Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer.
Postoperative circulating tumor DNA as markers of recurrence risk in stages II to III colorectal cancer.
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术后循环肿瘤 DNA 作为 II 期至 III 期结直肠癌复发风险的标志物
DOI：
10.1186/s13045-021-01089-z
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发表时间：
2021-05-17
影响因子：
28.5
通讯作者：
Xu RH
中科院分区：
文献类型：
--
作者：
Chen G;Peng J;Xiao Q;Wu HX;Wu X;Wang F;Li L;Ding P;Zhao Q;Li Y;Wang D;Shao Y;Bao H;Pan Z;Ding KF;Cai S;Wang F;Xu RH
目前尚缺乏准确的术后危险分层方法来指导局限性结直肠癌(CRC)的辅助化疗。在这里，我们进行了一项前瞻性、观察性、多中心的研究，以探讨循环肿瘤DNA(CtDNA)在预测复发风险中的作用。方法从2017年9月至2020年3月，前瞻性地收集了276例II/III期大肠癌患者，并保留了240例可评估的患者进行分析，其中收集了1290份系列血浆样本。通过425个癌症相关基因的定向测序小组，检测了原发肿瘤和血浆中的体细胞变异。结果240例患者中，154例(64.2%)术前ctDNA阳性。术后第3~7天，ctDNA阳性与极高的复发风险相关(危险比(HR)10.98；95%可信区间(CI)5.31~22.72；P<； 0.001)。在17例接受ACT的ctDNA阳性患者中，有5例实现了ctDNA清除和无复发状态。同样，在化疗后的第一个采样点，ctDNA阳性患者复发的可能性是对照组的12倍(HR，12.76；95%CI，5.39-30.19；P<； 0.001)。在明确治疗后的监测中，ctDNA阳性也与极高的复发风险相关(HR，32.02；95%CI，10.79-95.08；P<； 0.001)。在所有多变量分析中，在调整已知的临床病理危险因素后，ctDNA阳性仍然是无复发生存率的最重要和最独立的预测因素。序列ctDNA分析诊断复发的总准确率为92.0%，可以在放射成像之前发现疾病复发，平均提前5.01个月。结论术后连续ctDNA检测预测了II/III期结直肠癌患者的高复发风险，并在放射成像之前发现了疾病复发。CT DNA可用于指导手术后的治疗决策。
BackgroundPrecise methods for postoperative risk stratification to guide the administration of adjuvant chemotherapy (ACT) in localized colorectal cancer (CRC) are still lacking. Here, we conducted a prospective, observational, and multicenter study to investigate the utility of circulating tumor DNA (ctDNA) in predicting the recurrence risk.MethodsFrom September 2017 to March 2020, 276 patients with stage II/III CRC were prospectively recruited in this study and 240 evaluable patients were retained for analysis, of which 1290 serial plasma samples were collected. Somatic variants in both the primary tumor and plasma were detected via a targeted sequencing panel of 425 cancer-related genes. Patients were treated and followed up per standard of care.ResultsPreoperatively, ctDNA was detectable in 154 of 240 patients (64.2%). At day 3–7 postoperation, ctDNA positivity was associated with remarkably high recurrence risk (hazard ratio [HR], 10.98; 95%CI, 5.31–22.72;P< 0.001). ctDNA clearance and recurrence-free status was achieved in 5 out of 17 ctDNA-positive patients who were subjected to ACT. Likewise, at the first sampling point after ACT, ctDNA-positive patients were 12 times more likely to experience recurrence (HR, 12.76; 95%CI, 5.39–30.19;P< 0.001). During surveillance after definitive therapy, ctDNA positivity was also associated with extremely high recurrence risk (HR, 32.02; 95%CI, 10.79–95.08;P< 0.001). In all multivariate analyses, ctDNA positivity remained the most significant and independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors. Serial ctDNA analyses identified recurrence with an overall accuracy of 92.0% and could detect disease recurrence ahead of radiological imaging with a mean lead time of 5.01 months.ConclusionsPostoperative serial ctDNA detection predicted high relapse risk and identified disease recurrence ahead of radiological imaging in patients with stage II/III CRC. ctDNA may be used to guide the decision-making in postsurgical management.
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影响因子：
16.2
作者：
Feng, Rui-Mei;Zong, Yi-Nan;Xu, Rui-Hua
通讯作者：
Xu, Rui-Hua
影响因子：
28.4
作者：
Reinert, Thomas;Henriksen, Tenna Vesterman;Andersen, Claus Lindbjerg
通讯作者：
Andersen, Claus Lindbjerg
DOI：
10.1056/nejmoa1713709
发表时间：
2018-03-29
期刊：
The New England journal of medicine
影响因子：
--
作者：
Grothey A;Sobrero AF;Shields AF;Yoshino T;Paul J;Taieb J;Souglakos J;Shi Q;Kerr R;Labianca R;Meyerhardt JA;Vernerey D;Yamanaka T;Boukovinas I;Meyers JP;Renfro LA;Niedzwiecki D;Watanabe T;Torri V;Saunders M;Sargent DJ;Andre T;Iveson T
通讯作者：
Iveson T
影响因子：
78.8
作者：
Abbosh, Christopher;Birkbak, Nicolai J.;Swanton, Charles
通讯作者：
Swanton, Charles
影响因子：
28.4
作者：
Tie, Jeanne;Cohen, Joshua D.;Gibbs, Peter
通讯作者：
Gibbs, Peter