| Summary: | Purpose<p style="box-sizing: border-box; margin: 0px 0px 16px; padding: 0px;">In the European HIT-SIOP PNET4 randomized controlled trial, children with standard risk medulloblastoma were allocated to hyperfractionated radiation therapy (HFRT arm, including a partially focused boost) or standard radiation therapy (STRT arm), followed, in both arms, by maintenance chemotherapy. Event-free survival was similar in both arms. Previous work showed that the HFRT arm was associated with worse growth and better questionnaire-based executive function, especially in children <8 years of age at diagnosis. Therefore, the aim of this study was to compare performance-based cognitive outcomes between treatment arms.</p>Methods and Materials<p style="box-sizing: border-box; margin: 0px 0px 16px; padding: 0px;">Neuropsychological data were collected prospectively in 137 patients. Using the Wechsler Intelligence Scales, Kaufman Assessment Battery for Children, and Raven's Progressive Matrices, we estimated full-scale intelligence quotient (FSIQ) and, when available, verbal IQ (VIQ), performance IQ (PIQ), working memory index (WMI), and processing speed index (PSI).</p>Results<p style="box-sizing: border-box; margin: 0px 0px 16px; padding: 0px;">Among the 137 participants (HFRT arm n=71, STRT arm n=66, 63.5% males), mean (±SD) ages at diagnosis and assessment respectively were 9.3 (±3.2) years of age (40.8% < 8 years of age at diagnosis) and 14.6 (±4.3) years of age. Mean (±SD) FSIQ was 88 (±19), and mean intergroup difference was 3.88 (95% confidence interval: −2.66 to 10.42, <em style="box-sizing: border-box; margin: 0px; padding: 0px;">P</em>=.24). No significant differences were found in children >8 years of age at diagnosis. In children <8 years of age at diagnosis, a marginally significant trend toward higher VIQ was found in those treated in the HFRT arm; a similar trend was found for PSI but not for PIQ, WMI, or FSIQ (mean intergroup differences were: 12.02 for VIQ [95% CI: 2.37-21.67; <em style="box-sizing: border-box; margin: 0px; padding: 0px;">P</em>=.02]; 3.77 for PIQ [95% CI: −5.19 to 12.74; <em style="box-sizing: border-box; margin: 0px; padding: 0px;">P</em>>.10]; 5.20 for WMI [95% CI: −2.07 to 12.47; <em style="box-sizing: border-box; margin: 0px; padding: 0px;">P</em>>.10]; 10.90 for PSI [95% CI: −1.54 to 23.36; <em style="box-sizing: border-box; margin: 0px; padding: 0px;">P</em>=.08]; and 5.28 for FSIQ [95% CI: −4.23 to 14.79; <em style="box-sizing: border-box; margin: 0px; padding: 0px;">P</em>>.10]).</p>Conclusions<p style="box-sizing: border-box; margin: 0px 0px 16px; padding: 0px;">HFRT was associated with marginally higher VIQ in children <8 years of age at diagnosis, consistent with a previous report using questionnaire-based data. However, overall cognitive ability was not significantly different.</p>
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