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. 2019 Aug 1;5(8):1118-1123.
doi: 10.1001/jamaoncol.2019.0512.

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

Yuxuan Wang  1 , Lu Li  2 , Joshua D Cohen  1   3 , Isaac Kinde  4 , Janine Ptak  1 , Maria Popoli  1 , Joy Schaefer  1 , Natalie Silliman  1 , Lisa Dobbyn  1 , Jeanne Tie  5   6   7   8 , Peter Gibbs  5   6   7 , Cristian Tomasetti  2   9 , Kenneth W Kinzler  1 , Nickolas Papadopoulos  1 , Bert Vogelstein  1   10 , Louise Olsson  11
Affiliations

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

Yuxuan Wang et al. JAMA Oncol. .

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Kinde reported personal fees and other from PapGene Inc outside of the submitted work; and a patent to US20140227705A1 issued, licensed, and with royalties paid. Dr Tomasetti reported royalties from PapGene. Drs Kinzler and Vogelstein reported book royalties from McGraw Hill, royalties from Sysmex Corporation, Qiagen GmbH, Good Start Genetics LLC, Personal Genome Diagnostics, PapGene Inc, BioMed Valley Discoveries Inc, Pierce Biotechnology Inc, Life Technologies Corporation. Drs Kinzler and Vogelstein are founders and equity holders of PapGene Inc, scientific founder and equity holder of Personal Genome Diagnostics, scientific founders of Inostics, paid consultants to Sysmex, founding advisers to Morphotek, paid consultants to Eisai, founders and equity holders of Neophore, advisers and equity holders of Cage Pharma, and advisors and equity holders of Nexus. Dr Papadopoulos reported royalties from Qiagen GmbH, Good Start Genetics LLC, Personal Genome Diagnostics, and PapGene Inc. Dr Papadopoulos is a founder and equity holder of PapGene Inc and Personal Genome Diagnostics, and equity holder of Neophore. The terms of these arrangements are managed by the Johns Hopkins University in accordance with its conflict of interest policies. No other disclosures were reported.

Figures

Figure.
Figure.. Patient Enrollment, Follow-up, and Outcome
During follow-up, blood samples were collected 1 month after the surgical procedure, and then every 3 to 6 months. Computed tomography scans were performed every 6 to 12 months. Eighteen of the 58 patients received adjuvant chemotherapy at the discretion of their oncologist, who was blinded to the circulating tumor DNA (ctDNA) results. Each patient cohort (with or without adjuvant chemotherapy) was further divided by disease recurrence and ctDNA status.
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References

    1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30. doi:10.3322/caac.21387 - DOI - PubMed
    1. Schmoll HJ, Van Cutsem E, Stein A, et al. . ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol. 2012;23(10):2479-2516. doi:10.1093/annonc/mds236 - DOI - PubMed
    1. Young PE, Womeldorph CM, Johnson EK, et al. . Early detection of colorectal cancer recurrence in patients undergoing surgery with curative intent: current status and challenges. J Cancer. 2014;5(4):262-271. doi:10.7150/jca.7988 - DOI - PMC - PubMed
    1. Goldberg RM, Fleming TR, Tangen CM, et al. . Surgery for recurrent colon cancer: strategies for identifying resectable recurrence and success rates after resection. Eastern Cooperative Oncology Group, the North Central Cancer Treatment Group, and the Southwest Oncology Group. Ann Intern Med. 1998;129(1):27-35. doi:10.7326/0003-4819-129-1-199807010-00007 - DOI - PubMed
    1. McAfee MK, Allen MS, Trastek VF, Ilstrup DM, Deschamps C, Pairolero PC. Colorectal lung metastases: results of surgical excision. Ann Thorac Surg. 1992;53(5):780-785. doi:10.1016/0003-4975(92)91435-C - DOI - PubMed