title: Assessing the response to targeted therapies in renal cell carcinoma: technical insights and practical considerations.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Urology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: a.bex@nki.nl.
authors.forename: Axel
authors.initials: A
authors.lastname: Bex
authors.affiliation: Université Paris Descartes Sorbonne Paris Cité, INSERM UMR-S970, and Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Radiologie, Paris, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Fournier
authors.affiliation: IRCIV, Institut Gustave Roussy, Villejuif, and IR4M, UMR8081 Université Paris-Sud 11, CNRS, Villejuif, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lassau
authors.affiliation: Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Mulders
authors.affiliation: Mount Vernon Cancer Centre, Northwood, Middlesex, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Nathan
authors.affiliation: Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.affiliation: Queen Mary University of London, Barts and London School of Medicine, West Smithfield, London, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Powles
mesh_terms: D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D058990:Molecular Targeted Therapy; D016896:Treatment Outcome
keywords: Anatomic imaging; Computed tomography; Functional imaging; Imaging; Magnetic resonance imaging; Positron emission tomography; Renal cell carcinoma; Targeted therapy; Treatment response; Ultrasonography