Pediatric Ependymoma 

Updated: Sep 21, 2021
Author: Eugene I Hwang, MD; Chief Editor: Max J Coppes, MD, PhD, MBA 

Overview

Practice Essentials

Ependymoma is the third most common brain tumor in children, accounting for approximately 10% of primary central nervous system (CNS) neoplasms. It is a neuroepithelial tumor that arises within, or adjacent to, the ependymal lining of the ventricular system or the central canal of the spinal cord. Recent efforts have separated ependymoma into three distinct regional compartments, including the spinal column, the posterior fossa (see image below), and the supratentorium, with approximately two-thirds of pediatric ependymomas arising in the posterior fossa. Further advances have begun to delineate distinct molecular subtypes within the regional compartments, as detailed later in this article.

MRI showing an ependymoma of the fourth ventricle, MRI showing an ependymoma of the fourth ventricle, compressing the cerebellum and brain stem.

With surgery and radiotherapy, overall 5-year survival rates have been reported to range between 50% and 81%.[1, 2, 3]  Individual prognosis depends on age, extent of resection, and, increasingly, known biological variations. The role of chemotherapy for infants and patients with postoperative residual disease is currently under investigation.

Pathophysiology

Ependymomas typically arise from the ependymal lining of the ventricular system, most often the floor, roof, or lateral recesses of the fourth ventricle, as depicted below. The most recent evidence suggests that radial glia cells are the stem cells of origin for this disease. Approximately one third of ependymomas are supratentorial, arising from the surface of the lateral or third ventricles; however, they may be entirely extraventricular. They may also occur in the central canal of the spinal cord and in the filum terminale, although the latter site is uncommon in children.

Sagittal section of an ependymoma of the fourth ve Sagittal section of an ependymoma of the fourth ventricle.

Histologically, ependymoma has historically been broadly separated into three grades, although almost all pediatric ependymomas fall into one of two major subsets, grade II (cellular) and grade III (anaplastic). Grade II ependymoma is well differentiated and lacks mitosis and vascularity. Grade III ependymoma is poorly differentiated and has a high mitotic index, necrosis, calcifications, and endothelial proliferation. These display a higher frequency of ependymal rosettes clustering around a central lumen. Both histological subtypes are locally invasive into adjacent brain, and distinguishing between the grades can be very difficult. Clear cell ependymomas often exhibit cysts with characteristic clear cells with perinuclear halos and rounded nuclei, and also have high proliferation indices. Myxopapillary ependymomas are considered a distinct, grade I variant of ependymoma primarily occurring in the region of the cauda equina and are relatively rare in children. Subependymoma is another grade I ependymoma that may occur in any regional compartment, but that is likewise predominantly a disease of adult populations.

Ependymomas in the posterior fossa frequently infiltrate the brain stem, and as many as one third may project through the foramina to involve the medulla and upper spinal cord. Spread via cerebrospinal fluid (CSF) throughout the subarachnoid space is reported, primarily with the higher-grade tumors. Extraneural metastases to liver, lung, or bone are rare.

Prognosis has historically relied on age, presence of metastatic disease, extent of resection, and the appearance of significant histologic anaplasia. However, more recently, significant insight into the molecular underpinnings of ependymoma have resulted in a re-evaluation of the most important prognostic characteristics. Some molecular features of ependymoma have been previously associated with worse outcome, including chromosome 1q gain, telomerase expression and the presence of homozygous deletions of CDKN2A.[4]

As such, clinical and molecular analysis, including genomics and expression profiling, has begun to result in dividing childhood ependymoma by region (supratentorial, infratentorial, spinal) as well as by molecular phenotype. Using this categorization method, new groups of high risk disease are becoming evident.

Posterior fossa ependymoma, the most common site in childhood, may be generally divided into two groups: group A and group B. Group A tumors (also called CpG island methylator phenotype, or CIMP+) are more common, generally occur in younger children and have poorer outcomes, with roughly 20-30% 10-year progression-free survival.[5] Group A tumors have a generally balanced genome but exhibit an increased level of 1q gain, which is a marker of poor outcome. Group B tumors have better survival, with a 10-year progression free survival of almost 60%, and overall survival rates above 80%. Group B tumors occur more commonly in adults and older children, with an increased incidence ratio of female:male and have increased numbers of cytogenetic abnormalities, such as whole chromosomal gain/loss.

Supratentorial ependymomas may now be divided into groups exhibiting either YAP1 or C11orf95-RELA fusions. YAP1 fusion-positive tumors, which most typically affect younger children, have relatively good outcomes with nearly universal 10-year overall survival, although these tumors also recur. In contrast, ependymomas exhibiting RELA-fusion positivity have very poor outcomes, with rapid recurrence and progression and a 10-year progression-free survival of no better than 20%.[5] These tumors also more commonly display CDKN2A deletions, which are also postulated to be a marker of poor outcome.

Etiology

Epidemiological studies investigating parental occupational exposures, environmental exposures, and maternal nutritional intake have failed to identify linkages with any of the childhood brain tumors.

DNA sequences similar to SV40 virus and the virus-encoded large T-antigen have been found in several ependymomas, but no conclusions regarding causation have been determined. SV40 and related polyoma viruses can induce ependymoma in monkeys and other mammalian species.

Neurofibromatosis type 2 (NF2) is a genetic disorder that is known to predispose to ependymoma, typically spinal tumors.

Epidemiology

United States statistics

Approximately 200 new cases are reported annually in children.[6] Ependymoma represents the third most common brain tumor in children, following astrocytoma and medulloblastoma.

International statistics

In the United Kingdom, an estimated 30-35 new pediatric cases are diagnosed annually. More than 300 new pediatric cases per year are reported in Europe.

Race-, sex-, and age-related demographics

No specific race is predisposed to ependymoma. However, analysis of data from the Central Brain Tumor Registry of the United States shows that the incidence of ependymoma is significantly lower among African American and Native American children (by 33% and 36%, respectively), compared with non-Hispanic White children. In addition, eastern European ancestry is associated with an elevated risk of ependymoma in non-Hispanic Whites and in Hispanics.[7]

Ependymomas are more common in males.

The incidence of ependymoma peaks below 4 years of age, with almost a third of patients presenting in that time frame. The age of presentation is also related to the location of the primary disease, with spinal disease presenting at a mean age of 12.2 years, supratentorial disease at a mean of 7.8 years and infratentorial disease presenting at a mean age of 5 years.[8] Spinal cord ependymoma rarely occurs in children younger than 12 years.

Prognosis

Prognostic factors

Extent of tumor resection

Resection is the most important prognostic factor. Patients with gross total and near-total resections have reported survival rates of 51-80%, versus 0-26% in those with subtotal resections (< 90% removal of total tumor mass, visible tumor present on MRI).

Age

Very young patients (< 1 y), unrelated to radiation treatment, have a significantly worse prognosis (5-y survival rate of 25%).[9]  The 5-year survival rate for children aged 1-4 years is also significantly less than for children older than 5 years (46% versus >70%). Some promising results using high-dose chemotherapy and delayed or omitted radiotherapy have been recently shown in this age group.

Other factors

Historically, anaplastic features and supratentorial location have conferred a worse prognosis. More recent reports have largely dismissed histology and tumor location as significant prognostic indicators (with the exception of better outcome observed in spinal cord tumors and myxopapillary tumors of the cauda equina). Metastatic disease is probably a poor prognostic factor; however, patient numbers are too scarce to draw a conclusion.

Morbidity/mortality

The 5-year overall survival rate has been reported to vary widely with local resection and irradiation, with a 5-year overall survival rate in the 50-60% range. However, more recently, the natural history of ependymoma has been noted to be more prolonged than previously appreciated due to the potential for late relapses and slow recurrence; therefore, survival rates do not plateau at the typically reported 5-years post-diagnosis. A more recent study noted 10-year overall survival of 50%, but only 29% progression free survival in the same timeline.[10]

Although historically age, the extent of tumor resection, and histology have been the primary predictors for survival, these characteristics are undergoing significant revision in the context of increased comprehension of the biology of ependymoma (as detailed previously).

Direct distortion and destruction of normal brain tissue by tumor, as well as increased intracranial pressure and surgical trauma, may cause some degree of irreversible neurologic impairment. Also, the volume and location of radiotherapy necessary to treat the tumor may result in cognitive impairment. The expanded use of conformal radiotherapy for localized disease has helped to ameliorate some of these effects. Radiotherapy to the hypothalamic-pituitary axis may result in deficits of growth hormone, thyroid hormone, gonadotropin, and adrenocorticotropic hormone.

Children with relapsed ependymoma often are subjected to a prolonged cycle of repeated relapses and stabilizations, with repeated surgical procedures, radiotherapy, and medical management leading to potentially significant morbidity, including organ toxicity, neurologic deterioration and cognitive/social difficulties.

Complications

Complications include the following:

  • Obstructive hydrocephaly

  • Neurologic impairment

  • Radiation-induced effects

    • Neurocognitive decline

    • Endocrinologic dysfunction

    • Mineralizing microangiopathy with ischemia or infarct

    • Secondary CNS malignancies

    • Transient headaches, fatigue, nausea, vomiting, and anorexia

Patient Education

The patient and his/her family members should be referred for psychosocial counseling.

The following patient education resources are available from WebMD:

 

 

Presentation

History

The initial presentation for ependymoma in childhood varies according to the location(s) of the ependymoma. Most children present with non-specific symptoms related to increased intracranial pressure.   

The classic triad of raised ICP consists of morning headaches, vomiting, and lethargy. The classic headache of increased ICP is pain present upon rising, relieved by vomiting, and gradually decreasing during the day.

School-aged children more commonly complain of vague, intermittent headaches and fatigue. They may demonstrate declining academic performance and exhibit personality changes.

Infants may present with irritability, anorexia, and developmental delay or regression.

Supratentorial lesions may be associated with seizures and focal cerebral deficits.

Posterior fossa tumors may lead to cerebellar dysfunction, resulting in balance and gait disturbances that frequently are associated with vomiting and lower cranial nerve findings such as diplopia, facial weakness, tinnitus, vertigo, and hearing loss.

Spinal cord tumors may cause symptoms of spinal cord compression, such as back pain and loss of bladder and/or bowel control.

Physical Examination

The following are findings in patients with increased ICP:

A funduscopic examination reveals papilledema. Infants may have only optic pallor.

Palsy of cranial nerve VI, resulting in the inability to abduct one or both eyes, is common.

Infants may demonstrate the setting sun sign, observed as an impaired upgaze and a forced downward deviation of both eyes. Measurement of head circumference in infants with open cranial sutures may reveal macrocephaly.

Localized deficits in truncal steadiness, upper extremity coordination, and gait may be observed with posterior fossa tumors.

The inability to deviate both eyes conjugatively (gaze palsy), or the inability to adduct one eye on attempted lateral gaze may be seen with tumor invasion into the brainstem.

Extension of posterior fossa tumors through the foramina of Luschka may impair function of the lower cranial nerves (primarily VI, VII, VIII, IX, and X).

 

DDx

Differential Diagnoses

 

Workup

Imaging Studies

The following studies are indicated in patients with ependymoma:

  • Head CT scan with and without contrast

    • This study has greater than 95% sensitivity for detection of brain tumors.

    • On CT scan, hydrocephalus is present in almost all patients.

    • The tumor typically appears as hyperdense and homogeneously contrast-enhancing lesion arising from, or adjacent to, the ventricular system.

    • Cystic areas and calcifications are frequent.

  • Head and spine MRI with and without gadolinium should be obtained as ependymoma may presented with neuraxis dissemination.

    • These studies must be performed in all patients with CT scan or clinical findings consistent with ependymoma. Other tumors such as medulloblastoma and cerebellar astrocytoma may have similar appearance on CT scans. MRI can be useful in such instances by better demonstrating the anatomic origin and extent of tumor. With MRI, ependymoma is typically noted to be isointense to hypointense on T1-weighted images and hyperintense on T2-weighted images, relative to white matter. Ependymomas commonly show at least heterogenous enhancement with gadolinium contrast. See the following image.

      MRI showing an ependymoma of the fourth ventricle, MRI showing an ependymoma of the fourth ventricle, compressing the cerebellum and brain stem.
    • MRI is the most sensitive means of detecting spinal cord lesions and should always be performed because of the potential for subarachnoid seeding, which is especially likely from tumors that arise in the posterior fossa.

    • A postoperative MRI is required both for the measurement of the extent of surgical resection and the detection of residual disease.

Procedures

A CSF cytologic examination is useful for detection of microscopic leptomeningeal dissemination.

A CT scan or MRI must be performed prior to the lumbar puncture (LP) to exclude the presence of hydrocephaly. The presence of hydrocephaly would place the patient at risk for herniation as a consequence of the procedure. In general, the LP is deferred as long as 2 weeks postoperatively in order to avoid identifying tumor cells that may have been disseminated as a result of surgery.

Histologic Findings

Ependymomas develop from the neuroepithelial lining of the ventricle and the central canal of the spinal cord. They are generally well-demarcated tumors that often display areas of calcification, hemorrhage, and cysts.

They vary morphologically from well differentiated with no anaplasia and little polymorphism (cellular or low-grade) to highly cellular lesions with significant mitotic activity, anaplasia, and necrosis, which may resemble glioblastoma multiforme (anaplastic or high-grade). See the image shown below.

Section displaying high cellularity, nuclear atypi Section displaying high cellularity, nuclear atypia, and numerous mitoses characteristic of an anaplastic ependymoma.

Of note, anaplasia has been variably predicted as a predictor of outcome. The definition of anaplasia in the context of ependymoma continues to be discussed, as variation in definitions has contributed to unclear importance of this as a prognostic characteristic.

Historically, they have been classified as cellular, epithelial, papillary, or mixed. However, this terminology is currently not used anymore. Tumors arising in the conus medullaris and filum terminale are termed myxopapillary because of their unique histopathologic features.

Ependymal rosettes are radially aligned, ependymal elements about a central lumen; although uncommon, they are a diagnostic feature of ependymoma. More common are pseudorosettes (see image below), an eosinophilic halo composed of cells with tapering processes surrounding a blood vessel.

Currently, molecular subtyping has not been a mandated component of upfront diagnosis and treatment planning, although this continues to evolve.

Section displaying typical perivascular pseudorose Section displaying typical perivascular pseudorosettes of a benign ependymoma.

Electron microscopy may be useful in the diagnosis by demonstrating true rosettes, microvilli, and cilia on the apical surface. Immunohistochemistry and cytogenetic analysis have not been shown to demonstrate meaningful associations.

Wang et al conducted a study of the tumor biology of myxopapillary ependymoma. Tumors from a cohort of 19 patients were analyzed by light microscopy, electron microscopy, immunohistochemistry, and fluorescence in situ hybridization.[11] Clinical characteristics, therapeutic options, and clinical follow-up data were analyzed. The most common presenting symptom was back pain. The main pathologic morphology observed was papillae embedded in a myxoid background, but other rare morphologies were also present. Immunostaining revealed epidermal growth factor receptor (EGFR) expression in 4 cases. No correlation was found between tumor recurrence and EGFR overexpression. Ultrastructural examination revealed adherens junctions and intracytoplasmic lumina with microvilli. There were no tumor recurrences in patients who underwent gross total resection. Local control rate was higher in patients who underwent subtotal resection followed by radiation therapy than it was for patients who underwent subtotal resection alone. The investigators concluded that a diagnosis of myxopapillary ependymoma should be made on the basis of histology, immunohistochemistry, imaging studies, and anatomic site.[11]

 

Treatment

Medical Care

Surgery

Surgery is the initial treatment for ependymoma. Patients with total or near total resections have significantly better survival rates than those in whom the resection is grossly incomplete.

Radiotherapy

Radiotherapy remains the standard postoperative therapy. Whether this improves long-term survival remains controversial, especially in infants and those with completely resected tumors, in whom the risk of long-term effects of radiotherapy may outweigh the potential benefits.

Involved-field radiotherapy

In patients with complete resection, 59.4 Gy (infratentorial tumor) and 55.8 Gy (supratentorial tumor) to the original tumor site plus a 1-2 cm margin is recommended.

In patients with subtotal resection, 59.4 Gy to the original tumor site plus a 1-2 cm margin for supratentorial and infratentorial tumors is recommended.

Craniospinal radiation is recommended only for those with leptomeningeal dissemination.

Conformal radiotherapy has been shown to be effective for those with localized, totally resected posterior fossa tumors.

Chemotherapy

The role of chemotherapy is unknown. Clinical trials evaluating the effectiveness of different chemotherapeutic agents for infants and for subtotally resected tumors are ongoing. Promising results have been demonstrated with cyclical oral etoposide in recurrent ependymoma, with response rates as high as 83%. However, induction of secondary leukemia in association with chronic use of this regimen has been reported.

In infants younger than 3 years, studies attempting to delay or omit radiotherapy by using postoperative chemotherapy are ongoing.[12, 13]

Although with current regimens the role of chemotherapy appears limited, measurable responses have been documented. As a single agent, cisplatin has been the most effective in phase II studies (30% response rate). Other platinum compounds such as carboplatin appear less effective.

One study has reported significant responses to vincristine and cyclophosphamide combined.

Trials investigating the effectiveness of preirradiation chemotherapy using platinum or alkylator-based regimens are ongoing in infants and patients with subtotally resected tumors. Preliminary results suggest some benefit in those with anaplastic tumors.

A Children's Oncology Group study evaluated the benefits of preirradiation multiagent chemotherapy in patients with subtotally resected tumors.

Surgical Care

The goal is for gross total or near total resection.

Posterior fossa tumors are approached through a suboccipital craniotomy and may be incompletely resectable because of infiltration of the floor, the fourth ventricle, or brainstem.

Supratentorial tumors tend to be large and may be intraventricular, extraventricular, or both. These tumors have a predilection for the frontal, temporal, and parietal lobes and third ventricle. Approach and degree of resection depend on the tumor's size and location.

A regional, leptomeningeal examination must be examined for metastatic foci.

Surgical estimates of the extent of resection may not be reliable; therefore, postoperative MRI evaluation for residual disease is required and generally should be performed within 72 hours of surgery to avoid confusion with postsurgical inflammation.

Posterior fossa tumors often present with obstructive hydrocephaly and may require the placement of a ventriculoperitoneal shunt if primary resection to reestablish CSF flow is unsuccessful.

The use of "second-look" surgery after 1-2 cycles of chemotherapy before radiotherapy has been studied, and the results are pending.

Ailon conducted a retrospective study of treatment with total resection alone for children with intracranial ependymoma.[14] The study included 26 children who were treated with total resection and who did not undergo subsequent radiation therapy. There were 12 cases of grade II posterior fossa ependymoma (PFE), and 14 of supratentorial ependymoma (STE) in their cohort. Immunostaining was performed to identify the presence of the antigen Ki-67, epidermal growth factor receptor, and the enzyme EZH2. Progression-free survival was inferior for patients with high levels of Ki-67 who were treated with resection alone. No differences in survival were found with regard to PFE and SE for patients who underwent both total resection and radiation therapy. Five-year progression-free survival for patients treated with total resection alone was 60% for those with PFE and 45% for those with STE. Overall survival for patients treated with total resection alone was 70% for those with PFE and 70% for those with STE. Survival was inferior for patients younger than 2 years. The investigators concluded that children who are older than 2 years and who have low levels of Ki-67 and who test negative for EZH2 might be candidates for observation following total resection.[14]

Consultations

Regular team members for the care of all patients include the following:

  • Neurosurgeon

  • Radiation oncologist

  • Pediatric oncologist or neuro-oncologist

  • Neurologist

  • Neuropsychologist

  • Neuroendocrinologist

As a result of the tumor, therapeutic intervention, or both, some patients may require the assistance of occupational and physical therapists for rehabilitation.

Diet and Activity

Diet

No specific dietary restrictions or requirements are indicated.

Patients who develop severe anorexia or weight loss as a result of therapy (particularly infants) may need supplemental nutrition to maintain daily requirements.

Activity

No activity restrictions are required unless dictated by underlying neurological deficits.

Patients with ventriculoperitoneal shunts may be restricted from high-impact sports such as diving.

 

Guidelines

Guidelines Summary

In the United Kingdom, the Children’s Brain Tumour Research Centre produced the Diagnosis of Brain Tumours in Children guideline, which was accredited by the National Institute for Health and Care Excellence. A summary of the guideline for healthcare professionals covers diagnosis, presenting symptoms of brain tumors in children by subspecialty, and when to refer for further assessment, imaging, or treatment.[15]

 

Medication

Medication Summary

The role of chemotherapy in the treatment of ependymoma has not been established.

Numerous drugs have been identified with activity against ependymoma in single-agent chemotherapy regimens in phase II trials. Of these, platinum compounds have been the most active (eg, cisplatin is the most effective single agent, with a 30% response rate).

Despite these findings, combination chemotherapeutic regimens for ependymoma have yielded disappointing results. The most encouraging data have been reported in infants using postoperative therapy consisting of cisplatin, cyclophosphamide, etoposide, and vincristine, with deferred radiation (2-y survival rate of 74%).

Current trials are evaluating the benefits of this regimen in older children with postoperative residual disease. At present, no definitive conclusions can be drawn.

An example of the dosing and administration of preirradiation chemotherapeutic agents used in a recent investigational protocol for children older than 3 years with postoperative residual disease is provided below.[16]

Antineoplastic agents

Class Summary

These agents disrupt DNA replication, which inhibits tumor growth and promotes tumor cell death. Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. After cells divide, they enter a period of growth (phase G1), followed by DNA synthesis (phase S). The next phase is a premitotic phase (G2), then finally a mitotic cell division (phase M).

The cell division rate varies for different tumors. Most common cancers increase very slowly in size compared to normal tissues, and the rate may decrease further in large tumors. This difference allows normal cells to recover more quickly than malignant ones from chemotherapy and is the rationale behind current cyclic dosage schedules.

Antineoplastic agents interfere with cell reproduction. Some agents are cell cycle specific, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not phase-specific. Cellular apoptosis (ie, programmed cell death) is also a potential mechanism of many antineoplastic agents.

Vincristine (Oncovin)

Plant-derived vinca alkaloid. Acts as a mitotic inhibitor by binding tubulin. Inhibits microtubule formation in the mitotic spindle, causing metaphase arrest.

Cisplatin (Platinol)

Heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation. This leads to interstrand and intrastrand DNA crosslinks and inhibition of DNA replication.

Cyclophosphamide (Cytoxan)

Exerts its cytotoxic effect by alkylation of DNA, leading to interstrand and intrastrand DNA crosslinks, DNA-protein crosslinks, and inhibition of DNA replication.

Etoposide (VePesid, VP-16)

Glycosidic derivative of podophyllotoxin that exerts its cytotoxic effect through stabilization of the normally transient covalent intermediates formed between DNA substrate and topoisomerase II, leading to single-stand and double-strand DNA breaks.

Antidote, cyclophosphamide-induced hemorrhagic cystitis

Class Summary

This agent is a detoxifying agent used as a protectant against hemorrhagic cystitis induced by cyclophosphamide.

Mesna (Mesnex)

In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity. Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity.

Colony-stimulating factors

Class Summary

These agents reduce the duration of neutropenia and the associated risk of infection in patients receiving myelosuppressive chemotherapy. They act as a hematopoietic growth factor that stimulates the development of granulocytes. They are used to treat or prevent neutropenia when receiving myelosuppressive cancer chemotherapy and to reduce the period of neutropenia associated with bone marrow transplantation. These agents are also used to mobilize autologous peripheral blood progenitor cells for bone marrow transplantation and in the management of chronic neutropenia.

Filgrastim (Neupogen, G-CSF)

Granulocyte colony-stimulating factor that activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils.

 

Follow-up

Further Outpatient Care

Radiotherapy

After the patient recovers from surgery, daily outpatient radiotherapy should begin. This is generally given for approximately 6 weeks (usual dose is 160-180 cGy per day).

Liu et al conducted a retrospective review of a territory-wide database to determine the optimal timing of radiation therapy (RT) for children who were diagnosed with ependymoma between 1995 and 2011.[17] Overall survival and event-free survival were compared between patients receiving up-front RT (ie, RT performed in fewer than 150 days of diagnosis), delayed RT (performed 150 days or longer after diagnosis), or no RT. The study cohort consisted of 31 patients with intracranial ependymoma (mean age, 3.5 years; 45% male). The primary tumor was supratentorial in 10 patients (32%) and infratentorial in 21 (68%). All patients underwent initial surgery; gross total resection was performed in 27 patients (87%). Twelve patients (39%) received upfront RT, 10 (32%) received delayed RT, and 9 (29%) received no RT. During the study period, there were 11 relapses (35%) and 10 deaths (32%). Five-year overall survival was 69.9%; 5-year event-free survival was 49.3%. In univariate analysis, gross total resection was associated with improved overall survival event-free survival; OS and EFS was better patients who received RT than in those who did not. Upfront RT resulted in better OS and EFS than delayed RT. No significant effect on survival was observed with regard to age, sex, tumor location, RT dosage, and protocol used. The investigators recommended early initiation of adjuvant RT in the multimodal management of pediatric ependymomas.[17]

Physical and neurologic examination

Monitoring of clinical response and potential treatment-related side effects should be on a weekly basis during radiotherapy. Protocols using investigational chemotherapy regimens dictate how frequently these examinations are conducted during treatment.

Following completion of therapy, assessments are generally performed every 3 months for the first year to 18 months, then every 6 months for the next 2 years, and annually thereafter, provided no interim complications occur.

Baseline neuropsychology and developmental testing should be performed at the completion of therapy and annually thereafter.

Imaging studies

An MRI with contrast of the head should be obtained at the completion of radiotherapy and then generally in conjuncture with the physical and neurologic examination schedule or sooner if clinically indicated.

Although the optimal timing of posttreatment imaging for the evaluation of both response to therapy and recurrence has yet to be determined, most clinicians agree that routine surveillance should be performed at least every 3-6 months during the first 2 years and every 6-12 months for the following 2-3 years after treatment.

Further MRI evaluations at 3-year to 5-year intervals may be useful for the detection of late events such as radiation-induced secondary tumors. Investigational chemotherapeutic regimens also may dictate the imaging study schedules.

An MRI of the spine should be obtained at the completion of treatment and then once yearly for the first 2 years after therapy, unless there is evidence of leptomeningeal dissemination at diagnosis or during therapy, in which case the frequency of such tests is increased in accordance with the response to treatment. Routine spinal evaluations beyond 2 years from the completion of treatment may not be practical since local recurrences are far more likely than isolated neuraxial disease.

Laboratory studies

A weekly CBC count during radiotherapy (to monitor for hematopoietic toxicity and to determine whether intervention should be carried out to maintain hemoglobin levels at or higher than 9 g/dL to maximize radiation effect) is all that is required unless dictated by investigational chemotherapeutic regimens or clinically indicated.

Further Inpatient Care

Admit only patients with ependymoma who are eligible for investigational chemotherapy.

Investigational chemotherapy may cause complications such as fever, neutropenia, or suspected infection; therefore, hospitalization may be necessary.

Inpatient and Outpatient Medications

No medications are needed unless the patient is enrolled in an investigational chemotherapeutic regimen.

Dexamethasone may be necessary to reduce the inflammatory response associated with the tumor and/or therapy.

Transfer

Transfer the patient to a pediatric center that can provide appropriate MRI imaging studies, neurosurgical intervention, and radiotherapy. Follow-up with a neuro-oncologist may be necessary.