Abstract

Abstract Introduction Hypoxia in tumors is associated with resistance to chemotherapy. 18-F-FAZA is a PET tracer developed to characterize intratumoral hypoxic regions. Tumor metabolism is measured with 18-F-FDG PET. Goal of this study is to investigate hypoxic changes in relation to metabolic alterations in patients with advanced NSCLC during chemotherapy. Methods PET-CT with 18-F-FDG and 18-F-FAZA tracers were used prior to the first cycle and after the second cycle of chemotherapy. Volumes of interest were manually drawn on visual inspection. For FAZA, mean and maximum (max) tumor to background (FAZAT/B) ratios, and for FDG, SUVmax and SUVmean, were calculated. Measurements were corrected for partial volume using a NEMA image quality phantom. The fractional hypoxic volume, defined as the tumor fraction with a T/B ratio above 1.2 was calculated. The hypoxic and metabolic distribution within the primary tumor was studied with skewness and kurtosis. Differences between baseline and second measurement were calculated with the Wilcoxon signed rank test. Results FDG and FAZA scans were performed in 9 patients. Median FAZAT/Bmax was 2.8 (1.9-4.7) at baseline and 3.3 (1.3-5.5) and after 2 cycles, respectively, while SUVmax was 14.8 (5.8-32.5) at baseline and 14.6 (1.9-24.9) after 2 cycles. Fractional hypoxic volume was 78% (17-100%) at baseline and 74% (0-100%) after 2 cycles of therapy. No significant changes in hypoxia or metabolism were observed during chemotherapy. Hypoxic and metabolic heterogeneity within the primary tumor remained unchanged. At baseline skewness was different between FDG and FAZA (p=0.02). After 2 cycles this difference did not persist (p=0.31). There was no difference at baseline or after 2 cycles in kurtosis between FDG and FAZA. Tumor response measured with CT was 2 PR, 5 SD and 2 PD. Conclusion In this exploratory study the fractional hypoxic volume and the heterogeneity of hypoxic and metabolic areas remained unchanged during chemotherapy. The intratumoral difference in FAZA and FDG distribution changed from baseline to that after 2 cycles of chemotherapy. Citation Format: Gerald S.M.A. Kerner, Vikram R. Bollineni, Thijo J.N. Hiltermann, Jan Pruim, Harry J.M. Groen. Effects of chemotherapy on tumor hypoxia measured with 18-F-FAZA PET/CT and compared to FDG-PET/CT in advanced non-small-cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2662. doi:10.1158/1538-7445.AM2013-2662

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