Interobserver agreement of qualitative analysis and tumor delineation of 18F-fluoromisonidazole and 3′-deoxy-3′- 18F-fluorothymidine PET images in lung cancer

Abstract

As the preparation phase of a multicenter clinical trial using 18Ffluoro- 2-deoxy-D-glucose (18F-FDG), 18F-fluoromisonidazole (18FFMISO), and 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) in non-small cell lung cancer (NSCLC) patients, we investigated whether 18 nuclear medicine centers would score tracer uptake intensity similarly and define hypoxic and proliferative volumes for 1 patient and we compared different segmentation methods. Methods: Ten 18F-FDG, ten 18F-FMISO, and ten 18F-FLT PET/CT examinations were performed before and during curative-intent radiotherapy in 5 patients with NSCLC. The gold standards for uptake intensity and volume delineation were defined by experts. The between-center agreement (18 nuclear medicine departments connected with a dedicated network, SFMN-net [French Society of Nuclear Medicine]) in the scoring of uptake intensity (5-level scale, then divided into 2 levels: 0, normal; 1, abnormal) was quantified by κ-coefficients (κ). The volumes defined by different physicians were compared by overlap and k. The uptake areas were delineated with 22 different methods of segmentation, based on fixed or adaptive thresholds of standardized uptake value (SUV). Results: For uptake intensity, the k values between centers were, respectively, 0.59 for 18F-FDG, 0.43 for 18F-FMISO, and 0.44 for 18F-FLT using the 5-level scale; the values were 0.81 for 18F-FDG and 0.77 for both 18F-FMISO and 18F-FLT using the 2-level scale. The mean overlap and mean κ between observers were 0.13 and 0.19, respectively, for 18F-FMISO and 0.2 and 0.3, respectively, for 18FFLT. The segmentation methods yielded significantly different volumes for 18F-FMISO and 18F-FLT (P < 0.001). In comparison with physicians, the best method found was 1.5×maximum SUV (SUVmax) of the aorta for 18F-FMISO and 1.3×SUVmax of the muscle for 18F-FLT. The methods using the SUV of 1.4 and the method using 1.5×the SUVmax of the aorta could be used for 18F-FMISO and 18F-FLT. Moreover, for 18F-FLT, 2 other methods (adaptive threshold based on 1.5 or 1.6×muscle SUVmax) could be used. Conclusion: The reproducibility of the visual analyses of 18F-FMISO and 18F-FLT PET/CT images was demonstrated using a 2-level scale across 18 centers, but the interobserver agreement was low for the 18F-FMISO and 18FFLT volume measurements. Our data support the use of a fixed threshold (1.4) or an adaptive threshold using the aorta background to delineate the volume of increased 18F-FMISO or 18F-FLT uptake. With respect to the low tumor-on-background ratio of these tracers, we suggest the use of a fixed threshold (1.4). COPYRIGHT © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.