Hyperfractionated versus conventional radiotherapy followed by chemotherapy in standard-risk medulloblastoma: Results from the randomized multicenter HIT-SIOP PNET 4 trial

Birgitta Lannering, Stefan Rutkowski, Francois Doz, Barry Pizer, Göran Gustafsson, Aurora Navajas, Maura Massimino, Roel Reddingius, Martin Benesch, Christian Carrie, Roger Taylor, Lorenza Gandola, Thomas Bjor̈k-Eriksson, Jordi Giralt, Foppe Oldenburger, Torsten Pietsch, Dominique Figarella-Branger, Keith Robson, Marco Forni, Steven C. CliffordMonica Warmuth-Metz, Katja Von Hoff, Andreas Faldum, Véronique Mosseri, Rolf Kortmann

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: 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. Patients and 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 cm2 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)3187-3193
Number of pages7
JournalJournal of Clinical Oncology
Volume30
Issue number26
DOIs
Publication statusPublished - Sep 10 2012

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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