title: Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.
abstract: BACKGROUND
  The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST).
  
  
  METHODS
  We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts.
  
  
  RESULTS
  Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others.
  
  
  CONCLUSIONS
  Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities.
authors: Clinical and Epidemiological Research Unit, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux; Clinical Epidemiology Unit, INSERM CIC 14.01 (Clinical Epidemiology), Bordeaux. Electronic address: c.bellera@bordeaux.unicancer.fr.
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authors: Bellera
authors: Department of Medical Oncology, Centre Oscar Lambret, Comprehensive Cancer Centre, Lille, France.
authors: N
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authors: Penel
authors: Department of Biostatistics, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; Biostatistics Unit, Institut Claudius Regaud, Comprehensive Cancer Centre, Toulouse.
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authors: Ouali
authors: Department of Surgery, Institut Gustave Roussy, Comprehensive Cancer Centre, Villejuif, France.
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authors: Bonvalot
authors: Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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authors: Casali
authors: Faculty of Health Sciences, Aarhus University, Aarhus, Denmark.
authors: O S
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authors: Nielsen
authors: Department of Radiotherapy, Institut Claudius Régaud, Comprehensive Cancer Center, Toulouse.
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authors: Delannes
authors: Department of Biostatistics, European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
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authors: Litière
authors: Methodological and Quality of Life Unit in Oncology (EA3181), CHU Besançon, Besançon.
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authors: Biostatistics and Quality of Life Unit (EA4184), Centre Georges-François Leclerc, Comprehensive Cancer Centre, Dijon, France.
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authors: Dabakuyo
authors: Division of Cancer Medicine and Sarcoma Center, The University of Texas M.D. Anderson Cancer Center, Houston, USA.
authors: R S
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authors: Department of Medical Oncology, Centre Léon Bérard, Comprehensive Cancer Centre, Lyon; Claude Bernard Lyon I University, Lyon; Medical Oncology Unit, Edouard Herriot Hospital, Lyon.
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authors: Blay
authors: Department of Medical Oncology, Institut Bergonié, Comprehensive Cancer Centre, Bordeaux.
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authors: Bui
authors: Department of Biology and Pathology, Centre Georges-François Leclerc, Comprehensive Cancer Centre, Dijon, France.
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authors: Department of Radiation Oncology and Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, USA.
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authors: Department of Medical Oncology, La Timone Hospital University, Marseille, France.
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authors: Biostatistics Unit, Institut Claudius Regaud, Comprehensive Cancer Centre, Toulouse.
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authors: Filleron
authors: Department of Surgery and Sarcoma Unit, Sarcoma Service, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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authors: Fiore
authors: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
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authors: Gelderblom
authors: Department of Medical Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.
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authors: Grosclaude
authors: Department of Surgery and Sarcoma Unit, Sarcoma Service, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
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authors: Gronchi
authors: Department of Radiation Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
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authors: Haas
authors: Division of Surgical Oncology and Thoracic Surgery, Mannheim University Medical Center, Mannheim.
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authors: Hohenberger
authors: Sarcoma Center, Ludwig-Maximilian University Munich, Munich; Department of Internal Medicine, Klinikum Grosshadern Medical Center, University of Munich, Munich, Germany.
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authors: Issels
authors: Department of Medical Oncology, Institut Bergonié, Comprehensive Cancer Centre, Bordeaux.
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authors: Italiano
authors: Burgundy Digestive Cancer Registry, INSERM U866, University of Burgundy, Dijon, France.
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authors: Jooste
authors: Department of Oncology, Herlev Hospital-University Copenhagen, Herlev, Denmark.
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authors: Krarup-Hansen
authors: Department of Radiotherapy, Institut Gustave Roussy, Comprehensive Cancer Centre, Villejuif, France.
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authors: Le Péchoux
authors: Department of Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
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authors: Mussi
authors: Department of Surgery and Department of Pediatric and Adolescent Oncology, Institut Gustave Roussy, Comprehensive Cancer Centre, Villejuif.
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authors: Oberlin
authors: Division of Cancer Medicine and Sarcoma Center, The University of Texas M.D. Anderson Cancer Center, Houston, USA.
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authors: Patel
authors: Department of Medical Oncology, Institut Curie, Comprehensive Cancer Centre, Paris, France.
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authors: Piperno-Neumann
authors: Department of Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, USA.
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authors: Raut
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authors: Ray-Coquard
authors: Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
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authors: Rutkowski
authors: Department of Medical Oncology, University of Michigan, Ann Arbor, USA.
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authors: Schuetze
authors: Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors: S
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authors: Sleijfer
authors: Department of Surgical Oncology, Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, France.
authors: E
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authors: Stoeckle
authors: Department of Biostatistics, European Organisation for Research and Treatment of Cancer, Brussels, Belgium.
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authors: Van Glabbeke
authors: Department of Oncology, Sheffield Cancer Research Centre, Weston Park Hospital, Sheffield, UK.
authors: P
authors: P
authors: Woll
authors: Montpellier Cancer Institute, Comprehensive Cancer Centre, Montpellier, France.
authors: S
authors: S
authors: Gourgou-Bourgade
authors: Clinical and Epidemiological Research Unit, Institut Bergonie, Comprehensive Cancer Centre, Bordeaux; Clinical Epidemiology Unit, INSERM CIC 14.01 (Clinical Epidemiology), Bordeaux.
authors: S
authors: S
authors: Mathoulin-Pélissier
mesh_terms: D032921:Consensus; D003697:Delphi Technique; D018450:Disease Progression; D018572:Disease-Free Survival; D023381:Endpoint Determination / Q000145:classification / Q000592:standards*; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000145:classification / Q000592:standards*; D012107:Research Design / Q000592:standards*; D012509:Sarcoma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D009626:Terminology as Topic; D013997:Time Factors; D017211:Treatment Failure
keywords: efficacy measure; gastrointestinal stromal tumors; guidelines; randomized controlled trial; sarcoma; time-to-event end point