Citations 2
Clinical predictors of outcome in advanced adrenocortical carcinoma: a multicenter international ENSAT study
Mangone, Alessandra , Altieri, Barbara , Ferrante, Emanuele , Bancos, Irina, Luconi, Michaela , Ziółkowska, Barbara, Nekić, Anja Barač , Libe, Rossella, Pittaway, James F H, Laganà, Marta, Dalmazi, Guido Di , Kimpel, Otilia , Fard, Bahar Bahrani , Kotecka-Blicharz, Agnieszka, Kastelan, Darko, Bennett, Gillian , Schauer, Marc P, Elhassan, Yasir , Detomas, Mario, Zanatta, Lorenzo, Sadiq, Maaz Tahir , Mantovani, Giovanna, Ronchi, Cristina L, Ronchi, Cristina L. , Luconi, Michaela , Bancos, Irina , Ceccato, Filippo , Di Dalmazi, Guido , Kimpel, Otilia , Canu, Letizia , Kastelan, Darko , Bouys, Lucas , Elhassan, Yasir S , Detomas, Mario , Mantovani, Giovanna , Ronchi, Cristina L , Bancos, Irina , Ziółkowska, Barbara , Libé, Rossella , Ceccato, Filippo , Pittaway, J , Laganà, Marta , Peverelli, Erika , Canu, Letizia , Kotecka-Blicharz, Agnieszka , Kaštelan, Darko , Tizianel, Irene , Schauer, Marc Philipp , Zanatta, Lorenzo
European Journal of Endocrinology | March 5, 2026 | Volume: 194 | Issue: 3 | Pages: 381-392
Abstract Objective 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. Methods 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 ± mitotane (n = 178), or second-line regimens (gemcitabine + capecitabine ± 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. Results Tumor burden, cortisol excess, ECOG-PS, and NLR ≥5 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 >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 < .01) and second-line therapies (P = .04). Conclusions 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.
ENSAT registry-based randomized clinical trials for adrenocortical carcinoma
Baudin, Éric , Chrisoulidou, Alexandra , Angelousi, Anna , Lamas, Cristina , Dijkum, Els J.�M. Nieveen van , Ceccato, Filippo , Tiberi, Guido A M, Ettaieb, Hester, Kiriakopoulos, Andreas , Kaštelan, Darko , Osher, Esthr, Yiannakopoulou, Eugenia , Arnaldi, Giorgio , Assié, Guillaume , Bourdeau, Isabelle , Newell‐Price, John , Nowak, Karolina M. , Romero, Mario, Martino, Maria Cristina De , Bugalho, Maria João , Dennedy, Michael Conall , Loli, Paula, Rodien, Patrice , Feelders, Richard A. , Aylwin, Simon , Morelli, Valentina , Vroonen, Laurent , Trofimiuk–Müldner, Małgorzata , Kroiß, Matthias , Mihai, Radu , Beuschlein, Felix , Ceccato, Filippo , Kroiss, Matthias , Dennedy, M Conall , Beuschlein, Felix , Newell-Price, John , Kastelan, Darko , Crona, Joakim , Terzolo, Massimo , Ronchi, Cristina L. , Borson‐Chazot, Françoise , Reimondo, Giuseppe , Canu, Letizia , Paiva, Isabel , Sherlock, Mark , Vantyghem, Marie‐Christine , Krijger, Ronald R. de , Slycke, Sam Van , Shafigullina, Zulfiya R. , Bancos, Irina , Quinkler, Marcus , Luconi, Michaela , Naruse, Mitsuhide , Igaz, Péter , Casa, Silvia Della , Berruti, Alfredo , Faßnacht, Martin
European Journal of Endocrinology | November 9, 2020 | Volume: 184 | Issue: 2 | Pages: R51-R59
Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.