Standardization of Dynamic Contrast-Enhanced Ultrasound for the Evaluation of Antiangiogenic Therapies: The French Multicenter Support for Innovative and Expensive Techniques Study

ObjectivesThe objectives of this study are to describe the standardization and dissemination of dynamic contrast-enhanced ultrasound (DCE-US) for the evaluation of antiangiogenic treatments in solid tumors across 19 oncology centers in France and to define a quality score to account for the variability of the evaluation criteria used to collect DCE-US data. Materials and MethodsThis prospective Soutien aux Techniques Innovantes Coûteuses (Support for Innovative and Expensive Techniques) DCE-US study included patients with metastatic breast cancer, melanoma, colon cancer, gastrointestinal stromal tumors, renal cell carcinoma and patients with primary hepatocellular carcinoma tumors treated with antiangiogenic therapy. The DCE-US method was made available across 19 oncology centers in France. Overall, 2339 DCE-US examinations were performed by 65 radiologists in 539 patients.One target site per patient was studied. Standardized DCE-US examinations were performed before treatment (day 0) and at days 7, 15, 30, and 60. Dynamic contrast-enhanced ultrasound data were transferred from the different sites to the main study center at the Institut Gustave-Roussy for analysis. Quantitative analyses were performed with a mathematical model to determine 7 DCE-US functional parameters using raw linear data. Radiologists had to evaluate 6 criteria that were potentially linked to the precision of the evaluation of these parameters: lesion size, target motion, loss of target, clear borders, total acquisition of wash-in, and vascular recognition imaging window adapted to the lesion size.Eighteen DCE-US examinations were randomly selected from the Soutien aux Techniques Innovantes Coûteuses (Support for Innovative and Expensive Techniques) database. Each examination was quantified twice by 8 engineers/radiologists trained to evaluate the perfusion parameters. The intraobserver variability was estimated on the basis of differences between examinations performed by the same radiologist. The mean coefficient of variability associated with each quality criterion was estimated. The final quality score, ranging from 0 to 5, was defined according to the value of coefficient of variability for each criterion. ResultsA total of 2062 examinations were stored with raw linear data. Five criteria were found to have a major impact on quality: lesion size, motion, loss of target, borders, and total acquisition of wash-in. Only 3% of the examinations were of poor quality (quality of 0); quality was correlated with the radiologists’ experience, such that it was significantly higher for radiologists who had performed more than 60 DCE-US examinations (P < 0.0001). ConclusionsThe DCE-US methodology has been successfully provided to several centers across France together with strict rules for quality assessment. Only 3% of examinations carried out at these centers were considered not interpretable.

[1]  Wolfhard Semmler,et al.  Quantitative Contrast-Enhanced Ultrasound for Imaging Antiangiogenic Treatment Response in Experimental Osteolytic Breast Cancer Bone Metastases , 2012, Investigative radiology.

[2]  Linda Chami,et al.  Quantitative functional imaging by Dynamic Contrast Enhanced Ultrasonography (DCE-US) in GIST patients treated with masatinib , 2012, Investigational New Drugs.

[3]  Panagiotis Samaras,et al.  Quantitative Perfusion Analysis of Malignant Liver Tumors: Dynamic Computed Tomography and Contrast-Enhanced Ultrasound , 2012, Investigative radiology.

[4]  K. Hoyt,et al.  Quantitative Mapping of Tumor Vascularity Using Volumetric Contrast-Enhanced Ultrasound , 2011, Investigative radiology.

[5]  L Barozzi,et al.  The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast Enhanced Ultrasound (CEUS): Update 2011 on non-hepatic applications , 2011, Ultraschall in der Medizin.

[6]  Kumar Sharma,et al.  Ultrasound Molecular Imaging of Tumor Angiogenesis With an Integrin Targeted Microbubble Contrast Agent , 2011, Investigative radiology.

[7]  Andrew Needles,et al.  Assessment and Monitoring Tumor Vascularity With Contrast-Enhanced Ultrasound Maximum Intensity Persistence Imaging , 2011, Investigative radiology.

[8]  D. Cosgrove,et al.  Contrast Ultrasonography: Necessity of Linear Data Processing for the Quantification of Tumor Vascularization , 2010, Ultraschall in der Medizin.

[9]  M. Kudo Current status of molecularly targeted therapy for hepatocellular carcinoma: clinical practice , 2010, International Journal of Clinical Oncology.

[10]  A. Roche,et al.  Dynamic contrast-enhanced ultrasonography (DCE-US): a new tool for the early evaluation of antiangiogenic treatment , 2010, Targeted Oncology.

[11]  P. Reichardt Optimal Use of Targeted Agents for Advanced Gastrointestinal Stromal Tumours , 2010, Oncology.

[12]  S. Koscielny,et al.  Metastatic Renal Cell Carcinoma Treated with Sunitinib: Early Evaluation of Treatment Response Using Dynamic Contrast-Enhanced Ultrasonography , 2010, Clinical Cancer Research.

[13]  Xin Huang,et al.  Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell Carcinoma , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  Linda Chami,et al.  Dynamic contrast-enhanced ultrasonography (DCE-US) with quantification of tumor perfusion: a new diagnostic tool to evaluate the early effects of antiangiogenic treatment , 2007, European radiology.

[15]  J. Soria,et al.  Phase I Trial of Sorafenib in Combination with IFN α-2a in Patients with Unresectable and/or Metastatic Renal Cell Carcinoma or Malignant Melanoma , 2007, Clinical Cancer Research.

[16]  Linda Chami,et al.  To predict progression-free survival and overall survival in metastatic renal cancer treated with sorafenib: pilot study using dynamic contrast-enhanced Doppler ultrasound. , 2006, European journal of cancer.

[17]  M. Horsfield,et al.  A simple, reproducible method for monitoring the treatment of tumours using dynamic contrast-enhanced MR imaging , 2006, British Journal of Cancer.

[18]  M. Christian,et al.  [New guidelines to evaluate the response to treatment in solid tumors]. , 2000, Bulletin du cancer.

[19]  M. van Glabbeke,et al.  New guidelines to evaluate the response to treatment in solid tumors , 2000, Journal of the National Cancer Institute.

[20]  Linda Chami,et al.  Advanced hepatocellular carcinoma: early evaluation of response to bevacizumab therapy at dynamic contrast-enhanced US with quantification--preliminary results. , 2011, Radiology.

[21]  Linda Chami,et al.  Dynamic contrast-enhanced ultrasonography (DCE-US) and anti-angiogenic treatments. , 2011, Discovery medicine.

[22]  M. Kochman Gastrointestinal Stromal Tumors Treated with Imatinib: Monitoring Response with Contrast-Enhanced Sonography , 2007 .