Repeatability of quantitative (18)F-FLT uptake measurements in solid tumors: an individual patient data multi-center meta-analysis

INTRODUCTION: 3′-deoxy-3′-[(18)F]fluorothymidine ((18)F–FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative (18)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 (18)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 (18)F–FLT repeatability cohorts in solid tumors. (18)F–FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUV(max), SUV(mean), SUV(peak), 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 (18)F–FLT uptake metrics (R(2) ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUV(peak) (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(max) ≥ 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 (18)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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00259-017-3923-x) contains supplementary material, which is available to authorized users.