title: Bisphosphonate and risk of cancer recurrence: protocol for a systematic review, meta-analysis and trial sequential analysis of randomised controlled trials.
abstract: BACKGROUND
  No consensus exists on the associations between adjuvant treatment with bisphosphonates and cancer recurrence risk among patients with primary early-stage cancers. We plan to perform a comprehensive systematic review, study-level meta-analysis and trial sequential analysis of randomised controlled trials to comprehensively summarise evidence of the bisphosphonate treatment for difference cancers.
  
  
  METHODS
  We will report our results according to the PRISMA guideline. The primary outcomes include any cancer recurrence and bone metastasis and secondary outcomes include events of local recurrence, regional recurrence or non-skeletal distant metastasis, disease-free survival and overall survival. We will perform systematic electronic searches and other manual searches. To be conservative, all statistical analyses will be conducted with random-effects models. Cumulative meta-analyses and trial sequential analyses will be performed to assess whether and when firm evidence is reached. Various sensitivity analyses and rigid publication bias analyses will be performed to challenge the consistency and robustness of results. We will also grade the quality of evidence with the GRADE system.
  
  
  BACKGROUND
  Ethical approval is not required in this study. The findings will be submitted for publication in a peer-reviewed journal and also presented at relevant national and international conferences.
  
  
  BACKGROUND
  PROSPERO CRD42014014699.
authors.affiliation: Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, China.
authors.forename: Yupeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Urology Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Preventive Medicine, School of Public Health, Harbin Medical University, Harbin, China.
authors.forename: Yuxue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Radiology, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, China.
authors.forename: Fulan
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Colorectal Cancer Surgery, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Breast Cancer Surgery, The Third Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Da
authors.initials: D
authors.lastname: Pang
authors.affiliation: Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, China.
authors.forename: Yashuang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000517:prevention & control / Q000556:secondary; D004164:Diphosphonates / Q000627:therapeutic use*; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D000078202:Systematic Reviews as Topic; D015201:Meta-Analysis as Topic
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates
keywords: bisphosphontes; cancer recurrence; meta-analysis; randomised controlle trial; systematic review; trial sequential analysis