Abstract B011: Molecularly guided treatment pathways in ependymoma: Integrating surgery, radiotherapy, and systemic strategies

Abstract Ependymoma comprises 1.5–2% of central nervous system tumors overall and up to 12% of pediatric brain tumors, with prognosis shaped by tumor location, molecular subtype, and extent of resection. Despite advances, recurrence and late treatment morbidity remain major challenges. Current treatment pathways were evaluated based on consensus guidelines, WHO 2021 classification, and recent clinical and translational studies. Emphasis was placed on the role of surgery, radiotherapy, chemotherapy, molecular stratification, and salvage therapy. Maximal safe resection is the cornerstone of therapy and the strongest modifiable prognostic factor. For intracranial disease, postoperative focal radiotherapy using conformal photon or proton modalities is standard, while craniospinal irradiation is reserved for disseminated cases. In the spinal compartment, gross total resection can be curative for grade 2 tumors, though MYCN-amplified variants require multimodality therapy. Chemotherapy has not shown consistent benefit in upfront settings, but is utilized in infants to delay radiation or in recurrent disease. Treatment stratification now incorporates molecular markers: supratentorial ZFTA fusion–positive tumors behave aggressively, YAP1 fusion–positive tumors have favorable prognosis, posterior fossa group A tumors are aggressive with chromosome 1q gain, while group B tumors are less aggressive and arise in older children. Emerging advances include proton therapy for re-irradiation, integration of 1q gain and EZHIP-driven H3K27me3 loss into prognostic models, and exploration of targeted systemic approaches. Contemporary treatment pathways for ependymoma rely on maximal safe resection and precision radiotherapy, with therapy tailored to molecular subtype and risk category. Recurrent disease remains a critical area of unmet need, with investigational therapies under study. Future directions aim to integrate precision radiation, molecular risk-adaptation, and novel systemic or immunologic strategies to optimize survival and reduce long-term morbidity. Generative AI was used to assist with language editing of this abstract. Citation Format: Charlene Mansour, Vyom Shah, Frances Lai, Jay Patel, Jacqueline Norrell, Morana Vojnic. Molecularly guided treatment pathways in ependymoma: Integrating surgery, radiotherapy, and systemic strategies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Fusion-Positive Cancer: From Discovery to Therapy; 2026 Jan 13-15; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(1_Suppl):Abstract nr B011.