{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:23:54Z","timestamp":1791829434381,"version":"4.3.4"},"reference-count":65,"publisher":"The Endocrine Society","issue":"12","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with a high recurrence and mortality rate even after complete resection. Therefore, intensification of adjuvant therapies is crucial, although their effectiveness remains controversial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to determine the efficacy and safety of available treatments by considering the prognostic factors affecting disease outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The search was conducted across 3 databases (PubMed, Embase, and CENTRAL) in October 2024. Eligible studies compared overall survival (OS) and recurrence-free survival (RFS) in patients with ACC treated with and without systemic (mitotane, cytotoxic chemotherapy) or localized (radiotherapy) nonsurgical treatments. In total, 86 studies met the inclusion criteria for the systematic review, and 62 for the meta-analysis. Two reviewers extracted data independently. Adjusted hazard ratios (aHR) with 95% CI were calculated for survival outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mitotane significantly improves OS (aHR: 0.54; CI: 0.41-0.70) and RFS (aHR: 0.60; CI: 0.43-0.84), even in stage I-III disease (OS aHR: 0.71; CI: 0.52-0.98; RFS aHR: 0.65; CI: 0.50-0.85). Radiotherapy showed a trend toward improved OS (aHR: 0.66; CI: 0.38-1.15) and RFS (aHR: 0.65; CI: 0.35-1.23), with significant benefits in stage I-III (OS aHR: 0.68; CI: 0.50-0.93; RFS aHR: 0.71; CI: 0.63-0.81). The impact of cytotoxic chemotherapy on OS remains uncertain (aHR: 0.61; CI: 0.08-4.78).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Mitotane significantly improves survival outcomes in patients with ACC, while radiotherapy exhibits potential benefits, particularly in localized disease. Further research is needed to verify the efficacy of cytotoxic chemotherapy, and randomized controlled trials are required to provide robust evidence of different treatment approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf457","type":"journal-article","created":{"date-parts":[[2025,8,10]],"date-time":"2025-08-10T11:41:42Z","timestamp":1754826102000},"page":"3599-3608","source":"Crossref","is-referenced-by-count":3,"title":["Efficacy and Safety of Radiotherapy and Systemic Treatments in Adrenocortical Carcinoma: Systematic Review and Meta-Analysis"],"prefix":"10.1210","volume":"110","author":[{"given":"Anita","family":"Pfeffer","sequence":"first","affiliation":[{"name":"Pediatric Center, T\u0171zolt\u00f3 Street Department, Semmelweis University , Budapest 1094 ,","place":["Hungary"]},{"name":"Centre for Translational Medicine, Semmelweis University , Budapest 1085 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00f3ra","family":"Beke","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University , Budapest 1085 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorottya","family":"Bak\u00f3","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University , Budapest 1085 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rk","family":"Hern\u00e1df\u0151i","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University , Budapest 1085 ,","place":["Hungary"]},{"name":"Department of Neurology, Bethesda Children\u2019s Hospital , Budapest 1146 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"K\u00f3i","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University , Budapest 1085 ,","place":["Hungary"]},{"name":"Department of Stochastics, Institute of Mathematics, Budapest University of Technology and Economics , Budapest 1111 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s","family":"Fogarasi","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University , Budapest 1085 ,","place":["Hungary"]},{"name":"Department of Neurology, Bethesda Children\u2019s Hospital , Budapest 1146 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"P\u00e1rniczky","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University , Budapest 1085 ,","place":["Hungary"]},{"name":"Department of Pulmonology, Heim P\u00e1l National Pediatric Institute , Budapest 1089 ,","place":["Hungary"]},{"name":"Institute of Pancreatic Diseases, Semmelweis University , Budapest 1085 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Hegyi","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine, Semmelweis University , Budapest 1085 ,","place":["Hungary"]},{"name":"Institute of Pancreatic Diseases, Semmelweis University , Budapest 1085 ,","place":["Hungary"]},{"name":"Institute for Translational Medicine, Medical School, University of Pe\u0301cs , Pe\u0301cs 7624 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4298-2746","authenticated-orcid":false,"given":"Mikl\u00f3s","family":"Garami","sequence":"additional","affiliation":[{"name":"Pediatric Center, T\u0171zolt\u00f3 Street Department, Semmelweis University , Budapest 1094 ,","place":["Hungary"]},{"name":"Centre for Translational Medicine, Semmelweis University , Budapest 1085 ,","place":["Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"issue":"11","key":"2025111718532695000_dgaf457-B1","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1016\/j.ejca.2013.02.034","article-title":"Adrenocortical carcinoma: a population-based study on incidence and survival in The Netherlands since 1993","volume":"49","author":"Kerkhofs","year":"2013","journal-title":"Eur J Cancer"},{"issue":"5","key":"2025111718532695000_dgaf457-B2","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1007\/s00268-005-0329-x","article-title":"Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress?","volume":"30","author":"Kebebew","year":"2006","journal-title":"World J Surg"},{"issue":"6","key":"2025111718532695000_dgaf457-B3","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1530\/EJE-13-0519","article-title":"Adrenocortical carcinoma: clinical outcomes and prognosis of 330 patients at a tertiary care center","volume":"169","author":"Ayala-Ramirez","year":"2013","journal-title":"Eur J Endocrinol"},{"key":"2025111718532695000_dgaf457-B4","doi-asserted-by":"crossref","first-page":"952418","DOI":"10.3389\/fendo.2022.952418","article-title":"Prognostic factors and mitotane treatment of adrenocortical cancer. Two decades of experience from an institutional case series","volume":"13","author":"T\u0151ke","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"9","key":"2025111718532695000_dgaf457-B5","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1093\/oncolo\/oyae029","article-title":"Adrenocortical carcinomas: molecular pathogenesis, treatment options, and emerging immunotherapy and targeted therapy approaches","volume":"29","author":"Chukkalore","year":"2024","journal-title":"Oncologist"},{"issue":"12","key":"2025111718532695000_dgaf457-B6","doi-asserted-by":"crossref","first-page":"5948","DOI":"10.1210\/jc.2019-00915","article-title":"National treatment practice for adrenocortical carcinoma: have they changed and have we made any progress?","volume":"104","author":"Tierney","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"2025111718532695000_dgaf457-B7","doi-asserted-by":"crossref","first-page":"1134643","DOI":"10.3389\/fendo.2023.1134643","article-title":"Prognostic predictors of adrenocortical carcinoma: a single-center thirty-year experience","volume":"14","author":"Pan","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"4","key":"2025111718532695000_dgaf457-B8","doi-asserted-by":"crossref","first-page":"276","DOI":"10.4103\/iju.iju_77_22","article-title":"Impact of multimodal therapy on margin status on overall survival for patients undergoing adrenalectomy for localized adrenocortical carcinoma","volume":"38","author":"Hickey","year":"2022","journal-title":"Indian J Urol"},{"issue":"1","key":"2025111718532695000_dgaf457-B9","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1245\/s10434-015-4810-y","article-title":"Curative resection of adrenocortical carcinoma: rates and patterns of postoperative recurrence","volume":"23","author":"Amini","year":"2016","journal-title":"Ann Surg Oncol"},{"issue":"1","key":"2025111718532695000_dgaf457-B10","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.surg.2018.04.068","article-title":"Longitudinal patterns of recurrence in patients with adrenocortical carcinoma","volume":"165","author":"Glenn","year":"2019","journal-title":"Surgery"},{"issue":"2","key":"2025111718532695000_dgaf457-B11","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.critrevonc.2014.05.009","article-title":"Adrenocortical carcinoma: the management of metastatic disease","volume":"92","author":"Fay","year":"2014","journal-title":"Crit Rev Oncol Hematol"},{"issue":"12","key":"2025111718532695000_dgaf457-B12","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.6004\/jnccn.2021.7035","article-title":"Benefit of postoperative radiotherapy for patients with nonmetastatic adrenocortical carcinoma: a population-based analysis","volume":"19","author":"Wu","year":"2021","journal-title":"J Natl Compr Canc Netw"},{"key":"2025111718532695000_dgaf457-B13","doi-asserted-by":"crossref","first-page":"20406223211033103","DOI":"10.1177\/20406223211033103","article-title":"Adrenocortical carcinoma: current state of the art, ongoing controversies, and future directions in diagnosis and treatment","volume":"12","author":"Shariq","year":"2021","journal-title":"Ther Adv Chronic Dis"},{"issue":"1_Part_1","key":"2025111718532695000_dgaf457-B14","doi-asserted-by":"crossref","first-page":"74","DOI":"10.7326\/0003-4819-59-1-74","article-title":"Treatment of adrenocortical cancer with O,P'-DDD","volume":"59","author":"Netto","year":"1963","journal-title":"Ann Intern Med"},{"issue":"4","key":"2025111718532695000_dgaf457-B15","doi-asserted-by":"crossref","first-page":"672","DOI":"10.7326\/0003-4819-53-4-672","article-title":"Chemotherapy of adrenocortical cancer with O,P\u2019DDD","volume":"53","author":"Bergenstal","year":"1960","journal-title":"Ann Intern Med"},{"issue":"3","key":"2025111718532695000_dgaf457-B16","doi-asserted-by":"crossref","first-page":"101415","DOI":"10.1016\/j.beem.2020.101415","article-title":"New perspectives for mitotane treatment of adrenocortical carcinoma","volume":"34","author":"Puglisi","year":"2020","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"issue":"2","key":"2025111718532695000_dgaf457-B17","first-page":"62","article-title":"Role of mitotane in adrenocortical carcinoma\u2014review and state of the art","volume":"14","author":"Paragliola","year":"2018","journal-title":"Eur Endocrinol"},{"issue":"9","key":"2025111718532695000_dgaf457-B18","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.3390\/cancers12092615","article-title":"Unwanted hormonal and metabolic effects of postoperative adjuvant mitotane treatment for adrenocortical cancer","volume":"12","author":"Basile","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"19","key":"2025111718532695000_dgaf457-B19","doi-asserted-by":"crossref","first-page":"5001","DOI":"10.3390\/cancers13195001","article-title":"Metabolic and endocrine toxicities of mitotane: a systematic review","volume":"13","author":"Bianchini","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"9","key":"2025111718532695000_dgaf457-B20","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1038\/s41416-021-01513-8","article-title":"Adjuvant platinum-based chemotherapy in radically resected adrenocortical carcinoma: a cohort study","volume":"125","author":"Kimpel","year":"2021","journal-title":"Br J Cancer"},{"issue":"1","key":"2025111718532695000_dgaf457-B21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clgc.2022.10.011","article-title":"A systematic review of published clinical trials in the systemic treatment of adrenocortical carcinoma: an Initiative Led on Behalf of the Global Society of Rare Genitourinary Tumors","volume":"21","author":"de Padua","year":"2023","journal-title":"Clin Genitourin Cancer"},{"key":"2025111718532695000_dgaf457-B22","doi-asserted-by":"crossref","unstructured":"Pfeffer A, Beke N, Bak\u00f3 D, et al \u00a0Data from: Supplementary Material for \u201cEfficacy and Safety of Radiotherapy and Systemic Treatments in Adrenocortical Carcinoma: Systematic Review and Meta-Analysis\u201d. Zenodo Repository. 2025. Deposited 26 August 2025. 10.5281\/zenodo.15882187","DOI":"10.1210\/clinem\/dgaf457"},{"key":"2025111718532695000_dgaf457-B23","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2025111718532695000_dgaf457-B24","author":"Higgins"},{"issue":"4","key":"2025111718532695000_dgaf457-B25","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1002\/jrsm.1563","article-title":"Citationchaser: a tool for transparent and efficient forward and backward citation chasing in systematic searching","volume":"13","author":"Haddaway","year":"2022","journal-title":"Res Synth Methods"},{"key":"2025111718532695000_dgaf457-B26","doi-asserted-by":"crossref","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"Rob 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"2025111718532695000_dgaf457-B27","doi-asserted-by":"crossref","first-page":"i4919","DOI":"10.1136\/bmj.i4919","article-title":"ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions","volume":"355","author":"Sterne","year":"2016","journal-title":"BMJ"},{"issue":"4","key":"2025111718532695000_dgaf457-B28","doi-asserted-by":"crossref","first-page":"280","DOI":"10.7326\/0003-4819-158-4-201302190-00009","article-title":"Assessing bias in studies of prognostic factors","volume":"158","author":"Hayden","year":"2013","journal-title":"Ann Intern Med"},{"issue":"4","key":"2025111718532695000_dgaf457-B29","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.jclinepi.2010.04.026","article-title":"GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables","volume":"64","author":"Guyatt","year":"2011","journal-title":"J Clin Epidemiol"},{"issue":"9418","key":"2025111718532695000_dgaf457-B30","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1016\/S0140-6736(04)16044-3","article-title":"Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis","volume":"363","author":"Renehan","year":"2004","journal-title":"Lancet"},{"key":"2025111718532695000_dgaf457-B31"},{"key":"2025111718532695000_dgaf457-B32","author":"Higgins"},{"issue":"2","key":"2025111718532695000_dgaf457-B33","doi-asserted-by":"crossref","first-page":"e1230","DOI":"10.1002\/cl2.1230","article-title":"PRISMA2020: an R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis","volume":"18","author":"Haddaway","year":"2022","journal-title":"Campbell Syst Rev"},{"issue":"5","key":"2025111718532695000_dgaf457-B34","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.3390\/jcm9051532","article-title":"Academia Europaea Position Paper on Translational Medicine: the cycle model for translating scientific results into community benefits","volume":"9","author":"Hegyi","year":"2020","journal-title":"J Clin Med"},{"issue":"8","key":"2025111718532695000_dgaf457-B35","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1038\/s41591-021-01458-8","article-title":"Accelerating the translational medicine cycle: the Academia Europaea pilot","volume":"27","author":"Hegyi","year":"2021","journal-title":"Nat Med"},{"issue":"11","key":"2025111718532695000_dgaf457-B36","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.annonc.2020.08.2099","article-title":"Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Fassnacht","year":"2020","journal-title":"Ann Oncol"},{"issue":"2","key":"2025111718532695000_dgaf457-B37","doi-asserted-by":"crossref","first-page":"508","DOI":"10.3390\/cancers12020508","article-title":"Adjuvant therapy in adrenocortical carcinoma: reflections and future directions","volume":"12","author":"Bedrose","year":"2020","journal-title":"Cancers (Basel)"},{"key":"2025111718532695000_dgaf457-B38","doi-asserted-by":"crossref","first-page":"9362108","DOI":"10.1155\/2018\/9362108","article-title":"Benefits of adjuvant mitotane after resection of adrenocortical carcinoma: a systematic review and meta-analysis","volume":"2018","author":"Tang","year":"2018","journal-title":"Biomed Res Int"},{"issue":"4","key":"2025111718532695000_dgaf457-B39","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1530\/EJE-18-0608","article-title":"European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors","volume":"179","author":"Fassnacht","year":"2018","journal-title":"Eur J Endocrinol"},{"issue":"10","key":"2025111718532695000_dgaf457-B40","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/S2213-8587(23)00193-6","article-title":"Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study","volume":"11","author":"Terzolo","year":"2023","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"1","key":"2025111718532695000_dgaf457-B41","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.surg.2023.04.070","article-title":"The effect of hormonal secretion on survival in adrenocortical carcinoma: a multi-center study","volume":"175","author":"Sada","year":"2024","journal-title":"Surgery"},{"issue":"6","key":"2025111718532695000_dgaf457-B42","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1530\/EJE-18-0450","article-title":"Influence of hormonal functional status on survival in adrenocortical carcinoma: systematic review and meta-analysis","volume":"179","author":"Vanbrabant","year":"2018","journal-title":"Eur J Endocrinol"},{"issue":"7","key":"2025111718532695000_dgaf457-B43","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.1210\/jc.2005-2730","article-title":"Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients","volume":"91","author":"Abiven","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"2025111718532695000_dgaf457-B44","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1056\/NEJMc076267","article-title":"Adjuvant mitotane in adrenocortical carcinoma","volume":"357","author":"Bertherat","year":"2007","journal-title":"N Engl J Med"},{"issue":"6","key":"2025111718532695000_dgaf457-B45","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.amjsurg.2015.09.020","article-title":"Outcomes after resection of cortisol-secreting adrenocortical carcinoma","volume":"211","author":"Margonis","year":"2016","journal-title":"Am J Surg"},{"key":"2025111718532695000_dgaf457-B46","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fendo.2016.00099","article-title":"Prognostic factors for adrenocortical carcinoma outcomes","volume":"7","author":"Scollo","year":"2016","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"17","key":"2025111718532695000_dgaf457-B47","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1056\/NEJM199004263221705","article-title":"Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy","volume":"322","author":"Luton","year":"1990","journal-title":"N Engl J Med"},{"issue":"2","key":"2025111718532695000_dgaf457-B48","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0022-5347(17)40734-8","article-title":"The Cleveland Clinic experience with adrenal cortical carcinoma","volume":"141","author":"Bodie","year":"1989","journal-title":"J Urol"},{"issue":"1","key":"2025111718532695000_dgaf457-B49","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s13014-020-01533-3","article-title":"Efficacy of adjuvant radiotherapy for treatment of adrenocortical carcinoma: a retrospective study and an updated meta-analysis","volume":"15","author":"Zhu","year":"2020","journal-title":"Radiat Oncol"},{"issue":"Suppl 1","key":"2025111718532695000_dgaf457-B50","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.4103\/jcrt.JCRT_996_15","article-title":"Adjuvant radiotherapy after surgical resection for adrenocortical carcinoma: a systematic review of observational studies and meta-analysis","volume":"15","author":"Viani","year":"2019","journal-title":"J Cancer Res Ther"},{"issue":"5","key":"2025111718532695000_dgaf457-B51","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1590\/s1677-5538.ibju.2017.0095","article-title":"Adjuvant radiotherapy for the primary treatment of adrenocortical carcinoma: are we offering the best?","volume":"43","author":"Srougi","year":"2017","journal-title":"Int Braz J Urol"},{"issue":"2","key":"2025111718532695000_dgaf457-B52","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.ijrobp.2015.01.007","article-title":"Adjuvant radiation therapy improves local control after surgical resection in patients with localized adrenocortical carcinoma","volume":"92","author":"Sabolch","year":"2015","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"7","key":"2025111718532695000_dgaf457-B53","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1245\/s10434-018-6510-x","article-title":"Adjuvant radiation is associated with improved survival for select patients with non-metastatic adrenocortical carcinoma","volume":"25","author":"Nelson","year":"2018","journal-title":"Ann Surg Oncol"},{"issue":"11","key":"2025111718532695000_dgaf457-B54","doi-asserted-by":"crossref","first-page":"4501","DOI":"10.1210\/jc.2006-1007","article-title":"Efficacy of adjuvant radiotherapy of the tumor bed on local recurrence of adrenocortical carcinoma","volume":"91","author":"Fassnacht","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2025111718532695000_dgaf457-B55","doi-asserted-by":"crossref","first-page":"941","DOI":"10.3390\/cancers12040941","article-title":"Efficacy of the EDP-M scheme plus adjunctive surgery in the management of patients with advanced adrenocortical carcinoma: the Brescia experience","volume":"12","author":"Lagan\u00e0","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"23","key":"2025111718532695000_dgaf457-B56","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1056\/NEJMoa1200966","article-title":"Combination chemotherapy in advanced adrenocortical carcinoma","volume":"366","author":"Fassnacht","year":"2012","journal-title":"N Engl J Med"},{"issue":"2","key":"2025111718532695000_dgaf457-B57","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1245\/s10434-022-12725-4","article-title":"Mitotane with or without cisplatin and etoposide for patients with a high risk of recurrence in stages 1-3 adrenocortical cancer after surgery","volume":"30","author":"Sarvestani","year":"2023","journal-title":"Ann Surg Oncol"},{"issue":"2","key":"2025111718532695000_dgaf457-B58","first-page":"493","article-title":"Mitotane sensitizes adrenocortical cancer cells to ionizing radiations by involvement of the cyclin B1\/CDK complex in G2 arrest and mismatch repair enzymes modulation","volume":"37","author":"Cerquetti","year":"2010","journal-title":"Int J Oncol"},{"issue":"4","key":"2025111718532695000_dgaf457-B59","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.amjsurg.2020.02.043","article-title":"Risk factors associated with positive resection margins in patients with adrenocortical carcinoma","volume":"220","author":"Skertich","year":"2020","journal-title":"Am J Surg"},{"issue":"1","key":"2025111718532695000_dgaf457-B60","doi-asserted-by":"crossref","first-page":"S466","DOI":"10.1016\/j.ijrobp.2014.05.1454","article-title":"Toxicity of concurrent radiation therapy with mitotane compared to radiation therapy alone in the adjuvant treatment of adrenocortical carcinoma","volume":"90","author":"Sabolch","year":"2014","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2025111718532695000_dgaf457-B61","doi-asserted-by":"crossref","first-page":"961650","DOI":"10.3389\/fendo.2022.961650","article-title":"Pediatric adrenocortical carcinoma","volume":"13","author":"Ilanchezhian","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"3","key":"2025111718532695000_dgaf457-B62","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1055\/s-0032-1304627","article-title":"Surgical aspects in the treatment of adrenocortical carcinomas in children: data of the GPOH-MET 97 trial","volume":"224","author":"Hubertus","year":"2012","journal-title":"Klin Padiatr"},{"issue":"S4","key":"2025111718532695000_dgaf457-B63","doi-asserted-by":"crossref","first-page":"e29025","DOI":"10.1002\/pbc.29025","article-title":"Adrenocortical tumours in children and adolescents: the EXPeRT\/PARTNER diagnostic and therapeutic recommendations","volume":"68","author":"Virgone","year":"2021","journal-title":"Pediatr Blood Cancer"},{"issue":"22","key":"2025111718532695000_dgaf457-B64","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1200\/JCO.20.02871","article-title":"Treatment of pediatric adrenocortical carcinoma with surgery, retroperitoneal lymph node dissection, and chemotherapy: the Children's Oncology Group ARAR0332 Protocol","volume":"39","author":"Rodriguez-Galindo","year":"2021","journal-title":"J Clin Oncol"},{"issue":"6","key":"2025111718532695000_dgaf457-B65","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1055\/s-0032-1327579","article-title":"Systemic treatment of adrenocortical carcinoma in children: data from the German GPOH-MET 97 trial","volume":"224","author":"Redlich","year":"2012","journal-title":"Klin Padiatr"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaf457\/64017376\/dgaf457.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/12\/3599\/64017376\/dgaf457.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/110\/12\/3599\/64017376\/dgaf457.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T23:53:56Z","timestamp":1763423636000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/110\/12\/3599\/8231666"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,11]]},"references-count":65,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,8,11]]},"published-print":{"date-parts":[[2025,11,18]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaf457","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,12]]},"published":{"date-parts":[[2025,8,11]]}}}