Contrast-Enhanced Ultrasound for Kidney Cancer Subtyping and Staging

Study Overview
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Brief Summary
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The purpose of this study is to determine if contrast-enhanced ultrasound can detect abnormal features of kidney lesions in patients with suspected kidney cancer with the same accuracy as conventional ultrasound and contrast-enhanced magnetic resonance imaging (MRI)

Detailed Description
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This is a pilot cross-sectional study that compares contrast enhanced ultrasound to conventional ultrasound and contrasted MRI. Eligible patients will include anyone who has suspected kidney cancer and is scheduled for surgery, up to an anticipated total of 40 participants. Subject participation will be only for the day of CEUS study. There will be no follow-up period for this study. However, if results are encouraging, a longitudinal observational study may follow, and these same subjects would be eligible for enrollment. Eligible subjects will undergo a contrast enhanced ultrasound. Following completion of imaging, all CEUS, MRI (within 4 months) and B-mode (at time of CEUS) US studies will be de-identified. Blinded radiologists will interpret images and provide an overall assessment of risk of malignancy to each kidney using the Bosniak criteria for each kidney lesion present. The Bosniak criteria places cystic lesions into one of 5 categories (I, II, IIF, III and IV) based on lesion characteristics. CEUS based diagnosis will be compared to the diagnoses on routine B-mode US and contrast-enhanced MRI.

Official Title
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Contrast-Enhanced Ultrasound for Kidney Cancer Subtyping and Staging

Conditions
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Kidney Cancer

Intervention / Treatment
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* Drug: Perflutren lipid microsphere
* Drug: Sulfur hexafluoride lipid microspheres


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A suspected diagnosis of kidney cancer with a solid or partially solid lesion and planned surgical nephrectomy within 3 months before surgery Able to provide informed consent Willing to comply with protocol requirements At least 18 years of age Exclusion Criteria: Critically ill or medically unstable or in an intensive care setting and whose critical course during a potential observation period would be unpredictable Known hypersensitivity to sulfur hexafluoride or to any component of perflutren lipid (Definity®) or sulfur hexafluoride (Lumason®) Right to left shunt, severe pulmonary hypertension (Pulmonary artery pressure >90mmHg), or adult respiratory distress syndrome Has any other medical condition or other circumstances that would significantly decrease the chances of obtaining reliable data or of achieving the study objectives Unstable cardiopulmonary disease including any of the following: Severe congestive heart failure (class IV in accordance with the classification of the New York Heart Association) Unstable angina Symptomatic arrhythmia (i.e. tachycardia, bradycardia, supraventricular tachycardia, ventricular fibrillation, ventricular tachycardia, atrial flutter or fibrillation) Myocardial infarction within 14 days prior to the date of proposed microbubble administration. Any woman who is pregnant or has reason to believe she is pregnant (the possibility of pregnancy has to be excluded by negative urine β-HCG results, obtained the same day as the CEUS, or on the basis of patient history, e.g.: tubal ligation, hysterectomy or a minimum of 1 year without menses) Obesity that limits obtainment of acceptable images

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Perflutren Lipid Microsphere or Lumason<br>Patients with suspected kidney cancer and planned surgery will be imaged using contrast-enhanced ultrasound with either perflutren or Lumason. | Drug: Perflutren lipid microsphere<br>* Baseline B-mode US will be performed to confirm the lesions being imaged (unless it is a subject with no lesions, then a basic B-mode US will be performed. Perflutren is a diagnostic drug that is intended to be used for contrast enhancement. The vial contains a clear, colorless, sterile, non-pyrogenic, hypertonic solution which is activated by mechanical agitation with Vialmix®.It will be dispensed in inactivated form to a study team member. The contrast agent will be activated just prior to administration (ideally to be used within 5 minutes of activation). Contrast agent Definity (or Lumason) will be activated according to package insert instructions, including use of VialMix®, the device used to activate Definity. Administration will occur IV in coordination with sonography staff trained specifically in contrast ultrasound imaging.The total imaging time is anticipated to be less than 30 minutes.<br>* Other names: Microbubble contrast agent;Drug: Sulfur hexafluoride lipid microspheres<br>* Baseline B-mode US will be performed to confirm the lesions being imaged (unless it is a subject with no lesions, then a basic B-mode US will be performed. Lumason will be used as a secondary contrast agent only if Definity(perflutren) is unavailable.This drug will be administered using the dosing range and administration type within the Lumason prescribing information. The contrast agent will be activated just prior to administration (ideally to be used within 5 minutes of activation). Contrast agent Definity (or Lumason) will be activated according to package insert instructions, including use of VialMix®, the device used to activate Definity. Administration will occur IV in coordination with sonography staff trained specifically in contrast ultrasound imaging.The total imaging time is anticipated to be less than 30 minutes.<br>* Other names: Lumason;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3D CEUS Generated Metrics in Kidney Mass: Wash_In_Slope | A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash_In_Slope parameter was generated. This metric indicates the change in contrast with time in the mass using bolus imaging. Bolus imaging injects a small amount of contrast agent and monitors the contrast agent as it flows in (wash-in) and out (wash-out) of the body/mass. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White.The Wash_In_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of curve. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass: Wash_In_intercept | A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash_In_intercept parameter was generated. This metric indicates the intensity level prior to infusion of contrast. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=white. This value was calculated using an equation for a line which has a slope and the intercept. The values were negative because they were calculated (not measured). | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass: Wash_Out_Slope | A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash_Out_Slope parameter was generated. This metric indicates the change in contrast with time in the mass using bolus imaging. Bolus imaging injects a small amount of contrast agent and monitors the contrast agent as it flows in (wash-in) and out (wash-out) of the body/mass. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) value range was between 0=black and 255=White. The wash Out slope decreases as the contrast agent clears the body/mass. Decreasing brightness is related to the slope of the curve. This results in a negative number. This value was generated by fitting the data to a linear equation. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass: Wash_Out_Intercept | A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash_Out_Intercept parameter was generated. This metric indicates the intensity level of contrast at a steady state of enhancement in the mass. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. This value was calculated using an equation for a line that has a slope and an intercept. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass: FR_a | A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) FR_a parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=white. The intensity was plotted by time. FR_a parameters were devised from an exponential fit. The exponential fit of the data provides the height of the curve. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass: FR_beta | A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) FR_beta parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, 255=White. The intensity was plotted by time. FR_beta parameters were devised from an exponential fit. Exponential fit of the data provides the slope of the curve. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass: Volume | A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) volume parameter was generated. The volumes were generated using the ellipsoid equation on the CEUS image of the kidney mass. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Wash_In_Slope | The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated Wash_In_Slope parameter was studied. This metric indicates the change in contrast intensity with time in the mass using bolus imaging. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The Wash_In_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of the curve. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Wash_In_intercept | The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated Wash_In_intercept parameter was studied. This metric indicates the intensity level prior to infusion of contrast. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. This value was calculated using an equation for a line which has a slope and the intercept. The values were negative because they were calculated (not measured). | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Wash_Out_Slope | The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated Wash_Out_Slope parameter was studied. This metric indicates the change in contrast intensity with time in the mass using bolus imaging. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. Decreasing brightness is related to the slope of the curve. The Wash Out slope decreases as the contrast agent clears the body/mass. Decreasing brightness is related to the slope of the curve. This results in a negative number. This value was generated by fitting the data to a linear equation. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Wash_Out_Intercept | The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated Wash_Out_Intercept parameter was studied. This metric indicates the intensity level of contrast at steady state of enhancement in the mass. The contrast-enhanced ultrasonogram (CEUS) Wash_Out_Intercept parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. This value was calculated using an equation for a line which has a slope and the intercept. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. FR_a | The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated FR_a parameter was studied. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The intensity was plotted by time. FR_a parameters were devised from an exponential fit. The exponential fit of the data provides the height of the curve. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. FR_beta | The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated FR_ beta parameter was studied. The contrast-enhanced ultrasonogram (CEUS) FR_beta parameter was generated. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The intensity was plotted by time. FR_beta parameters were devised from an exponential fit. The exponential fit of the data provides the slope of the curve. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Volume | The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated volume parameter was studied. The volumes were generated using the ellipsoid equation on the CEUS image of the kidney mass. | Baseline- up to 3 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Wash_In_Slope | The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black and 255=White. The Wash_In_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of the curve. The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated Wash_In_Slope parameter was studied. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to American Joint Cancer Committee. All masses in this study were in stage 0, I, II or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Wash_In_intercept | The association between tumor stage and CEUS-generated Wash_In_intercept parameter was studied. These values were generated by fitting the data to a linear equation. This metric indicates the intensity level prior to infusion of contrast. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. This value was calculated using an equation for a line that has a slope and an intercept. The values were negative because they were calculated (not measured). Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Wash_Out_Slope | The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated Wash_Out_Slope parameter was studied. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The Wash_Out_Slope decreases as the contrast agent clears the body/mass. Decreasing brightness is related to the slope of the curve. This results in a negative number. This value was generated by fitting the data to a linear equation. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the AJCC. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm, Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Wash_Out_Intercept | The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated Wash_Out_Intercept parameter was studied. This metric indicates the intensity level of contrast at a steady state of enhancement in the mass. The contrast-enhanced ultrasonogram (CEUS) Wash_Out_Intercept parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. This value was calculated using an equation for a line that has a slope and the intercept. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. FR_a | The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated FR_a parameter was studied. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The intensity was plotted by time. FR_a parameters were devised from an exponential fit. The exponential fit of the data provides the height of the curve. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. FR_beta | The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated FR_ beta parameter was studied. The contrast-enhanced ultrasonogram (CEUS) FR_beta parameter was generated. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The intensity was plotted by time. FR_beta parameters were devised from an exponential fit. The exponential fit of the data provides the slope of the curve. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes. | Baseline- up to 3 minutes | 
| 3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Volume | The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated volume was studied. The contrast-enhanced ultrasonogram (CEUS) volume was generated. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes. | Baseline- up to 3 minutes | 
| Pooled Kidney Mass Stage vs. 3D CEUS-generated Wash in Metrics | The association between pooled tumor stage (tumor stages 0,1,2 versus tumor stage 3) and CEUS-generated Wash_In_Slope parameter was studied. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal values range between 0=black and 255=White. The Wash_In_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of the curve. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size >7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes. | Baseline- up to 3 minutes | 
| Pooled Kidney Mass Stage Using 3D CEUS-generated Wash Out Metrics | The association between pooled tumor stage (tumor stages 0,1,2 versus tumor stage 3) and CEUS-generated Wash_Out_Slope parameter was studied. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The Wash_Out_Slope decreases as the contrast agent clears the body/mass. Decreasing brightness is related to the slope of the curve. This results in a negative number. This value was generated by fitting the data to a linear equation. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the AJCC. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found, Stage I = tumor size ≤7 cm, Stage II = tumor size >7 cm, Stage III includes tumors growing into a major vein or tissue, with no spread to lymph nodes. | Baseline- up to 3 minutes |