Circulating epigenetic biomarkers for detection of recurrent colorectal cancer

Erin L. Symonds, Susanne K. Pedersen, David Murray, Susan E. Byrne, Amitesh Roy, Christos Karapetis, Paul Hollington, Philippa Rabbitt, Frederick S. Jones, Lawrence LaPointe, Eva Segelov, Graeme P. Young

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    Abstract

    BACKGROUND

    The sensitive detection of recurrent colorectal cancer (CRC) by the measurement of circulating tumor DNA (ctDNA) might improve the chance of a cure. This study compared a quantitative methylated ctDNA test with carcinoembryonic antigen (CEA) in the setting of surveillance for recurrence.

    METHODS

    Blood samples collected either during surveillance or within 12 months of the confirmation of recurrence were assayed for ctDNA (methylated branched‐chain amino acid transaminase 1 [BCAT1]/Ikaros family zinc‐finger 1 protein [IKZF1]) and CEA. The optimal ctDNA threshold was determined by receiver operating characteristic analysis, and the test performance for the detection of recurrence was compared with CEA (5 ng/mL threshold).

    RESULTS

    The study cohort comprised 144 eligible patients and included 50 recurrence events. The sensitivity of the methylated ctDNA test for recurrence was 66.0% (95% confidence interval [CI], 57.1%‐69.3%), which was significantly higher than the sensitivity of CEA (31.9%; 95% CI, 22.8%‐36.6%; P < .001). The sensitivity for resectable recurrence (n = 20) was also higher (ctDNA, 60.0%; CEA, 20.0%; P = .01). The specificity did not differ between the tests (ctDNA, 97.9%; 95% CI, 93.2%‐99.6%; CEA, 96.4%; 95% CI, 91.4%‐99.0%). When adjustments were made for other predictors of the presence of recurrence, a positive ctDNA test was an independent predictor (odds ratio, 155.7; 95% CI, 17.9‐1360.6; P < .001), whereas CEA was not (odds ratio, 2.5; 95% CI, 0.3‐20.6; P = .407).

    CONCLUSIONS

    The quantitative ctDNA test showed superior sensitivity in comparison with CEA without a difference in the specificity for detecting recurrent CRC. Longitudinal studies are warranted to further assess the utility (specifically the survival benefit) of methylated BCAT1/IKZF1 ctDNA in the surveillance of patients with CRC.

    Original languageEnglish
    Pages (from-to)1460-1469
    Number of pages10
    JournalCancer
    Volume126
    Issue number7
    Early online date7 Jan 2020
    DOIs
    Publication statusPublished - 1 Apr 2020

    Bibliographical note

    This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

    Keywords

    • blood test
    • branched-chain amino acid transaminase 1 (BCAT1)
    • circulating tumor DNA (ctDNA)
    • colorectal cancer
    • Ikaros family zinc-finger 1 protein (IKZF1)
    • methylation
    • recurrence

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  • Cite this

    Symonds, E. L., Pedersen, S. K., Murray, D., Byrne, S. E., Roy, A., Karapetis, C., Hollington, P., Rabbitt, P., Jones, F. S., LaPointe, L., Segelov, E., & Young, G. P. (2020). Circulating epigenetic biomarkers for detection of recurrent colorectal cancer. Cancer, 126(7), 1460-1469. https://doi.org/10.1002/cncr.32695