Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening

Mathias M Petersen; Jakob Kleif; Jason Liggett; Morten Rasmussen; Lars N Jørgensen; Jesper Vilandt; Jakob B Seidelin; Carla M T Beertsen; Annemieke C Heijboer; Claudia Jaensch; Peter Bondeven; Kåre A Gotschalck; Uffe Schou Løve; Susan H Gawel; Berit Andersen; Ib J Christensen; Eric Mayer; Gerard J Davis; Christina Therkildsen

doi:10.1016/j.gie.2024.06.015

Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening

Mathias M Petersen, Jakob Kleif, Jason Liggett, Morten Rasmussen, Lars N Jørgensen, Jesper Vilandt, Jakob B Seidelin, Carla M T Beertsen, Annemieke C Heijboer, Claudia Jaensch, Peter Bondeven, Kåre A Gotschalck, Uffe Schou Løve, Susan H Gawel, Berit Andersen, Ib J Christensen, Eric Mayer, Gerard J Davis, Christina Therkildsen

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

BACKGROUND AND AIMS: Implementation of screening modalities have reduced the burden of colorectal cancer (CRC), but high false positive rates pose a major problem for colonoscopy capacity. We aimed to create a tailored screening algorithm that expands the fecal immunochemical test (FIT) with a blood specimen and current age to improve selection of individuals for diagnostic colonoscopy.

METHODS: In this prospective multi-center study, eight blood-based biomarkers (CEA, Ferritin, hsCRP, HE4, Cyfra21-1, Hepsin, IL-8 and OPG) were investigated in 1,977 FIT positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on ARCHITECT i2000®, ARCHITECT c8000® or Luminex xMAP® machines. FIT analyses and blood-based biomarker data were combined with clinical data (i.e., age and colonoscopy findings) in a cross-validated logistic regression model (algorithm) benchmarked against a model solely using the FIT result (FIT model) applying different cutoffs for FIT positivity.

RESULTS: The cohort included individuals with CRC (n = 240), adenomas (n = 938) or no neoplastic lesions (n = 799). The cross-validated algorithm combining the eight biomarkers, quantitative FIT result and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (AUC 0.77 versus 0.67, p < 0.001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the AUCs were 0.68 versus 0.64 for the algorithm and FIT model, respectively.

CONCLUSIONS: The algorithm presented here can improve patient allocation to colonoscopy, reducing colonoscopy burden without compromising cancer and adenomas detection rates or vice versa.

Originalsprog	Engelsk
Tidsskrift	Gastrointestinal Endoscopy
ISSN	0016-5107
DOI	https://doi.org/10.1016/j.gie.2024.06.015
Status	E-pub ahead of print - 20 jun. 2024

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10.1016/j.gie.2024.06.015

Citationsformater

Petersen, M. M., Kleif, J., Liggett, J., Rasmussen, M., Jørgensen, L. N., Vilandt, J., Seidelin, J. B., Beertsen, C. M. T., Heijboer, A. C., Jaensch, C., Bondeven, P., Gotschalck, K. A., Løve, U. S., Gawel, S. H., Andersen, B., Christensen, I. J., Mayer, E., Davis, G. J., & Therkildsen, C. (2024). Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening. Gastrointestinal Endoscopy. Advance online publication. https://doi.org/10.1016/j.gie.2024.06.015

@article{244d5035df484a59bac0d2eb443b0a2a,

title = "Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening",

abstract = "BACKGROUND AND AIMS: Implementation of screening modalities have reduced the burden of colorectal cancer (CRC), but high false positive rates pose a major problem for colonoscopy capacity. We aimed to create a tailored screening algorithm that expands the fecal immunochemical test (FIT) with a blood specimen and current age to improve selection of individuals for diagnostic colonoscopy.METHODS: In this prospective multi-center study, eight blood-based biomarkers (CEA, Ferritin, hsCRP, HE4, Cyfra21-1, Hepsin, IL-8 and OPG) were investigated in 1,977 FIT positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on ARCHITECT i2000{\textregistered}, ARCHITECT c8000{\textregistered} or Luminex xMAP{\textregistered} machines. FIT analyses and blood-based biomarker data were combined with clinical data (i.e., age and colonoscopy findings) in a cross-validated logistic regression model (algorithm) benchmarked against a model solely using the FIT result (FIT model) applying different cutoffs for FIT positivity.RESULTS: The cohort included individuals with CRC (n = 240), adenomas (n = 938) or no neoplastic lesions (n = 799). The cross-validated algorithm combining the eight biomarkers, quantitative FIT result and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (AUC 0.77 versus 0.67, p < 0.001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the AUCs were 0.68 versus 0.64 for the algorithm and FIT model, respectively.CONCLUSIONS: The algorithm presented here can improve patient allocation to colonoscopy, reducing colonoscopy burden without compromising cancer and adenomas detection rates or vice versa.",

author = "Petersen, {Mathias M} and Jakob Kleif and Jason Liggett and Morten Rasmussen and J{\o}rgensen, {Lars N} and Jesper Vilandt and Seidelin, {Jakob B} and Beertsen, {Carla M T} and Heijboer, {Annemieke C} and Claudia Jaensch and Peter Bondeven and Gotschalck, {K{\aa}re A} and L{\o}ve, {Uffe Schou} and Gawel, {Susan H} and Berit Andersen and Christensen, {Ib J} and Eric Mayer and Davis, {Gerard J} and Christina Therkildsen",

year = "2024",

month = jun,

day = "20",

doi = "10.1016/j.gie.2024.06.015",

language = "English",

journal = "Gastrointestinal Endoscopy",

issn = "0016-5107",

publisher = "Mosby, Inc",

}

Petersen, MM, Kleif, J, Liggett, J, Rasmussen, M, Jørgensen, LN, Vilandt, J, Seidelin, JB, Beertsen, CMT, Heijboer, AC, Jaensch, C, Bondeven, P, Gotschalck, KA, Løve, US, Gawel, SH, Andersen, B, Christensen, IJ, Mayer, E, Davis, GJ & Therkildsen, C 2024, 'Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening', Gastrointestinal Endoscopy. https://doi.org/10.1016/j.gie.2024.06.015

Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening. / Petersen, Mathias M; Kleif, Jakob; Liggett, Jason et al.
I: Gastrointestinal Endoscopy, 20.06.2024.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening

AU - Petersen, Mathias M

AU - Kleif, Jakob

AU - Liggett, Jason

AU - Rasmussen, Morten

AU - Jørgensen, Lars N

AU - Vilandt, Jesper

AU - Seidelin, Jakob B

AU - Beertsen, Carla M T

AU - Heijboer, Annemieke C

AU - Jaensch, Claudia

AU - Bondeven, Peter

AU - Gotschalck, Kåre A

AU - Løve, Uffe Schou

AU - Gawel, Susan H

AU - Andersen, Berit

AU - Christensen, Ib J

AU - Mayer, Eric

AU - Davis, Gerard J

AU - Therkildsen, Christina

PY - 2024/6/20

Y1 - 2024/6/20

N2 - BACKGROUND AND AIMS: Implementation of screening modalities have reduced the burden of colorectal cancer (CRC), but high false positive rates pose a major problem for colonoscopy capacity. We aimed to create a tailored screening algorithm that expands the fecal immunochemical test (FIT) with a blood specimen and current age to improve selection of individuals for diagnostic colonoscopy.METHODS: In this prospective multi-center study, eight blood-based biomarkers (CEA, Ferritin, hsCRP, HE4, Cyfra21-1, Hepsin, IL-8 and OPG) were investigated in 1,977 FIT positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on ARCHITECT i2000®, ARCHITECT c8000® or Luminex xMAP® machines. FIT analyses and blood-based biomarker data were combined with clinical data (i.e., age and colonoscopy findings) in a cross-validated logistic regression model (algorithm) benchmarked against a model solely using the FIT result (FIT model) applying different cutoffs for FIT positivity.RESULTS: The cohort included individuals with CRC (n = 240), adenomas (n = 938) or no neoplastic lesions (n = 799). The cross-validated algorithm combining the eight biomarkers, quantitative FIT result and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (AUC 0.77 versus 0.67, p < 0.001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the AUCs were 0.68 versus 0.64 for the algorithm and FIT model, respectively.CONCLUSIONS: The algorithm presented here can improve patient allocation to colonoscopy, reducing colonoscopy burden without compromising cancer and adenomas detection rates or vice versa.

AB - BACKGROUND AND AIMS: Implementation of screening modalities have reduced the burden of colorectal cancer (CRC), but high false positive rates pose a major problem for colonoscopy capacity. We aimed to create a tailored screening algorithm that expands the fecal immunochemical test (FIT) with a blood specimen and current age to improve selection of individuals for diagnostic colonoscopy.METHODS: In this prospective multi-center study, eight blood-based biomarkers (CEA, Ferritin, hsCRP, HE4, Cyfra21-1, Hepsin, IL-8 and OPG) were investigated in 1,977 FIT positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on ARCHITECT i2000®, ARCHITECT c8000® or Luminex xMAP® machines. FIT analyses and blood-based biomarker data were combined with clinical data (i.e., age and colonoscopy findings) in a cross-validated logistic regression model (algorithm) benchmarked against a model solely using the FIT result (FIT model) applying different cutoffs for FIT positivity.RESULTS: The cohort included individuals with CRC (n = 240), adenomas (n = 938) or no neoplastic lesions (n = 799). The cross-validated algorithm combining the eight biomarkers, quantitative FIT result and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (AUC 0.77 versus 0.67, p < 0.001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the AUCs were 0.68 versus 0.64 for the algorithm and FIT model, respectively.CONCLUSIONS: The algorithm presented here can improve patient allocation to colonoscopy, reducing colonoscopy burden without compromising cancer and adenomas detection rates or vice versa.

U2 - 10.1016/j.gie.2024.06.015

DO - 10.1016/j.gie.2024.06.015

M3 - Journal article

C2 - 38908453

SN - 0016-5107

JO - Gastrointestinal Endoscopy

JF - Gastrointestinal Endoscopy

ER -

Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening

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