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Information from PDQ -- for Health Professionals
Childhood ependymoma
208/08627
** GENERAL INFORMATION **
This treatment information summary on childhood ependymoma is an overview of
prognosis, diagnosis, classification, and patient treatment. The National
Cancer Institute created the PDQ database to increase the availability of new
treatment information and its use in treating patients. Information and
references from the most recently published literature are included after
review by pediatric oncology specialists.
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.
Approximately 50% of brain tumors in children are infratentorial, with three
fourths of these located in the cerebellum or fourth ventricle. Common
infratentorial (posterior fossa) tumors include the following:
1. cerebellar astrocytoma (usually pilocytic but also fibrillary and high-
grade)
2. medulloblastoma (primitive neuroectodermal tumor)
3. ependymoma (low-grade or anaplastic)
4. brain stem glioma (often diagnosed neuroradiographically without biopsy; may
be high-grade or low-grade)
5. atypical teratoid
Supratentorial tumors include those tumors that occur in the sellar or
suprasellar region and/or other areas of the cerebrum. Sellar/suprasellar
tumors comprise approximately 20% of childhood brain tumors and include the
following:
1. craniopharyngioma
2. diencephalic (chiasm, hypothalamic, and/or thalamic) gliomas generally of
low-grade
3. germ cell tumors (germinoma or nongerminomatous)
Other tumors that occur supratentorially include the following:
1. low-grade astrocytoma or glioma (grade 1 or grade 2)
2. high-grade or malignant astrocytoma (anaplastic astrocytomas, glioblastomas
multiforme (grade 3 or grade 4))
3. mixed glioma (low-grade or high-grade)
4. oligodendroglioma (low-grade or high-grade)
5. primitive neuroectodermal tumor (cerebral neuroblastoma)
6. ependymoma (low-grade or anaplastic)
7. meningioma
8. choroid plexus tumors (papilloma and carcinoma)
9. pineal parenchymal tumors (pineoblastoma, pineocytoma, or mixed pineal
parenchymal tumor)
10. neuronal and mixed neuronal glial tumor (ganglioglioma, desmoplastic
infantile ganglioglioma, dysembryoplastic neuroepithelial tumor)
11. metastasis (rare) from extra neural malignancies
Important general concepts that should be understood by those caring for a
child with brain tumor include the following:
1. Selection of an appropriate therapy can only occur if the correct diagnosis
is made and the stage of the disease is accurately determined.
2. Children with primary brain tumors represent a major therapy challenge that,
for optimal results, requires the coordinated efforts of pediatric specialists
in fields such as neurosurgery, neurology, rehabilitation, neuropathology,
radiation oncology, medical oncology, neuroradiology, endocrinology, and
psychology, who have special expertise in the care of patients with these
diseases.[1-3]
3. More than one half of children diagnosed with brain tumors will survive 5
years from diagnosis. In some subgroups of patients, an even higher rate of
survival and cure is possible. Each child's treatment should be approached
with curative intent, and the possible long-term sequela of the disease and its
treatment should be considered before therapy is begun.
4. For the majority of children with brain tumors, the optimal treatment
regimen has not been determined. Children who have brain tumors should be
considered for enrollment in clinical trials when an appropriate study is
available. Such clinical trials are being carried out by institutions and/or
national cooperative groups.
5. Guidelines for pediatric cancer centers and their role in the treatment of
pediatric patients with cancer have been outlined by the American Academy of
Pediatrics.[4]
6. The cause of the vast majority of childhood brain tumors remains
unknown.[5,6]
This summary discusses the treatment of childhood ependymoma, which comprises
approximately 10% of all childhood brain tumors [7,8] or less than 200 cases
per year in the United States.
Information about ongoing clinical trials is available from the NCI
(http://cancer.gov/clinical_trials/).
References:
1. Heideman RL, Packer RJ, Albright LA, et al.: Tumors of the central
nervous system. In: Pizzo PA, Poplack DG, eds.: Principles and Practice
of Pediatric Oncology. Philadelphia, Pa: Lippincott-Raven, 3rd ed.,
1997, pp 633-697.
2. Pollack IF: Brain tumors in children. New England Journal of Medicine
331(22): 1500-1507, 1994.
3. Cohen ME, Duffman PK, eds: Brain Tumors in Children: Principles of
Diagnosis and Treatment, 2nd ed. New York: Raven Press, 1994.
4. Sanders J, Glader B, Cairo M, et al.: Guidelines for the pediatric cancer
center and role of such centers in diagnosis and treatment. American
Academy of Pediatrics Section Statement Section on Hematology/Oncology.
Pediatrics 99(1): 139-141, 1997.
5. Kuijten RR, Bunin GR: Risk factors for childhood brain tumors. Cancer
Epidemiology, Biomarkers and Prevention 2(3): 277-288, 1993.
6. Kuijten RR, Strom SS, Rorke LB, et al.: Family history of cancer and
seizures in young children with brain tumors: a report from the
Childrens Cancer Group (United States and Canada). Cancer Causes and
Control 4(5): 455-464, 1993.
7. Miller RW, Young JL Jr, Novakovic B: Childhood cancer. Cancer 75(1
suppl): 395-405, 1994.
8. Pollack IF, Gerszten PC, Martinez AJ, et al.: Intracranial ependymomas of
childhood: long-term outcome and prognostic factors. Neurosurgery
37(4): 655-666; discussion 666-667, 1995.
** CELLULAR CLASSIFICATION **
The classification of brain tumors is based on both histopathological
characteristics and location in the brain. Ependymomas are divided into the
following categories:
- subependymoma (WHO Grade I)
- ependymoma (WHO Grade II). Variants include cellular, papillary,
epithelial, clear cell, and mixed.
- malignant (also known as anaplastic) ependymoma (WHO Grade III)
The most recent World Health Organization classification of brain tumors
maintains the term "ependymoma" for tumors which are histologically benign and
malignant ependymoma for those which 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 based on
histologic classification alone.[2-5]
There are some subtypes of tumors which have been classified with ependymomas
although they carry a different prognosis. Ependymoblastomas, which generally
behave more like medulloblastomas or cortical neuroectodermal tumors, are
considered as separate entities from ependymomas.[1] Myxopapillary
ependymomas, which are typically benign and present in the filum terminale and
cauda equina, are also considered as a separate entity. 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. Kleihues P, Burger PC, Scheithauer BW: The new WHO classification of
brain tumours. Brain Pathology 3(3): 255-268, 1993.
2. Goldwein JW, Leahy JM, Packer RJ, et al.: Intracranial ependymomas in
children. International Journal of Radiation Oncology, Biology, Physics
19(6): 1497-1502, 1990.
3. Rousseau P, Habrand JL, Sarrazin D, et al.: Treatment of intracranial
ependymomas of children: review of a 15-year experience. International
Journal of Radiation Oncology, Biology, Physics 28(2): 381-386, 1994.
4. Chiu JK, Woo SY, Ater J, et al.: Intracranial ependymoma in children:
analysis of prognostic factors. Journal of Neuro-Oncology 13(3):
283-290, 1992.
5. Pollack IF, Gerszten PC, Martinez AJ, et al.: Intracranial ependymomas of
childhood: long-term outcome and prognostic factors. Neurosurgery
37(4): 655-666; discussion 666-667, 1995.
** STAGE 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
occur throughout the entire neuraxis. Thirty percent of ependymomas arise
outside of the posterior fossa.[1-3] 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 must be imaged in at least 2 planes with contiguous
MR slices performed after gadolinium enhancement. 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)
[1,4-6], age and extent of resection have consistently been the most important
factors.[5-7] These prognostic variables must be evaluated in the context of
the treatment received.
References:
1. Goldwein JW, Leahy JM, Packer RJ, et al.: Intracranial ependymomas in
children. International Journal of Radiation Oncology, Biology, Physics
19(6): 1497-1502, 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. Annals of Neurology 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.
International Journal of Radiation Oncology, Biology, Physics 23(2):
313-319, 1992.
4. Shaw EG, Evans RG, Scheithauer BW, et al.: Postoperative radiotherapy of
intracranial ependymoma in pediatric and adult patients. International
Journal of Radiation Oncology, Biology, Physics 13(10): 1457-1462, 1987.
5. Horn B, Heideman R, Geyer R, et al.: A multi-institutional retrospective
study of intracranial ependymoma in children: identification of risk
factors. Journal of Pediatric Hematology/Oncology 21(3): 203-211, 1999.
6. Pollack IF, Gerszten PC, Martinez AJ, et al.: Intracranial ependymomas of
childhood: long-term outcome and prognostic factors. Neurosurgery
37(4): 655-666; discussion 666-667, 1995.
7. Bouffet E, Perilongo G, Canete A, et al.: Intracranial ependymomas in
children: a critical review of prognostic factors and a plea for
cooperation. Medical and Pediatric Oncology 30(6): 319-329; discussion
329-331, 1998.
** 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 2 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 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] Chemotherapy has been shown to be active in
patients with ependymoma [3] but a small prospective, randomized trial suggests
that its activity is limited.[4] Children younger than 3 years of age are
particularly susceptible to the adverse effect of radiation on brain
development. Debilitating effects on growth and neurologic development have
frequently been observed, especially in younger children.[5-7] For this
reason, the role of chemotherapy in allowing a delay in the administration of
radiation therapy is under study.[8-10] Studies are underway evaluating the
role of early radiation therapy for local control in infants. 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.[11]
The designations in PDQ that treatments are "standard" or "under clinical
evaluation" are not to be used as a basis for reimbursement determinations.
References:
1. Pollack IF, Gerszten PC, Martinez AJ, et al.: Intracranial ependymomas of
childhood: long-term outcome and prognostic factors. Neurosurgery
37(4): 655-666; discussion 666-667, 1995.
2. Horn B, Heideman R, Geyer R, et al.: A multi-institutional retrospective
study of intracranial ependymoma in children: identification of risk
factors. Journal of Pediatric Hematology/Oncology 21(3): 203-211, 1999.
3. Goldwein JW, Glauser TA, Packer RJ, et al.: Recurrent intracranial
ependymomas in children: survival, patterns of failure, and prognostic
factors. Cancer 66(3): 557-563, 1990.
4. Evans AE, Anderson JR, Lefkowitz-Boudreaux IB, et al.: Adjuvant
chemotherapy of childhood posterior fossa ependymoma: cranio-spinal
irradiation with or without CCNU, vincristine, and prednisone: a
Children's Cancer Group study. Medical and Pediatric Oncology 27(1):
8-14, 1996.
5. 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. Journal of Neurosurgery 70(5): 707-713,
1989.
6. Johnson DL, McCabe MA, Nicholson HS, et al.: Quality of long-term
survival in young children with medulloblastoma. Journal of
Neurosurgery 80(6): 1004-1010, 1994.
7. Packer RJ, Sutton LN, Goldwein JW, et al.: Improved survival with the use
of adjuvant chemotherapy in the treatment of medulloblastoma. Journal
of Neurosurgery 74(3): 433-440, 1991.
8. 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. New England Journal of Medicine 328(24):
1725-1731, 1993.
9. Geyer JR, Zeltzer PM, Boyett JM, et al.: Survival of infants with
primitive neuroectodermal tumors or malignant ependymomas of the CNS
treated with eight drugs in 1 day: a report from the Childrens Cancer
Group. Journal of Clinical Oncology 12(8): 1607-1615, 1994.
10. 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. Journal
of Clinical Oncology 19(5): 1288-1296, 2001.
11. Good CD, Wade AM, Hayward RD, et al.: Surveillance neuroimaging in
childhood intracranial ependymoma: how effective, how often, and for how
long? Journal of Neurosurgery 94(1): 27-32, 2001.
** 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 if there is minimal residual disease present after
surgery.[1,2] Postoperatively, studies such as cerebral spinal fluid (CSF)
cytological evaluation should be conducted to determine the extent of residual
disease and dissemination. 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 approximately 20% to 40% relapse risk in spite of
postoperative radiation therapy.
-- Post surgical treatment options --
Surgery alone:
Limited experience with surgery alone for completely resected supratentorial
tumors suggest that, in select cases, this may be an option.[3]
No residual disease, no disseminated disease:
The traditional postsurgical treatment for these patients has been radiation
therapy consisting of 5400 to 5580 cGy to the tumor bed. It is not necessary
to treat the entire CNS (whole brain and spine) since these tumors usually
recur at the local site.[2,4] When possible, patients should be treated in a
center experienced with this therapy. There is no evidence that adjuvant
chemotherapy improves the outcome for patients with ependymoma. Trials are
ongoing to evaluate the role of radiation therapy and chemotherapy in these
patients. Consult PDQ for information on clinical trials.
Residual disease; no disseminated disease:
Consideration of re-resection should be made since patients who have complete
resections have better disease control. The traditional postsurgical treatment
for these patients has been radiation therapy consisting of 5400 to 5580 cGy to
the tumor bed. It is not necessary to treat the entire CNS (whole brain and
spine) since these tumors usually recur at the local site. When possible,
patients should be treated in a center experienced with this therapy. There is
no evidence that adjuvant chemotherapy, including high-dose chemotherapy with
stem cell rescue, is of any benefit.[5] Trials are ongoing to evaluate the
possible role of radiation therapy and chemotherapy in these patients. Consult
PDQ for information on clinical trials.
Children with 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 has been 5400 to 5580 cGy. Doses of approximately 3600 cGy 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
to bulk areas of spinal disease between 4140 cGy and 5040 cGy 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. Consult PDQ for
information on clinical trials.
Postsurgical management of children younger than 3 years of age:
Because of the known effects of radiation on growth and neurocognitive
development, its use immediately after surgery in children under 3 years of age
is limited. Some patients younger than 3 years of age with newly diagnosed
ependymoma will respond, at least partially, to chemotherapy.[6,7] For this
reason, strong consideration should be given to entering patients younger than
3 years of age in studies that use chemotherapy to delay the need for radiation
therapy.[8] Although chemotherapy is being used to prevent neurologic damage
caused by radiation therapy in very young patients, neurologic deficits may be
present in children prior to the initiation of therapy, and progressive
neurologic damage has been noted during therapy.[9] The need and timing of
radiation therapy for children who have successfully completed chemotherapy and
have no residual disease is still to be determined.
References:
1. Hukin J, Epstein F, Lefton D, et al.: Treatment of intracranial
ependymoma by surgery alone. Pediatric Neurosurgery 29(1): 40-45, 1998.
2. Horn B, Heideman R, Geyer R, et al.: A multi-institutional retrospective
study of intracranial ependymoma in children: identification of risk
factors. Journal of Pediatric Hematology/Oncology 21(3): 203-211, 1999.
3. Goldwein JW, Leahy JM, Packer RJ, et al.: Intracranial ependymomas in
children. International Journal of Radiation Oncology, Biology, Physics
19(6): 1497-1502, 1990.
4. Evans AE, Anderson JR, Lefkowitz-Boudreaux IB, et al.: Adjuvant
chemotherapy of childhood posterior fossa ependymoma: cranio-spinal
irradiation with or without CCNU, vincristine, and prednisone: a
Children's Cancer Group study. Medical and Pediatric Oncology 27(1):
8-14, 1996.
5. 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. New England Journal of Medicine 328(24):
1725-1731, 1993.
6. Geyer JR, Zeltzer PM, Boyett JM, et al.: Survival of infants with
primitive neuroectodermal tumors or malignant ependymomas of the CNS
treated with eight drugs in 1 day: a report from the Childrens Cancer
Group. Journal of Clinical Oncology 12(8): 1607-1615, 1994.
7. Mulhern RK, Horowitz ME, Kovnar EH, et al.: Neurodevelopmental status of
infants and young children treated for brain tumors with preirradiation
chemotherapy. Journal of Clinical Oncology 7(11): 1660-1666, 1989.
8. 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. Journal
of Clinical Oncology 19(5): 1288-1296, 2001.
9. Pollack IF, Gerszten PC, Martinez AJ, et al.: Intracranial ependymomas of
childhood: long-term outcome and prognostic factors. Neurosurgery
37(4): 655-666; discussion 666-667, 1995.
** 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. Active agents include
cyclophosphamide, cisplatin, carboplatin, lomustine, and etoposide. Entry into
studies of novel therapeutic approaches should be considered. Consult PDQ for
information on current clinical trials.
References:
1. Pollack IF, Gerszten PC, Martinez AJ, et al.: Intracranial ependymomas of
childhood: long-term outcome and prognostic factors. Neurosurgery
37(4): 655-666; discussion 666-667, 1995.
2. Vanuytsel LJ, Bessell EM, Ashley SE, et al.: Intracranial ependymoma:
long-term results of a policy of surgery and radiotherapy.
International Journal of Radiation Oncology, Biology, Physics 23(2):
313-319, 1992.
3. Goldwein JW, Corn BW, Finlay JL, et al.: Is craniospinal irradiation
required to cure children with malignant (anaplastic) intracranial
ependymomas? Cancer 67(11): 2766-2771, 1991.
4. Merchant TE, Haida T, Wang MH, et al.: Anaplastic ependymoma: treatment
of pediatric patients with or without craniospinal radiation therapy.
Journal of Neurosurgery 86(6): 943-949, 1997.
Date Last Modified: 07/2002
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* Editorial Boards. If you have specific comments on the content of this *
* information, direct them to: PDQ Editorial Board, CIPS/NCI, 6116 *
* Executive Boulevard, Suite 3002B, MSC-8321, 20892-8321, fax: 301-480-8105.*
* *
* The PDQ database also contains listings of clinical trial protocols and *
* directories of organizations and physicians who treat cancer patients, *
* but this information is not available through CancerMail. For more *
* information on accessing PDQ, consult the CancerMail Contents List. *
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