title: Dynamics of tumor hypoxia assessed by 18F-FAZA PET/CT in head and neck and lung cancer patients during chemoradiation: possible implications for radiotherapy treatment planning strategies.
abstract: BACKGROUND
  To define the optimal time point for the integration of hypoxia (18)F-FAZA-PET/CT information into radiotherapy treatment planning to benefit from hypoxia modification or dose escalation treatment. Therefore, we performed a prospective cohort study, using serial hypoxic imaging ((18)F-FAZA-PET/CT) prior to and at several time-points during (chemo)radiotherapy (CHRT) in six head and neck squamous cell (HNSCC) and six non-small cell lung cancer (NSCLC) patients.
  
  
  METHODS
  The spatio-temporal dynamics of tumor hypoxia and fractional hypoxic volumes (FHV) were evaluated using a voxel-by-voxel analysis based on a (18)F-FAZA-T/B ratio of 1.4 at four time points in HNSCC patients, at baseline (FAZA-BL), at week one (FAZA-W1), two (FAZA-W2), and four (FAZA-W4) during CHRT and at three time points in NSCLC patients (baseline; W2, W4).
  
  
  RESULTS
  Ten out of twelve patients showed a substantial pre-treatment tumor hypoxia representing a FHV⩾1.4 assessed by (18)F-FAZA-PET/CT. The median FHV was 38% (FAZA-BL), 15% (FAZA-W1), 17% (FAZA-W2) and 1.5% (FAZA-W4) in HNSCC patients, and 34% (FAZA-BL), 26% (FAZA-W2) and 26% (FAZA-W4) in NSCLC patients, respectively. Stable tumor hypoxia was observed in three HNSCC patients and two NSCLC patients at FAZA-W2. In three HNSCC patients and two NSCLC patients FHVs declined to non-detectable hypoxia levels at FAZA-W4 during CHRT, while two NSCLC patients, showed increasing FHVs.
  
  
  CONCLUSIONS
  Our results indicate that, instead of using the FAZA-BL scan as the basis for the dose escalation, FAZA-W2 of CHRT is most suitable and might provide a more reliable basis for the integration of (18)F-FAZA-PET/CT information into radiotherapy treatment planning for hypoxia-directed dose escalation strategies.
authors.affiliation: University of Groningen, Department of Radiation Oncology, The Netherlands. Electronic address: bollinenivr@yahoo.com.
authors.forename: Vikram R
authors.initials: VR
authors.lastname: Bollineni
authors.affiliation: University of Groningen, Department of Nuclear Medicine and Molecular Imaging, The Netherlands.
authors.forename: Michel J B
authors.initials: MJ
authors.lastname: Koole
authors.affiliation: University of Groningen, Department of Nuclear Medicine and Molecular Imaging, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Pruim
authors.affiliation: University of Groningen, Department of Radiation Oncology, The Netherlands.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Brouwer
authors.affiliation: University of Groningen, Department of Radiation Oncology, The Netherlands.
authors.forename: Erwin M
authors.initials: EM
authors.lastname: Wiegman
authors.affiliation: University of Groningen, Department of Pulmonary Diseases, The Netherlands.
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
authors.affiliation: University of Groningen, Department of Radiation Oncology, The Netherlands.
authors.forename: Renske
authors.initials: R
authors.lastname: Vlasman
authors.affiliation: University of Groningen, Department of Otolaryngology, Head and Neck Surgery, The Netherlands.
authors.forename: Gyorgy B
authors.initials: GB
authors.lastname: Halmos
authors.affiliation: University of Groningen, Department of Medical Oncology, The Netherlands.
authors.forename: Sjoukje F
authors.initials: SF
authors.lastname: Oosting
authors.affiliation: University of Groningen, Department of Radiation Oncology, The Netherlands.
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
authors.affiliation: University of Groningen, Department of Radiation Oncology, The Netherlands.
authors.forename: Joachim
authors.initials: J
authors.lastname: Widder
authors.affiliation: University of Groningen, Department of Radiation Oncology, The Netherlands.
authors.forename: Roel J H M
authors.initials: RJ
authors.lastname: Steenbakkers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy; D015687:Cell Hypoxia / Q000502:physiology; D059248:Chemoradiotherapy; D015331:Cohort Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D009593:Nitroimidazoles; D049268:Positron-Emission Tomography / Q000379:methods; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; C498052:fluoroazomycin arabinoside
keywords: (18)F-FAZA-PET/CT; FHV; Head and neck tumors; Non-small-cell lung cancer; Tumor hypoxia