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lung tumors could be safely escalated to increase tumor
control. Most convincing was the noticeable reduction in
acute side effects leading radiation oncologists to consider
the application of the same techniques in pediatric CNS
tumors.
The advent of conformal radiation therapy set the stage
for a renewed look at the role of radiation therapy in the
treatment of children with ependymoma. A prospective
phase II trial (RT-1) was conducted at St. Jude Children’s
Research Hospital between 1997 and 2003. The primary
goals were to objectively document the side effects of
radiation therapy and to demonstrate that tumor control
with a 10-mm clinical target volume margin was equivalent
to conventional radiation therapy. Eighty-eight patients with
ependymoma were enrolled during a 5-year period and
most were under the age of 3 years at the time of
irradiation. For the first time, radiation therapy was a
component of frontline management in a clinical trial for
children under the age of 3 years. The rate of gross-total
resection (GTR) exceeded 85% as patients were systemat-
ically referred for second surgery prior to radiation therapy
to minimize the amount of residual tumor. Through this
process, the feasibility and safety of second surgery were
demonstrated. The reported 3-year progression-free survival
was 75% and the 3-year cumulative incidence of local
failure was 15% ]. These results were attributed to the
high rate of gross-total resection, newer radiation planning
and delivery methods, the relatively high dose tolerances
for the cervical spinal cord and optic chiasm, and a
cumulative planning target volume dose of 59.4 Gy with
100% coverage. As presented in the same report, the side
effects of radiation therapy were found to be limited in this
vulnerable patient population. Baseline and longitudinal
testing using the prospective battery of neurologic, endo-
crine, and cognitive testing continue to demonstrate that
most long-term survivors function within the range of
normal. Radiation dosimetry was found to correlate with
functional outcomes supporting the goal of target volume
reduction in this vulnerable group of patients ]. The
results of this study were widely accepted as a major
advance, especially for very young children. As these
results were unfolding, investigators in the Children’s
Oncology Group (COG) supported the development and
implementation of the ACNS0121 protocol which was
based on the concepts of conformal therapy developed at
St. Jude Children’s Research Hospital. The COG protocol
was activated in August 2003, widely accepted, and
reached its goal of 350 eligible patients in 4 years ].
In early 2009, an update in the series of patients treated
at St. Jude Children’s Research Hospital was published that
included 153 patients ]. With a median follow-up of
62 months (range 3–112 months) from the initiation of
radiation therapy, the 7-year event-free and overall surviv-
als were 69% and 81%, respectively The 7-year local
control rate was 87%. A subset of patients treated with
immediate postoperative radiation therapy were found to
have even high rates of local control (89%), event-free
(77%), and overall survival (85%) when estimated at
7 years. Extent of resection and tumor grade remain
important prognostic factors. Among the patients with
differentiated ependymoma treated with GTR and
59.4 Gy, there were very few failures. These data define
potential groups for treatment intensification or reduction.
More than a decade later, sufficient experience has been
gained to confirm the promise of conformal radiation
therapy in pediatric CNS tumors and document improve-
ments in disease control and preservation of functional
outcomes in childhood ependymoma. In this report, we will
summarize the data available from the treatment and
follow-up of children irradiated using conformal radiation
therapy including information on side effects.
Materials and methods
Conformal radiation therapy is defined as forward planned
three-dimensional conformal radiation therapy or inverse
planned intensity-modulated radiation therapy (IMRT)
using photons. The goal of treatment is to achieve
conformity of the prescription dose to the targeted volume
and to spare normal tissues including the noninvolved
brain, brainstem, spinal cord, optic chiasm, hypothalamus,
and functional subunits of the cerebral hemispheres or
cerebellum. The nomenclature used to define target vol-
umes for conformal radiation therapy were first issued by
the International Commission on Radiation Units and
Measurements (ICRU) in 1993 and first used in a clinical
trial for ependymoma beginning in 1997 , ]. The
ICRU defines the gross tumor volume (GTV) as the
imaging visible residual tumor or volume of greatest tumor
burden. The clinical target volume (CTV) is defined by a
margin surrounding the GTV that includes microscopic
tumor extension and depends on the tumor. The planning
target volume (PTV) is an additional margin surrounding
the CTV that is meant to account for variability in patient
positioning. To date, these definitions have been used with
one modification: The GTV has been defined to include
residual tumor and/or the tumor bed. This modification fits
with the concept of greatest tumor burden. Recent trials
have prescribed CTV margins of 10 mm and PTV margins
of 3–5 mm (Fig. ).
Conformal radiation therapy requires specialized hard-
ware and software. Both are now widely available. The first
step in conformal therapy planning is computed tomogra-
phy (CT) imaging in the treatment position. CT is the
fundamental data set for three-dimensional treatment
Childs Nerv Syst