An interventional study of Contrast Enhanced Mammography in DCIS, Breast Carcinoma in Situ and Calcification, sponsored by Clinical Hospital Center Rijeka. Not yet recruiting at 1 site in Croatia. Open to female participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2025-01-06.
Sponsored by Clinical Hospital Center Rijeka · Not applicable, Interventional, and Diagnostic
The study hypothesis is that the rate of inadequate surgical margins after conservative breast surgery for DICS and the rate of reoperation (re-excision or/and mastectomy) is lower in the group of patients who underwent standard preoperative mammography and CEM to assess the extent of DICS, compared to the group of patients for whom the preoperative assessment of the extent of in situ breast cancer was not performed using one of the imaging techniques with contrast medium such as contrast mammography or magnetic resonance imaging.
Ductal carcinoma in situ (DCIS) is the earliest form of malignant lesion in the breast, which in most cases is diagnosed by mammography screening, usually in the form of asymptomatic calcifications. The question of whether DCIS is a true malignancy of the breast, which pathological criteria are used for diagnosing and classifying DCIS, but also the questions of the nature of the disease and its overtreatment are controversial. Surgery is still the primary treatment of DCIS, and the status of the surgical margins is of paramount importance. Compared to invasive ductal carcinoma, the re-excision rate in DCIS is relatively high (30-40%), probably because the change is not palpable. Segmental distribution, with areas affected by the disease that are not calcified and therefore not detected, and stricter guidelines for appropriate surgical margins may also contribute to the re-excision rate. Because the diagnosis of DCIS is closely associated with mammographic detection of pathologic calcifications, it was assumed that magnetic resonance (MR) imaging would provide little or no value for their detection and visualization. However, a study conducted by Kuhl et al. showed that breast MRI has a significantly higher sensitivity than mammography in detecting DCIS. In addition, subsequent studies have shown that MRI is more accurate than mammography in assessing the distribution of DCIS. In recent years, mammography with an iodine contrast agent, known as contrast mammography (CEM), has been introduced, which, like MRI, is based on the evaluation of tumor angiogenesis. It is important to emphasize that the sensitivity of CEM in detecting malignant lesions corresponds to the sensitivity of MR. CEM has several advantages over breast MRI, the most important of which are the availability and the shorter imaging time, as well as the shorter time required to analyze the mammogram and read the findings. Numerous studies show that patients tolerate CEM better than MRI.
The study hypothesis is that the rate of inadequate surgical margins after conservative breast surgery for DICS and the rate of reoperation (re-excision or/and mastectomy) is lower in the group of patients who underwent standard preoperative mammography and CEM to assess the extent of DICS, compared to the group of patients for whom the preoperative assessment of the extent of in situ breast cancer was not performed using one of the imaging techniques with contrast medium, such as contrast mammography or magnetic resonance imaging. The interventional cohort involves 50 consecutive patients with newly diagnosed DCIS who will undergo surgery at CHC Rijeka in 2024, 2025, and 2026 and who agree to have a CEM performed before surgery as part of the diagnostic work-up in addition to standard mammography and who agree to participate in the trial. Patients diagnosed with ductal in situ carcinoma who underwent surgery at CHC Rijeka in the period from 2019 to 2024 and whose clinical data are available in the prospectively managed clinical register for breast diseases at CHC Rijeka and the Integrated Hospital Informatics System (IBIS), are included in the second (control) cohort.
Two clinical radiology specialists with experience in breast radiology will evaluate the morphologic and functional features of standard MMG and CEM by consensus, and assess the extent of disease using the BI-RADS lexicon for imaging with contrast mammography. Demographic and imaging data (morphological and functional characteristics on CME such as background parenchymal enhancement, presence/absence of a lesion, location of the lesion in breast quadrant, type of lesion, size of the lesion in mm and BI-RADS category are analyzed for each lesion) will be recorded. Only one lesion per breast is considered, and if multiple lesions are visible, the overall diameter of the suspicious area will be considered. The above parameters are compared with the grade of the DCIS tumor, i. e. the morphological and functional characteristics of G1 and G2 lesions compared to G3 lesions.
Exclusion Criteria:
Patients with mammographically newly detected ductal in situ carcinoma who undergo surgery at CHC Rijeka in 2024, 2025, and 2026 (consecutively), who agree to have a CEM performed prior to surgery as part of the diagnostic work-up in addition to standard mammography, and who agree to participate in the examination. Group number: 50 patients.
Diagnostic Test: Contrast Enhanced Mammography
Patients diagnosed with ductal in situ carcinoma who underwent surgery at CHC Rijeka in the period from 2019 to 2024 and whose clinical data are available in the prospectively managed clinical registry for breast diseases at CHC Rijeka and in the Hospital Information System (IBIS). Group number: 50 patients.
The CEM performance protocol involves the intravenous administration of non-ionic, low-osmolarity iodinated contrast medium using an automatic syringe that delivers the required bolus of contrast medium at a dose of 1.5 ml/kg body weight at a rate of 3 ml/s without compressing the breast. After a two-minute pause, necessary to allow the breast parenchyma to absorb (stain) the contrast agent, the patient is positioned for the mammogram and the breast is compressed. First the symptomatic and then the non-symptomatic breast is imaged in two or a total of four standard projections: craniocaudal (CC) and oblique mediolateral (MLO) projections of the breast. The delayed CC and MLO projections of the symptomatic breast are taken within eight minutes of the start of the examination. The delayed mammograms are used to assess the dynamics of the contrast uptake of the lesion and are compared to the same parameters of the breast MRI. The time required to perform the CEM is 8-10 minutes.
Also known as: CEM
Number of true positive CEMs in the Interventional group
Number of patients in whom the estimated size of DCIS (longest diameter in mm) is larger on CEM than on MMG and in whom the actual size in PH report is greater than the size on estimated on MMG
Time frame: 3 years
Number of false positive CEMs in the Interventional Group
Number of patients in whom the estimated size of DCIS (longest diameter in mm) on CEM is larger than on MMG, but the size in the PH report correlates better with the size estimated on MMG
Time frame: 3 years
Number of true negative CEMs in the Interventional Group
Number of patients with no difference in the radiological assessment of the size of DCIS (longest diameter in mm), and in whom the size in the PH report correlates with the size on MMG
Time frame: 3 years
Number of false negative CEMs in the Interventional Group
Number of patients with no difference in the radiological assessment of the size of DCIS (longest diameter in mm is similar on CEM and MMG), but in whom the size in the PH report is greater than the size on MMG and CEM
Time frame: 3 years
True positive rate of CEM vs. MMG (Sensitivity)
True positive rate = Number of true positive / (Number of true positive + Number of false negative)
Time frame: 3 years
True negative rate of CEM vs. MMG (Specificity)
True negative rate = Number of true negative / (Number of true negative + Number of false positive)
Time frame: 3 years
False positive rate of CEM vs. MMG (overestimation)
False positive rate = Number of false positive / (Number of false positive + Number of true negative)
Time frame: 3 years
False negative rate of CEM vs. MMG (underestimation)
False negative rate= Number of false negative / (Number of false negative + Number of true positive)
Time frame: 3 years
Accuracy of CEM vs. MMG
Accuracy = (Number of true positive + Number of true negative) / (Number of true positive+ Number of false positive + Number of true negative + Number of false negative)
Time frame: 3 years
Inadequate surgical margins rate in the Interventional Group
Percentage of patients with inadequate surgical margins (\<2mm)
Time frame: 3 years
Inadequate surgical margins rate in the Control Group
Percentage of patients with inadequate surgical margins (\<2mm)
Time frame: 3 years
Re-operation rate in the Interventional Group
Percentage of repeated surgical procedures in breast
Time frame: 3 years
Re-operation rate in the Control Group
Percentage of repeated surgical procedures in breast
Time frame: 3 years
Mastectomy rate in the Interventional Group
Percentage of patients with mastectomy
Time frame: 3 years
Mastectomy rate in the Control Group
Percentage of patients with mastectomy
Time frame: 3 years
Estimated percentage of breast resection volume based on CEM
Percentage of breast resection volume based on CEM findings according to the formula (4 x (radius of the lesion + 1 cm)3 ) : (radius of the breast 2 x projection of the breast)
Time frame: 3 years
Estimated percentage of breast resection volume based on MMG
Percentage of breast resection volume based on MMG findings according to the formula (4 x (radius of the lesion + 1 cm)3 ) : (radius of the breast 2 x projection of the breast)
Time frame: 3 years
Duration of complete preoperative diagnostic workup in the Intervention Group
Number of days between the date of the first clinical examination at CHC Rijeka (surgeon or radiologist) and the date of surgery
Time frame: 3 years
Duration of complete preoperative diagnostic workup in the Control Group
Number of days between the date of the first clinical examination at CHC Rijeka (surgeon or radiologist) and the date of surgery
Time frame: 3 years
Lesion extension of high-grade DCIS (G3) on CEM
Size of the lesion determined in millimetres.
Time frame: 3 years
Lesion extension of low-grade DCIS (G1-2) on CEM
Size of the lesion determined in millimetres.
Time frame: 3 years
Background parenchymal enhancement associated with high-grade DCIS (G3) on CEM
Background parenchymal enhancement (symmetric or asymmetric) is categorized as minimal, mild, moderate and marked.
Time frame: 3 years
Background parenchymal enhancement associated with low grade DCIS (G1-2) on CEM
Background parenchymal enhancement (symmetric or asymmetric) is categorized as minimal, mild, moderate and marked.
Time frame: 3 years
Distribution of NME associated with high-grade DCIS (G3) on CEM
Non-mass enhancement (NME) classified as: focal, linear, segmental, regional, multiple regions or diffuse.
Time frame: 3 years
Distribution of NME associated with low grade DCIS (G1-2) on CEM
Non-mass enhancement (NME) classified as: focal, linear, segmental, regional, multiple regions or diffuse.
Time frame: 3 years
Lesion conspicuity associated with high-grade DCIS (G3) on CEM
Lesion conspicuity (relative to background) is the degree of enhancement compared to background, described as low, moderate or high
Time frame: 3 years
Lesion conspicuity associated with low grade DCIS (G1-2) on CEM
Lesion conspicuity (relative to background) is the degree of enhancement compared to background, described as low, moderate or high
Time frame: 3 years
Morphologic features of mass lesion associated with high-grade DCIS (G3) on CEM
Mass lesions are defined by shape and margin: descriptors for mass shape and margin include oval, round, or irregular shape, with circumscribed or not circumscribed (irregular, spiculated) margin.
Time frame: 3 years
Morphologic features of mass lesion associated with low grade DCIS (G1-2) on CEM
Mass lesions are defined by shape and margin: descriptors for mass shape and margin include oval, round, or irregular shape, with circumscribed or not circumscribed (irregular, spiculated) margin.
Time frame: 3 years
Internal pattern of enhancement of mass lesion associated with high-grade DCIS (G3) on CEM
Internal pattern can be homogeneous, heterogeneous, or rim enhancement.
Time frame: 3 years
Internal pattern of enhancement of mass lesion associated low grade DCIS (G1-2) on CEM
Internal pattern can be homogeneous, heterogeneous, or rim enhancement.
Time frame: 3 years
Overall treatment cost in the Interventional Group
All costs related to diagnostic workup and related to surgical treatment will be evaluated for each patient (costs of the procedure, hospital days, readmission rate after the first treatment).
Time frame: 3 years
Overall treatment cost in the Control Group
All costs related to diagnostic workup and related to surgical treatment will be evaluated for each patient (costs of the procedure, hospital days, readmission rate after the first treatment).
Time frame: 3 years
Plan to share: No
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Clinical Hospital Center Rijeka