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Childhood brain stem glioma


Table of Contents

GENERAL INFORMATION
CELLULAR CLASSIFICATION
STAGE INFORMATION
TREATMENT OPTION OVERVIEW
UNTREATED CHILDHOOD BRAIN STEM GLIOMA
Diffuse intrinsic brain stem gliomas
Focal or low-grade brain stem gliomas
Neurofibromatosis
RECURRENT CHILDHOOD BRAIN STEM GLIOMA

GENERAL INFORMATION

This treatment information summary on childhood brain stem glioma 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 have been 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 occasionally invasive or high-grade)

2. medulloblastoma (primitive neuroectodermal tumor)

3. ependymoma

4. brain stem glioma (often diagnosed neuroradiographically without biopsy; may be high- or low-grade)

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. germinoma

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, glioblastomas multiforme (grade 3 or grade 4))

3. mixed glioma

4. oligodendroglioma

5. primitive neuroectodermal tumor (cerebral neuroblastoma)

6. ependymoma

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)

Important general concepts that should be understood by those caring for a child with 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 when 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 clinical trials when an appropriate study is available. Such clinical trials are being carried out by institutions and cooperative groups. In the United States, the two major cooperative groups are the Pediatric Oncology Group and the Childrens Cancer Group.

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 brain stem glioma.

For information on current clinical trials for children with brain tumors, consult the PDQ Protocol File.

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

Brain stem gliomas are classified according to the location, extent of spread, and histology. Brain stem gliomas may occur in the pons, the midbrain, the tectum, the cervicomedullary junction, or the dorsum as exophytic masses. The majority of childhood brain stem gliomas are diffuse, intrinsic tumors that involve the pons, often with contiguous involvement of other brain stem sites.[1-3] Another subset is the prognostically more favorable focal pilocytic astrocytomas. The latter apparently arise in the tectum of the midbrain, the surface of the pons, or the cervicomedullary junction.

Some childhood brain stem tumors are more focal, apparently arising in the tectum of the midbrain or cervicomedullary junction.[2-6] These local tumors tend to have a better prognosis.

Primary tumors of the brain stem are often diagnosed on neuroimaging studies and clinical findings. Histologic confirmation is usually unnecessary in diffuse, intrinsic tumors and is often not obtained. The majority of diffuse, intrinsic tumors are fibrillary or malignant gliomas. There is often a substantial amount of histologic variability in an individual tumor. Biopsy specimens of intrinsic brain stem gliomas may be misleading because of sampling error. New approaches with stereotactic needle biopsy may make biopsy safer. Biopsy is almost never indicated for diffuse intrinsic tumors involving the pons unless the diagnosis is in doubt. Biopsy may be indicated for brain stem tumors that are not diffuse and intrinsic when the tumor is progressive or when surgical debulking is possible. Surgical resections have been recommended for cervicomedullary tumors. Tectal and cervicomedullary gliomas tend to be low- grade astrocytomas, either pilocytic or fibrillary. Focal pilocytic astrocytomas of the brain stem may occasionally occur.

References:

  1. Cohen ME, Duffner PK, Heffner RR, et al.: Prognostic factors in brainstem gliomas. Neurology 36(5): 602-605, 1986.

  2. Albright AL, Guthkelch AN, Packer RJ, et al.: Prognostic factors in pediatric brain-stem gliomas. Journal of Neurosurgery 65(6): 751-755, 1986.

  3. Halperin EC, Wehn SM, Scott JW, et al.: Selection of a management strategy for pediatric brainstem tumors. Medical and Pediatric Oncology 17(2): 116-125, 1989.

  4. Epstein F, McCleary EL: Intrinsic brain-stem tumors of childhood: surgical indications. Journal of Neurosurgery 64(1): 11-15, 1986.

  5. Edwards MS, Wara WM, Ciricillo SF, et al.: Focal brain-stem astrocytomas causing symptoms of involvement of the facial nerve nucleus: long-term survival in six pediatric cases. Journal of Neurosurgery 80(1): 20-25, 1994.

  6. Pollack IF, Pang D, Albright AL, et al.: The long-term outcome in children with late-onset aqueductal stenosis resulting from benign intrinsic tectal tumors. Journal of Neurosurgery 80(4): 681-688, 1994.


STAGE INFORMATION

There is no generally applied staging system for childhood brain stem gliomas.[1,2] It is uncommon for these tumors to have spread outside the brain stem itself at the time of initial diagnosis. Diffuse intrinsic tumors of the brain stem are associated with a very low likelihood of long-term survival. The less common tumors of the midbrain, especially in the tectal plate region, have been viewed separately from those of the brain stem because they are more likely to be low grade and to have a greater likelihood of long-term survival (approximately 80% 5-year progression-free survival versus less than 20% for tumors of the pons and medulla).[1-6] Similarly, dorsally exophytic and cervicomedullary tumors may have a better prognosis than diffuse pontine gliomas. Spread of malignant brain stem tumors is usually contiguous; metastasis via the subarachnoid space has been reported in up to 30% of cases diagnosed antemortem.[7] Such dissemination may occur prior to local relapse but usually occurs simultaneously with or after local disease relapse.

References:

  1. Cohen ME, Duffner PK, Heffner RR, et al.: Prognostic factors in brainstem gliomas. Neurology 36(5): 602-605, 1986.

  2. Albright AL, Guthkelch AN, Packer RJ, et al.: Prognostic factors in pediatric brain-stem gliomas. Journal of Neurosurgery 65(6): 751-755, 1986.

  3. Halperin EC, Wehn SM, Scott JW, et al.: Selection of a management strategy for pediatric brainstem tumors. Medical and Pediatric Oncology 17(2): 116-125, 1989.

  4. Epstein F, McCleary EL: Intrinsic brain-stem tumors of childhood: surgical indications. Journal of Neurosurgery 64(1): 11-15, 1986.

  5. Edwards MS, Wara WM, Ciricillo SF, et al.: Focal brain-stem astrocytomas causing symptoms of involvement of the facial nerve nucleus: long-term survival in six pediatric cases. Journal of Neurosurgery 80(1): 20-25, 1994.

  6. Pollack IF, Pang D, Albright AL, et al.: The long-term outcome in children with late-onset aqueductal stenosis resulting from benign intrinsic tectal tumors. Journal of Neurosurgery 80(4): 681-688, 1994.

  7. Packer RJ, Allen J, Nielsen S, et al.: Brainstem glioma: clinical manifestations of meningeal gliomatosis. Annals of Neurology 14(2): 177-182, 1983.


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.[4,5] 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.

  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.


UNTREATED CHILDHOOD BRAIN STEM GLIOMA


Diffuse intrinsic brain stem gliomas

The usual treatment of children with diffuse, intrinsic brain stem glioma is radiation therapy to the involved area. A radiation dose of 5,500-6,000 cGy is conventionally used at dose fractions ranging between 150-200 cGy. Hyperfractionated (twice daily) radiation therapy techniques have been used to deliver a higher dose, and studies using doses as high as 7,800 cGy have been completed. There is no evidence that these increased radiation therapy doses improve the duration or rate of survival for patients with diffuse and/or primary pontine tumors.[1] Ongoing studies are evaluating the efficacy of various radiosensitizers as a means for enhancing the therapeutic effect of this modality.

The role of chemotherapy in the treatment of patients with newly diagnosed brain stem gliomas has not been well defined.[2] To date neither adjuvant or neoadjuvant chemotherapy nor immunotherapy when added to radiation therapy has been demonstrated to improve survival for children with diffuse intrinsic tumors. Studies using chemotherapy with radiation are ongoing. Children younger than 3 years of age with diffuse intrinsic tumors may benefit from chemotherapy to delay or modify radiation therapy.[3]


Focal or low-grade brain stem gliomas

Selected patients, primarily those with low-grade dorsally exophytic and focal tumors, may be treated surgically.[4] Patients with extensive resection may be observed prior to the initiation of further therapy, preferably as part of a prospective clinical study. See the PDQ protocol file for a listing of ongoing trials.

Patients with small tectal lesions and hydrocephalus but no other neurological deficits may be treated with cerebrospinal fluid diversion and have follow-up with sequential neuroradiographic studies until there is evidence of progressive disease.[4]


Neurofibromatosis

Children with neurofibromatosis type I and brain stem gliomas may have a different prognosis than other patients who have intrinsic lesions. Patients with neurofibromatosis may present with a long history of symptoms or be identified on screening tests; a period of observation may be indicated before instituting any treatment.[5] Brain stem gliomas in these children may be indolent and may require no specific treatment for years.[6]

References:

  1. Freeman CR, Krischer JP, Sanford RA, et al.: Final results of a study of escalating doses of hyperfractionated radiotherapy in brain stem tumors in children: a Pediatric Oncology Group study. International Journal of Radiation Oncology, Biology, Physics 27(2): 197-206, 1993.

  2. Jenkin RD, Boesel C, Ertel I, et al.: Brain-stem tumors in childhood: a prospective randomized trial of irradiation with and without adjuvant CCNU, VCR, and prednisone. A report of the Children's Cancer Study Group. Journal of Neurosurgery 66(2): 227-233, 1987.

  3. 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.

  4. Vandertop WP, Hoffman HJ, Drake JM, et al.: Focal midbrain tumors in children. Neurosurgery 31(2): 186-194, 1992.

  5. Bilaniuk LT, Molloy PT, Zimmerman RA, et al.: Neurofibromatosis type 1: brain stem tumours. Neuroradiology 39(9): 642-653, 1997.

  6. 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.


RECURRENT CHILDHOOD BRAIN STEM GLIOMA

Recurrence may occur in both benign and malignant childhood brain stem gliomas and may develop many years after initial treatment. Disease may occur 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 to determine the extent of the 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. This confirmation is usually not necessary in children with diffuse, intrinsic tumors. Other tests, such as positron-emission tomography plus single-photon emission computed tomography, have not yet been shown to be useful in distinguishing necrosis from tumor recurrence in brain stem gliomas. 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.

Chemotherapy with agents such as a carboplatin and vincristine may be effective in children with low-grade, recurrent exophytic gliomas.[1] Patients with recurrent diffuse, intrinsic brain stem glioma should be considered for entry into trials of novel therapeutic approaches because there are no "standard" agents that have demonstrated a high degree of activity.

References:

  1. 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.

Date Last Modified: 08/1999



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