{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:35:42Z","timestamp":1762900542119,"version":"3.37.3"},"reference-count":30,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The response rate of advanced adrenocortical carcinoma (ACC) to standard\n                    chemotherapy with mitotane and etoposide\/doxorubicin\/cisplatin\n                    (EDP-M) is unsatisfactory, and benefit is frequently short lived. Immune\n                    checkpoint inhibitors (CPI) have been examined in patient\u2019s refractory\n                    to EDP-M, but objective response rates are only approximately 15%.\n                    High-dose rate brachytherapy (HDR-BT) is a catheter-based internal radiotherapy\n                    and expected to favorably combine with immunotherapies. Here we describe three\n                    cases of patients with advanced ACC who were treated with HDR-BT and the CPI\n                    pembrolizumab. None of the tumors were positive for established response markers\n                    to CPI. All patients were female, had progressed on EDP-M and received external\n                    beam radiation therapy for metastatic ACC. Pembrolizumab was initiated 7 or 23\n                    months after brachytherapy in two cases and prior to brachytherapy in one case.\n                    Best response of lesions treated with brachytherapy was complete (n=2)\n                    or partial response (n=1) that was ongoing at last follow up after 23,\n                    45 and 4 months, respectively. Considering all sites of tumor, response was\n                    complete and partial remission in the two patients with brachytherapy prior to\n                    pembrolizumab. The third patient developed progressive disease with severe\n                    Cushing\u2019s syndrome and died due to COVID-19. Immune-related adverse\n                    events of colitis (grade 3), gastroduodenitis (grade 3), pneumonitis (grade 2)\n                    and thyroiditis (grade 1) occurred in the two patients with systemic response.\n                    HDR-BT controlled metastases locally. Sequential combination with CPI therapy\n                    may enhance an abscopal antitumoral effect in non-irradiated metastases in ACC.\n                    Systematic studies are required to confirm this preliminary experience and to\n                    understand underlying mechanisms.<\/jats:p>","DOI":"10.1055\/a-2150-3944","type":"journal-article","created":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T22:47:00Z","timestamp":1695682020000},"page":"30-37","source":"Crossref","is-referenced-by-count":6,"title":["High-Dose Rate Brachytherapy Combined with PD-1 Blockade as a\n                    Treatment for Metastatic Adrenocortical Carcinoma \u2013 A Single Center Case\n                    Series"],"prefix":"10.1055","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0772-5242","authenticated-orcid":false,"given":"Paul","family":"Schwarzlmueller","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, University Hospital, LMU Munich, Munich,\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8709-7252","authenticated-orcid":false,"given":"Stefanie","family":"Corradini","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital, LMU Munich,\n                    Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-5410","authenticated-orcid":false,"given":"Max","family":"Seidensticker","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Hospital, LMU Munich, Munich,\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University\n                    Hospital, LMU Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Schreiner","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, University Hospital, LMU Munich, Munich,\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, University Hospital, LMU Munich, Munich,\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Triebig","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, University Hospital, LMU Munich, Munich,\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1822-0197","authenticated-orcid":false,"given":"Thomas","family":"Kn\u00f6sel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine, LMU Munich, Munich,\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Montserrat","family":"Pazos","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital, LMU Munich,\n                    Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Pfluger","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, University Hospital, LMU Munich,\n                    Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5873-8567","authenticated-orcid":false,"given":"Isabel","family":"Weigand","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, University Hospital, LMU Munich, Munich,\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claus","family":"Belka","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University Hospital, LMU Munich,\n                    Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Ricke","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Hospital, LMU Munich, Munich,\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9817-9875","authenticated-orcid":false,"given":"Martin","family":"Reincke","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, University Hospital, LMU Munich, Munich,\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Schmidmaier","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, University Hospital, LMU Munich, Munich,\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7628-3161","authenticated-orcid":false,"given":"Matthias","family":"Kroiss","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, University Hospital, LMU Munich, Munich,\n                    Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1056\/NEJMoa1200966","article-title":"Combination chemotherapy in advanced adrenocortical carcinoma","volume":"366","author":"M Fassnacht","year":"2012","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s40425-018-0424-9","article-title":"Avelumab in patients with previously treated metastatic adrenocortical\n                    carcinoma: phase 1b results from the JAVELIN solid tumor trial","volume":"6","author":"C Le Tourneau","year":"2018","journal-title":"J Immunother Cancer"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"6193","DOI":"10.1210\/jc.2019-00600","article-title":"Nivolumab in metastatic adrenocortical carcinoma: results of a phase 2\n                    trial","volume":"104","author":"B A Carneiro","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1186\/s40425-019-0722-x","article-title":"Phase II clinical trial of pembrolizumab efficacy and safety in advanced\n                    adrenocortical carcinoma","volume":"7","author":"M A Habra","year":"2019","journal-title":"J Immunother Cancer"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1200\/JCO.19.01586","article-title":"PD-1 Blockade in advanced adrenocortical carcinoma","volume":"38","author":"N Raj","year":"2020","journal-title":"J Clin Oncol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1908771","DOI":"10.1080\/2162402X.2021.1908771","article-title":"Combination immunotherapy with ipilimumab and nivolumab in patients with\n                    advanced adrenocortical carcinoma: a subgroup analysis of CA209-538","volume":"10","author":"O Klein","year":"2021","journal-title":"Oncoimmunology"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.critrevonc.2017.06.001","article-title":"Biomarkers of response to PD-1\/PD-L1 inhibition","volume":"116","author":"S Maleki Vareki","year":"2017","journal-title":"Crit Rev Oncol Hematol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40425-015-0047-3","article-title":"Programmed death ligand-1 expression in adrenocortical carcinoma: an exploratory\n                    biomarker study","volume":"3","author":"A P Fay","year":"2015","journal-title":"J Immunother Cancer"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/ejendo\/lvad054","article-title":"Outcome of immunotherapy in adrenocortical carcinoma: a retrospective cohort\n                    study","volume":"188","author":"H Remde","year":"2023","journal-title":"Eur J Endocrinol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.annonc.2020.08.2099","article-title":"Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN\n                    clinical practice guidelines for diagnosis, treatment and follow-up","volume":"31","author":"M Fassnacht","year":"2020","journal-title":"Ann Oncol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.ijrobp.2003.09.012","article-title":"Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is\n                    immune mediated","volume":"58","author":"S Demaria","year":"2004","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1259\/0007-1285-26-305-234","article-title":"Whole body irradiation; radiobiology or medicine?","volume":"26","author":"R H. Mole","year":"1953","journal-title":"Br J Radiol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.currproblcancer.2015.10.001","article-title":"Systematic review of case reports on the abscopal effect","volume":"40","author":"Y Abuodeh","year":"2016","journal-title":"Curr Probl Cancer"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature14292","article-title":"Radiation and dual checkpoint blockade activate non-redundant immune mechanisms\n                    in cancer","volume":"520","author":"C Twyman-Saint Victor","year":"2015","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.ijrobp.2021.04.009","article-title":"Fractionated radiation severely reduces the number of CD8+ T cells and\n                    mature antigen presenting cells within lung tumors","volume":"111","author":"E Reijmen","year":"2021","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1055\/a-0715-1946","article-title":"Advanced adrenocortical carcinoma \u2013 what to do when first-line therapy\n                    fails?","volume":"127","author":"F Megerle","year":"2019","journal-title":"Exp Clin Endocrinol Diabetes"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1210\/jc.2017-02591","article-title":"Mitotane monotherapy in patients with advanced adrenocortical carcinoma","volume":"103","author":"F Megerle","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"ref19","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\n                    adrenocortical carcinoma","volume":"91","author":"M Fassnacht","year":"2006","journal-title":"J Clin Endocrinol Metab"},{"key":"ref20","first-page":"15","article-title":"Treatment outcomes of adjuvant radiotherapy in adrenocortical carcinoma\n                    \u2013 a 13-years experience from a tertiary care centre","author":"D Khosla","year":"2023","journal-title":"Rare Tumors"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1038\/s41416-022-02082-0","article-title":"Efficacy and safety of radiation therapy in advanced adrenocortical\n                    carcinoma","volume":"128","author":"O Kimpel","year":"2023","journal-title":"Br J Cancer"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1002\/cncr.24331","article-title":"Radiotherapy in adrenocortical carcinoma","volume":"115","author":"B Polat","year":"2009","journal-title":"Cancer"},{"key":"ref23","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\n                    of adrenocortical carcinoma in adults, in collaboration with the European\n                    network for the study of adrenal tumors","volume":"179","author":"M Fassnacht","year":"2018","journal-title":"Eur J Endocrinol"},{"key":"ref24","first-page":"105","article-title":"Treatment with 90Y\/177Lu-DOTATOC in patients with metastatic\n                    adrenocortical carcinoma expressing somatostatin receptors","author":"S Grisanti","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"bvac091","DOI":"10.1210\/jendso\/bvac091","article-title":"Yttrium-90 selective internal radiation therapy plus cryoablation for recurrent\n                    adrenocortical carcinoma with liver metastases","volume":"6","author":"T Y Lin","year":"2022","journal-title":"J Endocr Soc"},{"key":"ref26","first-page":"14","article-title":"Loco-regional therapies in oligometastatic adrenocortical carcinoma","author":"C Roux","year":"2022","journal-title":"Cancers (Basel)"},{"key":"ref27","first-page":"24","article-title":"Harnessing the immunological effects of radiation to improve immunotherapies in\n                    cancer","author":"G Hannon","year":"2023","journal-title":"Int J Mol Sci"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S2213-2600(20)30391-X","article-title":"Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung\n                    cancer: a pooled analysis of two randomised trials","volume":"9","author":"W Theelen","year":"2021","journal-title":"Lancet Respir Med"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000867","article-title":"Tumor-draining lymph node is important for a robust abscopal effect stimulated\n                    by radiotherapy","volume":"8","author":"Z S Buchwald","year":"2020","journal-title":"J Immunother Cancer"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abg0117","article-title":"Sequence of alphaPD-1 relative to local tumor irradiation determines the\n                    induction of abscopal antitumor immune responses","volume":"6","author":"J Wei","year":"2021","journal-title":"Sci Immunol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e0157164","DOI":"10.1371\/journal.pone.0157164","article-title":"Optimizing timing of immunotherapy improves control of tumors by\n                    hypofractionated radiation therapy","volume":"11","author":"K H Young","year":"2016","journal-title":"PLoS One"}],"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2150-3944.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T13:21:35Z","timestamp":1730812895000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2150-3944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,25]]},"references-count":30,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2024,1,3]]},"published-print":{"date-parts":[[2024,1]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2150-3944","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"type":"print","value":"0018-5043"},{"type":"electronic","value":"1439-4286"}],"subject":[],"published":{"date-parts":[[2023,9,25]]}}}