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.
abstract: OBJECTIVE
  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
  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 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; 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.
authors.affiliation: National Institute of Health and Medical Research, INSERM U1178, Paris, France. Electronic address: hugocamaracosta@gmail.com.
authors.forename: Hugo
authors.initials: H
authors.lastname: Câmara-Costa
authors.affiliation: University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Resch
authors.affiliation: Saint Maurice Hospitals, Saint Maurice, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Kieffer
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Lalande
authors.affiliation: Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy.
authors.forename: Geraldina
authors.initials: G
authors.lastname: Poggi
authors.affiliation: University of Southampton, Faculty of Medicine, Southampton, United Kingdom.
authors.forename: Colin
authors.initials: C
authors.lastname: Kennedy
authors.affiliation: University of Southampton, Faculty of Medicine, Southampton, United Kingdom.
authors.forename: Kim
authors.initials: K
authors.lastname: Bull
authors.affiliation: Paediatric Oncology, University of Muenster, Muenster, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Calaminus
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Grill
authors.affiliation: Institut Curie and University Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Doz
authors.affiliation: University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.affiliation: Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Massimino
authors.affiliation: Department of Radiation Therapy, University of Leipzig, Leipzig, Germany.
authors.forename: Rolf-Dieter
authors.initials: RD
authors.lastname: Kortmann
authors.affiliation: Paediatric Oncology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Lannering
authors.affiliation: National Institute of Health and Medical Research, INSERM U1178, Paris, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Dellatolas
authors.affiliation: Rehabilitation Department for Children With Acquired Neurological Injury, Saint Maurice Hospitals, Saint Maurice, and Sorbonne Universités, UPMC Universités Paris, INSERM CNRS, Paris, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Chevignard
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000523:psychology / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D003071:Cognition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D003072:Cognition Disorders; D016001:Confidence Intervals; D061888:Craniospinal Irradiation / Q000379:methods; D019583:Dose Fractionation, Radiation; D005060:Europe; D056344:Executive Function / Q000502:physiology / Q000528:radiation effects; D005260:Female; D006801:Humans; D007360:Intelligence / Q000502:physiology / Q000528:radiation effects*; D007361:Intelligence Tests; D008130:Lomustine / Q000008:administration & dosage; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000523:psychology / Q000532:radiotherapy*; D008568:Memory / Q000502:physiology / Q000528:radiation effects; D011446:Prospective Studies; D012044:Regression Analysis; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D014750:Vincristine; D008130:Lomustine; D002945:Cisplatin