Assessing the performance of different outcomes for tumor growth studies with animal models.

The consistency of reporting results for patient-derived xenograft (PDX) studies is an area of concern. The PDX method commonly starts by implanting a derivative of a human tumor into a mouse, then comparing the tumor growth under different treatment conditions. Currently, a wide array of statistical methods (e.g., t-test, regression, chi-squared test) are used to analyze these data, which ultimately depend on the outcome chosen (e.g., tumor volume, relative growth, categorical growth). In this simulation study, we provide empirical evidence for the outcome selection process by comparing the performance of both commonly used outcomes and novel variations of common outcomes used in PDX studies. Data were simulated to mimic tumor growth under multiple scenarios, then each outcome of interest was evaluated for 10 000 iterations. Comparisons between different outcomes were made with respect to average bias, variance, type-1 error, and power. A total of 18 continuous, categorical, and time-to-event outcomes were evaluated, with ultimately 2 outcomes outperforming the others: final tumor volume and change in tumor volume from baseline. Notably, the novel variations of the tumor growth inhibition index (TGII)-a commonly used outcome in PDX studies-was found to perform poorly in several scenarios with inflated type-1 error rates and a relatively large bias. Finally, all outcomes of interest were applied to a real-world dataset.

Small target repeatability of 68Ga and 18F: effects of target concentration and imaging time on SUV measurements in clinically relevant phantoms.

Quantification of tumor uptake using PET imaging is important for the evaluation of therapy response. For 18F FDG PET scans, a change in uptake of 25% is commonly considered significant. For scans using novel radiopharmaceuticals, the threshold of significance is unclear. Factors including imaging time, tumor size, activity concentration, and radiopharmaceutical may affect the repeatablity of uptake metrics. This work evaluates the effect of these parameters on the repeatablity of maximum SUV (SUVmax) and mean SUV (SUVmean) in phantoms using 18F and 68Ga. An Esser PET phantom (Data Spectrum, Durham NC) was scanned on a Biograph Horizon PET/CT scanner (Siemens Medical Solutions, Malvern PA) using 18F and 68Ga. Data were acquired for 5 minutes with reconstructions between 0.5-5 minutes. The background activity mimicked clinical scans with target-to-background (T/B) ratios from 1.7-19.8. The SUVmax and SUVmean were measured for 5 slices. The mean, standard deviation, and coefficient of variation (COV) were calculated. The effects of radionuclide, imaging time, activity concentration, and target size on COV were evaluated using multivariate gamma regressions. COV for 68Ga was 40% higher and 54% higher on average than for 18F for SUVmax and SUVmean, respectively. Decreased lesion size, imaging time, and activity concentration were significantly associated with increased COV for both metrics (P < 0.001). COV was substantially reduced at high T/B for 68Ga. At the highest T/B the COV for SUVmax and SUVmean was within the typical range seen for 18F. COV is relatively high for small targets (8 mm) but is dramatically reduced with high radiotracer uptake.

Mass-Like Fat at the Medial Midfoot: A Common Pseudolesion.

Background Fatty masses are common and may be encountered in the foot and ankle. In some cases, normal subcutaneous fat may be mistaken for a discrete mass. Aims The aim of this study was to evaluate the common finding of prominent subcutaneous fat at the medial midfoot resembling a lipoma and to determine the prevalence of this pseudolesion by applying a series of potential size cutoff criteria. Materials and Methods Three musculoskeletal radiologists retrospectively evaluated 91 sequentially performed magnetic resonance imaging examinations of the ankle to measure fat resembling a discrete lipoma at the medial midfoot. Each blinded reader measured the largest area of continuous subcutaneous fat in orthogonal axial, coronal craniocaudal, and coronal transverse dimensions. Patient age, sex, and study indications were also recorded. Statistical analysis was performed with R and SAS 9.4 software Results A discrete fatty pseudolesion as defined by measuring at least 1 cm in all planes by measurements of at least two of three readers was present in 87% of cases (79 of 91). When a size criterion of 1.5 cm was used, a pseudolesion was documented in 14% of cases (13 of 91). There was a significant correlation between larger pseudolesion size and female sex in the axial plane; however, there was no correlation in the coronal craniocaudal and coronal transverse dimensions. Conclusions Subcutaneous fat at the medial midfoot often has a mass-like appearance that could be mistaken for a lipoma. It is important to recognize this pseudolesion variant and not to confuse the imaging appearance for a discrete mass.