Multi-Marker Longitudinal Algorithms Incorporating HE4 and CA125 in Ovarian Cancer Screening of Postmenopausal Women
Year: 2020
Type: article
Abstract: 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.
Source: Cancers
Authors: Aleksandra Gentry-Maharaj, Oleg Blyuss, Andy Ryan, Matthew Burnell, Chloe Karpinskyj, Richard Gunu, Jatinderpal K. Kalsi, Anne Dawnay, Ines P. Marino, Ranjit Manchanda, Karen Lu, Wei-Lei Yang, John F. Timms, Max Parmar, Steven J. Skates, Robert C. Bast, Ian J. Jacobs, Alexey Zaikin, Usha Menon
Institutions: MRC Clinical Trials Unit at UCL, University College London, University of Hertfordshire, Sechenov University, Barts Health NHS Trust, Universidad Rey Juan Carlos, St Bartholomew's Hospital, Queen Mary University of London, Cancer Research UK, The University of Texas MD Anderson Cancer Center, Harvard University, Massachusetts General Hospital, UNSW Sydney, N. I. Lobachevsky State University of Nizhny Novgorod
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,324
Funders: U.S. Department of Health and Human Services, Cancer Prevention and Research Institute of Texas, Barts Charity, Cancer Research UK, National Institute for Health and Care Research, University College London, Ministry of Education and Science of the Russian Federation, University of Texas MD Anderson Cancer Center, Medical Research Council, National Cancer Institute
Awards: G1176639099, U.T. M. D. Anderson Cancer Center SPORE in Ovarian Cancer, G1312554034, G1316926367, G1394336465, G1417479301, Early Detection of Ovarian Cancer with Tumor Associated Proteins and Autoantibodies, G1890702095, G2177378662, G2181212458, G2346618446, G2459698152, Proteomic, Genomic, and Longitudinal Pathways to Ovarian Cancer Biomarker Discovery, G4287663350, G4652843983, G4803905812, G4951670354, G5009597576, G5058239881, G535437275, G5482034194, G5724888378, G5735442093, G5751515744, G5839868777, G6453487649, G737619643, G7396772347, G7571973020, G7747638927, G848625396, G8488311367, HSM: Construction of graph-based network longitudinal algorithms to identify screening and prognostic biomarkers and therapeutic targets (GBNLA), The University of Texas M. D. Anderson Cancer Center SPORE in Ovarian Cancer, G8804857625, G8871309901, MD Anderson Cancer Center EDRN- Clinical Validation Center for Early Detection of Ovarian Cancer with a multiple marker algorithm
OpenAlex ID: W3042643553