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

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, Samantha Navarro, Shruti Goel, Matthew Rabinowitz, Paul R. Billings, Styrmir Sigurjonsson, Lars Dyrskjøt, Ryan Swenerton, Alexey Aleshin, Søren Laurberg, Anders Husted Madsen, Anne-Sofie Kannerup, Katrine Stribolt, Søren Palmelund Krag, Lene Hjerrild Iversen, Kåre Andersson Gotschalck, Cheng-Ho Jimmy Lin, Bernhard Zimmermann, Claus L. Andersen · 发表于：JAMA Oncology · 年份：2019 · DOI：10.1001/jamaoncol.2019.0528 · 被引用次数：1050 · 研究领域：Cancer Genomics and Diagnostics、Cancer Cells and Metastasis、Colorectal Cancer Screening and Detection

IMPORTANCE: 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). OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: Outcomes were ctDNA measurement, clinical recurrence, and recurrence-free survival. RESULTS: 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 de...