Adrenocortical Carcinoma in Childhood: A Systematic Review

Abstract

Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89%). Most patients were diagnosed with localized disease, whereas 23% had metastasis at primary diagnosis. Only 72% of the patients achieved complete resection. In 334 children (23%), recurrent disease was reported: 81%—local recurrence, 19% (n = 65)—distant metastases at relapse. Patients <4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies.

Radiotherapy for pediatric adrenocortical carcinoma – Review of the literature

“…In the pediatric setting, evidence for adjuvant RT is even more limited. In a recent systematic review on pACC, we demonstrated that the rate of local recurrences was higher than expected: 81% of reported relapses were due to local recurrences or lymph node metastases [10]. In contrast, local recurrences in the adult setting have been reported only in around 50-60% of patients [11].…”

“…Available information on RT from the literature is listed in Table 1. None of these were randomized controlled trials (RCTs) but retrospective analyses, with 76 patients managed with RT [10]. Additionally, we included data of 4 previous unreported patients upon receiving further information from the authors.…”

“…Therefore, in order to gain clear evidence on the efficacy of RT patients have to be enrolled in randomized controlled trials (RCTs) or at least in standardized prospective registry trials enabling research. Still, recently published pediatric data [2,10] showed improvements in local control and long-term outcomes in pACC patients managed with RT.…”

“…Excerpted data was double-reviewed for inclusion (MR, VW). The search strategy was performed according to Riedmeier et al [10].…”

“…On the remaining 50 patients, no additional information was available. Tumor stages were reported according to the international TNM classification system or the ENSAT criteria [10,23].…”