TY - JOUR
T1 - Assessing the response to targeted therapies in renal cell carcinoma
T2 - Technical insights and practical considerations
AU - Bex, Axel
AU - Fournier, Laure
AU - Lassau, Nathalie
AU - Mulders, Peter
AU - Nathan, Paul
AU - Oyen, Wim J.G.
AU - Powles, Thomas
N1 - Funding Information:
Financial disclosures: Axel Bex certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Axel Bex has participated in advisory boards for Pfizer, Bayer, GSK, and Novartis. He is the principal investigator of the EORTC SURTIME trial, supported in part by an educational grant from Pfizer. Nathalie Lassau has received a grant from the Institut National de Cancer for the DCE-US STIC study, and received payment from Pfizer, Novartis, Hoffmann-La Roche, Bracco, and Toshiba for lectures including service on a speakers’ bureau. Peter Mulders has no conflicts of interest to disclose. Paul Nathan has received payment for advisory boards and speaker fees from GSK, Pfizer, BMS, Novartis, Roche, and Bayer. Laure Fournier has received honoraria from Pfizer. Wim J.G. Oyen is a consultant for Wilex AG, Munich, Germany. Thomas Powles has received educational grants from Pfizer and GSK, and he has participated on advisory boards for Pfizer, Astellas, and GSK.
PY - 2014/4/1
Y1 - 2014/4/1
N2 - 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.
AB - 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.
KW - Anatomic imaging
KW - Computed tomography
KW - Functional imaging
KW - Imaging
KW - Magnetic resonance imaging
KW - Positron emission tomography
KW - Renal cell carcinoma
KW - Targeted therapy
KW - Treatment response
KW - Ultrasonography
UR - http://www.scopus.com/inward/record.url?scp=84894473765&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2013.11.031
DO - 10.1016/j.eururo.2013.11.031
M3 - Review article
C2 - 24341958
AN - SCOPUS:84894473765
SN - 0302-2838
VL - 65
SP - 766
EP - 777
JO - European Urology
JF - European Urology
IS - 4
ER -