26 Chapter 2 MATERIALS AND METHODS Patients In this prospective multi-center cohort study, patients aged 18 years and older with histologically or cytologically proven RCC with a clear cell component, recently (<6 months) diagnosed metastases, and a good or intermediate prognosis according to IMDC score1, were enrolled in the IMPACTRCC study conducted at four Dutch academic medical centers. A period of watchful waiting for 2 months was considered optional according to treating medical oncologist. Patients who received any previous systemic treatment for RCC in any setting were excluded, but previous radiotherapy and surgery (nephrectomy or metastasectomy) was permitted. Furthermore, patients were excluded in the presence of untreated central nervous system metastases or symptomatic intracerebral metastases, pregnant or breast-feeding women. Only patients without prior systemic treatment were enrolled, therefore the IMDC criteria ‘time from diagnosis to treatment <1 year’ was adapted into ‘time from primary diagnosis to diagnosis of metastatic disease <1 year’. Watchful waiting was terminated if radiological disease progression was established, in combination with a clinical need to start systemic treatment. Patient imaging Patients underwent CT, [18F]FDG and [89Zr]Zr-DFO-girentuximab-PET/CT at the start of the watchful waiting period. Further details on the imaging modalities (acquisition and reconstruction protocols) and the conjugation, radiolabeling and quality control of [89Zr]Zr-DFO-girentuximab are provided in the supplementary data. Image assessment All CT and [18F]FDG-PET/CT scans were reported according to standard clinical practice by an experienced local radiologist and nuclear physician, respectively. The assessment of CT lesions was performed according to RECIST 1.118; however, to ensure measurements and documentation of all lesions including non-target lesions of ≥10 mm, CT scans were independently revised by one or two experienced radiologists (E.H.A; T.C.K.). The [89Zr]Zr-DFO-girentuximab PET/CTs were assessed in a central reviewing system to ensure true lesion detection and reproducible inter-observer agreement. All [89Zr]Zr-DFO-girentuximab PET/CTs were assessed by three expert nuclear physicians independently (W.O.; A.H.B.; O.H.) through online central reviewing system designed by CTMM TRaIT. The three reports were harmonized to one final report by one designated reviewer. In case of different findings, a meeting was organized to reach consensus. The treating physician was blinded for the results of either PET/CT; however, for patient safety reasons, the nuclear physician was allowed to communicate findings that required (local) interventions (e.g., brain metastases). A tumor lesion was defined visually positive based on anatomical substrate on low-dose CT in combination with [18F]-FDG and/or [89Zr]Zr-DFO-girentuximab-uptake, or solely on prominent, non-physiological antibody-uptake. Quantification of positive lesions as defined by evaluation
RkJQdWJsaXNoZXIy MTk4NDMw