Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer
Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer
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DOI：
10.1001/jamaoncol.2019.0528
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发表时间：
2019-08-01
期刊：
影响因子：
28.4
通讯作者：
Andersen, Claus Lindbjerg
中科院分区：
文献类型：
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作者：
Reinert, Thomas;Henriksen, Tenna Vesterman;Andersen, Claus Lindbjerg
新的检测和监测残留病变的灵敏方法可以改善术后风险分层，这对辅助化疗(ACT)患者的选择、ACT持续时间、放射学监测的强度以及结直肠癌(CRC)患者的最终结局具有重要意义。目的利用结直肠癌患者手术前后、ACT术中、术后及监测期间血浆游离DNA超深测序的纵向数据，探讨循环肿瘤DNA(CtDNA)与复发的关系。设计、设置和参与者：在这项前瞻性的多中心队列研究中，ctDNA在I-III期结直肠癌的术前和术后环境中通过个性化的多重、基于聚合酶链式反应的下一代测序进行了量化。这项研究从2014年5月1日到2017年1月31日在丹麦奥胡斯大学医院、兰德斯医院和赫宁医院的外科部门招募了130名患者。829例患者分别于术前、术后30d、每隔3个月采血一次，连续采血3年。主要结果和测量结果是ctDNA测量、临床复发和无复发生存率。结果130例I-III期结直肠癌患者(平均年龄67.9[10.1]岁；男性74例(56.9%))进入研究；5例患者停止参与，125例患者用于分析。术前122例患者中108例(88.5%)检测到ctDNA。在明确治疗后，纵向ctDNA分析确定了16例复发中的14例(87.5%)。在术后第30天，ctDNA阳性患者复发的可能性是ctDNA阴性患者的7倍(危险比[HR]，7.2；95%CI，2.7-19.0；P
ImportanceNovel sensitive methods for detection and monitoring of residual disease can improve postoperative risk stratification with implications for patient selection for adjuvant chemotherapy (ACT), ACT duration, intensity of radiologic surveillance, and, ultimately, outcome for patients with colorectal cancer (CRC). ObjectiveTo investigate the association of circulating tumor DNA (ctDNA) with recurrence using longitudinal data from ultradeep sequencing of plasma cell-free DNA in patients with CRC before and after surgery, during and after ACT, and during surveillance. Design, Setting, and ParticipantsIn this prospective, multicenter cohort study, ctDNA was quantified in the preoperative and postoperative settings of stages I to III CRC by personalized multiplex, polymerase chain reaction-based, next-generation sequencing. The study enrolled 130 patients at the surgical departments of Aarhus University Hospital, Randers Hospital, and Herning Hospital in Denmark from May 1, 2014, to January 31, 2017. Plasma samples (n=829) were collected before surgery, postoperatively at day 30, and every third month for up to 3 years. Main Outcomes and MeasuresOutcomes were ctDNA measurement, clinical recurrence, and recurrence-free survival. ResultsA total of 130 patients with stages I to III CRC (mean [SD] age, 67.9 [10.1] years; 74 [56.9%] male) were enrolled in the study; 5 patients discontinued participation, leaving 125 patients for analysis. Preoperatively, ctDNA was detectable in 108 of 122 patients (88.5%). After definitive treatment, longitudinal ctDNA analysis identified 14 of 16 relapses (87.5%). At postoperative day 30, ctDNA-positive patients were 7 times more likely to relapse than ctDNA-negative patients (hazard ratio [HR], 7.2; 95% CI, 2.7-19.0; P