title: Hypoxia-targeted radiotherapy dose painting for head and neck cancer using (18)F-FMISO PET: a biological modeling study.
abstract: BACKGROUND
  This study investigates the use of (18)F-fluoromisonidazole (FMISO) PET-guided radiotherapy dose painting for potentially overcoming the radioresistant effects of hypoxia in head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  The study cohort consisted of eight patients with HNSCC who were planned for definitive radiotherapy. Hypoxic subvolumes were automatically generated on pre-radiotherapy FMISO PET scans. Three radiotherapy plans were generated for each patient: a standard (STD) radiotherapy plan to a dose of 70 Gy, a uniform dose escalation (UDE) plan to the standard target volumes to a dose of 84 Gy, and a hypoxia dose-painted (HDP) plan with dose escalation only to the hypoxic subvolume to 84 Gy. Plans were compared based on tumor control probability (TCP), normal tissue complication probability (NTCP), and uncomplicated tumor control probability (UTCP).
  
  
  RESULTS
  The mean TCP increased from 73% with STD plans to 95% with the use of UDE plans (p < 0.001) and to 93% with HDP plans (p < 0.001). The mean parotid NTCP increased from 26% to 44% with the use of UDE plans (p = 0.003), and the mean mandible NTCP increased from 2% to 27% with the use of UDE plans (p = 0.001). There were no statistically significant differences between any of the NTCPs between the STD plans and HDP plans. The mean UTCP increased from 48% with STD plans to 66% with HDP plans (p = 0.016) and dropped to 37% with UDE plans (p = 0.138).
  
  
  CONCLUSIONS
  Hypoxia-targeted radiotherapy dose painting for head and neck cancer using FMISO PET is technically feasible, increases the TCP without increasing the NTCP, and increases the UTCP. This approach is superior to uniform dose escalation.
authors: Radiation Oncology Centre , Austin Health, Victoria , Australia.
authors: Joe H
authors: JH
authors: Chang
authors: Morikatsu
authors: M
authors: Wada
authors: Nigel J
authors: NJ
authors: Anderson
authors: Daryl
authors: D
authors: Lim Joon
authors: Sze Ting
authors: ST
authors: Lee
authors: Sylvia J
authors: SJ
authors: Gong
authors: Dishan H
authors: DH
authors: Gunawardana
authors: John
authors: J
authors: Sachinidis
authors: Graeme
authors: G
authors: O'Keefe
authors: Hui K
authors: HK
authors: Gan
authors: Vincent
authors: V
authors: Khoo
authors: Andrew M
authors: AM
authors: Scott
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D015687:Cell Hypoxia; D015331:Cohort Studies; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives*; D008954:Models, Biological; D009367:Neoplasm Staging; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D050397:Radiotherapy, Intensity-Modulated
chemical_list: D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; D008920:Misonidazole