Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer
Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer
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DOI：
10.1200/jco.2007.15.8923
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发表时间：
2008-07-01
影响因子：
45.3
通讯作者：
Meropol, Neal J.
中科院分区：
文献类型：
--
作者：
Cohen, Steven J.;Punt, Cornelis J. A.;Meropol, Neal J.
目的随着转移性结直肠癌(MCRC)治疗选择的扩大，一种具有预后和预测作用的血液标记物可以指导治疗。我们验证了循环肿瘤细胞(CTCs)可以预测mCRC患者临床预后的假设。在一项前瞻性的多中心研究中，430例mCRC患者在基线和开始一线、二线或三线治疗后的外周血中检测了CTCs。结果根据CTC水平将患者分为预后不良组和预后良好组，CTC水平分别为3个或3个或3个/7.5毫升。中位无进展生存期(PFS；4.5个月比7.9个月；P=.0002)和总生存期(OS：9.4个月比18.5个月；P=0.0001)。治疗后1周至2周、3周至5周、6周至12周、13周至20周，差异持续存在。与两个时间点的不良CTC患者相比，基线不良CTC在3至5周内转为良好的患者的PFS和OS显著较长(PFS，6.2个月比1.6个月；P=0.02；OS，11.0个月比3.7个月；P=.0002)。在无进展的患者中，在成像后1个月内，良好的CTC与不良的CTC相比，与较长的生存期相关(18.8vs7.1个月；P=0.0001)。结论治疗前和治疗过程中CTC的数量是转移性结直肠癌患者PFS和OS的独立预测因子。CTC除了提供影像研究的信息外，还提供预后信息。
PurposeAs treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC.Patients and MethodsIn a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third- line therapy. CTCs were measured using an immunomagnetic separation technique.ResultsPatients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P = .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P = .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.ConclusionThe number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.