Three decades of radiotherapy advancements for pediatric ependymoma.
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Over the past 30 years, advancements in radiotherapy have transformed the treatment of pediatric ependymoma, improving tumor control and reducing treatment-related complications. Early protocols, such as RT1 and ACNS0121, demonstrated the efficacy of immediate post-operative radiotherapy, particularly for children as young as 12 months, setting benchmarks for modern treatment strategies. The introduction of conformal photon therapy revolutionized tumor targeting by minimizing radiation exposure to surrounding normal tissues, while proton therapy has emerged as the preferred modality in developed countries due to its superior normal tissue-sparing properties. Despite these advances, long-term comparative data between photon and proton therapy remains limited. Critical factors in radiotherapy planning include tumor location, patient age, molecular features, and the potential for neuraxis dissemination. Advances in imaging, such as high-resolution MRI and emerging molecular staging techniques, have enhanced precision in treatment planning and risk stratification. However, challenges persist for patients with residual or recurrent disease. Reirradiation has emerged as a promising option for relapse, demonstrating high rates of tumor control and low risks of complications when combined with timely surgical intervention and multidisciplinary care. This chapter highlights the importance of leveraging data from three separate clinical trials to refine treatment strategies and address cognitive outcomes, which have been identified as a major area of clinical importance and research. Future trials are expected to explore molecular risk stratification and the integration of systemic therapies alongside radiotherapy to optimize outcomes, ensuring continued progress in the care of children with ependymoma.