Article

Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer

Jeanne TieDepartment of Medical Oncology,Yuxuan WangLudwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USACristian TomasettiDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USALu LiDivision of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USASimeon SpringerLudwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USAIsaac KindePapGene Inc., Baltimore, MD 21211, USANatalie SillimanLudwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USAMark TaceyMelbourne EpiCentre, Department of Medicine, University of Melbourne, Parkville, Victoria 3010, AustraliaHui‐Li WongDepartment of Medical Oncology,Michael ChristieDepartment of Medical Oncology,Suzanne KosmiderDepartment of Medical Oncology, Western Health, St Albans, Victoria 3021, AustraliaIain SkinnerDepartment of Medical Oncology, Western Health, St Albans, Victoria 3021, AustraliaRachel WongDepartment of Medical Oncology, Eastern Health, Box Hill, Victoria 3128, AustraliaMalcolm SteelDepartment of Medical Oncology, Eastern Health, Box Hill, Victoria 3128, AustraliaBen TranDepartment of Medical Oncology,Jayesh DesaiDepartment of Medical Oncology,Ian T. JonesDepartment of Surgery, Royal Melbourne Hospital, Parkville, Victoria 3050, AustraliaAndrew HaydonDepartment of Medical Oncology, Alfred Hospital, Melbourne, Victoria 3004, AustraliaTheresa HayesDepartment of Medical Oncology, Warrnambool Hospital, Warrnambool, Victoria 3280, AustraliaTimothy PriceDepartment of Medical Oncology, Queen Elizabeth Hospital and University of Adelaide, Adelaide, South Australia 3174, AustraliaRobert L. StrausbergLudwig Institute for Cancer Research, New York, NY 10017, USALuis A. DíazLudwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USANickolas PapadopoulosLudwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USAKenneth W. KinzlerLudwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USABert VogelsteinLudwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USAPeter GibbsDepartment of Medical Oncology,

2016en

ABI

Abstract

Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing-based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.

Identifiers

DOI: 10.1126/scitranslmed.aaf6219

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