High-dose chemotherapy compared with standard chemotherapy and lung radiation in ewing sarcoma with pulmonary metastases: Results of the european ewing tumour working initiative of national groups, 99 trial and ewing 2008

Research output: Contribution to journalArticlepeer-review

Authors

  • Uta Dirksen
  • Bernadette Brennan
  • Marie Cécile Le Deley
  • Nathalie Cozic
  • Henk Van Den Berg
  • Vivek Bhadri
  • Bénédicte Brichard
  • Line Claude
  • Alan Craft
  • Susanne Amler
  • Natalie Gaspar
  • Hans Gelderblom
  • Robert Goldsby
  • Richard Gorlick
  • Holcombe E. Grier
  • Jean Marc Guinbretiere
  • Peter Hauser
  • Lars Hjorth
  • Katherine Janeway
  • Heribert Juergens
  • Ian Judson
  • Mark Krailo
  • Jarmila Kruseova
  • Thomas Kuehne
  • Ruth Ladenstein
  • Cyril Lervat
  • Stephen L. Lessnick
  • Ian Lewis
  • Claude Linassier
  • Perrine Marec-Berard
  • Neyssa Marina
  • Bruce Morland
  • Hélène Pacquement
  • Michael Paulussen
  • R. Lor Randall
  • Andreas Ranft
  • Gwénaël Le Teuff
  • Jeremy Whelan
  • Richard Womer
  • Odile Oberlin
  • Douglas S. Hawkins

Colleges, School and Institutes

External organisations

  • University Hospital Essen
  • Royal Manchester Children's Hospital
  • Centre Oscar Lambret
  • Université Paris-Saclay
  • Gustave Roussy
  • University of Amsterdam
  • Chris O’Brien Lifehouse
  • Cliniques Universitaires Saint Luc
  • Centre Leon Berard
  • Northern Institute for Cancer Research
  • Muenster University
  • Friedrich-Loeffler Institute
  • Leiden University Medical Center - LUMC
  • University of California
  • The University of Texas MD Anderson Cancer Center
  • Dana-Farber Cancer Institute
  • Hôpital René-Huguenin
  • Semmelweis University
  • Lunds Universitet
  • Universitaetskinderklinik Muenster
  • The Royal Marsden Hospital NHS Foundation Trust
  • University of Southern California
  • Charles University in Prague
  • University Children’s Hospital Basel
  • Medical University of Vienna
  • Ohio State University
  • University of Leeds
  • Centre Hospitalier Universitaire
  • Institute of Pediatric Onco-Haematology
  • Five Time Therapeutics
  • Birmingham Children's Hospital
  • Institut Curie
  • Witten/Herdecke University
  • UC Davis
  • University of Birmingham
  • University College Hospital
  • Pennsylvania State University
  • Seattle Children’s Hospital

Abstract

PURPOSE The R2Pulm trial was conducted to evaluate the effect of busulfan-melphalan high-dose chemotherapy with autologous stem-cell rescue (BuMel) without whole-lung irradiation (WLI) on event-free survival (main end point) and overall survival, compared with standard chemotherapy with WLI in Ewing sarcoma (ES) presenting with pulmonary and/or pleural metastases. METHODS From 2000 to 2015, we enrolled patients younger than 50 years of age with newly diagnosed ES and with only pulmonary or pleural metastases. Patients received chemotherapy with six courses of vincristine, ifosfamide, doxorubicin, and etoposide (VIDE) and one course of vincristine, dactinomycin, and ifosfamide (VAI) before either BuMel or seven courses of VAI and WLI (VAI plus WLI) by randomized assignment. The analysis was conducted as intention to treat. The estimates of the hazard ratio (HR), 95% CI, and P value were corrected for the three previous interim analyses by the inverse normal method. RESULTS Of 543 potentially eligible patients, 287 were randomly assigned to VAI plus WLI (n = 143) or BuMel (n = 144). Selected patients requiring radiotherapy to an axial primary site were excluded from randomization to avoid excess organ toxicity from interaction between radiotherapy and busulfan. Median follow-up was 8.1 years. We did not observe any significant difference in survival outcomes between treatment groups. Event-free survival was 50.6% versus 56.6% at 3 years and 43.1% versus 52.9% at 8 years, for VAI plus WLI and BuMel patients, respectively, resulting in an HR of 0.79 (95% CI, 0.56 to 1.10; P = .16). For overall survival, the HR was 1.00 (95% CI, 0.70 to 1.44; P = .99). Four patients died as a result of BuMel-related toxicity, and none died after VAI plus WLI. Significantly more patients in the BuMel arm experienced severe acute toxicities than in the VAI plus WLI arm. CONCLUSION In ES with pulmonary or pleural metastases, there is no clear benefit from BuMel compared with conventional VAI plus WLI.

Details

Original languageEnglish
Pages (from-to)3192-3202
Number of pages11
JournalJournal of Clinical Oncology
Volume37
Issue number34
Publication statusPublished - 1 Jan 2019

ASJC Scopus subject areas