The effect of vitamin D supplementation on survival in patients with colorectal cancer: Systematic review and Meta-analysis of Randomised Controlled Trials

Peter G Vaughan-Shaw; Louis F. Buijs; James P. Blackmur; Evropi Theodoratou; Lina Zgaga; Farhat V N Din; Susan M Farrington; Malcolm G Dunlop

doi:10.1038/s41416-020-01060-8

The effect of vitamin D supplementation on survival in patients with colorectal cancer: Systematic review and Meta-analysis of Randomised Controlled Trials

Peter G Vaughan-Shaw, Louis F. Buijs, James P. Blackmur, Evropi Theodoratou, Lina Zgaga, Farhat V N Din, Susan M Farrington, Malcolm G Dunlop

Research output: Contribution to journal › Article › peer-review

Abstract

Background
Low circulating vitamin D levels are associated with poor colorectal cancer (CRC) survival. We assess whether vitamin D supplementation improves CRC survival outcomes.

Methods
PubMed and Web of Science were searched. RCTs of vitamin D supplementation reporting CRC mortality were included. RCTs with high risk of bias were excluded from analysis. Random-effects meta-analysis models calculated estimates of survival benefit with supplementation. PROSPERO:CRD42020173397

Results
7 RCTs (n=957 CRC cases) were identified: three trials included patients with CRC at outset, four population trials reported survival in incident cases. Two RCTs were excluded from meta-analysis (high risk of bias; no hazard ratio). Whilst trials varied in inclusion criteria, intervention dose and outcomes, meta-analysis found a 30% reduction in adverse CRC outcomes with supplementation (n=815, HR=0.70; 95%CI:0.48-0.93). A beneficial effect was seen in trials of CRC patients (progression-free survival, HR=0.65; 95%CI:0.36-0.94), with suggestive effect in incident CRC cases from population trials (CRC-specific survival, HR=0.76; 95%CI:0.39-1.13). No heterogeneity or publication bias was noted.

Conclusions
Meta-analysis demonstrates a clinically meaningful benefit of vitamin D supplementation on CRC survival outcomes. Further well-designed, adequately powered RCTs are needed to fully evaluate benefit of supplementation in augmenting ‘real life’ follow-up and adjuvant chemotherapy regimens, as well as determining optimal dosing.

Original language	English
Journal	British Journal of Cancer
DOIs	https://doi.org/10.1038/s41416-020-01060-8
Publication status	Published - 15 Sept 2020

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10.1038/s41416-020-01060-8

MA for BJC SECOND REVISION cleanAccepted author manuscript, 158 KB

Colorectal cancer reduction through risk stratification of screening, follow-up and treatment
Theodoratou, E. (Principal Investigator)
UK-based charities
1/05/17 → 30/04/23
Project: Research
CRUK Edinburgh Centre Clinical Fellowship
Frame, M. (Principal Investigator)
UK-based charities
1/02/17 → 31/01/20
Project: Research
Integrative Genomics in Colorectal Cancer Susceptibility:Developing risk reducing interventions through understanding biology
Dunlop, M. (Principal Investigator), Campbell, H. (Co-investigator), Farrington, S. (Co-investigator) & Theodoratou, E. (Co-investigator)
UK-based charities
1/01/16 → 31/05/21
Project: Research

Farhat Din
- Edinburgh Cancer Research Centre
- Institute of Genetics and Cancer
- School of Genetics and Cancer - Personal Chair Bowel Cancer UK Royal College of Surgeons of
Person: Academic: Research Active

Cite this

@article{8d7b73c0c5dd4798ae9f16b5824ef28f,

title = "The effect of vitamin D supplementation on survival in patients with colorectal cancer: Systematic review and Meta-analysis of Randomised Controlled Trials",

abstract = "Background Low circulating vitamin D levels are associated with poor colorectal cancer (CRC) survival. We assess whether vitamin D supplementation improves CRC survival outcomes. Methods PubMed and Web of Science were searched. RCTs of vitamin D supplementation reporting CRC mortality were included. RCTs with high risk of bias were excluded from analysis. Random-effects meta-analysis models calculated estimates of survival benefit with supplementation. PROSPERO:CRD42020173397 Results 7 RCTs (n=957 CRC cases) were identified: three trials included patients with CRC at outset, four population trials reported survival in incident cases. Two RCTs were excluded from meta-analysis (high risk of bias; no hazard ratio). Whilst trials varied in inclusion criteria, intervention dose and outcomes, meta-analysis found a 30\% reduction in adverse CRC outcomes with supplementation (n=815, HR=0.70; 95\%CI:0.48-0.93). A beneficial effect was seen in trials of CRC patients (progression-free survival, HR=0.65; 95\%CI:0.36-0.94), with suggestive effect in incident CRC cases from population trials (CRC-specific survival, HR=0.76; 95\%CI:0.39-1.13). No heterogeneity or publication bias was noted. Conclusions Meta-analysis demonstrates a clinically meaningful benefit of vitamin D supplementation on CRC survival outcomes. Further well-designed, adequately powered RCTs are needed to fully evaluate benefit of supplementation in augmenting {\textquoteleft}real life{\textquoteright} follow-up and adjuvant chemotherapy regimens, as well as determining optimal dosing. ",

author = "Vaughan-Shaw, \{Peter G\} and Buijs, \{Louis F.\} and Blackmur, \{James P.\} and Evropi Theodoratou and Lina Zgaga and Din, \{Farhat V N\} and Farrington, \{Susan M\} and Dunlop, \{Malcolm G\}",

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doi = "10.1038/s41416-020-01060-8",

language = "English",

journal = "British Journal of Cancer",

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T1 - The effect of vitamin D supplementation on survival in patients with colorectal cancer: Systematic review and Meta-analysis of Randomised Controlled Trials

AU - Vaughan-Shaw, Peter G

AU - Buijs, Louis F.

AU - Blackmur, James P.

AU - Theodoratou, Evropi

AU - Zgaga, Lina

AU - Din, Farhat V N

AU - Farrington, Susan M

AU - Dunlop, Malcolm G

PY - 2020/9/15

Y1 - 2020/9/15

N2 - Background Low circulating vitamin D levels are associated with poor colorectal cancer (CRC) survival. We assess whether vitamin D supplementation improves CRC survival outcomes. Methods PubMed and Web of Science were searched. RCTs of vitamin D supplementation reporting CRC mortality were included. RCTs with high risk of bias were excluded from analysis. Random-effects meta-analysis models calculated estimates of survival benefit with supplementation. PROSPERO:CRD42020173397 Results 7 RCTs (n=957 CRC cases) were identified: three trials included patients with CRC at outset, four population trials reported survival in incident cases. Two RCTs were excluded from meta-analysis (high risk of bias; no hazard ratio). Whilst trials varied in inclusion criteria, intervention dose and outcomes, meta-analysis found a 30% reduction in adverse CRC outcomes with supplementation (n=815, HR=0.70; 95%CI:0.48-0.93). A beneficial effect was seen in trials of CRC patients (progression-free survival, HR=0.65; 95%CI:0.36-0.94), with suggestive effect in incident CRC cases from population trials (CRC-specific survival, HR=0.76; 95%CI:0.39-1.13). No heterogeneity or publication bias was noted. Conclusions Meta-analysis demonstrates a clinically meaningful benefit of vitamin D supplementation on CRC survival outcomes. Further well-designed, adequately powered RCTs are needed to fully evaluate benefit of supplementation in augmenting ‘real life’ follow-up and adjuvant chemotherapy regimens, as well as determining optimal dosing.

AB - Background Low circulating vitamin D levels are associated with poor colorectal cancer (CRC) survival. We assess whether vitamin D supplementation improves CRC survival outcomes. Methods PubMed and Web of Science were searched. RCTs of vitamin D supplementation reporting CRC mortality were included. RCTs with high risk of bias were excluded from analysis. Random-effects meta-analysis models calculated estimates of survival benefit with supplementation. PROSPERO:CRD42020173397 Results 7 RCTs (n=957 CRC cases) were identified: three trials included patients with CRC at outset, four population trials reported survival in incident cases. Two RCTs were excluded from meta-analysis (high risk of bias; no hazard ratio). Whilst trials varied in inclusion criteria, intervention dose and outcomes, meta-analysis found a 30% reduction in adverse CRC outcomes with supplementation (n=815, HR=0.70; 95%CI:0.48-0.93). A beneficial effect was seen in trials of CRC patients (progression-free survival, HR=0.65; 95%CI:0.36-0.94), with suggestive effect in incident CRC cases from population trials (CRC-specific survival, HR=0.76; 95%CI:0.39-1.13). No heterogeneity or publication bias was noted. Conclusions Meta-analysis demonstrates a clinically meaningful benefit of vitamin D supplementation on CRC survival outcomes. Further well-designed, adequately powered RCTs are needed to fully evaluate benefit of supplementation in augmenting ‘real life’ follow-up and adjuvant chemotherapy regimens, as well as determining optimal dosing.

U2 - 10.1038/s41416-020-01060-8

DO - 10.1038/s41416-020-01060-8

M3 - Article

SN - 0007-0920

JO - British Journal of Cancer

JF - British Journal of Cancer

ER -

The effect of vitamin D supplementation on survival in patients with colorectal cancer: Systematic review and Meta-analysis of Randomised Controlled Trials

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Projects

Colorectal cancer reduction through risk stratification of screening, follow-up and treatment

CRUK Edinburgh Centre Clinical Fellowship

Integrative Genomics in Colorectal Cancer Susceptibility:Developing risk reducing interventions through understanding biology

Profiles

Farhat Din

Cite this