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Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women

Longitudinal CA125 algorithms are the current basis of ovarian cancer screening. We report on longitudinal algorithms incorporating multiple markers. In the multimodal arm of United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 50,640 postmenopausal women underwent annual screen...

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Autores principales: Gentry-Maharaj, Aleksandra, Blyuss, Oleg, Ryan, Andy, Burnell, Matthew, Karpinskyj, Chloe, Gunu, Richard, Kalsi, Jatinderpal K., Dawnay, Anne, Marino, Ines P., Manchanda, Ranjit, Lu, Karen, Yang, Wei-Lei, Timms, John F., Parmar, Mahesh, Skates, Steven J., Bast, Robert C., Jacobs, Ian J., Zaikin, Alexey, Menon, Usha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409061/
https://www.ncbi.nlm.nih.gov/pubmed/32708856
http://dx.doi.org/10.3390/cancers12071931
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author Gentry-Maharaj, Aleksandra
Blyuss, Oleg
Ryan, Andy
Burnell, Matthew
Karpinskyj, Chloe
Gunu, Richard
Kalsi, Jatinderpal K.
Dawnay, Anne
Marino, Ines P.
Manchanda, Ranjit
Lu, Karen
Yang, Wei-Lei
Timms, John F.
Parmar, Mahesh
Skates, Steven J.
Bast, Robert C.
Jacobs, Ian J.
Zaikin, Alexey
Menon, Usha
author_facet Gentry-Maharaj, Aleksandra
Blyuss, Oleg
Ryan, Andy
Burnell, Matthew
Karpinskyj, Chloe
Gunu, Richard
Kalsi, Jatinderpal K.
Dawnay, Anne
Marino, Ines P.
Manchanda, Ranjit
Lu, Karen
Yang, Wei-Lei
Timms, John F.
Parmar, Mahesh
Skates, Steven J.
Bast, Robert C.
Jacobs, Ian J.
Zaikin, Alexey
Menon, Usha
author_sort Gentry-Maharaj, Aleksandra
collection PubMed
description Longitudinal CA125 algorithms are the current basis of ovarian cancer screening. We report on longitudinal algorithms incorporating multiple markers. In the multimodal arm of United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 50,640 postmenopausal women underwent annual screening using a serum CA125 longitudinal algorithm. Women (cases) with invasive tubo-ovarian cancer (WHO 2014) following outcome review with stored annual serum samples donated in the 5 years preceding diagnosis were matched 1:1 to controls (no invasive tubo-ovarian cancer) in terms of the number of annual samples and age at randomisation. Blinded samples were assayed for serum human epididymis protein 4 (HE4), CA72-4 and anti-TP53 autoantibodies. Multimarker method of mean trends (MMT) longitudinal algorithms were developed using the assay results and trial CA125 values on the training set and evaluated in the blinded validation set. The study set comprised of 1363 (2–5 per woman) serial samples from 179 cases and 181 controls. In the validation set, area under the curve (AUC) and sensitivity of longitudinal CA125-MMT algorithm were 0.911 (0.871–0.952) and 90.5% (82.5–98.6%). None of the longitudinal multi-marker algorithms (CA125-HE4, CA125-HE4-CA72-4, CA125-HE4-CA72-4-anti-TP53) performed better or improved on lead-time. Our population study suggests that longitudinal HE4, CA72-4, anti-TP53 autoantibodies adds little value to longitudinal serum CA125 as a first-line test in ovarian cancer screening of postmenopausal women.
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spelling pubmed-74090612020-08-26 Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women Gentry-Maharaj, Aleksandra Blyuss, Oleg Ryan, Andy Burnell, Matthew Karpinskyj, Chloe Gunu, Richard Kalsi, Jatinderpal K. Dawnay, Anne Marino, Ines P. Manchanda, Ranjit Lu, Karen Yang, Wei-Lei Timms, John F. Parmar, Mahesh Skates, Steven J. Bast, Robert C. Jacobs, Ian J. Zaikin, Alexey Menon, Usha Cancers (Basel) Article Longitudinal CA125 algorithms are the current basis of ovarian cancer screening. We report on longitudinal algorithms incorporating multiple markers. In the multimodal arm of United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), 50,640 postmenopausal women underwent annual screening using a serum CA125 longitudinal algorithm. Women (cases) with invasive tubo-ovarian cancer (WHO 2014) following outcome review with stored annual serum samples donated in the 5 years preceding diagnosis were matched 1:1 to controls (no invasive tubo-ovarian cancer) in terms of the number of annual samples and age at randomisation. Blinded samples were assayed for serum human epididymis protein 4 (HE4), CA72-4 and anti-TP53 autoantibodies. Multimarker method of mean trends (MMT) longitudinal algorithms were developed using the assay results and trial CA125 values on the training set and evaluated in the blinded validation set. The study set comprised of 1363 (2–5 per woman) serial samples from 179 cases and 181 controls. In the validation set, area under the curve (AUC) and sensitivity of longitudinal CA125-MMT algorithm were 0.911 (0.871–0.952) and 90.5% (82.5–98.6%). None of the longitudinal multi-marker algorithms (CA125-HE4, CA125-HE4-CA72-4, CA125-HE4-CA72-4-anti-TP53) performed better or improved on lead-time. Our population study suggests that longitudinal HE4, CA72-4, anti-TP53 autoantibodies adds little value to longitudinal serum CA125 as a first-line test in ovarian cancer screening of postmenopausal women. MDPI 2020-07-17 /pmc/articles/PMC7409061/ /pubmed/32708856 http://dx.doi.org/10.3390/cancers12071931 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gentry-Maharaj, Aleksandra
Blyuss, Oleg
Ryan, Andy
Burnell, Matthew
Karpinskyj, Chloe
Gunu, Richard
Kalsi, Jatinderpal K.
Dawnay, Anne
Marino, Ines P.
Manchanda, Ranjit
Lu, Karen
Yang, Wei-Lei
Timms, John F.
Parmar, Mahesh
Skates, Steven J.
Bast, Robert C.
Jacobs, Ian J.
Zaikin, Alexey
Menon, Usha
Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women
title Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women
title_full Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women
title_fullStr Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women
title_full_unstemmed Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women
title_short Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women
title_sort multi-marker longitudinal algorithms incorporating he4 and ca125 in ovarian cancer screening of postmenopausal women
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409061/
https://www.ncbi.nlm.nih.gov/pubmed/32708856
http://dx.doi.org/10.3390/cancers12071931
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