Sarah Verhoeff

56 Chapter 3 Patients without IMDC risk-factors had a median WW-period of 21.3 months, which was 16.1 and 7.5 for patients with one, respectively two risk-factors (one-sided likelihood-ratio ptrend= 0.051). Patients with “W&W criteria” (n=21) showed a median WW-period of 21.3 months compared to 9.3 months in those without (n=19) (HR 1.9; 95%CI 0.9-3.9; one-sided log-rank p=0.034) Figure 5. Figure 5. Validation extended IMDC criteria. The WW-period for the unfavorable (blue) vs. favorable (red) WW-group. The pink and light blue line correspond with the observations by Rini et al. of unfavorable and favorable group, resp (median time on WW of 8.4 vs. 22.2 months, p = 0.0056). Patients that meet the “W&W criteria” (<2 IMDC criteria and ≤2 organ sites) (red) have a longer WW-period of 21.3 months compared to 9.3 months in patients with an unfavorable prognosis. In multivariable analyses, adding [18F]FDG SUV max to the “W&W criteria” significantly improved a Cox model for WW-time. This was observed for [18F]FDG-uptake as a continuous variable or based on the median split, and by analyzing “W&W criteria” in two groups or the underlying IMDC and involved organ sites as continuous variables (all p<0.001). The addition of “W&W criteria” or its two underlying variables did not improve a Cox model with [18F]FDG-PET/CT (all p>0.32). Similarly, the addition of [89Zr]Zr-DFO-girentuximab-uptake did not improve a Cox model for WW based on the “W&W criteria” or its two underlying variables (all p>0.27). In table 2B we report the multivariable analyses for WW-time and time until RECIST-defined PD for a full multivariable model including both PET scans, number of organ sites and IMDC-criteria with accompanying Wald p-values. Regarding discriminating patients according to WW-time, a Cox model for WW-time including the underlying “W&W criteria” showed an overall C-index of 0.618 (95%CI: 0.506-0.729), which was 0.722 (95%CI: 0.610-0.834) for a model containing only [18F]FDG gm SUV max continuously and 0.579 (95%CI: 0.466-0.691) for only [89Zr]Zr-DFO-girentuximab gm SUV max continuously. Adding [18F]FDG-uptake to the model with IMDC and number of organ sites increased the overall C-index to 0.732 (95%CI: 0.619-0.844; p=0.086 for improvement in C-index), which was 0.615