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

B Kasenda¹, A J M Ferreri², E Marturano², D Forst³, J Bromberg⁴, H Ghesquieres⁵, C Ferlay⁵, J Y Blay⁵, K Hoang-Xuan⁶, E J Pulczynski⁷, A Fosså⁸, Y Okoshi⁹, S Chiba⁹, K Fritsch¹⁰, A Omuro⁶, B P O'Neill¹¹, O Bairey¹², S Schandelmaier¹³, V Gloy¹³, N Bhatnagar¹⁴, S Haug¹⁵, S Rahner¹⁶, T T Batchelor¹⁷, G Illerhaus¹⁸, M Briel¹⁹

Affiliations

¹ Department of Oncology, University Hospital of Basel, Basel Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland benjamin.kasenda@gmail.com benjamin.kasenda@rmh.nhs.uk.
² Unit of Lymphoid Malignancies, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy.
³ Partners Neurology Residency Program, Harvard Medical School, Boston, USA.
⁴ Department of Neuro-Oncology, Daniel den Hoed Cancer Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
⁵ Department of Hematology, Centre Léon Bérard, University of Lyon, Lyon.
⁶ Department of Neurology Mazarin, LOC National Expert Center, APHP, IHU, UPMC, CRICM, GH Pitié-Salpêtrière, Paris, France.
⁷ Department of Haematology, Nordic Lymphoma Group, University Hospital Aarhus, Aarhus, Denmark.
⁸ Norwegian Department of Oncology, Nordic Lymphoma Group, Radium Hospital, Oslo, Norway.
⁹ Faculty of Medicine, Department of Hematology, University of Tsukuba, Tsukuba, Japan.
¹⁰ Department of Hematology/Oncology, University Hospital Freiburg, Freiburg, Germany.
¹¹ Department of Neurology, Mayo Medical School, Rochester, USA.
¹² Institute of Hematology, Rabin Medical Center, Beilinson Hospital, Tel Aviv Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹³ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
¹⁴ Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
¹⁵ Psychiatry and Psychotherapy, University Hospital Freiburg, Freiburg.
¹⁶ Medical Faculty, University of Freiburg, Freiburg, Germany.
¹⁷ Partners Neurology Residency Program, Harvard Medical School, Boston, USA Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital, Boston, USA.
¹⁸ Stuttgart Cancer Center, Eva-Mayr-Stihl Tumor Center, Stuttgart, Germany.
¹⁹ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.

PMID: 25701456
PMCID: PMC4735103
DOI: 10.1093/annonc/mdv076

Meta-Analysis

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

B Kasenda et al. Ann Oncol. 2015 Jul.

. 2015 Jul;26(7):1305-13.

doi: 10.1093/annonc/mdv076. Epub 2015 Feb 20.

Authors

Affiliations

¹ Department of Oncology, University Hospital of Basel, Basel Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland benjamin.kasenda@gmail.com benjamin.kasenda@rmh.nhs.uk.
² Unit of Lymphoid Malignancies, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy.
³ Partners Neurology Residency Program, Harvard Medical School, Boston, USA.
⁴ Department of Neuro-Oncology, Daniel den Hoed Cancer Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
⁵ Department of Hematology, Centre Léon Bérard, University of Lyon, Lyon.
⁶ Department of Neurology Mazarin, LOC National Expert Center, APHP, IHU, UPMC, CRICM, GH Pitié-Salpêtrière, Paris, France.
⁷ Department of Haematology, Nordic Lymphoma Group, University Hospital Aarhus, Aarhus, Denmark.
⁸ Norwegian Department of Oncology, Nordic Lymphoma Group, Radium Hospital, Oslo, Norway.
⁹ Faculty of Medicine, Department of Hematology, University of Tsukuba, Tsukuba, Japan.
¹⁰ Department of Hematology/Oncology, University Hospital Freiburg, Freiburg, Germany.
¹¹ Department of Neurology, Mayo Medical School, Rochester, USA.
¹² Institute of Hematology, Rabin Medical Center, Beilinson Hospital, Tel Aviv Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
¹³ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
¹⁴ Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
¹⁵ Psychiatry and Psychotherapy, University Hospital Freiburg, Freiburg.
¹⁶ Medical Faculty, University of Freiburg, Freiburg, Germany.
¹⁷ Partners Neurology Residency Program, Harvard Medical School, Boston, USA Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital, Boston, USA.
¹⁸ Stuttgart Cancer Center, Eva-Mayr-Stihl Tumor Center, Stuttgart, Germany.
¹⁹ Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.

PMID: 25701456
PMCID: PMC4735103
DOI: 10.1093/annonc/mdv076

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.

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

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Figures

**Figure 1.**
(A) Overall and progression-free survival of the whole cohort; (B) overall survival grouped by time of diagnosis (in 19 cases, exact date was missing); (C) overall survival grouped by age groups.

**Figure 2.**
(A) Overall survival in patients receiving any HD-MTX-based therapy versus therapies not containing HD-MTX; (B) overall survival in patients receiving any HD-MTX + other chemotherapy versus HD-MTX monotherapy; (C) overall survival in patients receiving HD-MTX plus at least two other i.v. drugs (aggressive) versus HD-MTX plus oral chemotherapy; (D) overall survival in patients receiving HD-MTX-based chemotherapy with or without whole-brain radiotherapy. CTX, chemotherapy; HD-MTX, high-dose methotrexate; HR, hazard ratio.

See this image and copyright information in PMC

References

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

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

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