25 Lesion detection by [89Zr]Zr-DFO-girentuximab and [18F]FDG PET/CT in mccRCC patients INTRODUCTION Renal cell carcinoma (RCC) accounts for 2% of all malignancies worldwide, with an estimated 403,262 new cases in 2018. Seventy percent have a clear cell component. Metastatic clear cell (mcc) RCC has a variable course, with a subgroup of patients showing slow disease progression. In those patients, it is safe to observe the course of disease in a period of so-called watchful waiting, avoiding unnecessary side-effects and costs of systemic treatment. To identify patients eligible for watchful waiting, prognostic schemes such as the International Metastatic Database Consortium (IMDC) risk model have been used to differentiate between patients with a good, intermediate or poor prognosis1,2. For staging mRCC, European Society of Medical Oncology (ESMO) guidelines mandate contrast-enhanced computed tomography (CT) of chest, abdomen and pelvis3. Previously, an international phase II study in mRCC patients eligible for watchful waiting showed that higher numbers of IMDC adverse risk factors (p=0.0403) and higher numbers of metastatic disease organ sites (p=0.0414) were associated with a shorter period of watchful waiting4. These results substantiate the clinical value of imaging, which may be further enhanced by molecular imaging with [18F]FDG or emerging radiopharmaceuticals targeting tumor-associated antigens like carbonic anhydrase IX (CAIX) to identify patients in need of urgent systemic or local therapy. CAIX is over-expressed in 94% of ccRCC-tumors due to a mutational loss of Von Hippel Lindau protein5-7. Prognostic implications of immunohistochemically determined CAIX-expression are unequivocal7-12. In-vivo assessment of CAIX-expression can be performed with radiolabeled girentuximab (anti-CAIX antibody) PET-imaging. This technique visualizes primary and metastatic ccRCC lesions13-15. The value of [18F]FDG-PET/CT combined with CT in diagnosing and staging mRCC is not established; however, [18F]FDG-PET/CT may have prognostic value, with a positive scan being unfavourable16,17. The Imaging PAtients for Cancer drug selecTion (IMPACT)-RCC study (ClinicalTrials.gov: NCT02228954) was designed to assess the added value of [89Zr]ZrDFO-girentuximab-PET/CT and [18F]FDG-PET/CT at presentation in predicting the duration of watchful waiting in patients with good or intermediate prognosis mccRCC. Here, we report the lesion detection of [89Zr]Zr-DFO-girentuximab-PET/CT and [18F]FDG-PET/ CT in mccRCC in addition to CT. We determined the lesion detection yield of the three modalities, assessed inter-observer agreement in [89Zr]Zr-DFO-girentuximab-uptake interpretation, and investigated determinants of quantitative [89Zr]Zr-DFO-girentuximab and [18F]FDG-uptake. 2
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