title: Organ preservation with chemoradiation in advanced laryngeal cancer: The problem of generalizing results from randomized controlled trials.
abstract: BACKGROUND
  The primary goal of treatment in advanced laryngeal cancer is to achieve optimal oncologic outcomes while preserving function and quality of life. Combination of chemotherapy and radiation has been popularized as an alternative to surgery for patients facing total laryngectomy. However, survival analyses from large, population-based databases have not duplicated results reported from randomized trials.
  
  
  METHODS
  A comprehensive literature review was undertaken to try to better understand the reasons why results differ among randomized trials and population cohort studies.
  
  
  RESULTS
  A variety of reasons are discussed, including differences in patient staging, selection bias, complexity bias, inconsistent terminology, patient compliance and treatment expertise.
  
  
  CONCLUSIONS
  Personalized treatment considering all factors is critical for optimal outcomes. In general, evidence supports total laryngectomy for patients with T4 cancers. Definitive chemoradiotherapy strategies are acceptable alternatives for T3 cancers, provided that all resources for the administration of the treatment, follow-up and surgical salvage are available.
authors.affiliation: Department of Surgery, School of Medicine, Universidad de Antioquia, Fundación Colombiana de Cancerología - Clínica Vida, Medellin, Colombia.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Sanabria
authors.affiliation: Fundaçao Geraldo Correia/Hospital São João de Deus, Divinopolis, MG, Brazil.
authors.forename: Aline L F
authors.initials: ALF
authors.lastname: Chaves
authors.affiliation: Department of Head and Neck Surgery and Otorhinolaryngology, A.C. Camargo Cancer Center, Sao Paulo, SP, Brazil.
authors.forename: Luiz P
authors.initials: LP
authors.lastname: Kowalski
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Wolf
authors.affiliation: Department of Hematology and Medical Oncology, The Winship Cancer Institute of Emory University, Atlanta, GA, USA.
authors.forename: Nabil F
authors.initials: NF
authors.lastname: Saba
authors.affiliation: Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Arlene A
authors.initials: AA
authors.lastname: Forastiere
authors.affiliation: Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA, USA; Department of Otolaryngology, Emory University School of Medicine, Atlanta, GA, USA; Department of Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Beitler
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Nibu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.affiliation: Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, Oviedo, Spain; Fundación de Investigación e Innovación Biosanitaria del Principado de Asturias, Oviedo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Suárez
authors.affiliation: Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, Oviedo, Spain; Department of Otolaryngology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Rodrigo
authors.affiliation: Department of Radiation Oncology, Institute of Oncology, Ljubljana, Slovenia.
authors.forename: Primož
authors.initials: P
authors.lastname: Strojan
authors.affiliation: University of Udine School of Medicine, Udine, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rinaldo
authors.affiliation: Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Remco
authors.initials: R
authors.lastname: de Bree
authors.affiliation: Department of Medicine, Division of Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Missak
authors.initials: M
authors.lastname: Haigentz
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Takes
authors.affiliation: Coordinator of the International Head and Neck Scientific Group. Electronic address: a.ferlito@uniud.it.
authors.forename: Alfio
authors.initials: A
authors.lastname: Ferlito
mesh_terms: D059248:Chemoradiotherapy; D015331:Cohort Studies; D006801:Humans; D007822:Laryngeal Neoplasms / Q000473:pathology / Q000628:therapy*; D007825:Laryngectomy; D009367:Neoplasm Staging; D059351:Organ Sparing Treatments; D017063:Outcome Assessment, Health Care; D010349:Patient Compliance; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
keywords: Advanced laryngeal cancer; Bias; Chemoradiotherapy; Controlled clinical trials; Laryngeal neoplasm; Laryngectomy; Organ preservation; Outcomes assessment