title: Prognostic value of tumour blood flow, [¹⁸F]EF5 and [¹⁸F]FDG PET/CT imaging in patients with head and neck cancer treated with radiochemotherapy.
abstract: OBJECTIVE
  In order to improve the treatment of squamous cell carcinoma of the head and neck, precise information on the treated tumour's biology is required and the prognostic importance of different biological parameters needs to be determined. The aim of our study was to determine the predictive value of pretreatment PET/CT imaging using [(18)F]FDG, a new hypoxia tracer [(18)F]EF5 and the perfusion tracer [(15)O]H₂O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy.
  
  
  METHODS
  The study group comprised 22 patients with confirmed squamous cell carcinoma of the head and neck who underwent a PET/CT scan using the above tracers before any treatment. Patients were later treated with a combination of radiochemotherapy and surgery. Parametric blood flow was calculated from dynamic [(15)O]H₂O PET images using a one-tissue compartment model. [(18)F]FDG images were analysed by calculating standardized uptake values (SUV) and metabolically active tumour volumes (MATV). [(18)F]EF5 images were analysed by calculating tumour-to-muscle uptake ratios (T/M ratio). A T/M ratio of 1.5 was considered a significant threshold and used to determine tumour hypoxic subvolumes (HS) and hypoxic fraction area. The findings were finally correlated with the pretreatment clinical findings (overall stage and TNM stage) as well as the outcome following radiochemotherapy in terms of local control and overall patient survival.
  
  
  RESULTS
  Tumour stage and T-classification did not show any significant differences in comparison to the patients' metabolic and functional characteristics measured on PET. Using the Cox proportional hazards model, a shorter overall survival was associated with MATV (p = 0.008, HR = 1.108), maximum [(18)F]EF5 T/M ratio (p = 0.0145, HR = 4.084) and tumour HS (p = 0.0047, HR = 1.112). None of the PET parameters showed a significant effect on patient survival in the log-rank test, although [(18)F]EF5 maximum T/M ratio was the closest (p = 0.109). By contrast, tumour blood flow was not correlated with any of the clinical endpoints. There were no statistically significant correlations among [(18)F]FDG SUVmax, [(18)F]EF5 T/M ratio and blood flow.
  
  
  CONCLUSIONS
  Our study in a limited number of patients confirmed the importance of MATV in the prognosis of locally advanced squamous cell carcinoma of the head and neck. It is of interest that high uptake of the hypoxia tracer [(18)F]EF5 showed a stronger correlation with a poor clinical outcome than [(18)F]FDG uptake. This confirms the importance of hypoxia in treatment outcome and suggests that [(18)F]EF5 may act as a surrogate marker of radioresistance.
authors.affiliation: Turku PET Centre, Kiinamyllynkatu 4-8, 20521, Turku, Finland, gaber.komar@utu.fi.
authors.forename: Gaber
authors.initials: G
authors.lastname: Komar
authors.forename: Kaisa
authors.initials: K
authors.lastname: Lehtiö
authors.forename: Marko
authors.initials: M
authors.lastname: Seppänen
authors.forename: Olli
authors.initials: O
authors.lastname: Eskola
authors.forename: Helena
authors.initials: H
authors.lastname: Levola
authors.forename: Paula
authors.initials: P
authors.lastname: Lindholm
authors.forename: Hannu
authors.initials: H
authors.lastname: Sipilä
authors.forename: Jan
authors.initials: J
authors.lastname: Seppälä
authors.forename: Reidar
authors.initials: R
authors.lastname: Grénman
authors.forename: Olof
authors.initials: O
authors.lastname: Solin
authors.forename: Heikki
authors.initials: H
authors.lastname: Minn
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D017341:Etanidazole / Q000031:analogs & derivatives*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006258:Head and Neck Neoplasms / Q000098:blood supply* / Q000175:diagnosis* / Q000628:therapy; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011379:Prognosis; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D055815:Young Adult; D005466:Fluorocarbons
chemical_list: D017341:Etanidazole; D019788:Fluorodeoxyglucose F18; D006845:Hydrocarbons, Fluorinated; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons