TY - JOUR
T1 - Optimizing Screening for Colorectal Cancer
T2 - An Algorithm Combining Fecal Immunochemical Test, Blood-Based Cancer-Associated Proteins and Demographics to Reduce Colonoscopy Burden
AU - Petersen, Mathias M.
AU - Kleif, Jakob
AU - Jørgensen, Lars N.
AU - Hendel, Jakob W.
AU - Seidelin, Jakob B.
AU - Madsen, Mogens R.
AU - Vilandt, Jesper
AU - Brandsborg, S. ren
AU - Rasmussen, J. rn S.
AU - Andersen, Lars M.
AU - Khalid, Ali
AU - Ferm, Linnea
AU - Gawel, Susan H.
AU - Martens, Frans
AU - Andersen, Berit
AU - Rasmussen, Morten
AU - Davis, Gerard J.
AU - Christensen, Ib J.
AU - Therkildsen, Christina
N1 - Funding Information:
We thank the patients for their participation and the research nurses, secretaries and technicians at the participating hospitals for their skillful work with subject recruitment, blood collection and data recording. This work was supported by The Andersen Foundation, The Augustinus Foundation, The Beckett Foundation, The Inger Bonnéns Fund, The Hans & Nora Buchards Fund, The Walter Christensen Fund, The P.M. Christiansen Fund, The Kong Chr. X's Fund, The Aase & Ejnar Danielsens Fund, The Family Erichsens Fund, The Knud & Edith Eriksens Fund, The Svend Espersens Fund, The Elna & Jørgen Fagerholts Cancer Research Foundation, The Sofus Carl Emil Friis Scholarship, The Torben & Alice Frimodts Fund, The Eva & Henry Frænkels Fund, The Gangsted Foundation, Thora & Viggo Groves Memorial Scholarship, The H-Foundation, Erna Hamiltons Scholarship, Søren & Helene Hempels Scholarship, The Sven & Ina Hansens Fund, The Henrik Henriksen Fund, Carl & Ellen Hertz’ Scholarship, Jørgen Holm & Elisa F. Hansen Memorial Scholarship, The Jochum Foundation, The KID Foundation, The Kornerup Foundation, The Linex Foundation, The Dagmar Marshalls Fund, The Midtjyske Fund, The Axel Muusfeldts Fund, The Børge Nielsens Fund, Michael Hermann Nielsens Memorial Scholarship, The Arvid Nilssons Fund, The Obelske Family Fund, The Krista & Viggo Petersens Fund, The Willy & Ingeborg Reinhards Fund, The Kathrine & Vigo Skovgaards Fund, The Toyota Foundation, The Vissing Foundation, The P. Carl Petersen Fund, The Danish Cancer Research Foundation, Hvidovre Hospitals Research Pool.
Publisher Copyright:
© 2023 The Authors
PY - 2023/6
Y1 - 2023/6
N2 - Background: Fecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT
+) screening population and thereby reduce the colonoscopy burden. Materials and methods: From the Danish National Colorectal Cancer Screening Program, 4048 FIT
+ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling. Results: The discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs. Conclusion: A screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.
AB - Background: Fecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT
+) screening population and thereby reduce the colonoscopy burden. Materials and methods: From the Danish National Colorectal Cancer Screening Program, 4048 FIT
+ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling. Results: The discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs. Conclusion: A screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.
KW - Biomarkers
KW - Colorectal neoplasia
KW - Early detection
KW - Logistic regression modeling
KW - Minimal invasive liquid biopsy
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85149675107&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/36878807
U2 - 10.1016/j.clcc.2023.02.001
DO - 10.1016/j.clcc.2023.02.001
M3 - Article
C2 - 36878807
SN - 1533-0028
VL - 22
SP - 199
EP - 210
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
IS - 2
ER -