Repeatability of quantitative F-FLT uptake measurements in solid tumors: an individual patient data multi-center meta-analysis.

Introduction: 3'-deoxy-3'-[F]fluorothymidine (F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts.

Methods: A systematic search in PubMed, EMBASE.com and the Cochrane Library from inception-October 2016 yielded five F-FLT repeatability cohorts in solid tumors. F-FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUV, SUV, SUV, proliferative volume and total lesion uptake (TLU) were calculated. Repeatability was assessed using the repeatability coefficient (RC = 1.96 × SD of test-retest differences), linear regression analysis, and the intra-class correlation coefficient (ICC). The impact of different lesion selection criteria was also evaluated.

Results: Images from four cohorts containing 30 patients with 52 lesions were obtained and analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma, and 33 in non-small cell lung cancer patients). A good correlation was found between test-retest data for all F-FLT uptake metrics (R ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUV (RC: 23.1%), without significant differences in RC between different SUV metrics. Repeatability of proliferative volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection methods based on SUV ≥ 4.0 improved the repeatability of volumetric metrics (RC: 26-28%), but did not affect the repeatability of SUV metrics.

Conclusions: In multi-center studies, differences ≥ 25% in F-FLT SUV metrics likely represent a true change in tumor uptake. Larger differences are required for FLT metrics comprising volume estimates when no lesion selection criteria are applied.