With an annual cumulative occurrence of approximately 15,000 in North America, all childhood cancers are rare. Very rare cancers as defined by both the European Cooperative Study Group for Rare Pediatric Cancers (EXPeRT) and the Children’s Oncology Group (COG) fall into two principal categories: those so uncommon (fewer than 2 cases/million) that their study is challenging even through cooperative group efforts (e.g. pleuropulmonary blastoma, desmoplastic small round cell tumor) and those that are far more common in adults and therefore rarely studied in children (e.g. thyroid, melanoma, gastrointestinal stromal tumor). [1](#ref-0001) Treatment strategies for these latter tumors are typically based on adult guidelines, although the pediatric variants of these tumors may harbor different genetic signatures and demonstrate different behavior. If melanoma and differentiated thyroid cancer are excluded, other rare cancer types account for only 2% of the cancers in children aged 0 to 14.[1](#ref-0001) This article highlights several of the most common rare tumor types.

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.

Purpose Pediatric patients with metastatic solid tumors historically have a poor overall survival. Some pediatric patients may still be potentially curable with aggressive local therapy to metastatic disease. The purpose of this study is to report results of the use of SBRT in the treatment of pediatric metastatic disease. Materials and Methods Pediatric patients who received SBRT between the years 2000-2020. Study endpoints included local control (LC), progression free survival (PFS), overall survival (OS), cumulative incidence (CI) of death or local failure and toxicity. The endpoints with respect to survival and LC were calculated using the Kaplan-Meier estimate. The cumulative incidence of local failure was calculated using death as a competing risk. Results 16 patients with 36 lesions irradiated met inclusion criteria. The median OS and PFS was 17 months and 15.7 months, respectively. The 1-year OS was 75%. The 6- and 12-month LC was 85% and 78%, respectively. There were no local failures in lesions receving a BED10≥100 Gy. Patients who had ≤5 metastatic lesions at first recurrence had a superior 1-year OS of 100% versus 50% with >5 lesions. One patient (6.3%) experienced a grade 3 CNS toxicity. Conclusions LC was excellent with SBRT delivered to metastatic disease, particularly for lesions receiving a BED10≥100 Gy. High-grade toxicity was rare in our patient population. Patients with ≤5 metastatic sites have a significantly better OS compared to >5 sites. Future prospective trials with multi-institutional collaboration will be necessary to evaluate appropriate patient selection and the optimal radiation dose regimen.