Pediatric Astrocytoma 

Updated: Aug 18, 2017
Author: Lauren R Weintraub, MD; Chief Editor: Max J Coppes, MD, PhD, MBA 

Overview

Background

Brain tumors comprise approximately 20% of all childhood malignancies, second only to acute lymphoblastic leukemia in frequency. Astrocytoma is the most common brain tumor (see image shown below), accounting for more than half of all primary CNS malignancies.

This MRI shows a pilocytic astrocytoma of the cere This MRI shows a pilocytic astrocytoma of the cerebellum.

 

Astrocytomas comprise a wide range of neoplasms that differ in their extent of invasiveness, morphological features, tendency for progression, and clinical course. The most widely accepted grading schema for astrocytomas is the World Health Organization [WHO] that assigns a grade from I to IV based on the degree of anaplasia of tumor cells, proliferation index values and genetic alterations. WHO grade I tumors include pilocytic astrocytomas and subependymal giant cell astrocytomas. WHO grade II tumors include diffuse astrocytomas, oligodendrogliomas and pleomorphic xanthoastrocytomas. WHO grade III tumors include anaplastic astrocytomas and anaplastic pleomorphic xanthoastrocytomas. WHO grade IV tumors include glioblastoma multiforme and diffuse midline gliomas.[1]

Most astrocytomas are indolent low-grade (ie, WHO grade I-II) tumors for which surgical resection alone is sufficient to cure.  The prognosis decreases for low-grade tumors in unresectable locations and remains very poor for high-grade astrocytomas in spite of the addition of radiotherapy and chemotherapy.

Pathophysiology

Pilocytic astrocytomas (ie, WHO grade I) arise throughout the neuraxis, but preferred sites include the optic nerve, optic chiasm/hypothalamus, thalamus and basal ganglia, cerebral hemispheres, cerebellum, and brain stem. These tumors show low cellularity, low proliferative and mitotic activity, and rarely metastasize or undergo malignant transformation. In general, they do not aggressively infiltrate surrounding tissue and regressive changes in long-standing lesions are common. These tumors are the principle CNS neoplasm of neurofibromatosis type 1 (NF1).  

Pilomyxoid astrocytoma (PMA) is a recently defined variant of pediatric low-grade astrocytoma. PMAs have been classified with pilocytic astrocytomas but have been found to have different histologic features and to behave more aggressively than pilocytic astrocytomas. PMAs have a tendency to disseminate and, in some reports, have a worse prognosis compared with pilocytic astrocytomas.

Diffuse astrocytomas (ie, WHO grade II) may arise in any area of the CNS but most commonly develop in the cerebrum, particularly the frontal and temporal lobes. The brain stem and spinal cord are the next most frequently affected sites, whereas the cerebellum is a distinctly uncommon site. These tumors are moderately cellular, infiltrative, and often enlarging, which distorts but does not destroy neighboring anatomical structures. Mitotic activity is generally absent. 

Anaplastic astrocytoma (ie, WHO grade III) arises in the same locations as diffuse astrocytomas, with a preference for the cerebral hemispheres. These tumors show increased cellularity, distinct nuclear atypia, marked mitotic activity, and a tendency to infiltrate through neighboring tissue. 

Glioblastoma multiforme (ie, WHO grade IV) tumors occur most often in the subcortical white matter of the cerebral hemispheres. Combined frontotemporal location with infiltration into the adjacent cortex, basal ganglia, and contralateral hemisphere is typical. Glioblastoma is the most frequent tumor of the brain stem in children, while the cerebellum and spinal cord are rare sites. These tumors are highly cellular, with high proliferative and mitotic activity. Although rapid and extensive invasion of surrounding tissue is common, distant metastasis within or outside the CNS is rare. Refer to the image below.

This section displays a typical field of a gliobla This section displays a typical field of a glioblastoma multiforme (grade IV) with pseudopalisading neovascularity, nuclear atypia, numerous mitoses, and areas of hemorrhage.

Increasing evidence indicates that the differences between the clinicopathologic entities of astrocytomas (ie, WHO grades I-IV) reflect specific genetic alterations.[2, 3]  Recent studies show that the majority of pilocytic astrocytomas possess a characteristic BRAF–KIAA1549 gene fusion.[4, 5]   Additional mutations found in low-grade gliomas include BRAFV600E and NF1. Mutations in TP53, EGFR, H3K27M, PDGFRA and PTEN are found in high-grade astrocytomas (WHO grade III and IV).  

Epidemiology

Frequency

United States

Astrocytoma is the most common brain tumor of childhood. Researchers report that the annual incidence is approximately 14 new cases per million children younger than 15 years.

Mortality/Morbidity

In low-grade astrocytomas, complete surgical resection is associated with 5-year survival rates as high as 95-100% without further treatment. Patients with subtotal resections may have only a 60-80% survival rate over similar periods; however, after partial resection, long-term progression-free intervals may ensue. Current operative mortality rates are less than 1%. Morbidity depends largely on tumor location and is highest in diencephalic tumors, in which the incidence of hemiparesis or visual field deficits may be 10-20%. Cortical-based tumors may be associated with seizures.

In high-grade astrocytomas, the most recent 5-year survival rate is 15-30% for supratentorial lesions and less than 10% for pontine tumors. Neurologic morbidity, such as neurocognitive impairment, neuroendocrinologic deficiency, motor and coordination impairment, and cranial nerve dysfunction may occur from tumor invasion, surgical resection, and/or treatment with radiation and chemotherapy. Seizure disorders may develop depending on the tumor location.

Race

No specific racial predisposition is observed.

Sex

The male-to-female ratio is approximately 1:1, except for supratentorial low-grade gliomas, in which it is approximately 2:1.

Age

Most cases occur in the first decade of life, with the peak incidence occurring in children aged 5-9 years. High-grade supratentorial tumors occur slightly later, with a median age at diagnosis of 9-10 years.

 

Presentation

History

Patients often report a history of illness for more than 3 months prior to diagnosis.

  • Increased intracranial pressure

    • Initial symptoms are usually nonspecific, nonlocalizing, and related to increased intracranial pressure (ICP). These signs occur in as many as 75% of patients regardless of tumor location.

    • The classic triad of a raised ICP consists of morning headaches, vomiting, and lethargy. The headache is characterized by pain upon arising that is relieved by vomiting and lessens during the day.

    • School-aged children more commonly report vague intermittent headaches and fatigue. They may have a declining academic performance and may exhibit personality changes.

    • Infants may present with irritability, anorexia, developmental delay, or regression.

    • Leroy et al conducted a retrospective study to determine whether severe anorexia might be a harbinger of low-grade astrocytomas of the fourth ventricle in pediatric patients.[6] Their review included 34 patients (16 boys, 18 girls; mean age, 8 years) who underwent surgical treatment of low-grade astrocytoma between 1991 and 2012. Of the study cohort, 31 patients had pilocytic astrocytoma, and 3 had diffuse astrocytoma. Seven of the patients presented with notable anorexia; the average body mass index (BMI) in this group was ≤2 standard deviation (SD). Twenty-seven of the patients had no anorexia; the average BMI in this group was +1 SD. There were no significant differences in these groups with regard to hydrocephalus or tumor location. For all the children with anorexia, BMI improved markedly during the postoperative follow-up period, which lasted on average 6 years. The investigators concluded that unexplained or atypical anorexia, in association with negative etiologic assessment, should prompt cerebral imaging. They indicated that clinical improvement after surgical resection could suggest a possible interaction between tumor tissue and appetite-suppressing peptide secretion.[6]

  • Seizures: Seizures are present at diagnosis in at least 25% of patients with supratentorial astrocytomas. They may precede diagnosis by several months to 1-2 years.

  • Signs related to tumor location

    • Focal motor deficits occur in as many as 60% of patients with hemispheric and central diencephalic tumors. They are more common in individuals with high-grade gliomas.

    • Seizures occur in 30-50% of children, may be focal, and are a more common presenting finding in low-grade gliomas.

    • Hypothalamic tumors may be associated with neuroendocrine abnormalities, growth hormone deficiency, diabetes insipidus, and precocious pubertal development. These tumors may also impinge on the optic chiasm, resulting in optic atrophy and visual deficits.

    • Patients with diencephalic tumors may present with the classic diencephalic syndrome (ie, emesis, emaciation, unusual euphoria), but the syndrome is rare in children older than 3 years.

    • Patients with astrocytomas of the cerebellum may present with weakness, dysmetria, tremor, and ataxia.

    • Astrocytomas of the brain stem are characterized by the presence of isolated cranial nerve deficits and contralateral hemiparesis.

    • Astrocytomas of the visual pathways may be brought to medical attention because of strabismus, proptosis, nystagmus, or developmental delay. Young children rarely report the slow and progressive visual loss characteristic of these tumors. Infants frequently display head tilt, head bobbing, and nystagmus. Astrocytomas in children with neurofibromatosis type 1 (NF1) may be asymptomatic at the time of diagnosis and may be detected on screening studies.

    • Patients with astrocytomas of the spinal cord most frequently present with pain (70% of patients have pain localized to the vertebral segments adjacent to the tumor), weakness, gait disturbance, and sphincter dysfunction. Paresthesias and loss of sensation occur later in the disease course.

Physical

See the list below:

  • Increased intracranial pressure

    • A funduscopic examination reveals papilledema. Infants may have only optic pallor.

    • Palsy of cranial nerve VI is common and results in the inability to abduct one or both eyes.

    • Infants may demonstrate the setting sun sign, observed as an impaired upgaze and a forced downward deviation of both eyes. Measurement of head circumference in infants with open sutures may reveal macrocephaly.

  • Other signs

    • Strength and motor testing may reveal weakness and monoplegia or hemiplegia.

    • Localized deficits in truncal steadiness, upper extremity coordination, and gait may be observed with tumors of the posterior fossa and basal ganglia.

    • Multiple and bilateral cranial nerve deficits, especially VI and VII; long tract signs; and ataxia are associated with brainstem tumors.

    • Visual acuity is frequently reduced to less than 20/200 with optic gliomas. The pattern of visual loss in those patients with intraorbital tumors is most commonly a decrease in central vision, whereas bitemporal hemianopsia is most often noted in those patients with chiasmatic tumors. The involved eye generally shows optic pallor and nystagmus. Mild proptosis is usually present with primary intraorbital tumors.

    • Spinal astrocytomas often cause weaknesses of a variable extent and severity, ranging from monoparesis to quadriparesis. Pain along the involved vertebral segment may occur when the patient sneezes or coughs. Papilledema and hydrocephaly are present in 15% of patients and are attributed to increased cerebrospinal fluid (CSF) viscosity from an elevated protein content.

Causes

See the list below:

  • Epidemiologic studies investigating parental occupational exposure, environmental exposure, and maternal nutritional intake failed to identify linkages with any of the childhood brain tumors.

  • An association with NF1 is present in 50-80% of patients with isolated optic nerve astrocytomas and in as many as 20% of those with chiasmal or deeper optic tract tumors. NF1 and tuberous sclerosis are also associated with other low-grade astrocytomas. Twenty percent of children with NF1 have low-grade gliomas, especially visual pathway tumors.

  • Astrocytoma is the most frequent CNS tumor in people with the Li-Fraumeni syndrome (germline mutation of the p53 tumor suppressor gene on the short arm of chromosome 17).

  • Ionizing radiation to the head for prior malignancies causes secondary supratentorial malignant astrocytomas in a small number of patients.

 

DDx

 

Workup

Imaging Studies

The following studies are indicated in patients with suspected astrocytoma:

  • Head CT imaging with and without contrast

    • CT imaging has higher than 95% sensitivity for the detection of brain tumors.

    • On CT scans, most supratentorial low-grade astrocytomas are hypodense with variable contrast enhancement. Calcifications may be present. High-grade tumors show a more heterogeneous density pattern and a more diffuse contrast enhancement.

    • Patients with cerebellar astrocytomas may demonstrate hydrocephalus and contrast enhancement on CT scans. A prominent cystic component is often present.

    • Brainstem astrocytomas typically enhance poorly after contrast and lack calcifications on CT scans. They may appear isodense or hypodense.

  • Head and spine MRI with and without gadolinium

    • MRI is the imaging modality of choice for brainstem astrocytomas. See the images shown below.

      This MRI shows a pilocytic astrocytoma of the cere This MRI shows a pilocytic astrocytoma of the cerebellum.
      This MRI shows a supratentorial glioblastoma multi This MRI shows a supratentorial glioblastoma multiforme.
    • MRI of the head must be performed in all patients with CT scan or clinical findings consistent with astrocytoma. Other tumors, such as medulloblastoma and ependymoma, may have a similar appearance on CT scans. MRI is useful in such instances by better demonstrating the anatomic origin and extent of tumor.

    • MRI is the imaging modality of choice for detecting primary or disseminated spinal cord lesions. Perform an MRI of the spine in all tumors with malignant characteristics.

    • A postoperative MRI is required to measure the extent of surgical resection and the detection of residual disease. Postoperative MRI evaluation must be performed within 72 hours of surgery in order to delineate residual tumor from the postsurgical inflammatory changes that are visualized on MRI at this time.

Procedures

See the list below:

  • CSF cytological examination: This examination is useful in malignant astrocytomas for the detection of microscopic leptomeningeal dissemination.

  • Lumbar puncture: CT imaging or MRI must be performed prior to the lumbar puncture (LP) to rule out the presence of hydrocephaly in those patients suspected of having a brain tumor. Hydrocephaly places the patient at risk for herniation as a consequence of the procedure. In general, the LP is deferred as long as 2 weeks postoperatively in order to avoid identifying tumor cells that may have disseminated as a result of surgery.

Histologic Findings

See the list below:

  • Childhood astrocytomas represent different histopathologic entities, such as pure astrocytoma (commonly pilocytic and fibrillary type in children), oligodendroglioma, and mixed tumors of both cell types. Astrocytomas are composed of glial fibrillary acidic protein (GFAP)–positive bipolar or stellate cells. Oligodendrogliomas are characterized by monotonous collections of spheroidal cells. The classification of gliomas is based primarily on their degree of anaplasia, rather than on histologic type.

  • Tumors that are modestly cellular and contain few or none of the histologic criteria of malignancy are designated low-grade or grade I and II lesions, according to the WHO. Unifying features are their slowly evolving nonaggressive clinical behavior and relatively benign histological appearance.

  • Grade I is primarily designated for the typical pilocytic astrocytoma (see image below), accounting for 85% of cerebellar low-grade gliomas.[7] It is composed of astrocytes interwoven with a fine fibrillary background and often has a characteristic microcystic component and Rosenthal fibers. The newly described pilomyxoid variant of low-grade astrocytoma has unusual histologic features, including abundance of myxoid background, the absence of Rosenthal fibers, and the presence of an angiocentric pattern. Whether or not this is a variant of pilocytic astrocytoma or a distinct entity remains unclear. Grade II is reserved for diffuse astrocytomas composed of moderately cellular astrocytes, oligodendrocytes, or both.

    This section displays the typical biphasic pattern This section displays the typical biphasic pattern of a pilocytic astrocytoma, consisting of dense, relatively anuclear, fibrillar areas alternating with looser cystic fields.
  • High-grade tumors are characterized by the presence of several histologic features of malignancy that include hypercellularity, cytologic and nuclear atypia, mitoses, necrosis, and endothelial proliferation (see top image below). These tumors are clinically aggressive, regionally invasive, and capable of neuraxial dissemination. Grade III refers to anaplastic astrocytoma (see top image below) and grade IV is designated for glioblastoma multiforme (see bottom image below).

    This section displays the high cellularity, mitosi 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 gliobla This section displays a typical field of a glioblastoma multiforme (grade IV) with pseudopalisading neovascularity, nuclear atypia, numerous mitoses, and areas of hemorrhage.
  • The most common lesions of the brain stem are diffuse midline gliomas (80%), previously referred to as diffuse intrinsic pontine gliomas (DIPGs), and characterized by an H3K27M mutation and carry an extremely poor prognosis.[8] Exophytic tumors arising from the brain stem are more likely to be low-grade.

See Brain Cancer Staging for summarized information.

 

Treatment

Medical Care

See the list below:

  • 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 hydrocephalus 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.  Although there is no standard chemotherapy, the most commonly used regimen consists of temozolomide given concurrently with radiation therapy followed by maintenance temozolomide and bevacizumab.  Investigational therapies include dendritic cell vaccines and immune checkpoint inhibitors.[9, 10]

    • 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 an effort to avoid or delay irradiation. Other drug regimens may also be effective.

  • 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 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.

  • 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%. 

    • Biologic therapy targeting molecular markers in pediatric high-grade astrocytomas, such as tyrosine kinase inhibitors that inhibit epidermal growth factor receptor (EGFR), dendritic cell vaccines and immune checkpoint inhibitors are also being investigated.

  • Astrocytoma of the brain stem

    • Surgery has no role in those patients with diffuse brainstem gliomas. 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. 

    • Chemotherapy with carboplatin and vincristine is typically used as an initial therapy to avoid or delay irradiation in children. This combination chemotherapy has produced responses in the majority of newly diagnosed patients. Other regimens may also be effective.[11]

  • 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.

See Brain Cancer Treatment Protocols for summarized information.

Consultations

See the list below:

  • 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

Diet

See the list below:

  • 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.

Activity

See the list below:

  • 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.

 

Medication

Antineoplastic agents

Class Summary

These agents disrupt DNA replication, which inhibits tumor growth and promotes tumor cell death. Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. After cells divide, they enter a period of growth (phase G1), followed by DNA synthesis (phase S). The next phase is a premitotic phase (G2), then finally a mitotic cell division (phase M).

The cell division rate varies for different tumors. Most common cancers increase very slowly in size compared to normal tissues, and the rate may decrease further in large tumors. This difference allows normal cells to recover from chemotherapy more quickly than malignant ones and is the rationale behind current cyclic dosage schedules.

Antineoplastic agents interfere with cell reproduction. Some agents are cell cycle specific, while others (eg, alkylating agents, anthracyclines, cisplatin) are not phase-specific. Cellular apoptosis (ie, programmed cell death) is also a potential mechanism of many antineoplastic agents.

Temozolomide (Temodar)

Prodrug that is hydrolyzed to MTIC at physiologic pH. Exerts its effect by site-specific DNA cross-linking resulting from the methylation guanine at the O6 and N7 positions. Bioavailability is 100%; approximately 35% crosses the blood-brain barrier.

Carboplatin (Paraplatin)

Analog of cisplatin. This is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA crosslinks and inhibition of DNA replication.

Vincristine (Oncovin)

Plant-derived vinca alkaloid. Acts as a mitotic inhibitor by binding tubulin.

Monoclonal antibody

Bevacizumab

Recombinant humanized monoclonal antibody to VEGF; blocks the angiogenic molecule VEGF thereby inhibiting tumor angiogenesis, starving tumor of blood and nutrients.

 

Follow-up

Further Outpatient Care

See the list below:

  • Chemotherapy: Chemotherapy for low-grade astrocytomas is currently administered in an outpatient setting for approximately 1 year.

  • Radiotherapy: Begin daily outpatient local radiotherapy after recovery from surgery for a high-grade astrocytoma or early recurrent and/or progressive low-grade astrocytoma. This is generally administered over 6 weeks (usual dose is 160-180 Gy/d).

  • Physical and neurologic examination

    • For resected low-grade astrocytomas, outpatient examinations every 1-3 months are sufficient.

    • For patients requiring radiotherapy, perform weekly monitoring of clinical response and potential treatment-related adverse effects during radiotherapy and then every 1-3 months thereafter for at least 1 year.

    • Protocols using investigational chemotherapy in place of, or following, radiotherapy dictate how frequently these examinations are conducted.

    • After 12-18 months from completion of therapy, these examinations are generally reduced to every 6 months for the next 2 years and annually thereafter, provided no interim complications occur.

    • Routinely perform baseline neuropsychology and developmental testing at the completion of therapy and annually thereafter.

  • Imaging studies

    • Postoperative MRI evaluation must be performed within 72 hours of surgery in order to delineate residual tumor from the postsurgical inflammatory changes that are visualized on MRI at this time.

    • MRI with contrast of the head should be performed every 3 months for the first 12-18 months after surgery and 4-6 weeks following the completion of radiotherapy. Subsequent imaging may be performed in conjunction with the physical and neurologic examination schedule, unless clinically indicated sooner. If a child is treated on an investigational clinical trial regimen, the protocol dictates the frequency of the imaging studies required.

    • Perform MRI of the spine annually in those patients with high-grade tumors unless evidence of leptomeningeal spread is noted at diagnosis, in which case the frequency of such examination is increased in accordance with the response to treatment.

  • Laboratory studies

    • Weekly CBC counts and annual neuroendocrine studies (eg, thyroid function tests, growth hormone, luteinizing hormone [LH]/follicle-stimulating hormone [FSH], estradiol) are all that is required during radiotherapy unless otherwise dictated by investigational regimens or if clinically indicated.

    • The CBC count is used to monitor hematopoietic toxicity and determine whether intervention should be carried out to maintain hemoglobin levels at or above 10 g/dL in order to maximize radiation efficacy.

Inpatient & Outpatient Medications

See the list below:

  • Dexamethasone and antiseizure medications may be necessary to reduce the respective inflammatory response (edema) and seizure activity associated with the tumor and/or therapy.

  • Investigational protocols may dictate other medications, including chemotherapy.

Transfer

See the list below:

  • Transfer patient to a pediatric center that can provide appropriate MRI imaging studies; pediatric neurosurgery; and pediatric hematology, oncology, or neuro-oncology. Pediatric radiation oncology and neurology may also be necessary for treatment and follow-up.

Complications

See the list below:

  • Obstructive hydrocephaly

  • Neurologic impairment

  • Radiation-induced effects

    • Neurocognitive decline

    • Endocrinologic dysfunction

    • Mineralizing microangiopathy with ischemia or infarct

    • Secondary CNS malignancies

    • Transient headaches, fatigue, nausea, vomiting, and anorexia

  • Chemotherapy-induced effects

    • Myelosuppression, infection, nausea, vomiting, anorexia, renal damage, hepatic damage, hearing damage, neurotoxicity, and secondary malignancies may occur.

    • Investigational chemotherapy for either high-grade or low-grade tumors may cause complications such as fever, neutropenia, or suspected infection; therefore, hospitalization may be necessary.

    • Infertility and impairment of growth may also be long-term sequelae of therapy.

Prognosis

See the list below:

  • Low-grade astrocytoma

    • The 10-year survival rate for completely resected low-grade cerebellar astrocytomas is near 100%, with little or no morbidity. It is 60-95% for all low-grade tumors, including those incompletely resected and treated with radiotherapy.

    • Supratentorial tumors may result in residual motor deficits or seizure disorder. Radiotherapy may lead to neurocognitive impairment, neuroendocrine dysfunction, or ischemia and infarct.

  • High-grade astrocytoma: Those who survive (< 30%) are often left with some degree of motor, neurocognitive, or endocrinologic dysfunction.

  • Astrocytoma of the brain stem

    • Patients with dorsal exophytic and cervicomedullary tumors treated by complete surgical resection have survival rates of more than 90%.

    • Survival may be 50-100% for those with small focal tumors of the midbrain or tectal region treated with surgery and/or radiotherapy. In sharp contrast, patients with diffuse pontine lesions rarely survive.

    • Surgery to these areas can result in paralysis of multiple cranial nerves, mutism, and a compromised respiratory effort.

  • Astrocytoma of the visual pathway

    • The 10-year survival rate for patients with intracranial tumors (chiasm or deeper) is 40-85%, in contrast to the 90-100% for those with intraorbital tumors.

    • Fewer than half of all patients have improvement in their visual deficits noted at diagnosis.

    • As many as 50% of prepubertal children develop endocrinologic dysfunction from radiotherapy.

  • Astrocytoma of the spinal cord: The overall survival rate for patients with low-grade astrocytomas with various degrees of resection and postoperative radiotherapy is 67% at 20 years, whereas those with high-grade tumors rarely survive.

  • Khelifa-Gallois et al conducted a study of functional outcomes in adolescents and adults who were treated for a low-grade cerebellar astrocytoma in childhood.[12] The study cohort consisted of 18 adolescents and 46 adults. Data regarding academic achievement, professional status, and neurologic, cognitive and behavioral disturbances were collected through the use of self-completed and parental questionnaires for adolescents and of phone interviews for adults. For the adolescents, a control group filled in the same questionnaires. Mean time of lapse from surgery was 7.8 years for adolescents and 12.9 years for adults. Five adults (11%) had major sequelae related to postoperative complications, postoperative mutism, and/or brain stem involvement. For all the other participants reported cognitive difficulties and difficulties related to mild neurologic sequelae (ie, fine motor skills, balance) although academic achievement was similar to that of control participants. The investigators concluded that long-term functional outcomes of patients with low-grade cerebellar astrocytoma are generally favorable in the absence of postoperative complications and brain stem involvement.[12]

Patient Education

See the list below:

  • Refer patients and their family members for psychosocial counseling.