title: Challenges and opportunities in primary CNS lymphoma: A systematic review.
abstract: Historically, high-dose methotrexate (HD-MTX) plus consolidation chemotherapy and/or whole brain radiotherapy (WBRT) has been the gold standard on Primary Central Nervous System Lymphoma (PCNSL) management. We sought to examine and summarize the data, on clinical trial (CT) setting, investigating multi-modality treatment to PCNSL.
  
  
  
  We performed a systematic review of electronic databases (Medline, EMBASE, Cochrane Database and clinicaltrials.gov) and a manual search to identify original PCNSL phase 2 and phase 3 CT from the last 10years. After a 4stage Prisma based selection process, 32 published (3 Randomized CT and 29 phases 2 CT) studies ultimately were selected for review. Four ongoing clinical trials found on clinicaltrial.gov were reviewed. Two investigators reviewed titles, abstracts, and articles independently. Two investigators abstracted data sequentially and evaluated each study independently.
  
  
  
  Treatment of PCNSL requires a multidisciplinary approach. HD-MTX represents the most accepted standard of care induction therapy for newly diagnosed PCNSL. When HD-MTX is given with WBRT for consolidation delayed neurotoxicity can be an important complication, particularly in elderly patients. Studies have suggested that WBRT may be deferred until relapse without compromising survival and deferring WBRT may be the best approach in elderly patients. Results from dose-reduced WBRT and consolidative HD-Ara-C are encouraging. High-dose chemotherapy in combination with autologous stem cell transplantation (HDC-ASCT) as chemotherapy alone has emerged as an important consolidative treatment for selected population. The optimal salvage therapy is still to be defined.
  
  
  
  WBRT for consolidation is a well-studied modality; however emerging options to selected population such as HDC-ASCT, dose-reduced WBRT or chemotherapy alone are associated with similar survival outcome and less neurotoxicity in selected series. Ongoing and future clinical trials will better define the best approach on this rare disease.
authors.affiliation: Department of Hematology, Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Mariana N
authors.initials: MN
authors.lastname: Kerbauy
authors.affiliation: Department of Radiation Oncology, Hospital Sírio-Libanês, São Paulo, Brazil; Department of Radiation Oncology, University of Toronto, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. Electronic address: fymoraes@gmail.com.
authors.forename: Fabio Y
authors.initials: FY
authors.lastname: Moraes
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Lok
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Hematology, Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Lucila N
authors.initials: LN
authors.lastname: Kerbauy
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Spratt
authors.affiliation: Department of Hematology, Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Fabio P S
authors.initials: FP
authors.lastname: Santos
authors.affiliation: Department of Hematology, Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Guilherme F
authors.initials: GF
authors.lastname: Perini
authors.affiliation: Department of Radiation Oncology, University of Toronto, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Berlin
authors.affiliation: Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Chung
authors.affiliation: Department of Hematology, Hospital Israelita Albert Einstein, São Paulo, Brazil.
authors.forename: Nelson
authors.initials: N
authors.lastname: Hamerschlak
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Joachim
authors.initials: J
authors.lastname: Yahalom
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging; D016543:Central Nervous System Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D003131:Combined Modality Therapy; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging* / Q000628:therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D011878:Radiotherapy / Q000379:methods; D016879:Salvage Therapy / Q000379:methods; D033581:Stem Cell Transplantation / Q000379:methods
keywords: Drug therapy; Hematology; Lymphoma Central Nervous System Neoplasms; Non-Hodgkin lymphoma; Radiotherapy; Stem cell transplantation