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Caˆmara-Costa et al.

International Journal of Radiation Oncology Biology Physics

of participants with perioperative complications and cere- bellar mutism, and results remained unchanged.

completing this test, both in the sample as a whole and in those less than 8 years of age at diagnosis. These effect sizes were large for VIQ and medium for PSI. Other dif- ferences between treatment arms for the remaining cogni- tive measurements were small and nonsignificant. Longitudinal results, although unpowered, indicated no significant effects of treatment allocation on the cognitive outcomes, neither at Time 1 and Time 2, nor from the first to the second assessment. In the present study, treatment was randomly allocated, and follow-up rates for the cognitive assessment were reasonable (63%), which allowed composition of 2 het- erogeneous groups regarding IQ outcomes. However, some limitations should be taken into account. The measure- ments used to assess cognitive performance differed ac- cording to country and, thus, might reflect distinct underlying constructs of cognitive ability. This limitation justifies caution in the interpretation of the results and generalization of these findings. Importantly, these results highlight the urgent need for an international consensus in the measurements used to assess cognitive ability (34) . Moreover, participants were slightly younger at diagnosis than nonparticipants. However, this difference is not likely to have biased our results, as the only significant differ- ences were observed for the subgroup of participants with younger age at diagnosis. Furthermore, the analysis per age category had not been planned in the initial protocol but was carried out in order to bring complementary informa- tion to confirm or refute the observation by Kennedy et al (25) of benefits of HFRT to executive function. Finally, results of the regression analyses remained unchanged even when controlling for the marginally significant excess of perioperative complications, namely cerebellar mutism in the HFRT arm.

Longitudinal analyses

Thirty-five participants (25.6%) underwent 2 cognitive as- sessments. These participants were characterized by longer intervals between diagnosis and the last assessment ( P Z .01) and higher rates of cerebellar mutism ( P Z .03). None of the remaining baseline characteristics was different between participants with cognitive assessment performed at 2 time points and those who had data at 1 time point. The last assessment was performed at a mean interval from the first evaluation of 2.9 years, with the mean interval being similar in both arms. Cognitive measurements did not differ significantly be- tween time point 1 and time point 2 ( Table 3 ). However, there was a tendency for PIQ to increase from the first to the second assessment (difference of 5.9 [95% CI: 1.1-10.7], P Z .019). Moreover, the difference between cognitive outcomes on the 2 occasions of testing, derived by [Time 2 Time 1] did not differ between HFRT and STRT arms ( Table 4 ).

Discussion

The results suggest that treatment allocation contributed to explain specifically the VIQ scores of participants less than 8 years of age at diagnosis. For this subgroup, those allo- cated to the HFRT arm had higher VIQ scores than par- ticipants in the STRT arm. Those allocated to HFRT also had a strong trend, falling short of statistical significance, to higher PSI scores in the reduced number of participants

Mean differences in cognitive outcomes according to treatment allocation and age at diagnosis

Table 2

HFRT

STRT

P *

Outcome

N

M SD

Range

N

M SD

Range

FSIQ

71 40 31 58 31 27 70 39 31 68 38 30 29 18 11

90.3 90.7 89.7 96.3 95.8 96.8 89.7 90.4 88.9 92.3 95.2 83.3 81.1 86.8 90

19.7 21.8 16.8 17.1 17.4 17.1 24.6 15.8 13.8 14.8 11.9 14.7 15.6 13.1 21

40-137 40-137

66 41 25 55 34 21 66 41 25 61 39 22 28 17 11

86.4 87.6 84.5 92.4 97.1 84.8 87.1 88.3 85.1 89.1 88.6 75.4 75.1 75.9 90

18.9 19.3 18.6 20.6 22.1 15.7 17.1 16.8 17.7 15.3 16.1 14.2 15.5 16.3 14.8

40-122 40-118 40-122 43-145 47-145 43-112 40-122 40-118 41-122 55-120 56-120 55-110 50-100 50-100

.24 .49 .27 .28 .79 .02 .43 .66 .40 .21 .69 .16 .05 .27

FSIQ (age > 8) FSIQ (age < 8)

65.5-128.5

VIQ

55-128 55-128 60-126 40-140 40-140 55-124 55-124 65-118 50-112 50-112 62-103 65-128.5

VIQ (age > 8) VIQ (age < 8)

PIQ

PIQ (age > 8) PIQ (age < 8)

WMI

WMI (age > 8) WMI (age < 8)

PSI

PSI (age > 8) PSI (age < 8)

50-96 .08 Abbreviations: FSIQ Z full scale intelligence quotient; PIQ Z performance intelligence quotient; PSI Z processing speed index; VIQ Z verbal intelligence quotient; WMI Z working memory index. Other abbreviations as in Table 1 . * Student t test.