title: The effectiveness and safety of proton beam radiation therapy in children with malignant central nervous system (CNS) tumours: protocol for a systematic review.
abstract: The aim of this study is to use a systematic review framework to identify and synthesise the evidence on the use of proton beam therapy (PBT) for the treatment of children with CNS tumours and where possible compare this to the use of photon radiotherapy (RT).
  
  
  
  Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction. Twelve electronic databases have been searched, and further citation, hand searching and reference checking will be employed. Studies assessing the effects of PBT used either alone or as part of a multimodality treatment regimen in children with CNS tumours will be included. Relevant economic evaluations will also be identified. The outcomes are survival (overall, progression-free, event-free, disease-free), local and regional control rates, short- and long-term adverse events, functional status measures and quality of survival. Two reviewers will independently screen and select studies for inclusion in the review. All interventional study designs will be eligible for inclusion in the review. However, initial scoping searches indicate the evidence base is likely to be limited to case series studies, with no studies of a higher quality being identified. Quality assessment will be undertaken using pre-specified criteria and tailored to study design if applicable. Studies will be combined using a narrative synthesis, with differences in results between studies highlighted and discussed in relation to the patient population, intervention and study quality. Where appropriate, if no studies of a comparative design are identified, outcomes will be compared against a range of estimates from the literature for similar populations and treatment regimens from the best available evidence from studies that include the use of advanced conventional photon therapy.
  
  
  
  The evidence base for the use of PBT in children with CNS tumours is likely to be relatively sparse, highly heterogeneous and potentially of a low quality with small sample sizes. Furthermore, selection and publication biases may limit the internal and external validity of studies. However, any tentative results from the review on potential treatment effects can be used to plan better quality research studies that are of a design appropriate for outcome comparison with conventional therapy.
  
  
  
  PROSPERO CRD42015029583.
authors.affiliation: Cancer Research UK Clinical Trials Unit (CRCTU), Institute of Cancer and Genomic Science, University of Birmingham, Birmingham, UK. c.main@bham.ac.uk.
authors.forename: Caroline
authors.identifier: 0000-0002-9686-3438
authors.initials: C
authors.lastname: Main
authors.affiliation: Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Dandapani
authors.affiliation: Royal Stoke University Hospital, Stroke-on-Trent, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Pritchard
authors.affiliation: Leeds General Infirmary, Leeds, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Dodds
authors.affiliation: Cancer Research UK Clinical Trials Unit (CRCTU), Institute of Cancer and Genomic Science, University of Birmingham, Birmingham, UK.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Stevens
authors.affiliation: The Clatterbridge Cancer Centre, Liverpool, UK.
authors.forename: Nicky
authors.initials: N
authors.lastname: Thorp
authors.affiliation: Swansea University, Swansea, UK.
authors.forename: Roger E
authors.initials: RE
authors.lastname: Taylor
authors.affiliation: Cancer Research UK Clinical Trials Unit (CRCTU), Institute of Cancer and Genomic Science, University of Birmingham, Birmingham, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Wheatley
authors.affiliation: Alder Hey Children's NHS Foundation Trust, Liverpool, UK.
authors.forename: Barry
authors.initials: B
authors.lastname: Pizer
authors.affiliation: Leeds General Infirmary, Leeds, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Morrall
authors.affiliation: Leeds General Infirmary, Leeds, UK.|Centre for Reviews and Dissemination (CRD), University of York, York, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Phillips
authors.affiliation: Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: English
authors.affiliation: Cancer Research UK Clinical Trials Unit (CRCTU), Institute of Cancer and Genomic Science, University of Birmingham, Birmingham, UK.|Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Kearns
authors.affiliation: Queen's Medical Centre, Nottingham University Hospitals' NHS Trust, Nottingham, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Wilne
authors.affiliation: Cancer Research UK Clinical Trials Unit (CRCTU), Institute of Cancer and Genomic Science, University of Birmingham, Birmingham, UK.
authors.forename: Jayne S
authors.initials: JS
authors.lastname: Wilson
mesh_terms: D002490:Central Nervous System / Q000473:pathology*; D016543:Central Nervous System Neoplasms / Q000532:radiotherapy*; D002648:Child; D006801:Humans; D061766:Proton Therapy / Q000009:adverse effects / Q000379:methods*; D011522:Protons; D012107:Research Design; D000078202:Systematic Reviews as Topic
chemical_list: D011522:Protons
keywords: Central nervous system tumours; Children; Conventional photon RT; Proton beam RT; Systematic reviews