A Deep Learning Decision Support Tool to Improve Risk Stratification and Reduce Unnecessary Biopsies in BI-RADS 4 Mammograms.

Purpose: To evaluate the performance of a biopsy decision support algorithmic model, the intelligent-augmented breast cancer risk calculator (iBRISK), on a multicenter patient dataset. Materials and Methods: iBRISK was previously developed by applying deep learning to clinical risk factors and mammographic descriptors from 9700 patient records at the primary institution and validated using another 1078 patients. All patients were seen from March 2006 to December 2016. In this multicenter study, iBRISK was further assessed on an independent, retrospective dataset (January 2015-June 2019) from three major health care institutions in Texas, with Breast Imaging Reporting and Data System (BI-RADS) category 4 lesions. Data were dichotomized and trichotomized to measure precision in risk stratification and probability of malignancy (POM) estimation. iBRISK score was also evaluated as a continuous predictor of malignancy, and cost savings analysis was performed. Results: The iBRISK model's accuracy was 89.5%, area under the receiver operating characteristic curve (AUC) was 0.93 (95% CI: 0.92, 0.95), sensitivity was 100%, and specificity was 81%. A total of 4209 women (median age, 56 years [IQR, 45-65 years]) were included in the multicenter dataset. Only two of 1228 patients (0.16%) in the "low" POM group had malignant lesions, while in the "high" POM group, the malignancy rate was 85.9%. iBRISK score as a continuous predictor of malignancy yielded an AUC of 0.97 (95% CI: 0.97, 0.98). Estimated potential cost savings were more than $420 million. Conclusion: iBRISK demonstrated high sensitivity in the malignancy prediction of BI-RADS 4 lesions. iBRISK may safely obviate biopsies in up to 50% of patients in low or moderate POM groups and reduce biopsy-associated costs.Keywords: Mammography, Breast, Oncology, Biopsy/Needle Aspiration, Radiomics, Precision Mammography, AI-augmented Biopsy Decision Support Tool, Breast Cancer Risk Calculator, BI-RADS 4 Mammography Risk Stratification, Overbiopsy Reduction, Probability of Malignancy (POM) Assessment, Biopsy-based Positive Predictive Value (PPV3) Supplemental material is available for this article. Published under a CC BY 4.0 license.See also the commentary by McDonald and Conant in this issue.

Real-World Perspectives and Practices for Pneumonitis/Interstitial Lung Disease Associated With Trastuzumab Deruxtecan Use in Human Epidermal Growth Factor Receptor 2-Expressing Metastatic Breast Cancer.

Trastuzumab deruxtecan (T-DXd) is an antibody drug conjugate with a topoisomerase I payload that targets the human epidermal growth factor receptor 2 (HER2). T-DXd is approved for patients with previously treated HER2-positive or HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/ISH-) metastatic/unresectable breast cancer (BC). In a second-line HER2-positive metastatic BC (mBC) population (DESTINY-Breast03 [ClinicalTrials.gov identifier: NCT03529110]), T-DXd demonstrated significantly improved progression-free survival (PFS) over ado-trastuzumab emtansine (12-month rate: 75.8% v 34.1%; hazard ratio, 0.28; P < .001), and in patients with HER2-low mBC treated with one prior line of chemotherapy (DESTINY-Breast04 [ClinicalTrials.gov identifier: NCT03734029]), T-DXd demonstrated significantly longer PFS and overall survival than physician's choice chemotherapy (10.1 v 5.4 months; hazard ratio, 0.51; P < .001, and 23.4 v 16.8 months; hazard ratio, 0.64; P < .001, respectively).Interstitial lung disease (ILD) is an umbrella term used for a group of diseases characterized by lung injury including pneumonitis, which can lead to irreversible lung fibrosis. ILD is a well-described adverse event associated with certain anticancer therapies, including T-DXd. An important part of T-DXd therapy for mBC consists of monitoring for and managing ILD. Although information on ILD management strategies is included in the prescribing information, additional information on patient selection, monitoring, and treatment can be beneficial in routine clinical practice. The objective of this review is to describe real-world, multidisciplinary clinical practices and institutional protocols used for patient selection/screening, monitoring, and management related to T-DXd-associated ILD.

Cancer.

Malignancy is the second leading cause of death in the United States, following heart disease. In most cancers, early detection is one of the most important factors in determining prognosis. As clinicians it is therefore important to be aware of potential clues of underlying malignancy on physical examination. Given the wide range of malignancies, and the heterogeneous nature of their presentations, this article is by no means exhaustive. Instead, it discusses in depth some of the more frequently encountered physical examination findings that may suggest malignancy. Specifically, it covers lymphadenopathy, cutaneous findings related to various cancers, and malignancy related thrombosis.

The association between time-of-day of habitual exercise training and changes in relevant cancer health outcomes among cancer survivors.

OBJECTIVE: To assess the relationship between time-of-day of exercise training and changes in relevant cancer health outcomes among cancer survivors. METHODS: Retrospective analysis of data collected from 2016-2019 from a hospital-based exercise oncology program. Descriptive statistics were calculated for demographic, clinical, and exercise timing characteristics (e.g. AM, PM, or mix) among survivors with available data for exercise training time (n = 233). For the total sample and a breast cancer sub-analysis, univariate analysis of covariance, adjusted for age, was carried out by exercise training time, for change in the following outcomes collected during the program's assessment sessions: cardiorespiratory fitness and muscular endurance (human performance variables), physical function, anthropometrics, self-reported fatigue, and quality of life (QoL). Change in body mass index (BMI) and body weight was included in the breast cancer analysis. RESULTS: Overall, 37.3% of survivors habitually engaged in AM exercise (e.g. ≥ 75% AM training), 34.3% in PM exercise, and 28.3% in a mix of AM and PM exercise training throughout the program. Median time in the program was 17 weeks. Significant improvements in most human performance and physical function variables were observed in the total sample regardless of exercise training time-of-day. Among breast cancer survivors, PM but not AM or mixed was associated with improvements in fitness, and lower-body muscular endurance and function. Mixed exercise timing was linked with greater increase in waist circumference (total sample: 3.02cm, 95%CI 1.55, 4.49; breast cancer: 3.57cm 95%CI 0.96, 6.18), body weight (breast cancer: 1.6kg, 95%CI 0.3, 2.8) and BMI (breast cancer: 0.6kg/m2, 95%CI 0.1, 1.0). AM and PM exercise, but not mixed, was associated with improvements in fatigue and QoL. CONCLUSION: Time-of-day of exercise training may differentially impact changes in human performance and physical function variables. Mixed exercise training time may result in less favorable outcomes related of weight management variables among cancer survivors.

A Phase 1 dose-escalation study of disulfiram and copper gluconate in patients with advanced solid tumors involving the liver using S-glutathionylation as a biomarker.

BACKGROUND: Disulfiram and metals inactivate key oncoproteins resulting in anti-neoplastic activity. The goal of this study was to determine the maximum tolerated dose of copper when administered with disulfiram in patients with advanced solid tumors and liver involvement. METHODS: Disulfiram 250 mg was administered daily in 28-day cycles. Four doses of copper gluconate were tested (2, 4, 6, and 8 mg of elemental copper) in a standard 3 + 3 dose escalation design. Patients were evaluated for dose limiting toxicities and response. Protein S-glutathionylation was evaluated as a pharmacodynamic marker. RESULTS: Twenty-one patients were enrolled and 16 patients were evaluable for dose limiting toxicities. Among the 21 patients, there was a median of 4 lines of prior chemotherapy. Five Grade 3 toxicities were observed (anorexia, elevated aspartate aminotransferase or AST, elevated alkaline phosphatase, fever, and fatigue). Response data was available for 15 patients. Four patients had stable disease with the longest duration of disease control being 116 days. The median duration of treatment for evaluable patients was 55 days (range 28-124). Reasons for discontinuation included functional decline, disease progression, and disease-associated death. Increased S-glutathionylation of serum proteins was observed with treatment. CONCLUSION: Disulfiram 250 mg daily with copper gluconate (8 mg of elemental copper) was well-tolerated in patients with solid tumors involving the liver and was not associated with dose limiting toxicities. While temporary disease stabilization was noted in some patients, no objective responses were observed. Treatment was associated with an increase in S-glutathionylation suggesting that this combination could exert a suppressive effect on cellular growth and protein function. TRIAL REGISTRATION: NCT00742911 , first posted 28/08/2008.

Novel Preoperative Patient-centered Surgical Wellness Program Impacts Length of Stay Following Pancreatectomy.

BACKGROUND/AIM: We created a novel, preoperative wellness program (WP) that promotes recovery. This study assessed its impact on patient outcomes after pancreatectomy. PATIENTS AND METHODS: Pancreatoduodenectomies (PD) and distal pancreatectomies (DP) performed from 2015 to 2018 were reviewed using our institutional NSQIP database. Patients in the WP had their medical conditions optimized and were provided with the following: chlorhexidine, topical mupirocin, incentive spirometer, and immune-nutrition supplements. RESULTS: Out of a total of 669 pancreatectomy patients (411 PD, 258 DP), 308 were enrolled in the WP (188 PD, 120 DP). In the PD subgroup, on multivariable analysis (MVA), the WP patients had shorter lengths of hospital stay (LOS) (12 vs. 10 days, p<0.001). On MVA, WP patients had less post-op transfusion (20 vs. 10%, p=0.027). For the combined groups on MVA, LOS continued to be significant (OR=0.89, 95%CI=0.82-0.97, p<0.007). CONCLUSION: A preoperative patient centered WP may reduce the length of stay.

Impact of a Novel Preoperative Patient-centered Surgical Wellness Program.

OBJECTIVE: The objective of this study was to evaluate if a preoperative wellness bundle significantly decreases the risk of hospital acquired infections (HAI). BACKGROUND: HAI threaten patient outcomes and are a significant burden to the healthcare system. Preoperative wellness efforts may significantly decrease the risk of infections. METHODS: A group of 12,396 surgical patients received a wellness bundle in a roller bag during preoperative screening at an urban academic medical center. The wellness bundle consisted of a chlorhexidine bath solution, immuno-nutrition supplements, incentive spirometer, topical mupirocin for the nostrils, and smoking cessation information. Study staff performed structured patient interviews, observations, and standardized surveys at key intervals throughout the perioperative period. Statistics compare HAI outcomes of patients in the wellness program to a nonintervention group using the Fisher's exact test, logistic regression, and Poisson regression. RESULTS: Patients in the nonintervention and intervention groups were similar in demographics, comorbidity, and type of operations. Compliance with each element was high (80% mupirocin, 72% immuno-nutrition, 71% chlorhexidine bath, 67% spirometer). The intervention group had statistically significant reductions in surgical site infections, Clostridium difficile, catheter associated urinary tract infections, and patient safety indicator 90. CONCLUSIONS: A novel, preoperative, patient-centered wellness program dramatically reduced HAI in surgical patients at an urban academic medical center.

Description of Mexican Cleft Surgeons' Experience With Foreign Surgical Volunteer Missions in Mexico.

BACKGROUND AND PURPOSE: Mexican cleft surgeons provide multidisciplinary comprehensive cleft lip and palate care to children in Mexico. Many Mexican cleft surgeons have extensive experience with foreign, visiting surgeons. The purpose of this study was to characterize Mexican cleft surgeons' domestic and volunteer practice and to learn more about Mexican cleft surgeons' experience with visiting surgeons. METHODS: A cross-sectional validated e-mail survey tool was sent to Mexican cleft surgeons through 2 Mexican plastic surgery societies and the Asociación Mexicana de Labio y Paladar Hendido y Anomalías Craneofaciales, the national cleft palate society that includes plastic and maxillofacial surgeons who specialize in cleft surgery. We utilized validated survey methodology, including neutral fact-based questions and repeated e-mails to survey nonresponders to maximize validity of statistical data; response rate was 30.6% (n = 81). RESULTS: Mexican cleft surgeons performed, on average, 37.7 primary palate repairs per year with an overall complication rate of 2.5%; 34.6% (n = 28) of respondents had direct experience with patients operated on by visiting surgeons; 53.6% of these respondents performed corrective surgery because of complications from visiting surgeons. Respondents rated 48% of the functional outcomes of visiting surgeons as "acceptable," whereas 43% rated aesthetic outcomes of visiting surgeons as "poor"; 73.3% of respondents were never paid for the corrective surgeries they performed. Thirty-three percent of Mexican cleft surgeons believe that there is a role for educational collaboration with visiting surgeons. CONCLUSIONS: Mexican cleft surgeons have a high volume of primary cleft palate repairs in their domestic practice with good outcomes. Visiting surgeons may play an important role in Mexican cleft care through educational collaborations that complement the strengths of Mexican cleft surgeons.

Predictors, Quality Markers, and Economics of Volunteering Internationally: Results from a Comprehensive Survey of American Society of Plastic Surgeons Members.

BACKGROUND: Plastic surgeons have a long history of international volunteer work. To date, there have been no outcome-based studies among surgeons who volunteer internationally. The purpose of this study was to describe predictors of volunteering, clinical quality markers, and economics of international volunteering among American plastic surgeons. METHODS: A cross-sectional validated e-mail survey tool was sent to all board-certified plastic surgeons by the American Society of Plastic Surgeons. The survey response rate was 15 percent (745 total individuals), of which 283 respondents traveled within the past 5 years. Analysis was performed in R. Stepwise multivariate logistic regression was performed to determine the predictors of death/complication. RESULTS: Respondents reported high use of medical records, follow-up care, and host affiliation. Fewer than half of all respondents reported use of international safety surgery guidelines, and the majority of respondents reported volunteering abroad outside of their scope of practice. The majority of children younger than 5 years were not cared for by a pediatric anesthesiologist. The majority of participants reported personally spending more than $1000 on their last trip and performing surgery estimated to be worth on average $28,000 each. CONCLUSIONS: International surgical volunteer trips attempt to ease the global burden of surgical disease. The authors' study reports variation in quality of care provided on these trips. Most significantly, the majority of children younger than 5 years were not cared for by a pediatric anesthesiologist, and many plastic surgeons operated outside of their scope of practice.