This article was written for The Childhood Brain Tumor Foundation,Germantown, MD 20876
Infantile Brain Tumors
by Brian Rood, MD, pediatric oncologist
Children's National Medical Center, Washington, D.C.
and
research investigator at the
Children's Research Institute
Approximately 70% of brain tumors in children under 2 years
of age are made up of 3 distinct types: medulloblastoma, ependymoma, and
low-grade gliomas.
Less commonly, infants may be diagnosed with teratomas (mature or
immature) or the atypical teratoid-rhabdoid tumor. Medulloblastoma
always occurs in the lower compartment (posterior fossa) of the brain but
ependymoma and glioma can occur in either the upper or the lower
compartments.
Overall, 60-70% of infantile brain tumors arise in the upper
(supratentorial) compartment.
Posterior fossa tumors can disrupt the flow of the cerebral
spinal fluid (CSF) that baths the brain and spinal cord. This can lead to a
build up of pressure in the head, which causes nausea, vomiting, headache, and
lethargy. In
the infantile group, these symptoms often present as persistent vomiting,
lethargy, irritability, failure to adequately gain weight, and loss of
developmental milestones. In the youngest of patients, in whom the
bones of the skull have not yet fused, disproportionate head growth and a
bulging fontanelle can be signs of increased intracranial pressure. Less commonly,
infants will present with seizures or focal findings of weakness in the face,
eye muscles or extremities. In some cases, extremity weakness can appear
as a rapidly developing hand preference. Many infants present with non-specific
findings which are attributed to more common maladies. Therefore, these
patients are often treated for infectious or gastrointestinal diagnoses prior to
the discovery of their brain tumor.
Historically, brain tumors in children were treated by
surgical excision and, for those tumors with a propensity toward recurrence with
metastatic potential, cranial irradiation. Radiation therapy directed to the
developing supratentorial brain has profound effects including neuro-cognitive
deficits and hypopituitarism; a hormonal deficiency that can result in growth
failure, hypothyroidism, failure of sexual maturation, inability to respond to
physical stresses and electrolyte imbalances. The severity of these sequelae is inversely
proportional to the developmental maturity of the brain. Therefore, current
treatment approaches strive to use chemotherapy to delay or eliminate the need
for radiotherapy in children less than 3 years of age.
The treatment of brain tumors with chemotherapy is
complicated by the presence of the blood brain barrier (BBB). The BBB normally
functions to protect the brain from toxins and infectious agents in the
bloodstream. A
functional BBB prevents the effective passage of chemotherapeutic agents from
the blood into the brain tumor. In the areas immediately adjacent to the
brain tumor, the BBB is often porous due to the blood vessel recruitment
activity of the tumor. However, the BBB is still able to impede the
optimal exposure of all brain tumor cells to systemically infused
chemotherapy.
Two methods have been developed to overcome this difficulty, high dose
chemotherapy with stem cell rescue and intrathecal administration of
chemotherapy.
Increasing the dose of systemically administered chemotherapy in order to
overwhelm the BBB, and achieve higher levels in the brain tumor, is limited by
the toxicity to the blood forming cells of the bone marrow. This toxicity
presents risks for bleeding, anemia, and infection. Blood forming stem cells,
harvested from the peripheral blood, stored and infused after the chemotherapy,
reconstitute the bone marrow and ameliorate the dose limiting toxicity of high
dose chemotherapy.
The second approach, intrathecal administration, involves instilling the
chemotherapeutic agent through the BBB directly into the cerebral spinal fluid
using a surgically placed reservoir. Both of these approaches are most effective
for patients with minimal disease remaining after surgery and the first courses
of conventionally delivered chemotherapy.
Although these techniques have resulted in long term
control of brain tumors without radiation in some patients, chemotherapy alone
can not induce durable responses in a significant proportion of patients. In many cases, the
use limited field irradiation is considered to help prevent local
recurrences.
3-D conformal radiotherapy is one way in which this can be done. 3-D
conformal radiotherapy attempts to minimize toxicity by integrating many beams,
precisely directing radiotherapy to the desired site while leaving untargeted
areas minimally exposed. Intensity Modulated Radiotherapy (IMRT) is a
specific conformal technique in which each of the individual beams are shaped in
respect to their energy in order to more tightly focus the treatment area and
better avoid sensitive normal brain structures. Another emerging technique for
focusing radiation is proton beam irradiation. Proton beams have an energy
signature that rapidly drops off as a function of the distance traveled;
allowing for planning that spares sensitive tissue on the far side of the
treatment target. Depending on the tumor size and location, these techniques can
offer an advantage in delivering focused radiation to the young child.
In general, chemotherapy can make it possible to delay,
decrease or eliminate the radiation normally given to the entire brain and spine in an attempt to prevent relapse
distant from the site of the primary tumor. The success of these chemotherapy delivery
techniques in decreasing neuropsychological sequelae while delivering effective
therapy remains an area of investigation.
The treatment of pediatric brain tumors continues to be a
very challenging endeavor and all too often, the therapy induces unwelcome
long-term side effects. This is especially true in young children due
in part to the unacceptable neuropsychological effects of radiation on the
developing cortical brain. It is hoped that chemotherapy, administered
in novel ways, can reduce, delay or, in some special circumstances, remove
radiotherapy from the treatment of brain tumors in the very young.
Dr. Brian R.. Rood is a Research Investigator, Children's
Research Program, Assistant Professor of Pediatrics at The