Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis
BMJ 2016; 355 doi: http://dx.doi.org/10.1136/bmj.i6188 (Published 05 December 2016)
Parambir S Dulai, clinical fellow1, Siddharth Singh, assistant professor1 2, Evelyn Marquez, research fellow1, Rohan Khera, research fellow3, Larry J Prokop, librarian4, Paul J Limburg, professor5, Samir Gupta, associate professor6 7, Mohammad Hassan Murad, professor9
Correspondence to: S Singh sis040 at ucsd.edu
The Meta-analyses of Colon Cancer and Vitamin D in VitaminDWiki
- Colorectal cancer is associated with Vitamin D (17 meta-analyses so far) – July 2018
- Colorectal cancer 60 percent less likely: high vs low Vitamin D level – meta-analysis Dec 2016
- Colorectal Cancer recurrence not prevented by 1,000 IU of vitamin D – meta-analysis Dec 2016
- Risk of Cancer increased due to Vitamin D Receptor – meta-analysis of 73 studies Jan 2016
- Colon cancer 30 percent more likely if low vitamin D – 12th meta-analysis Aug 2015
- Colon cancer risk reduced by many vitamins – 13 percent reduction by Vitamin D – meta-analysis Jan 2015
- Cancer (colon, breast, lymph) survival about 2X better with high level vitamin D – meta-analysis July 2014
- Cancer survival 4 percent more likely with just a little more vitamin D (4 ng) - meta-analysis July 2014
- Colorectal and Breast Cancer – Vitamin D is associated with fewer deaths – meta-analysis Feb 2014
- 10 percent of colon cancer linked to Vitamin D Receptor – meta-analysis April 2012
- Meta-graphs of vitamin D and Cancer – Dec 2011
- Colon cancer probability increases with decreased vitamin D – Meta-analysis July 2011
- Non-cancer colon growths 7 percent less likely with each 10 ng increase in vitamin D – Oct 2011
- Colorectal cancer 26 percent less likely for every 10 ng of vitamin D – meta-analysis Aug 2011
- Colon polyps reduced 15 percent by increasing vitamin D by 20 ng – meta-analysis June 2011
- Meta-analysis of 3 cancers - 10 ng more vitamin D decrease colorectal by 15 percent– May 2010
- Meta-analysis found vitamin D association with colon but not prostate nor breast cancer May 2010
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.
Data sources Medline, Embase, Web of Science, from inception to 15 October 2015; clinical trial registries.
Study selection 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.
Data extraction 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.
Registration PROSPERO (CRD42015029598).