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 refers to 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 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. A doctor should be
consulted if any of these problems occur:
- 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:
- 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 the patient through 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).
Childhood ependymoma is diagnosed and removed in surgery.
If a brain tumor is suspected, 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.
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 where it is found in the brain.
- 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).
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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.
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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.
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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
pediatriconcologist, a doctor who specializes
in treating children with cancer. The pediatric oncologist works with
other pediatric health 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:
- 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.
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.
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.
- 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 growth and development in young
children and is not standard treatment for children younger than 3 years. For this reason, conformal radiation therapy that limits damage to healthy brain tissue is being studied in infants and children with ependymoma.
Damage to the brain in young children treated for ependymoma is not always due to the effects of 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 spinal column, 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.
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 clinical trials database.
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 condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
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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 doctor for clinical trials that are not listed here but may be right for you.
Newly Diagnosed Childhood Ependymoma
Newly diagnosed childhood ependymoma is a tumor that has not been treated. The patient may
have received drugs or treatment, however, to relieve
symptoms caused by the tumor.
Initial treatment for newly diagnosed childhood ependymoma is
usually surgery, with or without
additional treatment.
After surgery, treatment depends on the age of the child, the
amount of tumor that was removed, and whether cancercells have spread to other parts of the
central nervous system.
When the tumor is completely removed by surgery and cancer cells
have not spread within the central nervous system, treatment may include the
following:
- Radiation therapy
to the tumor bed (where the tumor was before it was removed), for children aged 3 years or older.
- A clinical trial of watchful waiting, for children aged 1 year or older.
- A clinical trial
of conformal radiation therapy.
- A clinical trial of chemotherapy with or without radiation therapy.
When a part of the tumor remains after surgery, but cancer cells
have not spread within the central nervous system, treatment may include the
following:
- Second-look surgery.
- Radiation therapy to the tumor bed, for children aged 3 years or older.
- A clinical trial of chemotherapy followed by second-look surgery and conformal radiation therapy, for children aged 1 year or older.
When cancer cells have spread within the central nervous system,
treatment may include the following:
- Radiation therapy to the whole brain and spine.
- A clinical trial of radiation therapy and chemotherapy.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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
Standard treatment of recurrent
childhood ependymomas may include
the following:
- Surgery.
- Radiation
therapy, including stereotactic radiation therapy with or without chemotherapy.
- Chemotherapy with or without radiation therapy.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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.
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To Learn More About Childhood Brain Tumors
For more information from the National Cancer Institute about childhood brain tumors, see the following:
For more childhood cancer information and other general cancer resources from the National Cancer Institute, see the following:
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This information is provided by the National Cancer Institute.
This information was last updated on July 3, 2008.
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood ependymoma. This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board.
Information about the following is included in this summary:
- Histopathologic classification.
- Stage information.
- Treatment options.
This summary is intended as a resource to inform and assist clinicians and other health professionals who care for pediatric cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric and Adult Treatment Editorial Boards use a formal evidence ranking system in developing their level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is also available in a patient version, which is written in less technical language, and in Spanish. The PDQ childhood brain tumor treatment summaries are in the process of being substantially revised. This revision process was prompted by changes in the nomenclature and classification for pediatric central nervous system tumors. New PDQ childhood brain tumor treatment summaries will be added, and some existing summaries will be replaced or their content combined with other PDQ childhood brain tumor treatment summaries in the near future.
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General Information
The National Cancer Institute provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public.
In recent decades, dramatic improvements in survival have been achieved for children and adolescents with cancer. 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.
Refer to the PDQ summary Childhood Brain and Spinal Cord Tumors Treatment Overview for information about the general classification of childhood brain and spinal cord tumors.
Incidence and Molecular Determinants
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary Levels of Evidence for more information.)
Childhood ependymoma comprises approximately 9% of all childhood brain tumors representing approximately 200 cases per year in the United States.[1][2]
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 , and others have been related to poorer prognosis.[3][4][5][Level of evidence: 3iiiB][6][7][Level of evidence: 3iiiDi]
References:
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 July 14, 2009.
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 July 14, 2009.
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.
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.
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.
Preusser M, Heinzl H, Gelpi E, et al.: Ki67 index in intracranial ependymoma: a promising histopathological candidate biomarker. Histopathology 53 (1): 39-47, 2008.
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.
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Histopathologic Classification of Childhood Ependymoma
The classification of brain tumors is based on both histopathological
characteristics and location in the brain. Ependymomas are divided into the
following categories:
- Subependymoma (World Health Organization [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 most recent WHO classification of brain tumors
maintains the term “ependymoma” for tumors that are histologically benign and
malignant ependymoma for those that have malignant characteristics.[1] These
categories are based on the nuclear/cytoplasmic ratio, number of nuclei and
mitotic figures, and the degree of nuclear atypia. Contemporary studies have
failed to show significant differences in how these tumors behave on the basis of
histologic classification alone,[2][3][4][5] although a small experience from a single-institution study suggested that patients with clear cell ependymoma may be at higher risk for treatment failure,[6] confirmation is required in a larger group of unselected patients.
Myxopapillary
ependymomas, which typically present in the filum terminale and
cauda equina, are also considered a separate entity. Ependymoblastomas (for more information, refer to the PDQ summary Childhood Central Nervous System Embryonal Tumors), which generally
behave more like medulloblastomas or cortical neuroectodermal tumors, are
considered separate entities from ependymomas and are now classified with the embryonal tumors.[1]
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:
Kleihues P, Burger PC, Scheithauer BW: The new WHO classification of brain tumours. Brain Pathol 3 (3): 255-68, 1993.
Goldwein JW, Leahy JM, Packer RJ, et al.: Intracranial ependymomas in children. Int J Radiat Oncol Biol Phys 19 (6): 1497-502, 1990.
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.
Chiu JK, Woo SY, Ater J, et al.: Intracranial ependymoma in children: analysis of prognostic factors. J Neurooncol 13 (3): 283-90, 1992.
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.
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.
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Stage Information
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary Levels of Evidence for more information.)
Although there is no formal staging system, ependymomas can be divided into
supratentorial and infratentorial tumors. They usually originate in the
ependymal linings of ventricles in the posterior fossa or supratentorial
region, and have access to the cerebral spinal fluid (CSF) and therefore may
spread throughout the entire neuraxis. Thirty percent of childhood ependymomas arise
outside of the posterior fossa.[1][2][3] Every patient with ependymoma should be
evaluated with diagnostic imaging of the spinal cord and whole brain. 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),[1][4][5][6][7][8][9][10][Level of evidence: 3iiiDi] age, histology, and extent of resection have consistently been the most important
factors.[5][6][11][12] Molecular diagnostics are evolving, but have yet to be validated in a prospective manner.[13][14] These prognostic variables must be evaluated in the context of
the treatment received.
References:
Goldwein JW, Leahy JM, Packer RJ, et al.: Intracranial ependymomas in children. Int J Radiat Oncol Biol Phys 19 (6): 1497-502, 1990.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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Treatment Option Overview
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary Levels of Evidence for more information.)
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 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.
In the past, treatment for childhood ependymoma has included surgery with 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] Chemotherapy has been shown to be active in
patients with recurrent ependymoma.[7] One relatively small, prospective, randomized trial suggests
that chemotherapy activity in newly diagnosed cases is limited,[8] 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.[9][Level of evidence: 3iiiC] Debilitating effects on growth and neurologic development have
frequently been observed, especially in younger children.[10][11][12] For this
reason, conformal radiation approaches that minimize damage to normal brain tissue are under evaluation for infants and children with ependymoma.[13] 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.[14]
References:
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.
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.
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.
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.
Kothbauer KF: Neurosurgical management of intramedullary spinal cord tumors in children. Pediatr Neurosurg 43 (3): 222-35, 2007.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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Treatment of Newly Diagnosed Childhood Ependymoma
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary Levels of Evidence for more information.)
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. If not performed preoperatively, MRI of the entire neuraxis should be obtained to evaluate for disease dissemination. Even myxopapillary ependymomas, considered to be a somewhat benign histologic subtype of ependymoma, have a relatively high incidence of central nervous system (CNS) tumor dissemination at diagnosis and at follow-up, thus underscoring the need for 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 and is under evaluation for children younger than 3 years. It is not necessary
to treat the entire CNS (whole brain and spine) because these tumors usually
recur at the local site.[2][5][6][Level of evidence: 3iiiA][7][Level of evidence: 3iiiA] When possible, patients should be treated in a
center experienced with this therapy. There is no evidence that adjuvant
chemotherapy, including the use of myeloablative chemotherapy,[8] 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%.[9] Limited experience suggests that surgery alone for completely resected supratentorial nonanaplastic tumors,[10] and intradural spinal cord ependymomas [11][Level of evidence: 3iiiDi] may, in select cases, be an appropriate approach to treatment.
- Residual disease; no disseminated disease:
Second-look surgery should be considered because patients who have complete
resections have better disease control. 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.[6][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,[9][12] although the outcome for patients with residual tumor within the spinal canal may be better.[13] There is
no evidence that adjuvant chemotherapy, including high-dose chemotherapy with
stem cell rescue, is of any benefit.[14]
- 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.[15][16][17][18] 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.[9] 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.[19]
Chemotherapy is able to induce objective responses in some children younger than 3 years with newly diagnosed ependymoma,[15][16][17] though not all chemotherapy regimens induce objective responses.[18] Up to 40% of infants and young children with totally resected disease may achieve long-term survival with chemotherapy alone.[20][Level of evidence: 2Di] The need and timing of
radiation therapy for children who have successfully completed chemotherapy and
have no residual disease is still to be determined.
Current approaches to treating young children with ependymoma do not generally employ chemotherapy to delay use of radiation therapy.
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.[9] The current Children's Oncology Group (COG) protocol for children with ependymoma includes young children aged 12 to 36 months and is evaluating whether conformal radiation therapy can minimize neurologic late effects while producing long-term survival.
Myxopapillary ependymoma
Historically, the management of myxopapillary ependymoma consisted of an attempt at en bloc resection of the tumor with no further treatment in the case of a gross total resection. However, based on the finding that dissemination of these tumors to other parts of the neuraxis can occur,[3] and evidence that focal irradiation may improve progression-free survival,[21] many practitioners now favor the use of irradiation following surgical resection of the primary mass.
Treatment options under clinical evaluation
The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
A COG trial (COG-ACNSO121) is now closed to accrual and analysis is pending. The study evaluated several questions of therapy for different subgroups of children aged 1 year and older with ependymoma as described below:
No Residual Disease; No Disseminated Disease:
- Children who have supratentorial nonanaplastic ependymoma for whom a gross total resection can be performed: These children are being carefully observed following surgical resection to determine whether they can be cured with surgery alone.
- Children with supratentorial anaplastic ependymoma and children with infratentorial ependymoma who have a near total resection or better: These children receive conformal radiation therapy directed at the primary site to determine whether cure can be achieved with this approach while minimizing radiation-associated long-term toxicities. Children with supratentorial nonanaplastic ependymoma with a near–total resection or better but who are not eligible for the observation also receive conformal radiation.
Residual Disease; No Disseminated Disease:
- Children with initial incompletely resected ependymoma: These children receive chemotherapy in an attempt to achieve a complete resection with second surgery prior to conformal radiation therapy.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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:
Hukin J, Epstein F, Lefton D, et al.: Treatment of intracranial ependymoma by surgery alone. Pediatr Neurosurg 29 (1): 40-5, 1998.
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.
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.
Bagley CA, Kothbauer KF, Wilson S, et al.: Resection of myxopapillary ependymomas in children. J Neurosurg 106 (4 Suppl): 261-7, 2007.
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.
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.
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.
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.
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.
Goldwein JW, Leahy JM, Packer RJ, et al.: Intracranial ependymomas in children. Int J Radiat Oncol Biol Phys 19 (6): 1497-502, 1990.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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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. For ependymoma, delays
beyond 10 to 15 years have been reported.[1][2] Disease generally recurs at the
primary tumor site, even in children with malignant ependymomas.[3][4] 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 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. In addition, patients may be candidates for focal retreatment with various radiation modalities, including stereotactic radiosurgery.[5][Level of evidence: 3iiiDi] Active agents include
cyclophosphamide, cisplatin, carboplatin, lomustine, and etoposide. Entry into
studies of novel therapeutic approaches should be considered.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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:
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.
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.
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.
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.
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.
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More Information
About PDQ
Additional PDQ Summaries
Important:
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
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This information is provided by the National Cancer Institute.
This information was last updated on August 3, 2008.