Functional and behavioral outcomes in pediatric adrenal carcinoma under mitotane therapy: a caregiver-reported pilot study

Abstract Objective: Mitotane is the standard therapy for advanced pediatric adrenocortical carcinoma (pACC). With improving survival, treatment-related long-term side effects and their impact on everyday functioning are becoming increasingly relevant. This multicenter pilot study provides first insights into this underexplored topic and lays the groundwork for future prospective investigations. Design and methods: Caregivers of children with pACC treated with mitotane completed an online questionnaire. Based on these retrospective caregiver-reported data, treatment-related side effects and growth parameters were assessed. Using two validated instruments - Child and Adolescent Scale of Participation (CASP) and Strengths and Difficulties Questionnaire (SDQ) - caregivers rated functional participation and behavioral outcomes. We classified patients according to ongoing versus completed mitotane therapy and compared them with a sibling control group. Results: The cohort included 24 children with pACC from eight countries, predominantly with advanced tumors (stage III-IV: 66.7%, median age: 7.4 years, 41.7% females). Half had completed mitotane therapy, and half were still receiving it. Most patients experienced relevant side effects, with adrenal insufficiency being the most frequent ongoing limitation. Patients on ongoing mitotane therapy showed reduced functional participation and more pronounced behavioral difficulties, whereas those who had completed therapy had outcomes comparable to their siblings. Conclusion: The findings of this pilot study suggest temporary impairments in functional participation and psychosocial behavior during mitotane treatment, with improvement after therapy completion. In contrast, endocrine sequelae, particularly adrenal insufficiency, may persist beyond treatment. These observations underscore the need for standardized long-term endocrine follow-up and support the feasibility of larger, prospective studies to evaluate long-term neuropsychological outcome, especially in younger children.