Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer
Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer
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DOI：
10.1056/nejmoa022289
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发表时间：
2003-07-17
影响因子：
158.5
通讯作者：
Gallinger, S
中科院分区：
文献类型：
--
作者：
Ribic, CM;Sargent, DJ;Gallinger, S
背景：高频微卫星不稳定结肠癌具有与微卫星稳定肿瘤相区别的临床和病理特征。我们研究了微卫星不稳定状态作为预测II期和III期结肠癌患者使用氟尿嘧啶辅助化疗获益的有用性。方法：收集结肠癌患者的肿瘤标本，纳入氟尿嘧啶辅助化疗的随机试验。使用单核苷酸和二核苷酸标记评估微卫星不稳定性。结果：570例组织标本中，95例（16.7%）表现出高频微卫星不稳定性。在287例未接受辅助治疗的患者中，表现为高频微卫星不稳定性的肿瘤患者的5年总生存率优于表现为微卫星稳定性或低频不稳定性的肿瘤患者（死亡风险比为0.31[95%置信区间，0.14 ~ 0.72]；P=0.004）。在接受辅助化疗的患者中，高频微卫星不稳定性与总生存率的增加无关（死亡风险比为1.07[95%可信区间，0.62至1.86]；P=0.80）。不同微卫星不稳定状态的治疗效果差异有统计学意义（P=0.01）。根据调整分期和分级的多变量分析，辅助化疗改善了微卫星稳定肿瘤或低频微卫星不稳定肿瘤患者的总生存率（死亡风险比为0.72[95%可信区间，0.53至0.99]；P=0.04）。相比之下，高频微卫星不稳定组的辅助化疗没有获益。结论：氟尿嘧啶辅助化疗对伴有微卫星稳定肿瘤或低频微卫星不稳定肿瘤的II期或III期结肠癌患者有利，但对伴有高频微卫星不稳定肿瘤的患者无效。
Background: Colon cancers with high-frequency microsatellite instability have clinical and pathological features that distinguish them from microsatellite-stable tumors. We investigated the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II and stage III colon cancer.Methods: Tumor specimens were collected from patients with colon cancer who were enrolled in randomized trials of fluorouracil-based adjuvant chemotherapy. Microsatellite instability was assessed with the use of mononucleotide and dinucleotide markers.Results: Of 570 tissue specimens, 95 (16.7 percent) exhibited high-frequency microsatellite instability. Among 287 patients who did not receive adjuvant therapy, those with tumors displaying high-frequency microsatellite instability had a better five-year rate of overall survival than patients with tumors exhibiting microsatellite stability or low-frequency instability (hazard ratio for death, 0.31 [95 percent confidence interval, 0.14 to 0.72]; P=0.004). Among patients who received adjuvant chemotherapy, high-frequency microsatellite instability was not correlated with increased overall survival (hazard ratio for death, 1.07 [95 percent confidence interval, 0.62 to 1.86]; P=0.80). The benefit of treatment differed significantly according to the microsatellite-instability status (P=0.01). Adjuvant chemotherapy improved overall survival among patients with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability, according to a multivariate analysis adjusted for stage and grade (hazard ratio for death, 0.72 [95 percent confidence interval, 0.53 to 0.99]; P=0.04). By contrast, there was no benefit of adjuvant chemotherapy in the group with high-frequency microsatellite instability.Conclusions: Fluorouracil-based adjuvant chemotherapy benefited patients with stage II or stage III colon cancer with microsatellite-stable tumors or tumors exhibiting low-frequency microsatellite instability but not those with tumors exhibiting high-frequency microsatellite instability.