Citations

Abstract Background High mammographic breast density is the primary reason for missed cancers or delayed detection on mammography, and is associated with a higher rate of advanced and interval cancers which increase breast cancer mortality. Digital breast tomosynthesis (DBT) has been shown to reduce false positive findings relative to 2D mammography but does not eliminate the potential for tumor masking in dense breasts due to the similar x-ray attenuation characteristics of tumors and normal fibroglandular tissue. Molecular Breast Imaging (MBI) performed with a dedicated gamma camera to detect functional uptake of a radiotracer, Tc-99m sestamibi, has been shown to reveal breast cancers obscured by density on mammography. In single-institution studies, adding MBI to 2D mammography in women with dense breasts detected an additional 5 to10 invasive cancers per 1000 screened, with modest increases in recall rate (6 to 8%) at a lower cost-per-cancer detected than mammography alone. Despite this promising evidence, the lack of multicenter trial data has limited wider acceptance. Also, MBI has yet to be compared to DBT, which in some centers has replaced 2D mammography screening. We present interim results from a multicenter trial comparing cancer detection rate of DBT and MBI in screening of women with mammographically dense breasts. Methods In this ongoing, prospective, multicenter clinical trial, asymptomatic women aged 40-75 years with dense breasts on prior mammogram and no prior history of supplemental screening are invited to undergo two annual rounds of concurrent DBT and MBI. MBI is performed with injection of 300 MBq Tc-99m sestamibi with a dual-head semiconductor-based gamma camera. Screening tests are interpreted independently. Here, preliminary cancer detection rates (cancers per 1000 women screened), recall rates, and biopsy rates of DBT and MBI for initial screening are reported. Results In 537 women out of a planned 3000 who have completed the first round of screening, 7 cancers were detected: one by DBT only and 6 by MBI only, giving cancer detection rates of 1.9 for DBT vs. 11.2 for MBI and incremental cancer detection rate of 9.3 for MBI. The one DBT-only cancer was a node-negative 0.8 cm invasive lobular carcinoma. All 6 cancers detected by MBI were invasive; 5 of 6 were node negative (median size 1.0 cm; range 0.6 to 2.6 cm). Recall rate was 11% (60/537) for DBT alone; 16% (84/537) for MBI alone, and 21% (115/537) for the combination. Biopsy was prompted by DBT in 13 patients (PPV 8% [1/13]); by MBI in 23 patients (PPV 26% [6/23]); and by the combination of modalities in 33 (PPV 21% [7/33]). Conclusion These preliminary results demonstrate that MBI detects invasive breast cancers occult on DBT in dense breasts. Data from a second screening round will allow calculation of sensitivity and specificity, and determination of the impact of screening MBI in reducing advanced (> 2 cm) and interval cancers. Additional planned analyses will evaluate a denoising algorithm for further reduction in MBI radiation dose to match that of DBT. Citation Format: Rhodes D, Hunt K, Conners A, Zingula S, Whaley D, Ellis R, Gasal Spilde J, Mehta R, Polley M-Y, O'Connor M, Hruska C. Molecular breast imaging and tomosynthesis to eliminate the reservoir of undetected cancer in dense breasts: The Density MATTERS trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD4-05.

Abstract Despite improvements in outcomes in the last few decades for heart failure (HF) with reduced ejection fraction (HFrEF), there still remains a need for novel therapies as many patients incompletely recover with existing therapies and progress to advanced HF. In this review, we will discuss recent advances in the management of HFrEF with a focus on upcoming therapies that hold the greatest promise for clinical use. We will discuss novel pharmacological therapies and areas of uncertainty with existing therapies. We will also discuss the potential utility and controversy surrounding novel interventions for HF such as percutaneous mitral valve repair, atrial fibrillation ablation, and other emerging interventions with positive signals for benefit in HFrEF. Finally, we will summarize the current state of stem cell and gene therapy for HFrEF and future directions.

Objective This study aims for targeted biopsy validation of magnetic resonance fingerprinting (MRF) and diffusion mapping for characterizing peripheral zone (PZ) prostate cancer and noncancers. Materials and Methods One hundred four PZ lesions in 85 patients who underwent magnetic resonance imaging were retrospectively analyzed with apparent diffusion coefficient (ADC) mapping, MRF, and targeted biopsy (cognitive or in-gantry). A radiologist blinded to pathology drew regions of interest on targeted lesions and visually normal peripheral zone on MRF and ADC maps. Mean T1, T2, and ADC were analyzed using linear mixed models. Generalized estimating equations logistic regression analyses were used to evaluate T1 and T2 relaxometry combined with ADC in differentiating pathologic groups. Results Targeted biopsy revealed 63 cancers (low-grade cancer/Gleason score 6 = 10, clinically significant cancer/Gleason score ≥7 = 53), 15 prostatitis, and 26 negative biopsies. Prostate cancer T1, T2, and ADC (mean ± SD, 1660 ± 270 milliseconds, 56 ± 20 milliseconds, 0.70 × 10−3 ± 0.24 × 10−3 mm2/s) were significantly lower than prostatitis (mean ± SD, 1730 ± 350 milliseconds, 77 ± 36 milliseconds, 1.00 × 10−3 ± 0.30 × 10−3 mm2/s) and negative biopsies (mean ± SD, 1810 ± 250 milliseconds, 71 ± 37 milliseconds, 1.00 × 10−3 ± 0.33 × 10−3 mm2/s). For cancer versus prostatitis, ADC was sensitive and T2 specific with comparable area under curve (AUC; (AUCT2 = 0.71, AUCADC = 0.79, difference between AUCs not significant P = 0.37). T1 + ADC (AUCT1 + ADC = 0.83) provided the best separation between cancer and negative biopsies. Low-grade cancer T2 and ADC (mean ± SD, 75 ± 29 milliseconds, 0.96 × 10−3 ± 0.34 × 10−3 mm2/s) were significantly higher than clinically significant cancers (mean ± SD, 52 ± 16 milliseconds, 0.65 ± 0.18 × 10−3 mm2/s), and T2 + ADC (AUCT2 + ADC = 0.91) provided the best separation. Conclusions T1 and T2 relaxometry combined with ADC mapping may be useful for quantitative characterization of prostate cancer grades and differentiating cancer from noncancers for PZ lesions seen on T2-weighted images.

AbstractBackgroundLittle research has been done in teledermatology to examine the effects of standardized templates and subject‐specific learning modules.MethodsWe performed a prospective study examining the effects of standardized templates and standardized cutaneous oncology learning modules on teledermatology referrals at Mayo Clinic. This data was then compared to previous teledermatology referrals before standardized templates were adopted.ResultsA total of 42 teledermatology consultations were performed during the 4‐month study period. The use of standardized templates resulted in an absolute reduction in face‐to‐face referrals. Teledermatology consultation increased the absolute diagnostic and management concordance by 26.2% (P = 0.02) and 33.3% (P < 0.01), respectively, and decreased the absolute diagnostic and management discordance by 19.1% (P = 0.03) and 31.0% (P < 0.01), respectively. The largest knowledge gaps were identified in cutaneous oncology. Educational intervention improved theoretical referral rates and confidence in diagnosis and management overall.ConclusionThe implementation of standardized intake templates reduces the rate of face‐to‐face referrals. Teledermatology improves primary care‐based dermatological care and reduces theoretical referral rates.

PURPOSE Background parenchymal uptake (BPU), which describes the level of radiotracer uptake in normal fibroglandular tissue on molecular breast imaging (MBI), has been identified as a breast cancer risk factor. Our objective was to develop and validate a deep learning model using image convolution to automatically categorize BPU on MBI. METHODS MBI examinations obtained for clinical and research purposes from 2004 to 2015 were reviewed to classify the BPU pattern using a standardized five-category scale. Two expert radiologists provided interpretations that were used as the reference standard for modeling. The modeling consisted of training and validating a convolutional neural network to predict BPU. Model performance was summarized in data reserved to test the performance of the algorithm at the per-image and per-breast levels. RESULTS Training was performed on 24,639 images from 3,133 unique patients. The model performance on the withheld testing data (6,172 images; 786 patients) was evaluated. Using direct matching on the predicted classification resulted in an accuracy of 69.4% (95% CI, 67.4% to 71.3%), and if prediction within one category was considered, accuracy increased to 96.0% (95% CI, 95.2% to 96.7%). When considering the breast-level prediction of BPU, the accuracy remained strong, with 70.3% (95% CI, 68.0% to 72.6%) and 96.2% (95% CI, 95.3% to 97.2%) for the direct match and allowance for one category, respectively. CONCLUSION BPU provided a robust target for training a convolutional neural network. A validated computer algorithm will allow for objective, reproducible encoding of BPU to foster its integration into risk-stratification algorithms.

How dipeptide repeats cause pathology A repeat expansion in the chromosome 9 open reading frame 72 ( C9orf72 ) gene is the most common known cause of two neurodegenerative diseases: frontotemporal dementia and amyotrophic lateral sclerosis. This expansion leads to the abnormal production of proteins of repeating dipeptides, but their contribution to disease pathogenesis remains unclear. Zhang et al. engineered a mouse model to study the consequences of one of these dipeptides—prolinearginine dipeptide repeat protein, poly(PR)—in the brain. They found that poly(PR) caused neuron loss as well as motor and memory impairments. These detrimental effects resulted from poly(PR)-induced perturbation of heterochromatin function, a tightly packed form of DNA that represses gene expression. Science , this issue p. eaav2606