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good psychometric properties in this population and provides in-
formation that is complementary to but different from perfor-
mance measures , but its use as the only measure of
executive function is a limitation of the present study. The rela-
tively low (10-23%) rates of BRIEF scores in the clinical range for
executive dysfunction are similar to those observed using a
25-item neurocognitive questionnaire, based on the BRIEF, in the
Childhood Cancer Survivor Study and contrast with estimates of
64-85% rates of impaired executive function obtained by direct
assessment in adult survivors of medulloblastoma . This
discrepancy does not bias or explain the observed intergroup
differences. The better BRIEF subscale scores for behavioral
regulation and metacognition underlying the differences in global
scores for executive function, after HFRT relative to STRT, could
indicate a decrease of deficits in working memory, attention, and
processing speed that have been previously reported after STRT
The 3-fold greater differences in executive function and growth
decrement z-scores between treatment arms in study participants
aged 3-8 years at diagnosis is consistent with previous observation
of the greater effects of radiation, especially in combination with
chemotherapy, on the CNS and on bony growth in this age
group but must be treated with caution because stratification by
age was an unplanned, exploratory post hoc analysis in the present
study. The greater incidence of reported use of hearing aids after
HFRT than after STRT is a concern but of uncertain significance
because previously reported audiogram data from this study
were similar in the 2 treatment arms. Alteration of fields to
spare the cochlea has become standard of care subsequent to the
radiation therapy used in this study.
Time from diagnosis, both to height measurement and also to
GH replacement therapy, patient ages and genetic height potential,
and numbers receiving GH and thyroid hormone were similar
between the 2 treatment arms. Evidence of an additional central
GH or thyroid hormonal secretory deficit associated with HFRT
was lacking and, unlike spinal damage is reversible with
hormone therapies . The greater height decrement from
diagnosis observed after HFRT is therefore likely to be due to
relatively greater spinal shortening from radiation damage to both
bony matrix and growth plate and unlikely to result from
differences in skeletal maturity or, thence, time to final adult
height. This could be attributable to the higher biologically
effective craniospinal dose of HFRT on bone, as predicted for a
“late reacting” tissue (see next paragraph), a greater than predicted
Table 2 Outcome z-scores by treatment group in all participants for the 4 principal domains of quality of survival and for decrement
since diagnosis in height and weight z-score
Outcome n1, n2
Group mean (SD) z -scores Mean intergroup difference (95% CI)
P HFRT (a) STRT (b) (b) e (a)
Quality-of-survival measures
Executive Function BRIEF-GEC z-scor 68, 71 0.25 (0.87) 0.24 (1.06) 0.48 (0.16 to 0.81) .004
Health Status HUI3 z-scor 55, 59 0.12 (0.86) 0.14 (1.18) 0.26 ( 0.65 to 0.12) .40
SDQ behavioral difficulties z-score y 50, 50 0.11 (0.89) 0.11 (1.10) 0.23 ( 0.17 to 0.63) .25
Quality of Life z-score z 62, 66 0.07 (1.02) 0.07 (0.98) 0.14 ( 0.49 to 0.21) .42
Height and weightx
Height decrement from diagnosis 59, 56 1.27 (0.90) 0.84 (0.87) 0.43 (0.10 to 0.76) .011
Weight decrement from diagnosis 59, 60 0.42 (1.02) 0.21 (0.91) 0.20 (0.15 to 0.55) .27
Abbreviations: BRIEF-GEC Z Behavior Rating Inventory of Executive Function Global Executive Composite; CI Z confidence interval; HUI Z
Health Utilities Index; SDQ Z Strengths and Difficulties Questionnaire. Other abbreviations as in
* By proxy-report if aged <18 years; by self-report if aged 18 years. Higher BRIEF-GEC scores indicates worse executive function. Higher HUI3
scores indicate better health status.
y By proxy-report if aged <18 years; not available if aged 18 years. Higher SDQ scores indicate worse behavior.
z By self-report Quality of Life Inventory if aged <18 years; by self-report Core 30-item version of Quality of Life questionnaire, if aged 18 years.
Higher scores indicate better quality of life.
x Expressed as a z-score where mean Z 0, SD Z 1 for the healthy United Kingdom population. More negative scores indicate greater decrement in
height and weight z-scores between dates of diagnosis and follow-up.
HFRT
STRT
H e ig h t z -s c o re s
B a s e lin e (a )
X S (b )
D e c re m e n t (b -a )D e c re m e n t p e r y r
D e c re m e n t fro m M P H
-1 .6
-1 .4
-1 .2
-1 .0
-0 .8
-0 .6
-0 .4
-0 .2
0 .0
0 .2
0 .4
0 .6
P =0.405
P =0.122 P =0.011 P =0.016 P =0.005
n = 67 62 64 64 59 56 59 56 59 55
Fig. 2. Group mean height z-scores by treatment allocation.
Height z-scores (see Patients and Methods) (a) at baseline, (b) at
cross-sectional (XS) follow-up, (c) decrement Z (b) minus (a), (d)
decrement per year, (e) decrement from mid-parental height
z-score (MPH). Error bars indicate 95% confidence intervals.
Volume 88 Number 2 2014 Quality of survival in the PNET4 study 297