Evaluation of the High-resolution, Contrast Enhanced Low-dose Breast-CT

Study Overview
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Brief Summary
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The aim of this study is the clinical establishment of a native and contrast-enhanced computer tomography of the breast. The early detection of breast cancer is still a great challenge. Even though the implementation of the digital mammography combined with the mandatory screening-programs lead to significant improvements, sensitivity and specificity of these examinations need to be clearly classified as improvable. Generally, it is stated that the necessary transit from 2-D projected images to 3-D tomography will be crucially advantageous as magnetic resonance imaging has already shown. Similar or even major advantages can be expected by new approaches regarding CT with very high local resolution, better than 100µm in 3D and lower dose, under 5 Milligray (mGy), as demanded for a screening. A device that meets these demands and is also applicable for dynamic scans after intravenous administration of a contrast agent, has been developed with the support by the European Union (EU), German Research Foundation (DFG) and Federal Ministry of Education and Research (BMBF). Publications on technical and experimental results are already available. An evaluation in the clinical use is missing yet. The primary aim of this study is to evaluate systematically the performance of the native and dynamic, contrast-enhanced CT of the breast.

Official Title
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Evaluation of the High-resolution, Contrast Enhanced Low-dose Breast-CT

Conditions
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BI-RADS 4, BI-RADS 5, BI-RADS 6, High Risk of Breast Cancer Which Indicates a Mamma-MRI

Intervention / Treatment
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* Device: Native and dynamic contrast-enhanced CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sub Study 1: patients with mammographic or sonographic validated Breast Imaging Reporting and Data System (BI-RADS)-4 or BI-RADS-5-result or in BI-RADS-6-situation, i.e. with an already reliable carcinoma by punch biopsy, for which a clinical indication for a mamma-MRI consists. Age >= 40 maintained renal function (MDRD with GFR >= 60 ml/min/1,73m²) normal thyroid function, no clinical indication for an endocrine autonomy, normal TSH (not older than 8 weeks) Persons which are able to give written consent and are aware of the nature, meaning and extent of the study signed informed consent Substudy 2: patients with a doubtful and suspect clinical or mammographic or sonographic result (BI-RADS 3, 4a, 4b, 4c, 5) as well as patients with a reliable carcinoma by punch biopsy (BI-RADS 6), patients with high risk of breast cancer for which a clinical indication for a mamma-MRI consists. Age >= 40 maintained renal function (MDRD with GFR >= 60 ml/min/1,73m²) normal thyroid function, no clinical indication for an endocrine autonomy, normal TSH (not older than 8 weeks) Persons which are able to give written consent and are aware of the nature, meaning and extent of the study signed informed consent Exclusion Criteria: Substudy 1: Pregnancy or lactation Women with child-bearing potential without sufficient contraception Age <40 years Women with proven pathogenic Breast Cancer (BRCA) 1-mutation or heterozygote risk (>= 25%) Hospitalization of patient ordered by the court or local authorities Relationship of dependence or employment to sponsor or investigator additionally the following criteria apply, if conducting the dynamic contrast-enhanced breast-CT signs of a renal insufficiency (GFR < 60ml/min/1,73m²) clinical signs or signs of the labor chemistry for endocrine autonomy (increase of TSH) Patients with known allergies or intolerance reactions grade II or higher to contrast medium containing iodine Substudy 2: Pregnancy or lactation Women with child-bearing potential without sufficient contraception Age <40 years Women with proven pathogenic BRCA 1-mutation or heterozygote risk (>= 25%) Hospitalization of patient ordered by the court or local authorities Relationship of dependence or employment to sponsor or investigator additionally the following criteria apply, if conducting the dynamic contrast-enhanced breast-CT: end stage or advanced renal insufficiency clinical signs or signs of the labor chemistry for endocrine autonomy (increase of TSH) Patients with known allergies or intolerance reactions grade II or higher to contrast medium containing iodine

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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Female

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: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Native and dynamic contrast-enhanced CT<br>Patients will undergo a native high-resolution and a dynamic contrast-enhanced CT, both sides respectively. | Device: Native and dynamic contrast-enhanced CT<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub-Study 1: comparison of a-posteriori sensitivity using the native, contrast-enhanced or dynamic contrast-enhanced breast CT. | By using the images diagnostic criteria for identification and characterization of the pathologic and physiologic changes of the female breast will be elaborated. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of biological value of the diagnosed carcinoma in dependence with its detection mode. | Detection mode means the prospective visibility of a carcinoma in one or more independent imaging methods, respectively. Biological value will be calculated by amount of high and intermediate grade vs. low grade lesions, status of Ki-67 values, distribution of luminal a, luminal b, Her2/neu and basal, distribution of receptor status | 2 years | 
| Substudy 2: sensitivity of the native and the contrast-enhanced or dynamic contrast-enhanced high-resolution low-dose CT in comparison to the conventional examination procedures |  | 2 years | 
| Sub-study 2: specificity of the native and the contrast-enhanced or dynamic contrast-enhanced high-resolution low-dose CT in comparison to the conventional examination procedures |  | 2 years | 
| Substudy 2: Positive Predictive Value (PPV) of the native and the contrast-enhanced or dynamic contrast-enhanced high-resolution low-dose CT in comparison to the conventional examination procedures |  | 2 years | 
| Substudy 2: Negative Predictive Value (NPV) of the native and the contrast-enhanced or dynamic contrast-enhanced high-resolution low-dose CT in comparison to the conventional examination procedures |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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low dose CT, contrast-enhanced, breast cancer screening, computer tomography