Fuchs M A, Yuan C, Sato K, Niedzwiecki D, Ye X, Saltz L B, Mayer R J, Mowat R B, Whittom R, Hantel A, Benson A, Atienza D, Messino M, Kindler H, Venook A, Innocenti F, Warren R S, Bertagnolli M M, Ogino S, Giovannucci E L, Horvath E, Meyerhardt J A, Ng K
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.
Ann Oncol. 2017 Jun 1;28(6):1359-1367. doi: 10.1093/annonc/mdx109.
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.
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.
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.
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.
观察性研究表明，较高水平的25-羟基维生素D3（25(OH)D）与结直肠癌风险降低及结直肠癌患者生存率提高相关。然而，维生素D状态对III期结肠癌患者癌症复发和生存的影响尚不清楚。
我们前瞻性地研究了1016例III期结肠癌患者诊断后预测的血浆25(OH)D对预后的影响，这些患者参加了一项由美国国立癌症研究所资助的辅助治疗试验（CALGB 89803）。使用经过验证的回归模型计算预测的25(OH)D评分。我们使用Cox比例风险模型研究预测的25(OH)D评分对癌症复发和死亡率（无病生存期；DFS）的影响。
预测的25(OH)D评分处于最高五分位数的患者，结肠癌复发或死亡率（DFS）的调整后风险比（HR）为0.62（95%置信区间[CI]，0.44 - 0.86），而处于最低五分位数的患者为对照（P趋势 = 0.005）。较高的预测25(OH)D评分还与无复发生存期和总生存期的显著改善相关（P趋势分别为0.01和0.0004）。较高的预测25(OH)D评分带来的益处似乎在癌症预后预测指标和分子肿瘤特征分层中一致，包括微卫星不稳定性以及KRAS、BRAF、PIK3CA和TP53突变状态。
III期结肠癌诊断后预测的25(OH)D水平较高可能与复发减少和生存改善相关。有必要开展临床试验评估辅助治疗中补充维生素D的益处。
NCT00003835
