Axel Bex1, Laure Fournier2, Nathalie Lassau3, Peter Mulders4, Paul Nathan5, Wim J G Oyen6, Thomas Powles7. 1. Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: a.bex@nki.nl. 2. Université Paris Descartes Sorbonne Paris Cité, INSERM UMR-S970, and Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Radiologie, Paris, France. 3. IRCIV, Institut Gustave Roussy, Villejuif, and IR4M, UMR8081 Université Paris-Sud 11, CNRS, Villejuif, France. 4. Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands. 5. Mount Vernon Cancer Centre, Northwood, Middlesex, UK. 6. Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 7. Queen Mary University of London, Barts and London School of Medicine, West Smithfield, London, UK.
Abstract
CONTEXT: The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to significant necrosis without significant reduction in tumour size. In addition, the vascular effects of antiangiogenic therapy may occur long before there is any reduction in tumour size. OBJECTIVE: To perform a systematic review of conventional and novel imaging methods for the assessment of response to targeted agents in RCC and to discuss their use from a clinical perspective. EVIDENCE ACQUISITION: Relevant databases covering the period January 2006 to April 2013 were searched for studies reporting on the use of anatomic and functional imaging techniques to predict response to targeted therapy in RCC. Inclusion criteria were randomised trials, nonrandomised controlled studies, retrospective case series, and cohort studies. Reviews, animal and preclinical studies, case reports, and commentaries were excluded. A narrative synthesis of the evidence is presented. EVIDENCE SYNTHESIS: A total of 331 abstracts and 76 full-text articles were assessed; 34 studies met the inclusion criteria. Current methods of response assessment in RCC include anatomic methods--based on various criteria including Choi, size and attenuation CT, and morphology, attenuation, size, and structure--and functional techniques including dynamic contrast-enhanced (DCE) CT, DCE-magnetic resonance imaging, DCE-ultrasonography, positron emission tomography, and approaches utilising radiolabelled monoclonal antibodies. CONCLUSIONS: Functional imaging techniques are promising surrogate biomarkers of response in RCC and may be more appropriate than anatomic CT-based methods. By enabling quantification of tumour vascularisation, functional techniques can directly and rapidly detect the biologic effects of antiangiogenic therapies compared with the indirect detection of belated effects on tumour size by anatomic methods. However, larger prospective studies are needed to validate early results and standardise techniques.
CONTEXT: The introduction of targeted agents for the treatment of renal cell carcinoma (RCC) has resulted in new challenges for assessing response to therapy, and conventional response criteria using computed tomography (CT) are limited. It is widely recognised that targeted therapies may lead to significant necrosis without significant reduction in tumour size. In addition, the vascular effects of antiangiogenic therapy may occur long before there is any reduction in tumour size. OBJECTIVE: To perform a systematic review of conventional and novel imaging methods for the assessment of response to targeted agents in RCC and to discuss their use from a clinical perspective. EVIDENCE ACQUISITION: Relevant databases covering the period January 2006 to April 2013 were searched for studies reporting on the use of anatomic and functional imaging techniques to predict response to targeted therapy in RCC. Inclusion criteria were randomised trials, nonrandomised controlled studies, retrospective case series, and cohort studies. Reviews, animal and preclinical studies, case reports, and commentaries were excluded. A narrative synthesis of the evidence is presented. EVIDENCE SYNTHESIS: A total of 331 abstracts and 76 full-text articles were assessed; 34 studies met the inclusion criteria. Current methods of response assessment in RCC include anatomic methods--based on various criteria including Choi, size and attenuation CT, and morphology, attenuation, size, and structure--and functional techniques including dynamic contrast-enhanced (DCE) CT, DCE-magnetic resonance imaging, DCE-ultrasonography, positron emission tomography, and approaches utilising radiolabelled monoclonal antibodies. CONCLUSIONS: Functional imaging techniques are promising surrogate biomarkers of response in RCC and may be more appropriate than anatomic CT-based methods. By enabling quantification of tumour vascularisation, functional techniques can directly and rapidly detect the biologic effects of antiangiogenic therapies compared with the indirect detection of belated effects on tumour size by anatomic methods. However, larger prospective studies are needed to validate early results and standardise techniques.
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