Clinical trial NCT06217458: The Added Value of Contrast Enhanced Mammography to Standard Mammography in Assessing the Extent of DCIS
Official title: The Added Value of Contrast Enhanced Mammography (CEM) to Standard Mammography in Assessing the Extent of Ductal Carcinoma in Situ (DCIS)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: DCIS
Breast Carcinoma in Situ
Calcification
Keywords: Ductal in situ carcinoma
Calcifications
Breast surgery
Screening
Contrast Enhanced Mammography
Lead sponsor: Clinical Hospital Center Rijeka
Sponsor class: OTHER
First posted: 2024-01-22
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of true positive CEMs in the Interventional group
timeFrame: 3 years
measure: Number of false positive CEMs in the Interventional Group
timeFrame: 3 years
measure: Number of true negative CEMs in the Interventional Group
timeFrame: 3 years
measure: Number of false negative CEMs in the Interventional Group
timeFrame: 3 years
measure: True positive rate of CEM vs. MMG (Sensitivity)
timeFrame: 3 years
measure: True negative rate of CEM vs. MMG (Specificity)
timeFrame: 3 years
measure: False positive rate of CEM vs. MMG (overestimation)
timeFrame: 3 years
measure: False negative rate of CEM vs. MMG (underestimation)
timeFrame: 3 years
measure: Accuracy of CEM vs. MMG
timeFrame: 3 years
measure: Inadequate surgical margins rate in the Interventional Group
timeFrame: 3 years
measure: Inadequate surgical margins rate in the Control Group
timeFrame: 3 years
measure: Re-operation rate in the Interventional Group
timeFrame: 3 years
measure: Re-operation rate in the Control Group
timeFrame: 3 years
measure: Mastectomy rate in the Interventional Group
timeFrame: 3 years
measure: Mastectomy rate in the Control Group
timeFrame: 3 years
Secondary outcomes:
measure: Estimated percentage of breast resection volume based on CEM
timeFrame: 3 years
measure: Estimated percentage of breast resection volume based on MMG
timeFrame: 3 years
measure: Duration of complete preoperative diagnostic workup in the Intervention Group
timeFrame: 3 years
measure: Duration of complete preoperative diagnostic workup in the Control Group
timeFrame: 3 years
measure: Lesion extension of high-grade DCIS (G3) on CEM
timeFrame: 3 years
measure: Lesion extension of low-grade DCIS (G1-2) on CEM
timeFrame: 3 years
measure: Background parenchymal enhancement associated with high-grade DCIS (G3) on CEM
timeFrame: 3 years
measure: Background parenchymal enhancement associated with low grade DCIS (G1-2) on CEM
timeFrame: 3 years
measure: Distribution of NME associated with high-grade DCIS (G3) on CEM
timeFrame: 3 years
measure: Distribution of NME associated with low grade DCIS (G1-2) on CEM
timeFrame: 3 years
measure: Lesion conspicuity associated with high-grade DCIS (G3) on CEM
timeFrame: 3 years
measure: Lesion conspicuity associated with low grade DCIS (G1-2) on CEM
timeFrame: 3 years
measure: Morphologic features of mass lesion associated with high-grade DCIS (G3) on CEM
timeFrame: 3 years
measure: Morphologic features of mass lesion associated with low grade DCIS (G1-2) on CEM
timeFrame: 3 years
measure: Internal pattern of enhancement of mass lesion associated with high-grade DCIS (G3) on CEM
timeFrame: 3 years
measure: Internal pattern of enhancement of mass lesion associated low grade DCIS (G1-2) on CEM
timeFrame: 3 years
measure: Overall treatment cost in the Interventional Group
timeFrame: 3 years
measure: Overall treatment cost in the Control Group
timeFrame: 3 years
Other outcomes:
Locations:
city: Rijeka
country: Croatia
facility: Clinical Hospital Centre Rijeka
state: Primorsko Goranska County
Study officials:
References:
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citation: Kuhl CK, Strobel K, Bieling H, Wardelmann E, Kuhn W, Maass N, Schrading S. Impact of Preoperative Breast MR Imaging and MR-guided Surgery on Diagnosis and Surgical Outcome of Women with Invasive Breast Cancer with and without DCIS Component. Radiology. 2017 Sep;284(3):645-655. doi: 10.1148/radiol.2017161449. Epub 2017 Apr 26.
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citation: Klaric K, Sribar A, Budisavljevic A, Labinac L, Valkovic Zujic P. Evaluation of Contrast-Enhanced Mammography and Development of Flowchart for BI-RADS Classification of Breast Lesions. Diagnostics (Basel). 2023 Jun 3;13(11):1958. doi: 10.3390/diagnostics13111958.