Pediatric Astrocytoma Treatment & Management

  • Author: Tobey MacDonald, MD; Chief Editor: Max J Coppes, MD, PhD, MBA   more...
 
Updated: Feb 11, 2009
 

Medical Care

  • General
    • Treatment of astrocytomas depends on the location and grade of the tumor. Tumor location and associated morbidity may limit resection or render the tumor inoperable.
    • Patients who develop significant obstructive hydrocephaly that does not resolve may require the placement of a ventriculoperitoneal shunt.
  • Chemotherapy
    • Chemotherapy has had a limited role and limited success in the treatment of high-grade astrocytomas.
    • For low-grade astrocytomas that are inoperable because of location or have demonstrated early recurrence or progression, chemotherapy with carboplatin and vincristine has been successfully used in prepubertal children in an effort to avoid or delay irradiation. Other drug regimens may also be effective.
    • Chemotherapy has little impact on the overall survival of patients with high-grade tumors despite several regimens showing significant tumor response rates. To date, nitrosoureas (ie, bischloroethylnitrosourea [BCNU], cyclohexylchloroethylnitrosurea [CCNU]) and cisplatin show the most efficacy against these tumors. The most recent Children's Oncology Group (COG) study (CCG-9933) showed no benefit in survival for patients with residual postoperative high-grade astrocytomas receiving combinations of these agents in high-dose prior to irradiation.[1] The alkylating agent, temozolomide, shows promising results in recent clinical trials as adjuvant therapy with radiotherapy in some adults with high-grade gliomas,[2] especially those with tumors that have reduced activity of an enzyme (O6 -methylguanine-DNA-methyltransferase), which reverses alkylator-induced damage; pediatric studies have yet to show benefit.[3]
    • A completed COG trial suggests that a CCNU, thioguanine, and procarbazine regimen may be as effective.[1]
    • Admit for treatment those patients with high-grade astrocytomas who are eligible for available investigational chemotherapy. Investigational chemotherapy for low-grade tumors is currently administered in an outpatient setting.
  • Low-grade astrocytoma
    • Surgical resection is the primary treatment modality. If feasible, a complete resection is the goal of surgery in order to minimize the risk of local recurrence. However, long-term progression-free intervals may ensue even after partial resection. Low-grade tumors that recur or progress may be re-resected, and patients can undergo observation without further treatment if the risk of neurologic impairment from further growth is low and the tumor has undergone a significant interim period of dormancy.
    • Low-grade tumors that (1) are inoperable (diencephalic, brain stem), (2) are partially resected and posing a high risk of neurologic impairment if allowed to regrow, or (3) demonstrate early progression or recurrence may be treated with local radiotherapy to the area of the tumor plus a 2-cm margin. Radiotherapy is relatively contraindicated in children with neurofibromatosis type 1 (NF1) due to risks of radiation-induced secondary high-grade brain tumors, mutagenesis and intracranial vasculopathy. Alternatively, chemotherapy may be used in young children (prepubertal) in whom the clinician wishes to avoid or to delay radiotherapy because of its potential neurologic sequelae in this age group. To date, the most active chemotherapy regimen for these tumors is carboplatin and vincristine. These agents show objective response rates of 50-80% and produce prolonged stable disease. A COG trial suggests that a CCNU, thioguanine, and procarbazine regimen may be as effective.[1]
  • High-grade astrocytoma
    • Following surgical resection, patients are treated with local irradiation to 50-60 Gy with a 2-cm to 4-cm margin around the area of edema defined by imaging.
    • The addition of single-agent or multiple-agent chemotherapy preradiotherapy and postradiotherapy has little or no impact on the overall survival rate (0-30%) in this group of patients, despite of producing response rates as high as 45%. The most recent COG trial is investigating the benefit of irradiation and concurrent temozolomide postoperatively.
    • Biologic therapy targeting (molecular markers) in pediatric high-grade astrocytomas, such as tyrosine kinase inhibitors that inhibit epidermal growth factor receptor (EGFR), are also being investigated.
    • Adult trials have shown the benefit of bevacizumab and irinotecan in those with recurrent disease; studies are underway in children.
    • In infants with varying types of malignant brain tumors in whom irradiation is withheld, promising results have been reported with the use of high-dose chemotherapy, although patients with a histologic diagnosis of malignant astrocytoma make up only a small fraction of this group.
  • Astrocytoma of the brain stem
    • Surgery has no role in those patients with diffuse pontine lesions (eg, malignant brainstem glioma), the most common brainstem tumor. Surgery is feasible for many patients with exophytic and cystic tumors, and extensive resection may prolong survival even without further treatment. However, a surgical approach to focal midbrain, medulla, and tectal plate regions is hazardous and resections are generally limited.
    • Local radiotherapy to 54 Gy is used for patients with inoperable tumors and for those who have high-grade lesions or early recurrence/progression of low-grade tumors. Radiotherapy for diffuse pontine lesions and high-grade tumors usually results in early and significant neurologic improvement, although the overall outlook remains dismal.
    • Despite ongoing clinical trials, a chemotherapeutic role in the management of patients with brainstem tumors has yet to be established.
    • Trials are underway using radiosensitizing chemotherapy and biologic therapy, concurrent with radiotherapy, in attempts to improve survival.
  • Astrocytoma of the visual pathway
    • The natural history of visual pathway astrocytomas is erratic. Some patients experience long-term stabilization without treatment, whereas others develop progressive disease with neurologic deterioration culminating in death. This is especially true for children with neurofibromatosis. In contrast to those with chiasmatic lesions, patients with isolated optic nerve tumors rarely die of their disease; therefore, treatment efficacy must be based on visual outcome and freedom from treatment sequelae.
    • A period of observation without treatment is recommended in cases without severe proptosis, rapidly progressive visual decline, or extensive chiasmal tumors (with distortion or invasion of optic tracts, hypothalamus, or the third ventricular area).
    • Surgery is warranted only in those with chiasmatic or deeper intracranial involvement in order to rule out the possibility of an uncommon high-grade lesion. For these patients and for those with an isolated optic nerve tumor whose clinical characteristics do not meet the criteria above, the preferred treatment is local radiotherapy to 55 Gy. With radiotherapy, as many as 90% of patients show at least stabilization of visual decline and 10-year progression-free survival rates of 70-90%.
    • Chemotherapy with carboplatin and vincristine may be used as an initial therapy or to delay irradiation in prepubertal children. This combination chemotherapy has produced complete or partial responses in 45% of newly diagnosed patients. Other regimens may also be effective.
  • Intramedullary spinal cord astrocytomas
    • Complete surgical resections are difficult in astrocytomas because a distinct tumor-cord interface is often absent; however, nearly 80-90% of resections may be performed in most cases.
    • Treatment with radiotherapy is the same as that for other CNS astrocytomas. Lower radiation doses to 50 Gy are used because of radiation intolerance of the spinal cord. Treatment of low-grade tumors with radiotherapy yields 5-year survival rates of 65-70%. Patients with high-grade tumors generally die of their disease within months of diagnosis despite radiation and chemotherapy.
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Consultations

  • Radiation oncologist for high-grade, recurrent and/or progressive, or visual pathway tumors
  • Neuroendocrinologist evaluation
  • Occupational and/or physical therapist for rehabilitation
  • Regular team members, including the following:
    • Neurosurgeon
    • Pediatric oncologist
    • Neuro-oncologist
    • Neurologist
    • Neuropsychologist
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Diet

  • No specific dietary requirements or restrictions are indicated.
  • Patients who develop severe anorexia or weight loss as a result of therapy (particularly infants) may need supplemental nutrition to maintain daily requirements.
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Activity

  • No restrictions in activity are indicated unless dictated by underlying neurological deficits.
  • Patients with ventriculoperitoneal shunts may be restricted from high-impact sports, such as diving.
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Contributor Information and Disclosures
Author

Tobey MacDonald, MD  Clinical Director of Neuro-Oncology, Children's Hospital National Medical Center; Associate Professor, Department of Pediatric Hematology-Oncology, George Washington University

Tobey MacDonald, MD is a member of the following medical societies: American Association for Cancer Research, Children's Oncology Group, Pediatric Brain Tumor Consortium, and Society for Neuro-Oncology

Disclosure: Nothing to disclose.

Coauthor(s)

Roger J Packer, MD  Senior Vice President, Neuroscience and Behavioral Medicine, Director, Brain Tumor Institute, Children's National Medical CenterProfessor of Neurology and Pediatrics, The George Washington University

Roger J Packer, MD is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Pediatric Society, Child Neurology Society, Children's Oncology Group, Neurofibromatosis Clinical Trials Consortium, Pediatric Brain Tumor Consortium, and Society for Neuro-Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Samuel Gross, MD  Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University

Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Timothy P Cripe, MD, PhD  Professor of Pediatrics, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center; Clinical Director, Musculoskeletal Tumor Program, Co-Medical Director, Office for Clinical and Translational Research, Cincinnati Children's Hospital Medical Center; Director of Pilot and Collaborative Clinical and Translational Studies Core, Center for Clinical and Translational Science and Training, University of Cincinnati College of Medicine

Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA  Senior Vice President, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

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This MRI shows a juvenile pilocytic astrocytoma of the cerebellum.
This MRI shows a supratentorial glioblastoma multiforme.
This section displays the typical biphasic pattern of a juvenile pilocytic astrocytoma, consisting of dense, relatively anuclear, fibrillar areas alternating with looser cystic fields.
This section displays the high cellularity, mitosis, and nuclear atypia characteristic of an anaplastic astrocytoma (grade III).
This section displays a typical field of a glioblastoma multiforme (grade IV) with pseudopalisading neovascularity, nuclear atypia, numerous mitoses, and areas of hemorrhage.
 
 
 
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