title: Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.
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.
authors.affiliation: Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia. Department of Medical Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia. jeanne.tie@mh.org.au vogelbe@jhmi.edu peter.gibbs@mh.org.au.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Tie
authors.affiliation: Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Tomasetti
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
authors.forename: Simeon
authors.initials: S
authors.lastname: Springer
authors.affiliation: PapGene Inc., Baltimore, MD 21211, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Kinde
authors.affiliation: Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Silliman
authors.affiliation: Melbourne EpiCentre, Department of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Tacey
authors.affiliation: Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Medical Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Wong
authors.affiliation: Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Medical Oncology, Department of Pathology, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Christie
authors.affiliation: Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kosmider
authors.affiliation: Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia.
authors.forename: Iain
authors.initials: I
authors.lastname: Skinner
authors.affiliation: Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Medical Oncology, Eastern Health, Box Hill, Victoria 3128, Australia. Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Rachel
authors.initials: R
authors.lastname: Wong
authors.affiliation: Department of Medical Oncology, Eastern Health, Box Hill, Victoria 3128, Australia.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Steel
authors.affiliation: Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia. Department of Medical Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Tran
authors.affiliation: Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Medical Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Desai
authors.affiliation: Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia. Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Jones
authors.affiliation: Department of Medical Oncology, Alfred Hospital, Melbourne, Victoria 3004, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Haydon
authors.affiliation: Department of Medical Oncology, Warrnambool Hospital, Warrnambool, Victoria 3280, Australia.
authors.forename: Theresa
authors.initials: T
authors.lastname: Hayes
authors.affiliation: Department of Medical Oncology, Queen Elizabeth Hospital and University of Adelaide, Adelaide, South Australia 3174, Australia.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Price
authors.affiliation: Ludwig Institute for Cancer Research, New York, NY 10017, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Strausberg
authors.affiliation: Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.affiliation: Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
authors.forename: Nickolas
authors.initials: N
authors.lastname: Papadopoulos
authors.affiliation: Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Kinzler
authors.affiliation: Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA. jeanne.tie@mh.org.au vogelbe@jhmi.edu peter.gibbs@mh.org.au.
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.affiliation: Division of Systems Biology and Personalised Medicine, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia. Department of Medical Oncology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia. Ludwig Institute for Cancer Research, New York, NY 10017, USA. jeanne.tie@mh.org.au vogelbe@jhmi.edu peter.gibbs@mh.org.au.
authors.forename: Peter
authors.initials: P
authors.lastname: Gibbs
mesh_terms: D000074141:Circulating Tumor DNA / Q000032:analysis / Q000235:genetics*; D003110:Colonic Neoplasms / Q000097:blood / Q000235:genetics* / Q000601:surgery; D018572:Disease-Free Survival; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000235:genetics; D009367:Neoplasm Staging; D018365:Neoplasm, Residual / Q000097:blood / Q000235:genetics* / Q000601:surgery; D016016:Proportional Hazards Models; D011446:Prospective Studies
chemical_list: D000074141:Circulating Tumor DNA