5-Fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer.
5-Fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer.
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DOI：
10.1053/j.gastro.2010.12.035
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发表时间：
2011-04
期刊：
影响因子：
29.4
通讯作者：
Goel A
中科院分区：
文献类型：
--
作者：
Jover R;Nguyen TP;Pérez-Carbonell L;Zapater P;Payá A;Alenda C;Rojas E;Cubiella J;Balaguer F;Morillas JD;Clofent J;Bujanda L;Reñé JM;Bessa X;Xicola RM;Nicolás-Pérez D;Castells A;Andreu M;Llor X;Boland CR;Goel A
基于 5-FU 的辅助化疗不会增加微卫星不稳定结直肠肿瘤患者的生存时间。我们确定了具有 CpG 岛甲基化表型 (CIMP) 的结直肠肿瘤患者对基于 5-FU 的治疗的反应。我们分析了 302 名结直肠癌 (CRC) 患者的人群队列，中位随访时间为 50.7 个月。 CIMP 状态通过分析 CACNAG1、SOCS1、RUNX3、NEUROG1 和 MLH1 启动子来确定；如果至少 3 个启动子被甲基化，则肿瘤被认为是 CIMP 阳性 (CIMP+)。 29.5% (89/302) 患者的肿瘤为 CIMP+；这并不影响无病生存（对数等级=.26）。在 TNM II-III 期肿瘤 (n=196) 中，32.7% 为 CIMP+。在未接受 5-FU 辅助化疗的 II-III 期 CRC 患者中，CIMP+ 肿瘤患者的无病生存时间最长（对数等级=0.04）；接受化疗的 CIMP+ 肿瘤患者的无病生存时间较短（对数等级 = 0.02）。在 CIMP 阴性肿瘤患者中，辅助 5-FU 化疗显着延长了无病生存时间 (log-rank=.00001)。然而，在 CIMP+ 肿瘤患者中，辅助 5-FU 化疗并不影响无病生存时间（对数等级=.7）。多变量分析显示 5-FU 治疗与 CIMP 状态之间存在显着且独立的相互作用（风险比 [HR]=0.6；95% 置信区间 [CI]，0.5–0.8）。在 CIMP+ 肿瘤患者中，辅助化疗并不是预后的独立预测因素（HR=0.8；95% CI，0.3-2.0）。在未接受 5-FU 辅助化疗的患者中，CIMP 状态是生存的唯一独立预测因子（HR=2.0；95% CI，1.1–3.8） CIMP+ 结直肠肿瘤患者不会从基于 5-FU 的辅助化疗中获益。
5-FU-based adjuvant chemotherapy does not increase survival times of patients with colorectal tumors with microsatellite instability. We determined the response of patients with colorectal tumors with the CpG island methylator phenotype (CIMP) to 5-FU-based therapy. We analyzed a population-based cohort of 302 patients with colorectal cancer (CRC) for a median follow-up time of 50.7 months. CIMP status was determined by analysis of the CACNAG1, SOCS1, RUNX3, NEUROG1, and MLH1 promoters; tumors were considered to be CIMP-positive (CIMP+) if at least 3 promoters were methylated. Tumors from 29.5% (89/302) of patients were CIMP+; this did not influence disease-free survival (log rank=.26). Of tumors of TNM stages II–III (n=196), 32.7% were CIMP+. Among patients with CRC stages II–III who did not receive adjuvant 5-FU chemotherapy, those with CIMP+ tumors had longest times of disease-free survival (log rank=.04); patients with CIMP+ tumors who received chemotherapy had shorter times of disease-free survival (log rank=0.02). In patients with CIMP-negative tumors, adjuvant 5-FU chemotherapy significantly increased time of disease-free survival (log-rank=.00001). However, in patients with CIMP+ tumors, adjuvant 5-FU chemotherapy did not affect time of disease-free survival (log rank=.7). Multivariate analysis showed a significant, independent interaction between 5-FU treatment and CIMP status (hazard ratio [HR]=0.6; 95% confidence interval [CI], .5–.8). Among patients with CIMP+ tumors, adjuvant chemotherapy was not an independent predictor of outcome (HR=0.8; 95% CI, 0.3–2.0). In patients who did not receive adjuvant 5-FU chemotherapy, CIMP status was the only independent predictor of survival (HR=2.0; 95% CI, 1.1–3.8) Patients with CIMP+ colorectal tumors do not benefit from 5-FU–based adjuvant chemotherapy.
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影响因子：
29.4
作者：
Boland CR;Goel A
通讯作者：
Goel A
影响因子：
3.7
作者：
Goel A;Nagasaka T;Hamelin R;Boland CR
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作者：
Ogino S;Nosho K;Kirkner GJ;Kawasaki T;Meyerhardt JA;Loda M;Giovannucci EL;Fuchs CS
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Fuchs CS
影响因子：
29.4
作者：
Goel, Ajay;Xicola, Rosa M.;Llor, Xavier
通讯作者：
Llor, Xavier
影响因子：
7.3
作者：
Ferracin, M.;Gafa, R.;Negrin, M.
通讯作者：
Negrin, M.