title: Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography-guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study.
abstract: OBJECTIVE
  Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV(h)) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV(h) increases the tumor control probability. This study examined the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ((18)F-FMISO PET/CT)-guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients.
  
  
  METHODS
  (18)F-FMISO was administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and (18)F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated (18)F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate (18)F-FMISO PET/CT-guided IMRT plans.
  
  
  RESULTS
  The heterogeneous distribution of (18)F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing (18)F-FMISO PET/CT-guided IMRT for 10 HNC patients achieved 84 Gy to the GTV(h) and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTV(h) for 2 patients and were successful in 1, with normal tissue sparing.
  
  
  CONCLUSIONS
  It was feasible to dose escalate the GTV(h) to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA. leen2@mskcc.org
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Lee
authors.forename: James G
authors.initials: JG
authors.lastname: Mechalakos
authors.forename: Sadek
authors.initials: S
authors.lastname: Nehmeh
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Lin
authors.forename: Olivia D
authors.initials: OD
authors.lastname: Squire
authors.forename: Shangde
authors.initials: S
authors.lastname: Cai
authors.forename: Kelvin
authors.initials: K
authors.lastname: Chan
authors.forename: Pasquale B
authors.initials: PB
authors.lastname: Zanzonico
authors.forename: Carlo
authors.initials: C
authors.lastname: Greco
authors.forename: Clifton C
authors.initials: CC
authors.lastname: Ling
authors.forename: John L
authors.initials: JL
authors.lastname: Humm
authors.forename: Heiko
authors.initials: H
authors.lastname: Schöder
mesh_terms: D015687:Cell Hypoxia; D005240:Feasibility Studies; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods; D011446:Prospective Studies; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; D008920:Misonidazole