Diagnostic and Interventional Imaging (2014) 95, 525—526
EDITORIAL
Antiangiogenic therapy in metastatic renal cell carcinoma: More promises and more challenges for imaging
We are pleased to be offered the opportunity to comment on the article by Sami Ammari et al. [1]. The authors provide a comprehensive and excellent description of the current imaging challenges of metastatic renal cell cancer (RCC) evaluation after antiangiogenic therapy. The use of antiangiogenic therapy for the treatment of RCC has revolutionized the treatment of this disease. Prior standard options such as interferon were not much better than placebo and were associated with substantial toxicity that worsened the quality of life of many patients. Whether interferon ␣ and interleukine-2 have long been the single treatment options in metastastic RCC, antiangiogenic agents such as sorafenib, sunitinib, bevacizumab (in combination with interferon) [2], pazopanib and mTOR inhibitors such as temsirolimus [3] and everolimus [4] have been approved in the past few years. With an increasing number of therapeutic agents, the need for imaging biomarkers has become more critical than ever for demonstrating efficacy and potentially improving the cost—benefit ratio of the treatment. Assessment of the response of metastatic RCC to therapy has traditionally been based on changes in target lesion size. However, the mechanism of action of antiangiogenic therapies often leads to stabilization rather than regression with regards to tumor size. This particularity in tumor response makes RECIST 1.1 [5]—a system whose criteria are based exclusively on tumor size—inadequate to early and timely determine the patients who may take advantage of the treatment. As discussed by Ammari et al. [1], after antiangiogenic therapy, the presence of necrosis, which appears as areas of hypoattenuation on computed tomography (CT), is associated with a more favorable therapeutic outcome [6]. Previously, hypoattenuating lesions that developed central areas of enhancement during the course of the treatment were indicative of progressive disease [7]. Antiangiogenic therapies may induce early extensive necrosis without tumor shrinkage on CT images during and after treatment, findings that may sometimes simulate progressive disease. Given the morphologic changes induced by antiangiogenic therapy, new classifications that rely not only on size changes but also on attenuation changes have been developed in an attempt to improve the early assessment of both the treatment response and recurrences. These more recent classifications for evaluating response to therapy include the Choi criteria, modified Choi criteria, and Size and Attenuation CT (SACT) criteria. In this review, the authors provide a practical approach of these systems by explaining their differences, their limitations, their feasibility and reproducibility [1].
http://dx.doi.org/10.1016/j.diii.2014.06.001 2211-5684/© 2014 Éditions franc ¸aises de radiologie. Published by Elsevier Masson SAS. All rights reserved.
526 Besides the development of new criteria for conventional imaging methods, biomarkers and new functional and molecular imaging technologies that provide a quantitative assessment of the change in vascularity have been introduced [8]. These techniques include dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), dynamic contrast-enhanced CT, dynamic contrast-enhanced ultrasound, diffusion-weighted MRI, blood oxygenation level-dependent MRI and positron emission tomography (PET) with oxygen-labeled water. Each of these techniques provides quantitative or semi-quantitative data related to blood flow and some can also provide information on blood volume, cellularity or vessel permeability. To date, DCE-MRI and FDG—PET-CT are the most developed and used technologies. They hold great promise for the future, especially due to their potential for early prediction of treatment response to biotherapies, thereby preventing unnecessary treatment with accompanying adverse events and high costs. More recently, attempts have been made to target angiogenesis on imaging (e.g. selective PET tracers targeting integrins, VEGFR [9], EGFR [10], and targeted contrast-enhanced ultrasound imaging [11]) and will be possibly other potential candidates as early biomarkers. Beyond the spectrum of antiangiogenic therapy, this article highlights the new paradigm in cancer care where medical therapy for malignancy is jumping from standard chemotherapy to personalized medicine with targeted (molecular) therapies [12]. As a result, the future of imaging appears to have already skewed toward molecular imaging and hybrid imaging. But besides the great opportunities offered by new imaging technologies, the essential but ultimate challenge will be to demonstrate the clinical benefit (i.e. in overall survival and/or in quality of life) of any cancer imaging biomarker. Radiologists need to be prepared, as it will mean changes in training, in research and in clinical practice.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
Editorial
[2]
[3]
[4]
[5]
[6]
[7] [8]
[9] [10]
[11]
[12]
treatment: Application to metastatic renal cancers receiving anti-angiogenic treatment. Diagn Interv Imaging 2014;95:527— 39. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007;370:2103—11. Motzer RJ, Hudes GR, Curti BD, McDermott DF, Escudier BJ, Negrier S, et al. Phase I/II trial of temsirolimus combined with interferon alfa for advanced renal cell carcinoma. J Clin Oncol 2007;25:3958—64. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449—56. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228—47. Smith AD, Lieber ML, Shah SN. Assessing tumor response and detecting recurrence in metastatic renal cell carcinoma on targeted therapy: importance of size and attenuation on contrast-enhanced CT. AJR Am J Roentgenol 2010;194:157—65. Choi H. Response evaluation of gastrointestinal stromal tumors. Oncologist 2008;13:4—7. Grenier N, Cornelis F, Le Bras Y, Rigou G, Boutault JR, Bouzgarrou M. Perfusion imaging in renal diseases. Diagn Interv Imaging 2013;94:1313—22. Cai W, Chen X. Multimodality molecular imaging of tumor angiogenesis. J Nucl Med 2008;49:113S—28S. Gelovani JG. Molecular imaging of epidermal growth factor receptor expression-activity at the kinase level in tumors with positron emission tomography. Cancer Metastasis Rev 2008;27:645—53. Wei S, Fu N, Sun Y, Yang Z, Lei L, Huang P, et al. contrast-enhanced ultrasound imaging of Targeted angiogenesis in an orthotopic mouse tumor model of renal carcinoma. Ultrasound Med Biol 2014, http://dx.doi.org/10.1016/j.ultrasmedbio.2013.12.001. Comperat E, Camparo P. Histological classification of malignant renal tumours at a time of major diagnostic and therapeutic changes. Diagn Interv Imaging 2012;93:221—31.
S. Nougaret , B. Guiu ∗ Department of imaging, hôpital Saint-Eloi, CHU Montpellier, 34295 Montpellier cedex 5, France ∗ Corresponding
References [1] Ammari S, Thiam R, Cuenod C, Oudard S, Hernigou A, Grataloup C, et al. Radiological evaluation of response to
author. E-mail address: [email protected] (B. Guiu)
EDITORIAL
Antiangiogenic therapy in metastatic renal cell carcinoma: More promises and more challenges for imaging
We are pleased to be offered the opportunity to comment on the article by Sami Ammari et al. [1]. The authors provide a comprehensive and excellent description of the current imaging challenges of metastatic renal cell cancer (RCC) evaluation after antiangiogenic therapy. The use of antiangiogenic therapy for the treatment of RCC has revolutionized the treatment of this disease. Prior standard options such as interferon were not much better than placebo and were associated with substantial toxicity that worsened the quality of life of many patients. Whether interferon ␣ and interleukine-2 have long been the single treatment options in metastastic RCC, antiangiogenic agents such as sorafenib, sunitinib, bevacizumab (in combination with interferon) [2], pazopanib and mTOR inhibitors such as temsirolimus [3] and everolimus [4] have been approved in the past few years. With an increasing number of therapeutic agents, the need for imaging biomarkers has become more critical than ever for demonstrating efficacy and potentially improving the cost—benefit ratio of the treatment. Assessment of the response of metastatic RCC to therapy has traditionally been based on changes in target lesion size. However, the mechanism of action of antiangiogenic therapies often leads to stabilization rather than regression with regards to tumor size. This particularity in tumor response makes RECIST 1.1 [5]—a system whose criteria are based exclusively on tumor size—inadequate to early and timely determine the patients who may take advantage of the treatment. As discussed by Ammari et al. [1], after antiangiogenic therapy, the presence of necrosis, which appears as areas of hypoattenuation on computed tomography (CT), is associated with a more favorable therapeutic outcome [6]. Previously, hypoattenuating lesions that developed central areas of enhancement during the course of the treatment were indicative of progressive disease [7]. Antiangiogenic therapies may induce early extensive necrosis without tumor shrinkage on CT images during and after treatment, findings that may sometimes simulate progressive disease. Given the morphologic changes induced by antiangiogenic therapy, new classifications that rely not only on size changes but also on attenuation changes have been developed in an attempt to improve the early assessment of both the treatment response and recurrences. These more recent classifications for evaluating response to therapy include the Choi criteria, modified Choi criteria, and Size and Attenuation CT (SACT) criteria. In this review, the authors provide a practical approach of these systems by explaining their differences, their limitations, their feasibility and reproducibility [1].
http://dx.doi.org/10.1016/j.diii.2014.06.001 2211-5684/© 2014 Éditions franc ¸aises de radiologie. Published by Elsevier Masson SAS. All rights reserved.
526 Besides the development of new criteria for conventional imaging methods, biomarkers and new functional and molecular imaging technologies that provide a quantitative assessment of the change in vascularity have been introduced [8]. These techniques include dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), dynamic contrast-enhanced CT, dynamic contrast-enhanced ultrasound, diffusion-weighted MRI, blood oxygenation level-dependent MRI and positron emission tomography (PET) with oxygen-labeled water. Each of these techniques provides quantitative or semi-quantitative data related to blood flow and some can also provide information on blood volume, cellularity or vessel permeability. To date, DCE-MRI and FDG—PET-CT are the most developed and used technologies. They hold great promise for the future, especially due to their potential for early prediction of treatment response to biotherapies, thereby preventing unnecessary treatment with accompanying adverse events and high costs. More recently, attempts have been made to target angiogenesis on imaging (e.g. selective PET tracers targeting integrins, VEGFR [9], EGFR [10], and targeted contrast-enhanced ultrasound imaging [11]) and will be possibly other potential candidates as early biomarkers. Beyond the spectrum of antiangiogenic therapy, this article highlights the new paradigm in cancer care where medical therapy for malignancy is jumping from standard chemotherapy to personalized medicine with targeted (molecular) therapies [12]. As a result, the future of imaging appears to have already skewed toward molecular imaging and hybrid imaging. But besides the great opportunities offered by new imaging technologies, the essential but ultimate challenge will be to demonstrate the clinical benefit (i.e. in overall survival and/or in quality of life) of any cancer imaging biomarker. Radiologists need to be prepared, as it will mean changes in training, in research and in clinical practice.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
Editorial
[2]
[3]
[4]
[5]
[6]
[7] [8]
[9] [10]
[11]
[12]
treatment: Application to metastatic renal cancers receiving anti-angiogenic treatment. Diagn Interv Imaging 2014;95:527— 39. Escudier B, Pluzanska A, Koralewski P, Ravaud A, Bracarda S, Szczylik C, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007;370:2103—11. Motzer RJ, Hudes GR, Curti BD, McDermott DF, Escudier BJ, Negrier S, et al. Phase I/II trial of temsirolimus combined with interferon alfa for advanced renal cell carcinoma. J Clin Oncol 2007;25:3958—64. Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372:449—56. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228—47. Smith AD, Lieber ML, Shah SN. Assessing tumor response and detecting recurrence in metastatic renal cell carcinoma on targeted therapy: importance of size and attenuation on contrast-enhanced CT. AJR Am J Roentgenol 2010;194:157—65. Choi H. Response evaluation of gastrointestinal stromal tumors. Oncologist 2008;13:4—7. Grenier N, Cornelis F, Le Bras Y, Rigou G, Boutault JR, Bouzgarrou M. Perfusion imaging in renal diseases. Diagn Interv Imaging 2013;94:1313—22. Cai W, Chen X. Multimodality molecular imaging of tumor angiogenesis. J Nucl Med 2008;49:113S—28S. Gelovani JG. Molecular imaging of epidermal growth factor receptor expression-activity at the kinase level in tumors with positron emission tomography. Cancer Metastasis Rev 2008;27:645—53. Wei S, Fu N, Sun Y, Yang Z, Lei L, Huang P, et al. contrast-enhanced ultrasound imaging of Targeted angiogenesis in an orthotopic mouse tumor model of renal carcinoma. Ultrasound Med Biol 2014, http://dx.doi.org/10.1016/j.ultrasmedbio.2013.12.001. Comperat E, Camparo P. Histological classification of malignant renal tumours at a time of major diagnostic and therapeutic changes. Diagn Interv Imaging 2012;93:221—31.
S. Nougaret , B. Guiu ∗ Department of imaging, hôpital Saint-Eloi, CHU Montpellier, 34295 Montpellier cedex 5, France ∗ Corresponding
References [1] Ammari S, Thiam R, Cuenod C, Oudard S, Hernigou A, Grataloup C, et al. Radiological evaluation of response to
author. E-mail address: [email protected] (B. Guiu)
