title: Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy.
abstract: In radiotherapy of head and neck cancer (HNC) and non-small cell lung cancer (NSCLC), hypoxia is known to be an important prognostic factor for long-term survival and local tumor control. The PET tracer (18)F-fluoromisonidazole (FMISO) allows noninvasive assessment of tumor hypoxia. This study analyzed whether FMISO PET could predict tumor recurrence after radiotherapy.
  
  
  METHODS
  Forty patients with advanced HNC (n = 26) or NSCLC (n = 14) were studied before curative radiotherapy. Dynamic (0-15 min) and static PET scans were acquired up to 4 h after injection of 400 MBq of FMISO. Standardized uptake values (SUVs) and ratios to reference tissues (mediastinum or muscle) were calculated. In addition, time-activity curves up to 14 min after injection were classified visually. PET data were correlated with clinical follow-up data (presence or absence of local recurrence within 1 y), which were available for 21 patients.
  
  
  RESULTS
  For HNC, patients with local recurrence could be separated from disease-free patients by SUV 4 h after injection (all recurrences had an SUV > 2). For NSCLC, no such correlation was observed. The tumor-to-muscle ratios (T/Mu) and tumor-to-mediastinum ratios (T/Me) at 4 h after injection correlated with the risk of relapse in both tumor entities: All patients with a T/Me greater than 2.0 (NSCLC, n = 5) or with a T/Mu greater than 1.6 (HNC, n = 5) presented with tumor recurrence, whereas only 3 of the remaining 11 patients experienced recurrence (27%). Qualitative analysis of time-activity curves for 37 patients revealed 3 curve types (rapid washout, n = 9; intermediate [delayed washout], n = 12; and accumulation, n = 16). Eighteen patients categorized by curve type could be followed up: In 5 of 6 patients with an accumulation curve, disease recurred locally within 1 y, compared with 5 of 8 patients with a delayed-washout curve and 0 of 4 with a rapid-washout curve.
  
  
  CONCLUSIONS
  Our results indicate that outcome after radiotherapy can be predicted on the basis of kinetic behavior of FMISO in tumor tissue. An accumulation-type curve, high SUV, and high T/Mu and T/Me at 4 h after injection are highly suggestive of an incomplete response to treatment and might be used to select patients for intensified therapy protocols.
authors.affiliation: Department of Nuclear Medicine, University of Tuebingen, D-72076 Tuebingen, Germany. susanne-martina.eschmann@med.uni-tuebingen.de
authors.forename: Susanne-Martina
authors.initials: SM
authors.lastname: Eschmann
authors.forename: Frank
authors.initials: F
authors.lastname: Paulsen
authors.forename: Matthias
authors.initials: M
authors.lastname: Reimold
authors.forename: Helmut
authors.initials: H
authors.lastname: Dittmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Welz
authors.forename: Gerald
authors.initials: G
authors.lastname: Reischl
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Machulla
authors.forename: Roland
authors.initials: R
authors.lastname: Bares
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000532:radiotherapy*; D015687:Cell Hypoxia; D005260:Female; D005462:Fluorine Radioisotopes; D005858:Germany / Q000453:epidemiology; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000532:radiotherapy*; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives*; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000532:radiotherapy; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data; D011379:Prognosis; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole