Background: Neuroblastoma is the most common extracranial solid tumor in children, with about half of cases classified as high risk. Treatment varies by risk level, with high-risk patients undergoing aggressive multimodal therapy. Long-term survival has improved, but survivors face significant risks of late treatment effects, including adrenal insufficiency. This study investigates the incidence of adrenal insufficiency among neuroblastoma patients, focusing on high-risk versus non-high-risk cases. Procedure: This retrospective cohort study at a single tertiary children’s hospital reviewed records from 1998 to 2021, identifying 370 neuroblastoma patients, of which 137 had complete risk stratification. The primary outcome was the incidence of adrenal insufficiency, diagnosed based on clinical evaluation and response to hydrocortisone therapy. Demographic and clinical data were collected, and statistical analyses were performed to compare high-risk and non-high-risk groups. Results: Among 137 neuroblastoma patients, 9 (12.0%) high-risk and 3 (4.9%) non-high-risk patients were diagnosed with adrenal insufficiency. The cumulative incidence of adrenal insufficiency was 16.6% in high-risk and 3.5% in non-high-risk patients. High-risk patients with adrenal insufficiency had a median time of 10.2 months from neuroblastoma diagnosis to adrenal insufficiency diagnosis, with all cases occurring in patients with adrenal primary tumors. There were no significant differences in demographic or clinical characteristics between high-risk patients with and without adrenal insufficiency. Conclusions: The study found a higher cumulative incidence of adrenal insufficiency in high-risk neuroblastoma patients, particularly those with adrenal primary tumors. Despite the lack of significant prevalence difference between risk groups, the findings underscore the need for vigilant monitoring and screening for adrenal insufficiency in neuroblastoma patients during and after treatment. Future research should include larger, multi-institutional cohorts to better understand risk factors and optimize screening protocols.

BACKGROUND: Diagnostic mIBG (meta-iodobenzylguanidine) scans are an integral component of response assessment in children with high-risk neuroblastoma. The role of end of induction (EOI) Curie Scores (CS) was previously described in patients undergoing a single autologous hematopoietic cell transplant (AHCT) as consolidation therapy. OBJECTIVE: We now examine the prognostic significance of CS in patients randomized to tandem AHCT on the Children’s Oncology Group (COG) trial ANBL0532. STUDY DESIGN: A retrospective analysis of mIBG scans obtained from patients enrolled in COG ANBL0532 was performed. Evaluable patients had mIBG-avid, International Neuroblastoma Staging System (INSS) stage 4 disease, did not progress during induction therapy, consented to consolidation randomization, and received a tandem AHCT (n=80). Optimal CS cut points maximized the outcome difference (≤ vs >CS cut-off) according to the Youden index. RESULTS: For recipients of tandem AHCT, the optimal cut point at diagnosis was CS=12, with superior EFS from study enrollment for patients with CS<12 (3-year EFS 74.2±7.9%) vs CS>12 (59.2±7.1%) (p=0.002). At EOI, the optimal cut point was CS=0, with superior end-induction EFS for patients with CS=0 (72.9±6.4%) vs CS>0 (46.5±9.1%) (p=0.002). CONCLUSION: In the setting of tandem transplantation for children with high-risk neuroblastoma, Curie scores at diagnosis and end-induction may identify a more favorable patient group. Patients treated with tandem AHCT who exhibited a CS<12 at diagnosis or CS=0 at EOI had superior EFS compared to those with CS above these cut points.