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, Brian Patrick O'Neill, O. Bairey, S. Schandelmaier, V. Gloy, N. BhatnagarS. Haug, S. Rahner, T. T. Batchelor, G. Illerhaus, M. Brie

Research output: Contribution to journalArticle

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Abstract

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
Volume26
Issue number7
DOIs
StatePublished - Jul 1 2015

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Meta-Analysis
Lymphoma
Central Nervous System
Methotrexate
Confidence Intervals
Therapeutics
Radiotherapy
Survival
Alkylating Agents
Odds Ratio
Drug Therapy
Mortality
Brain

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)-a systematic review and individual patient data meta-analysis. / Kasenda, Benjamin; Ferreri, A. J M; Marturano, E.; Forst, D.; Bromberg, J.; Ghesquieres, H.; Ferlay, C.; Blay, J. Y.; Hoang-Xuan, K.; Pulczynski, E. J.; Fosså, A.; Okoshi, Y.; Chiba, S.; Fritsch, K.; Omuro, A.; O'Neill, Brian Patrick; Bairey, O.; Schandelmaier, S.; Gloy, V.; Bhatnagar, N.; Haug, S.; Rahner, S.; Batchelor, T. T.; Illerhaus, G.; Brie, M.

In: Annals of Oncology, Vol. 26, No. 7, 01.07.2015, p. 1305-1313.

Research output: Contribution to journalArticle

Kasenda, B, Ferreri, AJM, Marturano, E, Forst, D, Bromberg, J, Ghesquieres, H, Ferlay, C, Blay, JY, Hoang-Xuan, K, Pulczynski, EJ, Fosså, A, Okoshi, Y, Chiba, S, Fritsch, K, Omuro, A, O'Neill, BP, Bairey, O, Schandelmaier, S, Gloy, V, Bhatnagar, N, Haug, S, Rahner, S, Batchelor, TT, Illerhaus, G & Brie, M 2015, 'First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)-a systematic review and individual patient data meta-analysis', Annals of Oncology, vol. 26, no. 7, pp. 1305-1313. https://doi.org/10.1093/annonc/mdv076
Kasenda, Benjamin ; Ferreri, A. J M ; Marturano, E. ; Forst, D. ; Bromberg, J. ; Ghesquieres, H. ; Ferlay, C. ; Blay, J. Y. ; Hoang-Xuan, K. ; Pulczynski, E. J. ; Fosså, A. ; Okoshi, Y. ; Chiba, S. ; Fritsch, K. ; Omuro, A. ; O'Neill, Brian Patrick ; Bairey, O. ; Schandelmaier, S. ; Gloy, V. ; Bhatnagar, N. ; Haug, S. ; Rahner, S. ; Batchelor, T. T. ; Illerhaus, G. ; Brie, M. / First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)-a systematic review and individual patient data meta-analysis. In: Annals of Oncology. 2015 ; Vol. 26, No. 7. pp. 1305-1313.
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abstract = "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.",
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T1 - First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)-a systematic review and individual patient data meta-analysis

AU - Kasenda, Benjamin

AU - Ferreri, A. J M

AU - Marturano, E.

AU - Forst, D.

AU - Bromberg, J.

AU - Ghesquieres, H.

AU - Ferlay, C.

AU - Blay, J. Y.

AU - Hoang-Xuan, K.

AU - Pulczynski, E. J.

AU - Fosså, A.

AU - Okoshi, Y.

AU - Chiba, S.

AU - Fritsch, K.

AU - Omuro, A.

AU - O'Neill, Brian Patrick

AU - Bairey, O.

AU - Schandelmaier, S.

AU - Gloy, V.

AU - Bhatnagar, N.

AU - Haug, S.

AU - Rahner, S.

AU - Batchelor, T. T.

AU - Illerhaus, G.

AU - Brie, M.

PY - 2015/7/1

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N2 - 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.

AB - 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.

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KW - Systematic review

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