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Childhood cerebral astrocytoma/malignant glioma

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General Information
Cellular Classification
Stage Information
Treatment Option Overview
Low-grade Childhood Cerebral Astrocytoma
High-grade Childhood Cerebral Astrocytoma
Recurrent Childhood Cerebral Astrocytoma

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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).

Information from PDQ -- for Health Professionals

GENERAL INFORMATION

This treatment information summary on childhood cerebral astrocytomas/malignant gliomas is an overview of diagnosis, classification, patient treatment, and prognosis. 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 and 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 astrocytoma, glioblastoma
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 who has a 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 sequelae of the disease and its treatment should be considered before therapy is begun.

4. For the majority of childhood brain tumors, the optimal treatment regimen
has not been determined. Children who have brain tumors should be considered for enrollment in a clinical trial when an appropriate study is available. Such clinical trials are being carried out by institutions and 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 will discuss the treatment of childhood cerebral astrocytomas/malignant gliomas.

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.

CELLULAR CLASSIFICATION

Various classification schemata have been used to separate glial tumors into prognostic subsets.[1] 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 glioblastomas multiforme.[2] Various types of nonpilocytic astrocytomas, such as fibrillary protoplasmic and gemistiocytic, have been identified. Both malignant and benign varieties of oligodendrogliomas may occur. In young children, 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. Other parameters, such as mitotic index evaluators, that may be independently predictive of outcome (especially in low-grade tumors) may not yet have been incorporated into the classification schema.

References:

  1. Burger PC, Sheithauer BW, Vogel FS: Surgical pathology of the nervous system and its coverings. New York: Churchill Livingstone, 3rd ed., 1991.
  2. Kleihues P, Cavenee WK, eds.: Pathology and Genetics of Tumours of the Nervous System. Lyon, France: International Agency for Research on Cancer, 2000.

STAGE INFORMATION

Low-grade cerebral astrocytoma

Low-grade cerebral astrocytomas (pilocytic and fibrillary) have a relatively favorable prognosis, particularly if complete excision is possible.[1,2] There is no generally recognized staging system. Tumor spread 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. Low-grade astrocytomas have a predilection for certain anatomic locations. Tumors of the hypothalamus/optic chiasm are difficult to approach surgically and have historically been treated with radiation or chemotherapy. Recently, advances in surgical techniques have allowed certain large tumors to be aggressively resected. These tumors are addressed separately in this document. Low-grade tumors of the temporal lobe usually present as a seizure disorder, and are usually surgical candidates. Low-grade localized tumors of the thalamus may be surgically resected with the use of intraoperative navigational systems. Diffuse infiltrative lesions are treated by radiation or chemotherapy.

Patients with neurofibromatosis are a special group. In general, treatment is not required for incidental tumors found with surveillance scans. Symptomatic lesions are treated the same as in patients without neurofibromatosis.[3]

High-grade cerebral astrocytoma

High-grade or malignant astrocytoma (anaplastic astrocytoma, glioblastoma multiforme) may occur anywhere above the tentorium. Malignant astrocytoma is often locally invasive and extensive.[1,2] Spread via the subarachnoid space may occur. Metastasis outside of the central nervous system has been reported but is extremely rare. 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.[4] Although malignant astrocytoma carries a generally poor prognosis in younger patients, those with anaplastic astrocytoma disease and those in whom a gross total resection is possible may fare better.

References:

  1. Pollack IF: Brain tumors in children. New England Journal of Medicine 331(22): 1500-1507, 1994.
  2. Deutsch M, Ed.: Management of Childhood Brain Tumors. Boston: Kluwer Academic Publishers, 1990.
  3. Molloy PT, Bilaniuk LT, Vaughan SN, et al.: Brainstem tumors in patients with neurofibromatosis type 1: a distinct clinical entity. Neurology 45(10): 1897-1902, 1995.
  4. Pollack IF, Finkelstein SD, Woods J, et al.: Expression of p53 and prognosis in children with malignant gliomas. New England Journal of Medicine 346(6): 420-427, 2002.

TREATMENT OPTION OVERVIEW

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

Debilitating effects on growth and neurologic development have frequently been observed following radiation therapy, especially in younger children.[1-3] For this reason, the role of chemotherapy in allowing a delay in the administration of radiation therapy is under study, and preliminary results suggest that chemotherapy can be used to delay, and sometimes obviate, the need for radiation therapy in children with benign and malignant lesions.[4] Long-term management of these patients is complex and requires a multidisciplinary approach.

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. 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.
  2. 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.
  3. 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.
  4. 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.

LOW-GRADE CHILDHOOD CEREBRAL ASTROCYTOMA

The usual treatment for low-grade supratentorial astrocytoma is surgery. There is no evidence that radiation therapy is of benefit for patients with completely resected tumors. For patients with incompletely resected tumor, treatment options include observation, re-resection, radiation, and/or chemotherapy and must be individualized. Radiation therapy is often reserved until progressive disease is documented.[1,2] Radiation fields encompass the tumor, and doses of 5,400 cGy are common. 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.[3] However, excellent results in tumor and seizure control have been reported with magnetic resonance-based "total" tumor resection.[4] Low-grade tumors may respond to various chemotherapeutic regimens, including carboplatin.[5] Chemotherapy may delay the need for radiation therapy; its role in the treatment of children younger than 5 years of age with newly diagnosed, progressive lesions is under study.[5]

References:

  1. Fisher BJ, Leighton CC, Vujovic O, et al.: Results of a policy of surveillance alone after surgical management of pediatric low-grade gliomas. International Journal of Radiation Oncology, Biology, Physics 51(3): 704-710, 2001.
  2. Pollack IF, Claassen D, Al-Shboul Q, et al.: Low-grade gliomas of the cerebral hemispheres in children: an analysis of 71 cases. Journal of Neurosurgery 82(4): 536-547, 1995.
  3. Berger MS, Ghatan S, Haglund MM, et al.: Low-grade gliomas associated with intractable epilepsy: seizure outcome utilizing electrocorticography during tumor resection. Journal of Neurosurgery 79(1): 62-69, 1993.
  4. Packer RJ, Sutton LN, Patel KM, et al.: Seizure control following tumor surgery for childhood cortical low-grade gliomas. Journal of Neurosurgery 80(6): 998-1003, 1994.
  5. Packer RJ, Lange B, Ater J, et al.: Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. Journal of Clinical Oncology 11(5): 850-856, 1993.

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.[1] The ability to obtain a complete resection is associated with a better prognosis.[2] 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.[3] The radiation therapy dose is usually at least 5,400 cGy. A notable result was seen in children with glioblastoma multiforme who were treated on a prospective, randomized trial with adjuvant lomustine, vincristine, and prednisone.[4] In children with recurrent high-grade gliomas, one study has reported encouraging disease control in those with minimal bulk disease at the time of initiation of chemotherapy.[5] Children younger than 3 years of age may benefit from chemotherapy to delay, modify, or, in selected cases, obviate the need for radiation therapy.[6,7] Clinical trials that evaluate chemotherapy with or without radiation therapy are ongoing. Information about ongoing clinical trials is available from the NCI (Http: //cancer.gov/clinical_trials/).

References:

  1. Rasheed BK, McLendon RE, Herndon JE, et al.: Alterations of the TP53 gene in human gliomas. Cancer Research 54(5): 1324-1330, 1994.
  2. Wisoff 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. Journal of Neurosurgery 89(1): 52-59, 1998.
  3. Woo SY, Donaldson SS, Cox RS: Astrocytoma in children: 14 years' experience at Stanford University Medical Center. Journal of Clinical Oncology 6(6): 1001-1007, 1988.
  4. Sposto 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. Journal of Neuro-Oncology 7(2): 165-177, 1989.
  5. Finlay 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. Journal of Clinical Oncology 14(9): 2495-2503, 1996.
  6. 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.
  7. Duffner PK, Krischer JP, Burger PC, et al.: Treatment of infants with malignant gliomas: the Pediatric Oncology Group experience. Journal of Neuro-Oncology 28(2-3): 245-256, 1996.

RECURRENT CHILDHOOD CEREBRAL ASTROCYTOMA

Recurrent low-grade cerebral astrocytoma

Recurrence may take place in both benign and malignant childhood cerebral astrocytomas and may develop many years after initial treatment.[1] Disease may recur at the primary tumor site or, especially in malignant tumors, 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 and, at times, for more benign lesions. 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 status of the child.

Patients with recurrent cerebral astrocytoma after maximal surgery and irradiation may benefit from chemotherapy. They should be considered for entry into trials of novel therapeutic approaches. Drug combinations, such as carboplatin and vincristine, may be useful at the time of recurrence for children with low-grade gliomas.[2]

Recurrent high-grade cerebral astrocytoma

Recurrence may occur in both benign and malignant childhood cerebral astrocytomas and may develop many years after initial treatment. Disease may recur at the primary tumor site or, especially in malignant tumors, 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 and, at times, for more benign lesions. 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 treatment fails may benefit from additional treatment, including high-dose chemotherapy with bone marrow rescue. They should be considered for entry into trials of novel therapeutic approaches.[3,4] Information about ongoing clinical trials is available from the NCI (Http: //cancer.gov/clinical_trials/).

References:

  1. Leibel SA, Sheline GE, Wara WM, et al.: The role of radiation therapy in the treatment of astrocytomas. Cancer 35(6): 1551-1557, 1975.
  2. Packer RJ, Lange B, Ater J, et al.: Carboplatin and vincristine for recurrent and newly diagnosed low-grade gliomas of childhood. Journal of Clinical Oncology 11(5): 850-856, 1993.
  3. Finlay 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. Journal of Clinical Oncology 14(9): 2495-2503, 1996.
  4. McCowage GB, Friedman HS, Moghrabi A, et al.: Activity of high-dose cyclophosphamide in the treatment of childhood malignant gliomas. Medical and Pediatric Oncology 30(2): 75-80, 1998.
Date Last Modified: 11/2002

This information from PDQ is reviewed regularly by members of the PDQ 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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