title: First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)--a systematic review and individual patient data meta-analysis.
abstract: BACKGROUND
  To investigate prognosis and effects of first-line therapy in elderly primary central nervous system lymphoma (PCNSL) patients.
  
  
  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.
authors.affiliation: 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.
authors.forename: B
authors.initials: B
authors.lastname: Kasenda
authors.affiliation: Unit of Lymphoid Malignancies, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: A J M
authors.initials: AJ
authors.lastname: Ferreri
authors.affiliation: Unit of Lymphoid Malignancies, Department of Onco-Hematology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Marturano
authors.affiliation: Partners Neurology Residency Program, Harvard Medical School, Boston, USA.
authors.forename: D
authors.initials: D
authors.lastname: Forst
authors.affiliation: Department of Neuro-Oncology, Daniel den Hoed Cancer Center, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Bromberg
authors.affiliation: Department of Hematology, Centre Léon Bérard, University of Lyon, Lyon.
authors.forename: H
authors.initials: H
authors.lastname: Ghesquieres
authors.affiliation: Department of Hematology, Centre Léon Bérard, University of Lyon, Lyon.
authors.forename: C
authors.initials: C
authors.lastname: Ferlay
authors.affiliation: Department of Hematology, Centre Léon Bérard, University of Lyon, Lyon.
authors.forename: J Y
authors.initials: JY
authors.lastname: Blay
authors.affiliation: Department of Neurology Mazarin, LOC National Expert Center, APHP, IHU, UPMC, CRICM, GH Pitié-Salpêtrière, Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Hoang-Xuan
authors.affiliation: Department of Haematology, Nordic Lymphoma Group, University Hospital Aarhus, Aarhus, Denmark.
authors.forename: E J
authors.initials: EJ
authors.lastname: Pulczynski
authors.affiliation: Norwegian Department of Oncology, Nordic Lymphoma Group, Radium Hospital, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Fosså
authors.affiliation: Faculty of Medicine, Department of Hematology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Okoshi
authors.affiliation: Faculty of Medicine, Department of Hematology, University of Tsukuba, Tsukuba, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Chiba
authors.affiliation: Department of Hematology/Oncology, University Hospital Freiburg, Freiburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Fritsch
authors.affiliation: Department of Neurology Mazarin, LOC National Expert Center, APHP, IHU, UPMC, CRICM, GH Pitié-Salpêtrière, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Omuro
authors.affiliation: Department of Neurology, Mayo Medical School, Rochester, USA.
authors.forename: B P
authors.initials: BP
authors.lastname: O'Neill
authors.affiliation: Institute of Hematology, Rabin Medical Center, Beilinson Hospital, Tel Aviv Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Bairey
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Schandelmaier
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Gloy
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Bhatnagar
authors.affiliation: Psychiatry and Psychotherapy, University Hospital Freiburg, Freiburg.
authors.forename: S
authors.initials: S
authors.lastname: Haug
authors.affiliation: Medical Faculty, University of Freiburg, Freiburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rahner
authors.affiliation: Partners Neurology Residency Program, Harvard Medical School, Boston, USA Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital, Boston, USA.
authors.forename: T T
authors.initials: TT
authors.lastname: Batchelor
authors.affiliation: Stuttgart Cancer Center, Eva-Mayr-Stihl Tumor Center, Stuttgart, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Illerhaus
authors.affiliation: Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Basel, Switzerland Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Briel
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000401:mortality; D008727:Methotrexate / Q000627:therapeutic use*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate
keywords: PCNSL; elderly patients; individual patient data meta-analysis; primary central nervous system lymphoma; systematic review