Volume 65, Issue 4, Pages 766-777 (April 2014) Assessing the Response to Targeted Therapies in Renal Cell Carcinoma: Technical Insights and Practical Considerations  Axel Bex, Laure Fournier, Nathalie Lassau, Peter Mulders, Paul Nathan, Wim J.G. Oyen, Thomas Powles  European Urology  Volume 65, Issue 4, Pages 766-777 (April 2014) DOI: 10.1016/j.eururo.2013.11.031 Copyright © 2013 European Association of Urology Terms and Conditions

Fig. 1 Preferred Reporting Items for Systematic Reviews and Meta-analysis diagram outlining the study selection process. European Urology 2014 65, 766-777DOI: (10.1016/j.eururo.2013.11.031) Copyright © 2013 European Association of Urology Terms and Conditions

Fig. 2 Early response to sorafenib detected by dynamic contrast-enhanced computed tomography (CT). Transverse plane contrast-enhanced CT images of an adrenal metastasis in a patient with metastatic renal cell carcinoma (a) before therapy and (c) after 6 wk of therapy. On the corresponding parametric maps quantifying tissue blood volume, red pixels represent areas of high vascularity; blue areas represent poor vascularity. Before therapy, the size of the metastasis was 21mm and the sum of the longest diameters of target lesions according to Response Evaluation Criteria in Solid Tumours (RECIST) was 115mm. (b) Blood volume is measured at 10.7%. (d) On follow-up 6 wk later, high blood volume values (red pixels) have disappeared in the metastasis, with a mean blood volume measured at 3.3%, showing an early response according to functional imaging. The lesion, however, did not change size, measuring 18mm, with a sum of the longest diameters of target lesions at 108mm. The patient was therefore stable according to RECIST. European Urology 2014 65, 766-777DOI: (10.1016/j.eururo.2013.11.031) Copyright © 2013 European Association of Urology Terms and Conditions

Fig. 3 Early response to sunitinib assessed using dynamic contrast-enhanced ultrasonography (DCE-US) in a patient with metastatic renal cell carcinoma and an abdominal lesion. (a) B-mode, DCE-US, and corresponding computed tomography (CT) performed before treatment show high vascularity within the tumour. (b) DCE-US performed at day 7 demonstrates the beginning of necrosis within the tumour. (c) Contrast uptake curves with a strong decrease in area under the curve with a CT scan performed at 3 mo [31]. Reproduced with kind permission from Springer Science+Business Media: Current Urology Reports, Evaluation of treatment response in patients with metastatic renal cell carcinoma: role of state-of-the-art cross-sectional imaging, Volume 13, 2012, pp. 70–81, Katabathina VS, et al., Figure 3. Copyright Springer Science+Business Media, LLC 2011. European Urology 2014 65, 766-777DOI: (10.1016/j.eururo.2013.11.031) Copyright © 2013 European Association of Urology Terms and Conditions

Fig. 3 Early response to sunitinib assessed using dynamic contrast-enhanced ultrasonography (DCE-US) in a patient with metastatic renal cell carcinoma and an abdominal lesion. (a) B-mode, DCE-US, and corresponding computed tomography (CT) performed before treatment show high vascularity within the tumour. (b) DCE-US performed at day 7 demonstrates the beginning of necrosis within the tumour. (c) Contrast uptake curves with a strong decrease in area under the curve with a CT scan performed at 3 mo [31]. Reproduced with kind permission from Springer Science+Business Media: Current Urology Reports, Evaluation of treatment response in patients with metastatic renal cell carcinoma: role of state-of-the-art cross-sectional imaging, Volume 13, 2012, pp. 70–81, Katabathina VS, et al., Figure 3. Copyright Springer Science+Business Media, LLC 2011. European Urology 2014 65, 766-777DOI: (10.1016/j.eururo.2013.11.031) Copyright © 2013 European Association of Urology Terms and Conditions

Fig. 4 Response to sunitinib assessed using sequential [18F]-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in a patient with metastatic renal cell carcinoma. (A) Maximum intensity projection images of sequential whole-body PET scans. Baseline scan shows widespread FDG-avid metastatic lesions including multiple muscle deposits (arrowheads). The 4-wk scan shows a response in maximum standardised uptake value. The 16-wk therapy scan shows new FDG-avid muscle deposits consistent with progression. (B) Comparison of axial-fused PET-CT images at identical level through the chest at baseline and 4 wk after commencement of therapy showing a response to therapy. Adapted from Clinical Cancer Research 2011;17:6021–8, Kayani I, et al., Sequential FDG-PET/CT as a biomarker of response to sunitinib in metastatic clear cell renal cancer, with permission from AACR. European Urology 2014 65, 766-777DOI: (10.1016/j.eururo.2013.11.031) Copyright © 2013 European Association of Urology Terms and Conditions