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. 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.
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.
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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