Childhood Brain Stem Glioma Treatment (PDQ®): Treatment - Health Professional Information [NCI]
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Childhood Brain Stem Glioma Treatment
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 brain stem gliomas. 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.
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric and Adult Treatment Editorial Boards use a formal evidence ranking system in developing their level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either "standard" or "under clinical evaluation." These classifications 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 summary on Late Effects of Treatment for Childhood Cancer 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 summary Childhood Brain and Spinal Cord Tumors Treatment Overview for information about the general classification of childhood brain and spinal cord tumors.
Brain stem gliomas are classified according to their location, radiographic appearance, and histology (when obtained). Brain stem gliomas may occur in the pons, the midbrain, the tectum, the dorsum of the medulla at the cervicomedullary junction, or in multiple regions of the brain stem. The tumor may contiguously involve the cerebellar peduncles, cerebellum, and/or thalamus. The majority of childhood brain stem gliomas are diffuse, intrinsic tumors that involve the pons (diffuse intrinsic pontine gliomas [DIPG]), often with contiguous involvement of other brain stem sites.[1,2,3,4] The prognosis is poor for these tumors. A prognostically more favorable subset of tumors are focal pilocytic astrocytomas. These most frequently arise in the tectum of the midbrain, focally, within the pons, or at the cervicomedullary junction, and have a far better prognosis than diffuse intrinsic tumors.[2,3,5,6,7]
Primary tumors of the brain stem are most often diagnosed based on clinical findings and on neuroimaging studies, and there is a substantial amount of histologic variability within an individual tumor. DIPGs are generally fibrillary astrocytomas. However, histologic confirmation is usually unnecessary. Biopsy specimens of intrinsic brain stem gliomas may be misleading because of sampling error. Biopsy or resection may be indicated for brain stem tumors that are not diffuse and intrinsic. New approaches with stereotactic needle biopsy may make biopsy safer.
There is no generally applied staging system for childhood brain stem gliomas.[1,2,3] It is uncommon for these tumors to have spread outside the brain stem itself at the time of initial diagnosis. 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.
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 have a greater likelihood of long-term survival (approximately 80% 5-year progression-free survival vs. less than 20% for tumors of the pons and medulla).[1,2,3,5,6,7,8,9] Similarly, dorsally exophytic and cervicomedullary tumors are generally low grade and have a relatively favorable prognosis. Children younger than 3 years may have a more favorable prognosis, perhaps reflecting different biologic characteristics.
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 (including three-dimensional conformal 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.[1,2,3] 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.
Untreated Childhood Brain Stem Glioma
Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)
Diffuse Intrinsic Pontine Gliomas
Conventional treatment for children with diffuse intrinsic pontine glioma (DIPG) is radiation therapy to involved areas. Such treatment will result in transient benefit for most patients, but over 90% of patients will die within 18 months of diagnosis. The conventional dose of radiation therapy ranges between 54 Gy and 60 Gy given locally to the primary tumor site in single daily fractions.
Hyperfractionated (twice daily) radiation therapy techniques have been used to deliver a higher dose, and studies using doses as high as 78 Gy have been completed. Evidence demonstrates that these increased radiation therapy doses do not improve the duration or rate of survival for patients with DIPG whether given alone,[1,2] or in combination with chemotherapy. Studies evaluating the efficacy of various radiosensitizers as a means for enhancing the therapeutic effect of this modality are under study but to date have failed to show significant improvement in outcome.[2,3,4,5,6]
The utility of chemotherapy in the treatment of patients with newly diagnosed DIPG is unproven.[2,3,5,6,7,8,9,10,11][Level of evidence: 2A] To date, neither adjuvant or neoadjuvant chemotherapy, nor immunotherapy when added to radiation therapy has been demonstrated to improve survival for children with DIPG. Similarly, studies utilizing high-dose therapy with stem cell rescue have been ineffective in extending survival. Studies using new anticancer agents with alternative mechanisms of actions and brain stem radiation are ongoing.
Treatment options under clinical evaluation
- The Children's Oncology Group (COG) trial (COG-ACNS0222) is a phase II study of motexafin, gadolinium, and concomitant radiation therapy.
- The Pediatric Brain Tumor Consortium (PBTC) is conducting a phase I study of capecitabine and concomitant radiation therapy (PBTC-021). It is planned that this study will become a phase II trial once the phase I portion of the trial is complete.
Focal or Low-grade Brain Stem Gliomas
In general, maximal surgical resection should be attempted.[13,14] Patients with residual tumors may be candidates for additional therapy including radiation or adjuvant therapy including three-dimensional conformal approaches. Information about ongoing clinical trials is available from the NCI Web site.
Patients with small tectal lesions and hydrocephalus but no other neurological deficits may be treated with cerebrospinal fluid diversion alone and have follow-up with sequential neuroradiographic studies unless 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.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with untreated childhood brain stem glioma. 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.
Recurrent Childhood Brain Stem Glioma
Diffuse Intrinsic Pontine Gliomas
Given the dismal prognosis for patients with diffuse intrinsic pontine glioma, progression of the pontine lesion is anticipated generally within 1 year from initial radiation therapy. In most cases, biopsy at the time of clinical or radiologic progression is neither necessary nor recommended. To date, no salvage regimen has been shown to extend survival. Patients should be considered for entry into trials of novel therapeutic approaches because there are no standard agents that have demonstrated a clinically significant activity. Concomitant palliative care should be provided for these patients whether or not disease-directed therapy is administered.
Focal or low-grade brain stem gliomas
At the time of recurrence, a complete evaluation to determine the extent of the relapse may be indicated for selected low-grade lesions. Biopsy or surgical resection should be considered for confirmation of relapse when other entities such as secondary tumor and treatment-related brain necrosis, which may be clinically indistinguishable from tumor recurrence, are in the differential. Other tests, such as positron-emission tomography and single-photon emission computed tomography, have not yet been shown to be reliable in distinguishing necrosis from tumor recurrence in brain stem gliomas.
Treatment considerations at the time of recurrence or progression are dependent on prior treatment. Considerations include: further surgical resection, irradiation including three-dimensional conformal approaches, or chemotherapy. The need for surgical intervention must be individualized on the basis of the initial tumor type, the location within the brain stem, the length of time between initial treatment and the appearance of the mass lesion, and the clinical picture.
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 brain stem glioma. 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.
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Changes to This Summary (08 / 03 / 2009)
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.
Added text to state that children younger than 3 years may have a more favorable prognosis, perhaps reflecting different biologic characteristics (cited Broniscer et al. as reference 10).
- PDQ® - NCI's Comprehensive Cancer Database.
Full description of the NCI PDQ database.
ADDITIONAL PDQ SUMMARIES
- PDQ® Cancer Information Summaries: Adult Treatment
Treatment options for adult cancers.
- PDQ® Cancer Information Summaries: Pediatric Treatment
Treatment 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).
Date Last Modified: 2009-08-03