PDQ® Treatment Health Professionals
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:
2. medulloblastoma (primitive neuroectodermal tumor)
4. brain stem glioma (often diagnosed neuroradiographically without biopsy; may be high- or low-grade)
2. diencephalic (chiasm, hypothalamic, and/or thalamic) gliomas generally of low grade
2. high-grade or malignant astrocytoma (anaplastic astrocytoma, glioblastomas multiforme (grade 3 or grade 4))
3. mixed glioma
5. primitive neuroectodermal tumor (cerebral neuroblastoma)
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)
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.
For information on current clinical trials for children with brain tumors, consult the PDQ Protocol File.
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.
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.
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. Such dissemination may occur prior to local relapse but usually occurs simultaneously with or after local disease relapse.
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.
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. 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. 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.
Selected patients, primarily those with low-grade dorsally exophytic and focal tumors, may be treated surgically. 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.
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. Brain stem gliomas in these children may be indolent and may require no specific treatment for years.
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. 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.
Date Last Modified: 08/1999