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The Added Value of Contrast Enhanced Mammography to Standard Mammography in Assessing the Extent of DCIS

Not Applicable
Not yet recruiting
Conditions
Calcification
DCIS
Breast Carcinoma in Situ
Interventions
Diagnostic Test: Contrast Enhanced Mammography
Registration Number
NCT06217458
Lead Sponsor
Clinical Hospital Center Rijeka
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
Female
Target Recruitment
100
Inclusion Criteria
  • Patients with pathohistological diagnosis of ductal in situ carcinoma based on samples obtained by vacuum-assisted breast biopsy (VABB) or ultrasound-guided breast biopsy (CNB)
  • Presented at the meeting of the multidisciplinary breast team of the Clinical Hospital Center in Rijeka
  • Patients who underwent surgery at CHC Rijeka and whose pathohistological diagnosis in the final PH report was pure DCIS or microinvasive breast cancer (DCIS with microinvasion)
  • Patients who agree to participate in the study
Exclusion Criteria
  • Patients with contraindications for CEM: renal insufficiency (which is ruled out by presenting creatinine and/or eGFR results), iodine allergy, pregnancy/lactation, hyperthyroidism
  • Patients who have undergone a preoperative breast MRI
  • Patients who have both DCIS and invasive carcinoma in the preoperative PH report or the final PH report of the surgical material, with the exception of foci with microinvasion (< 1 mm).
  • Patients with ipsilateral DCIS recurrence or with previous ipsilateral breast surgery for invasive cancer.
  • Patients/subjects whose CEMs do not correspond to the diagnostic interpretation for technical reasons are excluded from the study: insufficient positioning, contrast agent extravasation, failed subtraction
  • Patients under 18 years of age

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
Interventional GroupContrast Enhanced MammographyPatients 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.
Primary Outcome Measures
NameTimeMethod
Number of false positive CEMs in the Interventional Group3 years

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

Number of true negative CEMs in the Interventional Group3 years

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

Number of true positive CEMs in the Interventional group3 years

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

Number of false negative CEMs in the Interventional Group3 years

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

True negative rate of CEM vs. MMG (Specificity)3 years

True negative rate = Number of true negative / (Number of true negative + Number of false positive)

True positive rate of CEM vs. MMG (Sensitivity)3 years

True positive rate = Number of true positive / (Number of true positive + Number of false negative)

False positive rate of CEM vs. MMG (overestimation)3 years

False positive rate = Number of false positive / (Number of false positive + Number of true negative)

False negative rate of CEM vs. MMG (underestimation)3 years

False negative rate= Number of false negative / (Number of false negative + Number of true positive)

Accuracy of CEM vs. MMG3 years

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)

Inadequate surgical margins rate in the Interventional Group3 years

Percentage of patients with inadequate surgical margins (\<2mm)

Inadequate surgical margins rate in the Control Group3 years

Percentage of patients with inadequate surgical margins (\<2mm)

Re-operation rate in the Control Group3 years

Percentage of repeated surgical procedures in breast

Re-operation rate in the Interventional Group3 years

Percentage of repeated surgical procedures in breast

Mastectomy rate in the Interventional Group3 years

Percentage of patients with mastectomy

Mastectomy rate in the Control Group3 years

Percentage of patients with mastectomy

Secondary Outcome Measures
NameTimeMethod
Estimated percentage of breast resection volume based on CEM3 years

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)

Background parenchymal enhancement associated with high-grade DCIS (G3) on CEM3 years

Background parenchymal enhancement (symmetric or asymmetric) is categorized as minimal, mild, moderate and marked.

Distribution of NME associated with low grade DCIS (G1-2) on CEM3 years

Non-mass enhancement (NME) classified as: focal, linear, segmental, regional, multiple regions or diffuse.

Lesion conspicuity associated with low grade DCIS (G1-2) on CEM3 years

Lesion conspicuity (relative to background) is the degree of enhancement compared to background, described as low, moderate or high

Morphologic features of mass lesion associated with low grade DCIS (G1-2) on CEM3 years

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.

Internal pattern of enhancement of mass lesion associated with high-grade DCIS (G3) on CEM3 years

Internal pattern can be homogeneous, heterogeneous, or rim enhancement.

Estimated percentage of breast resection volume based on MMG3 years

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)

Duration of complete preoperative diagnostic workup in the Intervention Group3 years

Number of days between the date of the first clinical examination at CHC Rijeka (surgeon or radiologist) and the date of surgery

Duration of complete preoperative diagnostic workup in the Control Group3 years

Number of days between the date of the first clinical examination at CHC Rijeka (surgeon or radiologist) and the date of surgery

Lesion extension of high-grade DCIS (G3) on CEM3 years

Size of the lesion determined in millimetres.

Lesion extension of low-grade DCIS (G1-2) on CEM3 years

Size of the lesion determined in millimetres.

Lesion conspicuity associated with high-grade DCIS (G3) on CEM3 years

Lesion conspicuity (relative to background) is the degree of enhancement compared to background, described as low, moderate or high

Background parenchymal enhancement associated with low grade DCIS (G1-2) on CEM3 years

Background parenchymal enhancement (symmetric or asymmetric) is categorized as minimal, mild, moderate and marked.

Distribution of NME associated with high-grade DCIS (G3) on CEM3 years

Non-mass enhancement (NME) classified as: focal, linear, segmental, regional, multiple regions or diffuse.

Morphologic features of mass lesion associated with high-grade DCIS (G3) on CEM3 years

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.

Internal pattern of enhancement of mass lesion associated low grade DCIS (G1-2) on CEM3 years

Internal pattern can be homogeneous, heterogeneous, or rim enhancement.

Overall treatment cost in the Interventional Group3 years

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).

Overall treatment cost in the Control Group3 years

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).

Trial Locations

Locations (1)

Clinical Hospital Centre Rijeka

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Rijeka, Primorsko Goranska County, Croatia

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