Rapid Access to Contrast-Enhanced spectral mammogRaphy in women recalled from breast cancer screening: the RACER trial study design.

BACKGROUND: In the Dutch breast cancer screening program, women recalled with a BI-RADS 0 score are referred for additional imaging, while those with BI-RADS 4/5 scores are also directed to an outpatient breast clinic. Approximately six out of ten women are recalled without being diagnosed with a malignancy. However, these recalls require additional imaging and doctor visits, which result in patient anxiety and increased health care costs. Conventional types of imaging used for additional imaging are full-field digital mammography and tomosynthesis. Contrast-enhanced spectral mammography has proved to have higher sensitivity and specificity than conventional imaging in women recalled from screening. Therefore, the aim is to study if CESM instead of conventional imaging is a more accurate, patient-friendly, and cost-effective strategy in the work-up of women recalled from breast cancer screening. METHODS: This prospective, multicenter, randomized controlled trial will be conducted at four centers and will include 528 patients recalled for suspicious breast lesions from the Dutch breast cancer screening program. Participants are randomized in two groups: (1) standard care using conventional breast imaging techniques as initial imaging after recall versus (2) work-up primarily based on CESM. Written informed consent will be collected prior to study inclusion. The primary outcome is the diagnostic accuracy for detection of breast cancer. Secondary outcomes are numbers of additional diagnostic exams, days until final diagnosis, health care costs, and experienced patient anxiety. DISCUSSION: Based on previously published retrospective studies, we expect to demonstrate in this prospective multicenter randomized controlled trial, that using CESM as a primary work-up tool in women recalled from breast cancer screening is a more accurate, cost-effective, and patient-friendly strategy. TRIAL REGISTRATION: Netherlands Trial Register, NL6413/NTR6589. Registered on 6 July, 2017.

Evaluation of single-view contrast-enhanced mammography as novel reading strategy: a non-inferiority feasibility study.

BACKGROUND: Guidelines recommend screening of high-risk women using breast magnetic resonance imaging (MRI). Contrast-enhanced mammography (CEM) has matured, providing excellent diagnostic accuracy. To lower total radiation dose, evaluation of single-view (1 V) CEM exams might be considered instead of double-view (2 V) readings as an alternative reading strategy in women who cannot undergo MRI. METHODS: This retrospective non-inferiority feasibility study evaluates whether the use of 1 V results in an acceptable sensitivity for detecting breast cancer (non-inferiority margin, - 10%). CEM images from May 2013 to December 2017 were included. 1 V readings were performed by consensus opinion of three radiologists, followed by 2 V readings being performed after 6 weeks. Cases were considered "malignant" if the final BI-RADS score was ≥ 4, enabling calculation of sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). Histopathological results or follow-up served as a gold standard. RESULTS: A total of 368 cases were evaluated. Mean follow-up for benign or negative cases was 20.9 months. Sensitivity decreased by 9.6% from 92.9 to 83.3% when only 1 V was used for evaluation (p < 0.001). The lower limit of the 90% confidence interval around the difference in sensitivity between 1 V and 2 V readings was - 15% and lies below the predefined non-inferiority margin of - 10%. Hence, non-inferiority of 1 V to 2 V reading cannot be concluded. AUC for 1 V was significantly lower, 0.861 versus 0.899 for 2 V (p = 0.0174). CONCLUSION: Non-inferiority of 1 V evaluations as an alternative reading strategy to standard 2 V evaluations could not be concluded. 1 V evaluations had lower diagnostic performance compared with 2 V evaluations. KEY POINTS: • To lower radiation exposure used in contrast-enhanced mammography, we studied a hypothetical alternative strategy: single-view readings (1 V) versus (standard) double-view readings (2 V). • Based on our predefined margin of - 10%, non-inferiority of 1 V could not be concluded. • 1 V evaluation is not recommended as an alternative reading strategy to lower CEM-related radiation exposure.

Assessing the Risk of Contrast-Induced Nephropathy Using a Finger Stick Analysis in Recalls from Breast Screening: The CINFIBS Explorative Study.

Purpose: To evaluate whether a handheld point-of-care (POC) device is able to predict and discriminate patients at potential risk of contrast-induced nephropathy (CIN) prior to iodine-based contrast media delivery. Methods and Materials: Between December 2014 and June 2016, women undergoing contrast-enhanced spectral mammography (CESM) with an iodine-based contrast agent were asked to have their risk of CIN assessed by a dedicated POC device (StatSensor CREAT) and a risk factor questionnaire based on national guidelines. Prior to contrast injection, a venous blood sample was drawn to compare the results of POC with regular laboratory testing. Results: A total of 351 patients were included; 344 were finally categorized as low risk patients by blood creatinine evaluation. Seven patients had a eGFR below 60 ml/min/1.73 m2, necessitating additional preparation prior to contrast delivery. The POC device failed to categorize six out of seven patients (86%), leading to (at that stage) unwanted contrast administration. Two patients subsequently developed CIN after 2-5 days, which was self-limiting after 30 days. Conclusion: The POC device tested was not able to reliably assess impairment of renal function in our patient cohort undergoing CESM. Consequently, we still consider classic clinical laboratory testing preferable in patients at potential risk for developing CIN.

Contrast-enhanced spectral mammography as work-up tool in patients recalled from breast cancer screening has low risks and might hold clinical benefits.

OBJECTIVE: Contrast-enhanced spectral mammography (CESM) is a reliable problem solving tool in the work-up of women recalled from breast cancer screening. We evaluated additional findings caused by CESM alone and outweighed them against the disadvantages of this technique. METHODS: From December 2012 to December 2015, all women recalled from screening who underwent CESM were considered for this study. Radiation exposure and number of adverse contrast reactions were analysed. An experienced breast radiologist reviewed all exams and identified cases with lesions detected by CESM alone and scored their conspicuity. From these cases, data on breast density and final diagnosis were collected. For malignant cases, tumour grade and receptor characteristics were also collected. RESULTS: During this study, 839 women underwent CESM after a screening recall, in which five minor adverse contrast reactions were observed. Median radiation dose per exam was 6.0mGy (0.9-23.4mGy). Seventy CESM-only lesions were detected in 65 patients. Of these 70 lesions, 54.3% proved to be malignant, most commonly invasive ductal carcinomas. The remaining CESM-only lesions were benign, predominantly fibroadenomas. No complications were observed during biopsy of these lesions. Retrospectively, the majority of the lesions were either occult or a 'minimal sign' on low-energy CESM images or the screening mammogram. CONCLUSION: Using CESM as a work-up tool for women recalled from screening carries low risk for the patient, while additionally detected tumour foci might hold important clinical implications which need to be further studied in large, randomized controlled trials.

Contrast-enhanced spectral mammography in recalls from the Dutch breast cancer screening program: validation of results in a large multireader, multicase study.

OBJECTIVES: Contrast-enhanced spectral mammography (CESM) is a promising problem-solving tool in women referred from a breast cancer screening program. We aimed to study the validity of preliminary results of CESM using a larger panel of radiologists with different levels of CESM experience. METHODS: All women referred from the Dutch breast cancer screening program were eligible for CESM. 199 consecutive cases were viewed by ten radiologists. Four had extensive CESM experience, three had no CESM experience but were experienced breast radiologists, and three were residents. All readers provided a BI-RADS score for the low-energy CESM images first, after which the score could be adjusted when viewing the entire CESM exam. BI-RADS 1-3 were considered benign and BI-RADS 4-5 malignant. With this cutoff, we calculated sensitivity, specificity and area under the ROC curve. RESULTS: CESM increased diagnostic accuracy in all readers. The performance for all readers using CESM was: sensitivity 96.9 % (+3.9 %), specificity 69.7 % (+33.8 %) and area under the ROC curve 0.833 (+0.188). CONCLUSION: CESM is superior to conventional mammography, with excellent problem-solving capabilities in women referred from the breast cancer screening program. Previous results were confirmed even in a larger panel of readers with varying CESM experience. KEY POINTS: • CESM is consistently superior to conventional mammography • CESM increases diagnostic accuracy regardless of a reader's experience • CESM is an excellent problem-solving tool in recalls from screening programs.