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

Benjamin Kasenda, A. J.M. Ferreri, E. Marturano, D. Forst, J. Bromberg, H. Ghesquieres, C. Ferlay, J. Y. Blay, K. Hoang-Xuan, E. J. Pulczynski, A. Fosså, Y. Okoshi, S. Chiba, K. Fritsch, A. Omuro, B. P. O'Neill, O. Bairey, S. Schandelmaier, V. Gloy, N. BhatnagarS. Haug, S. Rahner, T. T. Batchelor, G. Illerhaus, M. Brie

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87 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1305-1313
Number of pages9
JournalAnnals of Oncology
Issue number7
StatePublished - Jul 1 2015


  • Elderly patients
  • Individual patient data meta-analysis
  • Primary central nervous system lymphoma
  • Systematic review

ASJC Scopus subject areas

  • Hematology
  • Oncology


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