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

About 1 in 11 childhood brain tumors are ependymomas. Although cancer is rare in children, brain tumors are the most common type of childhood cancer other than leukemia and lymphoma.

This summary is about the treatment of primary brain tumors (tumors that begin in the brain). Treatment of metastatic brain tumors, which are tumors formed by cancer cells 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 may be 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

The central nervous system controls many important body functions.

Ependymomas most commonly form in these parts of the central nervous system (CNS):

  • 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. 

Anatomy of the brain, showing the cerebrum, cerebellum, brain stem, and other parts of the brain.

 

 

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 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 symptoms of childhood ependymoma vary and often depend on the child’s age and where the tumor is located.

The following symptoms and others may be caused by childhood ependymoma. Other conditions may cause the same symptoms. Check with your child’s doctor if you see any of these problems in your child:

  • Frequent headaches.
  • Seizures.
  • Frequent nausea and vomiting.
  • Loss of balance or trouble walking.

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. 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 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 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 may be done after the tumor is removed to find out how much 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:

  • Whether cancer cells remain after surgery.
  • The type of ependymoma and whether it begins in the brain or in the spinal cord.
  • The age of the child when the tumor is diagnosed.
  • Whether the cancer has spread to other parts of the central nervous system, such as the meninges (membranes covering the brain) and the spinal cord.
  • Whether the cancer has spread to other parts of the body, such as the bone or lung.
  • Whether the tumor has just been diagnosed or has recurred (come back).

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. It is important to know the stage in order to plan treatment.

There is no standard staging system for childhood ependymoma. Instead, the plan for cancer treatment after surgery depends on the following:

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

There are three ways that cancer spreads in the body.

The three ways that cancer spreads in the body are:

  • Through tissue. Cancer invades the surrounding normal tissue.
  • Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
  • Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.

When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.

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. Another procedure that may be done to find out if cancer has spread is a lumbar puncture. A lumbar puncture is a procedure used to collect cerebrospinal fluid from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.

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.
  • Rehabilitation specialist.
  • Radiation oncologist.
  • Medical oncologist.
  • Endocrinologist.
  • Psychologist.

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

Childhood brain and spinal cordtumors may cause symptoms that continue for months or years. Symptoms caused by the tumor may begin before diagnosis. 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

Surgery is used to diagnose and treat childhood ependymoma as described in the General Information section of this summary.

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 given after the surgery, to lower the risk that the cancer will come back, 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 and stage of the 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 period of days.

Certain ways of giving radiation therapy can help keep radiation away from healthy tissue:

  • Conformal radiation therapy uses a computer to create a 3-D 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 radiation therapy uses a head frame attached to the skull to aim radiation beams directly at the tumor.

Radiation therapy to the brain can affect the growth and development of children younger than 3 years. For this reason, conformal radiation therapy and proton-beam therapy that limit damage to healthy brain tissue are being studied in infants and children with ependymoma.

Damage to the brain in young children treated for ependymoma is not always caused by the radiation therapy. For example, when hydrocephalus (abnormal buildup of fluid in the brain) is found at diagnosis, it is linked with lower intelligence test scores following surgery and before radiation therapy.

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 and stage of the cancer being treated.

New types of treatment are being tested in clinical trials.

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

Watchful waiting

Watchful waiting is closely monitoring a patient’s condition without giving any treatment until symptoms appear or change.

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.

Treatment Options for Childhood Ependymoma

A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your child's doctor for clinical trials that are not listed here but may be right for your child.

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.

Treatment for newly diagnosed childhood ependymoma is usually surgery to remove the tumor. More treatment may be given after surgery. Treatment given after surgery depends on the following:

  • Age of the child.
  • Amount of tumor that was removed.
  • Whether cancercells have spread to other parts of the brain or spinal cord.

Treatment for children aged 3 and older  

If the tumor is completely removed by surgery and cancercells have not spread within the brain and spinal cord, treatment may include the following:

  • Radiation therapy to the tumor bed (the area where the tumor was removed). This may be conformal radiation therapy.
  • A clinical trial of radiation therapy followed by chemotherapy.

If a part of the tumor remains after surgery, but cancer cells have not spread within the brain and spinal cord, treatment may include the following:

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

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

  • Radiation therapy to the whole brain and spine.
  • A clinical trial of radiation therapy and chemotherapy.

Treatment for children younger than 3 years of age  

When the child is younger than 3 years, treatment may include the following:

  • Chemotherapy. Radiation therapy may be given later.
  • Radiation therapy. This may be conformal 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. General information about clinical trials is available from the NCI Web site.

Recurrent Childhood Ependymoma

Treatment of recurrent childhood ependymomas may include the following:

  • Surgery.
  • Radiation therapy, including stereotactic radiation therapy.
  • Chemotherapy, if chemotherapy was not used when the tumor was first diagnosed.
  • 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. 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:

About PDQ

PDQ is a comprehensive cancer database available on NCI's Web site.  

PDQ is the National Cancer Institute's (NCI's) comprehensive cancer information database. Most of the information contained in PDQ is available online at NCI's Web site. PDQ is provided as a service of the NCI. The NCI is part of the National Institutes of Health, the federal government's focal point for biomedical research.

PDQ contains cancer information summaries.  

The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries are available in two versions. The health professional versions provide detailed information written in technical language. The patient versions are written in easy-to-understand, nontechnical language. Both versions provide current and accurate cancer information.

Images in the PDQ summaries are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in the PDQ summaries, along with many other cancer-related images, are available in Visuals Online, a collection of over 2,000 scientific images.

The PDQ cancer information summaries are developed by cancer experts and reviewed regularly.  

Editorial Boards made up of experts in oncology and related specialties are responsible for writing and maintaining the cancer information summaries. The summaries are reviewed regularly and changes are made as new information becomes available. The date on each summary ("Date Last Modified") indicates the time of the most recent change.

PDQ also contains information on clinical trials.  

A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become "standard." In the United States, about two-thirds of children with cancer are treated in a clinical trial at some point in their illness.

Listings of clinical trials are included in PDQ and are available online at NCI's Web site. Descriptions of the trials are available in health professional and patient versions. For additional help in locating a childhood cancer clinical trial, call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The PDQ database contains listings of groups specializing in clinical trials.  

The Children's Oncology Group (COG) is the major group that organizes clinical trials for childhood cancers in the United States. Information about contacting COG is available on the NCI Web site or from the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).


This information is provided by the National Cancer Institute.

This information was last updated on February 1, 2013.


General Information

The PDQ childhood brain tumor treatment summaries are organized primarily according to the World Health Organization 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 has 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. Brain tumors are classified according to histology, but tumor location and extent of spread are important factors that affect treatment and prognosis. Immunohistochemical analysis, cytogenetic and molecular genetic findings, and measures of mitotic activity are increasingly used in tumor diagnosis and classification.

Incidence and Molecular Determinants

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

Molecular determinants of outcome for ependymomas are just being identified. Studies have identified numerous chromosomal aberrations and related molecular genetic changes. Gain of 1q25, overexpression of EGFR, hTERT expression, high levels of nucleolin, activation of the Notch pathway or Tenascin C, and others have been related to poorer prognosis.[6][7][8][9][10][11][12] In contrast, gains of 9, 15q, and 18, and loss of chromosome 6 were associated with improved prognosis.[13]

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 January 30, 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 January 30, 2013.

  6. 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.

  7. 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.

  8. Pezzolo A, Capra V, Raso A, et al.: Identification of novel chromosomal abnormalities and prognostic cytogenetics markers in intracranial pediatric ependymoma. Cancer Lett 261 (2): 235-43, 2008.

  9. Preusser M, Heinzl H, Gelpi E, et al.: Ki67 index in intracranial ependymoma: a promising histopathological candidate biomarker. Histopathology 53 (1): 39-47, 2008.

  10. 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.

  11. Puget S, Grill J, Valent A, et al.: Candidate genes on chromosome 9q33-34 involved in the progression of childhood ependymomas. J Clin Oncol 27 (11): 1884-92, 2009.

  12. Ridley L, Rahman R, Brundler MA, et al.: Multifactorial analysis of predictors of outcome in pediatric intracranial ependymoma. Neuro Oncol 10 (5): 675-89, 2008.

  13. 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.

Histopathologic Classification of Childhood Ependymal Tumors

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

  • Subependymoma (WHO Grade I).
  • Myxopapillary ependymoma (WHO Grade I).
  • Ependymoma (WHO Grade II). Variants include cellular, papillary, tanycytic, clear cell, and mixed.
  • Anaplastic (also known as malignant) ependymoma (WHO Grade III).

The subependymoma is a slow-growing benign neoplasm, typically attached to the ventricle wall, and is composed of glial tumor cell clusters embedded in a fibrillary matrix. The 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.

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 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 poorly intertwined.

The anaplastic ependymoma is considered a malignant glioma of ependymal differentiation and, compared to the Grade II ependymomas, shows increased cellularity and increased mitotic activity, often associated with microvascular proliferation and pseudopalisading necrosis.

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

Subependymomas and myxopapillary ependymomas are usually considered to be different than the Grade II and Grade III ependymomas. In Grade II and Grade III ependymomas, the relationship between histological features and survival has varied between 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][8][9][10][11] A single institution study suggests that patients with clear-cell ependymomas may be at higher risk for treatment failure than patients with other forms of Grade II ependymomas;[12] however, confirmation is required in the 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 for more information.)

The pathologic classification of pediatric brain tumors is a specialized area that is undergoing evolution; 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. Goldwein JW, Leahy JM, Packer RJ, et al.: Intracranial ependymomas in children. Int J Radiat Oncol Biol Phys 19 (6): 1497-502, 1990.

  7. Rousseau P, Habrand JL, Sarrazin D, et al.: Treatment of intracranial ependymomas of children: review of a 15-year experience. Int J Radiat Oncol Biol Phys 28 (2): 381-6, 1994.

  8. Chiu JK, Woo SY, Ater J, et al.: Intracranial ependymoma in children: analysis of prognostic factors. J Neurooncol 13 (3): 283-90, 1992.

  9. 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.

  10. 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.

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

  12. 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

Although there is no formal staging system, ependymomas can be divided into supratentorial, infratentorial, and spinal tumors. In children, approximately 30% of childhood ependymomas arise in supratentorial regions of the brain and 70% in the posterior fossa.[1][2][3] They usually originate in the ependymal linings of ventricles or central canal or ventriculus terminalis of the spinal cord, and have access to the cerebral spinal fluid (CSF). 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. Every patient with ependymoma should be evaluated with diagnostic imaging of the spinal cord and whole brain. This is ideally done prior to surgery to avoid confusion with postoperative blood. The most sensitive method available for evaluating spinal cord subarachnoid metastasis is spinal magnetic resonance imaging (MRI) performed with gadolinium. 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. While a number of factors have sometimes been associated with an unfavorable outcome (younger age at diagnosis, lower doses of radiation, anaplastic histology, subtotal resection, higher proliferation marker, MIB-1 labeling index), age, histology, and extent of resection have consistently been the most important factors.[1][4][5][6][7][8][9][10][11]; [12][Level of evidence: 3iiiDi]; [13][Level of evidence: 3iiiDii] Primary spinal cord ependymomas have a more favorable outcome than cranial variants.[14]

References:

  1. Goldwein JW, Leahy JM, Packer RJ, et al.: Intracranial ependymomas in children. Int J Radiat Oncol Biol Phys 19 (6): 1497-502, 1990.

  2. Kovnar E, Kun L, Burger J, et al.: Patterns of dissemination and recurrence in childhood ependymoma: preliminary results of Pediatric Oncology Group protocol #8532. Ann Neurol 30(3): 457, 1991.

  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. Shaw EG, Evans RG, Scheithauer BW, et al.: Postoperative radiotherapy of intracranial ependymoma in pediatric and adult patients. Int J Radiat Oncol Biol Phys 13 (10): 1457-62, 1987.

  5. 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.

  6. 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.

  7. 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.

  8. Horn B, Heideman R, Geyer R, et al.: A multi-institutional retrospective study of intracranial ependymoma in children: identification of risk factors. J Pediatr Hematol Oncol 21 (3): 203-11, 1999 May-Jun.

  9. 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.

  10. Bouffet E, Perilongo G, Canete A, et al.: Intracranial ependymomas in children: a critical review of prognostic factors and a plea for cooperation. Med Pediatr Oncol 30 (6): 319-29; discussion 329-31, 1998.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

Treatment Option Overview

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 very demanding and should be carried out in centers that have experience in that area in order to ensure optimal results.

Treatment for childhood ependymoma has included surgery followed by standard fractionated radiation therapy. There is evidence to suggest that more extensive surgical resections are related to an improved rate of survival.[1][2][3][4][5][6][7] In addition, in a small series of children with localized ependymoma, adjuvant radiation therapy appeared to improve progression-free survival (PFS), even after adjusting for the extent of resection. In fact, a benefit in PFS was observed for patients who received adjuvant radiation therapy after gross total resection compared with those who did not receive radiation therapy. Additional research will be necessary to confirm these findings.[8] Chemotherapy has been shown to be active in patients with recurrent ependymoma.[9] One relatively small, prospective, randomized trial suggests that chemotherapy activity in newly diagnosed cases is limited,[10] and current treatment approaches do not include chemotherapy as a component of primary therapy for most children with newly diagnosed ependymomas that are completely resected. Children younger than 3 years are particularly susceptible to the adverse effect of radiation on brain development.[11][Level of evidence: 3iiiC] Debilitating effects on growth and neurologic development have frequently been observed, especially in younger children.[12][13][14] For this reason, 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.[15][16] Long-term management of these patients is complex and requires a multidisciplinary approach.

There is evidence that surveillance neuroimaging in childhood ependymoma will identify tumors that have recurred when the patient is asymptomatic; however, it is unclear whether this detection will change the ultimate prognosis of the patient.[17]

References:

  1. 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.

  2. Horn B, Heideman R, Geyer R, et al.: A multi-institutional retrospective study of intracranial ependymoma in children: identification of risk factors. J Pediatr Hematol Oncol 21 (3): 203-11, 1999 May-Jun.

  3. 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.

  4. 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.

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

  6. 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.

  7. 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.

  8. 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.

  9. Goldwein JW, Glauser TA, Packer RJ, et al.: Recurrent intracranial ependymomas in children. Survival, patterns of failure, and prognostic factors. Cancer 66 (3): 557-63, 1990.

  10. Evans AE, Anderson JR, Lefkowitz-Boudreaux IB, et al.: Adjuvant chemotherapy of childhood posterior fossa ependymoma: cranio-spinal irradiation with or without adjuvant CCNU, vincristine, and prednisone: a Childrens Cancer Group study. Med Pediatr Oncol 27 (1): 8-14, 1996.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

Treatment of Newly Diagnosed Childhood Ependymoma

In the newly diagnosed patient, careful evaluation to fully determine the extent of disease must precede the treatment of ependymoma. Surgery should be performed in an attempt at maximal tumor reduction; children have improved progression-free survival (PFS) if there is minimal residual disease present after surgery.[1][2] Postoperatively, magnetic resonance imaging (MRI) should be performed to determine the extent of resection, although the rate of dissemination is low. If not performed preoperatively, MRI of the entire neuraxis should be obtained to evaluate for disease dissemination. Myxopapillary ependymomas, considered to be a benign histologic subtype of ependymoma, have a relatively high incidence of central nervous system (CNS) tumor dissemination at diagnosis and at follow-up, and require imaging of the complete cranial spinal axis at the time of diagnosis and during follow-up.[3][4] 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.

Postsurgical Treatment Options

Standard treatment options

Ependymoma (World Health Organization [WHO] Grade II) and anaplastic (WHO Grade III)

  • No residual disease; no disseminated disease:

    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.[5] It is not necessary to treat the entire CNS (whole brain and spine) because these tumors usually recur initially at the local site.[2][6][7]; [8][Level of evidence: 3iiiA] When possible, patients should be treated in a center experienced with the delivery of conformal radiation therapy to pediatric patients with brain tumors. There is no evidence that adjuvant chemotherapy, including the use of myeloablative chemotherapy,[9] improves the outcome for patients with totally resected, nondisseminated ependymoma. The 3-year PFS rate in 74 patients aged between 1 and 21 years treated with radiation therapy following surgery was 77.6% ± 5.8%.[10] In a second series of 153 patients, 107 received conformal irradiation immediately following up-front resection, the 7-year event-free survival was 76.9% ± 13.5%.[11][Level of evidence: 3iA] 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.[12][Level of evidence: 3iiiDi]; [13][14][Level of evidence: 3iiiDiii]

  • Residual disease; no disseminated disease:

    Second-look surgery should be considered because patients who have complete resections have better disease control.[15] The traditional postsurgical treatment for children aged 3 years and older has been radiation therapy consisting of 54 Gy to 55.8 Gy to the tumor bed. It is not necessary to treat the entire CNS (whole brain and spine) because these tumors usually recur at the local site.[7][Level of evidence: 3iiiA] In subtotally resected patients, treatment with radiation therapy results in 3-year to 5-year PFS in 30% to 50% of patients,[10][16] although the outcome for patients with residual tumor within the spinal canal may be better.[17] There is no evidence that adjuvant chemotherapy, including high-dose chemotherapy with stem cell rescue, is of any benefit.[18]

  • CNS disseminated disease:

    In children with disseminated disease, long-term survivors have been reported and aggressive therapy is warranted. Regardless of degree of surgical resection, these patients require radiation therapy to the entire CNS (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. When possible, patients should be treated in a center experienced with this therapy. Trials are ongoing to evaluate the possible role of radiation therapy and chemotherapy in these patients.

  • Management of children younger than 3 years:

    Because of the known effects of radiation on growth and neurocognitive development, radiation therapy immediately after surgery in children younger than 3 years has traditionally been limited, with attempts to delay its administration through the use of chemotherapy.[19][20][21][22]; [23][Level of evidence: 2A] When analyzing neurologic outcome following treatment of young children with ependymoma, it is important to consider that not all long-term deficits can be ascribed to radiation therapy, as deficits may be present in young children before therapy is begun.[10] For example, the presence of hydrocephalus at diagnosis is associated with lower intelligence quotient as measured following surgical resection and prior to administration of radiation therapy.[24]

    In a retrospective review based on Surveillance Epidemiology and End Results data of 184 children younger than 3 years, 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.[5] The recently completed Children’s Oncology Group protocol for children with ependymoma included children aged 1 year and older. The trial is a prospective evaluation of this same issue and results are forthcoming.

    Conformal radiation therapy is an alternative approach for minimizing radiation-induced neurologic damage in young children with ependymoma. The initial experience with this approach suggests that children younger than 3 years with ependymoma have neurologic deficits at diagnosis that improve with time following conformal radiation treatment.[10] However, another study suggested that there was a trend for intellectual deterioration over time even in older children treated with localized radiation therapy.[25][Level of evidence: 3iiiC] The need and timing of radiation therapy for children who have successfully completed chemotherapy and have no residual disease is still to be determined.

    Chemotherapy is able to induce objective responses in some children younger than 3 years with newly diagnosed ependymoma,[19][20][21] although not all chemotherapy regimens induce objective responses.[22] Up to 40% of infants and young children with totally resected disease may achieve long-term survival with chemotherapy alone.[26][Level of evidence: 2Di]

Treatment options under clinical evaluation

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.

  • COG-ACNS0831 (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 radiation therapy and then adding chemotherapy after radiation therapy results in improved survival, compared with previous studies of children who did not receive additional chemotherapy after radiation treatment.
     

Subependymoma

The true incidence of subependymomas is difficult to determine, because these tumors are frequently asymptomatic and may be found incidentally at autopsy. They probably comprise less than 5% of all ependymal tumors. Occasionally, subependymomas cause ventricular obstruction and, in these cases, treatment is indicated. Spontaneous intratumoral hemorrhage has also been observed.[27] In those cases requiring therapy, complete surgical removal is often curative.

Myxopapillary Ependymoma

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.[28]; [29][Level of evidence: 3iiiDi] However, based on the finding that dissemination of these tumors to other parts of the neuraxis can occur, particularly when completed resection is not obtained and evidence that focal irradiation may improve progression-free survival, many practitioners now favor the use of irradiation following surgical resection of the primary mass.[3][28]; [30][Level of evidence: 3iiiDiii]; [31][Level of evidence: 3iiiDi]

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

  2. Horn B, Heideman R, Geyer R, et al.: A multi-institutional retrospective study of intracranial ependymoma in children: identification of risk factors. J Pediatr Hematol Oncol 21 (3): 203-11, 1999 May-Jun.

  3. 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.

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

  5. 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.

  6. Evans AE, Anderson JR, Lefkowitz-Boudreaux IB, et al.: Adjuvant chemotherapy of childhood posterior fossa ependymoma: cranio-spinal irradiation with or without adjuvant CCNU, vincristine, and prednisone: a Childrens Cancer Group study. Med Pediatr Oncol 27 (1): 8-14, 1996.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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.

  24. 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.

  25. 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.

  26. 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.

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

  28. 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.

  29. 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.

  30. 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.

  31. 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.

Treatment of Recurrent Childhood Ependymoma

Recurrence is not uncommon in both benign and malignant childhood brain tumors and may develop many years after initial treatment.[1] For ependymoma, late recurrence beyond 10 to 15 years has been reported.[2][3] Disease generally recurs at the primary tumor site, even in children with malignant ependymomas.[4][5] Systemic relapse is extremely rare. At time of relapse, a complete evaluation for extent of recurrence is indicated for all patients. The need for surgical intervention must be individualized on the basis of the extent of the tumor, the length of time between initial treatment and the reappearance of the recurrent lesion, and the clinical picture. Patients with recurrent ependymomas who have not previously received radiation therapy and/or chemotherapy should be considered for treatment with these modalities.[6][Level of evidence: 3iiiB] In addition, patients may be candidates for focal retreatment with various radiation modalities, including stereotactic radiosurgery.[7][8][Level of evidence: 3iiiA]; [9][10][Level of evidence: 3iiiDi] Active agents include 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

Early phase therapeutic trials may be available for selected patients. These trials may be available via Children's Oncology Group phase I institutions, the Pediatric Brain Tumor Consortium, or other entities.

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 January 30, 2013.

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