title: FDG uptake in normal tissues assessed by PET during treatment has prognostic value for treatment results in head and neck squamous cell carcinomas undergoing radiochemotherapy.
abstract: Pronounced early side effects have been suggested to be a positive prognostic factor in patients undergoing chemo-radio-therapy (CRT) for head and neck squamous cell carcinomas (HNSCC). We assessed the utility of positron emission tomography (PET) during treatment to analyze the correlation of 18F-fluorodeoxyglucose (FDG) uptake in off target structures within the irradiated volume with outcome.
  
  
  
  Two independent cohorts of patients with locally advanced HNSCC, both treated within prospective clinical imaging trials with curatively intended CRT were retrospectively analyzed. The exploratory cohort included 50, the independent validation cohort 26 patients. Uptake of FDG in mucosa and submucosal soft tissues (MST) as well as in other structures was assessed at week 4 during treatment. Considered endpoints were local tumor control (LC) and overall survival (OS). The prognostic value of FDG uptake on the endpoints was measured by the concordance index (ci) using univariate and multivariate Cox regression analyses based on the continuous variables of the exploratory cohort.
  
  
  
  In the exploratory cohort FDG uptake in MST was prognostic for LC (hazard ratio HR=0.23, p=0.025) and OS (HR=0.30, p=0.003) in univariate analyses. These findings remained significant upon multivariate testing (LC HR=0.14, p=0.011; OS HR=0.20, p=0.001) and were confirmed in the validation cohort for LC (HR=0.15, p=0.034) and OS (HR=0.17, p=0.003). Also the SUVmeanthreshold of MST that was generated within the exploratory cohort (2.375) yielded significant differences in OS (p=0.006) and a statistical trend for LC (p=0.078) when applied to the validation cohort.
  
  
  
  FDG uptake in normal tissues within the irradiated volume measured by PET during treatment has significant prognostic value in HNSCC. This effect may potentially be of use for personalized treatment adaptation.
authors.affiliation: Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany. Electronic address: sebastian.zschaeck@uniklinikum-dresden.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zschaeck
authors.affiliation: Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay - National Center for Radiation Research in Oncology, Biostatistics and Modeling in Radiation Oncology Group, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology Dresden, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Löck
authors.affiliation: OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Leger
authors.affiliation: OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Haase
authors.affiliation: Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Bandurska-Luque
authors.affiliation: Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Appold
authors.affiliation: German Cancer Consortium (DKTK), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiopharmaceutical Cancer Research, Germany; Department of Nuclear Medicine, Medical Faculty and University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kotzerke
authors.affiliation: Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Tübingen, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Radiation Oncology, University Hospital and Medical Faculty, Eberhard Karls University Tübingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
authors.affiliation: Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology Dresden, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Richter
authors.affiliation: Department of Otorhinolaryngology, Medical Faculty and University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Gudziol
authors.affiliation: Department of Radiotherapy, Hospital Dresden-Friedrichstadt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schreiber
authors.affiliation: German Cancer Consortium (DKTK), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Department of Nuclear Medicine, Medical Faculty and University Hospital Carl Gustav Carus, Dresden, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Zöphel
authors.affiliation: Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology Dresden, Germany; National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology Dresden, Germany; National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany.
authors.forename: Mechthild
authors.initials: M
authors.lastname: Krause
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D059248:Chemoradiotherapy; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: FDG-PET; HNSCC; Mucositis; Side effects