title: Hypoxia-guided adaptive radiation dose escalation in head and neck carcinoma: a planning study.
abstract: OBJECTIVE
  To evaluate from a planning point of view the dose distribution of adaptive radiation dose escalation in head and neck squamous cell carcinoma (HNSCC) using (18)F-Fluoroazomycin arabinoside (FAZA) positron emission tomography/computed tomography (PET-CT).
  
  
  METHODS
  Twelve patients with locally advanced HNSCC underwent three FAZA PET-CT before treatment, after 7 fractions and after 17 fractions of a carboplatin-5FU chemo-radiotherapy regimen (70 Gy in 2 Gy per fraction over 7 weeks). The dose constraints were that every hypoxic voxel delineated before and during treatment (newborn hypoxic voxels) should receive a total dose of 86 Gy. A median dose of 2.47 Gy per fraction was prescribed on the hypoxic PTV defined on the pre-treatment FAZA PET-CT; a median dose of 2.57 Gy per fraction was prescribed on the newborn voxels identified on the first per-treatment FAZA PET-CT; a median dose of 2.89 Gy per fraction was prescribed on the newborn voxels identified on the second per-treatment FAZA PET-CT.
  
  
  RESULTS
  Ten of 12 patients had hypoxic volumes. Six of 10 patients completed all the FAZA PET-CT during radiotherapy. For the hypoxic PTVs, the average D50% matched the prescribed dose within 2% and the homogeneity indices reached 0.10 and 0.12 for the nodal PTV 86 Gy and the primary PTV 86 Gy, respectively. Compared to a homogeneous 70 Gy mean dose to the PTVs, the dose escalation up to 86 Gy to the hypoxic volumes did not typically modify the dose metrics on the surrounding normal tissues.
  
  
  CONCLUSIONS
  From a planning point of view, FAZA-PET-guided dose adaptive escalation is feasible without substantial dose increase to normal tissues above tolerance limits. Clinical prospective studies, however, need to be performed to validate hypoxia-guided adaptive radiation dose escalation in head and neck carcinoma.
authors.affiliation: Department of Radiation Oncology, and Center for Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Clinique (IREC), Université Catholique de Louvain, St-Luc University Hospital , Brussels , Belgium.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Servagi-Vernat
authors.forename: Sarah
authors.initials: S
authors.lastname: Differding
authors.forename: Edmond
authors.initials: E
authors.lastname: Sterpin
authors.forename: Francois-Xavier
authors.initials: FX
authors.lastname: Hanin
authors.forename: Daniel
authors.initials: D
authors.lastname: Labar
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.forename: John A
authors.initials: JA
authors.lastname: Lee
authors.forename: Vincent
authors.initials: V
authors.lastname: Grégoire
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D009593:Nitroimidazoles; D049268:Positron-Emission Tomography / Q000379:methods; 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