiotherapy (median 36 Gy, range 28.5-70 Gy). KPS ≥ 70% was the strongest prognostic factor for mortality [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.41-0.62]. After a median follow-up of 40 months, HD-MTX-based therapy was associated with improved survival (HR 0.70, 95% CI 0.53-0.93). There was no difference between HD-MTX plus oral chemotherapy and more aggressive HD-MTX-based therapies (HR 1.39, 95% CI 0.90-2.15). Radiotherapy was associated with an improved survival, but correlated with an increased risk for neurological side-effects (odds ratio 5.23, 95% CI 2.33-11.74).

Conclusions: Elderly PCNSL patients benefit from HD-MTX-based therapy, especially if combined with oral alkylating agents. More aggressive HD-MTX protocols do not seem to improve outcome. WBRT may improve outcome, but is associated with increased risk for neurological side-effects. Prospective trials for elderly PCNSL patients are warranted.

Keywords: PCNSL; elderly patients; individual patient data meta-analysis; primary central nervous system lymphoma; systematic review.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Aged
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / mortality
  • Humans
  • Lymphoma / drug therapy*
  • Lymphoma / mortality
  • Methotrexate / therapeutic use*
  • Prognosis
  • Survival Rate


  • Antimetabolites, Antineoplastic
  • Methotrexate