Mixed-Methods Study to Predict Upstaging of DCIS to Invasive Disease on Mammography.

BACKGROUND. The incidence of ductal carcinoma in situ (DCIS) has steadily increased, as have concerns regarding overtreatment. Active surveillance is a novel treatment strategy that avoids surgical excision, but identifying patients with occult invasive disease who should be excluded from active surveillance is challenging. Radiologists are not typically expected to predict the upstaging of DCIS to invasive disease, though they might be trained to perform this task. OBJECTIVE. The purpose of this study was to determine whether a mixed-methods two-stage observer study can improve radiologists' ability to predict upstaging of DCIS to invasive disease on mammography. METHODS. All cases of DCIS calcifications that underwent stereotactic biopsy between 2010 and 2015 were identified. Two cohorts were randomly generated, each containing 150 cases (120 pure DCIS cases and 30 DCIS cases upstaged to invasive disease at surgery). Nine breast radiologists reviewed the mammograms in the first cohort in a blinded fashion and scored the probability of upstaging to invasive disease. The radiologists then reviewed the cases and results collectively in a focus group to develop consensus criteria that could improve their ability to predict upstaging. The radiologists reviewed the mammograms from the second cohort in a blinded fashion and again scored the probability of upstaging. Statistical analysis compared the performances between rounds 1 and 2. RESULTS. The mean AUC for reader performance in predicting upstaging in round 1 was 0.623 (range, 0.514-0.684). In the focus group, radiologists agreed that upstaging was better predicted when an associated mass, asymmetry, or architectural distortion was present; when densely packed calcifications extended over a larger area; and when the most suspicious features were focused on rather than the most common features. Additionally, radiologists agreed that BI-RADS descriptors do not adequately characterize risk of invasion, and that microinvasive disease and smaller areas of DCIS will have poor prediction estimates. Reader performance significantly improved in round 2 (mean AUC, 0.765; range, 0.617-0.852; p = .045). CONCLUSION. A mixed-methods two-stage observer study identified factors that helped radiologists significantly improve their ability to predict upstaging of DCIS to invasive disease. CLINICAL IMPACT. Breast radiologists can be trained to better predict upstaging of DCIS to invasive disease, which may facilitate discussions with patients and referring providers.

Performance of preoperative breast MRI based on breast cancer molecular subtype.

PURPOSE: To assess the performance of preoperative breast MRI biopsy recommendations based on breast cancer molecular subtype. METHODS: All preoperative breast MRIs at a single academic medical center from May 2010 to March 2014 were identified. Reports were reviewed for biopsy recommendations. All pathology reports were reviewed to determine biopsy recommendation outcomes. Molecular subtypes were defined as Luminal A (ER/PR+ and HER2-), Luminal B (ER/PR+ and HER2+), HER2 (ER-, PR- and HER2+), and Basal (ER-, PR-, and HER2-). Logistic regression assessed the probability of true positive versus false positive biopsy and mastectomy versus lumpectomy. RESULTS: There were 383 patients included with a molecular subtype distribution of 253 Luminal A, 44 Luminal B, 20 HER2, and 66 Basal. Two hundred and thirteen (56%) patients and 319 sites were recommended for biopsy. Molecular subtype did not influence the recommendation for biopsy (p = 0.69) or the number of biopsy site recommendations (p = 0.30). The positive predictive value for a biopsy recommendation was 42% overall and 46% for Luminal A, 43% for Luminal B, 36% for HER2, and 29% for Basal subtype cancers. The multivariate logistic regression model showed no difference in true positive biopsy rate based on molecular subtype (p = 0.78). Fifty-one percent of patients underwent mastectomy and the multivariate model demonstrated that only a true positive biopsy (odds ratio: 5.3) was associated with higher mastectomy rates. CONCLUSION: Breast cancer molecular subtype did not influence biopsy recommendations, positive predictive values, or surgical approaches. Only true positive biopsies increased the mastectomy rate.

Predicting Upstaging of DCIS to Invasive Disease: Radiologists's Predictive Performance.

RATIONALE AND OBJECTIVES: The purpose of this study is to quantify breast radiologists' performance at predicting occult invasive disease when ductal carcinoma in situ (DCIS) presents as calcifications on mammography and to identify imaging and histopathological features that are associated with radiologists' performance. MATERIALS AND METHODS: Mammographically detected calcifications that were initially diagnosed as DCIS on core biopsy and underwent definitive surgical excision between 2010 and 2015 were identified. Thirty cases of suspicious calcifications upstaged to invasive ductal carcinoma and 120 cases of DCIS confirmed at the time of definitive surgery were randomly selected. Nuclear grade, estrogen and progesterone receptor status, patient age, calcification long axis length, and breast density were collected. Ten breast radiologists who were blinded to all clinical and pathology data independently reviewed all cases and estimated the likelihood that the DCIS would be upstaged to invasive disease at surgical excision. Subgroup analysis was performed based on nuclear grade, long axis length, breast density and after exclusion of microinvasive disease. RESULTS: Reader performance to predict upstaging ranged from an area under the receiver operating characteristic curve (AUC) of 0.541-0.684 with a mean AUC of 0.620 (95%CI: 0.489-0.751). Performances improved for lesions smaller than 2 cm (AUC: 0.676 vs 0.500; p = 0.002). The exclusion of microinvasive cases also improved performance (AUC: 0.651 vs 0.620; p = 0.005). There was no difference in performance based on breast density (p = 0.850) or nuclear grade (p = 0.270) CONCLUSION: Radiologists were able to predict invasive disease better than chance, particularly for smaller DCIS lesions (<2 cm) and after the exclusion of microinvasive disease.

A Simulation Paradigm for Evaluation of Subtle Liver Lesions at Pediatric CT: Performance and Confidence.

Purpose: To create and validate a systematic observer performance platform for evaluation of simulated liver lesions at pediatric CT and to test this paradigm to measure the effect of radiation dose reduction on detection performance and reader confidence. Materials and Methods: Thirty normal pediatric (from patients aged 0-10 years) contrast material-enhanced, de-identified abdominal CT scans obtained from July 1, 2012, through July 1, 2016, were retrospectively collected from the clinical database. The study was exempt from institutional review board approval. Zero to three simulated, low-contrast liver lesions (≤6 mm) were digitally inserted by using software, and noise was added to simulate reductions in volume CT dose index (representing radiation dose estimation) of 25% and 50%. Pediatric, abdominal, and resident radiologists (three of each) reviewed 90 data sets in three sessions using an online interface, marking each lesion location and rating confidence (scale, 0-100). Statistical analysis was performed by using software. Results: Mixed-effects models revealed a significant decrease in detection sensitivity as radiation dose decreased (P < .001). The mean confidence of the full-dose and 25% dose reduction examinations was significantly higher than that of the 50% dose reduction examinations (P = .011 and .012, respectively) but not different from one another (P = .866). Dose was not a significant predictor of time to complete each case, and subspecialty was not a significant predictor of sensitivity or false-positive results. Conclusion: Sensitivity for lesion detection significantly decreased as dose decreased; however, confidence did not change between the full-dose and 25% reduced-dose scans. This suggests that readers are unaware of this decrease in performance, which should be accounted for in clinical dose reduction efforts.Keywords: Abdomen/GI, CT, Liver, Observer Performance, Pediatrics, Perception Image© RSNA, 2019.

Evaluation of Acute Abdominal Pain in the Emergency Setting Using Computed Tomography Without Oral Contrast in Patients With Body Mass Index Greater Than 25.

PURPOSE: To evaluate the rate of delayed or missed diagnoses and need for additional computed tomography (CT) imaging in emergency department patients with abdominal pain who are imaged without oral contrast. MATERIALS AND METHODS: The institutional review board approved this Health Insurance Portability and Accountability Act-compliant retrospective study; informed consent was waived. All consecutive adult patients with body mass index greater than 25 undergoing a CT abdomen/pelvis with intravenous contrast and without oral contrast with nontraumatic acute abdominal pain during a 16-month period at our academic tertiary care center were included. Medical records were reviewed, imaging findings on admission CT, use of repeat CT examinations within 4 weeks of the original examination, and clinical outcomes were recorded. In patients undergoing repeat imaging, an investigator determined whether repeat imaging was influenced by the lack of oral contrast on the original examination. As the most common cause of bowel-related positive CT scans, an analysis of acute appendicitis was performed. RESULTS: Of the 1992 patients included in this study, 4 patients (0.2%) underwent repeat CT studies directly related to the absence of oral contrast on the original examination. Of the 1992 CT scans, 1193(59.8%) were interpreted as negative, none of which required surgery or direct intervention. In patients with acute appendicitis, there was a sensitivity of CT in this patient population of 100% with a specificity of 99.5%. CONCLUSIONS: In patients with body mass index greater than 25 presenting to the ED with acute abdominal pain, CT examinations can be acquired without oral contrast without compromising the clinical efficacy of CT.

Anti-breast cancer effects of histone deacetylase inhibitors and calpain inhibitor.

Development of new breast cancer therapies is needed, particularly as cells become refractory or develop increased drug resistance. In an effort to develop such treatments, class I and II histone deacetylases (HDACs), alone and in combination with other cytotoxic agents, are currently in clinical trial. Herein, we discuss the effects of histone deacetylase inhibitors (HDACi) when used in combination with calpeptin, an inhibitor of the regulatory protease, calpain. We present results of study in two breast cancer cells lines with distinct characteristics: MDA-MB-231 and MCF-7. When used in combination with calpeptin, two chemically distinct HDACi significantly inhibited growth and increased cell death by inducing cell-cycle arrest and apoptosis. MCF-7 cells exhibited a greater proportion of arrest at the G(1) phase, whereas triple-negative MDA-MB-231 cells exhibited increased cell cycle arrest at the S phase. Methylation of the imprinted and silenced proapoptoic tumor suppressor gene aplasia Ras homolog member I (ARHI) was reduced in both cell lines after treatment with HDACi. However, it was only re-expressed on such treatment in MDA-MB-231 cells, suggesting that re-expression operates under differential mechanisms in these two cell lines. Collectively, these results showed that the combination of HDACi and calpeptin inhibited the growth of two distinctly different types of breast cancer cells and could have wide clinical applications, though the mechanisms of inhibition are possibly different.