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JAMA Oncol. 2019 May 9. doi: 10.1001/jamaoncol.2019.0512. [Epub ahead of print]

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

Author information

1
Ludwig Center for Cancer Genetics and Therapeutics, and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
2
Biostatistics Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
3
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland.
4
PapGene Inc, Baltimore, Maryland.
5
Division of Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
6
Department of Medical Oncology, Western Health, Melbourne, Victoria, Australia.
7
Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
8
Department of Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
9
Division of Biostatistics and Bioinformatics, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
10
Howard Hughes Medical Institute, Baltimore, Maryland.
11
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

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 (nā€‰=ā€‰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.

PMID:
31070668
PMCID:
PMC6512291
[Available on 2020-05-09]
DOI:
10.1001/jamaoncol.2019.0512

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