paediatrics Brussels 17

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Volume 88 Number 2 2014

Quality of survival in the PNET4 study

Demographic characteristics and postoperative neurology in participants and nonparticipants by treatment

Table 1

Participants

Nonparticipants

n1, n2 (HFRT, STRT)

n1, n2 (HFRT, STRT)

Characteristic

HFRT

STRT

HFRT

STRT

Demographic characteristics Median [range] age at diagnosis (y) Median [range] age at assessment (y) Median [range] interval from diagnosis (y)

(74, 77)

(43, 50)

74, 77

8.7 [3.2-20.8] 9.7 [3.3-20.4]

43, 50

9.0 [4.2-17.6]

8.5 [5.0-17.8]

15.1 [9.1-26.4] * 14.5 [10.6-23.6] *

74, 77

14.9 [7.5-29.9] 15.9 [8.6-29.6]

43, 50

7.1 [4.2-9.9] *

6.5 [4.2-9.9] *

74, 77

5.7 [4.2-9.9]

5.8 [4.1-9.8]

43, 50

Males, n (%)

74, 77 68, 71

51 (69)

46 (60)

43, 50

25 (58)

29 (58)

Midparental height z -score (SD)

0.09 (0.80)

-0.10 (0.90)

4, 10

NT

NT

Premorbid developmental impairment, n (%)

47, 49

1 (1)

5 (6)

11, 18

2 (5)

0

Postoperative neurology, n (%) y

(74, 77)

(43, 50)

Impaired consciousness Impaired nerves III, IV, VI

72, 74 70, 71 64, 68 74, 77

1 (1)

2 (3)

41, 50 37, 45 29, 39 43, 50

2 (5)

2 (4)

32 (46) 36 (49)

22 (29) 37 (48)

16 (37) 19 (44)

13 (26) 23 (46)

Ataxia

Cerebellar mutism 3 (6) Abbreviations: HFRT Z hyperfractionated radiation therapy (see Patients and Methods); NT Z not tabulated as insufficient data; STRT Z standard radiation therapy (see Methods and Materials). * For nonparticipants, median age at assessment and interval from diagnosis was estimated using January 1, 2011, the midpoint of the assessment period, as the notional assessment date. y Percentages are expressed as a percentage of total number of participants or nonparticipants, using conservative assumption that the feature was not present in cases not reported. 6 (8) 4 (5) 6 (14)

0.10-0.76, P Z .011) ( Fig. 2 , Table 2 ), without a difference be- tween treatment arms in weight decrement ( Table 2 ). The mean group decrement from mid-parental height z -score (ie, genetic target) was also significantly greater after HFRT, by 0.55 ( Fig. 2 ).

group ( < 8.0 years at diagnosis) ( Table 3 ). As with the unstratified analysis, mean intergroup z -score differences were not appreciably altered by adjustment for sex and cerebellar mutism or by exclusion of the 6 patients with premorbid developmental impairment. The differences in executive function z -score were not, however, supported by any significant differences between treatment groups at any age with respect to scores on cognition- related subscale measures of health status (HUI3 cognition) or quality of life (PedsQL school functioning, QLQ-C30 cognitive functioning) (not shown).

Impact of demographic characteristics and clinical events

After adjustment in a regression model for age, sex, and the presence of cerebellar mutism (or, alternatively, all perioperative complications), the association between HFRT and lower (ie, better) executive function z -scores in participants of all ages was unchanged (adjusted mean intergroup difference 0.48, 95% CI 0.15-0.80, P Z .005). In a sensitivity analysis, exclusion of the 6 participants with premorbid developmental impairment did not materially alter the effect size of treatment allocation on executive function (mean intergroup z -score difference 0.44, 95% CI 0.11-0.77, P Z .01). We looked for an interaction between age category (see Pa- tients and Methods) and the effect of treatment allocation on the principal outcomes. These interactions, which the study was not powered to detect, fell short of statistical significance but were substantial for the outcomes in which a main effect of treatment allocation was found (interaction estimates 0.62, 95% CI 0.07 to 1.30, P Z .077 for executive function z -score; 0.48, 95% CI 0.20 to 1.16, P Z .16 for height decrement z -score). When younger and older participants were analyzed separately because of these in- teractions, the effects of treatment allocation on executive function and height decrement z -scores were 3-fold larger in the younger

Hormone and other therapies, ototoxicity, and adult social and employment outcomes

Approximately half of participants in each arm had received growth hormone (GH) and thyroxine replacement therapies ( Table 4 ). In both treatment arms, state benefits were being claimed in one-third, special educational support was required in more than half, and the majority used therapy services and reported problems with their appearance ( Table 4 ). Compared with those receiving STRT, use of hearing aids was reported in a significantly higher percentage in the HFRT group (10% and 23%, respectively; Table 4 ). This difference was, again, clearer in the group aged < 8 years at diagnosis (6 of 40 [15%] after STRT, 10 of 30 [33%] after HFRT) than in those older at diagnosis (4 of 51 [7.8%] after STRT, 6 of 40 [15%] after HFRT). However, neither the HUI3 hearing attribute (mean rank single attribute function scores 54.4 and 51.7 in the HFRT and STRT groups, respectively) nor the previously reported audiogram data from this study (see