{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:23:52Z","timestamp":1791829432602,"version":"4.3.4"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T00:00:00Z","timestamp":1709769600000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70113526"],"award-info":[{"award-number":["70113526"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AMEND"},{"name":"European Reference Network on Rare Endocrine Conditions"},{"name":"National Institute for Health"},{"name":"Care Research"},{"DOI":"10.13039\/501100018952","name":"Birmingham Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018952","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University Hospitals Birmingham"},{"name":"NHS Foundation Trust"},{"DOI":"10.13039\/501100000855","name":"University of Birmingham","doi-asserted-by":"publisher","award":["NIHR203326"],"award-info":[{"award-number":["NIHR203326"]}],"id":[{"id":"10.13039\/501100000855","id-type":"DOI","asserted-by":"publisher"}]},{"name":"HRA Pharma Rare Disease"},{"DOI":"10.13039\/100006662","name":"NIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006662","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Health and Social Care UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. The aim of the study was to investigate the role of circulating cell-free DNA (ccfDNA)-related biomarkers (BMs) for prognostication and monitoring of ACC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and Methods<\/jats:title>\n                    <jats:p>We investigated 34 patients with ACC and 23 healthy subjects (HSs) as controls. Circulating cell-free DNA was extracted by commercial kits and ccfDNA concentrations were quantified by fluorimeter (BM1). Targeted sequencing was performed using a customized panel of 27 ACC-specific genes. Leucocyte DNA was used to discriminate somatic variants (BM2), while tumour DNA was sequenced in 22\/34 cases for comparison. Serial ccfDNA samples were collected during follow-up in 19 ACC patients (median period 9 months) and analysed in relationship with standard radiological imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Circulating cell-free DNA concentrations were higher in ACC than HS (mean \u00b1 SD, 1.15 \u00b1 1.56 vs 0.05 \u00b1 0.05\u2005ng\/\u00b5L, P &amp;lt; .0001), 96% of them being above the cut-off of 0.146\u2005ng\/\u00b5L (mean HS + 2 SD, positive BM1). At ccfDNA sequencing, 47% of ACC showed at least 1 somatic mutation (positive BM2). A combined ccfDNA-BM score was strongly associated with both progression-free and overall survival (hazard ratio [HR] = 2.63; 95% CI, 1.13-6.13; P = .010, and HR = 5.98; 95% CI, 2.29-15.6; P = .0001, respectively). During disease monitoring, positive BM2 showed the best specificity (100%) and sensitivity (67%) to detect ACC recurrence or progress compared with BM1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ccfDNA-related BMs are frequently detected in ACC patients and represent a promising, minimally invasive tool to predict clinical outcome and complement surveillance imaging. Our findings will be validated in a larger cohort of ACCs with long-term follow-up.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvae022","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T18:20:00Z","timestamp":1709662800000},"page":"234-247","source":"Crossref","is-referenced-by-count":15,"title":["Circulating cell-free DNA-based biomarkers for prognostication and disease monitoring in adrenocortical carcinoma"],"prefix":"10.1093","volume":"190","author":[{"given":"Juliane","family":"Lippert","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, University of Wuerzburg , 97080 Wuerzburg , Germany"},{"name":"Institute of Human Genetics, University of Wuerzburg , 97070 Wuerzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Smith","sequence":"additional","affiliation":[{"name":"Institute of Metabolism and System Research, University of Birmingham , B152TT Birmingham , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Appenzeller","sequence":"additional","affiliation":[{"name":"Core Unit Bioinformatics, Comprehensive Cancer Center Mainfranken, University of Wuerzburg , 97070 Wuerzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6315-4176","authenticated-orcid":false,"given":"Laura-Sophie","family":"Landwehr","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, University of Wuerzburg , 97080 Wuerzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4821-0336","authenticated-orcid":false,"given":"Alessandro","family":"Prete","sequence":"additional","affiliation":[{"name":"Institute of Metabolism and System Research, University of Birmingham , B152TT Birmingham , United Kingdom"},{"name":"Centre for Endocrinology, Diabetes and Metabolism (CEDAM), Birmingham Health Partners , B152TT Birmingham , United Kingdom"},{"name":"NIHR Birmingham Biomedical Research Centre, University of Birmingham, University Hospitals Birmingham NHS Foundation Trust , B152GW Birmingham , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Steinhauer","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, University of Wuerzburg , 97080 Wuerzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Asia","sequence":"additional","affiliation":[{"name":"Endocrine Department, Queen Elizabeth Hospital Birmingham NHS Trust , B152GW Birmingham , United 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5106-9719","authenticated-orcid":false,"given":"Wiebke","family":"Arlt","sequence":"additional","affiliation":[{"name":"Institute of Metabolism and System Research, University of Birmingham , B152TT Birmingham , United Kingdom"},{"name":"MRC Laboratory of Medical Sciences , W120TN London , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6170-6398","authenticated-orcid":false,"given":"Martin","family":"Fassnacht","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, University of Wuerzburg , 97080 Wuerzburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2616-3249","authenticated-orcid":false,"given":"Barbara","family":"Altieri","sequence":"additional","affiliation":[{"name":"Division of 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