Supratentorial ependymoma: a comprehensive review of molecular classification, management strategies, and clinical outcomes (Part II of pediatric ependymomas across compartments)

Abstract Purpose To review the clinical, molecular, and imaging landscape of pediatric supratentorial ependymoma (ST-EP) and outline current management principles guiding surgical and adjuvant treatment decisions. Methods Synthesis of literature regarding biology, diagnosis, and management of ST-EP, focusing on recently emerging molecular subtypes. Results ST-EP is an important and clinically significant intracranial malignancy comprising roughly 30–40% of all ependymoma cases. The 2021 WHO molecular classification stratified ST-EP into ZFTA-fusion, YAP1-fusion, and NEC subtypes, fundamentally altering our understanding of this pathology. ZFTA-fused tumors represent the majority of ST-EP, are seen in older patients and harbor a relatively worse prognosis while YAP1-fused tumors, though rarer, are enriched for younger children and carry a substantially more favorable prognosis. Management of very young children presents a unique therapeutic challenge, balancing disease control against the neurocognitive sequelae of cranial irradiation and aggressive surgery in the developing brain. Conclusion Across molecular subtypes, maximal safe surgical resection remains the dominant prognostic factor, with adjuvant focal radiotherapy well-supported based on tumor grade and extent of resection. Maintenance chemotherapy following radiotherapy has not demonstrated a survival benefit. Further multi-institutional investigation is needed to formalize molecularly-stratified treatment protocols, better characterize NEC subgroups, and identify targeted therapeutics for high-risk disease. Clinical trial number Not applicable.