FLT and FMISO may lack FDG's interreader agreement for lung cancer

In an effort to hike up radiochemotherapy dose and improve lung cancer survival, oncologists have been looking for higher-precision alternatives to F-18 FDG PET, which experiences issues with tumor shrinkage and alterations in uptake during treatment. However, emerging F-18 labeled alternatives fluorothymidine (FLT) and fluoromisonidazole (FMISO) show relatively low interobserver agreement when characterizing tumor volumes and require special standardization, according to a French multi-center study published August 5 in the Journal of Nuclear Medicine.

Sébastien Thureau, MD, from the Henri Becquerel Cancer Center and the University of Rouen, France, and colleagues studied the assessment of non-small cell lung cancer (NSCLC) tumors using three F-18 based agents—F-18 FDG, F-18 FMISO and F-18 FLT—across 18 nuclear medicine institutions to see how readers would interpret tracer uptake intensity and define both proliferative and hypoxic volumes. Visual interpretation of FLT and FMISO PET/CT images across centers demonstrated sufficient interreader aggreement when uptake intensity was evaluated as either positive or negative, but agreement decreased significantly when evaluating volume measurements.

"This study showed excellent reproducibility of the analysis of F-18 FMISO and F-18 FLT PET/CT images when the images were analyzed using binary scales," wrote Thureau et al. "This reproducibility allows for the use of these images in multicenter studies. In contrast, the poor reproducibility of the delineation of hypoxia and proliferative volumes requires great caution about their use for the management of patients and for therapeutic decision-making."

For this study, five patients underwent F-18 FDG, FMISO and FLT PET/CT 10 times while undergoing curative radiotherapy for NSCLC. Results for uptake intensity after statistical analysis showed interreader agreement across sites for FDG was calculated at 0.59, for FLT it was 0.44 and for FMISO it was 0.43 when using a 5-level scale of interpretation. When considering scans positive or negative in a binary scale, those calculations went up to 0.81 for FDG and 0.77 for both FLT and FMISO.

"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 F-18 FMISO or F-18 FLT uptake," wrote the authors. "With respect to the low tumor-on-background ratio of these tracers, we suggest the use of a fixed threshold (1.4)."

It was suggested that gaps in interpretation and characterization of volumes could be due in part to a lack of clinician experience using the two novel agents and specifically in reading low-contrast PET/CT scans as FLT and FMISO imaging studies are prone to be.