{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T01:21:32Z","timestamp":1768440092558,"version":"3.49.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis and limited treatment options for metastases. However, new effective regimens are emerging for specific conditions in metastatic ACC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>We report a case of a 36-year-old man diagnosed with metastatic ACC who had a large left adrenal mass (158 mm \u00d7 112 mm) and multiple metastases in the liver and lungs. Genetic testing revealed a microsatellite instability-high (MSI-H) tumor, a splice mutation in MLH1, and a high tumor mutational burden (TMB). After the left adrenalectomy, he received sequential treatment with a combination of mitotane, etoposide, paraplatin (EP-M), and sintilimab. His condition has been assessed as a stable disease since the sixth cycle of the combined regimen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This case highlights the remarkable response of our patient\u2019s ACC with MSI-H tumor, MLH1 spice mutation, and high TMB to treatment with a novel combination of EP-M and sintilimab. Our findings suggest a promising therapeutic option for patients with similar molecular profiles.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1115893","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T06:01:31Z","timestamp":1694152891000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Case report: Remarkable response to a novel combination of mitotane, etoposide, paraplatin, and sintilimab in a patient with metastatic adrenocortical carcinoma"],"prefix":"10.3389","volume":"14","author":[{"given":"Yan","family":"Weng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Yi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin-Xiang","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shao-Ling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2015.00045","article-title":"Adrenocortical carcinoma (ACC): diagnosis, prognosis, and treatment","volume":"3","author":"Lib\u00e9","year":"2015","journal-title":"Front Cell Dev Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2894","article-title":"Long-term outcomes of adjuvant mitotane therapy in patients with radically resected adrenocortical carcinoma","volume":"102","author":"Berruti","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nrclinonc.2013.208","article-title":"Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer","volume":"11","author":"Drake","year":"2014","journal-title":"Nat Rev Clin Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 blockade in tumors with mismatch-repair deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-0386","article-title":"Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers","volume":"16","author":"Goodman","year":"2017","journal-title":"Mol Cancer Ther"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab865","article-title":"Cytoreductive surgery of the primary tumor in metastatic adrenocortical carcinoma: Impact on patients\u2019 survival","volume":"107","author":"Srougi","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200966","article-title":"Combination chemotherapy in advanced adrenocortical carcinoma","volume":"366","author":"Fassnacht","year":"2012","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1998.530","article-title":"Cytotoxic therapy with etoposide and cisplatin in advanced adrenocortical carcinoma","volume":"78","author":"Bonacci","year":"1998","journal-title":"Br J Cancer."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6733","article-title":"Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade","volume":"357","author":"Le","year":"2017","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000013517","article-title":"Pembrolizumab for metastatic adrenocortical carcinoma with high mutational burden: two case reports","volume":"97","author":"Mota","year":"2018","journal-title":"Med (Baltimore)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ejca.2020.02.038","article-title":"Tumour mutational burden as a biomarker for immunotherapy: Current data and emerging concepts","volume":"131","author":"Fumet","year":"2020","journal-title":"Eur J Cancer."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30445-9","article-title":"Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study","volume":"21","author":"Marabelle","year":"2020","journal-title":"Lancet Oncol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"304","DOI":"10.3390\/biomedicines9030304","article-title":"Immunotherapy in adrenocortical carcinoma: predictors of response, efficacy, safety, and mechanisms of resistance","volume":"9","author":"Araujo-Castro","year":"2021","journal-title":"Biomedicines"},{"key":"B15","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s40425-018-0424-9","article-title":"Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial","volume":"6","author":"Le Tourneau","year":"2018","journal-title":"J Immunother Cancer."},{"key":"B16","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1186\/s40425-019-0722-x","article-title":"Phase II clinical trial of pembrolizumab efficacy and safety in advanced adrenocortical carcinoma","volume":"7","author":"Habra","year":"2019","journal-title":"J Immunother Cancer."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019-00600","article-title":"Nivolumab in metastatic adrenocortical carcinoma: results of a phase 2 trial","volume":"104","author":"Carneiro","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1200\/JCO.19.01586","article-title":"PD-1 blockade in advanced adrenocortical carcinoma","volume":"38","author":"Raj","year":"2020","journal-title":"J Clin Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1093\/abt\/tby009","article-title":"Frontiers and opportunities: highlights of the 2nd annual conference of the chinese antibody society","volume":"1","author":"Zhang","year":"2018","journal-title":"Antib Ther"},{"key":"B20","doi-asserted-by":"publisher","first-page":"98","DOI":"10.3390\/biomedicines9020098","article-title":"The role of immunotherapy in the treatment of adrenocortical carcinoma","volume":"9","author":"Karwacka","year":"2021","journal-title":"Biomedicines"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1115893\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T06:01:34Z","timestamp":1694152894000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1115893\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,8]]},"references-count":20,"alternative-id":["10.3389\/fendo.2023.1115893"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1115893","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,8]]},"article-number":"1115893"}}