Bhavika K. Patel

Potential Cost Savings of Contrast-Enhanced Digital Mammography

OBJECTIVE The purpose of this article is to discuss whether the sensitivity and specificity of contrast-enhanced digital mammography (CEDM) render it a viable diagnostic alternative to breast MRI. CONCLUSION That CEDM couples low-energy images (comparable to the diagnostic quality of standard mammography) and subtracted contrast-enhanced mammograms make it a cost-effective modality and a realistic substitute for the more costly breast MRI.

Breast Radiation Dose With CESM Compared With 2D FFDM and 3D Tomosynthesis Mammography.

OBJECTIVE We aimed to compare radiation dose received during contrast-enhanced spectral mammography (CESM) using high- and low-energy projections with radiation dose received during 2D full field digital mammography (FFDM) and 3D tomosynthesis on phantoms and patients with varying breast thickness and density. MATERIALS AND METHODS A single left craniocaudal projection was chosen to determine the doses for 6214 patients who underwent 2D FFDM, 3662 patients who underwent 3D tomosynthesis, and 173 patients who underwent CESM in this retrospective study. Dose measurements were also collected in phantoms with composition mimicking nondense and dense breast tissue. RESULTS Average glandular dose (AGD) ± SD was 3.0 ± 1.1 mGy for CESM exposures at a mean breast thickness of 63 mm. At this thickness, the dose was 2.1 mGy from 2D FFDM and 2.5 mGy from 3D tomosynthesis. The nondense phantom had a mean AGD of 1.0 mGy with 2D FFDM, 1.3 mGy with 3D tomosynthesis, and 1.6 mGy with CESM. The dense breast phantom had a mean AGD of 1.3 mGy with 2D FFDM, 1.4 mGy with 3D tomosynthesis, and 2.1 mGy with CESM. At a compressed thickness of 4.5 cm, radiation exposure from CESM was approximately 25% higher in dense breast phantoms than in nondense breast phantoms. The dose in the dense phantom at a compressed thickness of 6 cm was approximately 42% higher than the dose in the nondense phantom at a compressed thickness of 4.5 cm. CONCLUSION CESM was found to increase AGD at a mean breast thickness of 63 mm by approximately 0.9 mGy and 0.5 mGy compared with 2D FFDM and 3D tomosynthesis, respectively. Of note, CESM provides a standard image (similar to 2D FFDM) that is obtained using the low-energy projection. Overall, the AGD from CESM falls below the dose limit of 3 mGy set by Mammography Quality Standards Act regulations.

Contrast-enhanced Digital Mammography: A Single-Institution Experience of the First 208 Cases.

Contrast‐enhanced digital mammography (CEDM) is the only imaging modality that provides both (a) a high‐resolution, low‐energy image comparable to that of digital mammography and (b) a contrast‐enhanced image similar to that of magnetic resonance imaging. We report the initial 208 CEDM examinations performed for various clinical indications and provide illustrative case examples. Given its success in recent studies and our experience of CEDM primarily as a diagnostic adjunct, CEDM can potentially improve breast cancer detection by combining the low‐cost conclusions of screening mammography with the high sensitivity of magnetic resonance imaging.

Contrast Enhanced Spectral Mammography: A Review☆☆☆★

Contrast-enhanced spectral mammography (CESM) provides low-energy 2D mammographic images comparable to standard digital mammography and a post-contrast recombined image to assess tumor neovascularity similar to magnetic resonance imaging (MRI). The utilization of CESM in the United States is currently low but could increase rapidly given many potential indications for clinical use. This article discusses historical background and literature review of indications and diagnostic accuracy of CESM to date. CESM is a growing technique for breast cancer detection and diagnosis that has levels of sensitivity and specificity on par with contrast-enhanced breast MRI. Because of its similar performance and ease of implementation, CESM is being adopted for multiple indications previously reserved for MRI, such as problem-solving, disease extent in newly diagnosed patients, and evaluating the treatment response of neoadjuvant chemotherapy.

Computer-aided diagnosis of contrast-enhanced spectral mammography: A feasibility study

OBJECTIVE To evaluate whether the use of a computer-aided diagnosis-contrast-enhanced spectral mammography (CAD-CESM) tool can further increase the diagnostic performance of CESM compared with that of experienced radiologists. MATERIALS AND METHODS This IRB-approved retrospective study analyzed 50 lesions described on CESM from August 2014 to December 2015. Histopathologic analyses, used as the criterion standard, revealed 24 benign and 26 malignant lesions. An expert breast radiologist manually outlined lesion boundaries on the different views. A set of morphologic and textural features were then extracted from the low-energy and recombined images. Machine-learning algorithms with feature selection were used along with statistical analysis to reduce, select, and combine features. Selected features were then used to construct a predictive model using a support vector machine (SVM) classification method in a leave-one-out-cross-validation approach. The classification performance was compared against the diagnostic predictions of 2 breast radiologists with access to the same CESM cases. RESULTS Based on the SVM classification, CAD-CESM correctly identified 45 of 50 lesions in the cohort, resulting in an overall accuracy of 90%. The detection rate for the malignant group was 88% (3 false-negative cases) and 92% for the benign group (2 false-positive cases). Compared with the model, radiologist 1 had an overall accuracy of 78% and a detection rate of 92% (2 false-negative cases) for the malignant group and 62% (10 false-positive cases) for the benign group. Radiologist 2 had an overall accuracy of 86% and a detection rate of 100% for the malignant group and 71% (8 false-positive cases) for the benign group. CONCLUSIONS The results of our feasibility study suggest that a CAD-CESM tool can provide complementary information to radiologists, mainly by reducing the number of false-positive findings.

Clinical utility of contrast-enhanced spectral mammography as an adjunct for tomosynthesis-detected architectural distortion

OBJECTIVE Supplement tomosynthesis-detected architectural distortions (AD) with CESM to better characterize malignant vs benign lesions. METHODS Retrospective review CESM prior to biopsied AD. Pathology: benign, radial scar, or malignant. RESULTS 49 lesions (45 patients). 29 invasive cancers, 1 DCIS (range, 0.4-4.7cm); 9 radial scars; 10 benign. 37 (75.5%) ADs had associated enhancement. PPV 78.4% (29/37), sensitivity 96.7% (29/30); specificity, 57.9% (11/19); NPV, 91.7% (11/12). False-positive rate 21.6% (8/37); false-negative rate, 8.3% (1/12). Accuracy 81.6% (40/49). CONCLUSIONS High sensitivity and NPV of CESM in patients with AD is promising as an adjunct tool in diagnosing malignancy and avoiding unnecessary biopsy, respectively.

The Future of Contrast-Enhanced Mammography

OBJECTIVE The purpose of this article is to discuss facilitators of and barriers to future implementation of contrast-enhanced mammography (CEM) in the United States. CONCLUSION CEM provides low-energy 2D mammographic images analogous to digital mammography and contrast-enhanced recombined images that allow assessment of neovascularity similar to that offered by MRI. The utilization of CEM in the United States is currently low but could increase rapidly given the many potential indications for its clinical use.

Assessing tumor extent on contrast-enhanced spectral mammography versus full-field digital mammography and ultrasound

OBJECTIVES To compare breast cancer size measurements on full-field digital mammography (FFDM), contrast-enhanced spectral mammography (CEDM), and ultrasound (US), with histologic tumor size used as the reference standard. Material and methods The HIPAA complaint, IRB approved study comprised 88 women with newly diagnosed breast cancer who underwent FFDM and CEDM;74 also had US. Breast density, histologic subtype, and maximum tumor measurements were recorded. RESULTS Pearson correlation coefficients for FFDM, US, and CEDM vs histopathology were 0.598, 0.639, and 0.859, respectively (P<0.001). The following correlation coefficients were calculated for dense breasts (n=48): histopathology vs FFDM (0.555), US (0.633), and CEDM (0.843) (P<0.001); for nondense breasts (n=40), they were FFDM (0.618), US (0.512), and CEDM (0.885) (P<0.001). For size difference, the mean (SD) for histopathology vs FFDM, US, and CEDM was -1.3 (11.9) mm, -2.8 (11.1) mm, and 2.9 (9.5) mm, respectively. Limits of agreement were -24.8 to 22.0mm, -24.5 to 18.8mm, and -15.6 to 21.4mm, respectively. CONCLUSIONS In patients with biopsy-proven malignancy, size measurements correlated well with histopathologic size, and were higher on CEDM than those for FFDM and US in patients with dense or nondense breasts. The added value of CEDM as a supplement to FFDM in determining tumor size, however, was greater in patients with dense breasts. CEDM may be a promising alternative preoperative measurement tool for breast cancer patients with dense breasts and/or limited access or contraindications to MRI.

A comparison of the diagnostic accuracy of magnetic resonance imaging to axillary ultrasound in the detection of axillary nodal metastases in newly diagnosed breast cancer

Patients with a diagnosis of invasive breast cancer are increasingly undergoing breast magnetic resonance imaging (MRI) for preoperative staging including evaluation of axillary lymph node metastases (ALNM). This retrospective study aims to evaluate the utility of adding axillary ultrasound (AUS) in the preoperative setting when an MRI is planned or has already been performed. This IRB approved, HIPAA compliant study reviewed a total of 271 patients with a new diagnosis of invasive breast cancer at a single institution, between June 1, 2010 and June 30, 2013. The study included patients who received both AUS and MRI for preoperative staging. Data were divided into two cohorts, patients who underwent MRI prior to AUS and those who underwent AUS prior to MRI. AUS and MRI reports were categorized according to BI‐RADS criteria as “suspicious” or “not suspicious” for ALNM. In the setting of a negative MRI and subsequent positive AUS, only one out of 25 cases (4%) were positive for metastases after correlating with histologic pathology. MRI detected metastatic disease in four out of 27 (15%) patients who had false‐negative AUS performed prior to MRI. Our results indicate the addition of AUS after preoperative MRI does not contribute significantly to increased detection of missed disease. MRI could serve as the initial staging imaging method of the axilla in the setting that AUS is not initially performed and may be valuable in identification of lymph nodes not identified on AUS.

Detection of residual disease after neoadjuvant therapy in breast cancer using personalized circulating tumor DNA analysis

Accurate detection of minimal residual disease (MRD) can guide individualized management of early stage cancer patients, but current diagnostic approaches lack adequate sensitivity. Circulating tumor DNA (ctDNA) analysis has shown promise for recurrence monitoring but MRD detection immediately after neoadjuvant therapy or surgical resection has remained challenging. We have developed TARgeted DIgital Sequencing (TARDIS) to simultaneously analyze multiple patient-specific cancer mutations in plasma and improve sensitivity for minute quantities of residual tumor DNA. In 77 reference samples at 0.03%-1% mutant allele fraction (AF), we observed 93.5% sensitivity. Using TARDIS, we analyzed ctDNA in 34 samples from 13 patients with stage II/III breast cancer treated with neoadjuvant therapy. Prior to treatment, we detected ctDNA in 12/12 patients at 0.002%-1.04% AF (0.040% median). After completion of neoadjuvant therapy, we detected ctDNA in 7/8 patients with residual disease observed at surgery and in 1/5 patients with pathological complete response (odds ratio, 18.5, Fisher’s exact p=0.032). These results demonstrate high accuracy for a personalized blood test to detect residual disease after neoadjuvant therapy. With additional clinical validation, TARDIS could identify patients with molecular complete response after neoadjuvant therapy who may be candidates for nonoperative management. One Sentence Summary A personalized ctDNA test achieves high accuracy for residual disease.