Quality of survival and growth in children and young adults in the PNET4 European controlled trial of hyperfractionated versus conventional radiation therapy for standard-risk medulloblastoma.
OBJECTIVE
To compare quality of survival in "standard-risk" medulloblastoma after hyperfractionated radiation therapy of the central nervous system with that after standard radiation therapy, combined with a chemotherapy regimen common to both treatment arms, in the PNET4 randomised controlled trial.


METHODS
Participants in the PNET4 trial and their parents/caregivers in 7 participating anonymized countries completed standardized questionnaires in their own language on executive function, health status, behavior, health-related quality of life, and medical, educational, employment, and social information. Pre- and postoperative neurologic status and serial heights and weights were also recorded.


RESULTS
Data were provided by 151 of 244 eligible survivors (62%) at a median age at assessment of 15.2 years and median interval from diagnosis of 5.8 years. Compared with standard radiation therapy, hyperfractionated radiation therapy was associated with lower (ie, better) z-scores for executive function in all participants (mean intergroup difference 0.48 SDs, 95% confidence interval 0.16-0.81, P=.004), but health status, behavioral difficulties, and health-related quality of life z-scores were similar in the 2 treatment arms. Data on hearing impairment were equivocal. Hyperfractionated radiation therapy was also associated with greater decrement in height z-scores (mean intergroup difference 0.43 SDs, 95% confidence interval 0.10-0.76, P=.011).


CONCLUSIONS
Hyperfractionated radiation therapy was associated with better executive function and worse growth but without accompanying change in health status, behavior, or quality of life.
University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom. Electronic address: crk1@soton.ac.uk.
Colin
C
Kennedy
University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom.
Kim
K
Bull
Hôpitaux de Saint Maurice, Saint Maurice, France; Neurophysiology, University of Pierre et Marie-Curie Paris 6, Paris, France.
Mathilde
M
Chevignard
University of Southampton Faculty of Medicine and University Hospital Southampton National Health Service Foundation Trust, Southampton, United Kingdom.
David
D
Culliford
Kinder- und Jugendklinik der Universität Erlangen, Erlangen, Germany.
Helmuth G
HG
Dörr
Institut Curie and University Paris Descartes, Sorbonne Paris Cité, France.
François
F
Doz
Department of Radiation Therapy, University of Leipzig, Leipzig, Germany.
Rolf-Dieter
RD
Kortmann
Department of Pediatrics, The Sahlgren Academy, University of Gothenburg, Gothenburg, Sweden.
Birgitta
B
Lannering
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Maura
M
Massimino
Hospital Universitario Cruces, Baracaldo-Vizcaya, Spain.
Aurora
A
Navajas Gutiérrez
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Stefan
S
Rutkowski
Center for Pediatric Endocrinology, University College London, London, United Kingdom.
Helen A
HA
Spoudeas
Pediatric Oncology, University of Muenster, Muenster, Germany.
Gabriele
G
Calaminus
D000293:Adolescent; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001519:Behavior / Q000528:radiation effects; D002528:Cerebellar Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000379:methods; D019583:Dose Fractionation, Radiation; D004651:Employment / Q000706:statistics & numerical data; D005060:Europe; D056344:Executive Function / Q000502:physiology / Q000528:radiation effects*; D005260:Female; D005500:Follow-Up Studies; D006128:Growth / Q000528:radiation effects*; D006304:Health Status; D006309:Hearing / Q000528:radiation effects; D020249:Hormone Replacement Therapy / Q000379:methods; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000188:drug therapy / Q000532:radiotherapy*; D017063:Outcome Assessment, Health Care; D011788:Quality of Life; D011795:Surveys and Questionnaires; D017741:Survivors; D055815:Young Adult