paediatrics Brussels 17

1692 / 1708

in performance on the test of motor speed between
patients with infratentorial versus supratentorial
tumors at any time point.
There was a significant relationship between radia-
tion dose to the left temporal lobe and performance on
the visual perception test. However, the effect was very
small and may not be clinically significant. There was
no difference in performance on this test between left-
and right-handed individuals at any time point.
The absence of a significant association between
radiation dose to the hippocampi/temporal lobes and
performance on tests of verbal learning and memory,
visuospatial working memory, and vocabulary may be
due to low statistical power in detecting a difference,
since the motor function and spatial perception tests
are dependent on a complex interplay among multiple
neural pathways and may be more sensitive than the
other tests examined in this study.
Second, given the relatively small number of patients
enrolled in this study, we were not able to perform
a detailed analysis of all potential variables that might
contribute to cognitive outcomes. For example, con-
founding variables such as tumor location, recurrence
patterns, and surgical interventions may have contribut-
ed to the changes in neurocognitive function that we
report. Our data suggest potential recovery in function
over time from tumor and surgery-related intervention.
The relationships among other disease- or treatment-
related factors beyond radiation dose to the structures
evaluated remain unclear. Future studies enrolling a
larger and potentially more homogeneous patient popu-
lation would be helpful in further evaluating this interac-
tion. Similarly, longer-term follow-up will be important
in ascertaining whether the changes reported in this
study were impacted by acute effects associated with
the disease, surgery, and adjuvant therapy rather than
strictly cognitive late effects of radiation.
In addition, although the eligibility criteria for study
entry were comparable for both the patient and
control groups, there were no children age 0–4 years
in the control group, whereas this age group comprised
21% of the patient group. Because we used standard-
ized, age-adjusted scores for our analysis of the neuro-
cognitive tests, we would not expect this difference to
have an impact upon our results. Similarly, there were
a larger percentage of African Americans in the control
group than in the patient group, but we are not aware
of evidence to suggest that this would impact upon test
performance or interpretation of results.
Third, our series contains missing data, in that not all
patients were evaluated on all tests at all time points, and
missing patients varied among time points. This limita-
tion may be in part related to the poor prognosis and
severity of illness in our patients as well as the
complex social situations of families of pediatric
cancer patients, which may have limited their ability to
present for all scheduled appointments. Additionally,
some of the youngest patients were not tested until the
later time points. Our analyses presume that the existing
data are reflective of the entire group, but future studies
with potentially more complete datasets will be impor-
tant to provide confirmation.
In addition, while our data suggest that limiting radi-
ation dose to the temporal lobe and hippocampus is im-
portant in reducing the neurocognitive sequelae of
radiation to the brain, we do not have sufficient data
to determine a safe radiation tolerance of these struc-
tures. In order to effectively spare these areas using tech-
niques such as intensity-modulated RT, it will be critical
to better define the radiation tolerance and dose response
of these structures. Similarly, further evaluation for a
dose-volume effect in these structures will be important.
Finally, we report results on a limited number of neu-
rocognitive tests, and our analysis includes radiation
dose to only a limited number of brain structures.
Analysis of a broader spectrum of neurocognitive func-
tions and CNS anatomy in future studies will be impor-
tant. It is possible that the associations we report are
confounded by radiation dose to adjacent structures
that were not included in this analysis.
To conclude, we report a significant relationship
between radiation dose to the hippocampus and tempo-
ral lobes and performance on select neurocognitive tests
but do not find a relationship between RT dose to the
SVZ and neurocognitive function. To our knowledge,
this study is one of the first prospective studies to date
to examine the relationship between radiation dose to
NPC-containing niches and neurocognitive function.
Our results have important implications for ongoing
clinical trials such as RTOG 0933, which is a phase II
trial of hippocampal avoidance during whole brain RT
for brain metastases and has a primary objective of per-
formance on a test of verbal learning and memory.
Conflict of interest statement. None declared.
Funding
This work was supported by NIH/NINDS grant no.
R01 NS04285; Intellectual and Developmental Disabi-
lities Research Center-NIH/NICHD grant no. P30H-
D024061-16; the Intellectual and Developmental
Disabilities Research Center, grant no. HD-24061; Jo-
hns Hopkins University School of Medicine Institute f-
or Clinical and Translational Research; and the NIH/
National Center for Research Resources Clinical and
Translational Sciences Awards Program, grant no.
UL1-RR025005.
Redmond et al.: Radiation to neural progenitor niches and neurocognitive outcomes
NEURO-ONCOLOGY † M A R C H 2 0 1 3 367
at Universitaet Leipzig, Institut fuer Informatik/URZ, Bibliothek on August 25, 2014
Downloaded from