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Original Investigation
May 9, 2019

Prognostic Potential of Circulating Tumor DNA Measurement in Postoperative Surveillance of Nonmetastatic Colorectal Cancer

Author Affiliations
  • 1Ludwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 2Biostatistics Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 3Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 4PapGene Inc, Baltimore, Maryland
  • 5Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  • 6Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia
  • 7Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia
  • 8Department of Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  • 9Division of Biostatistics and Bioinformatics, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 10Howard Hughes Medical Institute, Baltimore, Maryland
  • 11Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
JAMA Oncol. 2019;5(8):1118-1123. doi:10.1001/jamaoncol.2019.0512
Key Points

Question  Can circulating tumor DNA provide a measurement of disease burden to stratify the risk of recurrence in patients with resected colorectal cancer during postoperative surveillance?

Findings  In this study of 58 patients with resected, nonmetastatic colorectal cancer, 45 patients with negative circulating tumor DNA levels were recurrence-free, whereas 10 of 13 patients with positive circulating tumor DNA levels relapsed during follow-up. Circulating tumor DNA positivity preceded radiologic or clinical evidence of recurrence in all 10 patients by a median of 3 months.

Meaning  Serial circulating tumor DNA levels during postoperative surveillance can be used as a triage test to stratify patients with resected colorectal cancer on the basis of their risk of recurrence.

Abstract

Importance  For patients with resected, nonmetastatic colorectal cancer (CRC), the optimal surveillance protocol remains unclear.

Objective  To evaluate whether serial circulating tumor DNA (ctDNA) levels detected disease recurrence earlier, compared with conventional postoperative surveillance, in patients with resected CRC.

Design, Setting, and Participants  This study included patients (n = 58) with stage I, II, or III CRC who underwent radical surgical resection at 4 Swedish hospitals from February 2, 2007, to May 8, 2013. Eighteen patients received adjuvant chemotherapy at the discretion of their clinicians, who were blinded to the ctDNA results. Blood samples were collected at 1 month after the surgical procedure and every 3 to 6 months thereafter for ctDNA analysis. Patients were followed up until metachronous metastases were detected, or for a median of 49 months. Data analysis was performed from March 1, 2009, to June 23, 2018.

Main Outcomes and Measures  Sensitivity and timing of ctDNA positivity were compared with those of conventional surveillance modalities (computed tomographic scans and serum carcinoembryonic antigen tests) for the detection of disease recurrence.

Results  This study included 319 blood samples from 58 patients, with a median (range) age of 69 (47-83) years and 34 males (59%). The recurrence rate among patients with positive ctDNA levels was 77% (10 of 13 patients). Positive ctDNA preceded radiologic and clinical evidence of recurrence by a median of 3 months. Of the 45 patients with negative ctDNA throughout follow-up, none (0%; 95% CI, 0%-7.9%) experienced a relapse, with a median follow-up of 49 months. However, 3 (6%; 95% CI, 1.3%-17%) of the 48 patients without relapse had a positive ctDNA result, which subsequently fell to undetectable levels during follow-up.

Conclusion and Relevance  Although these findings need to be validated in a larger, prospective trial, they suggest that ctDNA analysis could complement conventional surveillance strategies as a triage test to stratify patients with resected CRC on the basis of risk of disease recurrence.

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