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Childhood Cerebral Astrocytoma/Malignant Glioma Treatment (PDQ®)
- Purpose of This PDQ Summary
- General Information
- Cellular Classification
- Stage Information
- Treatment of Low-Grade Childhood Cerebral Astrocytoma
- Treatment of High-Grade Childhood Cerebral Astrocytoma
- Recurrent Childhood Cerebral Astrocytoma
- Get More Information From NCI
- Changes to This Summary (04/09/2008)
- More Information
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 cerebral astrocytoma/malignant glioma. 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:
- Cellular 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.
In the summary, treatments are described as “standard” or “conventional” and “under clinical evaluation.” These designations 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.
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 Late Effects of Treatment for Childhood Cancer summary 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 Childhood Brain and Spinal Cord Tumors Treatment Overview summary for information about the general classification of childhood brain and spinal cord tumors.
Various classification schemata have been used to separate glial tumors into prognostic subsets. According to the most recent classification of the World Health Organization, glial tumors are divided on the basis of histologic criteria into the following subsets: pilocytic astrocytomas, low-grade nonpilocytic astrocytomas, anaplastic gliomas, and glioblastoma multiforme. Various types of nonpilocytic astrocytomas, such as fibrillary protoplasmic and gemistocytic, have been identified. Both malignant and benign varieties of oligodendrogliomas may occur. In young children (especially those younger than 1 year at diagnosis), new variants such as dysembryoplastic neuroepithelial tumor and desmoplastic infantile gangliogliomas are increasingly recognized. Mixed gliomas are classified separately, as are gangliogliomas and other primary neuronal tumors. In general, the grade of the tumor is predictive of outcome; patients with higher-grade tumors have a poorer prognosis. High-grade gliomas with p53 expression and mutation are also associated with a poorer prognosis. MIB-1 labeling index, a marker of cellular proliferative activity, is predictive of outcome in childhood malignant brain tumors. Both histologic classification and proliferative activity evaluation have been shown to be independently associated with survival.1Burger PC, Sheithauer BW, Vogel FS: Surgical pathology of the nervous system and its coverings. 3rd ed. New York, NY: Churchill Livingstone, 1991.2Kleihues P, Cavenee WK, eds.: Pathology and Genetics of Tumours of the Nervous System. Lyon, France: International Agency for Research on Cancer, 2000.3Pollack IF, Finkelstein SD, Woods J, et al.: Expression of p53 and prognosis in children with malignant gliomas. N Engl J Med 346 (6): 420-7, 2002.4Pollack IF, Hamilton RL, Burnham J, et al.: Impact of proliferation index on outcome in childhood malignant gliomas: results in a multi-institutional cohort. Neurosurgery 50 (6): 1238-44; discussion 1244-5, 2002.
Low-Grade Cerebral Astrocytoma
Low-grade cerebral astrocytomas (grade I [pilocytic] and grade II) have a relatively favorable prognosis, particularly if complete excision is possible. In the World Health Organization brain tumor classification schema, all grade 1 tumors are pilocytic astrocytomas. The pilomyxoid variant of pilocytic astrocytoma may be a more aggressive variant and may be more likely to disseminate. There is no generally recognized staging system. Tumor spread, when it occurs, is usually by contiguous extension; dissemination to other central nervous system sites may rarely occur. Although metastasis is unlikely, tumors may be of multifocal origin, especially when associated with neurofibromatosis type 1 (NF-1). Low-grade astrocytomas have a predilection for certain anatomic locations in children, including the cerebellum, diencephalon (i.e., chiasm, hypothalamus, and thalamus), and brainstem.
Patients with NF-1 constitute a special group of patients with low-grade gliomas. In general, treatment is not required for incidental tumors found with surveillance scans. Symptomatic lesions or those that have radiographically progressed may require treatment.
High-Grade Cerebral Astrocytoma
High-grade or malignant astrocytoma (anaplastic astrocytoma [grade III] and glioblastoma multiforme [grade IV]) may occur anywhere above the tentorium. Malignant astrocytoma is often locally invasive and extensive. Spread via the subarachnoid space may occur. Metastasis outside of the central nervous system has been reported but is extremely infrequent until after multiple local relapses. There is no generally recognized staging system. Biologic markers, such as p53 overexpression and mutation status, may be useful predictors of outcome in patients with malignant gliomas. Although malignant astrocytoma carries a generally poor prognosis in younger patients, those with anaplastic astrocytoma and those in whom a gross total resection is possible may fare better.1Pollack IF: Brain tumors in children. N Engl J Med 331 (22): 1500-7, 1994.2Deutsch M, ed.: Management of Childhood Brain Tumors. Boston: Kluwer Academic Publishers, 1990.3Komotar RJ, Burger PC, Carson BS, et al.: Pilocytic and pilomyxoid hypothalamic/chiasmatic astrocytomas. Neurosurgery 54 (1): 72-9; discussion 79-80, 2004.4Molloy PT, Bilaniuk LT, Vaughan SN, et al.: Brainstem tumors in patients with neurofibromatosis type 1: a distinct clinical entity. Neurology 45 (10): 1897-902, 1995.5Pollack IF, Finkelstein SD, Woods J, et al.: Expression of p53 and prognosis in children with malignant gliomas. N Engl J Med 346 (6): 420-7, 2002.6Finlay JL, Boyett JM, Yates AJ, et al.: Randomized phase III trial in childhood high-grade astrocytoma comparing vincristine, lomustine, and prednisone with the eight-drugs-in-1-day regimen. Childrens Cancer Group. J Clin Oncol 13 (1): 112-23, 1995.
Treatment of Low-Grade Childhood Cerebral Astrocytoma
To determine and implement optimum treatment, treatment planned by a multidisciplinary team of cancer specialists who have experience treating childhood brain tumors is required.
The usual treatment for low-grade supratentorial astrocytoma is determined by location. Hemispheric tumors are often amenable to complete surgical resection. Low-grade diencephalic tumors can also be aggressively resected, with resultant long-term disease control; however, such resection may result in significant neurologic sequelae, especially in children younger than 2 years at diagnosis. Because of the infiltrative nature of some deep-seeded lesions, extensive surgical resection may not be appropriate and biopsy followed by either radiation or chemotherapy should be considered. Treatment options for patients with incompletely resected tumor must be individualized and may include observation, re-resection, chemotherapy, and radiation.
Radiation therapy is often reserved until progressive disease is documented, and its use may be further delayed through the use of chemotherapy, a strategy that is commonly employed in young children. Debilitating effects on growth and neurologic development have frequently been observed following radiation therapy, especially in younger children with extensive lesions. For those children with low-grade glioma for whom radiation therapy is indicated, conformal radiotherapeutic approaches appear effective and offer the potential for reducing the acute and long-term toxicities associated with this modality.
Evaluation with detailed electroencephalographic mapping and surgery designed to remove the tumor and adjacent epileptic foci has been recommended for those patients with low-grade tumor and seizures. Excellent results in tumor and seizure control, however, have been reported with magnetic resonance-based total tumor resection. Chemotherapy can be used to delay, and sometimes obviate, the need for radiation therapy in children with benign lesions. The most widely used regimen to treat progressive or symptomatic nonresectable, low-grade gliomas is a combination of carboplatin and vincristine. The 3-year progressive-free survival for children younger than 5 years is 74%, but most patients ultimately require further treatment. Other chemotherapeutic regimens have also been shown to be effective.
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.
- COG-ACNS0223: The Children’s Oncology Group (COG) is conducting a limited-institution phase I/II study of carboplatin, temozolomide, and vincristine for children with newly diagnosed low-grade gliomas.
The designations in PDQ that treatments are “standard” or “under clinical evaluation” are not to be used as a basis for reimbursement determinations.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with childhood low-grade cerebral astrocytoma. 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.1Pollack IF, Claassen D, al-Shboul Q, et al.: Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases. J Neurosurg 82 (4): 536-47, 1995.2Berger MS, Ghatan S, Haglund MM, et al.: Low-grade gliomas associated with intractable epilepsy: seizure outcome utilizing electrocorticography during tumor resection. J Neurosurg 79 (1): 62-9, 1993.3Wisoff JH, Abbott R, Epstein F: Surgical management of exophytic chiasmatic-hypothalamic tumors of childhood. J Neurosurg 73 (5): 661-7, 1990.4Albright AL: Feasibility and advisability of resections of thalamic tumors in pediatric patients. J Neurosurg 100 (5 Suppl Pediatrics): 468-72, 2004.5Fisher BJ, Leighton CC, Vujovic O, et al.: Results of a policy of surveillance alone after surgical management of pediatric low grade gliomas. Int J Radiat Oncol Biol Phys 51 (3): 704-10, 2001.6Packer RJ, Ater J, Allen J, et al.: Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas. J Neurosurg 86 (5): 747-54, 1997.7Gnekow AK, Kortmann RD, Pietsch T, et al.: Low grade chiasmatic-hypothalamic glioma-carboplatin and vincristin chemotherapy effectively defers radiotherapy within a comprehensive treatment strategy -- report from the multicenter treatment study for children and adolescents with a low grade glioma -- HIT-LGG 1996 -- of the Society of Pediatric Oncology and Hematology (GPOH). Klin Padiatr 216 (6): 331-42, 2004 Nov-Dec.8Merchant TE, Zhu Y, Thompson SJ, et al.: Preliminary results from a Phase II trail of conformal radiation therapy for pediatric patients with localised low-grade astrocytoma and ependymoma. Int J Radiat Oncol Biol Phys 52 (2): 325-32, 2002.9Marcus KJ, Goumnerova L, Billett AL, et al.: Stereotactic radiotherapy for localized low-grade gliomas in children: final results of a prospective trial. Int J Radiat Oncol Biol Phys 61 (2): 374-9, 2005.10Packer RJ, Sutton LN, Patel KM, et al.: Seizure control following tumor surgery for childhood cortical low-grade gliomas. J Neurosurg 80 (6): 998-1003, 1994.11Laithier V, Grill J, Le Deley MC, et al.: Progression-free survival in children with optic pathway tumors: dependence on age and the quality of the response to chemotherapy--results of the first French prospective study for the French Society of Pediatric Oncology. J Clin Oncol 21 (24): 4572-8, 2003.12Prados MD, Edwards MS, Rabbitt J, et al.: Treatment of pediatric low-grade gliomas with a nitrosourea-based multiagent chemotherapy regimen. J Neurooncol 32 (3): 235-41, 1997.13Gururangan S, Cavazos CM, Ashley D, et al.: Phase II study of carboplatin in children with progressive low-grade gliomas. J Clin Oncol 20 (13): 2951-8, 2002.14Grill J, Couanet D, Cappelli C, et al.: Radiation-induced cerebral vasculopathy in children with neurofibromatosis and optic pathway glioma. Ann Neurol 45 (3): 393-6, 1999.15Sharif S, Ferner R, Birch JM, et al.: Second primary tumors in neurofibromatosis 1 patients treated for optic glioma: substantial risks after radiotherapy. J Clin Oncol 24 (16): 2570-5, 2006.
Treatment of High-Grade Childhood Cerebral Astrocytoma
The therapy for both children and adults with supratentorial high-grade astrocytoma includes surgery, radiation therapy, and chemotherapy. Outcome in high-grade gliomas occurring in childhood may be more favorable than that in adults, but it is not clear if this difference is caused by biologic variations in tumor characteristics, therapies used, tumor resectability, or other factors that are not presently understood. The ability to obtain a complete resection is associated with a better prognosis. Radiation therapy is administered to a field that widely encompasses the entire tumor. Alternatively, it can be administered to the entire brain with a cone down to the tumor volume. The radiation therapy dose to the tumor bed is usually at least 54 Gy. Despite such therapy, overall survival rates remain poor. Among patients treated with surgery, radiation therapy and nitrosourea (lomustine)-based chemotherapy, 5-year progression-free survival was 19% ± 3%; survival was 40% in those who had total resections. In one trial, children with glioblastoma multiforme who were treated on a prospective randomized trial with adjuvant lomustine, vincristine, and prednisone fared better than those children treated with radiation therapy alone. In adults, the addition of temozolomide (Temodal) during and after radiation therapy resulted in improved 2-year event-free survival as compared to treatment with radiation therapy alone. Adult patients with glioblastoma multiforme with a methylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter benefited from temozolomide, whereas those who did not have a methylated MGMT promoter did not. The role of temozolomide given concurrently with radiation therapy for children with supratentorial high-grade gliomas has not yet been demonstrated but is under clinical evaluation. Children younger than 3 years may benefit from chemotherapy to delay, modify, or, in selected cases, obviate the need for radiation therapy. Clinical trials that evaluate chemotherapy with or without radiation therapy are ongoing. Information about ongoing clinical trials is available from the NCI Web site.
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.
- COG-ACNS0423: The Children's Oncology Group (COG) is conducting a pilot phase II study of adjuvant radiation therapy and temozolomide followed by maintenance temozolomide and lomustine for children with newly diagnosed disease. This is the first of a series of planned phase II studies evaluating agents during and after 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 childhood high-grade cerebral astrocytoma. 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.1Rasheed BK, McLendon RE, Herndon JE, et al.: Alterations of the TP53 gene in human gliomas. Cancer Res 54 (5): 1324-30, 1994.2Wisoff JH, Boyett JM, Berger MS, et al.: Current neurosurgical management and the impact of the extent of resection in the treatment of malignant gliomas of childhood: a report of the Children's Cancer Group trial no. CCG-945. J Neurosurg 89 (1): 52-9, 1998.3Woo SY, Donaldson SS, Cox RS: Astrocytoma in children: 14 years' experience at Stanford University Medical Center. J Clin Oncol 6 (6): 1001-7, 1988.4Fouladi M, Hunt DL, Pollack IF, et al.: Outcome of children with centrally reviewed low-grade gliomas treated with chemotherapy with or without radiotherapy on Children's Cancer Group high-grade glioma study CCG-945. Cancer 98 (6): 1243-52, 2003.5Sposto R, Ertel IJ, Jenkin RD, et al.: The effectiveness of chemotherapy for treatment of high grade astrocytoma in children: results of a randomized trial. A report from the Childrens Cancer Study Group. J Neurooncol 7 (2): 165-77, 1989.6Stupp R, Mason WP, van den Bent MJ, et al.: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352 (10): 987-96, 2005.7Hegi ME, Diserens AC, Gorlia T, et al.: MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352 (10): 997-1003, 2005.8Duffner 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, 1993.9Duffner PK, Krischer JP, Burger PC, et al.: Treatment of infants with malignant gliomas: the Pediatric Oncology Group experience. J Neurooncol 28 (2-3): 245-56, 1996 May-Jun.
Recurrent Childhood Cerebral Astrocytoma
Recurrent Low-Grade Cerebral Astrocytoma
Low-grade glioma may recur many years after initial treatment. Disease typically recurs at the primary tumor site. Multifocal or disseminated disease is rare but can occur. Most children whose low-grade fibrillary astrocytomas recur will harbor low-grade lesions; however, malignant transformation is possible. Biopsy or surgical resection may be necessary for confirmation of relapse because other entities, such as secondary tumor and radiation-related brain necrosis, may be clinically indistinguishable from tumor recurrence. The need for further surgical intervention must be individualized on the basis of the initial tumor type, the length of time between initial treatment and the reappearance of the mass lesion, and the clinical status of the child.
An individual plan needs to be tailored on the basis of patient age, tumor location, and prior treatment. Drug combinations, such as carboplatin and vincristine, may be useful at the time of recurrence for children with low-grade gliomas. For those children with recurrent low-grade glioma for whom radiation therapy is indicated, conformal radiotherapeutic approaches appear effective and offer the potential for reducing the acute and long-term toxicities associated with this modality.
Recurrent High-Grade Cerebral Astrocytoma
Most patients with high-grade gliomas will eventually have tumor recurrence, usually within 3 years of original diagnosis but perhaps many years after initial treatment. Disease may recur at the primary tumor site, at the margin of the resection/radiation bed, or at noncontiguous central nervous system sites. Systemic relapse is rare but may occur. At the time of recurrence, a complete evaluation for extent of relapse is indicated for all malignant tumors. Biopsy or surgical resection may be necessary for confirmation of relapse because other entities, such as secondary tumor and treatment-related brain necrosis, may be clinically indistinguishable from tumor recurrence. The need for surgical intervention must be individualized on the basis of the initial tumor type, the length of time between initial treatment and the reappearance of the mass lesion, and the clinical picture.
Patients for whom initial treatment fails may benefit from additional treatment. High-dose chemotherapy with hematopoietic stem cell transplant may be effective in a subset of patients with minimal residual disease at time of treatment. Such patients should also be considered for entry into trials of novel therapeutic approaches. Information about ongoing clinical trials is available from the NCI Web site.
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 cerebral astrocytoma. 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.1Leibel SA, Sheline GE, Wara WM, et al.: The role of radiation therapy in the treatment of astrocytomas. Cancer 35 (6): 1551-7, 1975.2Perilongo G, Carollo C, Salviati L, et al.: Diencephalic syndrome and disseminated juvenile pilocytic astrocytomas of the hypothalamic-optic chiasm region. Cancer 80 (1): 142-6, 1997.3Giannini C, Scheithauer BW: Classification and grading of low-grade astrocytic tumors in children. Brain Pathol 7 (2): 785-98, 1997.4Packer RJ, Lange B, Ater J, et al.: Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. J Clin Oncol 11 (5): 850-6, 1993.5Gnekow AK, Kortmann RD, Pietsch T, et al.: Low grade chiasmatic-hypothalamic glioma-carboplatin and vincristin chemotherapy effectively defers radiotherapy within a comprehensive treatment strategy -- report from the multicenter treatment study for children and adolescents with a low grade glioma -- HIT-LGG 1996 -- of the Society of Pediatric Oncology and Hematology (GPOH). Klin Padiatr 216 (6): 331-42, 2004 Nov-Dec.6Merchant TE, Zhu Y, Thompson SJ, et al.: Preliminary results from a Phase II trail of conformal radiation therapy for pediatric patients with localised low-grade astrocytoma and ependymoma. Int J Radiat Oncol Biol Phys 52 (2): 325-32, 2002.7Marcus KJ, Goumnerova L, Billett AL, et al.: Stereotactic radiotherapy for localized low-grade gliomas in children: final results of a prospective trial. Int J Radiat Oncol Biol Phys 61 (2): 374-9, 2005.8Ruggiero A, Cefalo G, Garré ML, et al.: Phase II trial of temozolomide in children with recurrent high-grade glioma. J Neurooncol 77 (1): 89-94, 2006.9Finlay JL, Goldman S, Wong MC, et al.: Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children's Cancer Group. J Clin Oncol 14 (9): 2495-503, 1996.10McCowage GB, Friedman HS, Moghrabi A, et al.: Activity of high-dose cyclophosphamide in the treatment of childhood malignant gliomas. Med Pediatr Oncol 30 (2): 75-80, 1998.
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Changes to This Summary (04/09/2008)
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
- PDQ® - NCI's Comprehensive Cancer Database.Full description of the NCI PDQ database.
Additional PDQ Summaries
- PDQ® Cancer Information Summaries: Adult TreatmentTreatment options for adult cancers.
- PDQ® Cancer Information Summaries: Pediatric TreatmentTreatment options for childhood cancers.
- PDQ® Cancer Information Summaries: Supportive and Palliative Care Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.
- PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer) Tests or procedures that detect specific types of cancer.
- PDQ® Cancer Information Summaries: Prevention Risk factors and methods to increase chances of preventing specific types of cancer.
- PDQ® Cancer Information Summaries: Genetics Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.
- PDQ® Cancer Information Summaries: Complementary and Alternative Medicine Information about complementary and alternative forms of treatment for patients with cancer.
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).
This information was last updated on 2008-04-09