title: Dose painting in radiotherapy for head and neck squamous cell carcinoma: value of repeated functional imaging with (18)F-FDG PET, (18)F-fluoromisonidazole PET, diffusion-weighted MRI, and dynamic contrast-enhanced MRI.
abstract: The purpose of this work was to evaluate the potential of functional imaging with (18)F-FDG PET, (18)F-fluoromisonidazole PET, diffusion-weighted MRI, and dynamic contrast-enhanced MRI to provide an appropriate and reliable biologic target for dose painting in radiotherapy for head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Fifteen patients with locally advanced HNSCC, treated with concomitant chemoradiotherapy, were prospectively enrolled in a bioimaging protocol. Sequential PET ((18)F-FDG and (18)F-fluoromisonidazole) and MRI (T1, T2, dynamic enhanced, and diffusion-weighted sequences) were performed before, during, and after radiotherapy.
  
  
  RESULTS
  Median follow-up was 30.7 mo (range, 6.3-56.3 mo); in 7 patients, disease recurred. Disease-free survival correlated negatively with the maximum tissue-to-blood (18)F-fluoromisonidazole ratio (T/B(max)) on the baseline (18)F-fluoromisonidazole scan (P = 0.04), with the size of the initial hypoxic volume (P = 0.04), and with T/B(max) on the (18)F-fluoromisonidazole scan during treatment (P = 0.02). All locoregional recurrences were within the (18)F-FDG-avid regions on baseline (18)F-FDG PET; 3 recurrences mapped outside the hypoxic volume on baseline (18)F-fluoromisonidazole PET. Lesions (primary tumor and lymph nodes) where a locoregional recurrence developed during follow-up had significantly lower apparent diffusion coefficients on diffusion-weighted MRI during week 4 of radiotherapy (0.0013 vs. 0.0018 mm(2)/s, P = 0.01) and at 3 wk after treatment (0.0014 vs. 0.0018 mm(2)/s, P = 0.01) and a significantly higher initial slope on baseline dynamic enhanced MRI (26.2 vs. 17.5/s, P = 0.03) than did lesions that remained controlled.
  
  
  CONCLUSIONS
  These results confirm the added value of (18)F-FDG PET and (18)F-fluoromisonidazole PET for radiotherapy planning of HNSCC and suggest the potential of diffusion-weighted and dynamic enhanced MRI for dose painting and early response assessment.
authors.affiliation: Department of Radiation Oncology, Leuvens Kankerinstituut, University Hospitals Leuven, Leuven, Belgium. piet.dirix@uzleauven.be
authors.forename: Piet
authors.initials: P
authors.lastname: Dirix
authors.forename: Vincent
authors.initials: V
authors.lastname: Vandecaveye
authors.forename: Frederik
authors.initials: F
authors.lastname: De Keyzer
authors.forename: Sigrid
authors.initials: S
authors.lastname: Stroobants
authors.forename: Robert
authors.initials: R
authors.lastname: Hermans
authors.forename: Sandra
authors.initials: S
authors.lastname: Nuyts
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000532:radiotherapy*; D003287:Contrast Media; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D019583:Dose Fractionation, Radiation; D005260:Female; D019788:Fluorodeoxyglucose F18; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D011881:Radiotherapy, Computer-Assisted / Q000379:methods; D020266:Radiotherapy, Conformal / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18