title: An exploratory study of volumetric analysis for assessing tumor response with (18)F-FAZA PET/CT in patients with advanced non-small-cell lung cancer (NSCLC).
abstract: BACKGROUND
  Hypoxia is associated with resistance to chemotherapy and radiotherapy and is randomly distributed within malignancies. Characterization of changes in intratumoral hypoxic regions is possible with specially developed PET tracers such as (18)F-fluoroazomycin arabinoside ((18)F-FAZA) while tumor metabolism can be measured with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG). The purpose of this study was to study the effects of chemotherapy on (18)F-FAZA and (18)F-FDG uptake simultaneously in non-small-cell lung cancer (NSCLC) patients
  
  
  METHODS
  At baseline and after the second chemotherapy cycle, both PET/CT with (18)F-FDG and (18)F-FAZA was performed in seven patients with metastasized NSCLC. (18)F-FAZA and (18)F-FDG scans were aligned with deformable image registration using Mirada DBx. The primary tumors were contoured, and on the (18)F-FDG scan, volumes of interest (VOI) were drawn using a 41 % adaptive threshold technique. Subsequently, the resulting VOI was transferred to the (18)F-FAZA scan. (18)F-FAZA maximum tumor-to-background (T/Bgmax) ratio and the fractional hypoxic volume (FHV) were assessed. Measurements were corrected for partial volume effects. Finally, a voxel-by-voxel analysis of the primary tumor was performed to assess regional uptake differences.
  
  
  RESULTS
  In the primary tumor of all seven patients, median (18)F-FDG standard uptake value (SUVmax) decreased significantly (p = 0.03). There was no significant decrease in (18)F-FAZA uptake as measured with T/Bgmax (p = 0.24) or the FHV (p = 0.35). Additionally, volumetric voxel-by-voxel analysis showed that low hypoxic tumors did not significantly change in hypoxic status between baseline and two cycles of chemotherapy, whereas highly hypoxic tumors did. Individualized volumetric voxel-by-voxel analysis revealed that hypoxia and metabolism were not associated before and after 2 cycles of chemotherapy.
  
  
  CONCLUSIONS
  Tumor hypoxia and metabolism are independent dynamic events as measured by (18)F-FAZA PET and (18)F-FDG PET, both prior to and after treatment with chemotherapy in NSCLC patients.
authors.affiliation: Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O.Box 30.001, 9700 RB, Groningen, The Netherlands. g.s.m.a.kerner@umcg.nl.
authors.forename: Gerald S M A
authors.initials: GS
authors.lastname: Kerner
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Vikram R
authors.initials: VR
authors.lastname: Bollineni
authors.affiliation: Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O.Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Thijo J N
authors.initials: TJ
authors.lastname: Hiltermann
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Nanna M
authors.initials: NM
authors.lastname: Sijtsema
authors.affiliation: Philips Technologie GmbH Innovative Technologies, Aachen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Alphons H H
authors.initials: AH
authors.lastname: Bongaerts
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.|Department of Nuclear Medicine, Tygerberg Hospital, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Jan
authors.initials: J
authors.lastname: Pruim
authors.affiliation: Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O.Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
keywords: 18F-FAZA; 18F-FDG; Chemotherapy; NSCLC