University of Groningen Lesion detection by [Zr-89]Zr-DFO-girentuximab and [F-18]FDG-PET/CT in patients with newly diagnosed metastatic renal cell carcinoma Verhoeff,

Purpose The main objective of this preliminary analysis of the IMaging PAtients for Cancer drug selecTion (IMPACT)-renal cell cancer (RCC) study is to evaluate the lesion detection of baseline contrast-enhanced CT, [Zr]Zr-DFO-girentuximab-PET/CT and [F]FDG-PET/CT in detecting ccRCC lesions in patients with a good or intermediate prognosis metastatic clear cell renal cell carcinoma (mccRCC) according to the International Metastatic Database Consortium (IMDC) risk model. Methods Between February 2015 and March 2018, 42 newly diagnosed mccRCC patients with good or intermediate prognosis, eligible for watchful waiting, were included. Patients underwent CT, [Zr]Zr-DFO-girentuximab-PET/CT and [F]FDG-PET/ CTat baseline. Scans were independently reviewed and lesions of ≥10mm and lymph nodes of ≥15mm at CTwere analyzed. For lesions with [Zr]Zr-DFO-girentuximab or [F]FDG-uptake visually exceeding background uptake, maximum standardized uptake values (SUVmax) were measured. Results A total of 449 lesions were detected by ≥1 modality (median per patient: 7; ICR 4.25–12.75) of which 42% were in lung, 22% in lymph nodes and 10% in bone. Combined [Zr]Zr-DFO-girentuximab-PET/CT and CT detected more lesions than CT alone: 91% (95%CI: 87–94) versus 56% (95%CI: 50–62, p = 0.001), respectively, and more than CT and [F]FDG-PET/CT Sarah R. Verhoeff and Suzanne C. van Es contributed equally to this work. This article is part of the Topical Collection onOncology –Genitourinary. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00259-019-04358-9) contains supplementary material, which is available to authorized users. * Carla M. L. van Herpen Carla.vanherpen@radboudumc.nl 1 Department of Medical Oncology, Radboud University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands 2 Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 3 Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam, The Netherlands 4 Departments of Medical Oncology and Radiology & Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands 5 Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands 6 Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands 7 Department of Nuclear Medicine andMolecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands 8 Department of Radiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands 9 Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam, The Netherlands 10 Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands 11 Department of Radiology and Nuclear Medicine, Rijnstate, Arnhem, The Netherlands 12 Department of Biomedical Sciences, Humanitas University, Milan, Italy European Journal of Nuclear Medicine and Molecular Imaging https://doi.org/10.1007/s00259-019-04358-9

[1]  W. Oyen,et al.  Positron Emission Tomography/Computed Tomography with 89Zr-girentuximab Can Aid in Diagnostic Dilemmas of Clear Cell Renal Cell Carcinoma Suspicion. , 2018, European urology.

[2]  N. Rioux-Leclercq,et al.  The two glycolytic markers GLUT1 and MCT1 correlate with tumor grade and survival in clear-cell renal cell carcinoma , 2018, PloS one.

[3]  Mark Lubberink,et al.  Quantification, improvement, and harmonization of small lesion detection with state-of-the-art PET , 2017, European Journal of Nuclear Medicine and Molecular Imaging.

[4]  A. Belldegrun,et al.  Adjuvant Weekly Girentuximab Following Nephrectomy for High-Risk Renal Cell Carcinoma: The ARISER Randomized Clinical Trial , 2017, JAMA oncology.

[5]  S. Vanbelle Comparing dependent kappa coefficients obtained on multilevel data , 2017, Biometrical journal. Biometrische Zeitschrift.

[6]  Yiyan Liu The Place of FDG PET/CT in Renal Cell Carcinoma: Value and Limitations , 2016, Front. Oncol..

[7]  E. Plimack,et al.  Active surveillance in metastatic renal-cell carcinoma: a prospective, phase 2 trial. , 2016, The Lancet. Oncology.

[8]  Arun Z. Thomas,et al.  Prediction of Pulmonary Metastasis in Renal Cell Carcinoma Patients with Indeterminate Pulmonary Nodules. , 2016, European urology.

[9]  P. Russo,et al.  Subcentimeter pulmonary nodules are not associated with disease progression in patients with renal cell carcinoma. , 2015, The Journal of urology.

[10]  H. Hollema,et al.  89Zr-Bevacizumab PET Visualizes Heterogeneous Tracer Accumulation in Tumor Lesions of Renal Cell Carcinoma Patients and Differential Effects of Antiangiogenic Treatment , 2015, The Journal of Nuclear Medicine.

[11]  T. Choueiri,et al.  Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy. , 2014, European urology.

[12]  W. Oyen,et al.  Indium-111-labeled girentuximab immunoSPECT as a diagnostic tool in clear cell renal cell carcinoma. , 2013, European urology.

[13]  E. Oosterwijk,et al.  Application of Monoclonal Antibody G250 Recognizing Carbonic Anhydrase IX in Renal Cell Carcinoma , 2013, International journal of molecular sciences.

[14]  T. Choueiri,et al.  External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. , 2013, The Lancet. Oncology.

[15]  Shinichi Nakagawa,et al.  A general and simple method for obtaining R2 from generalized linear mixed‐effects models , 2013 .

[16]  Steven P. Larson,et al.  Positron emission tomography/computed tomography identification of clear cell renal cell carcinoma: results from the REDECT trial. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  M. Okada,et al.  [New response evaluation criteria in solid tumours-revised RECIST guideline (version 1.1)]. , 2009, Gan to kagaku ryoho. Cancer & chemotherapy.

[18]  Wanling Xie,et al.  Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  A. Belldegrun,et al.  CA9 gene: single nucleotide polymorphism predicts metastatic renal cell carcinoma prognosis. , 2009, The Journal of urology.

[20]  J. Cheville,et al.  Carbonic anhydrase IX is not an independent predictor of outcome for patients with clear cell renal cell carcinoma. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  K. Grankvist,et al.  Prognostic impact of carbonic anhydrase IX expression in human renal cell carcinoma , 2007, BJU international.

[22]  W. Oyen,et al.  Targeting of metastatic renal cell carcinoma with the chimeric monoclonal antibody G250 labeled with (131)I or (111)In: an intrapatient comparison. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[23]  C. Siegel The usefulness of F-18 deoxyglucose whole-body positron emission tomography (PET) for re-staging of renal cell cancer. , 2003, The Journal of urology.

[24]  Steve Horvath,et al.  Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[25]  R. Figlin,et al.  Number of metastatic sites rather than location dictates overall survival of patients with node-negative metastatic renal cell carcinoma. , 2003, Urology.

[26]  N. Munshi,et al.  Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. , 2001, The New England journal of medicine.

[27]  R. Brakenhoff,et al.  Molecular cloning and immunogenicity of renal cell carcinoma‐associated antigen G250 , 2000, International journal of cancer.

[28]  C. Porta,et al.  Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. , 2019, Annals of oncology : official journal of the European Society for Medical Oncology.