Clinical trial NCT02798562: Evaluation of the High-resolution, Contrast Enhanced Low-dose Breast-CT
Official title: Evaluation of the High-resolution, Contrast Enhanced Low-dose Breast-CT
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: BI-RADS 4
BI-RADS 5
BI-RADS 6
High Risk of Breast Cancer Which Indicates a Mamma-MRI
Keywords: low dose CT
contrast-enhanced
breast cancer screening
computer tomography
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2016-06-14
Enrollment: 400
Sex: FEMALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Sub-Study 1: comparison of a-posteriori sensitivity using the native, contrast-enhanced or dynamic contrast-enhanced breast CT.
timeFrame: 2 years
Secondary outcomes:
measure: Comparison of biological value of the diagnosed carcinoma in dependence with its detection mode.
timeFrame: 2 years
measure: 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
timeFrame: 2 years
measure: 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
timeFrame: 2 years
measure: 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
timeFrame: 2 years
measure: 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
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Klinik für Diagnostische und Interventionelle Radiologie
name: Christiane Kuhl, Univ.-Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weigel M, Vollmar SV, Kalender WA. Spectral optimization for dedicated breast CT. Med Phys. 2011 Jan;38(1):114-24. doi: 10.1118/1.3523599.
citation: Nowak T, Hupfer M, Althoff F, Brauweiler R, Eisa F, Steiding C, Kalender WA. Time-delayed summation as a means of improving resolution on fast rotating computed tomography systems. Med Phys. 2012 Apr;39(4):2249-60. doi: 10.1118/1.3697533.
citation: Beister M, Kolditz D, Kalender WA. Iterative reconstruction methods in X-ray CT. Phys Med. 2012 Apr;28(2):94-108. doi: 10.1016/j.ejmp.2012.01.003. Epub 2012 Feb 10.
citation: Kuhl C, Weigel S, Schrading S, Arand B, Bieling H, Konig R, Tombach B, Leutner C, Rieber-Brambs A, Nordhoff D, Heindel W, Reiser M, Schild HH. Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: the EVA trial. J Clin Oncol. 2010 Mar 20;28(9):1450-7. doi: 10.1200/JCO.2009.23.0839. Epub 2010 Feb 22.
citation: Kuhl CK. The "coming of age" of nonmammographic screening for breast cancer. JAMA. 2008 May 14;299(18):2203-5. doi: 10.1001/jama.299.18.2203. No abstract available.
citation: Kuhl CK, Schrading S, Bieling HB, Wardelmann E, Leutner CC, Koenig R, Kuhn W, Schild HH. MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study. Lancet. 2007 Aug 11;370(9586):485-92. doi: 10.1016/S0140-6736(07)61232-X.