title: Impact of pre- and early per-treatment FDG-PET based dose-escalation on local tumour control in fractionated irradiated FaDu xenograft tumours.
abstract: To investigate local tumour control after dose-escalation based on [18F]2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) obtained before and early during fractionated irradiation.
  
  
  
  85 mice bearing FaDu xenografts underwent FDG-PET twice: first immediately prior to the first 2-Gy fraction of irradiation (PET1_0) and second after 18°Gy (PET2_18). After these 9 fractions, animals were randomly allocated to: (1) continuation of 2-Gy fractions (cumulative dose of 60°Gy; n=31), (2) dose-escalation with 3-Gy fractions (cumulative EQD2-dose 86.25°Gy [α/β-value: 10]; n=25), or (3) with 4-Gy fractions (cumulative EQD2-dose 116°Gy; n=29). The effects of SUVmax0°Gy, SUVmax18°Gy, and dose on local tumour control were analysed in two ways. First, the Cox proportional hazards model was used with two covariates: continuous SUVmaxvalues and dose. Second, the Kaplan-Meier method was used, with tumours classified according to SUVmax greater than or less than (1) median maximum standardized uptake value (SUVmax) at PET1_0 and PET2_18, or (2) the cut-off value 2.5.
  
  
  
  The multivariate Cox analysis revealed a significant negative association between higher SUVmaxdetermined before start of treatment and local control (HR=1.59, [95% CI 1.04, 2.42], p=0.031), whereas higher dose had a significant positive effect (HR=0.95, [0.93, 0.98], p<0.001). In contrast, FDG uptake at 18Gy did not correlate with local control (HR=1.14, [0.53, 2.45], p=0.73). Neither FDG uptake prior to irradiation nor at 18Gy correlated with local control irrespective of the delivered dose (log-rank test) when using the median SUVmaxvalues for stratification (SUVmax0Gy: 60Gy: p=0.25, 86.25Gy: p=0.47, 116Gy: p=0.88 and SUVmax18Gy: 60Gy: p=0.42, 86.25Gy: p=0.34, 116Gy: p=0.99). By contrast, stratifying the animals by the cut-off 2.5 at PET1_0 reveals a significant difference in local control for the 60Gy group (p=0.034), but not for the other dose groups. At PET2_18, no significant effect for any dose group was detected.
  
  
  
  The multivariate Cox analysis revealed a significantly higher hazard of recurrence for mice with higher SUVmaxdetermined before start of treatment. These results support the hypothesis that patients with high pre-therapeutic FDG uptake should be considered at increased risk of local failure and therefore as possible candidates for dose escalation strategies.
authors.affiliation: OncoRay - National Centre for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Dept. of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ) Heidelberg, Germany. Electronic address: christina.jentsch@uniklinikum-dresden.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Jentsch
authors.affiliation: PET Centre, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bergmann
authors.affiliation: OncoRay - National Centre for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Dept. of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Brüchner
authors.affiliation: Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Mosch
authors.affiliation: OncoRay - National Centre for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Dept. of Radiation Oncology (MAASTRO Lab), GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands.
authors.forename: Ala
authors.initials: A
authors.lastname: Yaromina
authors.affiliation: OncoRay - National Centre for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Dept. of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology, Germany; German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ) Heidelberg, Germany.
authors.forename: Mechthild
authors.initials: M
authors.lastname: Krause
authors.affiliation: Department of Radiation Oncology, Eberhard Karls University Tübingen, Germany; German Cancer Consortium (DKTK) Tübingen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zips
authors.affiliation: OncoRay - National Centre for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Dept. of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ) Heidelberg, Germany.
authors.forename: Esther G C
authors.initials: EGC
authors.lastname: Troost
authors.affiliation: OncoRay - National Centre for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology, Germany; German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ) Heidelberg, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Löck
authors.affiliation: OncoRay - National Centre for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Dept. of Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; PET Centre, Helmholtz-Zentrum Dresden-Rossendorf, Germany; German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ) Heidelberg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kotzerke
authors.affiliation: OncoRay - National Centre for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; PET Centre, Helmholtz-Zentrum Dresden-Rossendorf, Germany; Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Germany; German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ) Heidelberg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Steinbach
authors.affiliation: University of Texas M.D. Anderson Cancer Centre, Department of Biostatistics, Houston, United States.
authors.forename: Howard
authors.initials: H
authors.lastname: Thames
authors.affiliation: OncoRay - National Centre for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Dept. of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology, Germany; German Cancer Consortium (DKTK) Dresden and German Cancer Research Center (DKFZ) Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Baumann
authors.affiliation: OncoRay - National Centre for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; Dept. of Nuclear Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; PET Centre, Helmholtz-Zentrum Dresden-Rossendorf, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Beuthien-Baumann
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local; D049268:Positron-Emission Tomography / Q000379:methods*; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D023041:Xenograft Model Antitumor Assays
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: Dose escalation; FDG positron emission tomography; FaDu xenografts; Fractionated irradiation; Local tumour control; Squamous cell carcinoma