What is ependymoma?

Ependymoma: Diagnosis and Management

Ependymomas are rare central nervous system tumors originating from ependymal cells lining the ventricles and central canal, with distinct molecular subgroups that determine prognosis and treatment approaches. 1

Epidemiology and Classification

• Ependymomas account for 1.8% of all primary CNS tumors and 6.8% of all gliomas, with an annual incidence of 0.43 per 100,000 population 1
• These tumors are proportionally more common in children (5.2% of primary CNS tumors) and affect males more frequently than females (1.3:1) 1
• According to the 2016 WHO classification, ependymal tumors are categorized into three distinct grades of malignancy (WHO grades I, II, and III) 1
• Nine molecular subgroups have been identified across different anatomical compartments (supratentorial, posterior fossa, spinal) with distinct genetic alterations and outcomes 1

Clinical Presentation

• Clinical presentation depends primarily on patient age, tumor location, and tumor size 1
• Symptoms vary based on location:
  • Infratentorial (posterior fossa) ependymomas arise from the floor of the fourth ventricle 1
  • Supratentorial ependymomas can be located within the brain parenchyma rather than in the ventricles 1
  • Spinal ependymomas typically present with symptoms related to spinal cord compression 1

Diagnosis

• MRI with contrast enhancement is the modality of choice for diagnosing ependymal tumors 1
• Intracranial ependymomas typically appear as well-circumscribed mass lesions with heterogeneous appearance on T1-, T2-, and post-contrast MRI 1
• CT can better depict calcifications, which are most commonly observed in subependymomas 1
• Disease staging requires craniospinal MRI and CSF cytology (not earlier than 2-3 weeks after surgery) due to risk of CSF dissemination 1
• Molecular diagnostic assessment is increasingly important for accurate classification:
  • Supratentorial ependymomas may harbor RELA fusions (more aggressive) or YAP1 fusions 1
  • Posterior fossa ependymomas are divided into PF-EPN-A (worse prognosis) and PF-EPN-B subgroups 2

Treatment Approach

Surgery

• Surgery is the crucial initial treatment in both children and adults, with gross total resection being the mainstay of treatment whenever feasible 1
• Postoperative MRI should be performed to evaluate the extent of resection 1
• A second-look surgery should be considered when the first resection has not been satisfactory 1
• In posterior fossa tumors, encasement of cranial nerves and brainstem vasculature might limit resectability 1

Radiation Therapy

• In pediatric patients with intracranial ependymomas (WHO grades II or III), surgery is followed by local radiotherapy regardless of residual tumor volume 1
• In adults, radiotherapy is employed for:
  • Anaplastic ependymoma WHO grade III
  • Incomplete resection of WHO grade II ependymoma 1
• For spinal ependymomas, radiotherapy is reserved for incompletely resected tumors 1

Chemotherapy

• Chemotherapy has a limited role in primary treatment but may be considered in specific situations:
  • For young children <12 months to delay radiation 1
  • For adults with recurrent disease when further surgery and irradiation are no longer feasible 1, 3
  • In children, to increase likelihood of complete resection in second-look surgery 3
• When chemotherapy is used, platinum-based regimens are most common 3

Management of Recurrent Disease

• Re-operation and/or re-irradiation should be proposed whenever possible for recurrent disease 1
• If only incomplete resection was achievable at first surgery due to functional restrictions, the same limitations will likely be faced at re-operation 1
• For patients no longer eligible for local treatments, chemotherapy might be warranted, particularly in those with good performance status 1
• In adults with recurrent disease, either platinum compounds or temozolomide (with a more favorable toxicity profile) should be considered 1

Prognosis

• Population-based epidemiological data report 5-year overall survival of 83.4% and 10-year overall survival of 79.1% 1
• Key prognostic factors include:
  • Extent of resection (gross total resection associated with longer overall survival) 1
  • Tumor location (infratentorial location associated with longer overall survival in some studies) 1
  • Molecular subgroup (RELA fusion-positive supratentorial and PF-EPN-A tumors have worse outcomes) 1, 2
  • Patient age (younger patients with certain molecular subtypes have poorer outcomes) 2

Future Directions

• Molecular classification is changing the post-resection approach to treatment and prognosis 2
• Targeted therapies based on molecular subgroups are being developed 1
• Immunotherapeutic interventions may offer new treatment options in the future 2