Table of Contents

HK J Paediatr (New Series)
Vol 3. No. 1, 1998

HK J Paediatr (New Series) 1998;3:21-28

Feature Article

Pediatric Neuro-Oncology: An Overview for The General Practitioner

RL Heideman


Abstract

This manuscript will emphasize the clinical manifestations of central nervous system tumors in children, as well as provide an overview of the clinical features and treatment of the most frequently encountered of these tumors; medulloblastoma, the low grade glial neoplasms and ependymoma.

Keyword : Astrocytoma; Brain tumor; Children; Ependymoma; Medulloblastoma


Abstract in Chinese

Introduction

As a group, central nervous system (CNS) tumors represent the second most frequent malignancy in children under the age of 15 years. Data obtained from the period 1973 to 1989 demonstrated an annual incidence of about 28 cases per million children per year as compared to a rate of about 2-10 for the other common solid tumors, and 31 for acute lymphoblastic leukemia.1-2 Of concern is a recent study which suggests an increasing incidence of CNS tumors in North America, Australia and some areas of Europe.3

Clinical Presentation: The Neurology of CNS Tumors

The signs and symptoms of a CNS tumors in children depend more on the age, developmental level, and location than the tumor histology.

Increased intracranial pressure

Obstruction of cerebrospinal fluid (CSF) flow and increased intracranial pressure (ICP) are responsible for some of the earliest clinical manifestations of CNS tumors. The classic signs of raised ICP are morning headaches, vomiting which is unassociated with nausea, and lethargy. The onset and progression of these symptoms is generally slow; more acutely evolving symptoms strongly suggest a rapidly growing midline or posterior fossa tumor and the need for immediate evaluation.

The initial signs of increased ICP are commonly nonspecific and non-localizing in nature. In schoolage children, declining academic performance, fatigue, personality changes, and complaints of intermittent headaches are common. Although the "classic" headache of increased ICP, pain present on arising that is relieved by vomiting and which diminishes during the day is well recognized, vague nonspecific complaints of head pain may be more common and are often overlooked by busy practitioners. Most commonly, these complaints are dismissed as sinusitis or recurrent viral illness. Repeated or persistent complaints of this nature, particularly when associated emesis and declining school performance should suggest the possibility of a CNS tumor and a prompt, careful history and evaluation.

The signs and symptoms of CNS tumors in infants and very young children may be more subtle; irritability, anorexia, developmental delay, and regression of intellectual and motor abilities are frequent early signs of increased ICP. Increasing head size with or without a bulging fontanelle, persistent emesis and failure to thrive are particularly characteristic whereas focal signs are uncommon. Likewise, the development of a hand preference over a relatively short interval in a young child is cause for concern; children less than 3-5 years of age are typically ambidextrous and a hand preference may reflect the onset of hemiparesis.

Common signs and symptoms of infratentorial (Brain Stem and Cerebellar) tumors

Development of poor balance with truncal unsteadiness, loss of upper extremity coordination, and cranial nerve abnormalities strongly suggest an infratentorial tumor. Early in the course of tumors that fill the posterior fossa, focal deficits may be absent or limited to ataxia and the non-localizing symptoms of increased ICP. In contrast, tumors arising in the cerebellar hemispheres (cerebellar astrocytomas) more commonly cause lateralizing signs such as appendicular dysmetria early in their course, often predating signs and symptoms of increased ICP.

Esotopia is a common abnormality in many CNS tumors. The inability to abduct one eye (palsy of nerve VI) may be a false localizing sign. Because of the long intracranial course of the VI nerve, increased ICP from any source may cause esotropia; such findings do not necessarily imply a posterior fossa tumor. However, when the VI is bilaterally affected and there is inability to deviate both eyes conjugately an intrinsic brain stem lesion should be suspected. The suspicion of brainstem pathology is increased when deficits of cranial nerves V, VII and IX are also present. Masses involving the cerebellopontine angle result in facial weakness and hearing loss, often with associated unilateral cerebellar deficits. Weakness of the upper and lower portions of the face (a peripheral 7th nerve palsy) suggests brain stem or posterior fossa tumors, while weakness of the lower portion of the face (central 7th nerve palsy) suggests involvement above the pons.

Common signs and symptoms of supratentorial tumors

Children with supratentorial tumors may demonstrate a variety of signs and symptoms which depend on the size and location of the tumor. Many of these signs, including headaches, are nonspecific and non-localizing in nature and may precede the signs of increased ICP.

Seizures are second in frequency to headaches as a presenting features of supratentorial lesions. Approximately 25% of children with supratentorial tumors will have seizures as their initial symptom. Slow growing, cortically located gliomas are most likely to result in a convulsion; as many as 50% of patients with low grade glial lesions may have such an event in contrast to 20% of those with glioblastoma multiforme.4,5 Although the majority of seizures are grand mal, less dramatic episodes with incomplete loss of consciousness (complex partial seizures) or transient focal events without loss of consciousness (partial seizures) may also occur. All children with focal and complex partial seizures and most with unexplained generalized seizures require computed tomography (CT) or magnetic resonance imaging (MRI) to rule out tumor as a cause. However, an initially normal CT scan in a patient does not rule out the possibility of tumor and repeat imaging may be indicated; many low grade tumors which are commonly associated with seizures are poorly seen on CT and may even be difficult to detect with MR.

Upper motor neuron signs such as hemiparesis, hyperreflexia, and clonus, as well as associated sensory losses may also be present in a child with an underlying supratentorial malignancy. In some patients with lesions involving "silent" areas of the cortex such as the frontal or parietal- occipital lobes, increased ICP may occur without associated focal deficits. A long history of behavioral problems may be present in children with frontal lobe tumors.

In any child with visual symptomatology, the presence of optic nerve or chiasmatic dysfunction should be sought. Testing the pupillary responses to a bright light may reveal absence or a delay in the direct reflex in the tested eye with an apparently normal but non-consensual response in the companion eye; such an "afferent pupillary defect" indicates an optic pathway lesion on the tested side. Tumors of the chiasm may result in classical bitemporal hemianopsia, but more frequently cause complex visual field loss. Further visual field testing is mandatory to delineate the extent of visual pathway involvement.

Tumors which involve the hypothalamus may cause minimal or no motor or visual difficulties. In infants, these tumors may cause failure to thrive and emaciation in a seemingly euphoric child with increased appetite, the so-called "diencephalic syndrome."

A specific symptom complex, "Parinaud's syndrome," should be looked for in any child with hydrocephalus or symptoms of increased ICP; this syndrome is caused by tumor compression of the midbrain and is frequent in patients with pineal area tumors. Its most characteristic manifestation is impaired or absent upward gaze and slightly dilated pupils that constrict on accommodation but not to light.

Many primary CNS tumors in children, particularly embryonal tumor varieties such as medulloblastoma and other primitive neuroectodermal and germ cell tumors, have disseminated by the time of diagnosis. Although such dissemination is often asymptomatic, spinal cord and cauda equina involvement may cause back or radicular pain, bowel or bladder dysfunction, and long tract findings such as abnormally brisk reflexes and a positive Babinski sign. Thus, the initial examination should include a search for local tenderness of the spine, focal extremity weakness, or sensory loss.

After treatment, careful and focused neurologic examinations are integral to the detection of early recurrence and to the recognition of treatment-related sequelae. Although neurologic examination may not be as objective as MRI or CT, it does play a role in evaluating the response of the lesion to treatment. Indeed, in some cases, such as infiltrating gliomas and leptomeningeal disease, neurologic evaluation may be more sensitive to changes in tumor size than imaging.

Diagnostic Imaging of CNS Tumors

Initial evaluation

A child with a presumed CNS tumor can be evaluated initially by either CT or MRI, in the medically stable, cooperative child, MRI with and without enhancement is the procedure of choice. For a medically unstable child or one difficult to sedate, CT with or without contrast will provide much of the information needed for initial treatment planning.

The CT is an indispensable aid in the diagnosis of CNS tumors. When performed with and without contrast medium, it can detect 95 Ic of such lesions. MRI has similarly become an important diagnostic tool and has several advantages when compared with CT. Although MRI is more sensitive to movement artifact and requires longer scanning time than CT. images can be obtained in multiple planes, and bone artifacts are avoided. An additional advantage is that abnormal tissue not seen with CT, a common occurrence in some infiltrating low grade astrocytomas, may be visible on T2-weighted MR images. Of note, corticosteroid use can significantly diminish the contrast enhancing and peritumoral (T2 signal) of tumors of both CT and MR scans; caution must be exercised in the measurement of tumor response in patients recently started on dexamethasone or other steroids.6

Leptomeningeal spread may occur, both before and after diagnosis, in a significant number of children with PNETs, anaplastic gliomas and germinomas. Finding of such spread influences prognosis and affects management; all such patients should have spinal imaging and CSF cytology evaluations before postoperative therapy. Unenhanced MR is inadequate for the evaluation of spinal subarachnoid space, but GD-DPTA-enhanced imaging appears to be a superior to CT-myelography in delineating spinal cord nodules and spinal "sugar coating." Even though enhanced MR of the spine may be a reliable technique for the initial evaluation of spinal leptomeningeal tumor spread, attaining these results requires meticulous, contiguous axial imaging and prolonged scanning times. CSF cytologic examination alone is inadequate to assess subarachnoid spread, particularly in patients with PNETs and germ cell tumors where as many as 50% of patients with these diseases have evidenced subarachnoid disease on MR despite normal CSF analysis. Thus, both procedures are necessary to evaluate and treat these patients properly. Although lumbar puncture and myelography are not without theoretical risks, especially in patients with posterior fossa tumors, such procedures can usually be performed safely in most patients 10 to 21 days after the initial operation and intracranial decompression.

Follow-up Evaluation

Most investigators agree that routine surveillance should be performed every 3 to 6 months during the first 2 years and every 6 to 12 months for the following 2 to 3 years after diagnosis and treatment.7,8 For embryonal tumors such as medulloblastoma and others with a high incidence of neuraxis dissemination, surveillance spinal MR during the first 18-24 months post therapy may also be helpful. Routine spine evaluations beyond this time may not be practical because local recurrences (with or without leptomeningeal dissemination) are more likely than isolated neuraxis disease.

Common Childhood Brain Tumors

Medulloblastoma

Demography, pathology and clinical presentation

Medulloblastoma is a tumor that arises predominantly from the area of the cerebellar vermis and accounts for about 20% of primary CNS neoplasms in children. It is the most common of posterior fossa tumors.

Medulloblastoma is the prototypic and the most common (80%) of the group tumors classified as "Embryonal" neoplasms by the current WHO classification of CNS tumors.9 The tumors of this group are similar in both their predilection for early leptomeningeal dissemination and their microscopic appearance as densely cellular neoplasms composed of small, round cells with a high nuclear cytoplasmic ratio. Despite the clinical and histologic similarity of these tumors, the prognosis of medulloblastoma appears to be generally more favorable than the primitive neuroectodermal tumor (PNET), ependymoblastoma, and medulloepithelioma which make up the rest of this group. Because of this, many investigators prefer to maintain medulloblastoma (also called posterior fossa PNET) as a specific entity differing from the others of this group by virtue of location and outcome.

The earliest and most persistent signs and symptoms are the nonspecific, non-localizing findings of increased ICP resulting from obstruction of the fourth ventricle. Papilledema, headache, emesis, and lethargy are present in 70% to 90% of patients at diagnosis. Because many of these symptoms are intermittent and subtle, they are often overlooked, and the duration of symptoms of 3 months or more prior to diagnosis is not uncommon.

With increasing tumor size, progressively worsening ataxia involves the lower extremities, often with relative sparing of the upper extremities and trunk become evident. Pressure, as well as tumor infiltration of the brain stem often leads to diplopia from abducens nerve palsy; multiple other cranial nerve findings may also be present.

On CT, prominent hydrocephalus and a solid, homogenous, isodense to hyperdense, contrast-enhancing midline mass is characteristic. Midline cerebellar astrocytomas may occasionally give rise to diagnostic confusion. MRI may be useful in such instances by better demonstrating the anatomic origin and extent of tumor.

Treatment

Surgery

Medulloblastomas are approached surgically through a suboccipital craniotomy. Modern neurosurgical techniques permit complete or nearly complete resection. Complete resections should not be attempted in patients with brain stem invasion; attempted resection of these areas may cause significant neurologic morbidity and even mortality. Recent studies have demonstrated that, in the absence of gross areas of brainstem infiltration, small amounts of residual tumor in this location are not associated with a poorer outcome.

Radiation Therapy

Medulloblastoma is one of the most radiosensitive primary CNS tumors of childhood. Total neuraxis therapy is standard in all patients, and survival may be compromised in patients who do not receive such treatment. Many authors have demonstrated the need for total doses of 5000 to 5500 cGy to the area of the primary tumor (3500 cGy whole brain plus 1500-2000 cGy boost to the area of the tumor), showing that local control of the primary tumor and survival decline at doses below this.10,11 However, the most appropriate dose for craniospinal therapy remains a subject of debate. The most appropriate treatment for the patient who is younger than 3 years is debatable. Because of the high incidence of neuropsychologic deficits associated with irradiation in young children, most investigators now pursue a strategy of primary chemotherapy. This approach is based on the desire to at least delay the probable need for craniospinal irradiation and its frequent association with developmental delay, intellectual decline and neuroendocrine deficiencies in these young patients.12,13

Chemotherapy

Of all primary CNS tumors, medulloblastoma appears to be one of the most chemosensitive. Disease response has been reported for a number of single and multiple agent phase If trials. Among the most active single agents are the classical alkylators such as cyclophosphamide, and melphalan, and the platinum coordination complexes cisplatin and carboplatin. Because the efficacy of chemotherapy appeared to patients who currently would be classified as high risk (younger age, incomplete resection, Chang stage T3B, T4, M1-4), most recent treatment protocols include chemotherapy only for high risk patients with average risk patients generally receiving radiation therapy alone. Of note, however, is the striking 85% progression free survival rate at 5 years in newly diagnosed children treated with radiotherapy plus adjuvant CCNU, vincristine and cisplatin.14 Although controversy may ensue over the degree to which these patients represent the yet evolving clinical criteria associated with poor prognosis, the survival of these patients remains among the best reported for any group with this disease. Because of this, many investigators feel that similar chemotherapy may be indicated in all patients, regardless of their risk features. Thus, it is likely that the use of chemotherapy will become common even in standard risk patients where it may decrease the incidence of local recurrence and perhaps justify attempts at reducing craniospinal radiation doses.

Low Grade Supratentorial and Cerebellar Gliomas

Demography, pathology and clinical presentation

Collectively, low grade astrocytic tumors are the most common CNS neoplasms in children. Supratentorial low grade astrocytic tumors comprise about 35% of childhood CNS tumors. Two thirds of these arise in the cerebral hemispheres with the remainder arising in the deep midline structures of the diencephalon (thalamus, hypothalamus, third ventricle) and basal ganglia. An additional 20% of childhood tumors are low grade astrocytomas arising in the cerebellum. Tumor of the optic nerves and chiasm, only 5% of childhood CNS tumors, are also dominantly low grade astrocytomas.

Current classifications systems identify these tumors based on their grade or degree of anaplasia rather than histologic type.9 Neoplasms which are only modestly cellular and contain few or none of the histologic criteria of malignancy and are designated as "low-grade" or grade I and II lesions in these classifications. Among the several different histologic patterns which constitute low grade tumors, only the pilocytic and fibrillary varieties are commonly seen in children. Those tumors with mitoses, increased cellularity and other microscopic features associated with aggressive tumors are designated as "highgrade" or grade III and IV tumors. The later are clinically aggressive tumors with poor prognoses and are fortunately infrequent in children; high grade astrocytomas comprise only about 10% of childhood CNS tumors. High grade lesions will not be further discussed here, but interested readers may find information regarding their treatment and prognosis in other recent publications.15-17

Regardless of tumor location, 75% of patients present with nonspecific and non-localizing features related to increased ICP. Seizures are another common manifestation and occur in at least 25% of patients with supratentorial astrocytomas; their onset may precede the diagnosis of a tumor by several months to as much as 2 years.4,5

The more specific signs of supratentorial tumors relate to their location. Focal motor deficits and pyramidal tract findings such as weakness and monoplegia or hemiplegias are particularly common and may occur in up to 40% of patients with hemispheric and thalamic tumors. Hypothalamic tumors are often associated with optic atrophy, and neuroendocrine abnormalities. Growth hormone deficiency, diabetes insipidus, and precocious pubertal development may be present in one third of such patients.

The signs and symptoms of the low grade astrocytomas of the visual pathways depend on their location and the age of the patient. Young children rarely complain of the slow and progressive visual loss characteristic of these tumors. More commonly, children under age 3 are brought to medical attention because of strabismus, proptosis, nystagmus, or developmental difficulties. Of note, the incidence of these tumors may be as high as 25% in children with neurofibromatosis. The pattern of visual loss in patients with intraorbital tumors is most commonly that of a decrease in central vision. In patients with chiasmatic tumors, bitemporal hemianopic loss is often noted. Growth and endocrine disturbances, as well as precocious puberty and the diencephalic syndrome may occur with intracranial tumors of the chiasmatic-hypothalamic area. Although CT and MRI are essential for the follow-up of patients with visual pathway tumors, declines in vision or responses to therapy may not be associated with changes in tumor size and stable vision does not exclude tumor growth. Thus, both detailed ophthalmologic evaluations, including visual fields and acuity testing are important in followup.

On CT scans, most low-grade gliomas are typically hypodense lesions with variable contrast enhancement with calcification being a common finding. With MR these tumors are typically hypointense on short T1 weighted images, hyperintense on T2 images and commonly display poor contrast enhancement. Of note, however, is a frequently noted and perhaps characteristic MR appearance of pilocytic astrocytoma, the majority of which are discreet appearing lesions which show prominent contrast enhancement.18,19

Although some investigators have suggested that centrally placed diencephalic tumors may have a worse prognosis than hemispheric tumors20-21 these conclusions must be viewed with caution as tumor location is probably not an independent prognostic variable when extent of resection and tumor grade are considered.

Treatment

Surgery

The surgical approach to all low grade glial tumors is similar. Operative morbidity depends largely on tumor location and is highest in diencephalic tumors where a 10% to 20% incidence of hemiparesis or visual field deficits may occur. Although gross total excisions are possible in 40% to 80% of hemispheric tumors, less than 40% of diencephalic tumors are similarly resectable. With few exceptions22 most studies suggest that survival of hemispheric tumors is directly related to the extent of resection. (488,492,1062)

The extent of resection also correlates well with outcome in cerebellar gliomas. Because the relapse free survivals of patients with gross total tumor resections is as high as 90% for periods of up to 30 years, aggressive attempts at resection are warranted with the exception of instances where there is invasion of the cerebellar peduncles. The appearance of residual tumor on postoperative scans is an indication for reoperation. Likewise, patients with recurrent disease are candidates for reoperation prior to the use of radiation therapy.23-25

The principal indications for neurosurgical intervention in patients with isolated intraorbital tumors are cosmesis in a severely proptotic blind or seeing eye and pain or jeopardy to the health of the globe and the cornea caused by severe proptosis.26 Some also suggest that resection is wise in the very young, in whom evaluation of tumor progression is difficult.27 In many instances, the tumor can be removed with preservation of the globe. However, if complete resection is to be done, the resected segment of the optic nerve should be as long as possible (preferably to the chiasm) to diminish the risk of local recurrence.26 Surgery is rarely indicated for chiasmatic and deeper lesions.

Radiation therapy

The role of radiation in patients with low-grade astrocytomas depends on the degree of tumor resection. Individuals who have had completely resected tumors have 5-year survival rates as high as 95% to 100% and do not require postoperative radiation.28,29 However, there is debate about its utility in patients with incomplete resections. There have been no prospective randomized studies, and those studies from which data can be abstracted frequently include both adult and pediatric patients accrued over several decades in which all low-grade tumors regardless of site or histology are combined.30 With this in mind, reports that demonstrate that radiation may improve survivals in these patients31,32 should be viewed carefully. A recent review, progression-free survival of subtotally resected children was improved by the administration of irradiation, although overall survival was unaffected.33 For most children, especially those less than 5 years of age, it is reasonable to delay the use of radiation; subsequent tumor progression may be treated with chemotherapy to delay or avoid irradiation.

The role of radiation therapy in incompletely resected cerebellar tumors is unclear. Although some single institution studies suggest that radiation may improve the survivals of these patients, more recent studies with larger numbers of patients are unable to demonstrate a significant advantage for such treatment.23,34 Because no substantive data indicate otherwise, radiation may reasonably be withheld until there is evidence of recurrent disease, at which time the child may be treated with repeat surgical excision, stereotactic radiosurgery, or external irradiation.

Among patients with visual pathway tumors, recent studies indicate that irradiation may help preserve of vision in patients with progressive orbital or chiasmatic tumors; up to 44% of patients have been reported to show improvement, and as many as 90% show at least stabilization of visual decline after radiation therapy.35,36 For patients with chiasmal and deeper intracranial involvement where survival is the major consideration, Radiation appears to improve both overall and progression free survival of patients with large chiasmatic hypothalamic.36,37

Chemotherapy

A positive role for chemotherapy in supratentorial low-grade gliomas has evolved with recent single and multi-institution trials which demonstrate a benefit for a variety of combinations which generally include and alkylating or platinating agent. Among the most active agents identified is carboplatin which, when given as a single agent in patients with recurrent disease, is associated with an 80% or more rate of combined objective response and prolonged stable disease.38,39 The addition of other agents such as vincristine appears to increase the rate of objective responses to as high as 50% in patients with recurrent disease and 50% in newly diagnosed patients.40,41 The use of more intensive and myelosuppressive treatments (nitrosoureas, topoisomerase II and alkylator combinations) does not appear to improve the response rate or outcome of LGG and the use of these drugs seems unwarranted.

Among patients with visual pathway tumors, chemotherapy is an alternative to radiation in the treatment of progressive disease. The widest experience has been with the combination of actinomycin D and vincristine which has produced prolonged disease stabilization and regression for up to 2-3 yrs in as many as 80% of a small group of pts.42 More recently, carboplatin with or without the addition of other agents has shown good activity in these tumors, similar to other low grade tumors as noted above.

Ependymomas

Epidemiology, pathology and clinical presentation

Ependymomas constitute 5% to 10% of all primary childhood CNS tumors and usually arise within or adjacent to the ependymal lining of the ventricular system or the central canal of the spinal cord. Ninety percent of tumors are intracranial, with up to 60% or more of these occurring in the posterior fossa.

Ependymomas generally appear as well demarcated tumors in vivo. Microscopically, these are often tumors of small cells that may resemble either medulloblastoma or even astrocytoma depending on the degree of cellularity and background. Although it is not commonly seen, the ependymal rosette is a characteristic and diagnostic feature of this tumor.

Current terminology for ependymomas distinguishes between "benign" or low grade versus "malignant", high grade, or anaplastic even though such names have not correlated well with clinical outcome.43 Another tumor with a similar name, the ependymoblastoma can be a source of some confusion for clinicians. This tumor is considered to be a member of the family of embryonal tumors and should not be thought of as an ependymoma.

The initial signs and symptoms of ependymomas are usually nonspecific and non-localizing and related to increased ICP. Supratentorial lesions, may be associated with seizures and focal cerebral deficits, similar to those accompanying other tumors in this location. Posterior fossa tumors may lead to cerebellar dysfunction and are more commonly associated with lower cranial nerve findings (VI, VII, VIII, IX and X are particularly common) and may mimic medulloblastoma both symptomatically and radiographically.

Although there is great variability in the CT appearance of these tumors, they generally appear as hyperdense and homogeneously contrast enhancing lesions. With MR, T1 weighted sequences are characteristically iso- to hypointense with respect to white matter, and most enhance with Gd-DTPA. Because of the potential for subarachnoid seeding, especially from posterior fossa tumors, CSF cytology and spinal MRI should be included in the postoperative evaluation of these patients.

Treatment

Surgery

Surgery plays an important role in the outcome of patients with ependymoma and may be the single most important prognostic factor; with subtotal resections have 5 year progression free survivals are only 21%-26% vs 51%-60% for those with complete or near complete resection.44-46 Attempts at gross total resection of tumors in the posterior fossa are more difficult than in supratentorial locations because of their tendency to infiltrate the brain stem, fill the lateral recess and extend through the foramen of Luschka to encase the lower cranial nerves. Multiple cranial nerve palsies as a result of both tumor and surgery generally necessitates a tracheostomy and gastric feeding device in these patients; assuming that cranial nerves have not been sacrificed, there may be resolution of neurologic impairment in several months.47

Radiation therapy

Local postoperative radiation therapy increases the overall survival of patients with ependymoma from 15%-23% to 35%-63% at 5 years.46,48 Patients with supratentorial lesions should receive wide local field irradiation. Because posterior fossa tumor often extends down the cervical cord, the treatment fields for these tumors should include the upper cervical spine to the level of the C3-C4 interface, or two vertebral bodies below the lowest extent of disease. Because local relapse is the dominant mode of failure, occurring in as many as 83% to 97% of patients, prophylactic spinal irradiation is generally no longer given. Even when such treatment was common, its use was not generally associated with improved survival.46,49,50

Chemotherapy

A number of single chemotherapy regimens have been identified as having activity against ependymoma in phase II trials. Of these, the platinum compounds have been the most active.51,52 Despite the observation of good objective responses in several trials however, chemotherapy has had no significant impact on clinical outcome.

Summary

While the outcome for many CNS tumors has improved measurably over the last decade, much remains to he done. The investigation and utility of chemotherapy in CNS tumors has been slower in these tumors than in other common solid tumors of children.53 However, increasing interest in these difficult tumors by pediatric oncologists and radiotherapists has lead to a substantial increase in clinical trials of new and innovative treatments. The increase in the pace of new agent investigation, investigations in high-dose chemotherapy and gene therapy as well as the application of intrathecal therapy suggest the likelihood of continued and steady progress with drug and biologic therapy. Likewise, the recent development of stereotactic irradiation and the emerging use of conformal irradiation promise to limit the adverse effects of wide field irradiation through the application of more focused and controlled particle beams.

Readers interested in broader and more comprehensive reviews of pediatric CNS tumors and their treatment may wish to consult the following references.54,55


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