Assessment of the Tumor Redox Status in Head and Neck Cancer by Cu-62-ATSM PET

作者：Tsujikawa Tetsuya^*; Asahi Satoko; Oh Myungmi; Sato Yoshitaka; Narita Norihiko; Makino Akira; Mori Tetsuya; Kiyono Yasushi; Tsuchida Tatsuro; Kimura Hirohiko; Fujieda Shigeharu; Okazawa Hidehiko

来源：PLos One, 2016, 11(5): e0155635.

DOI：10.1371/journal.pone.0155635

Purpose
Tumor redox is an important factor for cancer progression, resistance to treatments, and a poor prognosis. The aim of the present study was to define tumor redox (over-reduction) using Cu-62-diacetyl-bis(N-4-methylthiosemicarbazone) (Cu-62-ATSM) PET and compare its prognostic potential in head and neck cancer (HNC) with that of 2-deoxy-2-[F-18]fluoro-D-glucose (F-18-FDG).
Methods
Thirty HNC patients (stage II-IV) underwent pretreatment Cu-62-ATSM and F-18-FDG PET scans. Maximum standardized uptake values (SUVATSM and SUVFDG) and tumor-to-muscle activity concentration ratios (TMRATSM and TMRFDG) were measured. Reductive-tumor-volume (RTV) was then determined at four thresholds (40%, 50%, 60%, and 70% SUVATSM), and total-lesion-reduction (TLR) was calculated as the product of the mean SUV and RTV for Cu-62-ATSM. In F-18-FDG, metabolic-tumor-volume (MTV) and total-lesion-glycolysis (TLG) were obtained at a threshold of 40%. A ROC analysis was performed to determine% thresholds for RTV and TLR showing the best predictive performance, and these were then used to determine the optimal cut-off values to stratify patients for each parameter. Progression-free-survival (PFS) and cause-specific-survival (CSS) were evaluated by the Kaplan-Meier method.
Results
The means +/- standard deviations of PFS and CSS periods were 16.4 +/- 13.4 and 19.2 +/- 12.4 months, respectively. A ROC analysis determined that the 70% SUVATSM threshold for RTV and TLR was the best for predicting disease progression and cancer death. Optimal cut-offs for each index were SUVATSM = 3.6, SUVFDG = 7.9, TMRATSM = 3.2, TMRFDG = 5.6, RTV = 2.9, MTV = 8.1, TLR = 14.0, and TLG = 36.5. When the cut-offs for TMRATSM and TLR were set as described above in Cu-62-ATSM PET, patients with higher TMRATSM (p = 0.03) and greater TLR (p = 0.02) showed significantly worse PFS, while patients with greater TLR had significantly worse CSS (p = 0.02). Only MTV in 18F-FDG PET predicted differences in PSF and CSS (p = 0.03 and p = 0.03, respectively).
Conclusion
Tumor redox parameters measured by 62Cu-ATSM PET may be determinants of HNC patient outcomes and help define optimal patient-specific treatments.

• 出版日期2016-5-17