title: Prognostic Evaluation of Disease Outcome in Solid Tumors Investigated With 64Cu-ATSM PET/CT.
abstract: OBJECTIVE
  Cu-ATSM is a very promising PET radiopharmaceutical for tumor imaging of hypoxia. One of the advantages of this compound compared with other hypoxia-avid tracers is the high tumor-to-background signal offered, which guaranties facilitated tumor delineation. This study analyzes optimal semiquantitative and quantitative parameters obtained by Cu-ATSM PET/CT in the same cohort of patients with special focus on their correlation to disease outcome.
  
  
  METHODS
  A prospective recruitment of 18 consecutive patients (M:F, 13:5; mean age, 60.7 years) with locally advanced non-small cell lung cancer (n = 7) or head and neck cancer (HNC) was performed. Each participant received 105 to 500 MBq of tracer according to body size and was scanned in a 3-dimensional mode PET/CT 60 minutes after tracer injection. PET images were reconstructed and visualized on a GE Advanced 4.6 workstation for the definition of semiquantitative and quantitative parameters: SUVmax, SUVratio-to-muscle, hypoxic tumor volume (HTV), and hypoxic burden (HB = HTV × SUVmean). These data were subsequently correlated to disease outcome, expressed in terms of progression-free survival calculated on a follow-up period with a median of 14.6 months.
  
  
  RESULTS
  All patients showed a moderately to highly increased uptake of Cu-ATSM in tumor lesions, with a mean SUVmax of 5.2 (range, 1.9-8.3) and mean SUVratio of 4.4 (range, 1.6-6.8). In addition, a broad range of HTV and HB was defined as mean values of 99.3 cm (range, 2.5-453.7 cm) and 301 (4.2-1134), respectively. Receiver operating characteristic analysis identified as reference cutoffs with respect to disease outcome with the following values: SUVmax >2.5 (AUC, 0.57; sensitivity, 88.9%; specificity, 50%), SUVratio ≤4.4 (AUC, 0.60; sensitivity, 50; specificity, 83.3%), HTV >160.7 cm (AUC, 0.61; sensitivity, 55.6%; specificity, 75%), and HB >160.7 (AUC, 0.67; sensitivity, 58.3%; specificity, 83.3%). In our cohort, HB showed a statistically significant difference in terms of mean values on the analysis of variance test with respect to disease progression (P = 0.04). On univariate analysis, Cox regression confirmed these findings and showed a significant correlation to progression-free survival for HB (P = 0.05) and HTV (P = 0.02).
  
  
  CONCLUSIONS
  In our cohort, the definition of optimal semiquantitative and quantitative parameters on Cu-ATSM PET/CT seems feasible and in line with previously published data. However, when considering the prognostic role with respect to disease outcome, the more robust parameters are represented by HTV and HB.
authors.affiliation: From the *Department of Nuclear Medicine, Humanitas Clinical and Research Center, Rozzano, Milan; †Alma Mater Studiorum University of Bologna, Doctoral Course in Specialized Medical Sciences, and ‡Department of Nuclear Medicine, University Hospital S. Orsola-Malpighi, Bologna; §Department of Nuclear Medicine, Ospedale Santa Maria della Misericordia, Rovigo, Italy; ∥Department of Radiology, University of Southern California, Los Angeles, CA; ¶Department of Medical Oncology, Ospedale degli Infermi, Faenza; #Department of Radiation Oncology, Bellaria Hospital, Bologna; **Department of Medical Oncology, Istituto Oncologico Romagnolo, Ravenna; and ††Division of Thoracic Surgery, University Hospital S. Orsola-Malpighi, Bologna, Italy.
authors.forename: Egesta
authors.initials: E
authors.lastname: Lopci
authors.forename: Ilaria
authors.initials: I
authors.lastname: Grassi
authors.forename: Domenico
authors.initials: D
authors.lastname: Rubello
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Colletti
authors.forename: Silvia
authors.initials: S
authors.lastname: Cambioli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gamboni
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salvi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Cicoria
authors.forename: Filippo
authors.initials: F
authors.lastname: Lodi
authors.forename: Claudio
authors.initials: C
authors.lastname: Dazzi
authors.forename: Sandro
authors.initials: S
authors.lastname: Mattioli
authors.forename: Stefano
authors.initials: S
authors.lastname: Fanti
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging*; D056831:Coordination Complexes; D005260:Female; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging*; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009942:Organometallic Compounds; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; D014057:Tomography, X-Ray Computed
chemical_list: D056831:Coordination Complexes; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D013882:Thiosemicarbazones; C089548:copper (II) diacetyl-di(N(4)-methylthiosemicarbazone)