European standard clinical practice recommendations for newly diagnosed ependymoma of childhood and adolescence

Abstract

Ependymomas are tumors of glial origin representing the second most common malignant brain tumors of childhood. Peak incidence in childhood is under 3 years of age. Most paediatric ependymomas arise intracranially and are molecularly divided into four groups, namely supratentorial ependymoma, ZFTA fusion-positive (ST-ZFTA), supratentorial ependymoma, YAP1 fusion-positive (ST-YAP1), posterior fossa group A (PF-A), and posterior fossa group B (PF-B) ependymoma. Spinal ependymomas in children are rare. An integrated diagnosis requires a combination of histological and molecular features as well as tumour localization. Staging with pre- and early post-surgery magnetic resonance imaging of the neuraxis, accompanied by cerebrospinal fluid (CSF) analysis 14 days post surgery must be performed. CSF at primary surgery is highly recommended to both detect and inform biomarkers. Patients should ideally be treated in specialized centers and, whenever possible, within a prospective clinical trial. Molecular classification has become increasingly important and will be applied to enable patient stratification in upcoming clinical trials. However, there are not yet specific treatment recommendations for distinct molecular groups. Apart from the molecular group, the extent of neurosurgical resection is the most consistent prognostic factor. Therefore, the feasibility of second-look surgery targeting complete resection should always be evaluated if residual disease. Adjuvant radiotherapy has been shown to be effective in consolidating local control and is therefore recommended following complete resection. Focal radiotherapy is the standard of care for patients with non-disseminated ependymoma, and craniospinal radiotherapy is recommended in older children with metastatic disease. For very young children with metastatic disease, radiotherapy avoidance strategies using systemic therapy is recommended to reduce the risk of neurocognitive effects. Highly conformal techniques such as proton beam therapy or intensity-modulated radiation therapy are preferred. Chemotherapy bridging therapy may be applied until patients reach 12–18 months of age, or to facilitate complete resections where further surgery is planned.