Organizational Breast Cancer Data Mart: A Solution for Assessing Outcomes of Imaging and Treatment.

PURPOSE: In the United States, a comprehensive national breast cancer registry (CR) does not exist. Thus, care and coverage decisions are based on data from population subsets, other countries, or models. We report a prototype real-world research data mart to assess mortality, morbidity, and costs for breast cancer diagnosis and treatment. METHODS: With institutional review board approval and Health Insurance Portability and Accountability Act (HIPPA) compliance, a multidisciplinary clinical and research data warehouse (RDW) expert group curated demographic, risk, imaging, pathology, treatment, and outcome data from the electronic health records (EHR), radiology (RIS), and CR for patients having breast imaging and/or a diagnosis of breast cancer in our institution from January 1, 2004, to December 31, 2020. Domains were defined by prebuilt views to extract data denormalized according to requirements from the existing RDW using an export, transform, load pattern. Data dictionaries were included. Structured query language was used for data cleaning. RESULTS: Five-hundred eighty-nine elements (EHR 311, RIS 211, and CR 67) were mapped to 27 domains; all, except one containing CR elements, had cancer and noncancer cohort views, resulting in a total of 53 views (average 12 elements/view; range, 4-67). EHR and RIS queries returned 497,218 patients with 2,967,364 imaging examinations and associated visit details. Cancer biology, treatment, and outcome details for 15,619 breast cancer cases were imported from the CR of our primary breast care facility for this prototype mart. CONCLUSION: Institutional real-world data marts enable comprehensive understanding of care outcomes within an organization. As clinical data sources become increasingly structured, such marts may be an important source for future interinstitution analysis and potentially an opportunity to create robust real-world results that could be used to support evidence-based national policy and care decisions for breast cancer.

Analytic Hierarchy Process Analysis of Patient Preferences for Contrast-Enhanced Mammography Versus MRI as Supplemental Screening Options for Breast Cancer.

OBJECTIVE: To guide implementation of supplemental breast screening by assessing patient preferences for contrast-enhanced mammography (CEM) versus MRI using analytic hierarchy process (AHP) methodology. METHODS: In an institutional review board-approved, HIPAA-compliant protocol, from March 23 to June 3, 2022, we contacted 579 women who had both CEM screening and MRI. Women were e-mailed an invitation to complete an online survey developed using an AHP-based model to elicit preferences for CEM or MRI. Methods for categorical data analysis were used to evaluate factors affecting preferences, under the Bonferroni correction for multiplicity. RESULTS: Complete responses were received from 222 (38.3%) women; the 189 women with a personal history of breast cancer had a mean age 61.8 years, and the 34 women without a personal history of breast cancer had a mean age of 53.6 years. Of 222 respondents, 157 (70.7%, confidence interval [CI]: 64.7-76.7) were determined to prefer CEM to MRI. Breast positioning was the most important criterion for 74 of 222 (33.3%) respondents, with claustrophobia, intravenous line placement, and overall stress most important for 38, 37, and 39 women (17.1%, 16.7%, and 17.6%), respectively, and noise level, contrast injection, and indifference being emphasized least frequently (by 10 [4.5%], 11 [5.0%], and 13 [5.9%] women, respectively). CEM preference was most prevalent (MRI least prevalent) for respondents emphasizing claustrophobia (37 of 38 [97%], CI: 86.2-99.9); CEM preference was least prevalent (MRI most prevalent) for respondents emphasizing breast positioning (40 of 74 [54%], CI: 42.1-65.7). CONCLUSIONS: AHP-based modeling reveals strong patient preferences for CEM over MRI, with claustrophobia favoring preference for CEM and breast positioning relatively favoring preference for MRI. Our results should help guide implementation of screening CEM and MRI.

Visual adaptation to medical images: a comparison of digital mammography and tomosynthesis.

Purpose: Radiologists and other image readers spend prolonged periods inspecting medical images. The visual system can rapidly adapt or adjust sensitivity to the images that an observer is currently viewing, and previous studies have demonstrated that this can lead to pronounced changes in the perception of mammogram images. We compared these adaptation effects for images from different imaging modalities to explore both general and modality-specific consequences of adaptation in medical image perception. Approach: We measured perceptual changes induced by adaptation to images acquired by digital mammography (DM) or digital breast tomosynthesis (DBT), which have both similar and distinct textural properties. Participants (nonradiologists) adapted to images from the same patient acquired from each modality or for different patients with American College of Radiology-Breast Imaging Reporting and Data System (BI-RADS) classification of dense or fatty tissue. The participants then judged the appearance of composite images formed by blending the two adapting images (i.e., DM versus DBT or dense versus fatty in each modality). Results: Adaptation to either modality produced similar significant shifts in the perception of dense and fatty textures, reducing the salience of the adapted component in the test images. In side-by-side judgments, a modality-specific adaptation effect was not observed. However, when the images were directly fixated during adaptation and testing, so that the textural differences between the modalities were more visible, significantly different changes in the sensitivity to the noise in the images were observed. Conclusions: These results confirm that observers can readily adapt to the visual properties or spatial textures of medical images in ways that can bias their perception of the images, and that adaptation can also be selective for the distinctive visual features of images acquired by different modalities.

CT-derived body composition associated with lung cancer recurrence after surgery.

OBJECTIVES: To evaluate the impact of body composition derived from computed tomography (CT) scans on postoperative lung cancer recurrence. METHODS: We created a retrospective cohort of 363 lung cancer patients who underwent lung resections and had verified recurrence, death, or at least 5-year follow-up without either event. Five key body tissues and ten tumor features were automatically segmented and quantified based on preoperative whole-body CT scans (acquired as part of a PET-CT scan) and chest CT scans, respectively. Time-to-event analysis accounting for the competing event of death was performed to analyze the impact of body composition, tumor features, clinical information, and pathological features on lung cancer recurrence after surgery. The hazard ratio (HR) of normalized factors was used to assess individual significance univariately and in the combined models. The 5-fold cross-validated time-dependent receiver operating characteristics analysis, with an emphasis on the area under the 3-year ROC curve (AUC), was used to characterize the ability to predict lung cancer recurrence. RESULTS: Body tissues that showed a standalone potential to predict lung cancer recurrence include visceral adipose tissue (VAT) volume (HR = 0.88, p = 0.047), subcutaneous adipose tissue (SAT) density (HR = 1.14, p = 0.034), inter-muscle adipose tissue (IMAT) volume (HR = 0.83, p = 0.002), muscle density (HR = 1.27, p < 0.001), and total fat volume (HR = 0.89, p = 0.050). The CT-derived muscular and tumor features significantly contributed to a model including clinicopathological factors, resulting in an AUC of 0.78 (95% CI: 0.75-0.83) to predict recurrence at 3 years. CONCLUSIONS: Body composition features (e.g., muscle density, or muscle and inter-muscle adipose tissue volumes) can improve the prediction of recurrence when combined with clinicopathological factors.

Prospective Multicenter Diagnostic Performance of Technologist-Performed Screening Breast Ultrasound After Tomosynthesis in Women With Dense Breasts (the DBTUST).

PURPOSE: To assess diagnostic performance of digital breast tomosynthesis (DBT) alone or combined with technologist-performed handheld screening ultrasound (US) in women with dense breasts. METHODS: In an institutional review board-approved, Health Insurance Portability and Accountability Act-compliant multicenter protocol in western Pennsylvania, 6,179 women consented to three rounds of annual screening, interpreted by two radiologist observers, and had appropriate follow-up. Primary analysis was based on first observer results. RESULTS: Mean participant age was 54.8 years (range, 40-75 years). Across 17,552 screens, there were 126 cancer events in 125 women (7.2/1,000; 95% CI, 5.9 to 8.4). In year 1, DBT-alone cancer yield was 5.0/1,000, and of DBT+US, 6.3/1,000, difference 1.3/1,000 (95% CI, 0.3 to 2.1; P = .005). In years 2 + 3, DBT cancer yield was 4.9/1,000, and of DBT+US, 5.9/1,000, difference 1.0/1,000 (95% CI, 0.4 to 1.5; P < .001). False-positive rate increased from 7.0% for DBT in year 1 to 11.5% for DBT+US and from 5.9% for DBT in year 2 + 3 to 9.7% for DBT+US (P < .001 for both). Nine cancers were seen only by double reading DBT and one by double reading US. Ten interval cancers (0.6/1,000 [95% CI, 0.2 to 0.9]) were identified. Despite reduction in specificity, addition of US improved receiver operating characteristic curves, with area under receiver operating characteristic curve increasing from 0.83 for DBT alone to 0.92 for DBT+US in year 1 (P = .01), with smaller improvements in subsequent years. Of 6,179 women, across all 3 years, 172/6,179 (2.8%) unique women had a false-positive biopsy because of DBT as did another 230/6,179 (3.7%) women because of US (P < .001). CONCLUSION: Overall added cancer detection rate of US screening after DBT was modest at 19/17,552 (1.1/1,000; CI, 0.5- to 1.6) screens but potentially overcomes substantial increases in false-positive recalls and benign biopsies.

Impact of Original and Artificially Improved Artificial Intelligence-based Computer-aided Diagnosis on Breast US Interpretation.

OBJECTIVE: For breast US interpretation, to assess impact of computer-aided diagnosis (CADx) in original mode or with improved sensitivity or specificity. METHODS: In this IRB approved protocol, orthogonal-paired US images of 319 lesions identified on screening, including 88 (27.6%) cancers (median 7 mm, range 1-34 mm), were reviewed by 9 breast imaging radiologists. Each observer provided BI-RADS assessments (2, 3, 4A, 4B, 4C, 5) before and after CADx in a mode-balanced design: mode 1, original CADx (outputs benign, probably benign, suspicious, or malignant); mode 2, artificially-high-sensitivity CADx (benign or malignant); and mode 3, artificially-high-specificity CADx (benign or malignant). Area under the receiver operating characteristic curve (AUC) was estimated under each modality and for standalone CADx outputs. Multi-reader analysis accounted for inter-reader variability and correlation between same-lesion assessments. RESULTS: AUC of standalone CADx was 0.77 (95% CI: 0.72-0.83). For mode 1, average reader AUC was 0.82 (range 0.76-0.84) without CADx and not significantly changed with CADx. In high-sensitivity mode, all observers' AUCs increased: average AUC 0.83 (range 0.78-0.86) before CADx increased to 0.88 (range 0.84-0.90), P < 0.001. In high-specificity mode, all observers' AUCs increased: average AUC 0.82 (range 0.76-0.84) before CADx increased to 0.89 (range 0.87-0.92), P < 0.0001. Radiologists responded more frequently to malignant CADx cues in high-specificity mode (42.7% vs 23.2% mode 1, and 27.0% mode 2, P = 0.008). CONCLUSION: Original CADx did not substantially impact radiologists' interpretations. Radiologists showed improved performance and were more responsive when CADx produced fewer false-positive malignant cues.

Training Radiologists to Interpret Contrast-enhanced Mammography: Toward a Standardized Lexicon.

OBJECTIVE: Using terms adapted from the BI-RADS Mammography and MRI lexicons, we trained radiologists to interpret contrast-enhanced mammography (CEM) and assessed reliability of their description and assessment. METHODS: A 60-minute presentation on CEM and terminology was reviewed independently by 21 breast imaging radiologist observers. For 21 CEM exams with 31 marked findings, observers recorded background parenchymal enhancement (BPE) (minimal, mild, moderate, marked), lesion type (oval/round or irregular mass, or non-mass enhancement), intensity of enhancement (none, weak, medium, strong), enhancement quality (none, homogeneous, heterogeneous, rim), and BI-RADS assessment category (2, 3, 4A, 4B, 4C, 5). "Expert" consensus of 3 other radiologists experienced in CEM was developed. Kappa statistic was used to assess agreement between radiologists and expert consensus, and between radiologists themselves, on imaging feature categories and final assessments. Reproducibility of specific feature descriptors was assessed as fraction of consensus-concordant responses. RESULTS: Radiologists demonstrated moderate agreement for BPE, (mean kappa, 0.43; range, 0.05-0.69), and lowest reproducibility for "minimal." Agreement was substantial for lesion type (mean kappa, 0.70; range, 0.47-0.93), moderate for intensity of enhancement (mean kappa, 0.57; range, 0.44-0.76), and moderate for enhancement quality (mean kappa, 0.59; range, 0.20-0.78). Agreement on final assessment was fair (mean kappa, 0.26; range, 0.09-0.44), with BI-RADS category 3 the least reproducible. Decision to biopsy (BI-RADS 2-3 vs 4-5) showed moderate agreement with consensus (mean kappa, 0.54; range, -0.06-0.87). CONCLUSION: With minimal training, agreement for description of CEM findings by breast imaging radiologists was comparable to other BI-RADS lexicons.

Contrast Enhanced Digital Mammography (CEDM) Helps to Safely Reduce Benign Breast Biopsies for Low to Moderately Suspicious Soft Tissue Lesions.

RATIONALE AND OBJECTIVES: To preliminarily asses if Contrast Enhanced Digital Mammography (CEDM) can accurately reduce biopsy rates for soft tissue BI-RADS 4A or 4B lesions. MATERIALS AND METHODS: Eight radiologists retrospectively and independently reviewed 60 lesions in 54 consenting patients who underwent CEDM under Health Insurance Portability and Accountability Act compliant institutional review board-approved protocols. Readers provided Breast Imaging Reporting & Data System ratings sequentially for digital mammography/digital breast tomosynthesis (DM/DBT), then with ultrasound, then with CEDM for each lesion. Area under the curve (AUC), true positive rates and false positive rates, positive predictive values and negative predictive values were calculated. Statistical analysis accounting for correlation between lesion-examinations and between-reader variability was performed using OR/DBM (for SAS v.3.0), generalized linear mixed model for binary data (proc glimmix, SAS v.9.4, SAS Institute, Cary North Carolina), and bootstrap. RESULTS: The cohort included 49 benign, two high-risk and nine cancerous lesions in 54 women aged 34-74 (average 50) years. Reader-averaged AUC for CEDM was significantly higher than DM/DBT alone (0.85 versus 0.66, p < 0.001) or with US (0.85 versus 0.75, p = 0.001). CEDM increased true positive rates from 0.74 under DB/DBT, and 0.89 with US, to 0.90 with CEDM, (p = 0.019 DM/DBT versus CEDM, p = 0.78 DM/DBT + US versus CEDM) and decreased false positive rates from 0.47 using DM/DBT and 0.61 with US to 0.39 with CEDM (p = 0.017 DM/DBT versus CEDM, p = 0.001 DM/DBT+ US versus CEDM). For an expected cancer rate of 10%, CEDM positive predictive values was 20.5% (95% CI: 16%-27%) and negative predictive values 98.3% (95% CI: 96%-100%). CONCLUSION: Addition of CEDM for evaluation of low-moderate suspicion soft tissue breast lesions can substantially reduce biopsy of benign lesions without compromising cancer detection.

A Prospective Study of Automated Breast Ultrasound Screening of Women with Dense Breasts in a Digital Breast Tomosynthesis-based Practice.

OBJECTIVE: To assess prospectively the interpretative performance of automated breast ultrasound (ABUS) as a supplemental screening after digital breast tomosynthesis (DBT) or as a standalone screening of women with dense breast tissue. METHODS: Under an IRB-approved protocol (written consent required), women with dense breasts prospectively underwent concurrent baseline DBT and ABUS screening. Examinations were independently evaluated, in opposite order, by two of seven Mammography Quality Standards Act-qualified radiologists, with the primary radiologist arbitrating disagreements and making clinical management recommendations. We report results for 1111 screening examinations (598 first year and 513 second year) for which all diagnostic workups are complete. Imaging was also retrospectively reviewed for all cancers. Statistical assessments used a 0.05 significance level and accounted for correlation between participants' examinations. RESULTS: Of 1111 women screened, primary radiologists initially "recalled" based on DBT alone (6.6%, 73/1111, CI: 5.2%-8.2%), of which 20 were biopsied, yielding 6/8 total cancers. Automated breast ultrasound increased recalls overall to 14.4% (160/1111, CI: 12.4%-16.6%), with 27 total biopsies, yielding 1 additional cancer. Double reading of DBT alone increased the recall rate to 10.7% (119/1111), with 21 biopsies, with no improvement in cancer detection. Double reading ABUS increased the recall rate to 15.2% (169/1111, CI: 13.2%-17.5%) of women, of whom 22 were biopsied, yielding the detection of 7 cancers, including one seen only on double reading ABUS. Inter-radiologist agreement was similar for recall recommendations from DBT (κ = 0.24, CI: 0.14-0.34) and ABUS (κ = 0.23, CI: 0.15-0.32). Integrated assessments from both readers resulted in a recall rate of 15.1% (168/1111, CI: 13.1%-17.4%). CONCLUSION: Supplemental or standalone ABUS screening detected cancers not seen on DBT, but substantially increased noncancer recall rates.

Diagnostic Performance of MRI, Molecular Breast Imaging, and Contrast-enhanced Mammography in Women with Newly Diagnosed Breast Cancer.

Background Staging newly diagnosed breast cancer by using dynamic contrast material-enhanced MRI is limited by access, high cost, and false-positive findings. The utility of contrast-enhanced mammography (CEM) and 99mTc sestamibi-based molecular breast imaging (MBI) in this setting is largely unknown. Purpose To compare extent-of-disease assessments by using MRI, CEM, and MBI versus pathology in women with breast cancer. Materials and Methods In this HIPAA-compliant prospective study, women with biopsy-proven breast cancer underwent MRI, CEM, and MBI between October 2014 and April 2018. Eight radiologists independently interpreted each examination result prospectively and were blinded to interpretations of findings with the other modalities. Visibility of index malignancies, lesion size, and additional suspicious lesions (malignant or benign) were compared during pathology review. Accuracy of index lesion sizing and detection of additional lesions in women without neoadjuvant chemotherapy were compared. Results A total of 102 women were enrolled and 99 completed the study protocol (mean age, 51 years ± 11 [standard deviation]; range, 32-77 years). Lumpectomy or mastectomy was performed in 71 women (79 index malignancies) without neoadjuvant chemotherapy and in 28 women (31 index malignancies) with neoadjuvant chemotherapy. Of the 110 index malignancies, MRI, CEM, and MBI depicted 102 (93%; 95% confidence interval [CI]: 86%, 97%), 100 (91%; 95% CI: 84%, 96%), and 101 (92%; 95% CI: 85%, 96%) malignancies, respectively. In patients without neoadjuvant chemotherapy, pathologic size of index malignancies was overestimated with all modalities (P = .02). MRI led to overestimation of 24% (17 of 72) of malignancies by more than 1.5 cm compared with 11% (eight of 70) with CEM and 15% (11 of 72) with MBI. MRI depicted more (P = .007) nonindex lesions, with sensitivity similar to that of CEM or MBI, resulting in lower positive predictive value of additional biopsies (13 of 46 [28%; 95% CI: 17%, 44%] for MRI; 14 of 27 [52%; 95% CI: 32%, 71%] for CEM; and 11 of 25 [44%; 95% CI: 24%, 65%] for MBI (overall P = .01). Conclusion Contrast-enhanced mammography, molecular breast imaging, and MRI showed similar detection of all malignancies. MRI depicted more nonindex suspicious benign lesions than did contrast-enhanced mammography or molecular breast imaging, leading to lower positive predictive value of additional biopsies. All three modalities led to overestimation of index tumor size, particularly MRI. © RSNA, 2019 Online supplemental material is available for this article.

Digital Mammography versus Digital Mammography Plus Tomosynthesis in Breast Cancer Screening: The Oslo Tomosynthesis Screening Trial.

Background Digital breast tomosynthesis (DBT) is replacing digital mammography (DM) in the clinical workflow. Currently, there are limited prospective studies comparing the diagnostic accuracy of both examinations and the role of synthetic mammography (SM) and computer-aided detection (CAD). Purpose To compare the accuracy of DM versus DM + DBT in population-based breast cancer screening. Materials and Methods This prospective study, performed from November 2010 to December 2012, included 24 301 women (mean age, 59.1 years ± 5.7 [standard deviation]) with 281 cancers, of which 51 were interval cancers. Each examination was independently interpreted with four reading modes: DM, DM + CAD, DM + DBT, and SM + DBT. Sensitivity and specificity were compared for DM versus DM + DBT, DM versus DM + CAD, DM + DBT versus SM + DBT, and DM versus DM + DBT at double reading. Reader-adjusted performance characteristics of reading modes were evaluated on the basis of pre-arbitration (initial interpretation) scores. Statistical analysis was based on cluster bootstrap analysis using 10 000 random resamples. Results Sensitivity was 54.1% (152 of 281) for DM and 70.5% (198 of 281) for DM + DBT. Reader-adjusted difference was 12.6% (95% confidence interval [CI]: 5.2%, 19.7%; P = .001). Specificity was 94.2% (false-positive fraction [FPF], 5.8%; 1388 of 24 020) for DM and 95.0% (FPF, 5.0%; 1209/24 020) for DM + DBT, with a reader-adjusted difference in FPF of -1.2% (95% CI: -1.7%, -0.7%; P < .001). Sensitivity was 69.0% (194 of 281) for SM + DBT and 70.5% (198 of 281) for DM + DBT, with a reader-adjusted difference of 1.0% (95% CI: -6.2%, 8.5%; P = .77). Specificity was 95.4% (FPF, 4.6%; 1111 of 24 020) for SM + DBT and 95.0% (FPF, 5.0%;1209 of 24 020) for DM + DBT, with reader-adjusted 95% CIs for FPF of 4.7%, 5.4% and 5.0%, 5.7%, respectively, and a difference of -0.3% (95% CI: -0.8%, 0.2%; P = .23). Differences in sensitivity and specificity with the addition of CAD were small and not significant (P > .2). Conclusion Addition of digital breast tomosynthesis to digital mammography resulted in significant gains in sensitivity and specificity. Synthetic mammography in combination with digital breast tomosynthesis had similar sensitivity and specificity to digital mammography in combination with digital breast tomosynthesis. © RSNA, 2019 See also the editorial by Lång in this issue.

Evaluation of diagnostic accuracy in free-response detection-localization tasks using ROC tools.

Diagnostic systems designed to detect possibly multiple lesions per patient (e.g. multiple polyps during CT colonoscopy) are often evaluated in "free-response" studies that allow for diagnostic responses unconstrained in their number and locations. Analysis of free-response studies requires extensions of the traditional receiver operating characteristic (ROC) analysis, which are termed free-response ROC (FROC) methodology. Despite substantial developments in this area, FROC tools and approaches are much more cumbersome than traditional ROC methods. Alternative approaches that use well-known ROC tools (e.g. ROI-ROC) require defining and physically delineating regions of interest (ROI) and combine FROC data within ROIs. We propose an approach that allows analyzing FROC data using conventional ROC tools without delineating the actual ROIs or reducing data. The design parameters of FROC study are used to make FROC data analyzable using ROC tools and to calibrate the corresponding FROC and ROC curves on both conceptual and numerical levels. Differences in the performance indices of the nonparametric FROC and the new approach are shown to be asymptotically negligible and typically rather small in practice. Data from a large multi-reader study of colon cancer detection are used to illustrate the new approach.

Grouped Amorphous Calcifications at Mammography: Frequently Atypical but Rarely Associated with Aggressive Malignancy.

Purpose To determine rate of malignancy at stereotactic biopsy of amorphous calcifications with different distributions using current imaging, clinical, and histopathologic criteria. Materials and Methods From January 2009 to September 2013, this retrospective study reviewed a large set of stereotactic biopsies to identify amorphous calcifications and their clinical, imaging, and histopathologic characteristics. Calcification distribution was correlated with malignancy rate after adjusting for known risk factors using logistic regression. Results Of 1903 sequential biopsies, 546 (28.7%) were for amorphous calcifications. After excluding atypical lesions not excised and patients with more than one biopsy in the same year, 497 lesions from 494 women (median age, 52 years; age range, 30-81 years) remained. Fifty-two (10.5%; 95% confidence interval [CI]: 7.9, 13.5) lesions proved malignant, with 17 of 52 (42.7%) being invasive cancers (median, 0.3 cm; range, 0.1-1.3 cm) and all 17 of them being estrogen and progesterone receptor positive and node negative. Malignancy rates in a segmental (six of 21 [28.6%]), linear (eight of 32 [25.0%]), or multiple group same quadrant (nine of 36 [25.0%]) distribution were significantly higher than malignancy rate in a solitary group of amorphous calcifications (25 of 356 [7.0%]) (P = .004, P = .003, and P = .002, respectively). Of 356 grouped amorphous calcifications, 102 (28.7%) yielded atypical results prompting excision, with three of 102 (2.9%) upgraded to ductal carcinoma in situ at excision. In women younger than 50 years without a personal history of cancer, grouped amorphous calcifications showed four of 127 (3.1%) (95% CI: 0.9, 7.9) were malignant and 39 of 127 (30.7%) were atypical at final histopathology. Conclusion Biopsy of amorphous calcifications remains necessary, with an overall malignancy rate of 10.5%; only 17 of 497 (3.4%) biopsies showed invasive cancer, and all of these were estrogen and progesterone receptor positive. Grouped amorphous calcifications in women younger than 50 years without history of breast or ovarian cancer showed a low malignancy rate of 3.1% (four of 127).

Performance of breast cancer screening using digital breast tomosynthesis: results from the prospective population-based Oslo Tomosynthesis Screening Trial.

PURPOSE: Digital breast tomosynthesis (DBT) has the potential to overcome limitations of conventional mammography. This study investigated the effects of addition of DBT on interval and detected cancers in population-based screening. METHODS: Oslo Tomosynthesis Screening Trial (OTST) was a prospective, independent double-reading trial inviting women 50-69 years biennially, comparing full-field digital mammography (FFDM) plus DBT with FFDM alone. Performance indicators and characteristics of screen-detected and interval cancers were compared with two previous FFDM rounds. RESULTS: 24,301 consenting women underwent FFDM + DBT screening over a 2-year period. Results were compared with 59,877 FFDM examinations during prior rounds. Addition of DBT resulted in a non-significant increase in sensitivity (76.2%, 378/496, vs. 80.8%, 227/281, p = 0.151) and a significant increase in specificity (96.4%, 57229/59381 vs. 97.5%, 23427/24020, p < .001). Number of recalls per screen-detected cancer decreased from 6.7 (2530/378) to 3.6 (820/227) with DBT (p < .001). Cancer detection per 1000 women screened increased (6.3, 378/59877, vs. 9.3, 227/24301, p < .001). Interval cancer rate per 1000 screens for FFDM + DBT remained similar to previous FFDM rounds (2.1, 51/24301 vs. 2.0, 118/59877, p = 0.734). Interval cancers post-DBT were comparable to prior rounds but significantly different in size, grade, and node status from cancers detected only using DBT. 39.6% (19/48) of interval cancers had positive nodes compared with only 3.9% (2/51) of additional DBT-only-detected cancers. CONCLUSIONS: DBT-supplemented screening resulted in significant increases in screen-detected cancers and specificity. However, no significant change was observed in the rate, size, node status, or grade of interval cancers. ClinicalTrials.gov: NCT01248546.

Identification of Distant Metastatic Disease in Uterine Cervical and Endometrial Cancers with FDG PET/CT: Analysis from the ACRIN 6671/GOG 0233 Multicenter Trial.

Purpose To assess the accuracy of staging positron emission tomography (PET)/computed tomography (CT) in detecting distant metastasis in patients with local-regionally advanced cervical and high-risk endometrial cancer in the clinical trial by the American College of Radiology Imaging Network (ACRIN) and the Gynecology Oncology Group (GOG) (ACRIN 6671/GOG 0233) and to compare central and institutional reader performance. Materials and Methods In this prospective multicenter trial, PET/CT and clinical data were reviewed for patients enrolled in ACRIN 6671/GOG 0233. Two central readers, blinded to site read and reference standard, reviewed PET/CT images for distant metastasis. Central review was then compared with institutional point-of-care interpretation. Reference standard was pathologic and imaging follow-up. Test performance for central and site reviews of PET/CT images was calculated and receiver operating characteristic analysis was performed. Generalized estimating equations and nonparametric bootstrap procedure for clustered data were used to assess statistical significance. Results There were 153 patients with cervical cancer and 203 patients with endometrial cancer enrolled at 28 sites. Overall prevalence of distant metastasis was 13.7% (21 of 153) for cervical cancer and 11.8% (24 of 203) for endometrial cancer. Central reader PET/CT interpretation demonstrated sensitivity, specificity, positive predictive value (PPV), and negative predictive value of 54.8%, 97.7%, 79.3%, and 93.1% for cervical cancer metastasis versus 64.6%, 98.6%, 86.1%, and 95.4% for endometrial cancer, respectively. By comparison, local institutional review demonstrated sensitivity, specificity, PPV, and negative predictive value of 47.6%, 93.9%, 55.6%, and 91.9% for cervical cancer metastasis and 66.7%, 93.9%, 59.3%, and 95.5% for endometrial cancer, respectively. For central readers, the specificity and PPV of PET/CT detection of cervical and endometrial cancer metastases were all significantly higher compared with that of local institutional review (P < .05). Central reader area under the receiver operating characteristic curve (AUC) values were 0.78 and 0.89 for cervical and endometrial cancer, respectively; these were not significantly different from local institutional AUC values (0.75 and 0.84, respectively; P > .05 for both). Conclusion FDG PET/CT demonstrates high specificity and PPV for detecting distant metastasis in cervical and endometrial cancer and should be included in the staging evaluation. Blinded central review of imaging provides improved specificity and PPV for the detection of metastases and should be considered for future oncologic imaging clinical trials. © RSNA, 2017.

Ultrasound as the Primary Screening Test for Breast Cancer: Analysis From ACRIN 6666.

BACKGROUND: Mammography is not widely available in all countries, and breast cancer incidence is increasing. We considered performance characteristics using ultrasound (US) instead of mammography to screen for breast cancer. METHODS: Two thousand eight hundred nine participants were enrolled at 20 sites in the United States, Canada, and Argentina in American College of Radiology Imaging 6666. Two thousand six hundred sixty-two participants completed three annual screens (7473 examinations) with US and film-screen (n = 4351) or digital (n = 3122) mammography and had biopsy or 12-month follow-up. Cancer detection, recall, and positive predictive values were determined. All statistical tests were two-sided. RESULTS: One hundred ten women had 111 breast cancer events: 89 (80.2%) invasive cancers, median size 12 mm. The number of US screens to detect one cancer was 129 (95% bootstrap confidence interval [CI] = 110 to 156), and for mammography 127 (95% CI = 109 to 152). Cancer detection was comparable for each of US and mammography at 58 of 111 (52.3%) vs 59 of 111 (53.2%, P = .90), with US-detected cancers more likely invasive (53/58, 91.4%, median size 12 mm, range = 2-40 mm), vs mammography at 41 of 59 (69.5%, median size 13 mm, range = 1-55 mm, P < .001). Invasive cancers detected by US were more frequently node-negative, 34 of 53 (64.2%) vs 18 of 41 (43.9%) by mammography (P = .003). For 4814 incidence screens (years 2 and 3), US had higher recall and biopsy rates and lower PPV of biopsy (PPV3) than mammography: The recall rate was 10.7% (n = 515) vs 9.4% (n = 453, P = .03), the biopsy rate was 5.5% (n = 266) vs 2.0% (n = 97, P < .001), and PPV3 was 11.7% (31/266) vs 38.1% (37/97, P < .001). CONCLUSIONS: Cancer detection rate with US is comparable with mammography, with a greater proportion of invasive and node-negative cancers among US detections. False positives are more common with US screening.

Recall Rate Reduction with Tomosynthesis During Baseline Screening Examinations: An Assessment From a Prospective Trial.

RATIONALE AND OBJECTIVES: Assess results of a prospective, single-site clinical study evaluating digital breast tomosynthesis (DBT) during baseline screening mammography. MATERIALS AND METHODS: Under an institutional review board-approved Health Insurance Portability and Accountability Act (HIPAA)-compliant protocol, consenting women between ages 34 and 56 years scheduled for their initial and/or baseline screening mammogram underwent both full field digital mammography (FFDM) and DBT. The FFDM and the FFDM plus DBT images were interpreted independently in a reader by mode balanced approach by two of 14 participating radiologists. A woman was recalled for a diagnostic work-up if either radiologist recommended a recall. We report overall recall rates and related diagnostic outcome from the 1080 participants. Proportion of recommended recalls (Breast Imaging Reporting and Data System 0) were compared using a generalized linear mixed model (SAS 9.3) with a significance level of P = .0294. RESULTS: The fraction of women without breast cancer recommended for recall using FFDM alone and FFDM plus DBT were 412 of 1074 (38.4%) and 274 of 1074 (25.5%), respectively (P < .001). Large inter-reader variability in terms of recall reduction was observed among the 14 readers; however, 11 of 14 readers recalled fewer women using FFDM plus DBT (5 with P < .015). Six cancers (four ductal carcinomas in situ [DCIS] and two invasive ductal carcinomas [IDC]) were detected. One IDC was detected only on DBT and one DCIS cancer was detected only on FFDM, whereas the remaining cancers were detected on both modalities. CONCLUSIONS: The use of FFDM plus DBT resulted in a significant decrease in recall rates during baseline screening mammography with no reduction in sensitivity.

Impact of the new density reporting laws: radiologist perceptions and actual behavior.

RATIONALE AND OBJECTIVES: To assess radiologists' perceptions of how the new Breast Density Notification Act (BDNA) of Pennsylvania would affect their breast density reporting and their actual reporting patterns after implementation. MATERIALS AND METHODS: Under an institutional review board-approved protocol, we surveyed 21 radiologists about how they believe the new law affected their breast density reporting patterns and analyzed actual changes for 16 respondents before and after the law took effect. Three hundred consecutive reports were assessed for each radiologist before and after the effective date. The distributions of reported density Breast Imaging Reporting and Data System (BI-RADS) (1-4) were compared using a type III test in the context of an ordinal mixed model accounting for between-reader variability and adjusting for age (PROC GLIMMIX, SAS, version 9.3) using a two-sided .05 significance level. RESULTS: Seventeen radiologists responded to the survey; however, one retired shortly after responding. Of the 16 respondents, 56% (nine of 16) did not favor the law, 13% (two of 16) were in favor, and 31% (five of 16) were neutral. The fraction perceived that after implementation, they rated more, equally, or less frequently breasts as scattered fibroglandular densities (BI-RADS 2) versus heterogeneously dense rating (BI-RADS 3) was 50% (eight of 16), 44% (seven of 16), and 6% (one of 16), respectively. In practice, 44% (seven of 16) performed differently than their survey answers. Fourteen of 16 radiologists increased the frequency of reported BI-RADS 2 scores after BDNA implementation with seven having statistically significant (P < .05) increases after adjusting for age differences. CONCLUSIONS: Radiologists' reporting patterns changed, at least for a short duration, after the new density reporting law and for some of the radiologists in an unexpected way.

Effect of the Availability of Prior Full-Field Digital Mammography and Digital Breast Tomosynthesis Images on the Interpretation of Mammograms.

PURPOSE: To assess the effect of and interaction between the availability of prior images and digital breast tomosynthesis (DBT) images in decisions to recall women during mammogram interpretation. MATERIALS AND METHODS: Verbal informed consent was obtained for this HIPAA-compliant institutional review board-approved protocol. Eight radiologists independently interpreted twice deidentified mammograms obtained in 153 women (age range, 37-83 years; mean age, 53.7 years ± 9.3 [standard deviation]) in a mode by reader by case-balanced fully crossed study. Each study consisted of current and prior full-field digital mammography (FFDM) images and DBT images that were acquired in our facility between June 2009 and January 2013. For one reading, sequential ratings were provided by using (a) current FFDM images only, (b) current FFDM and DBT images, and (c) current FFDM, DBT, and prior FFDM images. The other reading consisted of (a) current FFDM images only, (b) current and prior FFDM images, and (c) current FFDM, prior FFDM, and DBT images. Fifty verified cancer cases, 60 negative and benign cases (clinically not recalled), and 43 benign cases (clinically recalled) were included. Recall recommendations and interaction between the effect of prior FFDM and DBT images were assessed by using a generalized linear model accounting for case and reader variability. RESULTS: Average recall rates in noncancer cases were significantly reduced with the addition of prior FFDM images by 34% (145 of 421) and 32% (106 of 333) without and with DBT images, respectively (P < .001). However, this recall reduction was achieved at the cost of a corresponding 7% (23 of 345) and 4% (14 of 353) reduction in sensitivity (P = .006). In contrast, availability of DBT images resulted in a smaller reduction in recall rates (false-positive interpretations) of 19% (76 of 409) and 26% (71 of 276) without and with prior FFDM images, respectively (P = .001). Availability of DBT images resulted in 4% (15 of 338) and 8% (25 of 322) increases in sensitivity, respectively (P = .007). The effects of the availability of prior FFDM images or DBT images did not significantly change regardless of the sequence in presentation (P = .81 and P = .47 for specificity and sensitivity, respectively). CONCLUSION: The availability of prior FFDM or DBT images is a largely independent contributing factor in reducing recall recommendations during mammographic interpretation.

Ultrasound Guided Core Biopsy versus Fine Needle Aspiration for Evaluation of Axillary Lymphadenopathy in Patients with Breast Cancer.

Rationale and Objectives. To compare the sensitivities of ultrasound guided core biopsy and fine needle aspiration (FNA) for detection of axillary lymph node metastases in patients with a current diagnosis of ipsilateral breast cancer. Materials and Methods. From December 2008 to December 2010, 105 patients with breast cancer and abnormal appearing lymph nodes in the ipsilateral axilla consented to undergo FNA of an axillary node immediately followed by core biopsy of the same node, both with ultrasound guidance. Experienced pathologists evaluated the aspirate cytology without knowledge of the core histology. Cytology and core biopsy results were compared to sentinel node excision or axillary dissection pathology. Sensitivities were compared using McNemar's test. Results. Of 70 patients with axillary node metastases, FNA was positive in 55/70 (78.6%) and core was positive in 61/70 (87.1%) (P = 0.18). The FNA and core results were discordant in 14/70 (20%) patients. Ten cases were FNA negative/core positive. Four cases were FNA positive/core negative. Conclusion. Core biopsy detected six (8.6%) more cases of metastatic lymphadenopathy than FNA but the difference in sensitivities was not statistically significant. Core biopsy should be considered if the node is clearly imaged and readily accessible. FNA is a good alternative when a smaller needle is desired due to node location or other patient factors. This trial is registered with NCT01920139.