Predicted vitamin D status and colon cancer recurrence and mortality in CALGB 89803 (Alliance)

Abstract

Background: Observational studies suggest that higher levels of 25-hydroxyvitamin D3 (25(OH)D) are associated with a reduced risk of colorectal cancer and improved survival of colorectal cancer patients. However, the influence of vitamin D status on cancer recurrence and survival of patients with stage III colon cancer is unknown.

Patients and methods: We prospectively examined the influence of post-diagnosis predicted plasma 25(OH)D on outcome among 1016 patients with stage III colon cancer who were enrolled in a National Cancer Institute-sponsored adjuvant therapy trial (CALGB 89803). Predicted 25(OH)D scores were computed using validated regression models. We examined the influence of predicted 25(OH)D scores on cancer recurrence and mortality (disease-free survival; DFS) using Cox proportional hazards.

Results: Patients in the highest quintile of predicted 25(OH)D score had an adjusted hazard ratio (HR) for colon cancer recurrence or mortality (DFS) of 0.62 (95% confidence interval [CI], 0.44-0.86), compared with those in the lowest quintile (Ptrend = 0.005). Higher predicted 25(OH)D score was also associated with a significant improvement in recurrence-free survival and overall survival (Ptrend = 0.01 and 0.0004, respectively). The benefit associated with higher predicted 25(OH)D score appeared consistent across predictors of cancer outcome and strata of molecular tumor characteristics, including microsatellite instability and KRAS, BRAF, PIK3CA, and TP53 mutation status.

Conclusion: Higher predicted 25(OH)D levels after a diagnosis of stage III colon cancer may be associated with decreased recurrence and improved survival. Clinical trials assessing the benefit of vitamin D supplementation in the adjuvant setting are warranted.

Clinicaltrials.gov identifier: NCT00003835.

Keywords: colorectal neoplasm; prospective studies; survival analysis; vitamin D.

© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1.

Derivation of the study cohort. Q1, questionnaire 1 (midway through adjuvant therapy); Q2, questionnaire 2 (6 months after completion of adjuvant therapy); caloric intake exclusion,  4200 calories/day for men and  3500 calories/day for women.

Figure 2.

(A) Disease-free survival according to tertile of post-diagnosis predicted 25(OH)D levels. (B) Recurrence-free survival according to tertile of post-diagnosis predicted 25(OH)D levels. (C) Overall survival according to tertile of post-diagnosis predicted 25(OH)D levels. 25(OH)D, 25-hydroxyvitamin D.

Figure 3.

Adjusted hazard ratios (HR) and 95% confidence intervals (CI) comparing highest to lowest tertiles of predicted 25(OH)D level for disease-free survival across strata of predictors of patient outcome and tumor molecular features. FU/LV, 5-fluorouracil and leucovorin; IFL, irinotecan; MET, metabolic equivalent; MSI, microsatellite instability; MSS, microsatellite stable.