27 Lesion detection by [89Zr]Zr-DFO-girentuximab and [18F]FDG PET/CT in mccRCC patients reports for [18F]FDG and [89Zr]Zr-DFO-girentuximab-PET/CT was performed by drawing regionsof-interest using Inveon Research Workplace software (IRW, version 4.1). The maximum and mean standardized uptake values (SUV) were calculated. SUVmax was used for tumor tracer-uptake; SUVmean for measuring uptake in healthy organs and blood pool. Statistical analysis To compare the agreement in individual lesion detection between observers, we used dependent pair wise or multi-observers kappa-coefficients with the delta method19. Lesion detection rates per imaging modality and combined imaging modalities (CT combined with PET/CT) were estimated and compared (by Wald tests) using mixed effect logistic regression models accounting for within patient and lesion clustering by random intercepts. We evaluated lesion detection rates overall and according to organ sites. Furthermore, we compared the median number of affected organ sites across patients assessed by CT only, or in conjunction with either PET/CT using Wilcoxon signed rank tests. To assess biodistribution of [89Zr]Zr-DFO-girentuximab, we estimated the average SUV mean per organ and compared variability within and between patients (one-sample T-test). SUVmax was evaluated using descriptive methods besides mixed effects linear regression models, taking within patient clustering into account as random intercepts (using intra-class correlation coefficient (ICC) to estimate variation in uptake due to between-patient heterogeneity). These models were also used to assess determinants of tracer-uptake (introduced as fixed effects and compared by Wald tests). SUVmax was natural log-transformed to obtain appropriate model fit, resulting in geometric means or percent changes in SUVmax as interpretation of fixed effects. We fitted these models under restricted maximum likelihood using Satterthwaite approximations to degrees of freedom. We used the marginal R2 to estimate the variance in tracer-uptake explained by the fixed effects of these models20, then fitted under maximum likelihood. We report estimates with 95% confidence intervals (CI), and statistical tests were two-sided with threshold for significance of 5%, without adjusting for multiple testing. Analyses were performed in R (version 3.2.1), particularly using libraries multi-agree (version 2.1), lme4 (version1.1- 11), lmerTest (version2.0-20), and MuMIn (version1.10.0). RESULTS Patients From February 2015 until March 2018, 42 mccRCC patients were included. All patients had a histopathological diagnosis of the primary tumor, either through (partial) nephrectomy or biopsy in 36 and six patients, respectively. A total of 14 patients had a favorable prognosis. Of the remaining 28 patients, 13 had a predicted intermediate prognosis with one risk factor and 15 patients with two risk factors. This was primarily due to the diagnosis of metastases <1 year after the primary diagnosis (80%) and/or the presence of anemia (51%). There was no correlation between histology (e.g., mixed vs. pure clear cell) and the estimated prognosis according to IMDC. 2
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