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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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7409061 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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