title: Effectiveness of an (18)F-FDG-PET based strategy to optimize the diagnostic trajectory of suspected recurrent laryngeal carcinoma after radiotherapy: The RELAPS multicenter randomized trial.
abstract: OBJECTIVE
  The purpose of this study is to evaluate the efficacy of (18)F-FDG-PET as first-line diagnostic investigation, prior to performing a direct laryngoscopy with biopsy under general anesthesia, in patients suspected of recurrent laryngeal carcinoma after radiotherapy.
  
  
  METHODS
  150 patients suspected of recurrent T2-4 laryngeal carcinoma at least two months after prior (chemo)radiotherapy with curative intent for resectable disease were randomized to direct laryngoscopy (CWU: conventional workup strategy) or to (18)F-FDG-PET only followed by direct laryngoscopy if PET was assessed 'positive' or 'equivocal' (PWU: PET based workup strategy), to compare the effectiveness of these strategies. Primary endpoint was the number of indications for direct laryngoscopies classified as unnecessary based on absence of recurrence, both on direct laryngoscopy and on six month follow up. Safety endpoints comprised resectability of recurrent lesions and completeness of surgical margins following salvage laryngectomy.
  
  
  RESULTS
  Intention-to-treat analyses were performed on all randomized patients (CWU: n=74, PWU: n=76). Tumor recurrence was similar in both groups: 45 patients (30%; 21 CWU, 24 PWU) within six months. In 53 patients in the CWU arm (72%, 95% CI: 60-81) unnecessary direct laryngoscopies were performed compared to 22 in the PWU arm (29%, 95% CI: 19-40) (p<0·0001). The percentage of salvage laryngectomies (resectability) and positive surgical margins were similar between CWU and PWU (81%, 63% respectively, p=0·17, and 29%, 7%, respectively, p=0.20). The prevalence of the combination of local unresectability and positive margins is in the CWU group 24% and in the PWU group 8%. No difference (p=0.32) in disease specific survival between both groups was found.
  
  
  CONCLUSIONS
  In patients with suspected laryngeal carcinoma after radiotherapy, PET as the first diagnostic procedure can reduce the need for direct laryngoscopy by more than 50% without jeopardizing quality of treatment.
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands; Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, The Netherlands. Electronic address: r.bree@vumc.nl.
authors.forename: Remco
authors.initials: R
authors.lastname: de Bree
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lisa
authors.initials: L
authors.lastname: van der Putten
authors.affiliation: Department of Statistics, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Harm
authors.initials: H
authors.lastname: van Tinteren
authors.affiliation: Department of Otorhinolaryngology - Head & Neck Surgery, University Medical Center Groningen, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Wedman
authors.affiliation: Department of Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.affiliation: Department of Head and Neck Surgical Oncology, UMC Utrecht Cancer Center, University Medical Center Utrecht, The Netherlands; Department of Otorhinolaryngology, University Medical Center Utrecht, The Netherlands.
authors.forename: Luuk M
authors.initials: LM
authors.lastname: Janssen
authors.affiliation: Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Otolaryngology, Academic Medical Center Amsterdam, The Netherlands; Amsterdam Center for Language and Communication, University of Amsterdam, The Netherlands.
authors.forename: Michiel W M
authors.initials: MW
authors.lastname: van den Brekel
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Emile F I
authors.initials: EF
authors.lastname: Comans
authors.affiliation: Department of Nuclear Medicine, University Medical Center Groningen, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Pruim
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, Radboud University Nijmegen Center, The Netherlands.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Takes
authors.affiliation: Department of Nuclear Medicine, University Medical Center Utrecht, The Netherlands.
authors.forename: Monique G G
authors.initials: MG
authors.lastname: Hobbelink
authors.affiliation: Department of Nuclear Medicine, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Renato
authors.initials: R
authors.lastname: Valdés Olmos
authors.affiliation: Department of Otorhinolaryngology - Head & Neck Surgery, University Medical Center Groningen, The Netherlands.
authors.forename: Bernard F A M
authors.initials: BF
authors.lastname: van der Laan
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Boers
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Otto S
authors.initials: OS
authors.lastname: Hoekstra
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: C René
authors.initials: CR
authors.lastname: Leemans
mesh_terms: D000368:Aged; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007822:Laryngeal Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D007828:Laryngoscopy; D007830:Larynx / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D016879:Salvage Therapy; D016896:Treatment Outcome
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: FDG-PET; Laryngeal carcinoma; Laryngoscopy; Radiotherapy; Recurrence