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

Int J Radiat Oncol Biol Phys. 2015 Aug 1;92(5):978-985. doi: 10.1016/j.ijrobp.2015.04.023. Epub 2015 Apr 17.

Abstract

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 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cerebellar Neoplasms / drug therapy
  • Cerebellar Neoplasms / psychology
  • Cerebellar Neoplasms / radiotherapy*
  • Child
  • Child, Preschool
  • Cisplatin / administration & dosage
  • Cognition / drug effects
  • Cognition / physiology
  • Cognition / radiation effects*
  • Cognition Disorders
  • Confidence Intervals
  • Craniospinal Irradiation / methods
  • Dose Fractionation, Radiation
  • Europe
  • Executive Function / physiology
  • Executive Function / radiation effects
  • Female
  • Humans
  • Intelligence / physiology
  • Intelligence / radiation effects*
  • Intelligence Tests
  • Lomustine / administration & dosage
  • Maintenance Chemotherapy / methods
  • Male
  • Medulloblastoma / drug therapy
  • Medulloblastoma / psychology
  • Medulloblastoma / radiotherapy*
  • Memory / physiology
  • Memory / radiation effects
  • Prospective Studies
  • Regression Analysis
  • Vincristine / administration & dosage
  • Young Adult

Substances

  • Vincristine
  • Lomustine
  • Cisplatin