{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T01:55:29Z","timestamp":1793498129721,"version":"4.5.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"AIRC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana Ricerca Cancro","doi-asserted-by":"crossref","award":["IG 2021\u201325920"],"award-info":[{"award-number":["IG 2021\u201325920"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministero Italiano dell\u2018Universit\u00e0 e della Ricerca"},{"name":"Progetti di Ricerca di Interesse Nazionale","award":["20222KAYY5"],"award-info":[{"award-number":["20222KAYY5"]}]},{"DOI":"10.13039\/100031478","name":"Next Generation EU","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Community"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Advanced adrenocortical carcinoma (ACC) is treated with mitotane alone or combined with cytotoxic chemotherapy, yet outcomes remain poor and prognostic models in this setting are lacking. This study aimed to evaluate the prognostic value of clinical parameters in a large cohort of patients with advanced ACC undergoing systemic therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Multicenter, international cohort study investigating 418 patients with advanced ACC (61.5% = women, median age = 52 years) from 11 centers. Patients received mitotane monotherapy (n = 161), etoposide + doxorubicin + cisplatin \u00b1 mitotane (n = 178), or second-line regimens (gemcitabine + capecitabine \u00b1 mitotane or temozolomide + mitotane, n = 79). Variables included age, cortisol excess, performance status (ECOG-PS), tumor burden, and neutrophil-to-lymphocyte ratio (NLR) at start of therapy. Outcomes were overall survival (OS), time to progression (TTP), and best objective response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Tumor burden, cortisol excess, ECOG-PS, and NLR \u22655 independently predicted shorter OS (hazard ratio [HR] 1.55-2.68). We developed an integrated ENSAT Risk Score for Advanced ACC combining these variables: tumor burden (0-2), cortisol excess (0\/1), ECOG-PS (0-2), and NLR (0\/1). A score &amp;gt;2 (poor-risk) was significantly associated with worse OS and TTP across all treatment groups (HRs for OS: 3.05-3.96; TTP: 2.53-3.08). It also predicted poorer response to mitotane (P &amp;lt; .01) and second-line therapies (P = .04).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The ENSAT Risk Score for Advanced ACC is a practical, prognostic tool for patients with advanced ACC receiving systemic therapy. Based on accessible clinical and biochemical markers, it can support treatment decisions and facilitate informed discussions in routine care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejendo\/lvag046","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T12:42:58Z","timestamp":1772714578000},"page":"381-392","source":"Crossref","is-referenced-by-count":4,"title":["Clinical predictors of outcome in advanced adrenocortical carcinoma: a multicenter international ENSAT study"],"prefix":"10.1093","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1035-8551","authenticated-orcid":false,"given":"Alessandra","family":"Mangone","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan , 20122, Milan ,","place":["Italy"]},{"name":"Endocrinology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico , Via Francesco Sforza 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