title: Metformin and improved treatment outcomes in radiation therapy - A review.
abstract: BACKGROUND
  Metformin, a primary treatment for diabetes mellitus (DM) patients, is associated with improved outcomes for diabetic cancer patients fuelling further investigation on its mechanisms of action. The radiosensitising properties of metformin are increasingly reported in pre-clinical studies. This review discusses whether metformin should be offered to radiotherapy (RT) cancer patients as a means to improve their treatment outcomes.
  
  
  METHODS
  A database search was conducted for articles published with metformin as the main intervention between 2010 and 2016. Three groups of RT cancer patients were analysed: diabetic patients using metformin, diabetic patients not using metformin and non-diabetic patients not using metformin. Data on survival and recurrence metrics were extracted.
  
  
  RESULTS
  Thirteen studies were included. Conflicting evidence exists with regards to the impact of metformin administration on recurrence and survival outcomes following radiotherapy. Three studies reported improved tumour response determined by recurrence rates while five studies did not observe differences or metformin use was not the associated reason. One study revealed inconsistent tumour response results. Metformin was reported as improving survival outcomes in 2 studies and not improving outcomes in 5 studies. 4 studies showed indefinite results.
  
  
  CONCLUSIONS
  Although metformin may improve tumour response in the non-randomized, retrospective studies analysed, it may not necessarily confer survival benefits. Future prospective and randomised trials are required to translate the positive impact of metformin documented in pre-clinical and retrospective studies into improve management of RT cancer patients.
authors.affiliation: Applied Radiation Therapy Trinity Research Group, Trinity College Dublin, Ireland; Division of Radiation Oncology, National Cancer Centre, Singapore.
authors.forename: Nur Atiqah Binte
authors.initials: NAB
authors.lastname: Samsuri
authors.affiliation: Applied Radiation Therapy Trinity Research Group, Trinity College Dublin, Ireland. Electronic address: leechm@tcd.ie.
authors.forename: Michelle
authors.initials: M
authors.lastname: Leech
authors.affiliation: Applied Radiation Therapy Trinity Research Group, Trinity College Dublin, Ireland.
authors.forename: Laure
authors.initials: L
authors.lastname: Marignol
mesh_terms: D003920:Diabetes Mellitus / Q000188:drug therapy*; D018572:Disease-Free Survival; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D009369:Neoplasms / Q000150:complications / Q000532:radiotherapy*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Cancer; Diabetes; Metformin; Radiation therapy