Brain Tumors in Children: Evaluation and Management
Adam S. Levy, MD
ccording to the National Cancer Institute’s
A Surveillance, Epidemiology, and End Results
(SEER) data, the incidence of central nervous
system (CNS) tumors is 27 per 1 million children less
than 19 years old. After leukemias, CNS tumors are
the second most common neoplasm in children. Brain
tumors are the most common solid tumors of children
and account for the greatest mortality from cancer in
children.1,2 Approximately 11,000 children in the
United States will be diagnosed with cancer each year,
and of these just over 2000 will be CNS tumors.
Over the last 30 years, there appears to be a slow
increase in the overall incidence of childhood cancers
in the US, including CNS tumors in children. The
overall 5-year survival for patients younger than 19
years with CNS tumors is around 65%.3 The outcome
for children with CNS tumors has shown improvement
over the last several decades, but remains guarded for
a large subset of children with certain brain tumors. In
comparison to the outcome for children with leuke-
mias, the outcome for children with brain tumors has
not had as dramatic improvement over the past three
decades.
CNS tumors represent a diverse group of neoplasms
of the brain and spine with varying histology. The
clinical presentation is often dictated by the location of
the tumor in terms of the neurological deficit or
obstructive hydrocephalus. The onset may be indolent
or rapid depending on the histology and aggressive-
ness of the tumor.
The goal of this article is to discuss the common
presentations of pediatric CNS tumors, to detail the
appropriate initial evaluation and management, to review
the more common CNS tumors, and to discuss treatment
modalities. Long-term follow-up for survivors and the
From the The Children’s Hospital at Montefiore, Bronx, New York.
Curr Probl Pediatr Adolesc Health Care 2005;35:230 –245
1538-5442/$ - see front matter
© 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.cppeds.2005.04.001
230
effects on the family of a child with a CNS tumor will be
addressed. Finally, palliative care strategies for children
with CNS tumors will be discussed.
Common Presentations of CNS
Tumors
The presentation of a child with a CNS tumor may
be subtle or dramatic and is dependent on a combina-
tion of the patient’s age, the tumor location, and the
tumor histology.
In infancy, brain tumors may present insidiously.
Indeed, the only sign of a CNS lesion may be an
increased head circumference secondary to hydro-
cephalus. When the head circumference is dispropor-
tionately large compared with the length or weight, the
pediatrician must consider an intracranial process as
the cause. While it may be more common that the
relatively increased head circumference is familial,
this conclusion must be reached with great caution,
and a trend of increasing head circumference out of
proportion to the length and weight must be further
evaluated. Unusual fullness or bulging of the fonta-
nelle may also be a sign of hydrocephalus or increas-
ing intracranial pressure. Also, from increased intra-
cranial pressure, infants or toddlers may present with
irritability or Parinaud’s syndrome (paralysis of con-
jugate upward movement of the eyes and poorly
reactive pupils). Developmental delay may be the
main symptom at diagnosis, but more typical would be
a loss of previously attained milestones. Thus, a young
toddler who is not yet walking may not be particularly
worrisome, but a toddler who had been walking well
and then becomes ataxic warrants further evaluation.
Likewise, a child who has a primary speech delay
should be approached differently than a child whose
speech regresses.
Toddlers and school-age children may present in a
variety of ways. New onset seizure (unrelated to fever)
is more likely to be secondary to a seizure disorder,
Curr Probl Pediatr Adolesc Health Care, July 2005
but an intracranial mass must be considered. The level
of evaluation and timing of studies for patients pre-
senting with new onset seizure is debated, though
many would agree that a magnetic resonance imaging
(MRI) of the brain is warranted for new onset seizure
that is not associated with fever.
Many of the symptoms of a brain tumor result from
increased intracranial pressure (ICP) from either hydro-
cephalus or the mass effect of the tumor itself. The
classic presentation of increased ICP is morning head-
ache with vomiting. Frequently, there is no nausea
associated with the emesis. On lying down overnight,
obstructive hydrocephalus may be worsened as the sleep
position does not allow gravity to promote cerebrospinal
fluid (CSF) flow. The increased ICP causes headache and
may trigger emesis, and the headache is often relieved
following the emesis. It is not unusual for patients with a
brain tumor to present with emesis that had been diag-
nosed as acute gastroenteritis. Isolated emesis without
accompanying diarrhea or dyspepsia should alert the
pediatrician to the possibility of increased ICP.
In older children and adolescents, brain tumors may
present secondary to endocrine dysfunction. Some tu-
mors, such as prolactinomas, are the primary cause of
endocrine dysfunction. Other times, tumor compression
on the pituitary may cause pituitary dysfunction.
Depending on the tumor location, children may present
with a focal neurological deficit. Diplopia secondary to
cranial nerve deficits is not an uncommon presenting sign
of a brain tumor. For tumors located near the motor
cortex, specific losses of physical function may be the
presenting symptom. Tumors affecting the brainstem
commonly present with ataxia. Spinal cord tumors may
present with incontinence to urine or stool as well as
other focal deficits.
With ICP increasing to a critical level, a patient’s
mental status may be affected and the patient’s vital
signs may be altered. Specifically, the triad of hyper-
tension, bradycardia, and tachypnea (Cushing’s Triad)
should alert the clinician to the possibility of increased
ICP. This is usually a late sign of increased ICP.
Hypertension compensates for the raised ICP in an
effort to normalize intracranial blood flow.
Initial Evaluation and Management of
Suspected CNS Tumor
The initial evaluation of a suspected CNS tumor
depends on the presenting signs, symptoms, and avail-
Curr Probl Pediatr Adolesc Health Care, July 2005
able resources at the health center. For example, a
patient presenting with signs and symptoms of in-
creased ICP requires specific management including
high-dose corticosteroids, relative fluid restriction,
head elevation, and possibly neurosurgical interven-
tion. Urgent brain imaging is also indicated.
Obtaining an urgent computerized tomography (CT)
scan may be more realistic than obtaining an MRI scan
as MRIs are less commonly available and are likely to
require prolonged sedation for pediatric patients. Thus,
while an MRI may be the ideal scan to evaluate a
patient for a brain tumor, an initial evaluation with a
CT scan is more common and still likely to be useful.
CT scans allow accurate evaluation of ventricle size
and detection of hemorrhage or stroke. CT scans will
also frequently detect brain tumors, especially those
associated with calcification.
In general, the diagnostic test of choice is an MRI
with and without contrast (Gadolinium). FLAIR se-
quences are often useful in determining tumor infiltra-
tion or surrounding edema.4 Diffusion-weighted im-
aging can help differentiate cysts from solid tumors
and identify areas of necrosis.5,6 However, while
standard MRI provides excellent images of anatomical
structure of the brain and spinal cord, standard MRI
does not provide information regarding tissue func-
tion, metabolic state, blood supply, and malignant
potential.7 Such information would be clinically useful
in determining surgical approach, response to therapy,
and monitoring for relapse.
Newer imaging techniques, broadly referred to as
functional imaging, are under development and being
used more frequently in clinical practice. Magnetic
resonance spectroscopy (MRS) allows for the mea-
surement of biologically important molecules such as
choline, creatine, N-acetyl aspartate, glutamate, lac-
tate, and lipid. The profile of the concentration of these
molecules may differ among tumor, normal brain, or
fibrosis and scarring.8 Some studies suggest that tumor
histology can be determined by the signal pattern of
the molecules.9 Enhanced tumor localization with
MRS may also help determine the ideal location for
tissue biopsy10 and may predict outcome and response
to therapy.11
Positron emission tomography (PET) scan is a sen-
sitive and specific imaging tool to evaluate the tissue
metabolism. 18Fluorodeoxyglucose, a glucose analog,
is taken up by tissues with high-glucose metabolism,
and this uptake can be measured by PET. Again,
glucose metabolism may be markedly distinct in tumor
231
compared with normal brain or fibrosis and may in the
future become a more standard tool to help direct
clinical decisions.7
In some circumstances, the radiographic presenta-
tion may be diagnostic obviating the need for tissue
diagnosis. The most common examples of this are
diffuse intrinsic brain stem tumors and optic pathway
tumors that are usually low-grade gliomas (to be
discussed in detail later). In most other settings, tissue
is needed to confirm the tumor histology. As such, the
majority of pediatric patients presenting with a CNS
tumor will require a neurosurgical procedure.
Neurosurgical Approach to CNS
Tumors
The neurosurgical approach to a CNS tumor depends
on the clinical status of the patient, the location of the
lesion, and the suspected histology of the lesion based
on the imaging studies. Urgent surgical intervention
may be indicated to manage hydrocephalus, hemor-
rhage, or the acute mass effect of a tumor. In these
settings, the primary goal is to manage the acute
life-threatening problem. In such circumstances it may
be necessary to perform a second neurosurgical pro-
cedure to deal more definitively with the tumor.
Fortunately, most of the time the presentation of a
CNS tumor is not this acute, thereby allowing for
thoughtful planning. At a minimum, the primary goal
of nonurgent neurosurgical intervention is to obtain
tissue for a histological diagnosis. Depending on the
location of the mass, this may be accomplished by a
biopsy, partial resection, or complete resection (also
referred to as a gross total resection).
In general, the outcome for children with brain
tumors is associated with the extent of surgical resec-
tion.12,13 Thus, there is a tendency for experienced
pediatric neurosurgeons to favor a relatively aggres-
sive approach. However, the desire to accomplish a
maximal resection or tumor debulking must be tem-
pered by the possible neurological insult from aggres-
sive surgery. For this reason, it is preferable for
neurosurgical interventions to be made by surgeons
with experience with pediatric CNS tumors in the
setting of a tertiary care hospital where the case can be
discussed with a pediatric oncologist and a radiation
oncologist with pediatric CNS tumor experience.
In a situation where the tumor location precludes
complete resection, a biopsy alone will likely help
232
determine adjuvant therapy (either chemotherapy or
radiation therapy). Following adjuvant therapy, a com-
plete resection may then be more safely accom-
plished.14
Recent advances in neurosurgical techniques have
enhanced the ability to biopsy and resect tumors more
safely. State-of-the-art neurosurgical techniques in-
clude intraoperative navigation systems (neuronaviga-
tion), intraoperative MRI, and frameless strereotaxy
that allow intraoperative guidance with the ability to
visualize the tumor in multiple planes.15 Cortical
mapping is frequently needed for tumors in close
proximity to the motor and speech cortex.16
Unfortunately, complications from either the tumor
or the surgery are not uncommon. Postoperative swell-
ing or edema commonly results in worsening of
symptoms in the immediate postoperative period.17
Focal neurological deficits following surgery are com-
mon but generally have some or complete resolution
over time. Hydrocephalus may occur before surgery
but may also develop even after a complete tumor
resection either from edema, a hematoma, or an
alteration of CSF dynamics that is not clearly de-
fined.15
Following the resection of a posterior fossa tumor,
approximately 10% of patients may develop “Posterior
Fossa Syndrome,” also known as cerebellar mutism.
This syndrome is characterized by postoperative mut-
ism, ataxia, 6th and 7th nerve palsies, and hemipare-
sis,18 and this syndrome is more commonly associated
with malignant tumors as compared with benign le-
sions. The onset is typically within days of surgery and
recovery may take weeks to months with up to 20% of
patients having permanent features.15
Other postoperative complications include wound
infection, pseudomeningocele, aseptic meningitis,
bacterial meningitis, stroke, and seizures. Given the
technical and clinical considerations involved in the
neurosurgical management of pediatric CNS tumors,
the importance of referral to an experienced pediatric
neurosurgeon with state-of-the-art operative tools at a
center with experience treating such patients cannot be
overemphasized.
Radiation Therapy Approach to
Pediatric CNS Tumors
For those pediatric brain tumor patients that cannot
be cured by surgery alone, radiation therapy is fre-
Curr Probl Pediatr Adolesc Health Care, July 2005
quently the definitive adjunctive treatment of choice.
The majority of brain tumor patients with high-grade
or malignant tumors will receive radiation to either the
tumor, the resection bed, the whole brain, or the entire
craniospinal axis.
Radiation therapy takes advantage of the inherent
differences in radiosensitivity between tumor cells and
normal tissues. In general, normal tissue is better able
to tolerate the insult of ionizing radiation than tumor
cells. Ionizing radiation causes DNA damage either
directly or indirectly by the formation of free radicals
that chemically interact with DNA.19,20 Since the
damaging effects are thought to be the result of
free-radical formation, many clinicians transfuse pa-
tients as needed to maintain relatively normal hemo-
globin concentrations in the blood in an effort to
ensure adequate oxygen delivery to the tumor during
radiation therapy.
Just as some tumors are more radiosensitive than
others, normal tissues vary in degree of radiosensitiv-
ity. As compared with hematopoietic stem cells, neu-
rons are significantly less radiosensitive. This is clin-
ically evident in patients receiving craniospinal
radiation for whom myelosuppression is more likely to
cause an interruption in radiation therapy than acute
radiation effects on the CNS.
An acceptable therapeutic ratio can also be achieved
by targeted delivery of radiation.20 A main focus of
radiation therapy advances has been to more precisely
deliver radiation to the tumor target. To repeatedly
deliver radiation to a limited target volume, methods
have been developed to place a patient in a reproduc-
ible position over the days to weeks of therapy.19 For
younger pediatric patients, the positioning needed for
radiation administration can be so challenging that
anesthesia is frequently necessary. Essentially an im-
mobilization device such as a plastic facemask is
customized for the patient. The mask is placed on the
child and then attached to the treatment table in an
effort to limit movement as much as possible. With
technology that is designed to deliver radiation with
precision on the order of millimeters, patient move-
ment cannot be allowed.
Radiation oncologists utilize MRIs, CT scans, and
sophisticated computer systems in conjunction with
medical physicists to define the target volume of the
radiation dose and determine the treatment plan to
deliver a given amount of radiation to the target
volume. The target volume includes the gross tumor
volume and surrounding tissue at risk for spread of
Curr Probl Pediatr Adolesc Health Care, July 2005
microscopic disease.19 For tumors with high malig-
nant potential to spread throughout the CNS, cranio-
spinal radiation with a boost to the tumor may be
indicated. The radiation dose is based on the type of
tumor and its location in the body.
There have been recent advances in the ability to
deliver radiation therapy in the full doses needed to
provide tumor response while limiting the exposure of
normal surrounding tissue.21 If one considers deliver-
ing a single high-energy beam to a tumor within the
brain surrounded by normal tissue, it is clear the
normal tissue between the energy source and the tumor
will receive the highest dose of energy. The normal
tissue on the other side of the tumor will receive a high
radiation dose as the beam exits the body. Three-
dimensional conformal radiation therapy allows the
radiation therapy team to select beam shapes and
angles that divide the total dose into multiple inter-
secting energy beams. Thus, the treatment high-energy
dose can more precisely conform to the target volume
while limiting the dose to normal tissue.21
Intensity-Modulated Radiation Therapy (IMRT) is a
relatively new approach that allows even greater
precision of radiation delivery by modulating the
intensity of each beam with individual radio-opaque
leaves. The individual leaves are moved in and out of
the radiation field during treatment such that the
energy beam can be sculpted to conform to irregular-
shaped tumors within the body.19,21
Radiosurgery utilizes multiple radiation beams all
converging on the same tumor target thereby deliver-
ing a single high-dose fraction of radiation to the
tumor. Radiosurgery is usually limited to use for small
treatment volumes.19,21
Proton Beam Therapy is particularly helpful in
limiting exposure of normal tissue. Unlike the photons
or more standard RT, protons enter the body with a
relatively low radiation dose and that energy is depos-
ited in the tumor target with very little energy passing
through the target into surrounding tissue. Normal
tissues distal to the target are not irradiated.21,22
Toxicity of radiation therapy is of particular concern
in pediatrics and can be characterized as acute and late
effects. Common acute effects include local skin
reactions, anorexia, nausea, somnolence, focal alope-
cia, mucositis (depending on radiation beam path),
otitis, and myelosuppression (with spinal radiation).
Long-term effects are of even greater concern and
include radionecrosis of normal tissue, vascular injury,
bone growth stunting, endocrine abnormalities, hear-
233
ing loss, secondary malignancies, cognitive deficits,
and neuropsychological effects.17,22,23
Chemotherapeutic Approach to
Pediatric CNS Tumors
Over the past several decades, chemotherapy has
gained increasing acceptance as an important thera-
peutic approach for a variety of brain tumors. For
patients with low-grade tumors, complete resection is
likely to be curative. However, when a complete
resection cannot be accomplished for low-grade tu-
mors, additional therapy must be considered. Like-
wise, for high-grade lesions regardless of the extent of
resection adjuvant therapy must be considered as
dissemination and recurrence after surgery alone are
likely. In general, the younger the patient, the more
likely the late effects of RT will be devastating.
The mainstay of brain tumor management in adults
has been surgery and radiation with chemotherapy in
some cases. However, because of the effects of radi-
ation therapy (RT) on the developing brain, there has
been a movement to try and avoid RT in children or at
least delay RT administration until the patient is older.
With advances in supportive care, chemotherapy can
be delivered more safely and with greater predictabil-
ity of side effects thereby justifying attempts to incor-
porate chemotherapy into a broader range of pediatric
CNS tumor treatment plans. The goal is to improve
survival and decrease the morbidity of RT. Of course
there is the added morbidity of the chemotherapy
itself.
Though chemotherapy regimens may appear haphaz-
ard, they are generally designed to provide comple-
mentary insults to the tumor while avoiding overlap-
ping dose-limiting toxicities. For example, the ideal
multi-agent chemotherapy regimen would include
drugs that have different mechanisms of action in an
effort to avoid intrinsic or acquired tumor resistance.
On the other hand, the toxicity profile must in some
ways be dissimilar so that the chemotherapy agents
can be given contemporaneously. In other pediatric
cancers such as acute lymphoblastic leukemia, multi-
agent chemotherapy regimens have successfully re-
sulted in impressive improvement in survival with
acceptable morbidity. For a subset of brain tumors
multi-agent chemotherapy has proven successful, but
for other brain tumors results have been equivocal or
proven to be unsuccessful (to be discussed below for
the common pediatric brain tumors).
234
The range of intensity of chemotherapy regimens for
pediatric brain tumors is great. Some treatment plans
call for single-agent oral chemotherapy that is gener-
ally very well tolerated24; in other settings high-dose
chemotherapy with stem cell rescue (autologous stem
cell transplant) is indicated.25 Despite the oncologist’s
usual comfort in chemotherapy administration, the
therapeutic index for chemotherapeutic agents is gen-
erally small. Thus, while families are often willing to
“try anything” in desperate situations, physicians must
be reminded to only provide rational therapy.
A variety of chemotherapy drugs are commonly used
in the treatment of pediatric brain tumors. In general,
single-agent Phase I trials are utilized to show feasi-
bility and perhaps some benefit in a specific tumor.
Over time agents with known benefit have been tried
in combination. The most common chemotherapy
agents for pediatric brain tumors will be detailed
below. For a detailed review of chemotherapy agents
used in pediatrics, see Balis and coworkers26 and
Banerjee and Mathay27 from which the discussion
below is derived (see also Table 1). Combination
treatment plans will be reviewed later as they relate to
specific tumor types.
Vincristine is a commonly used drug in the manage-
ment of low-grade gliomas as well as high-grade and
malignant brain tumors despite its limited documented
CNS penetration.28 Usually given as an intravenous
push in combination with other agents, vincristine is
relatively well tolerated with the most common side
effects being constipation, jaw pain with administra-
tion, and peripheral neuropathy which is usually re-
versible and related to cumulative doses. Vincristine is
a plant alkaloid that induces metaphase arrest through
the binding of tubulin.26
Etoposide also binds tubulin and interacts with
topoisomerase II resulting in cell cycle arrest.26 Eto-
poside is used intravenously in combination with
multiple agents to aggressively treat brain tumor
patients, but can also be prescribed orally in a more
palliative setting with potential effect and acceptable
side effects. Common toxicities include nausea, my-
elosuppresion, and alopecia. Frequently the greatest
concern with etoposide administration is the increased
risk of secondary malignancies.
Cisplatin and carboplatin are alkylating agents used
for a variety of CNS tumors given as intravenous
infusions. Cisplatin generally requires close manage-
ment of fluid and electrolyte balance and is more likely
to cause significant renal toxicity and hearing loss.
Curr Probl Pediatr Adolesc Health Care, July 2005
TABLE 1. Commonly used chemotherapeutic agents for the treatment of brain tumors
Chemotherapeutic agent Mechanism of action Tumors treated Side effects
Vincristine Induces metaphase arrest Low-grade gliomas as well as Constipation, jaw pain with
through the binding of high-grade and malignant administration, and
tubulin brain tumors peripheral neuropathy, which
is usually reversible and
related to cumulative doses
Etoposide Binds tubulin and interacts Malignant brain tumors Nausea, myelosuppression,
with topoisomerase II and alopecia; increased risk
resulting in cell-cycle arrest of secondary malignancies
Cisplatin, Carboplatin Alkylating agents Variety of CNS tumors Renal toxicity and hearing loss;
highly emetogenic
Cyclophosphamide Alkylating agent that inhibits High-grade or malignant brain Myelosuppression, nausea,
DNA synthesis tumors alopecia, hemorrhagic
cystitis, and impaired fertility
Nitrosureas: Alkylating agents Variety of CNS tumors Nausea and delayed
Lomustine (CCNU, given myelosuppression
orally), Carmustine (BCNU,
given IV)
Methotrexate Anti-metabolite; interferes with High grade or malignant brain Renal toxicity (high doses)
folate metabolism tumors Myelosuppression, neurological
sequelae, stomatitis, and
photosensitivity
Temozolomide Alkylating agent Low-grade as well as high-grade Nausea, constipation, and
pediatric brain tumors myelosuppression

Cisplatin is also one of the most emetogenic chemo-
therapeutic agents used. The toxicity profile of carbo-
platin is similar but usually less severe with respect to
nausea, ototoxicity, and renal toxicity.27 Both plati-
num compounds are myelosuppressive.
Cyclophosphamide is an alkylating agent that inhib-
its DNA synthesis. Cyclophosphamide is usually
given as an intravenous infusion for high-grade or
malignant brain tumors.27 Common side effects in-
clude myelosuppression, nausea, and alopecia. Other
concerning side effects include hemorrhagic cystitis
and impaired fertility.
The nitrosureas Lomustine (CCNU) and Carmustine
(BCNU) are alkylating agents that are given orally and
intravenously, respectfully.27 These agents have good
CNS penetration. The most common toxicities are
nausea and delayed myelosuppression.
Methotrexate is an antifolate drug that causes de-
creased DNA synthesis. It can be given by mouth,
intravenously, or intrathecally. Methotrexate has been
used recently to intensify therapy for pediatric patients
with high-grade or malignant brain tumors.29 Con-
cerning side effects are renal toxicity when given in
high doses. Myelosuppression is also possible as are
neurological sequelae, stomatitis, and photosensitivity.
Temozolomide is a relatively new oral alkylating
agent that has been used for low-grade as well as
high-grade pediatric brain tumors.27 It is generally
well tolerated but is known to cause nausea, constipa-
tion, and myelosuppression.
Tumor cells may have intrinsic resistance to a given
chemotherapy. That is, the tumor resists chemotherapy
cell kill based on some inherent tumor biology. On the
other hand, a tumor may be relatively sensitive to a
chemotherapeutic agent initially but resistance may be
acquired as tumor cells that are relatively less sensitive
survive. The concept of tumor resistance in brain
tumors is similar to other pediatric neoplasms. Adju-
vant therapies are under development to obviate mech-
anisms of resistance. In other pediatric tumors, che-
motherapy dose intensification and multi-agent
chemotherapy regimens have often improved overall
survival, though the intensification of chemotherapy is
at the expense of added iatrogenic toxicity.
The use of chemotherapy in CNS tumors has the
added obstacle of the blood brain barrier (BBB),
which under normal circumstances limits many large
molecules from leaving the peripheral bloodstream to
penetrate the CNS. The BBB is conceptualized as tight
endothelial cell junctions that allow small lipophilic
molecules to permeate into the CNS while excluding
large hydrophilic molecules.27 Thus, there is concern
that systemically administered chemotherapy may not
achieve optimal concentrations within the tumor.
Thus, CNS penetration of chemotherapy agents must
be considered when choosing among them. Despite

Curr Probl Pediatr Adolesc Health Care, July 2005 235

these theoretical concerns, it is thought that the pres-
ence of a CNS tumor partially disrupts the BBB
allowing for even large water-soluble molecules to be
effective chemotherapy agents. This is clinically evi-
dent in the uptake of gadolinium on MRI as well.27
Disruption of the BBB in an effort to enhance chemo-
therapy penetration into the CNS remains an area of
active research interest.
Clinical Trials
Great advances in the management of pediatric
tumors have been realized largely from the participa-
tion of patients and their care providers in clinical
trials. The culture within pediatric oncology is one that
expects enrollment of most patients on a treatment trial
and a study of tumor biology. The majority of patients
eligible for an available clinical trial in the United
States are enrolled in one. This is in sharp contrast to
adult cancer patients who are not likely to be enrolled
in a clinical trial. The relative rarity of pediatric
tumors makes clinical trial participation through con-
sortiums necessary as most single institutions will not
have enough pediatric tumor patients within a reason-
able time period to perform a clinical trial for a
specific disease. The Children’s Oncology Group
(COG) is an international consortium devoted to
clinical and laboratory research for patients with
pediatric tumors. Most tertiary care centers throughout
the US that treat pediatric cancer patients are COG
institutions and many nontertiary centers are affiliated
as well.
COG is divided by disease discipline and there are a
number of clinical and biology trials available for
children with brain tumors. The goal of each COG
subcommittee is to have an available clinical trial for
each specific disease. As such there is presently
available a distinct clinical trial for medulloblastoma,
high-grade gliomas, recurrent high-grade gliomas,
ependymomas, low-grade gliomas, brain stem glio-
mas, and others. Enrollment in a given study is at the
discretion of the treating oncologist and must be made
with the full informed consent of a parent and the
assent of older children. Patients may only be enrolled
at COG institutions that have institutional IRB ap-
proval for the clinical trial to be offered.
According to their website (www.pbtc.org), The
Pediatric Brain Tumor Consortium (PBTC) was
formed by the National Cancer Institute (NCI) in 1999
236
to improve the treatment of primary brain tumors in
children. The PBTC comprises 10 institutions with
extensive clinical experience and research focus on
pediatric brain tumors. The PBTC’s main focus is on
novel therapeutic approaches. Other goals are devel-
oping more accurate prognostic markers and neuroim-
aging techniques.
Family and Physician Resources
There are many local resources and foundations for
children with cancer and specifically for children with
brain tumors. Family education is vital so that they
understand the rationale behind their child’s treatment
plan and the resources available to families of children
with cancer. Centers with experience caring for chil-
dren with cancer should facilitate contact for families
under their care. CureSearch (www.curesearch.org) is
the parent organization of the Children’s Oncology
Group and the National Childhood Cancer Foundation
and can provide outstanding information for families
and physicians alike. The Children’s Brain Tumor
Foundation (www.cbtf.org) is another suggested re-
source for families of children with brain tumors.
Etiology of Pediatric Brain Tumors
For the vast majority of CNS tumors in children, the
etiology cannot be defined. Known risk factors include
high-dose therapeutic radiation (uncommonly a factor
in pediatric patients) and genetic syndromes including
neurofibromatosis type 1 and type 2, Li-Fraumeni
syndrome, Turcot syndrome, Gorlin syndrome, tuber-
ous sclerosis, and von Hippel-Lindau syndrome.30-32
Several environmental factors have been extensively
studied but remain inconclusive. A common concern
of patients and their families is the risk of exposure to
cellular phone use, but at least two large studies failed
to show an association between brain tumor develop-
ment and cellular phone use.33,34 Another common
concern is the effect of nonionizing electromagnetic
fields that can be emitted from power lines. This has
been extensively studied and the data do not support a
correlation between electromagnetic fields and brain
tumors.32,35,36
Common Pediatric CNS Tumors
The World Health Organization (WHO) classifica-
tion is the most widely accepted classification system
Curr Probl Pediatr Adolesc Health Care, July 2005
and is categorized by histological appearance37 (Table
2). The WHO system classifies CNS tumors as tumors
of neuroepithelial tissue, tumors of peripheral nerves,
tumors of the meninges, lymphomas, and hematopoi-
etic neoplasms, germ cell tumors, tumors of the sellar
region, and metastatic tumors. In the pediatric popu-
lation tumors of neuroepithelial origin are by far the
most common and include astrocytic tumors, embry-
onal tumors, and ependymal tumors. The WHO clas-
sification also includes tumor Grades I, II, III, and IV,
which indicate varying malignant potential with Grade
IV tumors having the greatest malignant potential.
Despite the WHO system, many tumors remain diffi-
cult to classify and neuropathology remains one of the
more challenging subspecialties within pathology with
regard to definitive diagnosis.
While cumbersome, classification is important in
dictating treatment strategy and prognosis. Thus, fur-
ther delineation of the more common pediatric tumors
is warranted. Astrocytic tumors include low-grade
astrocytomas, anaplastic astrocytomas, and glioblas-
toma multiforme. Ependymal tumors include ependy-
momas of various subtypes. Embryonal tumors in-
clude medulloblastomas and supratentorial primitive
neuroectodermal tumors (PNETs).
Many clinicians find it useful to classify CNS lesion
by location as well as tumor type38 (Table 3). Supra-
tentorial tumors may present with symptoms or signs
that reflect their location. Tumors in proximity to the
optic chiasm or hypothalamus often present with
visual loss or visual field deficits, hormonal abnormal-
ities, and behavioral changes. Tumors in the region of
the pineal gland can present with abnormalities of eye
movements. Hemispheric lesions can present with
focal neurologic signs or induce seizures. Supratento-
rial tumors can also present with signs of increased
ICP secondary to obstruction of flow of cerebrospinal
fluid. Infratentorial tumors (cerebellar tumors, pilo-
cytic astrocytomas, medulloblastomas) can present
with gait abnormalities, ataxia, and signs of increased
ICP as a result of obstruction of the fourth ventricle.39
The frequency of certain CNS tumor types in chil-
dren is markedly distinct from that observed in adults
in whom metastatic lesions and high-grade gliomas are
much more common. Approximately half of all pedi-
atric brain tumors are low-grade cerebellar astrocyto-
mas (gliomas). PNETs (of which medulloblastomas
are a subset) are the most common malignant CNS
tumors in pediatric patients and account for over 20%
of all pediatric brain tumors. Other gliomas represent
Curr Probl Pediatr Adolesc Health Care, July 2005
TABLE 2. Classification strategies for common pediatric brain tumors
by histology/tissue type: WHO classification
Neuroepithelial tumors
Astrocytic
Low-grade astrocytoma
Anaplastic astrocytoma
Glioblastoma multiforme
Embryonal
Medulloblastomas
Supratentorial primitive neuroectodermal tumors (PNETs)
Atypical teratoid/rhabdoid tumor
Ependymal
Various subtypes of ependymomas
TABLE 3. Classification strategies for brain tumors by location: with
associated symptoms signs
Location Associated symptoms/signs
Supratentorial Signs of increased intracranial pressure
Optic chiasm Visual field defects, visual loss, hormonal
Hypothalamic abnormalities, behavior changes
Pineal Abnormal eye movements
Hemispheric Focal neurologic signs, seizures
Infratentorial
Cerebellar Gait abnormalities, ataxia
Brain stem tumors Signs of increased intracranial pressure/
Medulloblastoma 4th ventricle obstruction/Cranial nerve
dysfunction
approximately 20% of pediatric brain tumors, and
ependymomas account for approximately 10%.30-32
Low-Grade Gliomas
Low-grade gliomas are the most common brain
tumors in children accounting for just over half of all
pediatric brain tumors. Within “low-grade gliomas”
there are variations in histology, but in general treat-
ment decisions are made based on the general diagno-
sis of low-grade glioma rather than the subtype. For
example, children eligible for the most recent Chil-
dren’s Oncology Group Protocol for low-grade glio-
mas included those with fibrillary, protoplasmic, and
mixed variants. Other types include pilocytic astrocy-
tomas, pleomorphic xanthroastrocytomas, and sub-
ependymal giant cell astrocytomas.
Gross total resection is likely to cure a low-grade
glioma. Frequently complete resection is not possible.
Following incomplete resection, the options are obser-
vation alone with regularly scheduled MRIs or adju-
vant treatment. Some data suggest that low-grade
gliomas may be stable or even regress following
partial resection.40 As such, intervention is only nec-
essary if the patient is symptomatic or if the tumor is
237
located where even minimal increase in size could
have profound detrimental effect. Treatment is clearly
indicated if there is tumor progression following
incomplete resection or recurrence.
Children with neurofibromatosis Type 1 have an
increased risk of developing CNS tumors, especially
low-grade optic pathway gliomas. The natural pro-
gression of these tumors is not predictable and treat-
ment can be deferred until there is clear progression or
impending neurological compromise. Given the poten-
tial added toxicity and increased risk of secondary
malignancies in patients with neurofibromatosis, RT is
avoided when possible for these patients.
RT has been the standard therapy for progressive or
recurrent low-grade gliomas. However, given the ef-
fects of RT on young children, chemotherapy is
generally the first-line therapy for children under 10
years of age. A recent Children’s Oncology Group
study (No. 9952) randomly compared two chemo-
therapy plans. Regimen A utilized vincristine and
carboplatin, while Regimen B included thioguanine,
procarbazine, CCNU, and vincristine given for ap-
proximately 1 year or until progression. The results are
not yet published regarding efficacy and safety. An-
other approach has been oral temozolomide, which
provides ease of administration with promising poten-
tial tumor control.24 A new Phase I trial through the
COG incorporates vincristine, carboplatin, and temo-
zolomide (ACNS0126).
Medulloblastomas
Medulloblastomas are the most common malignant
CNS tumor in pediatrics. The peak incidence occurs in
children between 5 and 9 years old.30 Given the
location of medulloblastomas in the posterior fossa,
the typical presenting signs are consistent with hydro-
cephalus resulting from compression or invasion of the
fourth ventricle. Other typical symptoms include irri-
tability, decline in school performance, headache,
emesis, truncal ataxia, nystagmus, and cranial nerve
palsies.30,41 The time course of symptoms is usually 2
to 6 months before diagnosis.42 Medulloblastomas
present with distant spread of disease in approximately
20% of patients and rarely can spread outside the
CNS.41 A small percentage of patients with medullo-
blastoma have a germline mutation such as one found
in Gorlin’s syndrome, Turcot’s syndrome, Li-Frau-
menmi syndrome, or ataxia telangiectasia, but for most
patients the etiology is unknown.30,41,42
238
Diagnosis of medulloblastoma can be predicted by
radiographic appearance and location, but requires
histological confirmation. Given the tendency to
spread throughout the CNS, an MRI of the spine is
indicated to rule out “drop-metastases.” It is important
that the spine MRI be performed either before surgery
or 10 to 14 days after surgery as postoperative blood
products in the CNS may be confused with metastatic
disease.42 Cytological evaluation of CSF is also part of
the standard metastatic evaluation. Of note, CSF
obtained from a lumbar puncture more accurately
reflects the presence of CSF seeding than CSF ob-
tained from ventricular sampling.43 Since medullo-
blastomas only rarely metastasize outside the CNS,
extent of disease evaluation of bone and bone marrow
is not standard but must be considered if clinically
indicated.
Surgical resection is a cornerstone in management of
medulloblastoma; however, a gross total resection has
not been shown to improve outcome compared with
near total resection. Patients with residual tumor less
than 1.5 cm2 have had the same outcome as those with
no radiographically detected residual disease.44 Post-
operative MRIs obtained more than 48 to 72 hours
after surgery may be difficult to interpret based on
edema, gliosis, and residual blood product degrada-
tion; as such, postoperative MRI should be obtained
within 1 or 2 days after surgery to accurately assess the
amount of residual tumor.42
Patients with medulloblastoma can be stratified ac-
cording to age, stage, and risk group. Average risk
patients are those 3 years or older with less than 1.5
cm2 of residual tumor and no evidence of dissemina-
tion. High-risk patients are less than 3 years old or
those with greater than 1.5 cm2 of residual tumor or
evidence of dissemination either by radiograph or by
cytological analysis of CSF.
Treatment with surgery alone is not sufficient to
ensure durable remission. Standard approaches for
children over 3 years old include surgery followed by
radiation therapy to the posterior fossa and complete
neuraxis as well as combination chemotherapy. The
present Children’s Oncology Group clinical trial
(ACNS0331) for standard risk medulloblastoma in
children 3 to 7 years old seeks to determine if the total
dose of craniospinal RT and the target volume to the
primary tumor site can be reduced. Following surgery,
patients are randomized to either standard-dose cra-
niospinal RT (23.4 Gy) or reduced-dose craniospinal
RT (18 Gy). Patients are then randomized to receive a
Curr Probl Pediatr Adolesc Health Care, July 2005
radiation boost to either the entire posterior fossa or a
local boost to the tumor bed. During RT, patients
receive weekly vincristine. Following RT, patients
receive chemotherapy including vincristine, CCNU,
cisplatin, and cyclophosphamide. Children 8 years of
age and older receive standard craniospinal RT dosing,
as the concern for RT toxicity is outweighed by the
concern of distant recurrence in this older age group.
There is no standard approach for high-risk patients,
but a common approach in young children with
medulloblastoma is to utilize more intensive chemo-
therapy with myeloablative chemotherapy and autolo-
gous stem cell rescue. This approach has been shown
to be feasible with an overall 3-year survival of 60%.
While this survival rate is not acceptable, it is encour-
aging that this survival rate was achieved with avoid-
ing or delaying RT in many patients.29
High-Grade Gliomas
Like “low-grade glioma,” “high-grade glioma” is a
general pathological description that encompasses
anaplastic astrocytomas (WHO III), glioblastoma mul-
tiforme (WHO IV), and the less common gliosarcoma.
High-grade gliomas account for approximately 15% of
pediatric CNS tumors and may arise throughout the
CNS.30 As a class of tumors, high-grade gliomas are
relatively refractory to adjuvant therapy. The chance
of cure depends on the extent of resection. Patients
who undergo a resection of less than 90% of the tumor
volume have significantly worse outcome than those
who undergo a greater resection.45 Even following a
gross total resection, recurrence is the rule. With the
exception of the youngest patients, children with
high-grade gliomas receive RT even following a gross
total resection. Even those who undergo a gross total
resection and receive adjuvant RT with or without
chemotherapy have less than 50% 5-year survival rate.
The histology within high-grade gliomas is predictive
of outcome as described by WHO grade. That is, the
outcome for glioblastoma multiforme (WHO IV) is
worse than for anaplastic astrocytomas (WHO III).37
The current standard therapeutic approach includes
maximal surgical resection followed by conformal RT
to the area of the tumor with concurrent and mainte-
nance oral temozolomide (Children’s Oncology Group
Trial ACNS0126). For children younger than 3 years
old, multi-agent chemotherapy with or without my-
eloablative chemotherapy and autologous stem cell
rescue has been used with limited success unless a
gross total resection was obtained.46,47 These regi-
Curr Probl Pediatr Adolesc Health Care, July 2005
mens may allow RT to be deferred until the patient is
older. So, while not curative, many believe the expo-
sure to intensive chemotherapy is warranted.
Ependymomas
Ependymomas constitute approximately 9% of pe-
diatric CNS tumors and can arise throughout the CNS.
Ependymal epithelium that lines the ventricles is
thought to be the cell of origin for these tumors. The
most common sites for ependymomas to occur are the
fourth, third, and lateral ventricles as well as the
lumbosacral spinal cord.48 The peak incidence occur-
rence is children less than 6 years old and the great
majority are intracranial.49 Approximately 10% of
ependymomas occur in the spine, but there is an
increased frequency of ependymomas of the spinal
cord in patients with neurofibromatosis type II.30
The overall survival for all children with ependy-
moma is between 50 and 60%.48 However, ependy-
momas include a range of histologic variants ranging
from benign to anaplastic (WHO III) and prognosis is
dependent on histology as well as extent of resection.
While ependymomas are responsive to chemotherapy,
no study has shown that chemotherapy affects overall
survival. However, chemotherapy has been shown to
allow for delayed RT in young patients with ependy-
moma.50,51
For older children, standard therapy includes resec-
tion followed by focal RT.49,52 The current clinical
trial available through the Children’s Oncology Group
(ACNS0121) takes into account extent of resection
and ependymoma histology. Patients with differenti-
ated histology (that is, low malignant potential) who
experience a gross total resection will not receive
adjuvant therapy and will be followed with observa-
tion alone. Patients with a gross total resection of an
ependymoma with anaplastic (malignant) histology
will receive conformal RT as will patients with micro-
scopic disease regardless of histology. Patients follow-
ing a subtotal resection regardless of histology will
receive a trial of chemotherapy with vincristine, car-
boplatin, cyclophosphamide, and etoposide with the
hope that response will make second surgery with a
complete resection possible. Patients then receive
conformal RT.
Craniopharyngiomas
Craniopharyngiomas account for approximately 5%
of all pediatric brain tumors with a peak incidence in
children between 5 and 14 years old. While benign in
239
that they do not disseminate, their local effect on the
optic pathway and pituitary can result in significant
visual and endocrine effects at presentation or follow-
ing therapy.53 Diagnosis is based on MRI findings, but
CT scan is particularly helpful to distinguish cranio-
pharyngiomas in children as 80% will have tumor-
associated calcifications best seen on CT.53,54
Given the endocrine abnormalities associated with
craniopharygiomas, it is helpful to involve a pediatric
endocrinologist in the patient’s care soon after presen-
tation. Delayed endocrine defects may require pro-
longed management.
Treatment of craniopharyngiomas remains contro-
versial, with limited evidence-based data from clinical
trials to support surgical resection versus radiation
therapy. This is a polarizing issue without clear con-
sensus.53,55,56 Many believe that for older patients RT
is the preferred modality and therefore reserve surgery
for younger patients in an effort to avoid toxicity from
RT. Chemotherapy has not been used with consistent
success and in general is reserved for patients that
have multiple recurrences and that are not candidates
for further surgery or RT.
Brain Stem Tumors
“Brain stem tumors” include diffuse intrinsic brain
stem gliomas, exophytic brain stem gliomas, and tectal
gliomas. Intrinsic brain stem gliomas have a classic
radiographic appearance obviating the need for bi-
opsy. Brain stem gliomas can present with cranial
nerve abnormalities or upper motor neuron signs, such
as contralateral hemiparesis, speech changes, stridor,
and hyperreflexia.39
Surgical excision is not possible because of the
tumor location. As such, RT and chemotherapy have
been utilized with minimal success. The 2-year pro-
gression-free survival remains less than 10% despite
RT intensification, chemotherapy intensification, and
combination therapy. The median time to progression
is generally 6 months and the median time to death is
less than 1 year.25,57,58
Patients that achieve a good initial response to
steroids and RT may enjoy a window of neurological
normalization, but almost all progress. New strategies
are needed. The Children’s Oncology Group presently
has a trial incorporating oral Temozolomide with RT
(ACNS0126) and a Phase I trial utilizing Motexafin-
Gadolinium as a radiosensitizer for involved field RT.
240
End of Therapy
Even when treatment has been successful and well-
tolerated, the end of therapy is frequently anxiety-
provoking for the patient and family. Many have
difficulty transferring from the active role of “doing
something” to treat the tumor to the more passive role
of observation. Patients must also adjust to the less
frequent reinforcement and support that they received
during the more intense treatment period.
Just as anticipatory guidance is an important role for
the general pediatrician, anticipatory guidance from
pediatric oncologists can help allay many fears and
ensure better follow-up. An open discussion about the
family’s feelings about the end of therapy is an
essential part of comprehensive and compassionate
care.
In general, the tumor follow-up and surveillance
after completion of therapy is straightforward. Most of
the time patients require follow-up MRIs at 3-month
intervals for the first years with a gradual decrease in
imaging frequency over the next few years until a
yearly follow-up MRI is adequate. It is important to
have the scans performed in a consistent manner so
that slight alterations in technique do not confound
interpretation. Many neuroradiologists prefer the scans
to be performed at their center under specific guide-
lines. For patients with residual MRI abnormalities or
enhancement, it is important to compare each new
scan to a true baseline scan such as the first scan
performed at the end of therapy. Subtle changes
between two subsequent scans may be more difficult
to appreciate than differences between each new scan
and the true baseline scan.
When a patient can be considered “cured” depends
on the type of tumor. In general, the longer off therapy
without recurrence, the less likely recurrence will
happen. Nonetheless, a small chance of recurrence
persists for several years after completion of therapy
for most patients. Other important medical surveil-
lance includes serial endocrine surveillance, audio-
grams, and neuropsychological evaluation.
For the patient, the return to routine activities can be
very challenging. Most patients have prolonged school
absences. The return to school can be very difficult
especially when the patient has suffered physical,
esthetic, cognitive, or emotional effects from the
tumor or therapy. Some centers have child-life spe-
cialists that visit the school to meet with teachers or
even the patient’s classmates to help answer questions
Curr Probl Pediatr Adolesc Health Care, July 2005
about the student’s absence and return. Other physi-
cians prefer to contact the school principal, teacher, or
nurse to discuss particular concerns regarding the
patient. Of course such contact must be made with the
parent’s permission and preferably with the patient’s
knowledge.
Another transition is regarding medical care. For
family convenience as well as medical concerns,
pediatric oncologists sometimes serve as the general
pediatrician for patients receiving therapy. After inten-
sive therapy, many patients’ families are unsure what
medical issues should be referred to their general
pediatrician and what issues require involvement of
the oncologist.
Following up with immunizations is another con-
cern. During chemotherapy, few oncologists give rou-
tine vaccinations. The recommendation is to provide
seasonal influenza vaccination. Immediately after che-
motherapy, the efficacy of vaccination is variable.
Three to 6 months after immune-suppressive chemo-
therapy, patients should receive routine vaccinations
again and vaccinations to catch up for those missed.
Long-Term Follow-up
With the increasing success for pediatric oncology
patients in general, there has been an enhanced aware-
ness regarding issues of long-term follow-up. Some
centers have clinic sessions devoted strictly to these
patients. Most centers do not have dedicated clinics for
long-term follow-up and rely on the oncologist to
coordinate and oversee this aspect of care. While
recurrence is the most common cause of late death,
neurological, neurocognitive, and endocrine distur-
bances are prevalent disabilities among pediatric brain
tumor long-term survivors.59
Deficits may result from the tumor itself or as a
consequence of surgery, RT, or chemotherapy. In
general most consider RT the most detrimental factor
in later cognitive development. Cognitive deficits are
most completely described among children surviving
posterior fossa tumors (specifically medulloblastomas
and ependymomas). These patients tend to suffer
significant losses in IQ scores likely from an inability
to keep learning at a normal pace rather than from a
loss of knowledge. Risk factors for a greater degree of
IQ loss include younger age at time of treatment,
longer time since treatment, female sex, and clinical
variables such as exposure to radiotherapy, radiother-
Curr Probl Pediatr Adolesc Health Care, July 2005
apy dose, and treatment volume, and presence of
hydrocephalus.60
There is a consensus that radiation to young children
is more likely to result in significant cognitive delay.
As discussed, studies have been directed at avoiding
RT in young patients or at least delaying RT by up
front chemotherapy in an effort to preserve intellectual
outcome.61
A recent study illustrated that survivors of medullo-
blastoma demonstrated significantly less development
of normal-appearing white matter (NAWM) volume
than healthy controls. As NAWM volume is known to
be associated with neurocognitive test performance,
the authors suggest volumetric monitoring of brain
development to be used to guide the care of survivors
and assess clinical trial toxicity.62 Pediatric medullo-
blastoma survivors also demonstrate abnormal hip-
pocampal development following treatment.63
Given the known neurocognitive effects of brain
tumors and their management, comprehensive neuro-
psychological testing is indicated for years after treat-
ment. Many clinical trials provide clear guidelines
regarding the precise testing required. Multiple testing
tools are often needed to provide a comprehensive
analysis from specialized psychologists.64
Endocrine complications are another major concern
for pediatric brain tumor survivors. Tumor invasion
and surgical causes of endocrine dysfunction can
occur but studies suggest the risk of endocrine dys-
function is increased by RT.65 The most frequent
endocrine abnormality secondary to lesions of the
hypothalamic-pituitary area is growth hormone defi-
ciency.66 Growth hormone replacement in growth
hormone deficient brain tumor survivors has been
shown to result in an overall greater final height in at
least one study.67
Pediatric brain tumor patients who receive RT for
posterior fossa tumors have been shown to have
diminished total body and lumbar spine bone mineral
density compared with the general population despite
management of growth hormone deficiency and hypo-
thyroidism.68 Hearing loss is not uncommon either
from cochlear exposure to RT or from cisplatin.42
As with other pediatric cancer patients, second
malignancies remain a concern for brain tumor survi-
vors. A recent study showed that the 15-year cumula-
tive incidence rate for malignant second neoplasms
(ie, not primary tumor recurrence) was 4%. While the
total number of patients with second malignancies was
small, there was no clear difference in estimated
241
incidence of second malignancy among patients that
received different types of therapy.69
Palliative Care
For many brain tumor patients, palliation becomes
the main goal of therapy. Often this transition from
cure-oriented care to palliative care is clear, but it may
be quite subtle.
The pediatric oncologist must consider the effect of
this transition on the wide range of people involved.
Usually the decision to pursue palliative care is made
with the patient’s parents. Parents may be resistant to
acknowledge that there is little or no hope for cure, but
parents are usually thankful that they and their child
had the opportunity to make decisions based on the
reality of the disease. Parents who pursue very aggres-
sive therapy despite a very poor prognosis often regret
subjecting their child to the difficulties of therapy.
However, many consider a worse regret would be to
think they had not “done everything.”
Physicians need to balance the hope of new drug
trials and chemotherapy protocols with realistic expec-
tations. Even for physicians and families that seek
novel or aggressive therapy, a conscious decision to
switch the goal of therapy is likely and appropriate at
some point.
The goal of palliative care to most oncologists is to
provide the patient the best quality of life possible.
This concept is not mutually exclusive with providing
chemotherapy depending on the chemotherapy regi-
men and expected toxicity. Some chemotherapy regi-
mens are well-tolerated, easy to take, and may prolong
the period of time that the patient has good function.
The intent, however, of palliative chemotherapy is not
to cause tumor eradication, but to enhance the pa-
tient’s quality of life.
Eventually, palliative chemotherapy becomes less
appropriate in the view of most oncologists as the
patient’s physical and cognitive condition worsens. At
this point, the goal of care is to provide comfort care
and support to the patient and family.
Except for the youngest patients, parents usually
need guidance regarding how to discuss the changes in
treatment with the patient. Most oncologists learn that
incorporating the patient in the discussion of treatment
goals is appropriate. Of course this needs to be done in
a developmentally sensitive manner. While parents
frequently request withholding information from their
242
child, it is important that patients feel they can trust
their doctor. It is likely that patients will conclude
what is going on or overhear conversations and then
learn that others are being deceptive.
Physicians have different approaches to these issues.
Some feel very strongly that patients of a certain age
must be told their prognosis. Other physicians will
actively withhold or misrepresent information out of
respect for the parents’ wishes. Other physicians
respect parents’ wishes by agreeing not to proactively
provide details to the patient but allow the patient the
opportunity to ask questions alone and with the par-
ents. Questions are answered truthfully in a way that is
appropriate for the child’s understanding and develop-
ment. This compromise acknowledges the parent’s
authority and respects the patient’s autonomy. While
many in health care feel compelled to disclose every
detail to a dying patient, others feel that patients will
ask what they want to know when they are ready to
hear the likely answer.
In addition to the patient and the patient’s parents,
the oncologist must consider the needs of the rest of
the patient’s family. Grandparents must cope with the
loss of their grandchild and the suffering of their
children. After experiencing major changes in family
dynamics, siblings must deal with their loss and
frequently experience survivor guilt.
In most cases, there is time to have thoughtful
discussions with parents and patients about where they
want the patient to die. Some prefer the concept of
having their child at home with coordinated home-
hospice care. It is not uncommon even for these
families to request hospitalization as death becomes
clearly more imminent. There are limited inpatient
hospice facilities for children. Many parents prefer to
have their child die in the hospital at which s/he was
treated where the staff is familiar and the parents have
confidence that the patient will be well cared for.
Whether the patient is at home or in the hospital, it
is important to discuss the parent’s and patient’s desire
regarding resuscitation. While a formal “Do Not Re-
suscitate” consent is not strictly required when resus-
citation would be medically futile, most clinicians and
hospital staff prefer an open discussion with the
parents and patient when appropriate to clarify their
wishes. This is particularly important for patients in
teaching hospitals so that house staff and nurses have
clear guidelines, and it is crucial for patients receiving
hospice at home so that when the patient dies ambu-
lance staff has clear direction.
Curr Probl Pediatr Adolesc Health Care, July 2005
 In general, malignancy is considered a contraindica-
tion for organ donation.70 In some circumstances, eye
donation may be possible. While most clinicians have
difficulty raising this prospect with families, many
parents will be thankful for the opportunity. It is
appropriate to check with the organ procurement
center so that parents are given accurate information
and the topic is raised only when donation is possible.
After a child’s death, health care providers must
balance the need to continue to provide support to the
family with the family’s need for privacy. The correct
balance can only be defined for each family. Many
families are grateful when members of the health care
team attend funerals or make contact after the child’s
death. Other families prefer more distance. At a
minimum it is important that families know they are
welcome to call for help and support. The relationship
does not end with the death of their child.
Finally, it is important to note the effect of a
patient’s death on colleagues and staff. While sea-
soned oncologists may have developed a successful
coping mechanism regarding patient death, the refer-
ring pediatrician, junior colleagues, and staff may need
guidance and support. Many centers have regular
memorial services for their patients. Some centers
have structured discussions to provide an outlet for
physicians, nurses, and other staff. Just as the health
care team looked to the lead physician for treatment
decisions, members of the team may look to the
attending physician at the time of a patient’s death.
Summary
Brain and spinal cord tumors represent the most
common solid tumors in children. Recent advances in
imaging techniques, neurosurgical techniques, chemo-
therapy approaches, and radiation oncology have re-
sulted in some improvement in overall survival and
morbidity. However, the prognosis for many children
with high-grade and malignant brain tumors remains
guarded in terms of mortality and long-term sequelae.
Given the rarity of tumors in children, patients are
likely best served at tertiary centers that can offer a
comprehensive multidiscipline approach.
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