{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:43:09Z","timestamp":1792676589764,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004040","name":"KU Leuven","doi-asserted-by":"publisher","award":["C24\/15\/037"],"award-info":[{"award-number":["C24\/15\/037"]}],"id":[{"id":"10.13039\/501100004040","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["12F3114N"],"award-info":[{"award-number":["12F3114N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G049312N"],"award-info":[{"award-number":["G049312N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0B4716N"],"award-info":[{"award-number":["G0B4716N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011851","name":"Kom op tegen Kanker","doi-asserted-by":"publisher","award":["2016\/10728\/2603"],"award-info":[{"award-number":["2016\/10728\/2603"]}],"id":[{"id":"10.13039\/501100011851","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp;amp; Gyne"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      We previously proposed two cell\u2010free (cf) DNA\u2010based scores (genome\u2010wide\n                      <jats:italic>Z<\/jats:italic>\n                      \u2010score and nucleosome score) as candidate non\u2010invasive biomarkers to further improve the presurgical diagnosis of ovarian malignancy. We aimed to investigate the added value of these cfDNA\u2010based scores in combination with the clinical and ultrasound predictors of the Assessment of Different NEoplasias in the adneXa (ADNEX) model to estimate the risk of ovarian malignancy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this prospective cohort study, 526 patients with an adnexal mass scheduled for surgery were recruited consecutively in three oncology referral centers. All patients underwent a transvaginal ultrasound examination, and adnexal masses were described according to the International Ovarian Tumor Analysis terms and definitions. cfDNA was extracted from preoperative plasma samples and genome\u2010wide\n                      <jats:italic>Z<\/jats:italic>\n                      \u2010scores and nucleosome scores were calculated. Logistic regression models were fitted for ADNEX predictors alone and after inclusion of the cfDNA\u2010based scores. We report likelihood ratios, area under the receiver\u2010operating\u2010characteristics curve (AUC), sensitivity, specificity and net benefit for thresholds between 5% and 40%, to assess the diagnostic performance of the models in discriminating between benign and malignant ovarian masses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The study included 272 benign, 86 borderline, 36 Stage\u2010I invasive, 113 Stage\u2010II\u2013IV invasive, and 19 secondary metastatic tumors. The likelihood ratios for adding the cfDNA\u2010based scores to the ADNEX model were statistically significant (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001 for ADNEX without CA\u2009125;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.001 for ADNEX including CA\u2009125). The accompanying increases in AUC were 0.013 when the cfDNA biomarkers were added to the ADNEX model without CA 125, and 0.003 when added to the ADNEX model including CA 125. Net benefit, sensitivity and specificity were similar for all models. The increase in net benefit at the recommended 10% threshold estimated risk of malignancy when adding the cfDNA\u2010based scores was 0.0017 and 0.0020, respectively, for the ADNEX model without CA\u2009125 and the ADNEX model with CA\u2009125. According to these results, adding cfDNA markers would require at least 453 patients per additional true\u2010positive test result at the 10% risk threshold.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Although statistically significant, cfDNA\u2010based biomarker scores have limited clinical utility in addition to established clinical and ultrasound\u2010based ADNEX predictors for discriminating between benign and malignant ovarian masses. \u00a9 2025 International Society of Ultrasound in Obstetrics and Gynecology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/uog.29314","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T21:03:32Z","timestamp":1755637412000},"page":"518-526","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Added value of cell\u2010free\n                    <scp>DNA<\/scp>\n                    over clinical and ultrasound information for diagnosing ovarian cancer"],"prefix":"10.1002","volume":"66","author":[{"given":"A.","family":"Vanderstichele","sequence":"first","affiliation":[{"name":"Division of Gynecological Oncology University Hospitals Leuven  Leuven Belgium"},{"name":"Department of Gynecology AZ Delta  Roeselare Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5422-5668","authenticated-orcid":false,"given":"J.","family":"Ceusters","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Immunology and Immunotherapy, Department of Oncology Leuven Cancer Institute, KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7224-3218","authenticated-orcid":false,"given":"D.","family":"Fischerova","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Centre, Department of Gynecology, Obstetrics and Neonatology, First Faculty of Medicine Charles University and General University Hospital in Prague  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. C.","family":"Testa","sequence":"additional","affiliation":[{"name":"Dipartimento Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS  Rome Italy"},{"name":"Dipartimento Universitario Scienze della Vita e Sanit\u00e0 Pubblica, Universit\u00e0 Cattolica del Sacro Cuore  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1398-9124","authenticated-orcid":false,"given":"W.","family":"Froyman","sequence":"additional","affiliation":[{"name":"Division of Gynecological Oncology University Hospitals Leuven  Leuven Belgium"},{"name":"Department of Development and Regeneration KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9808-7957","authenticated-orcid":false,"given":"C.","family":"Landolfo","sequence":"additional","affiliation":[{"name":"Dipartimento Scienze della Salute della Donna, del Bambino e di Sanit\u00e0 Pubblica, Fondazione Policlinico Universitario A. 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