Paul Schwarzlmueller, Stefanie Corradini, Max Seidensticker, Petra Zimmermann, Jochen Schreiner, Tanja Maier, Alexandra Triebig, Thomas Knösel, Montserrat Pazos, Thomas Pfluger, Isabel Weigand, Claus Belka, Jens Ricke, Martin Reincke, Ralf Schmidmaier, Matthias Kroiss
{"title":"高剂量率近距离放疗联合PD-1阻断治疗转移性肾上腺皮质癌——一个单中心病例系列。","authors":"Paul Schwarzlmueller, Stefanie Corradini, Max Seidensticker, Petra Zimmermann, Jochen Schreiner, Tanja Maier, Alexandra Triebig, Thomas Knösel, Montserrat Pazos, Thomas Pfluger, Isabel Weigand, Claus Belka, Jens Ricke, Martin Reincke, Ralf Schmidmaier, Matthias Kroiss","doi":"10.1055/a-2150-3944","DOIUrl":null,"url":null,"abstract":"<p><p>The response rate of advanced adrenocortical carcinoma (ACC) to standard chemotherapy with mitotane and etoposide/doxorubicin/cisplatin (EDP-M) is unsatisfactory, and benefit is frequently short lived. Immune checkpoint inhibitors (CPI) have been examined in patient's refractory to EDP-M, but objective response rates are only approximately 15%. High-dose rate brachytherapy (HDR-BT) is a catheter-based internal radiotherapy and expected to favorably combine with immunotherapies. Here we describe three cases of patients with advanced ACC who were treated with HDR-BT and the CPI pembrolizumab. None of the tumors were positive for established response markers to CPI. All patients were female, had progressed on EDP-M and received external beam radiation therapy for metastatic ACC. Pembrolizumab was initiated 7 or 23 months after brachytherapy in two cases and prior to brachytherapy in one case. Best response of lesions treated with brachytherapy was complete (n=2) or partial response (n=1) that was ongoing at last follow up after 23, 45 and 4 months, respectively. Considering all sites of tumor, response was complete and partial remission in the two patients with brachytherapy prior to pembrolizumab. The third patient developed progressive disease with severe Cushing's syndrome and died due to COVID-19. Immune-related adverse events of colitis (grade 3), gastroduodenitis (grade 3), pneumonitis (grade 2) and thyroiditis (grade 1) occurred in the two patients with systemic response. HDR-BT controlled metastases locally. Sequential combination with CPI therapy may enhance an abscopal antitumoral effect in non-irradiated metastases in ACC. Systematic studies are required to confirm this preliminary experience and to understand underlying mechanisms.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"High-Dose Rate Brachytherapy Combined with PD-1 Blockade as a Treatment for Metastatic Adrenocortical Carcinoma - A Single Center Case Series.\",\"authors\":\"Paul Schwarzlmueller, Stefanie Corradini, Max Seidensticker, Petra Zimmermann, Jochen Schreiner, Tanja Maier, Alexandra Triebig, Thomas Knösel, Montserrat Pazos, Thomas Pfluger, Isabel Weigand, Claus Belka, Jens Ricke, Martin Reincke, Ralf Schmidmaier, Matthias Kroiss\",\"doi\":\"10.1055/a-2150-3944\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The response rate of advanced adrenocortical carcinoma (ACC) to standard chemotherapy with mitotane and etoposide/doxorubicin/cisplatin (EDP-M) is unsatisfactory, and benefit is frequently short lived. Immune checkpoint inhibitors (CPI) have been examined in patient's refractory to EDP-M, but objective response rates are only approximately 15%. High-dose rate brachytherapy (HDR-BT) is a catheter-based internal radiotherapy and expected to favorably combine with immunotherapies. Here we describe three cases of patients with advanced ACC who were treated with HDR-BT and the CPI pembrolizumab. None of the tumors were positive for established response markers to CPI. All patients were female, had progressed on EDP-M and received external beam radiation therapy for metastatic ACC. Pembrolizumab was initiated 7 or 23 months after brachytherapy in two cases and prior to brachytherapy in one case. Best response of lesions treated with brachytherapy was complete (n=2) or partial response (n=1) that was ongoing at last follow up after 23, 45 and 4 months, respectively. Considering all sites of tumor, response was complete and partial remission in the two patients with brachytherapy prior to pembrolizumab. The third patient developed progressive disease with severe Cushing's syndrome and died due to COVID-19. Immune-related adverse events of colitis (grade 3), gastroduodenitis (grade 3), pneumonitis (grade 2) and thyroiditis (grade 1) occurred in the two patients with systemic response. HDR-BT controlled metastases locally. Sequential combination with CPI therapy may enhance an abscopal antitumoral effect in non-irradiated metastases in ACC. 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High-Dose Rate Brachytherapy Combined with PD-1 Blockade as a Treatment for Metastatic Adrenocortical Carcinoma - A Single Center Case Series.
The response rate of advanced adrenocortical carcinoma (ACC) to standard chemotherapy with mitotane and etoposide/doxorubicin/cisplatin (EDP-M) is unsatisfactory, and benefit is frequently short lived. Immune checkpoint inhibitors (CPI) have been examined in patient's refractory to EDP-M, but objective response rates are only approximately 15%. High-dose rate brachytherapy (HDR-BT) is a catheter-based internal radiotherapy and expected to favorably combine with immunotherapies. Here we describe three cases of patients with advanced ACC who were treated with HDR-BT and the CPI pembrolizumab. None of the tumors were positive for established response markers to CPI. All patients were female, had progressed on EDP-M and received external beam radiation therapy for metastatic ACC. Pembrolizumab was initiated 7 or 23 months after brachytherapy in two cases and prior to brachytherapy in one case. Best response of lesions treated with brachytherapy was complete (n=2) or partial response (n=1) that was ongoing at last follow up after 23, 45 and 4 months, respectively. Considering all sites of tumor, response was complete and partial remission in the two patients with brachytherapy prior to pembrolizumab. The third patient developed progressive disease with severe Cushing's syndrome and died due to COVID-19. Immune-related adverse events of colitis (grade 3), gastroduodenitis (grade 3), pneumonitis (grade 2) and thyroiditis (grade 1) occurred in the two patients with systemic response. HDR-BT controlled metastases locally. Sequential combination with CPI therapy may enhance an abscopal antitumoral effect in non-irradiated metastases in ACC. Systematic studies are required to confirm this preliminary experience and to understand underlying mechanisms.
期刊介绍:
Covering the fields of endocrinology and metabolism from both, a clinical and basic science perspective, this well regarded journal publishes original articles, and short communications on cutting edge topics.
Speedy publication time is given high priority, ensuring that endocrinologists worldwide get timely, fast-breaking information as it happens.
Hormone and Metabolic Research presents reviews, original papers, and short communications, and includes a section on Innovative Methods. With a preference for experimental over observational studies, this journal disseminates new and reliable experimental data from across the field of endocrinology and metabolism to researchers, scientists and doctors world-wide.