Approach Considerations
The extent of tumor resection is the most important prognostic factor associated with long-term survival for patients with nonmalignant forms of ependymoma, regardless of location. Thus, a gross total resection (GTR) is optimal. The feasibility and extent of the resection will vary with the location of the tumor and the clinical characteristics of the patient.
Resection is typically followed by histologic analysis and molecular testing to classify the tumor and guide prognostic estimates. Depending on the type of tumor, adjuvant treatment with radiation may be indicated. Currently, there are no ependymoma-specific molecular therapies, but this is an area of active research.
Due to the risk of ependymoma recurrence, MRI surveillance typically follows treatment.
Medical Care
Though surgical treatment is the primary treatment for ependymoma, medical management also plays a role. General medical management may include steroids for treatment of peritumoral edema and anticonvulsants. [4] In the case of incomplete tumor resection or recurrence, radiation is central to medical management. [56] Chemotherapy has shown potential in some prospective studies to delay radiotherapy in young children with intracranial ependymoma following resection but is not a mainstay of treatment. [57]
Supratentorial Ependymoma
Following incomplete resection, adjuvant conformal radiation treatment is the mainstay of medical treatment for supratentorial ependymoma for patients over the age of 18 months. [58] Because it spares many normal tissues and reduces the integral dose, proton therapy (PT) may be preferred to treat childhood cancer, however a systematic review of clinical outcome studies on PT published between 2007 and 2015 found insufficient evidence to either support or refute PT for treatment of ependymoma in children. [54]
Posterior Fossa Ependymoma
Resection of ependymomas located in the posterior fossa can be limited by the presence of nearby cranial nerves and other vital structures. Subtotal resection can be associated with increased rates of local recurrence, but adjuvant radiation therapy may be useful in limiting this effect, and the current standard of care for posterior fossa ependymomas includes conformal radiation therapy. [59] Adjuvant radiation therapy has been shown to be significantly associated with progression free and overall survival in posterior fossa ependymoma, but this effect may be isolated to the PF-A subtype. Some studies have proposed that PF-B subtype ependymomas can be treated with surgery alone, but this has yet to be studied in trials. [60]
Spinal Ependymoma
Adjuvant radiation therapy for spinal ependymoma varies based on the grade and recurrence status of the tumor. Adjuvant radiation therapy is not required if the spinal ependymoma if there is no evidence of metastasis and the grade of the tumor is WHO grade 2 or less. All grade 3 spinal ependymomas receive radiation therapy. [3] For patients who have postoperative residual tumor or early recurrence, radiation is considered on the basis of the individual patient's medical condition and neurological status. [61, 62]
Though no treatments targeting molecular subtypes of ependymoma are currently recommended, this is an area of active research. The relevance of molecular subtypes to the clinical characteristics of ependymomas is potentially suggestive of therapeutic targets related to these mutations. [13]
Surgical Care
Regardless of subtype or molecular characteristics, the primary treatment modality for ependymoma is surgical resection. Across subtypes, extent of resection is one of the strongest predictors of overall survival. Other treatment modalities are usually only considered in cases where residual tumor is present following resection or when gross total resection is not feasible. Second look surgery is also considered in such cases.
Postoperative imaging is recommended to determine the extent of surgical resection. If not performed preoperatively, complete evaluations by consulting physicians, including a neurooncologist and radiation oncologist, should be considered.
Supratentorial Ependymoma
The surgical approach to supratentorial lesions varies by location of the tumor, but the consistent goal is to achieve maximal resection.
Hydrocephalus can be managed with a perioperative external ventricular drain, ventriculoperitoneal shunt, or, more rarely, third ventriculostomy. A reasonable algorithm of management affords the opportunity to assess the need for permanent CSF diversion after tumor resection. This can be accomplished by clamping the external ventricular drain postoperatively and monitoring intracranial pressure and/or clinical signs.
Posterior Fossa Ependymoma
Children with posterior fossa lesions usually undergo surgery via a midline suboccipital approach. Despite the survival advantage of GTR, lesions of the posterior fossa are in close proximity to cranial nerves. This makes aggressive GTR risky and fraught with the possibility of long-term neurologic dysfunction and disability. Posterior fossa syndrome, also referred to as cerebellar mutism, is a recognized complication of posterior fossa surgery and most common when brainstem invasion is observed. [63, 64] Mutism can have a latency range of 1-7 days and duration of 6-365 days. Thus, consideration must be given to the balance between improved survival with GTR and potential postoperative morbidity.
The management of hydrocephalus in posterior fossa ependymoma resembles management in supratentorial ependymoma as described above.
Spinal Ependymoma
Intramedullary tumors are approached via standard laminectomy with the patient in the prone position. The strategies for intramedullary tumor removal depend upon the relationship of the tumor to the spinal cord. Most ependymomas are intramedullary and are not apparent upon inspection of the surface. Intraoperative ultrasound may be used to localize the tumor and to determine the rostrocaudal tumor borders.
Resection in the caudal spinal cord involves some further considerations. The role of surgery for filum terminale ependymoma depends on the size of the tumor and its relationship to the surrounding roots of the cauda equina. Gross total en bloc resection should be attempted whenever possible. This usually can be accomplished for small and moderate-sized tumors, which remain well circumscribed within the fibrous coverings of the filum terminale and easily separable from the cauda equina nerve roots. Recurrences following successful en bloc resection are rare.
Consultations
A team of specialists including a neurologist, neurosurgeon, neurooncologist, and radiation oncologist should evaluate patients with ependymomas to develop a coordinated treatment strategy. At some institutions, transferring the patient to another facility may be necessary if the proper consultations cannot be obtained. In most cases, surgical resection can be performed on an urgent, but not emergent, basis.
Postoperative consultations should include physical therapy and rehabilitative medicine representatives to facilitate recovery.
Diet
No restrictions of diet are required for patients with ependymomas.
Activity
No universal restrictions on activity are required for patients with ependymomas. Patients' activity depends on their overall neurological status.
In the case of patients with supratentorial ependymomas, a history of seizures may preclude operation of motor vehicles.
Long-Term Monitoring
Long-term monitoring of ependymoma patients with periodic brain/spine MRI is recommended following gross total resection. Current NCCN recommendations specify tumor site MRI once every 3-4 months during the first year following resection, then every 4-6 months during the second year, and every 6-12 months for 5-10 years.
Surveillance is motivated by the risk of recurrent disease, which carries a poor prognosis. Most recurrences are local, but distant recurrences have also been reported. The rate of recurrence varies by ependymoma subtype. Following recurrence, repeat resection is recommended if possible. Depending on the extent of this resection, either system or craniospinal radiation therapy is recommended.
Spinal ependymoma recurrence is less common than in intracranial cases, but still of concern, especially in cases of subtotal resection.
Supratentorial Ependymoma
Some retrospective studies have reported recurrence rates of over 50% in intracranial ependymoma following gross total resection and radiation treatment, most of which recurred locally. [65, 66]
Posterior Fossa Ependymoma
Studies have suggested that recurrence rate in posterior fossa ependymoma varies significantly by subtype: PF-A ependymomas recurred in over 50% of patients, while no recurrences were observed in patients with PF-B tumors. [67]
Spinal Ependymoma
Spinal ependymoma recurs less frequently than other types of ependymoma, but recurrence is still associated with worse survival and post-surgical surveillance is recommended. [3]
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CT scan without contrast. Fourth ventricle ependymoma.
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CT scan without contrast. Fourth ventricle ependymoma. Note blood in the fourth ventricle.
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CT scan without contrast in the patient with fourth ventricle ependymoma. Blood has refluxed into the third and lateral ventricles.
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CT scan without contrast in the patient with fourth ventricle ependymoma. Note blood traversing foramina.
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T1-weighted MRI. Rare case of a fourth ventricle ependymoma presenting as an intraventricular bleed.
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T1-weighted MRI without contrast demonstrating ependymoma located in the fourth ventricle.
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T2-weighted MRI demonstrating ependymoma in the fourth ventricle.
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Coronal T1-weighted MRI with contrast demonstrating ependymoma of the fourth ventricle.
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Gross surgical specimen of a fourth ventricle ependymoma.
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Histologic study of a classic ependymoma. Note the characteristic perivascular pseudorosettes.
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Cellular ependymoma. Cells with a high nuclear-cytoplasmic ratio. Few pseudorosettes or paucicellular areas are present.
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Myxopapillary ependymoma. Clusters of loosely arranged cuboidal cells separated by pools of mucin.
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Clear cell ependymoma. Round cells with cytoplasmic clearing. This may mimic an oligodendroglioma.
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MRI images of an ependymoma in the left ventricle. Courtesy of figshare.com [El Majdoub, Faycal; Elawady, Moataz; Blau, Tobias; Bührle, Christian; Hoevels, Mauritius; Runge, Matthias; et al. (2016): Intracranial Ependymoma: Long-Term Results in a Series of 21 Patients Treated with Stereotactic 125Iodine Brachytherapy. PLOS ONE. Dataset. Available at: https://figshare.com/articles/dataset/Intracranial_Ependymoma_Long_Term_Results_in_a_Series_of_21_Patients_Treated_with_Stereotactic_125_Iodine_Brachytherapy__/117659].
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MRI image of the sagittal neck with an ependymoma. Modification of a figure from nl-wiki, without author annotations. Courtesy of Wikimedia Commons [Author Lucien Monfils, available at: https://commons.wikimedia.org/wiki/File:Ependymoma.png].
Tables
Supratentorial ependymomas |
ZFTA (C11orf95): Zinc Finger Translocation Associated gene |
YAP1: Yes-Associated Protein 1 |
|
Posterior fossa ependymomas |
Posterior Fossa Group A molecular profile |
Posterior Fossa Group B molecular profile |
|
Spinal ependymomas |
NF2: Neurofibromatosis 2 gene |
MYCN Proto-oncogene |
|
MYCN Non-amplified |
|
Subependymoma |
Supratentorial |
Posterior fossa |
|
Spinal |
