title: Hyperfractionated versus conventional radiotherapy followed by chemotherapy in standard-risk medulloblastoma: results from the randomized multicenter HIT-SIOP PNET 4 trial.
abstract: OBJECTIVE
  To compare event-free survival (EFS), overall survival (OS), pattern of relapse, and hearing loss in children with standard-risk medulloblastoma treated by postoperative hyperfractionated or conventionally fractionated radiotherapy followed by maintenance chemotherapy.
  
  
  METHODS
  In all, 340 children age 4 to 21 years from 122 European centers were postoperatively staged and randomly assigned to treatment with hyperfractionated radiotherapy (HFRT) or standard (conventional) fractionated radiotherapy (STRT) followed by a common chemotherapy regimen consisting of eight cycles of cisplatin, lomustine, and vincristine.
  
  
  RESULTS
  After a median follow-up of 4.8 years (range, 0.1 to 8.3 years), survival rates were not significantly different between the two treatment arms: 5-year EFS was 77% ± 4% in the STRT group and 78% ± 4% in the HFRT group; corresponding 5-year OS was 87% ± 3% and 85% ± 3%, respectively. A postoperative residual tumor of more than 1.5 cm(2) was the strongest negative prognostic factor. EFS of children with all reference assessments and no large residual tumor was 82% ± 2% at 5 years. Patients with a delay of more than 7 weeks to the start of RT had a worse prognosis. Severe hearing loss was not significantly different for the two treatment arms at follow-up.
  
  
  CONCLUSIONS
  In this large randomized European study, which enrolled patients with standard-risk medulloblastoma from more than 100 centers, excellent survival rates were achieved in patients without a large postoperative residual tumor and without RT treatment delays. EFS and OS for HFRT was not superior to STRT, which therefore remains standard of care in this disease.
authors.affiliation: Department of Pediatrics, University of Gothenburg, The Queen Silvia Children's Hospital, S 41685 Göteborg, Sweden. birgitta.lannering@vgregion.se
authors.forename: Birgitta
authors.initials: B
authors.lastname: Lannering
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Francois
authors.initials: F
authors.lastname: Doz
authors.forename: Barry
authors.initials: B
authors.lastname: Pizer
authors.forename: Göran
authors.initials: G
authors.lastname: Gustafsson
authors.forename: Aurora
authors.initials: A
authors.lastname: Navajas
authors.forename: Maura
authors.initials: M
authors.lastname: Massimino
authors.forename: Roel
authors.initials: R
authors.lastname: Reddingius
authors.forename: Martin
authors.initials: M
authors.lastname: Benesch
authors.forename: Christian
authors.initials: C
authors.lastname: Carrie
authors.forename: Roger
authors.initials: R
authors.lastname: Taylor
authors.forename: Lorenza
authors.initials: L
authors.lastname: Gandola
authors.forename: Thomas
authors.initials: T
authors.lastname: Björk-Eriksson
authors.forename: Jordi
authors.initials: J
authors.lastname: Giralt
authors.forename: Foppe
authors.initials: F
authors.lastname: Oldenburger
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Dominique
authors.initials: D
authors.lastname: Figarella-Branger
authors.forename: Keith
authors.initials: K
authors.lastname: Robson
authors.forename: Marco
authors.initials: M
authors.lastname: Forni
authors.forename: Steven C
authors.initials: SC
authors.lastname: Clifford
authors.forename: Monica
authors.initials: M
authors.lastname: Warmuth-Metz
authors.forename: Katja
authors.initials: K
authors.lastname: von Hoff
authors.forename: Andreas
authors.initials: A
authors.lastname: Faldum
authors.forename: Véronique
authors.initials: V
authors.lastname: Mosseri
authors.forename: Rolf
authors.initials: R
authors.lastname: Kortmann
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002528:Cerebellar Neoplasms / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D034381:Hearing Loss / Q000209:etiology; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000532:radiotherapy*; D018714:Radiotherapy, Adjuvant; D012008:Recurrence; D015996:Survival Rate