title: Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis.
abstract: OBJECTIVE
  To assess the comparative efficacy and safety of candidate agents (low and high dose aspirin, non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), calcium, vitamin D, folic acid, alone or in combination) for prevention of advanced metachronous neoplasia (that is, occurring at different times after resection of initial neoplasia) in individuals with previous colorectal neoplasia, through a systematic review and network meta-analysis.
  
  
  METHODS
  Medline, Embase, Web of Science, from inception to 15 October 2015; clinical trial registries.
  
  
  METHODS
  Randomized controlled trials in adults with previous colorectal neoplasia, treated with candidate chemoprevention agents, and compared with placebo or another candidate agent. Primary efficacy outcome was risk of advanced metachronous neoplasia; safety outcome was serious adverse events.
  
  
  METHODS
  Two investigators identified studies and abstracted data. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed with surface under the cumulative ranking (SUCRA) probabilities (ranging from 1, indicating that the treatment has a high likelihood to be best, to 0, indicating the treatment has a high likelihood to be worst). Quality of evidence was appraised with GRADE criteria.
  
  
  RESULTS
  15 randomized controlled trials (12 234 patients) comparing 10 different strategies were included. Compared with placebo, non-aspirin NSAIDs were ranked best for preventing advanced metachronous neoplasia (odds ratio 0.37, 95% credible interval 0.24 to 0.53; SUCRA=0.98; high quality evidence), followed by low-dose aspirin (0.71, 0.41 to 1.23; SUCRA=0.67; low quality evidence). Low dose aspirin, however, was ranked the safest among chemoprevention agents (0.78, 0.43 to 1.38; SUCRA=0.84), whereas non-aspirin NSAIDs (1.23, 0.95 to 1.64; SUCRA=0.26) were ranked low for safety. High dose aspirin was comparable with low dose aspirin in efficacy (1.12, 0.59 to 2.10; SUCRA=0.58) but had an inferior safety profile (SUCRA=0.51). Efficacy of agents for reducing metachronous colorectal cancer could not be estimated.
  
  
  CONCLUSIONS
  Among individuals with previous colorectal neoplasia, non-aspirin NSAIDs are the most effective agents for the prevention of advanced metachronous neoplasia, whereas low dose aspirin has the most favorable risk:benefit profile.
  
  
  BACKGROUND
  PROSPERO (CRD42015029598).
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
authors.forename: Parambir S
authors.initials: PS
authors.lastname: Dulai
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA sis040@ucsd.edu.|Division of Biomedical Informatics, University of California San Diego, La Jolla, CA, USA.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Singh
authors.affiliation: Division of Gastroenterology, University of California San Diego, La Jolla, CA, USA.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Marquez
authors.affiliation: Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Rohan
authors.initials: R
authors.lastname: Khera
authors.affiliation: Department of Library Services, Mayo Clinic, Rochester, MN, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Prokop
authors.affiliation: Divison of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.|Moores Cancer Center, University of San Diego, La Jolla, CA, USA.
authors.forename: Samir
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Murad
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001499:Bayes Theorem; D002118:Calcium / Q000627:therapeutic use*; D018890:Chemoprevention; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D014803:Vitamin B Complex / Q000627:therapeutic use*; D014807:Vitamin D / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014815:Vitamins; D014803:Vitamin B Complex; D014807:Vitamin D; D005492:Folic Acid; D001241:Aspirin; D002118:Calcium