清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer

医学 结直肠癌 危险系数 内科学 前瞻性队列研究 循环肿瘤DNA 微小残留病 肿瘤科 队列 胃肠病学 癌症 外科 置信区间 白血病
作者
Thomas Reinert,Tenna Vesterman Henriksen,Emil Christensen,Shruti Sharma,Raheleh Salari,Himanshu Sethi,Michael Knudsen,Iver Nordentoft,Hsin-Ta Wu,Antony Tin,Mads H. Rasmussen,Søren Vang,Svetlana Shchegrova,Amanda Frydendahl,Ramya Srinivasan,Zoe J. Assaf,Mustafa Balcioglu,Alexander Olson,Scott Dashner,Dina Hafez
出处
期刊:JAMA Oncology [American Medical Association]
卷期号:5 (8): 1124-1124 被引量:741
标识
DOI:10.1001/jamaoncol.2019.0528
摘要

Novel 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).To 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.In 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.Outcomes were ctDNA measurement, clinical recurrence, and recurrence-free survival.A 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 < .001). Similarly, shortly after ACT ctDNA-positive patients were 17 times (HR, 17.5; 95% CI, 5.4-56.5; P < .001) more likely to relapse. All 7 patients who were ctDNA positive after ACT experienced relapse. Monitoring during and after ACT indicated that 3 of the 10 ctDNA-positive patients (30.0%) were cleared by ACT. During surveillance after definitive therapy, ctDNA-positive patients were more than 40 times more likely to experience disease recurrence than ctDNA-negative patients (HR, 43.5; 95% CI, 9.8-193.5 P < .001). In all multivariate analyses, ctDNA status was independently associated with relapse after adjusting for known clinicopathologic risk factors. Serial ctDNA analyses revealed disease recurrence up to 16.5 months ahead of standard-of-care radiologic imaging (mean, 8.7 months; range, 0.8-16.5 months). Actionable mutations were identified in 81.8% of the ctDNA-positive relapse samples.Circulating tumor DNA analysis can potentially change the postoperative management of CRC by enabling risk stratification, ACT monitoring, and early relapse detection.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
橙子完成签到 ,获得积分10
13秒前
xiaofeixia完成签到 ,获得积分10
19秒前
jlwang完成签到,获得积分10
23秒前
39秒前
44秒前
lty完成签到,获得积分20
47秒前
孟寐以求完成签到 ,获得积分10
48秒前
49秒前
fkdbdy发布了新的文献求助10
54秒前
朴子完成签到 ,获得积分10
58秒前
香蕉觅云应助勇往直前采纳,获得10
1分钟前
勇往直前完成签到,获得积分10
1分钟前
widesky777完成签到 ,获得积分0
1分钟前
carne完成签到,获得积分10
1分钟前
1分钟前
上善若水完成签到 ,获得积分10
1分钟前
勇往直前发布了新的文献求助10
1分钟前
Tumbleweed668完成签到,获得积分20
1分钟前
科研狗完成签到 ,获得积分0
1分钟前
科研通AI2S应助科研通管家采纳,获得10
1分钟前
Dongjie完成签到,获得积分10
1分钟前
蔡勇强完成签到 ,获得积分10
1分钟前
雷小牛完成签到 ,获得积分10
1分钟前
培培完成签到 ,获得积分10
1分钟前
ikun0000完成签到,获得积分10
2分钟前
午后狂睡完成签到 ,获得积分10
2分钟前
emxzemxz完成签到 ,获得积分10
2分钟前
yellowonion完成签到 ,获得积分10
2分钟前
岁月如歌完成签到,获得积分0
2分钟前
英俊的铭应助过眼云烟采纳,获得10
2分钟前
重重重飞完成签到 ,获得积分10
2分钟前
theo完成签到 ,获得积分10
2分钟前
allrubbish完成签到,获得积分10
2分钟前
凤兮完成签到 ,获得积分10
3分钟前
3分钟前
过眼云烟发布了新的文献求助10
3分钟前
之_ZH完成签到 ,获得积分10
3分钟前
淡淡菠萝完成签到 ,获得积分10
3分钟前
大饼完成签到 ,获得积分10
3分钟前
3分钟前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Immigrant Incorporation in East Asian Democracies 600
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3968532
求助须知:如何正确求助?哪些是违规求助? 3513358
关于积分的说明 11167309
捐赠科研通 3248700
什么是DOI,文献DOI怎么找? 1794453
邀请新用户注册赠送积分活动 875030
科研通“疑难数据库(出版商)”最低求助积分说明 804664