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Sci Transl Med. 2016 Jul 6;8(346):346ra92. doi: 10.1126/scitranslmed.aaf6219.

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

Author information

1
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.
2
Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21287, USA.
3
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.
4
Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
5
PapGene Inc., Baltimore, MD 21211, USA.
6
Melbourne EpiCentre, Department of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia.
7
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.
8
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.
9
Department of Medical Oncology, Western Health, St Albans, Victoria 3021, Australia.
10
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.
11
Department of Medical Oncology, Eastern Health, Box Hill, Victoria 3128, Australia.
12
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.
13
Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria 3010, Australia. Department of Surgery, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
14
Department of Medical Oncology, Alfred Hospital, Melbourne, Victoria 3004, Australia.
15
Department of Medical Oncology, Warrnambool Hospital, Warrnambool, Victoria 3280, Australia.
16
Department of Medical Oncology, Queen Elizabeth Hospital and University of Adelaide, Adelaide, South Australia 3174, Australia.
17
Ludwig Institute for Cancer Research, New York, NY 10017, USA.
18
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.
19
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.

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.

PMID:
27384348
PMCID:
PMC5346159
DOI:
10.1126/scitranslmed.aaf6219
[Indexed for MEDLINE]
Free PMC Article

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