1698 / 1708
accordance with each institution’s Institutional Review Board
requirements.
Intellectual and Academic Achievement Testing
The A9961 neurocognitive assessment schedule called for an
evaluation to be completed between 3 and 6 months post-RT, as
well as two follow-up assessments completed at 2 and 5 years
post-study entry. During the study, some of the assessments were
taken according to the planned schedule and others were taken at
varying time points. In order to make maximum use of the avail-
able data, analyses included patients who had at least one assess-
ment between diagnosis and 9 months after completion of
radiation (the baseline test). This is justified on the basis of
research showing the emergence of significant late-effects of ra-
diation after 9 months post-RT (Ris et al.[2]). The number of
times assessed and timing of these assessments are contained in
Table I. Table III shows the observed scores for each year after
radiation therapy.
The test battery in the original COG A9961 protocol included
age-appropriate, gold standard measures of general intellect
(Wechsler Preschool and Primary Scales of Intelligence-Revised,
Wechsler Intelligence Scale for Children-Third Edition, Wechsler
Adult Intelligence Scale-Revised, Wechsler Adult Intelligence
Scale-Third Edition), academic achievement (Wide Range
Achievement Test-Third Edition), visuomotor integration (Beery
Visual Motor Integration Test), adaptive functioning (Vineland
Adaptive Behavior Scale), and social-emotional status (Child
Behavior Checklist). However, the most complete data were for
the intellectual tests and academic measures and so this report
will concentrate on only Full-Scale IQ (FSIQ), Performance IQ
(PIQ), and Verbal IQ (VIQ) outcomes from the intellectual
tests and reading, spelling, and arithmetic outcomes from the
academic achievement tests. Per protocol, intellectual testing
was completed first followed by academic testing. However,
adherence to this order was not specifically documented as testers
were free to use clinical discretion to maximize the validity of the
results.
Statistical Methods
Differences in demographic and clinical characteristics were
investigated using exact chi-squared tests for categorical variables
and Wilcoxon rank sum tests for continuous variables. Random
coefficient models [12] (RCMs) were used to estimate the change
in neurocognitive outcomes over time and to investigate the effect
of covariates on the estimated change. RCMs are an approach for
analyzing multiple assessments on each patient over time. These
models take into account that measurements on the same patient
are correlated. RCMs allow for unbalanced data and use all avail-
able data. Although this study planned assessments at 3–6 months
post-radiation and at 2 and 5 years after study enrollment, patients
were assessed at a variety of times during the study. Time of the
TABLE II. (
Continued
)
At least baseline
intellectual testing, included in
analysis (N
¼
110)
No baseline intellectual
testing, not included in
analysis (n
¼
269)
At least baseline
academic achievement
testing, included in
analysis (n
¼
75)
No baseline academic
achievement testing,
not included in analysis
(n
¼
304)
Yes
N
6
47
5
48
Percent
5.5
17.5
6.7
15.8
No
N
104
222
70
256
Percent
94.5
82.5
93.3
84.2
Age at diagnosis
Median
7.38
8.14
8.16
7.79
Min
3.44
3.10
4.28
3.10
Max
16.82
19.49
16.17
19.49
TABLE III. Observed Intellectual and Achievement Scores
Timing of assessments
in years from completion
of radiation 6 months
FSIQ
a
mean
(SD)
VIQ mean
(SD)
PIQ mean
(SD)
Reading mean
(SD)
Spelling mean
(SD)
Arithmetic
mean (SD)
Baseline
b
96.2 (16.9)
98.6 (16.0)
93.2 (17.4)
98.8 (16.6)
97.1 (17.3)
94.7 (18.6)
1
96.0 (21.3)
100.0 (23.1)
92.5 (17.9)
98.0 (18.8)
102.4 (15.4)
96.0 (20.8)
2
90.1 (17.4)
91.5 (17.6)
90.8 (16.5)
97.8 (15.9)
96.8 (16.3)
93.7 (17.4)
3
99.5 (15.8)
99.6 (11.0)
97.3 (18.4)
92.7 (13.3)
93.0 (14.9)
105.0 (8.5)
4
79.6 (14.9)
83.0 (11.8)
79.4 (19.3)
103.0 (1.73)
93.0 (12.7)
95.7 (23.2)
5
93.5 (13.5)
94.5 (15.2)
92.7 (15.0)
94.0 (17.8)
88.4 (14.9)
92.2 (10.5)
6
75.6 (12.4)
79.9 (12.1)
78.0 (13.1)
78.5 (21.9)
75.0 (12.5)
68.0 (3.0)
a
Intellectual and achievement scores presented as standardized scores with mean of 100 and SD of 15;
b
Diagnosis to 9 months post-radiation.
Neurocognitive Outcome in Medulloblastoma
1353
Pediatr Blood Cancer
DOI 10.1002/pbc