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2015年ASCO年会将于5月29日--6月2日在美国芝加哥召开。5月30日下午消化系统（结直肠）肿瘤口头报告专场上，将会公布来自CALGB/SWOG 80405（Alliance）试验中关于维生素D状态与转移性结直肠癌生存期关系的结果。前瞻性流行病学数据显示，较高的25-羟基维生素D[25(OH)D]浓度与结直肠癌患者提高的生存期有关，然而，在转移性结直肠癌（mCRC）中25(OH)D和预后之间的关系是未知的。

研究方法：

在入组CALGB/SWOG 80405（一项随机，‍‍‍‍‍‍‍‍III期，化疗+贝伐珠单抗，西妥昔单抗，或者两者，先于KRAS野生型修正的试验），之前未经治疗的mCRC患者中，研究人员对他们血浆25(OH)D和总生存期（OS）之间的关系进行前瞻性评估。无进展生存期（PFS）是次要终点。血浆25(OH)D浓度在基线时通过放射免疫法测量，利用自填问卷调查收集饮食和生活习惯。Cox比例风险模型用于计算调整其他预后变量的风险比（HR）。

研究结果：

在1043例患者中，平均血浆25(OH)D浓度是17.2ng/mL（范围2.2～72.7）。男性黑人患者，生活在东北部患者，较低的饮食和补充维生素D摄入，ECOG体能状态1（vs.0），肿瘤RAS突变，较高体重指数，较低体能活动，以及在冬季和春季静脉抽血的患者，有明显较低的25(OH)D浓度。调整病理和临床预后因素（中位32.6 vs 24.5个月；HR 0.65，95% CI，0.51～0.83；P趋势=0.001）后的最低25(OH)D浓度患者相比较，最高25(OH)D五分值的患者会显著改善OS。增加的25(OH)D浓度也会明显与提高的PFS（中位12.2 vs 10.1个月；HR 0.79，95% CI，0.63～0.99；P趋势=0.01）相关。研究结果与患者特征亚组一致，包括RAS状态，排除静脉抽血3或6个月内死亡的患者后结果仍保持不变。

结论：

在经化疗+生物制剂治疗的mCRC患者中，较高血浆25(OH)D浓度与显著的生存期改善有关。随机维生素D补充试验是必要的且正在进行，而且在维生素D通路基因经SNPs修正机制目前正在研究中。

阅读英文摘要

Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance).（Abstract NO：3503）

Authors：Kimmie Ng, Alan P. Venook,et al.

Session Type：Oral Abstract Session

Background：Prospective epidemiologic data suggest that higher levels of 25-hydroxyvitamin D [25(OH)D] are associated with improved survival in patients with colorectal cancer, however the relationship between 25(OH)D and outcome in metastatic CRC (mCRC), specifically, is unknown. 

Methods：We prospectively assessed the association between plasma 25(OH)D and overall survival (OS) in previously untreated mCRC patients enrolled in CALGB/SWOG 80405, a randomized phase III trial of chemotherapy + bevacizumab, cetuximab, or both, prior to the KRAS wild type amendment. Progression-free survival (PFS) was a secondary endpoint. Plasma 25(OH)D levels were measured at baseline by radioimmunoassay, and dietary and lifestyle behaviors collected from self-administered questionnaires. Cox proportional hazards models were used to calculate hazard ratios (HR) adjusted for other prognostic variables. 

Results：Among 1,043 patients, median plasma 25(OH)D was 17.2 ng/mL (range 2.2-72.7). Male and black patients, those living in the northeast, patients with lower dietary and supplemental vitamin D intake, ECOG performance status 1 (vs. 0), tumoral RAS mutation, higher body-mass index, lower physical activity, and blood draw during the winter and spring had significantly lower levels of 25(OH)D. Patients in the highest quintile of 25(OH)D had significantly improved OS compared to those in the lowest after adjusting for pathologic and clinical prognostic factors (median 32.6 vs. 24.5 months; HR 0.65, 95% CI, 0.51-0.83; P trend = 0.001). Increasing concentrations of 25(OH)D were also significantly associated with improved PFS (median 12.2 vs. 10.1 months; HR 0.79, 95% CI, 0.63-0.99; P trend = 0.01). The results were consistent across subgroups of patient characteristics, including RAS status, and remained unchanged after excluding patients who died within 3 or 6 months of blood draw. 

Conclusions：Higher concentrations of plasma 25(OH)D are associated with significantly improved survival in mCRC patients treated with chemotherapy + biologics. Randomized trials of vitamin D supplementation are warranted and ongoing, and effect modification by SNPs in vitamin D pathway genes is currently being explored.

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