Refractory and relapsed paediatric ACC in the MET studies – A challenging situation necessitating novel diagnostic and therapeutic concepts

Abstract

Background: Paediatric adrenocortical carcinomas (ACC) are highly aggressive malignancies with a dismal prognosis in advanced and metastatic diseases. Little is known about outcome of patients with refractory and relapsed (r/r) disease. Procedure: National retrospective multicentre study including r/r ACC diagnosed in patients aged< 18 years registered in the MET studies between January 1997 and December 2021 Results: A total of 16 patients (5 male; median age 12.9 years) with refractory disease were included. Median time to progression was 0.6 years [0.0–1.3]. Site of progression was locoregional (n = 1), distant (n = 3), and combined (n = 12). 3-year overall (OS) and progression-free (PFS) survival were both 0%. Thirty patients with relapse (11 male; median age 7.3 years) were identified. Median time to relapse was 0.7 years [0.1–3.2]. Site of relapse was locoregional (n = 8), distant (n = 15), and combined (n = 7). At last follow-up, 20 patients had died of disease or complications or were alive with disease, 10 patients were in second complete remission (median follow-up: 6.8 years [0–10.5]). 3-year OS and PFS following relapse were 39.1% and 31.9%. Survival was superior in patients with distant relapse (59.6%) compared to locoregional (28.6%) and combined (14.3%) (p = 0.028) and in patients with complete surgical resection of all sites of recurrence (70.0%) compared to incomplete (21.4%) and no surgery (0%) (p = 0.003). Conclusions: For patients nonresponsive to first-line therapy or who experience relapse, prognosis is dismal and options are scarce. Site of relapse and resectability define prognosis. Novel therapeutic concepts are needed to improve the outcome of paediatric patients with r/r ACC.

Keywords

• Adrenocortical carcinoma
• Relapsed
• Refractory
• Children
• Outcome