Endocrine Abstracts

Background: Metastatic adrenocortical carcinoma (ACC) is a highly aggressive endocrine malignancy with event-free survival rates <10% in most paediatric reports. About 15-25% of patients present with metastases at diagnosis. Complete surgical resection is the mainstay of therapy while chemotherapy and mitotane proved to be ineffective in children with metastatic disease highlighting the need for new approaches. Details on children with metastatic ACC are scarce but desperately needed.

Methods: Data from children and adolescents with metastatic ACC registered with the German Malignant Endocrine Tumour (MET) studies of the German Society for Paediatric Oncology and Haematology (GPOH) were included. We investigated the number, size, and sites of metastases, resectability, and speed of disease spread in patients with primary metastatic disease and metastatic relapse for guiding treatment concepts in future clinical trials.

Results: By December 2022, 20 patients with M+-disease at diagnosis and 22 patients with metastatic relapse had been reported. Median age at diagnosis was 12.8 years and 8.3 years. 2-year event-free survival (EFS) was 15.8% and 22.7%, respectively. Metastases were present in the lungs (n=30), liver (n=15), distant lymph nodes (n=14), bones (n=6), and central nervous system (CNS; n=4). Concurrent metastases in two or more organs were evident in 21 patients. Oligometastatic cancer (herein defined as ≤3 metastases limited to one organ) was reported in 9 patients while it was polymetastatic in 33 patients. R₀ resection of all metastatic sites was achieved in 7 patients including 2 patients with two affected organs. In one patient with a single CNS metastasis, radiotherapy was applied. R₀ resection was not reported in any patient with polymetastatic disease. Sixteen (of 20) and 15 (of 22) patients, respectively, demonstrated progressive disease. In oligometastatic ACC, disease progression was evident after a median of 9.2 months (range, 1.2-37.9), in polymetastatic ACC after a median of 5.5 months (range, 0-34.1). In 4 patients with metastases at diagnosis and 7 patients with metastatic relapse first/second complete remission was achieved. All of these 11 patients presented with oligometastatic disease including one patient with metastases in two organs (liver and lung).

Conclusion: Number, site, and resectability of metastases define prognosis in children and adolescents with metastatic ACC. We observed distinct clinical courses (with different prognosis) in children and adolescents with oligo- and polymetastatic ACC. New treatment approaches are urgently needed in children and adolescents with metastatic ACC.