Ependymoma Treatment & Management

Updated: Apr 14, 2015
  • Author: Jeffrey N Bruce, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Treatment

Medical Care

Medical management of patients with ependymomas includes adjuvant therapy (ie, conventional radiation therapy, radiosurgery, chemotherapy), steroids for treatment of peritumoral edema, and anticonvulsants in patients with supratentorial ependymoma. [1, 2]

  • Adjuvant treatment of histologically confirmed intracranial ependymoma remains an actively debated topic.
  • The National Comprehensive Cancer Network (NCCN) suggests the following for adults: After a gross total resection (GTR) of an intracranial WHO grade II ependymoma, limited field fractionated external beam radiotherapy (LFFEBRT) can be considered versus mere observation. Postoperative LFFEBRT is recommended for WHO grade II ependymoma when subtotal resection is noted on postoperative MRI, and for grade III anaplastic ependymoma regardless of the extent of resection. [3] If postoperative spinal MRI or LP findings are positive, craniospinal radiation therapy is indicated regardless of grade or extent of resection. For recurrent ependymoma, the NCCN suggests that patients who have not received radiation therapy receive radiation therapy, and if a patient has received radiation therapy, then chemotherapy, radiation therapy, or supportive care should be considered. [4]
  • For children younger than 3 years, the use of chemotherapy has historically been fostered by the desire to avoid adverse radiation effects. Combination chemotherapy regimens comprising cisplatin, etoposide (VP-16), carboplatin, vincristine, and mechlorethamine, or ifosfamide, carboplatin, and etoposide (ICE), have been administered with variable success.
  • In older children and adults, radiotherapy is the standard treatment following resection for most patients with WHO grade II ependymoma. While surgery alone has been piloted for a very select group of patients (those with supratentorial tumors who undergo gross total resection with a wide resection margin), most tumors of the posterior fossa cannot be fully resected and are likely to recur without postoperative radiation. [27, 28]
  • Early attempts at defining appropriate treatment paradigms for intracranial ependymoma have depended heavily upon single-institution retrospective reviews.
  • In 1990, Goldwein and colleagues reviewed 36 children (aged 0.8-16.8 y) with recurrent intracranial ependymoma who were treated for a total of 52 separate relapses from 1970-1989. [29]
    • They concluded that some patients with histologically benign ependymoma at first relapse could benefit from aggressive therapy, with occasional long-term, progression-free survival possible. In contrast, patients with malignant lesions or patients who relapsed a second time were less likely to benefit from conventional therapy.
    • In their study, initial therapy for relapse consisted of surgery in 33 cases and chemotherapy in 38 cases. Twelve patients received radiation at the time of first relapse, and 5 of these 12 who initially had been treated with surgery and chemotherapy alone were irradiated to full dose.
    • The 2-year actuarial survival and progression-free survival rates were 29% and 23%, respectively. The 2-year survival rate after treatment of first relapse was 39%. Of the 52, 44 subsequent relapses (and 1 septic death) occurred, 3 of which occurred in the 5 patients treated with definitive radiation. Twenty-seven relapses occurred exclusively with local disease. Eight patients had relapse outside of as well as in the primary site. Survival rate was better for patients who had histologically benign lesions at relapse (53% vs 9%, P < 0.02), and for patients in the first versus subsequent relapse (P < 0.005). Cisplatin and VP-16 appeared to be the most active chemotherapeutic agents.
  • In 1992, Chiu and colleagues evaluated the clinical courses of 25 children aged 2 weeks to 15 years treated for intracranial ependymoma at M. D. Anderson Cancer Center. [30]
    • Nine patients had supratentorial primaries (5 high grade, 4 low grade), and 16 patients had infratentorial primaries (9 high grade, 7 low grade). Five patients underwent gross complete resection, and 20 patients had incomplete resection. Seven patients received craniospinal irradiation (25-36 Gy to the neuro-axis, 45-55 Gy to tumor bed), and 12 received local field irradiation (29-60 Gy, median 50 Gy). Five infants had adjuvant chemotherapy without radiotherapy, 6 children had postradiotherapy adjuvant chemotherapy, and 12 patients had salvage chemotherapy with various agents and number of courses.
    • Eight patients were alive, disease free, and without relapse from 1-12.5 years after diagnosis (median 42 mo). The primary failure pattern was local recurrence.
    • The data presented in this study suggested that the long-term cure rate of children with ependymoma is suboptimal; histologic grade may be of prognostic importance for supratentorial tumors; prognosis appears worse for girls and infants younger than 3 years; in well-staged patients, routine spinal irradiation could be omitted; and the role of adjuvant chemotherapy is unclear.
  • In 1998, an extensive review and analysis of all published literature on the topic of intracranial ependymoma highlighted the difficulty associated with extrapolating data from single-institution studies. [5]
    • Forty-five series were reviewed, including more than 1400 children. The largest series reported on 92 patients, and the accrual rate ranged from 0.32-12 patients per year. Notably, the extent of surgical resection was the only reported prognostic factor in these series that was consistently found to be a valid predictor of outcome.
    • These findings were confirmed by a prospectively randomized trial published that same year evaluating Children's Cancer Group Protocol 921. Predictors of long-term survival included an estimate of the extent of resection made at surgery (total compared with less than total, P =0.0001) and the amount of residual tumor on postoperative imaging as verified by centralized radiologic review. Other factors, including centrally reviewed tumor histopathologic type, location, metastasis, and tumor (M and T) stages, patient age, race, sex, and chemotherapy treatment regimen were not found to be correlated significantly with long-term survival.
  • More recently, in 2000, Stafford and colleagues evaluated the efficacy of stereotactic radiosurgery (SRS) for locally recurrent ependymoma and found that this technique may allow a high salvage rate in selected patients. In 12 patients (with a total of 17 tumors) treated with SRS, a medial survival of 3.4 years was achieved. In-field local control was achieved in 14 of the 17 tumor sites, and the estimated 3-year local control rate was 68%. Two patients developed treatment-related complications following therapy. [31]
  • Currently, no role exists for adjuvant therapy of spinal ependymoma after complete surgical resection. 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.
  • Conventional chemotherapy has yet to effect any improvement in outcome for ependymoma, [32, 33] and radiotherapy to the developing brain is to be avoided due to its substantial neurocognitive effects. Therefore, recent emphasis has been placed on molecular subclassification of these tumors. hTERT negativity is associated with a 5-year survival rate of 84% compared to 41% for hTERT positive tumors. [34] Several genes have been identified as having associations with risk of relapse, age of onset, and location of tumor. [35, 36] As more information regarding molecular signatures of ependymomas is gathered, more individualized therapies may be realized. [12]
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Surgical Care

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.

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 making 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. [37, 38] 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.

Hydrocephalus can be managed with a perioperative external ventricular drain, ventriculoperitoneal shunt, or, more rarely, third ventriculostomy. A reasonable algorithm of management affords the medical team 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.

Although the approach to supratentorial lesions varies according to location, the goal of gross total resection should be the same as in infratentorial surgery.

Intramedullary tumors are approached via standard laminectomy with the patient in the prone position. Considerations include the following:

  • Although somatosensory evoked potentials and direct motor evoked potentials are employed routinely, only rarely do they influence surgical decisions or technique.
  • Laminoplasty is performed in children but does not guarantee long-term stability.
  • The strategies for intramedullary tumor removal depend upon the relationship of the tumor to the spinal cord. Most tumors are totally 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.
  • The extent of tumor resection is guided by the anatomy of the lesion, intraoperative monitoring, the surgeon's experience, and the preliminary frozen-section histologic diagnosis.
  • The plane between an ependymoma and surrounding spinal cord is usually well defined and easily developed.
  • Large tumors may require internal decompression with an ultrasonic aspirator or laser.
  • A competent dural closure is essential to prevent CSF leaks.

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. Considerations include the following:

  • 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.
  • A portion of uninvolved filum terminale is generally present between the tumor and spinal cord.
  • Amputation of the afferent and efferent filum segments is required for tumor removal.
  • Internal decompression is not used for small and moderate-sized tumors because this may increase the risk of CSF dissemination.
  • Recurrences following successful en bloc resection are rare.
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Consultations

See the list below:

  • A team of specialists including a neurologist, neurosurgeon, neurooncologist, and radiation oncologist should evaluate patients with ependymomas to develop a coordinated treatment strategy.
  • Postoperative consultations should include physical therapy and rehabilitative medicine representatives to facilitate recovery.
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Diet

No restrictions of diet are required for patients with ependymomas.

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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.
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