Sarah Verhoeff

33 Lesion detection by [89Zr]Zr-DFO-girentuximab and [18F]FDG PET/CT in mccRCC patients girentuximab SUVmax were no longer related (estimated average change in uptake of 3% (95%CI −17 to 28) per doubling size], whereas the relation between size and [18F]FDG SUV max did not change substantially [estimated change in uptake of 32% (95%CI 11–58) per doubling size]. Thus, [89Zr] Zr-DFO-girentuximab-uptake was mainly dependent on lesion location, and little affected by size and uptake of the [18F]FDG (which together explained 63% compared to 61% by location alone). DISCUSSION This lesion detection analysis in newly diagnosed mccRCC patients with a good or intermediate prognosis according to IMDC criteria and eligible for watchful waiting, demonstrates that addition of [89Zr]Zr-DFO-girentuximab-PET/CT to CT in the diagnostic work-up increases overall detection of mccRCC lesions from 56% to 91%. The number of detected bone- and soft tissue lesions increased, and all renal and pancreatic lesions were detected with this combination of modalities. In this patient selection, [89Zr]Zr-DFO-girentuximab-PET/CT and CT resulted in the detection of more mccRCC lesions than [18F]FDG-PET/CT and CT (p = 0.006). Considering the expected proportion of false-positive lymph node lesions on [18F]FDG-PET/CT due to [18F]FDG uptake in reactive (mostly mediastinal) lymph nodes, this difference in detection rate is in favor of [89Zr]Zr-DFO-girentuximab-PET/CT and CT. A patient’s prognosis is estimated based on the number of involved organs on CT, total disease burden and period of watchful waiting, rather than the number of lesions4,21. In our study population 33% of the patients present with a predicted good prognosis mRCC and 43% of patients with synchronous metastases. This is comparable to previous datasets and reflects daily clinical practice4. Patients with lung-only metastases are thought to have a better prognosis than other involved organ sites such as liver and bone22,23. In our study population, based on CT only, seven patients (17%) presented with lung-only metastases. This number was revised after the addition of PET/CT because of the detection of additional bone and lymph node lesions by PET/CT in two patients. Furthermore, two patients were diagnosed with brain metastases by [89Zr]Zr-DFO-girentuximab PET/CT that required local treatment. Overall, the median number of two involved organs per patient as determined by CT alone increased to three per patient with the addition of PET/CT (range 1–7; p < 0.005), even without adjusting for the limited CT field-of-view. This is largely attributed to the detection of more soft-tissue and bone lesions, a well-known limitation of CT due to less soft tissue contrast and the limited ability to detect (non-lytic) bone lesions. This limited increase in the number of involved organ sites with the addition of PET/CT questions its additional value, since solely an increase in detection lesions will not lead to the implementation of [89Zr]Zr-DFO-girentuximab or [18F]FDG-PET/CT to our standard work-up. However, [89Zr]Zr-DFO-girentuximab and [18F]FDG PET/CT findings were clinical and possibly prognostic relevant in at least 10% of patients and warrants further investigation. 2