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


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.


CONCLUSIONS
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.


BACKGROUND
NCT00003835.
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston.
M A
MA
Fuchs
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston.
C
C
Yuan
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston.
K
K
Sato
Alliance Statistics and Data Center, Duke University Medical Center, Durham.
D
D
Niedzwiecki
Alliance Statistics and Data Center, Duke University Medical Center, Durham.
X
X
Ye
Memorial Sloan-Kettering Cancer Center, New York.
L B
LB
Saltz
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston.
R J
RJ
Mayer
Toledo Community Hospital Oncology Program, Toledo, USA.
R B
RB
Mowat
Hôpital du Sacré-Coeur de Montréal, Montreal, Canada.
R
R
Whittom
Edward Cancer Center, Naperville.
A
A
Hantel
Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago.
A
A
Benson
Virginia Oncology Associates, Norfolk.
D
D
Atienza
Southeast Cancer Control Consortium, Mission Hospitals-Memorial Campus, Asheville.
M
M
Messino
University of Chicago, Chicago.
H
H
Kindler
University of California at San Francisco Comprehensive Cancer Center, San Francisco.
A
A
Venook
Division of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill.
F
F
Innocenti
University of California at San Francisco Comprehensive Cancer Center, San Francisco.
R S
RS
Warren
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston.|Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston.
M M
MM
Bertagnolli
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston.|Division of MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston.
S
S
Ogino
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston.|Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston.
E L
EL
Giovannucci
Alliance Protocol Operations Office, Chicago, USA.
E
E
Horvath
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston.
J A
JA
Meyerhardt
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston.
K
K
Ng
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies; D014807:Vitamin D / Q000097:blood*
D014807:Vitamin D
colorectal neoplasm; prospective studies; survival analysis; vitamin D