TY - JOUR
T1 - Morbidity and mortality of bone metastases in advanced adrenocortical carcinoma
T2 - a multicenter retrospective study
AU - Berruti, Alfredo
AU - Libe, Rossella
AU - Lagana, Marta
AU - Ettaieb, Hester
AU - Sukkari, Mohamad Anas
AU - Bertherat, Jerome
AU - Feelders, Richard A.
AU - Grisanti, Salvatore
AU - Cartry, Jerome
AU - Mazziotti, Gherardo
AU - Sigala, Sandra
AU - Baudin, Eric
AU - Haak, Harm
AU - Habra, Mouhammed Amir
AU - Terzolo, Massimo
N1 - Funding Information:
Massimo Terzolo has received research grant from HRA and Novartis. Alfredo Berruti has received research grant from Janssen Cilag and honoraria from HRA for advisory board participation. The other authors have nothing to discose.
Funding Information:
A research grant from Associazione Italiana per la Ricerca sul Cancro (grant number IG17678) to M T. The authors would like to thank the Dutch Adrenal Network, for providing patient data. The study was sponsored and funded in part by the ‘Fondazione Internazionale di Ricerca in Medicina’ (FIRM) onlus.
Funding Information:
A research grant from Associazione Italiana per la Ricerca sul Cancro (grant number IG17678) to M T.
Funding Information:
The authors would like to thank the Dutch Adrenal Network, for providing patient data. The study was sponsored and funded in part by the ‘Fondazione Internazionale di Ricerca in Medicina’ (FIRM) onlus.
Publisher Copyright:
© 2019 European Society of Endocrinology Printed in Great Britain.
PY - 2019/5
Y1 - 2019/5
N2 - Introduction: Adrenocortical carcinoma (ACC) is a rare cancer that commonly spreads to the liver, lungs and lymph nodes. Bone metastases are infrequent.Objective: The aim of this report was to describe the clinical characteristics, survival perspective, prognostic factors and frequency of adverse skeletal-related events (SREs) in patients with ACC who developed bone metastasis.Methods: This is a retrospective, observational, multicenter, multinational study of patients diagnosed with bone metastases from ACC who were treated and followed up in three European countries (France, Italy and The Netherlands) and one center in the United States.Results: Data of 156 patients were captured. The median overall survival was 11 months. SREs occurred in 47% of patients: 17% bone fractures, 17% spinal cord compression, 1% hypercalcemia, 12% developed more than one SRE. In multivariate analysis, cortisol hypersecretion was the only prognostic factor significantly associated with a higher mortality risk (hazard ratio (HR) 2.24, 95% confidence interval (CI): 1.19-4.23, P = 0.013) and with the development of a SREs (of border line significance). The administration of antiresorptive therapies (bisphosphonates and denosumab) was associated with a lower risk of death, even if not significant, and their survival benefit appeared confined in patients attaining serum mitotane levels within the therapeutic range.Conclusion: Bone metastases in ACC patients are associated with poor prognosis and high risk of SREs. Cortisol hypersecretion was the only prognostic factor suggesting a potential benefit from antisecretory medications. The therapeutic role of bisphosphonates and denosumab to improve patient outcome deserves to be tested in a prospective clinical trial.
AB - Introduction: Adrenocortical carcinoma (ACC) is a rare cancer that commonly spreads to the liver, lungs and lymph nodes. Bone metastases are infrequent.Objective: The aim of this report was to describe the clinical characteristics, survival perspective, prognostic factors and frequency of adverse skeletal-related events (SREs) in patients with ACC who developed bone metastasis.Methods: This is a retrospective, observational, multicenter, multinational study of patients diagnosed with bone metastases from ACC who were treated and followed up in three European countries (France, Italy and The Netherlands) and one center in the United States.Results: Data of 156 patients were captured. The median overall survival was 11 months. SREs occurred in 47% of patients: 17% bone fractures, 17% spinal cord compression, 1% hypercalcemia, 12% developed more than one SRE. In multivariate analysis, cortisol hypersecretion was the only prognostic factor significantly associated with a higher mortality risk (hazard ratio (HR) 2.24, 95% confidence interval (CI): 1.19-4.23, P = 0.013) and with the development of a SREs (of border line significance). The administration of antiresorptive therapies (bisphosphonates and denosumab) was associated with a lower risk of death, even if not significant, and their survival benefit appeared confined in patients attaining serum mitotane levels within the therapeutic range.Conclusion: Bone metastases in ACC patients are associated with poor prognosis and high risk of SREs. Cortisol hypersecretion was the only prognostic factor suggesting a potential benefit from antisecretory medications. The therapeutic role of bisphosphonates and denosumab to improve patient outcome deserves to be tested in a prospective clinical trial.
KW - CLINICAL-PRACTICE GUIDELINES
KW - PROSTATE-CANCER PATIENTS
KW - ZOLEDRONIC ACID
KW - TARGETED THERAPIES
KW - EUROPEAN NETWORK
KW - BREAST-CANCER
KW - LUNG-CANCER
KW - PHASE-III
KW - MANAGEMENT
KW - HYPERCORTISOLISM
U2 - 10.1530/EJE-19-0026
DO - 10.1530/EJE-19-0026
M3 - Article
C2 - 30970324
SN - 0804-4643
VL - 180
SP - 311
EP - 320
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
IS - 5
ER -