title: Imaging of hypoxia with 18F-FAZA PET in patients with locally advanced non-small cell lung cancer treated with definitive chemoradiotherapy.
abstract: BACKGROUND
  For many cancers, tumour hypoxia is an adverse prognostic factor, and increases chemoradiation resistance; its importance in non-small cell lung cancer (NSCLC) is unproven. This study evaluated tumoural hypoxia using fluoroazomycin arabinoside ((18) F-FAZA) positron emission tomography (PET) scans among patients with locoregionally advanced NSCLC treated with definitive chemoradiation.
  
  
  METHODS
  Patients with stage IIIA-IIIB NSCLC underwent (18) F-FAZA PET scans and (18) F-2-deoxyglucose (FDG)-PET scans within 4 weeks of commencing and 8 weeks following conventionally-fractionated concurrent platinum-based chemoradiation (60 Gy). Intra-lesional hypoxic volumes of the primary and nodal masses were compared with FDG-PET metabolic volumes. Baseline tumoural hypoxia was correlated with disease free survival (DFS).
  
  
  RESULTS
  Seventeen patients underwent pre-treatment (18) F-FAZA PET and FDG-PET scans. Intra-lesional hypoxia was identified on 11 scans (65%). Baseline lesional hypoxic volumes were consistently smaller than FDG-PET volumes (P = 0.012). There was no statistical difference between the mean FDG-PET volumes in patients with or without baseline hypoxia (P = 0.38). Eight patients with baseline hypoxia had post treatment (18) F-FAZA scans and 6 of these (75%) had resolution of imageable hypoxia following chemoradiation. The DFS was not significantly different between the hypoxic or non-hypoxic groups (median 0.8 years and 1.3 years respectively, P = 0.42).
  
  
  CONCLUSIONS
  Intra-lesional hypoxia, as detected by (18) F-FAZA PET, was present in 65% of patients with locally-advanced NSCLC and resolved in the majority of patients following chemoradiation. Larger studies are required to evaluate the prognostic significance of the presence and resolution of hypoxia assessed by PET in NSCLC.
authors.affiliation: Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: Mateya E
authors.initials: ME
authors.lastname: Trinkaus
authors.forename: Rob
authors.initials: R
authors.lastname: Blum
authors.forename: Danny
authors.initials: D
authors.lastname: Rischin
authors.forename: Jason
authors.initials: J
authors.lastname: Callahan
authors.forename: Mathias
authors.initials: M
authors.lastname: Bressel
authors.forename: Tatiana
authors.initials: T
authors.lastname: Segard
authors.forename: Peter
authors.initials: P
authors.lastname: Roselt
authors.forename: Peter
authors.initials: P
authors.lastname: Eu
authors.forename: David
authors.initials: D
authors.lastname: Binns
authors.forename: Michael P
authors.initials: MP
authors.lastname: MacManus
authors.forename: David
authors.initials: D
authors.lastname: Ball
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000628:therapy; D015687:Cell Hypoxia; D059248:Chemoradiotherapy / Q000379:methods; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; C498052:fluoroazomycin arabinoside
keywords: FAZA; PET; chemoradiation; hypoxia; lung cancer