Ependymoma

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    Ependymoma is a type of brain tumor that may arise in the ventricles of the brain or in the spinal cord. It is also called an ependymal tumor. Learn about ependymoma and find information on how we support and care for children and teens with ependymoma before, during, and after treatment.

The Brain Tumor Center at Dana-Farber/Boston Children's Cancer and Blood Disorders Center cares for children with many different types of common and rare brain and spinal tumors, including astrocytomas, medulloblastomas, ependymoma, glioblastomas, and primitive neuroectodermal tumors (PNET).

Your child will receive care from some of the world’s most experienced pediatric brain tumor doctors and internationally recognized pediatric subspecialists.

Our team works closely together to develop a care plan that offers your child the highest possible quality of life after treatment, and takes the needs of your child and your family into account.

Children treated at the Brain Tumor Center have access to some of the most advanced diagnostics and therapies, including:

  • Quick and accurate diagnosis from our dedicated pediatric neuropathologist
  • Access to advanced technologies like the intraoperative MRI, which allows our neurosurgeons to see detailed images of the brain during surgery
  • Advanced pediatric radiation oncology services, including targeted radiosurgery and low-dose radiation therapy that minimize exposure to radiation
  • Outpatient and oral chemotherapy, which may minimize the number of times your child will need to visit the hospital
  • Innovative therapies offered through clinical trials at Dana-Farber, Boston Children's Hospital, and nationally
  • Specialized programs for the treatment of low- and high-grade gliomas, and medulloblastoma

Thanks to refined surgical techniques and improved chemotherapy and radiation therapy, the majority of children with brain and spinal cord tumors are now long-term survivors. However, they may face physical, social, and intellectual challenges that require specialized care.

Learn more about our Brain Tumor Center.

Information for: Patients | Healthcare Professionals

General Information About Childhood Ependymoma

Childhood ependymoma is a disease in which malignant (cancer) cells form in the tissues of the brain and spinal cord.

The brain controls vital functions such as memory and learning, emotion, and the senses (hearing, sight, smell, taste, and touch). The spinal cord is made up of bundles of nervefibers that connect the brain with nerves in most parts of the body.

Ependymomas form from ependymal cells that line the ventricles and passageways in the brain and the spinal cord. Ependymal cells make cerebrospinal fluid (CSF).

This summary is about the treatment of primary brain tumors (tumors that begin in the brain). Treatment of metastatic brain tumors, which are tumors that begin in other parts of the body and spread to the brain, is not discussed in this summary.

There are many different types of brain tumors. Brain tumors can occur in both children and adults. However, treatment for children is different than treatment for adults. See the following PDQ summaries for more information:

  • Childhood Brain and Spinal Cord Tumors Treatment Overview
  • Adult Brain Tumors Treatment

There are different types of ependymomas.

The World Health Organization (WHO) groups ependymal tumors into four main subtypes:

  • Subependymoma (WHO Grade I).
  • Myxopapillary ependymoma (WHO Grade I).
  • Ependymoma (WHO Grade II)
  • Anaplastic ependymoma (WHO Grade III).

The grade of a tumor describes how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Low-grade (Grade I) cancer cells look more like normal cells and tend to grow and spread more slowly than high-grade (Grade III) cancer cells.

The part of the brain that is affected depends on where the ependymoma forms.

Ependymomas can form anywhere in the fluid-filled ventricles and passageways in the brain and spinal cord. Most ependymomas form in the fourth ventricle and affect the cerebellum and the brain stem. Once an ependymoma forms, areas of the brain that may be affected include:

  • Cerebrum: The largest part of the brain, at the top of the head. The cerebrum controls thinking, learning, problem-solving, speech, emotions, reading, writing, and voluntary movement.
  • Cerebellum: The lower, back part of the brain (near the middle of the back of the head). The cerebellum controls movement, balance, and posture.
  • Brain stem: The part that connects the brain to the spinal cord, in the lowest part of the brain (just above the back of the neck). The brain stem controls breathing, heart rate, and the nerves and muscles used in seeing, hearing, walking, talking, and eating.
  • Spinal cord: The column of nerve tissue that runs from the brain stem down the center of the back. It is covered by three thin layers of tissue called membranes. The spinal cord and membranes are surrounded by the vertebrae (back bones). Spinal cord nerves carry messages between the brain and the rest of the body, such as a signal from the brain to cause muscles to move or from the skin to the brain for the sense of touch.
Drawing of brain anatomy showing the brain stem, pons, medulla, spinal cord, cerebellum, cerebrum, meninges, ventricles (fluid-filled spaces), and skull. Drawing of the inside of the brain showing ventricles (fluid-filled spaces), choroid plexus, hypothalamus, pineal gland, pituitary gland, optic nerve, brain stem, cerebellum, cerebrum, medulla, pons, and spinal cord.
Anatomy of the brain, showing the cerebrum, cerebellum, brain stem, and other parts of the brain. Anatomy of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal fluid shown in blue), and other parts of the brain.

The cause of most childhood brain tumors is unknown.

The signs and symptoms of childhood ependymoma depend on the child’s age and where the tumor is found.

The following signs and symptoms may be caused by childhood ependymoma or by other conditions. Check with a doctor if your child has any of the following:

  • Frequent headaches.
  • Seizures.
  • Nausea and vomiting.
  • Pain or stiffness in the neck.
  • Loss of balance or trouble walking.
  • Weakness in the legs.
  • Blurry vision.
  • Back pain.
  • A change in bowel function.
  • Trouble urinating.
  • Confusion or irritability.

Tests that examine the brain and spinal cord are used to detect (find) childhood ependymoma.

The following tests and procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Neurological exam: A series of questions and tests to check the brain, spinal cord, and nerve function. The exam checks a person’s mental status, coordination, and ability to walk normally, and how well the muscles, senses, and reflexes work. This may also be called a neuro exam or a neurologic exam.
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • MRI (magnetic resonance imaging) with gadolinium: A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the brain and spinal cord. A substance called gadolinium is injected into a vein and travels through the bloodstream. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • Lumbar puncture: A procedure used to collect cerebrospinal fluid (CSF) from the spinal column to check for cancer cells. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.
    Lumbar puncture; drawing shows a patient lying in a curled position on a table and a spinal needle (a long, thin needle) being inserted into the lower back. Inset shows a close-up of the spinal needle inserted into the cerebrospinal fluid (CSF) in the lower part of the spinal column.
    Lumbar puncture. A patient lies in a curled position on a table. After a small area on the lower back is numbed, a spinal needle (a long, thin needle) is inserted into the lower part of the spinal column to remove cerebrospinal fluid (CSF, shown in blue). The fluid may be sent to a laboratory for testing.

Childhood ependymoma is diagnosed and removed in surgery.

If the diagnostic tests show there may be a brain tumor, a biopsy is done by removing part of the skull and using a needle to remove a sample of the brain tissue. A pathologist views the tissue under a microscope to look for cancer cells. If cancer cells are found, the doctor will remove as much tumor as safely possible during the same surgery. An MRI is often done after the tumor is removed to find out whether any tumor remains.

Drawing of a craniotomy showing a section of the scalp that has been pulled back to remove a piece of the skull; the dura covering the brain has been opened to expose the brain. The layer of muscle under the scalp is also shown.
Craniotomy: An opening is made in the skull and a piece of the skull is removed to show part of the brain.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on:

  • Where the tumor has formed in the central nervous system (CNS).
  • Whether there are certain changes in the genes or chromosomes.
  • Whether any cancer cells remain after surgery to remove the tumor.
  • The type of ependymoma.
  • The age of the child when the tumor is diagnosed.
  • Whether the cancer has spread to other parts of the brain or spinal cord.
  • Whether the tumor has just been diagnosed or has recurred (come back).

Prognosis also depends on the type and dose of radiation therapy that is given.

Stages of Childhood Ependymoma

The area where the tumor is found and the child’s age are used in place of a staging system to plan cancer treatment.

Staging is the process used to find out how much cancer there is and if cancer has spread. There is no standard staging system for childhood ependymoma. Treatment is based on where the cancer is in the body and the age of the child.

The information from tests and procedures done to detect (find) childhood ependymoma is used to plan cancer treatment.

Some of the tests used to detect childhood ependymoma are repeated after the tumor is removed by surgery. (See the General Information section.) This is to find out how much tumor remains after surgery.

Recurrent Childhood Ependymoma

Recurrent childhood ependymoma is a tumor that has recurred (come back) after it has been treated. Childhood ependymoma commonly recurs, usually at the original cancer site. The tumor may come back as long as 15 years or more after initial treatment.

Treatment Option Overview

There are different types of treatment for children with ependymoma.

Different types of treatment are available for children with ependymoma. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.

Children with ependymoma should have their treatment planned by a team of health care providers who are experts in treating childhood brain tumors.

Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other pediatrichealth care providers who are experts in treating children with brain tumors and who specialize in certain areas of medicine. These may include the following specialists:

  • Pediatric neurosurgeon.
  • Neurologist.
  • Neuropathologist.
  • Neuroradiologist.
  • Pediatrician.
  • Rehabilitation specialist.
  • Radiation oncologist.
  • Medical oncologist.
  • Endocrinologist.
  • Psychologist.

Childhood brain and spinal cord tumors may cause signs and symptoms that begin before diagnosis and continue for months or years.

Childhood brain and spinal cordtumors may cause signs and symptoms that continue for months or years. Signs and symptoms caused by the tumor may begin before diagnosis. Signs and symptoms caused by treatment may begin during or right after treatment.

Some cancer treatments cause side effects months or years after treatment has ended.

These are called late effects. Late effects of cancer treatment may include the following:

  • Physical problems.
  • Changes in mood, feelings, thinking, learning, or memory.
  • Second cancers (new types of cancer).

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the effects cancer treatment can have on your child. (See the PDQ summary on Late Effects of Treatment for Childhood Cancer for more information).

Three types of standard treatment are used:

Surgery

If the results of diagnostic tests show there may be a brain tumor, a biopsy is done by removing part of the skull and using a needle to remove a sample of the brain tissue. A pathologist views the tissue under a microscope to check for cancer cells. If cancer cells are found, the doctor will remove as much tumor as safely possible during the same surgery.

Drawing of a craniotomy showing a section of the scalp that has been pulled back to remove a piece of the skull; the dura covering the brain has been opened to expose the brain. The layer of muscle under the scalp is also shown.
Craniotomy: An opening is made in the skull and a piece of the skull is removed to show part of the brain.

An MRI is often done after the tumor is removed to find out whether any tumor remains. If tumor remains, a second surgery to remove as much of the remaining tumor as possible may be done.

Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment to lower the risk that the cancer will come back after surgery is called adjuvant therapy.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type of cancer being treated. Childhood ependymoma may be treated with fractionated radiation therapy, which divides the total dose of radiation into several smaller, equal doses delivered over a number of days.

External radiation therapy can be given in different ways:

  • Three-dimensional (3D) conformal radiation therapy uses a computer to create a 3D picture of the tumor. The radiation beams are shaped to fit the tumor.
  • Proton-beam therapy is a type of high-energy, external radiation therapy that uses streams of protons (small, positively-charged particles of matter) to kill tumor cells.
  • Stereotactic radiosurgery is a type of radiation therapy that uses a head frame attached to the skull to keep the head still. A single large dose of radiation is aimed directly at the brain tumor. This causes less damage to nearby healthy tissue. Stereotactic radiosurgery is also called stereotaxic radiosurgery, radiosurgery, and radiation surgery. This procedure does not involve surgery.

Children younger than 3 years who receive radiation therapy to the brain have a higher risk of problems with growth and development than older children. 3D conformal radiation therapy and proton-beam therapy are being studied in children younger than 3 years to see if the effects of radiation on growth and development are lessened.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type of cancer being treated.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI Web site.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child's condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Follow-up tests for childhood ependymoma include an MRI (magnetic resonance imaging) of the brain and spinal cord every 3 months for the first 1 or 2 years after treatment. After 2 years, MRIs may be done every 6 months for the next 3 years.

Treatment Options for Childhood Ependymoma

Newly Diagnosed Childhood Ependymoma

A child with a newly diagnosedependymoma has not had treatment for the tumor. The child may have had treatment to relieve symptoms caused by the tumor.

Subependymoma

Treatment of newly diagnosed subependymoma (WHO Grade I) is:

  • Surgery.

Myxopapillary ependymoma

Treatment of newly diagnosed myxopapillary ependymoma (WHO Grade I) is:

  • Surgery with or without radiation therapy.

Childhood ependymoma or anaplastic ependymoma

Treatment of newly diagnosed childhood ependymoma (WHO Grade II) or anaplastic ependymoma (WHO Grade III) is:

  • Surgery.

After surgery, the plan for further treatment depends on the following:

  • Whether any cancercells remain after surgery.
  • Whether the cancer has spread to other parts of the brain or spinal cord.
  • The age of the child.

When the tumor is completely removed and cancer cells have not spread, treatment may include the following:

  • Radiation therapy.
  • A clinical trial of radiation therapy followed by chemotherapy.
  • A clinical trial of observation for patients whose tumor is completely removed or who have no sign of cancer after chemotherapy.

When part of the tumor remains after surgery, but cancer cells have not spread, treatment may include the following:

  • A second surgery to remove as much of the remaining tumor as possible.
  • Radiation therapy.
  • Chemotherapy followed by radiation therapy.
  • A clinical trial of chemotherapy given before and after radiation therapy.

When cancer cells have spread within the brain and spinal cord, treatment may include the following:

  • Radiation therapy to the brain and spinal cord.

Treatment for children younger than 3 years of age may include the following:

  • Chemotherapy.
  • Radiation therapy.
  • A clinical trial of 3-dimensional (3D) conformal radiation therapy or proton-beam radiation therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with newly diagnosed childhood ependymoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your child's doctor about clinical trials that may be right for your child. General information about clinical trials is available from the NCI Web site.

Recurrent Childhood Ependymoma

Treatment of recurrent childhood ependymoma may include the following:

  • Surgery.
  • Radiation therapy, including stereotactic radiosurgery, if radiation therapy was not used when the tumor was first diagnosed.
  • Chemotherapy, if chemotherapy was not used when the tumor was first treated.
  • A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent childhood ependymoma. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your child's doctor about clinical trials that may be right for your child. General information about clinical trials is available from the NCI Web site.

To Learn More About Childhood Brain Tumors

For more information about childhood brain tumors, see the following

For more childhood cancer information and other general cancer resources, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on January 31, 2014.


General Information About Childhood Ependymoma

The PDQ childhood brain tumor treatment summaries are organized primarily according to the World Health Organization (WHO) classification of nervous system tumors.[1][2] For a full description of the classification of nervous system tumors and a link to the corresponding treatment summary for each type of brain tumor, refer to the PDQ summary on Childhood Brain and Spinal Cord Tumors Treatment Overview.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2002, childhood cancer mortality decreased by more than 50%.[3] Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)

Primary brain tumors are a diverse group of diseases that together constitute the most common solid tumor of childhood. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis.

Ependymomas arise from ependymal cells that line the ventricles and passageways in the brain and the center of the spinal cord. Ependymal cells produce cerebrospinal fluid (CSF). These tumors are classified as supratentorial or infratentorial. In children, most ependymomas are infratentorial tumors that arise in or around the fourth ventricle. According to the WHO classification of brain tumors, ependymal tumors are classified into the following four main subtypes:

  • Subependymoma (WHO Grade I).
  • Myxopapillary ependymoma (WHO Grade I).
  • Ependymoma (WHO Grade II).
  • Anaplastic ependymoma (WHO Grade III).

The location of the tumor determines the clinical presentation. Treatment begins with surgery. The type of adjuvant therapy given, such as a second surgery, chemotherapy, or radiation therapy, depends on the following:

  • Subtype of ependymoma.
  • Whether the tumor was completely removed during the initial surgery.
  • Whether the tumor has disseminated throughout the central nervous system.
  • Child's age.

Incidence

Childhood ependymoma comprises approximately 9% of all childhood brain tumors, representing about 200 cases per year in the United States.[4][5]

Anatomy

Drawing of the inside of the brain showing  the lateral ventricle, third ventricle, and fourth ventricle, cerebrum, choroid plexus, hypothalamus, pineal gland, pituitary gland, optic nerve, tentorium, cerebellum,  brain stem, pons, medulla, and spinal cord.
Anatomy of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal fluid shown in blue), and other parts of the brain. The tentorium separates the cerebrum from the cerebellum. The infratentorium (posterior fossa) is the region below the tentorium that contains the brain stem, cerebellum, and fourth ventricle. The supratentorium is the region above the tentorium and denotes the region that contains the cerebrum.

Clinical Features

The clinical presentation of ependymoma is dependent on tumor location.

  • Infratentorial (posterior fossa) ependymoma: In children, approximately 65% to 75% of ependymomas arise in the posterior fossa.[6] Children with posterior fossa ependymoma may present with signs and symptoms of obstructive hydrocephalus due to obstruction at the level of the fourth ventricle. They may also present with ataxia, neck pain, or cranial nerve palsies.
  • Supratentorial ependymoma: Supratentorial ependymoma may result in headache, seizures, or location-dependent focal neurologic deficits.
  • Spinal cord ependymoma: Spinal cord ependymomas, which are often the myxopapillary variant, tend to cause back pain, lower extremity weakness, and/or bowel and bladder dysfunction.

Diagnostic Evaluation

Every patient suspected of having ependymoma should be evaluated with diagnostic imaging of the whole brain and spinal cord. The most sensitive method available for evaluating spinal cord subarachnoid metastasis is spinal magnetic resonance imaging (MRI) performed with gadolinium. This is ideally done before surgery to avoid confusion with postoperative blood. If MRI is used, the entire spine is generally imaged in at least two planes with contiguous MRI slices performed after gadolinium enhancement. In addition, CSF cytological evaluation should be conducted.[7]

Prognostic Factors

Unfavorable factors affecting outcome (except as noted) include the following:

  • Gain of chromosome 1q25. Gain of chromosome 1q25 is present in approximately 20% of pediatric intracranial ependymoma cases and has been reported as a negative prognostic factor by multiple research groups.[8][9][10][11]
  • Gene expression profile.

    Posterior fossa ependymoma can be divided into the following two groups based on distinctive patterns of gene expression.[12][13]

    • One expression-defined group occurs primarily in young children and is characterized by a largely balanced genomic profile with an increased occurrence of chromosome 1q gain and expression of genes and proteins previously shown to be associated with poor prognosis, such as tenascin C and epidermal growth factor receptor (EGFR).[8][14]
    • The second expression-defined group occurs primarily in older children and adults and is characterized by a more favorable prognosis and by numerous cytogenetic abnormalities involving whole chromosomes or chromosomal arms.[12]

    Other factors that have been reported to be associated with poor prognosis for pediatric ependymoma include expression of the enzymatic subunit of telomerase (hTERT) [15][16] and expression of the neural stem cell marker Nestin.[17][Level of evidence: 3iiiA]

  • Tumor location. Cranial variants of ependymoma have a less favorable outcome than primary spinal cord ependymomas.[18][19] Location within the spinal cord may also affect outcome, with tumors in the lower portion of the spinal cord having a worse prognosis.[20][Level of evidence: 3iiiA]
  • Younger age at diagnosis.[21][Level of evidence: 3iiiDii]
  • Anaplastic histology.[21][22][23]; [24][Level of evidence: 3iA]; [25][Level of evidence: 3iiiDi]
  • Subtotal resection.[21]
  • Lower doses of radiation.[26]
  • Higher proliferation marker.[27][28]
  • MIB-1 labeling index.[28]

Follow-up After Treatment

Surveillance neuroimaging, coupled with clinical assessments, are generally recommended after treatment for ependymoma. The frequency and duration have been arbitrarily determined and the utility is uncertain.[29] Most practitioners obtain MRI imaging of the brain and/or spinal cord every 3 months for the first 1 to 2 years after treatment. After 2 years, imaging every 6 months for the next 3 years is often undertaken.

References:

  1. Louis DN, Ohgaki H, Wiestler OD, et al., eds.: WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon, France: IARC Press, 2007.

  2. Louis DN, Ohgaki H, Wiestler OD, et al.: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114 (2): 97-109, 2007.

  3. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010.

  4. Gurney JG, Smith MA, Bunin GR: CNS and miscellaneous intracranial and intraspinal neoplasms. In: Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649., Chapter 3, pp 51-63. Also available online. Last accessed December 18, 2013.

  5. Central Brain Tumor Registry of the United States.: Statistical Report: Primary Brain Tumors in the United States, 1997-2001. Hinsdale, Ill: Central Brain Tumor Registry of the United States, 2004. Also available online. Last accessed December 18, 2013.

  6. Andreiuolo F, Puget S, Peyre M, et al.: Neuronal differentiation distinguishes supratentorial and infratentorial childhood ependymomas. Neuro Oncol 12 (11): 1126-34, 2010.

  7. Moreno L, Pollack IF, Duffner PK, et al.: Utility of cerebrospinal fluid cytology in newly diagnosed childhood ependymoma. J Pediatr Hematol Oncol 32 (6): 515-8, 2010.

  8. Mendrzyk F, Korshunov A, Benner A, et al.: Identification of gains on 1q and epidermal growth factor receptor overexpression as independent prognostic markers in intracranial ependymoma. Clin Cancer Res 12 (7 Pt 1): 2070-9, 2006.

  9. Korshunov A, Witt H, Hielscher T, et al.: Molecular staging of intracranial ependymoma in children and adults. J Clin Oncol 28 (19): 3182-90, 2010.

  10. Kilday JP, Mitra B, Domerg C, et al.: Copy number gain of 1q25 predicts poor progression-free survival for pediatric intracranial ependymomas and enables patient risk stratification: a prospective European clinical trial cohort analysis on behalf of the Children's Cancer Leukaemia Group (CCLG), Societe Francaise d'Oncologie Pediatrique (SFOP), and International Society for Pediatric Oncology (SIOP). Clin Cancer Res 18 (7): 2001-11, 2012.

  11. Godfraind C, Kaczmarska JM, Kocak M, et al.: Distinct disease-risk groups in pediatric supratentorial and posterior fossa ependymomas. Acta Neuropathol 124 (2): 247-57, 2012.

  12. Wani K, Armstrong TS, Vera-Bolanos E, et al.: A prognostic gene expression signature in infratentorial ependymoma. Acta Neuropathol 123 (5): 727-38, 2012.

  13. Witt H, Mack SC, Ryzhova M, et al.: Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20 (2): 143-57, 2011.

  14. Korshunov A, Golanov A, Timirgaz V: Immunohistochemical markers for intracranial ependymoma recurrence. An analysis of 88 cases. J Neurol Sci 177 (1): 72-82, 2000.

  15. Tabori U, Ma J, Carter M, et al.: Human telomere reverse transcriptase expression predicts progression and survival in pediatric intracranial ependymoma. J Clin Oncol 24 (10): 1522-8, 2006.

  16. Tabori U, Wong V, Ma J, et al.: Telomere maintenance and dysfunction predict recurrence in paediatric ependymoma. Br J Cancer 99 (7): 1129-35, 2008.

  17. Milde T, Hielscher T, Witt H, et al.: Nestin expression identifies ependymoma patients with poor outcome. Brain Pathol 22 (6): 848-60, 2012.

  18. McGuire CS, Sainani KL, Fisher PG: Both location and age predict survival in ependymoma: a SEER study. Pediatr Blood Cancer 52 (1): 65-9, 2009.

  19. Benesch M, Frappaz D, Massimino M: Spinal cord ependymomas in children and adolescents. Childs Nerv Syst 28 (12): 2017-28, 2012.

  20. Oh MC, Sayegh ET, Safaee M, et al.: Prognosis by tumor location for pediatric spinal cord ependymomas. J Neurosurg Pediatr 11 (3): 282-8, 2013.

  21. Tamburrini G, D'Ercole M, Pettorini BL, et al.: Survival following treatment for intracranial ependymoma: a review. Childs Nerv Syst 25 (10): 1303-12, 2009.

  22. Merchant TE, Jenkins JJ, Burger PC, et al.: Influence of tumor grade on time to progression after irradiation for localized ependymoma in children. Int J Radiat Oncol Biol Phys 53 (1): 52-7, 2002.

  23. Korshunov A, Golanov A, Sycheva R, et al.: The histologic grade is a main prognostic factor for patients with intracranial ependymomas treated in the microneurosurgical era: an analysis of 258 patients. Cancer 100 (6): 1230-7, 2004.

  24. Amirian ES, Armstrong TS, Aldape KD, et al.: Predictors of survival among pediatric and adult ependymoma cases: a study using Surveillance, Epidemiology, and End Results data from 1973 to 2007. Neuroepidemiology 39 (2): 116-24, 2012.

  25. Tihan T, Zhou T, Holmes E, et al.: The prognostic value of histological grading of posterior fossa ependymomas in children: a Children's Oncology Group study and a review of prognostic factors. Mod Pathol 21 (2): 165-77, 2008.

  26. Vaidya K, Smee R, Williams JR: Prognostic factors and treatment options for paediatric ependymomas. J Clin Neurosci 19 (9): 1228-35, 2012.

  27. Wolfsberger S, Fischer I, Höftberger R, et al.: Ki-67 immunolabeling index is an accurate predictor of outcome in patients with intracranial ependymoma. Am J Surg Pathol 28 (7): 914-20, 2004.

  28. Kurt E, Zheng PP, Hop WC, et al.: Identification of relevant prognostic histopathologic features in 69 intracranial ependymomas, excluding myxopapillary ependymomas and subependymomas. Cancer 106 (2): 388-95, 2006.

  29. Good CD, Wade AM, Hayward RD, et al.: Surveillance neuroimaging in childhood intracranial ependymoma: how effective, how often, and for how long? J Neurosurg 94 (1): 27-32, 2001.

Histopathologic Classification of Childhood Ependymal Tumors

In the most recent World Health Organization (WHO) classification of brain tumors, ependymal tumors are classified into the following four main subtypes:[1]

  1. Subependymoma (WHO Grade I): A subependymoma is a slow-growing neoplasm, typically attached to the ventricle wall and is composed of glial tumor cell clusters embedded in a fibrillary matrix.

    The true incidence of subependymomas (WHO Grade I) is difficult to determine. These tumors are frequently asymptomatic and may be found incidentally at autopsy. Subependymomas probably comprise less than 5% of all ependymal tumors.

  2. Myxopapillary ependymoma (WHO Grade I): A myxopapillary ependymoma arises almost exclusively in the location of the conus medullaris, cauda equina, and filum terminale of the spinal cord and is characterized histologically by tumor cells arranged in a papillary manner around vascularized myxoid stromal cores.
  3. Ependymoma (WHO Grade II): The ependymoma, which is considered a Grade II neoplasm originating from the walls of the ventricles or from the spinal canal, is composed of neoplastic ependymal cells. Ependymomas are subdivided, based on histological findings, into the following four subtypes:
    • Cellular ependymoma—the most common subtype; usually demonstrates significant cellularity without an increase in mitotic activity.
    • Papillary ependymoma—forms linear, epithelial-like surfaces along cerebrospinal fluid exposures.
    • Clear cell ependymoma—displays an oligodendroglial-like appearance with perinuclear halos; this variant is preferentially located in the supratentorial compartment of the brain.
    • Tanycytic ependymoma—the rarest form of Grade II ependymoma; most commonly found in the spinal cord; tumor cells are arranged in fascicles of variable width and cell density and are poorly intertwined.
  4. Anaplastic ependymoma (WHO Grade III): Also known as malignant ependymoma. An anaplastic ependymoma is considered a malignant glioma of ependymal differentiation and, compared with the Grade II ependymomas, shows increased cellularity and increased mitotic activity, often associated with microvascular proliferation and necrosis.

In children, approximately 65% to 75% of ependymomas arise in the posterior fossa. Although supratentorial and infratentorial ependymomas are believed to arise from radial glia cells, they have different genomic, gene expression, and immunohistochemical signatures.[2][3][4] Supratentorial tumors are more often characterized by neuronal differentiation.[3]

Subependymomas and myxopapillary ependymomas are usually considered to be clinically and pathologically distinct from the Grade II and Grade III ependymomas. In Grade II and Grade III ependymomas, the relationship between histological features and survival has varied among studies, although most recent larger studies and meta-analyses have demonstrated that histological grade is an independent predictor of event-free survival.[5][6][7] A single-institution study suggests that patients with clear-cell ependymomas may have a higher risk of treatment failure than do patients with other forms of WHO Grade II ependymomas;[8] however, confirmation is required in a larger group of unselected patients.

Ependymoblastomas, which generally behave more like medulloblastomas or cerebral neuroectodermal tumors, are considered separate entities from ependymomas and are now classified with the embryonal tumors.[1][5] (Refer to the PDQ summary on Childhood Central Nervous System Embryonal Tumors Treatment for more information.)

The pathologic classification of pediatric brain tumors is a specialized area that is evolving; review of the diagnostic tissue by a neuropathologist who has particular expertise in this area is strongly recommended.

References:

  1. Louis DN, Ohgaki H, Wiestler OD, et al., eds.: WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon, France: IARC Press, 2007.

  2. Taylor MD, Poppleton H, Fuller C, et al.: Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8 (4): 323-35, 2005.

  3. Andreiuolo F, Puget S, Peyre M, et al.: Neuronal differentiation distinguishes supratentorial and infratentorial childhood ependymomas. Neuro Oncol 12 (11): 1126-34, 2010.

  4. Grill J, Bergthold G, Ferreira C: Pediatric ependymomas: will molecular biology change patient management? Curr Opin Oncol 23 (6): 638-42, 2011.

  5. Louis DN, Ohgaki H, Wiestler OD, et al.: The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114 (2): 97-109, 2007.

  6. Tihan T, Zhou T, Holmes E, et al.: The prognostic value of histological grading of posterior fossa ependymomas in children: a Children's Oncology Group study and a review of prognostic factors. Mod Pathol 21 (2): 165-77, 2008.

  7. Shu HK, Sall WF, Maity A, et al.: Childhood intracranial ependymoma: twenty-year experience from a single institution. Cancer 110 (2): 432-41, 2007.

  8. Fouladi M, Helton K, Dalton J, et al.: Clear cell ependymoma: a clinicopathologic and radiographic analysis of 10 patients. Cancer 98 (10): 2232-44, 2003.

Stage Information for Childhood Ependymoma

Although there is no formal staging system, ependymomas can be divided into supratentorial, infratentorial, and spinal tumors. Approximately 30% of childhood ependymomas arise in supratentorial regions of the brain and 70% arise in the posterior fossa.[1] They usually originate in the ependymal linings of ventricles or central canal or ventriculus terminalis of the spinal cord and have access to the cerebrospinal fluid. Therefore, these tumors may spread throughout the neuraxis, although dissemination is noted in less than 10% of patients with Grade II and Grade III ependymomas. Myxopapillary ependymomas are more likely to disseminate to the nervous system early in the course of illness.

References:

  1. Villano JL, Parker CK, Dolecek TA: Descriptive epidemiology of ependymal tumours in the United States. Br J Cancer 108 (11): 2367-71, 2013.

Treatment Option Overview for Childhood Ependymoma

Many of the improvements in survival in childhood cancer have been made as a result of clinical trials that have attempted to improve on the best available, accepted therapy. Clinical trials in pediatrics are designed to compare new therapy with therapy that is currently accepted as standard. This comparison may be done in a randomized study of two treatment arms or by evaluating a single new treatment and comparing the results with those previously obtained with existing therapy.

Because of the relative rarity of cancer in children, all patients with aggressive brain tumors should be considered for entry into a clinical trial. To determine and implement optimum treatment, treatment planning by a multidisciplinary team of cancer specialists who have experience treating childhood brain tumors is required. Radiation therapy of pediatric brain tumors is technically demanding and should be performed in centers that have experience in that area to ensure optimal results.

Table 1. Standard Treatment Options for Childhood Ependymoma

Stage and/or Histopathologic Classification

Standard Treatment Options

Newly diagnosed childhood subependymoma

Surgery

Newly diagnosed childhood myxopapillary ependymoma

Surgery with or without radiation therapy

Newly diagnosed childhood ependymoma (WHO Grade II) or anaplastic ependymoma (WHO Grade III):

Surgery

Adjuvant therapy:

No residual disease, no disseminated disease

Radiation therapy

Residual disease, no disseminated disease

Second-look surgery

Radiation therapy

Preirradiation chemotherapy

Central nervous system disseminated disease

Radiation therapy

Children younger than 3 years

Chemotherapy

Radiation therapy

Recurrent childhood ependymoma

Surgery

Radiation therapy and/or chemotherapy

Treatment of Newly Diagnosed Childhood Subependymoma

The standard treatment option for newly diagnosed subependymoma (WHO Grade I) includes the following:

  1. Surgery.

In cases requiring therapy, complete surgical removal is often curative.

Occasionally, subependymomas cause ventricular obstruction and, in these cases, ventriculoperitoneal shunt placement is indicated. Spontaneous intratumoral hemorrhage has also been observed.[1]

References:

  1. Waldron JS, Tihan T: Epidemiology and pathology of intraventricular tumors. Neurosurg Clin N Am 14 (4): 469-82, 2003.

Treatment of Newly Diagnosed Childhood Myxopapillary Ependymoma

Myxopapillary ependymomas, considered to be a histologic subtype of ependymoma, have a relatively high incidence of central nervous system tumor dissemination at diagnosis and at follow-up. Imaging of the complete craniospinal axis at the time of diagnosis and during follow-up is indicated.[1][2]

Standard treatment options for newly diagnosed myxopapillary ependymoma (WHO Grade I) include the following:

  1. Surgery with or without adjuvant radiation therapy.

Historically, the management of myxopapillary ependymoma (WHO Grade I) consisted of an attempt at en bloc resection of the tumor with no further treatment in the case of a gross-total resection.[3]; [4][Level of evidence: 3iiiDi] However, based on the finding that dissemination of these tumors to other parts of the neuraxis can occur, particularly when complete resection is not obtained, and evidence that focal radiation therapy may improve progression-free survival, many practitioners now favor the use of radiation therapy after surgical resection of the primary mass.[1][3]; [5][Level of evidence: 3iiiDi]; [6][7][Level of evidence: 3iiiDiii]

References:

  1. Fassett DR, Pingree J, Kestle JR: The high incidence of tumor dissemination in myxopapillary ependymoma in pediatric patients. Report of five cases and review of the literature. J Neurosurg 102 (1 Suppl): 59-64, 2005.

  2. Bagley CA, Kothbauer KF, Wilson S, et al.: Resection of myxopapillary ependymomas in children. J Neurosurg 106 (4 Suppl): 261-7, 2007.

  3. Akyurek S, Chang EL, Yu TK, et al.: Spinal myxopapillary ependymoma outcomes in patients treated with surgery and radiotherapy at M.D. Anderson Cancer Center. J Neurooncol 80 (2): 177-83, 2006.

  4. Bagley CA, Wilson S, Kothbauer KF, et al.: Long term outcomes following surgical resection of myxopapillary ependymomas. Neurosurg Rev 32 (3): 321-34; discussion 334, 2009.

  5. Pica A, Miller R, Villà S, et al.: The results of surgery, with or without radiotherapy, for primary spinal myxopapillary ependymoma: a retrospective study from the rare cancer network. Int J Radiat Oncol Biol Phys 74 (4): 1114-20, 2009.

  6. Agbahiwe HC, Wharam M, Batra S, et al.: Management of pediatric myxopapillary ependymoma: the role of adjuvant radiation. Int J Radiat Oncol Biol Phys 85 (2): 421-7, 2013.

  7. Jeibmann A, Egensperger R, Kuchelmeister K, et al.: Extent of surgical resection but not myxopapillary versus classical histopathological subtype affects prognosis in lumbo-sacral ependymomas. Histopathology 54 (2): 260-2, 2009.

Treatment of Newly Diagnosed Childhood Ependymoma or Anaplastic Ependymoma

Standard treatment options for newly diagnosed ependymoma (WHO Grade II) or anaplastic ependymoma (WHO Grade III) include the following:

  1. Surgery.
  2. Adjuvant therapy.
    • Treatment options for no residual disease, no disseminated disease.
    • Treatment options for residual disease, no disseminated disease.
    • Treatment options for central nervous system (CNS) disseminated disease.
    • Treatment options for children younger than 3 years.

Typically, all patients undergo surgery to remove the tumor. Whether additional treatment is given depends on the extent of tumor resection and whether there is disseminated disease.

Surgery

Surgery should be performed in an attempt at maximal tumor reduction. Evidence suggests that more extensive surgical resection is related to an improved rate of survival.[1][2][3][4][5] Magnetic resonance imaging (MRI) should be performed postoperatively to confirm the extent of resection. If not performed preoperatively, MRI of the entire neuraxis to evaluate disease dissemination and cerebrospinal fluid cytopathology should be performed.

Patients with residual tumor or disseminated disease should be considered at high risk for relapse and should be treated on protocols specifically designed for them. Those with no evidence of residual tumor still have an approximate 20% to 40% relapse risk in spite of postoperative radiation therapy.

Anecdotal experience suggests that surgery alone for completely resected supratentorial nonanaplastic tumors and intradural spinal cord ependymomas may, in select cases, be an appropriate approach to treatment.[6][7][Level of evidence: 3iiiDi]; [8][9][Level of evidence: 3iiiDiii]

Adjuvant Therapy

Treatment options for no residual disease, no disseminated disease

Radiation therapy

The traditional postsurgical treatment for these patients has been radiation therapy consisting of 54 Gy to 55.8 Gy to the tumor bed for children aged 3 years and older.[10] It is not necessary to treat the entire CNS (whole brain and spine) because these tumors usually recur initially at the local site.[11]; [12][Level of evidence: 3iiiA] When possible, patients should be treated in a center experienced with the delivery of highly conformal radiation therapy (including intensity-modulated radiation therapy or charged-particle radiation therapy) to pediatric patients with brain tumors.

Evidence (radiation therapy):

  1. In one study, 74 patients aged 1 to 21 years were treated with radiation therapy after surgery.[13]
    • The 3-year progression-free survival (PFS) rate was 77.6% ± 5.8%.
  2. In a second series, 107 of 153 patients received conformal radiation therapy immediately after up-front resection.[5][Level of evidence: 3iA]
    • The 7-year event-free survival was 76.9% ± 13.5%.

Focal radiation therapy has been used in certain cases.[14] In a small series of children with localized ependymoma, surgery alone was compared with adjuvant radiation therapy. Adjuvant radiation therapy appeared to improve PFS, even after adjusting for the extent of resection. In fact, a PFS benefit was observed for patients who received adjuvant radiation therapy after gross-total resection, compared with those who did not receive radiation therapy.[15] Additional research will be necessary to confirm these findings.

Chemotherapy

There is no evidence to date that adjuvant chemotherapy, including the use of myeloablative chemotherapy,[16] improves the outcome for patients with totally resected, nondisseminated ependymoma. For this reason, current treatment approaches do not include chemotherapy as a standard component of primary therapy for children with newly diagnosed ependymomas that are completely resected.

A randomized trial evaluating the efficacy of postradiation chemotherapy in children who have had a gross-total resection is underway.

Treatment options for residual disease, no disseminated disease

Second-look surgery

Second-look surgery should be considered because patients who have complete resections have better disease control.[17] In some cases, further surgery can be undertaken after the initial attempted resection if the pediatric neurosurgeon believes that a gross-total resection could be obtained by an alternate surgical approach to the tumor. In other cases, further up-front surgery is not anticipated to result in a gross-total resection, therefore, adjuvant therapy is initiated with future consideration of second-look surgery.

Radiation therapy

The rationale for radiation therapy as described in the Treatment options for no residual disease, no disseminated disease subsection above also pertains to the treatment of children with residual, nondisseminated ependymoma. In patients with a subtotal resection, treatment with radiation therapy results in 3-year to 5-year PFS in 30% to 50% of patients,[13] although the outcome for patients with residual tumor within the spinal canal may be better.[18]

Preirradiation chemotherapy

One study demonstrated a benefit of preirradiation chemotherapy in children with near-total resection (>90% resection), with outcomes comparable to children achieving a gross-total resection followed by radiation therapy.[19] The Children’s Oncology Group (COG) has completed a study of preirradiation chemotherapy in children with residual disease after up-front surgery to determine whether children treated with chemotherapy can achieve a complete response with chemotherapy or second-look surgery. Results are pending.

There is no evidence that high-dose chemotherapy with stem cell rescue is of any benefit.[20]; [21][Level of evidence: 2A]

Treatment options for CNS disseminated disease

Radiation therapy

Regardless of the degree of surgical resection, these patients generally receive radiation therapy to the whole brain and spine, along with boosts to local disease and bulk areas of disseminated disease. The traditional local postsurgical radiation doses in these patients have been 54 Gy to 55.8 Gy. Doses of approximately 36 Gy to the entire neuraxis (i.e., the whole brain and spine) should also be administered but may be modulated depending on the age of the patient. Boosts between 41.4 Gy and 50.4 Gy to bulk areas of spinal disease should be administered, with doses depending on the age of the patient and the location of the tumor.

Chemotherapy

The role of chemotherapy in the management of children with disseminated ependymoma is unproven.[22]

Treatment options for children younger than 3 years

Children younger than 3 years are particularly susceptible to the adverse effects of radiation on brain development.[23][Level of evidence: 3iiiC] Debilitating effects on growth and neurologic development have frequently been observed, especially in younger children.[24][25][26] Consequently, radiation therapy immediately after surgery in children younger than 3 years has historically been limited, with attempts to delay its administration through the use of chemotherapy.[27][28][29][30]; [31][Level of evidence: 2A]

Chemotherapy

Some, but not all, chemotherapy regimens induce objective responses in children younger than 3 years with newly diagnosed ependymoma.[27][28][29][30] Up to 40% of infants and young children with totally resected disease may achieve long-term survival with chemotherapy alone.[32][Level of evidence: 2Di]

Radiation therapy

Because of the known effects of radiation on growth and neurocognitive development, the use of radiation therapy in children younger than 3 years has been limited.

Evidence (radiation therapy):

  1. A retrospective review based on Surveillance, Epidemiology, and End Results data reported on 184 children younger than 3 years.[10]
    • 3-year overall survival was shown to be significantly better for children who received postoperative radiation therapy (81%) than for those who did not (58%, P = .005), even when adjusting for tumor location or degree of resection.
  2. Conformal radiation therapy is an alternative approach for minimizing radiation-induced neurologic damage in young children with ependymoma. The need and timing of radiation therapy for children who have successfully completed chemotherapy and have no residual disease is still to be determined.
    • The initial experience with this approach suggested that children younger than 3 years with ependymoma have neurologic deficits at diagnosis that improve with time after conformal radiation treatment.[13]
    • Another study suggested that there was a trend for intellectual deterioration over time even in older children treated with localized radiation therapy.[23][Level of evidence: 3iiiC]

Conformal radiation approaches, such as 3-dimensional conformal radiation therapy, that minimize damage to normal brain tissue and charged-particle radiation therapy, such as proton-beam therapy, are under evaluation for infants and children with ependymoma.[13][33] When analyzing neurologic outcome after treatment of young children with ependymoma, it is important to consider that not all long-term deficits can be ascribed to radiation therapy because deficits may be present in young children before therapy begins.[13] For example, the presence of hydrocephalus at diagnosis is associated with lower intelligence quotient as measured after surgical resection and before administration of radiation therapy.[34]

The recently completed COG protocol (ACNS0121 [NCT00027846]) for children with ependymoma included children aged 1 year and older. The trial is a prospective evaluation of postoperative radiation therapy. Results are forthcoming.

Treatment Options Under Clinical Evaluation for Newly Diagnosed Childhood Ependymoma or Anaplastic Ependymoma

The following is an example of a national and/or institutional clinical trial that is currently being conducted or is under analysis. Information about ongoing clinical trials is available from the NCI Web site.

  1. COG-ACNS0831 (NCT01096368) (Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Younger Patients With Newly Diagnosed Ependymoma): The purpose of this phase III trial is as follows:No Residual Disease; No Disseminated Disease
    • The trial will determine whether adding chemotherapy after radiation therapy results in improved survival over radiation therapy alone.
    • The trial will determine whether children with supratentorial nonanaplastic ependymoma who receive a complete resection or who achieve a complete remission after being treated with chemotherapy can be successfully treated without radiation therapy.
    Residual Disease; No Disseminated Disease
    • The trial will determine whether adding chemotherapy before and after radiation therapy results in improved survival compared with previous studies of children who did not receive additional chemotherapy after radiation treatment.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with newly diagnosed childhood ependymoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. van Veelen-Vincent ML, Pierre-Kahn A, Kalifa C, et al.: Ependymoma in childhood: prognostic factors, extent of surgery, and adjuvant therapy. J Neurosurg 97 (4): 827-35, 2002.

  2. Abdel-Wahab M, Etuk B, Palermo J, et al.: Spinal cord gliomas: A multi-institutional retrospective analysis. Int J Radiat Oncol Biol Phys 64 (4): 1060-71, 2006.

  3. Kothbauer KF: Neurosurgical management of intramedullary spinal cord tumors in children. Pediatr Neurosurg 43 (3): 222-35, 2007.

  4. Zacharoulis S, Ji L, Pollack IF, et al.: Metastatic ependymoma: a multi-institutional retrospective analysis of prognostic factors. Pediatr Blood Cancer 50 (2): 231-5, 2008.

  5. Merchant TE, Li C, Xiong X, et al.: Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol 10 (3): 258-66, 2009.

  6. Volpp PB, Han K, Kagan AR, et al.: Outcomes in treatment for intradural spinal cord ependymomas. Int J Radiat Oncol Biol Phys 69 (4): 1199-204, 2007.

  7. Hukin J, Epstein F, Lefton D, et al.: Treatment of intracranial ependymoma by surgery alone. Pediatr Neurosurg 29 (1): 40-5, 1998.

  8. Little AS, Sheean T, Manoharan R, et al.: The management of completely resected childhood intracranial ependymoma: the argument for observation only. Childs Nerv Syst 25 (3): 281-4, 2009.

  9. Venkatramani R, Dhall G, Patel M, et al.: Supratentorial ependymoma in children: to observe or to treat following gross total resection? Pediatr Blood Cancer 58 (3): 380-3, 2012.

  10. Koshy M, Rich S, Merchant TE, et al.: Post-operative radiation improves survival in children younger than 3 years with intracranial ependymoma. J Neurooncol 105 (3): 583-90, 2011.

  11. Combs SE, Kelter V, Welzel T, et al.: Influence of radiotherapy treatment concept on the outcome of patients with localized ependymomas. Int J Radiat Oncol Biol Phys 71 (4): 972-8, 2008.

  12. Schroeder TM, Chintagumpala M, Okcu MF, et al.: Intensity-modulated radiation therapy in childhood ependymoma. Int J Radiat Oncol Biol Phys 71 (4): 987-93, 2008.

  13. Merchant TE, Mulhern RK, Krasin MJ, et al.: Preliminary results from a phase II trial of conformal radiation therapy and evaluation of radiation-related CNS effects for pediatric patients with localized ependymoma. J Clin Oncol 22 (15): 3156-62, 2004.

  14. Landau E, Boop FA, Conklin HM, et al.: Supratentorial ependymoma: disease control, complications, and functional outcomes after irradiation. Int J Radiat Oncol Biol Phys 85 (4): e193-9, 2013.

  15. Pejavar S, Polley MY, Rosenberg-Wohl S, et al.: Pediatric intracranial ependymoma: the roles of surgery, radiation and chemotherapy. J Neurooncol 106 (2): 367-75, 2012.

  16. Zacharoulis S, Levy A, Chi SN, et al.: Outcome for young children newly diagnosed with ependymoma, treated with intensive induction chemotherapy followed by myeloablative chemotherapy and autologous stem cell rescue. Pediatr Blood Cancer 49 (1): 34-40, 2007.

  17. Massimino M, Solero CL, Garrè ML, et al.: Second-look surgery for ependymoma: the Italian experience. J Neurosurg Pediatr 8 (3): 246-50, 2011.

  18. Wahab SH, Simpson JR, Michalski JM, et al.: Long term outcome with post-operative radiation therapy for spinal canal ependymoma. J Neurooncol 83 (1): 85-9, 2007.

  19. Garvin JH Jr, Selch MT, Holmes E, et al.: Phase II study of pre-irradiation chemotherapy for childhood intracranial ependymoma. Children's Cancer Group protocol 9942: a report from the Children's Oncology Group. Pediatr Blood Cancer 59 (7): 1183-9, 2012.

  20. Grill J, Kalifa C, Doz F, et al.: A high-dose busulfan-thiotepa combination followed by autologous bone marrow transplantation in childhood recurrent ependymoma. A phase-II study. Pediatr Neurosurg 25 (1): 7-12, 1996.

  21. Venkatramani R, Ji L, Lasky J, et al.: Outcome of infants and young children with newly diagnosed ependymoma treated on the "Head Start" III prospective clinical trial. J Neurooncol 113 (2): 285-91, 2013.

  22. Bouffet E, Capra M, Bartels U: Salvage chemotherapy for metastatic and recurrent ependymoma of childhood. Childs Nerv Syst 25 (10): 1293-301, 2009.

  23. von Hoff K, Kieffer V, Habrand JL, et al.: Impairment of intellectual functions after surgery and posterior fossa irradiation in children with ependymoma is related to age and neurologic complications. BMC Cancer 8: 15, 2008.

  24. Packer RJ, Sutton LN, Atkins TE, et al.: A prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results. J Neurosurg 70 (5): 707-13, 1989.

  25. Johnson DL, McCabe MA, Nicholson HS, et al.: Quality of long-term survival in young children with medulloblastoma. J Neurosurg 80 (6): 1004-10, 1994.

  26. Packer RJ, Sutton LN, Goldwein JW, et al.: Improved survival with the use of adjuvant chemotherapy in the treatment of medulloblastoma. J Neurosurg 74 (3): 433-40, 1991.

  27. Duffner PK, Horowitz ME, Krischer JP, et al.: The treatment of malignant brain tumors in infants and very young children: an update of the Pediatric Oncology Group experience. Neuro-oncol 1 (2): 152-61, 1999.

  28. Duffner PK, Horowitz ME, Krischer JP, et al.: Postoperative chemotherapy and delayed radiation in children less than three years of age with malignant brain tumors. N Engl J Med 328 (24): 1725-31, 1993.

  29. Geyer JR, Sposto R, Jennings M, et al.: Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group. J Clin Oncol 23 (30): 7621-31, 2005.

  30. Grill J, Le Deley MC, Gambarelli D, et al.: Postoperative chemotherapy without irradiation for ependymoma in children under 5 years of age: a multicenter trial of the French Society of Pediatric Oncology. J Clin Oncol 19 (5): 1288-96, 2001.

  31. Massimino M, Gandola L, Barra S, et al.: Infant ependymoma in a 10-year AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) experience with omitted or deferred radiotherapy. Int J Radiat Oncol Biol Phys 80 (3): 807-14, 2011.

  32. Grundy RG, Wilne SA, Weston CL, et al.: Primary postoperative chemotherapy without radiotherapy for intracranial ependymoma in children: the UKCCSG/SIOP prospective study. Lancet Oncol 8 (8): 696-705, 2007.

  33. MacDonald SM, Safai S, Trofimov A, et al.: Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose comparisons. Int J Radiat Oncol Biol Phys 71 (4): 979-86, 2008.

  34. Merchant TE, Lee H, Zhu J, et al.: The effects of hydrocephalus on intelligence quotient in children with localized infratentorial ependymoma before and after focal radiation therapy. J Neurosurg 101 (2 Suppl): 159-68, 2004.

Treatment of Recurrent Childhood Ependymoma

Recurrence is not uncommon for all grades of ependymoma and may develop many years after initial treatment.[1] Late recurrence beyond 10 to 15 years has been reported.[2][3] Disease generally recurs at the primary tumor site,[4][5] although concomitant neuraxis dissemination may also be seen. Systemic relapse is extremely rare. At time of relapse, a complete evaluation for extent of recurrence is indicated for all patients.

Surgery

The need for further surgical intervention is individualized based on the following:

  • Extent of the tumor.
  • Length of time between initial treatment and the reappearance of the recurrent lesion.
  • Clinical picture.

In some cases, surgically accessible lesions may be treated alternatively by radiation therapy.

Radiation Therapy and/or Chemotherapy

Patients with recurrent ependymomas who have not previously received radiation therapy and/or chemotherapy should be considered for treatment with the following modalities:[6][Level of evidence: 3iiiB]

  1. Focal retreatment with various radiation modalities, including stereotactic radiosurgery.[7][8][Level of evidence: 3iiiA]; [9][10][Level of evidence: 3iiiDi]
  2. Active anticancer agents, including cyclophosphamide, cisplatin, carboplatin, lomustine, and etoposide.

Regardless of treatment strategy, the prognosis for patients with recurrence is poor.[1] Entry into studies of novel therapeutic approaches should be considered.

Treatment Options Under Clinical Evaluation for Recurrent Childhood Ependymoma

Early-phase therapeutic trials may be available for selected patients. These trials may be available via Children's Oncology Group, the Pediatric Brain Tumor Consortium, or other entities. Information about ongoing clinical trials is available from the NCI Web site.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent childhood ependymoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Zacharoulis S, Ashley S, Moreno L, et al.: Treatment and outcome of children with relapsed ependymoma: a multi-institutional retrospective analysis. Childs Nerv Syst 26 (7): 905-11, 2010.

  2. Pollack IF, Gerszten PC, Martinez AJ, et al.: Intracranial ependymomas of childhood: long-term outcome and prognostic factors. Neurosurgery 37 (4): 655-66; discussion 666-7, 1995.

  3. Vanuytsel LJ, Bessell EM, Ashley SE, et al.: Intracranial ependymoma: long-term results of a policy of surgery and radiotherapy. Int J Radiat Oncol Biol Phys 23 (2): 313-9, 1992.

  4. Goldwein JW, Corn BW, Finlay JL, et al.: Is craniospinal irradiation required to cure children with malignant (anaplastic) intracranial ependymomas? Cancer 67 (11): 2766-71, 1991.

  5. Merchant TE, Haida T, Wang MH, et al.: Anaplastic ependymoma: treatment of pediatric patients with or without craniospinal radiation therapy. J Neurosurg 86 (6): 943-9, 1997.

  6. Messahel B, Ashley S, Saran F, et al.: Relapsed intracranial ependymoma in children in the UK: patterns of relapse, survival and therapeutic outcome. Eur J Cancer 45 (10): 1815-23, 2009.

  7. Kano H, Yang HC, Kondziolka D, et al.: Stereotactic radiosurgery for pediatric recurrent intracranial ependymomas. J Neurosurg Pediatr 6 (5): 417-23, 2010.

  8. Bouffet E, Hawkins CE, Ballourah W, et al.: Survival benefit for pediatric patients with recurrent ependymoma treated with reirradiation. Int J Radiat Oncol Biol Phys 83 (5): 1541-8, 2012.

  9. Merchant TE, Boop FA, Kun LE, et al.: A retrospective study of surgery and reirradiation for recurrent ependymoma. Int J Radiat Oncol Biol Phys 71 (1): 87-97, 2008.

  10. Kano H, Niranjan A, Kondziolka D, et al.: Outcome predictors for intracranial ependymoma radiosurgery. Neurosurgery 64 (2): 279-87; discussion 287-8, 2009.


This information is provided by the National Cancer Institute.

This information was last updated on December 18, 2013.

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