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Title: Neuropsychological Outcome of Children Treated for Standard Risk Medulloblastoma in the PNET4 European Randomized Controlled Trial of Hyperfractionated Versus Standard Radiation Therapy and Maintenance Chemotherapy

Purpose: 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. Methods and Materials: 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). Results: 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, P=.24). No significant differences were found in childrenmore » >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; P=.02]; 3.77 for PIQ [95% CI: −5.19 to 12.74; P>.10]; 5.20 for WMI [95% CI: −2.07 to 12.47; P>.10]; 10.90 for PSI [95% CI: −1.54 to 23.36; P=.08]; and 5.28 for FSIQ [95% CI: −4.23 to 14.79; P>.10]). Conclusions: 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.« less
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ; ;  [6] ;  [7] ;  [4] ;  [8] ;  [2] ;  [9] ;  [10] ;  [11] ;  [1] ;  [12]
  1. National Institute of Health and Medical Research, INSERM U1178, Paris (France)
  2. University Medical Center Hamburg-Eppendorf, Hamburg (Germany)
  3. Saint Maurice Hospitals, Saint Maurice (France)
  4. Institut Gustave Roussy, Villejuif (France)
  5. Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco (Italy)
  6. University of Southampton, Faculty of Medicine, Southampton (United Kingdom)
  7. Paediatric Oncology, University of Muenster, Muenster (Germany)
  8. Institut Curie and University Paris Descartes, Sorbonne Paris Cité, Paris (France)
  9. Fondazione IRCCS, Istituto Nazionale Tumori, Milan (Italy)
  10. Department of Radiation Therapy, University of Leipzig, Leipzig (Germany)
  11. Paediatric Oncology, University of Gothenburg, Gothenburg (Sweden)
  12. Rehabilitation Department for Children With Acquired Neurological Injury, Saint Maurice Hospitals, Saint Maurice, and Sorbonne Universités, UPMC Universités Paris, INSERM CNRS, Paris (France)
Publication Date:
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Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 92; Journal Issue: 5; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States