{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T21:52:24Z","timestamp":1775512344394,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Ovarian, fallopian tube, and primary peritoneal cancers often share clinical characteristics and are typically diagnosed at advanced stages due to nonspecific symptoms. The utility of tumor markers, particularly CA125 and HE4, in the diagnosis and follow-up of these cancers remains an area of active investigation. Objectives: The CEEGOG (Central and Eastern European Gynecologic Oncology Group) OX-01 study aimed to evaluate HE4\u2019s role alongside CA125 in follow-up for advanced-stage ovarian, fallopian tube, and primary peritoneal cancers. It assessed the potential for detecting recurrence using marker elevation and imaging methods, examining the necessity of dynamic monitoring and current cut-off values\u2019 accuracy for early relapse detection. Methods: In this multicenter prospective cohort study, 117 eligible patients with Stage III\u2013IV cancers were included. Patients had elevated CA125 or HE4 at diagnosis and achieved complete remission after first-line treatment. HE4 and CA125 levels were monitored every 3\u20134 months in the first two years and every six months thereafter. CT scans were performed if markers exceeded set thresholds or increased by over 20%. Results: During a median follow-up of 13.7 months, 73% of patients relapsed. Median HE4 levels were significantly higher in relapsed patients. A 10 IU\/mL increase from baseline in CA125 had a sensitivity of 83% and specificity of 93%, while a 15 pmol\/L increase in HE4 had a sensitivity of 74% and specificity of 92% for predicting relapse up to three months before CT scan detection. Conclusions: The study found that dynamic changes in HE4 and CA125 levels, rather than predefined cut-off values, are crucial for early relapse detection. These markers may offer a significant lead time over imaging, potentially enabling earlier intervention. Further research is needed to validate these findings.<\/jats:p>","DOI":"10.3390\/cancers16213566","type":"journal-article","created":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T04:28:43Z","timestamp":1729657723000},"page":"3566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Role of HE4 in the Follow-Up of Advanced Ovarian, Fallopian Tube, and Primary Peritoneal Cancer\u2014CEEGOG OX-01 Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7632-4069","authenticated-orcid":false,"given":"Jiri","family":"Presl","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine in Pilsen, University Hospital Pilsen, Charles University, 323 00 Pilsen, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel","family":"Havelka","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, KNTB a.s Zlin, 762 75 Zlin, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4858-1951","authenticated-orcid":false,"given":"Vit","family":"Weinberger","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital Brno and Medical Faculty, Masaryk University, 625 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3547-5896","authenticated-orcid":false,"given":"Petra","family":"Ovesna","sequence":"additional","affiliation":[{"name":"Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Fekete","sequence":"additional","affiliation":[{"name":"Department of Gynecological Oncology, St. Elizabeth Cancer Institute, 811 08 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filip","family":"Fruhauf","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Neonatology First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8935-0311","authenticated-orcid":false,"given":"Marcin","family":"Jedryka","sequence":"additional","affiliation":[{"name":"Gynecological Oncology Department, Lower Silesian Oncology, Pulmonology and Hematology Center, Wroclaw Medical University, 53-413 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9622-8557","authenticated-orcid":false,"given":"Branislav","family":"Bystricky","sequence":"additional","affiliation":[{"name":"Department of Oncology, Faculty Hospital Trencin, Faculty of Healthcare, Alexander Dubcek University of Trencin, 911 06 Trencin, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8749-4642","authenticated-orcid":false,"given":"Aleksandra","family":"Strojna","sequence":"additional","affiliation":[{"name":"Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University in Szczecin, 70-204 Szczecin, Poland"},{"name":"Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136 Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nataliya","family":"Volodko","sequence":"additional","affiliation":[{"name":"Department of Oncology and Radiology, Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Matylevich","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Division, NN Alexandrov National Cancer Centre, 223040 Minsk, Belarus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Herboltova","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine in Pilsen, Charles University, 306 05 Pilsen, Czech Republic"},{"name":"Department of Gynecology and Obstetrics, Jihlava Hospital, 586 01 Jihlava, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawel","family":"Blecharz","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, National Cancer Institute, M. Sklodowska-Curie Memorial Institute, 31-115 Cracow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Kalist","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, KNTB a.s Zlin, 762 75 Zlin, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie","family":"Ehrlichova","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine-Hematology and Oncology, University Hospital Brno and Medical Faculty, Masaryk University, 625 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Stranik","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine in Pilsen, University Hospital Pilsen, Charles University, 323 00 Pilsen, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ladislav","family":"Masak","sequence":"additional","affiliation":[{"name":"Department of Gynecological Oncology, St. Elizabeth Cancer Institute, 811 08 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Poncova","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Neonatology First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 08 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7598-5401","authenticated-orcid":false,"given":"Andrzej","family":"Czekanski","sequence":"additional","affiliation":[{"name":"Gynecological Oncology Department, Lower Silesian Oncology, Pulmonology and Hematology Center, Wroclaw Medical University, 53-413 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbora","family":"Chaloupkova","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, KNTB a.s Zlin, 762 75 Zlin, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Koblizkova","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital Brno and Medical Faculty, Masaryk University, 625 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vendula","family":"Smoligova","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine in Pilsen, University Hospital Pilsen, Charles University, 323 00 Pilsen, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marketa","family":"Hrabalova","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, KNTB a.s Zlin, 762 75 Zlin, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alena","family":"Jaksicova","sequence":"additional","affiliation":[{"name":"Department of Oncology, KNTB a.s Zlin, 762 75 Zlin, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Linkesch","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, KNTB a.s Zlin, 762 75 Zlin, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Libor","family":"Viktora","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital Brno and Medical Faculty, Masaryk University, 625 00 Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiri","family":"Bouda","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine in Pilsen, University Hospital Pilsen, Charles University, 323 00 Pilsen, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel","family":"Vlasak","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine in Pilsen, University Hospital Pilsen, Charles University, 323 00 Pilsen, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Kostun","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine in Pilsen, University Hospital Pilsen, Charles University, 323 00 Pilsen, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.ajpath.2015.11.011","article-title":"The Dualistic Model of Ovarian Carcinogenesis: Revisited, Revised, and Expanded","volume":"186","author":"Kurman","year":"2016","journal-title":"Am. 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