title: Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent.
abstract: OBJECTIVE
  The purpose of the study was to evaluate [(18)F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy.
  
  
  METHODS
  Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine (specific cytotoxin for hypoxic cells) in advanced (T3/4 and/or N2/3) head and neck cancer underwent serial [(18)F]fluorodeoxyglucose (FDG) and FMISO PET. We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort.
  
  
  RESULTS
  Based on blinded qualitative scoring by two readers, FMISO PET was positive in 13/15 patients at baseline: 12/15 of primary sites and 8/13 neck nodes were scored as positive. All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy, consistent with effective hypoxia-targeted therapy. With a median follow-up of 6.9 years, there have been only four locoregional failures, while three other patients have died of metachronous lung cancer. The 5-year overall survival was 50% (95% CI 27-73%), the 5-year failure-free survival was 44% (95% CI 22-68%) and the 5-year freedom from locoregional failure was 68% (95% CI 38-88%).
  
  
  CONCLUSIONS
  The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis. Evidence of the early resolution of FMISO abnormality during treatment, associated with excellent locoregional control in this patient cohort, supports further investigation of hypoxia-targeting agents in advanced head and neck cancer.
authors.affiliation: Centre for Molecular Imaging, Peter MacCallum Cancer Centre, Locked Bag No 1, A'Beckett St., Melbourne 8006, Australia. Rod.Hicks@petermac.org
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.forename: Danny
authors.initials: D
authors.lastname: Rischin
authors.forename: Richard
authors.initials: R
authors.lastname: Fisher
authors.forename: David
authors.initials: D
authors.lastname: Binns
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scott
authors.forename: Lester J
authors.initials: LJ
authors.lastname: Peters
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001596:Benzylamines; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy; D015687:Cell Hypoxia / Q000187:drug effects; D017024:Chemotherapy, Adjuvant / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage*; D015331:Cohort Studies; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods; D011379:Prognosis; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D000077704:Tirapazamine; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage*
chemical_list: D001596:Benzylamines; C475911:N,N-dimethyl-2-(2-amino-4-fluorophenylthio)benzylamine; D011838:Radiation-Sensitizing Agents; D019275:Radiopharmaceuticals; D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin