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Vol. 66, No. 2 2015
Northeast Florida Medicine
Pediatric Oncology
with a steep decline in the dose to adjacent uninvolved critical
structures (Figure 1A). More than a decade of experience with
this technique now exists. To further confine the radiation
dose to the tumor, other highly conformal modalities, such
as proton therapy, are increasingly utilized in children and
teenagers. Due to its properties as a particle, a proton radiation
beam deposits its dose at a specified depth based on its energy,
thereby eliminating the dose beyond the tumor (Figure 1B). In
contrast, with photons, the radiation dose is deposited along
the exit path of the beam beyond the tumor. Developing tissue
is particularly sensitive to radiation, and a reduction in any
dose not actively contributing to eradicating the tumor offers
a benefit, particularly in the pediatric population.
Ependymoma
Ependymomas comprise nearly 10 percent of CNS tumors
in the pediatric population, with approximately 200 cases
per year in the United States.
3
In children, the peak age at
occurrence is 5 years old, and these tumors more commonly
develop in the brain than the spine. Of those in the brain, two-
thirds develop in the infratentorium, usually along the fourth
ventricle. Brainstem invasion can occur. Surgical resection is
the initial step in management, and is both diagnostic and
therapeutic.The importance of gross total resection (GTR) on
local control and survival is well-established. In a prospective
non-randomized study of 153 pediatric patients, Merchant
et al reported a seven-year event-free survival rate of 77.3
percent with GTR versus 34.2 percent with near total or
subtotal resection (p<0.001).
4
Overall survival was similarly
compromised when GTR could not be achieved, yielding an
88 percent versus 52.4 percent rate (p<0.001). All patients
in this study received focal radiotherapy to the tumor and/
or tumor bed, the majority receiving a radiation dose of 59.4
Gray (Gy). In this study, the use of chemotherapy before
radiation therapy actually portended an inferior outcome,
likely due to the risk of progression prior to radiation therapy
(the seven-year event-free survival rate was 48.7 percent with
chemotherapy versus 75.9 percent without; p=0.008). An
open cooperative group study by the Children’s Oncology
Group (study ACNS 0831) is investigating the role of adju-
vant vincristine, cisplatin, etoposide, and cyclophosphamide
following GTR and radiation therapy.
Historically, the radiation target included the entire
neuraxis using craniospinal irradiation (CSI). After further
understanding of recurrence patterns, most of which are
local, the radiation field decreased in volume to the tumor
bed, including all of the surfaces with which the tumor was
in initial contact. Retrospective data support the recommen-
dation for postoperative radiotherapy, including after GTR.
In 2005, Rogers et al reported on 45 patients with posterior
fossa ependymoma, 71 percent of whom had undergone a
GTR.
5
Approximately one-third of these patients received
focal postoperative radiotherapy.The 10-year local control rate
was 50 percent with GTR alone and 100 percent with GTR,
followed by radiation therapy (p= 0.018). Timmerman et al
conducted a prospective study of 34 patients less than 3 years
old with anaplastic ependymoma.
6
Treatment was divided
between surgery only, surgery followed by radiation therapy,
or radiation therapy as salvage treatment after a recurrence.
All patients received chemotherapy. Twenty-one children
died because of disease recurrence. Thirteen patients did not
receive radiotherapy, and only three of them survived. Owing
to such findings, and despite a patient’s young age, radiation
therapy is not routinely omitted in infants and toddlers with
ependymoma, even after GTR and treatment with chemo-
therapy. ACNS 1021 is exploring whether radiotherapy can
be omitted in grade 2 supratentorial ependymomas.
Medulloblastoma
Unlike ependymoma, CSI continues as the standard of care
for treatment of medulloblastoma because of its high risk for
neuraxis dissemination. This histology significantly benefits
from trimodality therapy (surgery, postoperative radiation
therapy, and adjuvant chemotherapy). Approximately 500 cases
of medulloblastoma occur annually in the United States, with
the peak age of occurrence at 5 to 9 years.
7
Medulloblastoma
comprises approximately 15-20 percent of pediatric primary
CNS tumors.
8
Surgical resection is first performed, and yields
diagnostic value, in addition to its therapeutic role. The extent
of surgical resection may also be pivotal in the treatment of
medulloblastoma where < 90 percent resection or >1.5 cm2 of
residual tumor results in an increased risk of recurrence, with a
five-year event-free survival rateof 78percent versus 54percent.
9
Radiation therapy typically begins a month after surgery,
accompaniedby concurrent chemotherapy. A landmark study
demonstrated that a lower CSI dose does not compromise
the effectiveness of the treatments, provided chemotherapy is
administered concurrently.
10, 11
The craniospinal dose ranges
from 23.4 Gy to 36 Gy, and includes the entire brain and
the entire spinal canal to the thecal sac. Additional radiation
treatments are then delivered to either the entire posterior
fossa or the tumor bed for a total dose of approximately 54
Gy. It is important to minimize delays or missed treatments
during the course of radiotherapy, particularly for patients
with medulloblastoma. When more than 50 days elapse from
the first day of radiation to the last, both event-free survival
and overall survival decline, compared to patients treated in
fewer than 50 days.
12
