ID #131 CNS Neuroblastoma, FOXR2-activated: A Pooled Analysis of Published Clinical Outcomes

Abstract Background Central nervous system (CNS) neuroblastoma, FOXR2-activated is a recently defined embryonal tumor entity in the WHO CNS5 classification. It is characterized by FOXR2 activation and distinct molecular and histopathologic features. Given its recent recognition, the clinical spectrum, treatment approaches, and outcomes remain incompletely characterized. Methods A systematic review of the literature was performed in PubMed, Embase, and Scopus from inception through June 2025, following PRISMA guidelines. Reported cases of CNS neuroblastoma, FOXR2-activated with available clinical data were included. Extracted variables encompassed demographics, tumor location, treatment modalities, and survival outcomes. Pooled descriptive analyses were conducted. Results Ninety-four patients across six studies were identifies. Median age at diagnosis was 4.2 years (0.8-15 years), with no sex predominance. Tumors were predominantly supratentorial (88%). Chemotherapy was administered in 90% of patients. High-dose chemotherapy with autologous stem cell rescue was primarily utilized in younger children (median age ∼2 years), whereas radiotherapy (most commonly craniospinal irradiation) was preferentially delivered to older patients (median age ∼8 years). Radiotherapy was reported in 40% of patients overall. Multimodal therapy incorporating maximal safe resection and intensive adjuvant treatment was associated with favorable outcomes, with a pooled estimated 5-year survival of approximately 82%, despite aggressive histologic features. Conclusions CNS neuroblastoma, FOXR2-activated represents a biologically distinct pediatric embryonal tumor with encouraging survival when treated with intensive multimodal therapy. Younger patients are commonly managed with chemotherapy-intensive approaches to defer radiation, while older patients more frequently receive craniospinal irradiation. Accurate molecular diagnosis is essential for classification and treatment planning. Prospective, collaborative studies are needed to refine risk stratification, clarify the role of radiation therapy, and minimize long-term treatment-related toxicity.