title: Spatial distribution of FMISO in head and neck squamous cell carcinomas during radio-chemotherapy and its correlation to pattern of failure.
abstract: BACKGROUND
  Tumour hypoxia can be measured by FMISO-PET and negatively impacts local tumour control in patients with head and neck squamous cell carcinoma (HNSCC) undergoing radiotherapy. The aim of this post hoc analysis of a prospective clinical trial was to investigate the spatial variability of FMISO hypoxic subvolumes during radio-chemotherapy and the co-localisation of these volumes with later recurrences as a basis for individualised dose prescription trials with dose escalation defined by FMISO-PET.
  
  
  METHODS
  Sequential FMISO scans of 12 (of 25) patients presenting residual hypoxia taken before (FMISOpre) and during (FMISOw1-FMISOw5) radio-chemotherapy were analysed regarding the stability of the FMISO subvolumes and, in case of local failure, their correlation to local relapse.
  
  
  RESULTS
  Consecutive FMISO-PET positive volumes could be classified as moderately stable with Dice conformity indices of 62% and 58% up to the second week of treatment. Substantial volumetric variation during treatment was observed, with more than 20% geographic miss in all patients and more than 40% in half of the patients. The localisation of the maximum standardised uptake value (SUVmax) differed with a mean distance of 7.0 mm and 13.5 mm between the pre-therapeutic and first or second FMISO-PET during treatment. A stable hypoxic consensual volume (i.e. overlap of pre-therapeutic FMISO and intra-treatment FMISO subvolumes up to week two, generated by different contouring methods) was determined for six patients with imaging information of local recurrence. Three of these six local recurrences were located within this consensual volume.
  
  
  CONCLUSIONS
  Our data suggest that selective dose painting to hypoxic tumour subvolumes requires adaptation during treatment and sufficient margins. An alternative strategy is to escalate the dose to the gross tumour volume, accepting lesser escalation of dose outside hypoxic areas if indicated by constraints for organs at risk.
authors.affiliation: a Department of Radiation Oncology , University Hospital Carl Gustav Carus, Technische Universität Dresden , Dresden , Germany.|b German Cancer Consortium (DKTK) , Dresden , Germany , and German Cancer Research Center (DKFZ) Heidelberg , Germany.|c 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: Sebastian
authors.initials: S
authors.lastname: Zschaeck
authors.affiliation: c 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: c OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden , Helmholtz-Zentrum Dresden-Rossendorf , Germany.|d Department of Radiology , Medical Faculty and University Hospital Carl Gustav Carus , Dresden , Germany.
authors.forename: Nasreddin
authors.initials: N
authors.lastname: Abolmaali
authors.affiliation: c OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden , Helmholtz-Zentrum Dresden-Rossendorf , Germany.|e Paul Scherrer Institute , Villigen , Switzerland.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Perrin
authors.affiliation: c 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: Kristin
authors.initials: K
authors.lastname: Stützer
authors.affiliation: a Department of Radiation Oncology , University Hospital Carl Gustav Carus, Technische Universität Dresden , Dresden , Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Appold
authors.affiliation: f Institute of Radiopharmaceutical Cancer Research , Helmholtz-Zentrum Dresden-Rossendorf , Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.affiliation: b German Cancer Consortium (DKTK) , Dresden , Germany , and German Cancer Research Center (DKFZ) Heidelberg , Germany.|c OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden , Helmholtz-Zentrum Dresden-Rossendorf , Germany.|f Institute of Radiopharmaceutical Cancer Research , Helmholtz-Zentrum Dresden-Rossendorf , Germany.|g 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: a Department of Radiation Oncology , University Hospital Carl Gustav Carus, Technische Universität Dresden , Dresden , Germany.|h German Cancer Consortium (DKTK) , Tübingen , Germany , and German Cancer Research Center (DKFZ) Heidelberg , Germany.|i Department of Radiation Oncology , University Hospital and Medical Faculty, Eberhard Karls University Tübingen , Tübingen , Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
authors.affiliation: a Department of Radiation Oncology , University Hospital Carl Gustav Carus, Technische Universität Dresden , Dresden , Germany.|b German Cancer Consortium (DKTK) , Dresden , Germany , and German Cancer Research Center (DKFZ) Heidelberg , Germany.|c OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden , Helmholtz-Zentrum Dresden-Rossendorf , Germany.|f Institute of Radiopharmaceutical Cancer Research , Helmholtz-Zentrum Dresden-Rossendorf , Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Richter
authors.affiliation: j Department of Otorhinolaryngology , Medical Faculty and University Hospital Carl Gustav Carus , Dresden , Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Gudziol
authors.affiliation: a Department of Radiation Oncology , University Hospital Carl Gustav Carus, Technische Universität Dresden , Dresden , Germany.|b German Cancer Consortium (DKTK) , Dresden , Germany , and German Cancer Research Center (DKFZ) Heidelberg , Germany.|c OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden , Helmholtz-Zentrum Dresden-Rossendorf , Germany.|f Institute of Radiopharmaceutical Cancer Research , Helmholtz-Zentrum Dresden-Rossendorf , Germany.
authors.forename: Mechthild
authors.initials: M
authors.lastname: Krause
authors.affiliation: b German Cancer Consortium (DKTK) , Dresden , Germany , and German Cancer Research Center (DKFZ) Heidelberg , Germany.|c OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden , Helmholtz-Zentrum Dresden-Rossendorf , Germany.|g 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: a Department of Radiation Oncology , University Hospital Carl Gustav Carus, Technische Universität Dresden , Dresden , Germany.|b German Cancer Consortium (DKTK) , Dresden , Germany , and German Cancer Research Center (DKFZ) Heidelberg , Germany.|c OncoRay - National Center for Radiation Research in Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden , Helmholtz-Zentrum Dresden-Rossendorf , Germany.|f Institute of Radiopharmaceutical Cancer Research , Helmholtz-Zentrum Dresden-Rossendorf , Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy; D059248:Chemoradiotherapy; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy; D006801:Humans; D000860:Hypoxia / Q000000981:diagnostic imaging*; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D020266:Radiotherapy, Conformal; D050397:Radiotherapy, Intensity-Modulated; D000077195:Squamous Cell Carcinoma of Head and Neck; D014057:Tomography, X-Ray Computed
chemical_list: D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole