1625 / 1708
Discussion) suggested a higher incidence of ototoxicity after
HFRT. Self-reported social and employment outcomes, only
applicable to participants whose age at assessment was 18 years
(all of whom were also aged 8 years at diagnosis), seemed to be
similar in the 2 treatment arms excepting an excess, in the group
allocated to HFRT, of those driving a motor vehicle
(
Supplementary Table e3
).
Discussion
The PNET4 trial is the first clinical RCT of craniospinal HFRT
versus STRT for medulloblastoma and the first pediatric brain
tumor treatment trial to ascertain QoS information internationally
across Europe. Compared with survivors who had received STRT,
BRIEF scores for executive function in everyday life suggested a
possible benefit to those who had received HFRT 6 years after
enrollment in the PNET4 trial, but the fact that this group did not
show associated benefits on measures of health status or quality of
life is equally important. The HFRT group also suffered a greater
decrement from height
z
-score at diagnosis despite GH treatment,
and use of a hearing aid was more commonly reported after HFRT.
Because treatment allocation was random, differences in
outcomes are inherently unlikely to be attributable to known or
unknown differences in premorbid characteristics. Exclusion
from the analysis of participants reported to have premorbid
developmental impairment did not alter the findings. The simi-
larity of nonparticipant and participant baseline characteristics in
both treatment arms makes attrition bias unlikely, and the
retention rate for QoS follow-up information at 4-9 years from
diagnosis of 62% is high relative to a rate of
<
30%
(31)in other
pediatric neuro-oncology studies and a mean rate of 68% (range,
41-100%) at 1 year follow-up in RCTs for pediatric chronic
conditions
(42) .A system is now in place to include in future
trials the option of direct entry of patients’ responses to elec-
tronic versions of these questionnaires on personal computers or
other devices with Internet access, but its effect on ascertainment
in this context remains to be determined. Radiation therapy
fields, as distinct from fractionation schedules, were the same in
both treatment arms except for the (small) boost to the tumor bed
in HFRT, and there is no reason to suppose that field alignment
differed between the 2 arms.
The BRIEF questionnaire, which relates to everyday function,
has been widely used in patients with acquired brain injury with
Executive Function
Health Status
BRIEF GEC score
parent report
self report
0
20
40
60
80
100
n=49 n=51
n=19 n=20
P
=0.005
P
=0.098
12% 25%
5% 15%
HUI3 global health status utility score
parent report
self report
0.0
0.2
0.4
0.6
0.8
1.0
n=46 n=48
n=50 n=54
P
=0.430
P
=0.900
Behavioural Difficulties
Quality of life (<18 years)
Quality of life ( 18years)
SDQ Total Difficulties score
parent report
self report
0
4
8
12
16
20
n=50 n=50
n=40 n=43
P
=0.420
P
=0.250
14% 24%
15% 12%
PedsQL Total score
parent report
self report
0
20
40
60
80
100
n=51 n=52
n=40 n=44
P
=0.753
P
=0.570
41% 48%
53% 48%
QLQ C-30 Global health status score
0
20
40
60
80
100
n=22
n=22
P
=0.060
(7-17 yrs)
(18-29 yrs)
(7-17 yrs)
(11-29 yrs)
(11-29 yrs)
(7-17 yrs)
HFRT:
STRT:
(7-17 yrs)
(11-17 yrs)
self-report (18-29 yrs)
Fig. 1.
Scores on age-appropriate measures of quality of survival by treatment allocation. Error bars indicate SDs. Executive Function:
Higher scores indicate worse function. Percentages within bars refer to abnormally elevated scores. BRIEF GEC
Z
Behavior Rating
Inventory of Executive Function Global Executive Composite. Health Status: Higher scores indicate better health. HUI
Z
Health Utilities
Index. Behavioral Difficulties: Higher scores indicate worse function. Percentages within bars refer to borderline or abnormal scores. SDQ
Z
Strengths and Difficulties Questionnaire. Quality of life: Higher scores indicate better quality. Percentages within bars refer to “at risk”
scores. PedsQL
Z
Quality of Life Inventory; QLQ-C30
Z
core 30-question version of the European Organization for Research and
Treatment of Cancer Quality of Life Questionnaire. HFRT
Z
hyperfractionated radiation therapy; STRT
Z
standard radiation therapy.
Kennedy et al.
International Journal of Radiation Oncology Biology Physics
296