M A Fuchs1, C Yuan1,2, K Sato1, D Niedzwiecki3, X Ye3, L B Saltz4, R J Mayer1, R B Mowat5, R Whittom6, A Hantel7, A Benson8, D Atienza9, M Messino10, H Kindler11, A Venook12, F Innocenti13, R S Warren12, M M Bertagnolli1,14, S Ogino1,2,15, E L Giovannucci2,16,17, E Horvath18, J A Meyerhardt1, K Ng1. 1. Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston. 2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston. 3. Alliance Statistics and Data Center, Duke University Medical Center, Durham. 4. Memorial Sloan-Kettering Cancer Center, New York. 5. Toledo Community Hospital Oncology Program, Toledo, USA. 6. Hôpital du Sacré-Coeur de Montréal, Montreal, Canada. 7. Edward Cancer Center, Naperville. 8. Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago. 9. Virginia Oncology Associates, Norfolk. 10. Southeast Cancer Control Consortium, Mission Hospitals-Memorial Campus, Asheville. 11. University of Chicago, Chicago. 12. University of California at San Francisco Comprehensive Cancer Center, San Francisco. 13. Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill. 14. Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston. 15. Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston. 16. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston. 17. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston. 18. Alliance Protocol Operations Office, Chicago, USA.
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.
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.
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