Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer

作者：Jeanne Tie, Joshua David Cohen, Yuxuan Wang, Michael Christie, Koen Simons, Margaret S. Lee, Rachel Wong, Suzanne Kosmider, Sumitra S. Ananda, Joseph James McKendrick, Belinda Lee, Jin Hee Cho, Ian G. Faragher, Ian T. Jones, Janine Ptak, Mary J. Schaeffer, Natalie Silliman, Lisa Dobbyn, Li Lü, Cristian Tomasetti, Nicholas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein, Peter Gibbs · 发表于：JAMA Oncology · 年份：2019 · DOI：10.1001/jamaoncol.2019.3616 · 被引用次数：703 · 研究领域：Cancer Genomics and Diagnostics、Genetic factors in colorectal cancer、Cancer Cells and Metastasis

Importance: Adjuvant chemotherapy in patients with stage III colon cancer prevents recurrence by eradicating minimal residual disease. However, which patients remain at high risk of recurrence after completing standard adjuvant treatment cannot currently be determined. Postsurgical circulating tumor DNA (ctDNA) analysis can detect minimal residual disease and is associated with recurrence in colorectal cancers. Objective: To determine whether serial postsurgical and postchemotherapy ctDNA analysis could provide a real-time indication of adjuvant therapy efficacy in stage III colon cancer. Design, Setting, and Participants: This multicenter, Australian, population-based cohort biomarker study recruited 100 consecutive patients with newly diagnosed stage III colon cancer planned for 24 weeks of adjuvant chemotherapy from November 1, 2014, through May 31, 2017. Patients with another malignant neoplasm diagnosed within the last 3 years were excluded. Median duration of follow-up was 28.9 months (range, 11.6-46.4 months). Physicians were blinded to ctDNA results. Data were analyzed from December 10, 2018, through June 23, 2019. Exposures: Serial plasma samples were collected after surgery and after chemotherapy. Somatic mutations in individual patients' tumors were identified via massively parallel sequencing of 15 genes commonly mutated in colorectal cancer. Personalized assays were designed to quantify ctDNA. Main Outcomes and Measures: Detection of ctDNA and recurrence-free int...