title: Can postoperative radiotherapy be omitted in localised standard-risk Ewing sarcoma? An observational study of the Euro-E.W.I.N.G group.
abstract: The role of postoperative radiotherapy (PORT) in Ewing sarcoma (ES) is unclear. We assessed the impact of PORT on local control in patients with localised ES and good histological response to chemotherapy (<10% cells).
  
  
  
  All randomised patients in the EE99-R1 trial (comparing two consolidation chemotherapy regimens) undergoing surgery after induction chemotherapy were included. Local relapse (LR) cumulative incidence was estimated using a competing risk approach. Impact of PORT was assessed in multivariable models, adjusted for country, age, tumour site and volume, quality of resection and histological response. We also evaluated the heterogeneity of PORT effect by patient and tumour characteristics.
  
  
  
  One hundred forty-two (24%) of the 599 patients included from 1999 to 2009 received PORT (median dose: 45 Grays). With median follow-up of 6.2 years, 67 patients had an LR (with concomitant metastases in 28), leading to an 8-year LR-incidence = 11.9% (standard error [se] = 1.4%). Overall survival (OS) = 21% (se = 5%) 3 years after LR (31% in isolated LR). Controlling for possible confounders, we observed a statistically significant reduction of LR in patients treated by surgery + PORT compared to surgery alone (subdistribution-hazard ratio = 0.43, 95% confidence interval, 0.21-0.88, p = 0.02). The benefit of PORT was particularly marked for tumours larger than 200 ml at diagnosis and 100% necrosis. We observed a non-significant trend for benefit associated with PORT for disease-free, event-free and OS.
  
  
  
  Radiotherapy appears to improve local control. We now recommend PORT in case of incomplete removal of the tissues involved by the pre-chemotherapy tumour volume. Further studies are required to assess the balance between benefit and risks.
authors.affiliation: Biostatistics Unit, Gustave Roussy, Villejuif, France; CESP Centre for Research in Epidemiology and Population Health, INSERM U1018, Team-2, Paris-Sud University, Villejuif, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Foulon
authors.affiliation: Paediatric Oncology Department, Royal Manchester Children's Hospital, Manchester, United Kingdom.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Brennan
authors.affiliation: Department of Childhood and Adolescent Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gaspar
authors.affiliation: Department of Paediatric Oncology, University Hospital Münster, Münster, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Dirksen
authors.affiliation: Orthopedic Department, Royal Orthopaedic Hospital, Birmingham, United Kingdom.
authors.forename: Lee
authors.initials: L
authors.lastname: Jeys
authors.affiliation: National Institute for Health Research University College London Hospitals Biomedical Research Centre and Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Cassoni
authors.affiliation: Radiotherapy Department, Léon-Bérard Center, Lyon, France.
authors.forename: Line
authors.initials: L
authors.lastname: Claude
authors.affiliation: Radiotherapy Department, University College London Hospital National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Seddon
authors.affiliation: Institute for Paediatric Haematology and Oncology, Léon-Bérard Center, Lyon, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Marec-Berard
authors.affiliation: National Institute for Health Research University College London Hospitals Biomedical Research Centre and Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, United Kingdom.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Whelan
authors.affiliation: Paediatric Department, Vestische Kinder-und Jugendklinik, Datteln, Germany; Witten/Herdecke University, Datteln, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Paulussen
authors.affiliation: Orthopedic Surgery, University Hospital Münster, Münster, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Streitbuerger
authors.affiliation: Department of Childhood and Adolescent Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Oberlin
authors.affiliation: Department of Paediatric Oncology, University Hospital Münster, Münster, Germany.
authors.forename: Heribert
authors.initials: H
authors.lastname: Juergens
authors.affiliation: Orthopedic Department, Royal Orthopaedic Hospital, Birmingham, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Grimer
authors.affiliation: Biostatistics Unit, Gustave Roussy, Villejuif, France; CESP Centre for Research in Epidemiology and Population Health, INSERM U1018, Team-2, Paris-Sud University, Villejuif, France. Electronic address: marie-cecile.LEDELEY@gustaveroussy.fr.
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Le Deley
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D003131:Combined Modality Therapy; D009364:Neoplasm Recurrence, Local; D011184:Postoperative Period; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery; D016032:Randomized Controlled Trials as Topic
keywords: Comparative effectiveness research; Competing risk; Ewing sarcoma; Local control; Propensity score; Radiation therapy