@article{2fd91ef955594c66b49f3dd83958afd2,
title = "Multitarget Stool DNA Test Performance in an Average-Risk Colorectal Cancer Screening Population",
abstract = "INTRODUCTION: We set out to evaluate the performance of a multitarget stool DNA (MT-sDNA) in an average-risk colonoscopy-controlled colorectal cancer (CRC) screening population. MT-sDNA stool test results were evaluated against fecal immunochemical test (FIT) results for the detection of different lesions, including molecularly defined high-risk adenomas and several other tumor characteristics.METHODS: Whole stool samples (n = 1,047) were prospectively collected and subjected to an MT-sDNA test, which tests for KRAS mutations, NDRG4 and BMP3 promoter methylation, and hemoglobin. Results for detecting CRC (n = 7), advanced precancerous lesions (advanced adenoma [AA] and advanced serrated polyps; n = 119), and non-AAs (n = 191) were compared with those of FIT alone (thresholds of 50, 75, and 100 hemoglobin/mL). AAs with high risk of progression were defined by the presence of specific DNA copy number events as measured by low-pass whole genome sequencing.RESULTS: The MT-sDNA test was more sensitive than FIT alone in detecting advanced precancerous lesions (46% (55/119) vs 27% (32/119), respectively, P<0.001). Specificities among individuals with nonadvanced or negative findings (controls) were 89% (791/888) and 93% (828/888) for MT-sDNA and FIT testing, respectively. A positive MT-sDNA test was associated with multiple lesions (P = 0.005), larger lesions (P = 0.03), and lesions with tubulovillous architecture (P = 0.04). The sensitivity of the MT-sDNA test or FIT in detecting individuals with high-risk AAs (n = 19) from individuals with low-risk AAs (n = 52) was not significantly different.DISCUSSION: In an average-risk screening population, the MT-sDNA test has an increased sensitivity for detecting advanced precancerous lesions compared with FIT alone. AAs with a high risk of progression were not detected with significantly higher sensitivity by MT-sDNA or FIT.",
keywords = "ADENOMA, BIOMARKER, COLONOSCOPY, IMPACT, METHYLATION, MORTALITY, PROGRESSION",
author = "Bosch, {L. J. W.} and V. Melotte and S. Mongera and Daenen, {K. L. J.} and Coupe, {V. M. H.} and {van Turenhout}, {S. T.} and Stoop, {E. M.} and {de Wijkerslooth}, {T. R.} and Mulder, {C. J. J.} and C. Rausch and Kuipers, {E. J.} and E. Dekker and Domanico, {M. J.} and Lidgard, {G. P.} and Berger, {B. M.} and {van Engeland}, M. and B. Carvalho and Meijer, {G. A.}",
note = "Funding Information: Financial support: This study was performed within the framework of the Center for Translational Molecular Medicine (DeCoDe project, grant 030101), supported by Exact Sciences Corporation and supported by a SU2C-DCS International Translational Cancer Research Dream Team Grant (SU2C-AACR-DT1415, MEDOCC). Stand Up to Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research and the Dutch Cancer Society. The study was further funded by The Netherlands Organisation for Health Research and Development of the Dutch Ministry of Health (ZonMW 120720012 and 121010005) and the Nuts Ohra Foundation (Amsterdam, the Netherlands). Funding Information: Guarantor of the article: Gerrit A. Meijer, MD, PhD. Specific author contributions: L.J.W.B. and V.M., contributed equally to this work. L.J.W.B., V.M., E.D., B.M.B., M.v.E., B.C., and G.A.M.: study concept and design. L.J.W.B., V.M., S.M., K.L.J.D., S.T.v.T., E.M.S., T.R.d.W., C.R., and M.J.D.: acquisition of data. L.J.W.B., V.M., and B.C.: interpretation of data. L.J.W.B. and V.M.: drafting of manuscript. All authors: critical revision. L.J.W.B. and V.M.H.C.: statistical analysis. E.J.K. and G.A.M.: obtained funding. B.M.B. and G.A.M.: study supervision. Financial support: This study was performed within the framework of the Center for Translational Molecular Medicine (DeCoDe project, grant 030–101), supported by Exact Sciences Corporation and supported by a SU2C-DCS International Translational Cancer Research Dream Team Grant (SU2C-AACR-DT1415, MEDOCC). Stand Up to Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research and the Dutch Cancer Society. The study was further funded by The Netherlands Organisation for Health Research and Development of the Dutch Ministry of Health (ZonMW 120720012 and 121010005) and the Nuts Ohra Foundation (Amsterdam, the Netherlands). Potential competing interests: B.M.B., G.P.L., and M.J.D. are employees and equity holders of Exact Sciences Corporation. Publisher Copyright: {\textcopyright} 2019 by The American College of Gastroenterology.",
year = "2019",
month = dec,
doi = "10.14309/ajg.0000000000000445",
language = "English",
volume = "114",
pages = "1909--1918",
journal = "American Journal of Gastroenterology",
issn = "0002-9270",
publisher = "Nature Publishing Group",
number = "12",
}