PurposeTo assess (1) the repeatability and (2) the impact of reconstruction methods and delineation on the repeatability of 105 radiomic features in non-small-cell lung cancer (NSCLC) 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomorgraphy/computed tomography (PET/CT) studies.ProceduresEleven NSCLC patients received two baseline whole-body PET/CT scans. Each scan was reconstructed twice, once using the point spread function (PSF) and once complying with the European Association for Nuclear Medicine (EANM) guidelines for tumor PET imaging. Volumes of interest (n = 19) were delineated twice, once on PET and once on CT images.ResultsSixty-three features showed an intraclass correlation coefficient ≥ 0.90 independent of delineation or reconstruction. More features were sensitive to a change in delineation than to a change in reconstruction (25 and 3 features, respectively).ConclusionsThe majority of features in NSCLC [18F]FDG-PET/CT studies show a high level of repeatability that is similar or better compared to simple standardized uptake value measures.Electronic supplementary materialThe online version of this article (doi:10.1007/s11307-016-0940-2) contains supplementary material, which is available to authorized users.

In addition to tumor size measurements with CT, there is a need for quantitative measurements of metabolic active volumes, possibly adding to tracer uptake measurements in oncologic response evaluation with PET. The aim of this study was to evaluate the metabolic volume test-retest variability in 18 F-FDG and 39-deoxy-39-18 F-fluorothymidine ( 18 F-FLT) PET studies for various commonly used volumes of interest (VOIs) and the dependence of that variability on lesion size and relative radiotracer uptake. Methods: Twenty non-small cell lung cancer patients were scanned twice with 18 F-FDG (n 5 11) or 18 F-FLT (n 5 9). VOIs were defined on images reconstructed with normalization-and attenuation-weighted ordered-subset expectation maximization using 4 isocontours (A41%, A50%, and A70% thresholds, adapted for local background, and 50% threshold, uncorrected for background). Statistical analysis comprised intraclass correlation coefficients and BlandAltman analysis. Results: In the 18 F-FDG and 18 F-FLT groups, 34 and 20 lesions, respectively, were analyzed. Median volumes at the A50% threshold were 3.31 and 2.19 mL (interquartile range, 1.91-8.90 and 1.52-7.27 mL) for 18 F-FDG and 18 F-FLT, respectively. Intraclass correlation coefficients were greater than 0.9, with the exception of the A70%-based metabolic volumes for 18 F-FLT. For lesions greater than 4.2 mL, repeatability coefficients (RCs 5 1.96 · SD) of the percentage difference ranged from 22% to 37% for 18 F-FDG and from 39% to 73% for 18 F-FLT, depending on the VOI method being used. Repeatability was better for larger tumors, but there was no dependence on absolute uptake (standardized uptake value). Conclusion: Results indicate that changes of greater than 37% for 18 F-FDG and greater than 73% for 18 F-FLT (1.96 · SD) for lesions with A50% metabolic volumes greater than 4.2 mL represent a biologic effect. For smaller lesions (A50% VOI , 4.2 mL), an absolute change of 1.0 and 0.9 mL for 18 F-FDG and 18 F-FLT, respectively, is biologically relevant. Considering the balance between the success rate of automatic tumor delineation and repeatability of metabolic volume, a 50% threshold with correction for local background activity (A50%) seems optimal among the VOI methods evaluated.

MATV metabolically active tumor volume measured with 50% of SUVhp mean SUV of a sphere of 12-mm diameter with highest local intensity corrected for local background is recommended in multicenter FDG fluorine 18 fluorodeoxyglucose PET/CT studies on the basis of a high feasibility (96%) and repeatability ( LOA limit of agreement of 36.1%).

Change in 18 F-FDG uptake may predict response to anticancer treatment. The PERCIST suggest a threshold of 30% change in SUV to define partial response and progressive disease. Evidence underlying these thresholds consists of mixed stand-alone PET and PET/CT data with variable uptake intervals and no consensus on the number of lesions to be assessed. Additionally, there is increasing interest in alternative 18 F-FDG uptake measures such as metabolically active tumor volume and total lesion glycolysis (TLG). The aim of this study was to comprehensively investigate the repeatability of various quantitative whole-body 18 F-FDG metrics in non-small cell lung cancer (NSCLC) patients as a function of tracer uptake interval and lesion selection strategies. Methods: Eleven NSCLC patients, with at least 1 intrathoracic lesion 3 cm or greater, underwent double baseline whole-body 18 F-FDG PET/CT scans at 60 and 90 min after injection within 3 d. All 18 F-FDG-avid tumors were delineated with an 50% threshold of SUV peak adapted for local background. SUV max , SUV mean , SUV peak , TLG, metabolically active tumor volume, and tumor-to-blood and -liver ratios were evaluated, as well as the influence of lesion selection and 2 methods for correction of uptake time differences. Results: The best repeatability was found using the SUV metrics of the averaged PERCIST target lesions (repeatability coefficients , 10%). The correlation between test and retest scans was strong for all uptake measures at either uptake interval (intraclass correlation coefficient . 0.97 and R 2 . 0.98). There were no significant differences in repeatability between data obtained 60 and 90 min after injection. When only PERCIST-defined target lesions were included (n 5 34), repeatability improved for all uptake values. Normalization to liver or blood uptake or glucose correction did not improve repeatability. However, after correction for uptake time the correlation of SUV measures and TLG between the 60-and 90-min data significantly improved without affecting test-retest performance. Conclusion: This study suggests that a 15% change of SUV mean /SUV peak at 60 min after injection can be used to assess response in advanced NSCLC patients if up to 5 PERCIST target lesions are assessed. Lower thresholds could be used in averaged PERCIST target lesions (,10%).

PET can be used to monitor response during chemotherapy and assess biologic target volumes for radiotherapy. Previous simulation studies have shown that the performance of various automatic or semiautomatic tumor delineation methods depends on image characteristics. The purpose of this study was to assess test-retest variability of tumor delineation methods, with emphasis on the effects of several image characteristics (e.g., resolution and contrast). Methods: Baseline test-retest data from 19 non-small cell lung cancer patients were obtained using 18 F-FDG (n 5 10) and 39-deoxy-39-18 F-fluorothymidine ( 18 F-FLT) (n 5 9). Images were reconstructed with varying spatial resolution and contrast. Six different types of tumor delineation methods, based on various thresholds or on a gradient, were applied to all datasets. Test-retest variability of metabolic volume and standardized uptake value (SUV) was determined. Results: For both tracers, size of metabolic volume and testretest variability of both metabolic volume and SUV were affected by the image characteristics and tumor delineation method used. The median volume test-retest variability ranged from 8.3% to 23% and from 7.4% to 29% for 18 F-FDG and 18 F-FLT, respectively. For all image characteristics studied, larger differences (#10-fold higher) were seen in test-retest variability of metabolic volume than in SUV. Conclusion: Test-retest variability of both metabolic volume and SUV varied with tumor delineation method, radiotracer, and image characteristics. The results indicate that a careful optimization of imaging and delineation method parameters is needed when metabolic volume is used, for example, as a response assessment parameter.