title: Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials.
abstract: BACKGROUND
  The EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT.
  
  
  METHODS
  Individual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS (large resection, R0/marginal resection, R1) were pooled. Prognostic factors were assessed by univariate and multivariate analyses. Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor.
  
  
  RESULTS
  A total of 819 patients had been enrolled with a median follow-up of 8.2 years. Tumor size, high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival (RFS) and OS. Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS. A significant interaction between benefit of adjuvant CT and age, gender and R1 resection was observed for RFS and OS. Males and patients >40 years had a significantly better RFS in the treatment arms, while adjuvant CT was associated with a marginally worse OS in females and patients <40 years. Patients with R1 resection had a significantly better RFS and OS favoring adjuvant CT arms.
  
  
  CONCLUSIONS
  Adjuvant CT is not associated with a better OS in young patients or in any pathology subgroup. Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS. Based on these data, we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care.
authors.affiliation: Department of Medical Oncology and Surgery, Institut Gustave Roussy, Villejuif, France. Electronic address: axel.lecesne@gustaveroussy.fr.
authors.forename: A
authors.initials: A
authors.lastname: Le Cesne
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Ouali
authors.affiliation: Department of Medical Oncology, Christie Hospital, Manchester, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Leahy
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Department of Surgical Oncology, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Hoekstra
authors.affiliation: Department of Surgical Oncology, Charité Universitaetsmedizin BerlinCampus, Berlin, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Hohenberger
authors.affiliation: Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Van Coevorden
authors.affiliation: Department of Soft Tissue and Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Rutkowski
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen.
authors.forename: R
authors.initials: R
authors.lastname: Van Hoesel
authors.affiliation: Department of Oncology, Erasmus University Medical Center-Cancer Institute, Rotterdam.
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.affiliation: Department of Medical Oncology and Surgery, Institut Gustave Roussy, Villejuif, France.
authors.forename: S
authors.initials: S
authors.lastname: Bonvalot
authors.affiliation: Department of Medical Oncology, Christie Hospital, Manchester, UK.
authors.forename: W P
authors.initials: WP
authors.lastname: Steward
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gronchi
authors.affiliation: Department of Pathology, University Medical Center, Leiden, The Netherlands.
authors.forename: P C W
authors.initials: PCW
authors.lastname: Hogendoorn
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Litiere
authors.affiliation: EORTC Headquarters, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Marreaud
authors.affiliation: Department of Radio-Oncology, University Claude Bernard Lyon I and Centre Léon Bérard, Lyon, France.
authors.forename: J Y
authors.initials: JY
authors.lastname: Blay
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen.
authors.forename: W T A
authors.initials: WTA
authors.lastname: Van Der Graaf
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D011379:Prognosis; D012509:Sarcoma / Q000188:drug therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin
keywords: adjuvant chemotherapy; predictive factors; soft tissue sarcoma; treatment outcome