Impact of a Categorical AI System for Digital Breast Tomosynthesis on Breast Cancer Interpretation by Both General Radiologists and Breast Imaging Specialists.

Purpose To evaluate performance improvements of general radiologists and breast imaging specialists when interpreting a set of diverse digital breast tomosynthesis (DBT) examinations with the aid of a custom-built categorical artificial intelligence (AI) system. Materials and Methods A fully balanced multireader, multicase reader study was conducted to compare the performance of 18 radiologists (nine general radiologists and nine breast imaging specialists) reading 240 retrospectively collected screening DBT mammograms (mean patient age, 59.8 years ± 11.3 [SD]; 100% women), acquired between August 2016 and March 2019, with and without the aid of a custom-built categorical AI system. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity across general radiologists and breast imaging specialists reading with versus without AI were assessed. Reader performance was also analyzed as a function of breast cancer characteristics and patient subgroups. Results Every radiologist demonstrated improved interpretation performance when reading with versus without AI, with an average AUC of 0.93 versus 0.87, demonstrating a difference in AUC of 0.06 (95% CI: 0.04, 0.08; P < .001). Improvement in AUC was observed for both general radiologists (difference of 0.08; P < .001) and breast imaging specialists (difference of 0.04; P < .001) and across all cancer characteristics (lesion type, lesion size, and pathology) and patient subgroups (race and ethnicity, age, and breast density) examined. Conclusion A categorical AI system helped improve overall radiologist interpretation performance of DBT screening mammograms for both general radiologists and breast imaging specialists and across various patient subgroups and breast cancer characteristics. Keywords: Computer-aided Diagnosis, Screening Mammography, Digital Breast Tomosynthesis, Breast Cancer, Screening, Convolutional Neural Network (CNN), Artificial Intelligence Supplemental material is available for this article. © RSNA, 2024.

Key Challenges and Recommendations for In Vitro Testing of Tobacco Products for Regulatory Applications: Consideration of Test Materials and Exposure Parameters.

The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to identify, discuss and develop recommendations for optimal scientific and technical approaches for conducting in vitro assays, to assess potential toxicity within and across tobacco and various next generation nicotine and tobacco products (NGPs), including heated tobacco products (HTPs) and electronic nicotine delivery systems (ENDS). The third workshop (24-26 February 2020) summarised the key challenges and made recommendations concerning appropriate methods of test article generation and cell exposure from combustible cigarettes, HTPs and ENDS. Expert speakers provided their research, perspectives and recommendations for the three basic types of tobacco-related test articles: i) pad-collected material (PCM); ii) gas vapour phase (GVP); and iii) whole smoke/aerosol. These three types of samples can be tested individually, or the PCM and GVP can be combined. Whole smoke/aerosol can be bubbled through media or applied directly to cells at the air-liquid interface. Summaries of the speaker presentations and the recommendations developed by the workgroup are presented. Following discussion, the workshop concluded the following: that there needs to be greater standardisation in aerosol generation and collection processes; that methods for testing the NGPs need to be developed and/or optimised, since simply mirroring cigarette smoke testing approaches may be insufficient; that understanding and quantitating the applied dose is fundamental to the interpretation of data and conclusions from each study; and that whole smoke/aerosol approaches must be contextualised with regard to key information, including appropriate experimental controls, environmental conditioning, analytical monitoring, verification and performance criteria.

Key challenges for in vitro testing of tobacco products for regulatory applications: Recommendations for dosimetry.

The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to develop recommendations for optimal scientific and technical approaches for conducting in vitro assays to assess potential toxicity within and across tobacco and various next-generation products (NGPs) including heated tobacco products (HTPs) and electronic nicotine delivery systems (ENDSs). This publication was developed by a working group of the workshop members in conjunction with the sixth workshop in that series entitled "Dosimetry for conducting in vitro evaluations" and focuses on aerosol dosimetry for aerosol exposure to combustible cigarettes, HTP, and ENDS aerosolized tobacco products and summarizes the key challenges as well as documenting areas for future research.

In vitro evaluation of mutagenic, cytotoxic, genotoxic and oral irritation potential of nicotine pouch products.

Non-clinical in vitro studies were conducted to investigate the characteristics of extracts from tobacco free nicotine pouches alongside a reference snus product and/or 1R6F reference cigarette. In vitro investigations were conducted in the Neutral Red Uptake (NRU) cytotoxicity assay, Bacterial Reverse Mutation (Ames) assay, and in vitro Mammalian Cell Micronucleus (ivMN) assay. These products were also investigated for their oral irritation potential in the EpiGingival™ 3D tissue model. Results from the Ames, in vitro Micronucleus and NRU assays indicated that the tested products were non-mutagenic, non-genotoxic and non-cytotoxic in contrast to results obtained for the 1R6F reference cigarette. Results from Complete Artificial Saliva (CAS) extracts from these products also failed to be classified as irritants (as measured using the MTT assay), in the EpiGingival™ 3D tissue model.

Use of new approach methodologies (NAMs) to meet regulatory requirements for the assessment of tobacco and other nicotine-containing products.

Regulatory frameworks on tobacco and other nicotine-containing products (TNCP) continue to evolve as novel products emerge, including electronic nicotine delivery systems (e.g., electronic cigarettes or vaping products), heated tobacco products, or certain smokeless products (e.g., nicotine pouches). This article focuses on selected regulations for TNCPs that do not make health claims, and on the opportunities to use new approach methodologies (NAMs) to meet regulatory requirements for toxicological information. The manuscript presents a brief overview of regulations and examples of feedback from regulatory agencies whilst highlighting NAMs that have been successfully applied, or could be used, in a regulatory setting, either as stand-alone methods or as part of a weight-of-evidence approach to address selected endpoints. The authors highlight the need for agencies and stakeholders to collaborate and communicate on the development and application of NAMs to address specific regulatory toxicological endpoints. Collaboration across sectors and geographies will facilitate harmonized use of robust testing approaches to evaluate TNCPs without animal testing.

Use of new approach methodologies (NAMs) to meet regulatory requirements for the assessment of industrial chemicals and pesticides for effects on human health.

New approach methodologies (NAMs) are increasingly being used for regulatory decision making by agencies worldwide because of their potential to reliably and efficiently produce information that is fit for purpose while reducing animal use. This article summarizes the ability to use NAMs for the assessment of human health effects of industrial chemicals and pesticides within the United States, Canada, and European Union regulatory frameworks. While all regulations include some flexibility to allow for the use of NAMs, the implementation of this flexibility varies across product type and regulatory scheme. This article provides an overview of various agencies' guidelines and strategic plans on the use of NAMs, and specific examples of the successful application of NAMs to meet regulatory requirements. It also summarizes intra- and inter-agency collaborations that strengthen scientific, regulatory, and public confidence in NAMs, thereby fostering their global use as reliable and relevant tools for toxicological evaluations. Ultimately, understanding the current regulatory landscape helps inform the scientific community on the steps needed to further advance timely uptake of approaches that best protect human health and the environment.

Comparison of Abbreviated Breast MRI vs Digital Breast Tomosynthesis for Breast Cancer Detection Among Women With Dense Breasts Undergoing Screening.

Importance: Improved screening methods for women with dense breasts are needed because of their increased risk of breast cancer and of failed early diagnosis by screening mammography. Objective: To compare the screening performance of abbreviated breast magnetic resonance imaging (MRI) and digital breast tomosynthesis (DBT) in women with dense breasts. Design, Setting, and Participants: Cross-sectional study with longitudinal follow-up at 48 academic, community hospital, and private practice sites in the United States and Germany, conducted between December 2016 and November 2017 among average-risk women aged 40 to 75 years with heterogeneously dense or extremely dense breasts undergoing routine screening. Follow-up ascertainment of cancer diagnoses was complete through September 12, 2019. Exposures: All women underwent screening by both DBT and abbreviated breast MRI, performed in randomized order and read independently to avoid interpretation bias. Main Outcomes and Measures: The primary end point was the invasive cancer detection rate. Secondary outcomes included sensitivity, specificity, additional imaging recommendation rate, and positive predictive value (PPV) of biopsy, using invasive cancer and ductal carcinoma in situ (DCIS) to define a positive reference standard. All outcomes are reported at the participant level. Pathology of core or surgical biopsy was the reference standard for cancer detection rate and PPV; interval cancers reported until the next annual screen were included in the reference standard for sensitivity and specificity. Results: Among 1516 enrolled women, 1444 (median age, 54 [range, 40-75] years) completed both examinations and were included in the analysis. The reference standard was positive for invasive cancer with or without DCIS in 17 women and for DCIS alone in another 6. No interval cancers were observed during follow-up. Abbreviated breast MRI detected all 17 women with invasive cancer and 5 of 6 women with DCIS. Digital breast tomosynthesis detected 7 of 17 women with invasive cancer and 2 of 6 women with DCIS. The invasive cancer detection rate was 11.8 (95% CI, 7.4-18.8) per 1000 women for abbreviated breast MRI vs 4.8 (95% CI, 2.4-10.0) per 1000 women for DBT, a difference of 7 (95% CI, 2.2-11.6) per 1000 women (exact McNemar P = .002). For detection of invasive cancer and DCIS, sensitivity was 95.7% (95% CI, 79.0%-99.2%) with abbreviated breast MRI vs 39.1% (95% CI, 22.2%-59.2%) with DBT (P = .001) and specificity was 86.7% (95% CI, 84.8%-88.4%) vs 97.4% (95% CI, 96.5%-98.1%), respectively (P < .001). The additional imaging recommendation rate was 7.5% (95% CI, 6.2%-9.0%) with abbreviated breast MRI vs 10.1% (95% CI, 8.7%-11.8%) with DBT (P = .02) and the PPV was 19.6% (95% CI, 13.2%-28.2%) vs 31.0% (95% CI, 17.0%-49.7%), respectively (P = .15). Conclusions and Relevance: Among women with dense breasts undergoing screening, abbreviated breast MRI, compared with DBT, was associated with a significantly higher rate of invasive breast cancer detection. Further research is needed to better understand the relationship between screening methods and clinical outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02933489.

Chemical analysis and in vitro toxicological evaluation of aerosol from a novel tobacco vapor product: A comparison with cigarette smoke.

The recent rapid increase in the prevalence of emerging tobacco- and nicotine-containing products, such as e-cigarettes, is being driven in part by their reduced-risk potential compared to tobacco smoking. In this study, we examined emission levels for selected cigarette smoke constituents, so-called "Hoffmann analytes", and in vitro toxicity of aerosol from a novel tobacco vapor product (NTV). The NTV thermally vaporizes a nicotine-free carrier liquid to form an aerosol which then passes through tobacco, where it absorbs tobacco-derived flavors and nicotine. The NTV results were compared with those for 3R4F cigarette smoke. Chemical analysis of the NTV aerosol demonstrated that Hoffmann analyte levels were substantially lower than in 3R4F smoke and that the most were below quantifiable levels. Results from in vitro bacterial reverse mutation, micronucleus and neutral red uptake assays showed that, in contrast with 3R4F smoke, the NTV aerosol failed to demonstrate any measurable genotoxicity or cytotoxicity. The temperature of tobacco during NTV use was measured at approximately 30 °C, which may explain the lower Hoffmann analyte emission and in vitro toxicity levels. These results suggest that the aerosol from the NTV has a very different toxicological profile when compared with combustible cigarette smoke.

Clinical Performance of Synthesized Two-dimensional Mammography Combined with Tomosynthesis in a Large Screening Population.

Purpose To compare the clinical performance of synthesized two-dimensional (s2D) mammography combined with digital breast tomosynthesis (DBT) with that of full-field digital mammography (FFDM) alone and FFDM combined with DBT in a large community-based screening population by analyzing recall rate, positive predictive value, and cancer detection rate. Materials and Methods This was a retrospective study approved by the institutional review board and was HIPAA compliant with waiver of informed consent. A total of 78 810 screening mammograms from October 11, 2011, to June 30, 2016, were retrospectively collected. Of these, 32 076 were FFDM, 30 561 were DBT-FFDM, and 16 173 were DBT-s2D mammograms. Diagnostic performance of FFDM, DBT-FFDM, and DBT-s2D mammography was compared. Statistical significance was determined by using the Pearson χ2 test and was expressed as odds ratios and related confidence intervals determined by means of logistic regression analysis with pairwise comparisons. Results Recall rates were significantly lower with DBT-s2D mammography (4.3%, 687 of 16 173) when compared with DBT-FFDM (5.8%, 1785 of 30 561; odds ratio, 0.72; 95% confidence interval: 0.65, 0.78; P < .0001) and when compared with FFDM alone (8.7%, 2799 of 32 076; odds ratio, 0.46; 95% confidence interval: 0.43, 0.51). The cancer detection rate was similar among FFDM alone (5.3 of 1000 screening examinations), DBT-FFDM (6.4 of 1000 screening examinations), and DBT-s2D mammography (6.1 of 1000 screening examinations) with no significant difference (FFDM vs DBT-FFDM, P = .08; FFDM vs DBT-s2D, P = .27). The percentage of invasive cancers detected was significantly higher with DBT-s2D mammography (76.5%) than with DBT-FFDM (61.3%, P = .01), and positive predictive values with DBT-s2D mammography (40.8%) were significantly higher than those with DBT-FFDM (28.5%, P < .0001). Conclusion Screening with DBT-s2D mammography in a large community-based practice improved recall rate and positive predictive values without loss of cancer detection rate when compared with DBT-FFDM and FFDM alone. © RSNA, 2017.