Nationwide Analysis of Locoregional Management for Ductal Carcinoma In Situ in Males: An NCDB Analysis of the Surgical Approach to DCIS in Males.

BACKGROUND: Limited data exist regarding the optimal locoregional approach for males with ductal carcinoma in situ (DCIS). This study examined trends in management and survival for males with DCIS. METHODS: The National Cancer Database (NCDB) was queried for males with a diagnosis of DCIS from 2006 to 2017. Patients were categorized by locoregional management. Continuous variables were evaluated by Kruskal-Wallis and categorical variables by chi-square or Fisher's exact test. Univariable and multivariable logistic regressions were performed to evaluate for predictors of patients receiving partial mastectomy (PM) with radiation. Survival was analyzed by Kaplan-Meier. RESULTS: Between 2006 and 2017, 711 males with DCIS were identified. Most received mastectomy alone (57.1%). No change was observed in management approach from 2006 to 2017. Patients who underwent mastectomy alone were mostly hormone-positive (95.9% were estrogen-positive, 90.9% were progesterone-positive), although this cohort was least likely to receive hormone therapy (17.2%). Among those who underwent PM with radiation, only 61% of those who were hormone-positive received hormone therapy. Univariable analysis demonstrated that those of black race had lower odds of receiving PM with radiation (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.36-0.84), which persisted in the multivariable analysis with control for age and tumor size (OR, 0.32; 95% CI, 0.15-0.67). Overall survival did not differ significantly between the four treatment methods (p = 0.08). CONCLUSIONS: The management approach to male DCIS did not change from 2006 to 2017. Survival did not differ between treatment methods. Demographic and clinicopathologic features, including race, may influence locoregional treatments received, and further studies are needed to further understand this.

Food and Drug Administration Public Workshop Summary-Development Considerations of Antifungal Drugs to Address Unmet Medical Need.

Pressing challenges in the treatment of invasive fungal infections (IFIs) include emerging and rare pathogens, resistant/refractory infections, and antifungal armamentarium limited by toxicity, drug-drug interactions, and lack of oral formulations. Development of new antifungal drugs is hampered by the limitations of the available diagnostics, clinical trial endpoints, prolonged trial duration, difficulties in patient recruitment, including subpopulations (eg, pediatrics), and heterogeneity of the IFIs. On 4 August 2020, the US Food and Drug Administration convened a workshop that included IFI experts from academia, industry, and other government agencies to discuss the IFI landscape, unmet need, and potential strategies to facilitate the development of antifungal drugs for treatment and prophylaxis. This article summarizes the key topics presented and discussed during the workshop, such as incentives and research support for drug developers, nonclinical development, clinical trial design challenges, lessons learned from industry, and potential collaborations to facilitate antifungal drug development.

FDA Public Workshop Summary-Coccidioidomycosis (Valley Fever): Considerations for Development of Antifungal Drugs.

Coccidioidomycosis is a fungal disease endemic to the southwestern United States, Mexico, and Central and South America. Prevalence rates are increasing steadily, and new endemic areas of Coccidioides are emerging. Standard treatment is often administered for months to decades, and intolerance to medications and treatment failures are common. No new treatments for coccidioidomycosis have been approved in the United States in nearly 40 years. On 5 August 2020, the US Food and Drug Administration convened experts in coccidioidomycosis from academia, industry, patient groups, and other government agencies to discuss the disease landscape and strategies to facilitate product development for treatment of coccidioidomycosis. This article summarizes the key topics concerning drug development for coccidioidomycosis presented by speakers and panelists during the workshop, such as unmet need, trial designs, endpoints, incentives, research and development support, and collaborations to facilitate antifungal drug development.

Heterogeneity within molecular subtypes of breast cancer.

Breast cancer is the quintessential example of how molecular characterization of tumor biology guides therapeutic decisions. From the discovery of the estrogen receptor to current clinical molecular profiles to evolving single-cell analytics, the characterization and compartmentalization of breast cancer into divergent subtypes is clear. However, competing with this divergent model of breast cancer is the recognition of intratumoral heterogeneity, which acknowledges the possibility that multiple different subtypes exist within a single tumor. Intratumoral heterogeneity is driven by both intrinsic effects of the tumor cells themselves as well as extrinsic effects from the surrounding microenvironment. There is emerging evidence that these intratumoral molecular subtypes are not static; rather, plasticity between divergent subtypes is possible. Interconversion between seemingly different subtypes within a tumor drives tumor progression, metastases, and treatment resistance. Therapeutic strategies must, therefore, contend with changing phenotypes in an individual patient's tumor. Identifying targetable drivers of molecular heterogeneity may improve treatment durability and disease progression.

Effect of Body Weight and Age on the Pharmacokinetics of Dihydroartemisinin: Food and Drug Administration Basis for Dose Determination of Artesunate for Injection in Pediatric Patients With Severe Malaria.

For treatment of severe malaria, the World Health Organization recommends 3 mg/kg intravenous artesunate in pediatric patients weighing less than 20 kg. Here we describe the Food and Drug Administration's rationale for selecting 2.4 mg/kg in pediatric patients weighing less than 20 kg based on literature review and independent analyses.

National trends for axillary lymph node dissection and survival outcomes for clinical T3/T4 node-negative breast cancer patients undergoing mastectomy with positive lymph nodes.

PURPOSE: Previous studies have suggested axillary lymph node dissection (ALND) can be omitted in early breast cancer patients undergoing mastectomy with positive lymph nodes (LNs). We assessed the national utilization of ALND and overall survival (OS) for larger, locally advanced tumors in patients undergoing mastectomy with positive LNs. METHODS: The National Cancer Database from 2006 to 2016 was queried for mastectomy patients with clinical T3/T4, N0 tumors, and 1-2 positive LNs. Trends and outcomes for ALND were compared to sentinel lymph node biopsy (SLNB) alone. RESULTS: Thousand nine hundred and seventeen women were included. The proportion of ALND decreased from 70% pre-Z0011 to 52% post-Z0011. On Kaplan-Meier analysis, ALND had better OS compared to SLNB alone (p < 0.01). On multivariate analysis, age (p < 0.01), chemotherapy (p < 0.01), and hormonal therapy (p < 0.01) were associated with better OS. In patients who received adjuvant radiation therapy (ART) ALND improved OS on multivariate analysis (p < 0.01). CONCLUSION: This is the first large database study to demonstrate a national trend to forego ALND in mastectomy patients with large or locally advanced tumors (T3/T4abc) and 1-2 positive lymph nodes. This study suggests a survival benefit for ALND, particularly in patients receiving ART. Careful consideration and further investigations should be performed prior to omitting ALND this patient population.

Trends and Outcomes Associated With Axillary Management of Males With Clinical N0 Breast Cancer-An NCDB Analysis.

BACKGROUND: Sentinel Lymph Node Biopsy (SLNB) is standard of care for women with clinically N0 breast cancer. However, there are no randomized controlled studies in men determining optimal surgical axillary management. METHODS: Using the National Cancer Database, males diagnosed from 2006-2016 with clinical T1-4 N0 tumors treated with primary surgery were identified and categorized by axillary management. Clinicopathologic variables were compared between two timeframes, 2006-2011 and 2012-2016. Survival analysis was performed. RESULTS: We identified 2,646 males meeting criteria. Use of SLNB increased (65.9%-72.8%, P < 0.01). For those who underwent ALND, administration of radiation (31.1% versus 48.8%, P < 0.01) and endocrine therapy (70.2% versus 80.7%, P < 0.01) increased. There was no difference in survival between timeframes (P = 0.42). For those who underwent SLNB, tumor grade (P = 0.02) and pathologic T stage (P < 0.01) were higher and more patients underwent mastectomy (74.9% versus 79.4%, P = 0.02). Administration of chemotherapy decreased (35.1% versus 27.2%, P < 0.01) and endocrine therapy increased (72.1% versus 81.3%, P < 0.01). Survival of those who underwent sentinel lymph node biopsy (SLNB) diagnosed 2012-2016 was worse than those diagnosed 2006-2011 (P = 0.01). CONCLUSIONS: Use of SLNB alone has increased while ALND has declined in males with clinically N0 breast cancer. However, patients who underwent SLNB alone in the later time period had worse clinical characteristics and experienced differences in adjuvant therapy. This suggests increased acceptance of the use of SLNB for axillary management. Further analysis is warranted to evaluate methods of axillary staging and the impact on outcomes in males with breast cancer.

National Trend of Axillary Management in Clinical T3/T4 N0 Patients Having Breast Conserving Therapy.

BACKGROUND: The ACOSOG Z0011 trial has essentially eliminated axillary lymph node dissection (ALND) in breast conserving therapy (BCT) patients with clinical T1/T2 and 1-2 positive sentinel lymph nodes (SLNs). Currently, ALND is recommended for positive SLNs unless ACOSOG Z0011 criteria are applicable. We aimed to assess the national trends and axillary management before and after the publication of ACOSOG Z0011 for larger tumors. METHODS: An IRB-approved study evaluated the National Cancer Database from 2006 to 2016. Women with clinical T3/T4, N0 who otherwise fit ACOSOG Z0011 criteria were included. Neoadjuvant systemic therapy or known nodal disease was excluded. Clinicopathologic data were compared between two timeframes based on ACOSOZ Z0011 publication and by axillary management. Patients were categorized into SLNB alone (1-5 lymph nodes examined) and ALND (≥10 lymph nodes examined) groups. RESULTS: A total of 230 women fit inclusion criteria, of whom 36% underwent ALND. ALND use decreased from 54% in 2006 to 14% in 2016 (P < 0.01). Comparing ALND to SLNB alone within the pre-Z0011 era, comprehensive community cancer programs had higher proportions of ALND, whereas academic centers had higher rates of SLND alone (P = 0.03). Comparing similar axillary management between eras, SLNB-alone patients in the post-Z0011 era had higher pT and pN stages, were less likely to be Her2 positive, and were more likely to receive systemic treatment. CONCLUSIONS: There is a national trend to forgo ALND in women who have tumors larger than those included in the Z0011 criteria without any clear clinicopathologic indications.

Screening of populations at high risk for breast cancer.

The approach to screening patients at high risk for breast cancer has thus far been challenging to standardize, given limited high-level evidence in this population. The approach has evolved given the development of more effective screening modalities, including digital breast mammography, magnetic resonance imaging, and other emerging technologies. This review will discuss identification of high-risk patients, approaches to genetic counseling and testing, and evidence behind screening modalities and algorithms in this special population.

Reaching Spanish-speaking smokers online: a 10-year worldwide research program.

OBJECTIVE: To describe a 10-year proof-of-concept smoking cessation research program evaluating the reach of online health interventions throughout the Americas. METHODS: Recruitment occurred from 2002 - 2011, primarily using Google.com AdWords. Over 6 million smokers from the Americas entered keywords related to smoking cessation; 57 882 smokers (15 912 English speakers and 41 970 Spanish speakers) were recruited into online self-help automated intervention studies. To examine disparities in utilization of methods to quit smoking, cessation aids used by English speakers and Spanish speakers were compared. To determine whether online interventions reduce disparities, abstinence rates were also compared. Finally, the reach of the intervention was illustrated for three large Spanish-speaking countries of the Americas-Argentina, Mexico, and Peru-and the United States of America. RESULTS: Few participants had utilized other methods to stop smoking before coming to the Internet site; most reported using no previous smoking cessation aids: 69.2% of Spanish speakers versus 51.8% of English speakers (P < 0.01). The most used method was nicotine gum, 13.9%. Nicotine dependence levels were similar to those reported for in-person smoking cessation trials. Overall observed quit rate for English speakers was 38.1% and for Spanish speakers, 37.0%; quit rates in which participants with missing data were considered to be smoking were 11.1% and 10.6%, respectively. Neither comparison was significantly different. CONCLUSIONS: The systematic use of evidence-based Internet interventions for health problems could have a broad impact throughout the Americas, at little or no cost to individuals or to ministries of health.

Breast infections: A review of current literature.

Breast infections are common, affect women of all ages, and are associated with significant morbidity. Despite overall prevalence, treatment varies significantly based on provider or institution and no central treatment guidelines exist to direct the management of breast infections. This article provides a summary of the current trends in management of breast infections. The etiology, epidemiology, risk factors, presentation, diagnosis, and treatment of mastitis and breast abscesses (and their relative subdivisions) are explored based on the current literature. Trends in microbiology are reviewed and an approach to antibiotic coverage is proposed. Overall, there is a lack of randomized-controlled trials focused on the treatment of breast infections. This has resulted in an absence of clinical practice guidelines for the management of breast abscesses and variable practice patterns. The development of best-care protocols or pathways could provide more uniformity in care of breast infections.

Evaluation of the SmartClip™ Nonradioactive Seed, a Novel Wireless Localization Method for the Breast: Initial Clinical Experience and Surgical Outcome.

INTRODUCTION: Wire localization has been the gold standard for breast localization of non-palpable lesions for decades. This technique remains robust but has disadvantages relative to scheduling, complications of vasovagal reactions in placement, wire migration, or transection. With more modern technologies available, several implantable markers have been developed to allow uncoupling of localization by radiology and the surgical procedure on the same day. This study summarizes our experience with the EnVisio Navigation System™ utilizing SmartClip™ as the implantable tissue localization marker. METHODS: An IRB-approved retrospective database of benign and malignant breast disease was used to perform a review of 100 consecutive patients who underwent SmartClip™ localized breast and axillary procedures in 2021. Demographic information, localization accuracy, associated surgical procedure(s) with resultant pathology findings, margin status for malignancies, and re-excision rate were collected. RESULTS: The localized breast lesion or lymph node was excised and SmartClip™ retrieved in all cases, confirmed by intraoperative specimen radiograph. The distribution of gender and race/ethnicity among the patients who underwent surgery reflects the community population and frequency of breast cancer development among men versus women. 45.1% of the cases involved malignancy, as determined pre-operatively. Positive margins requiring re-excision constituted 18.2% of cases. In twenty-six patients, two or three SmartClips™ were placed per case for either a bracketed lesion, two separate breast lesions, and/or a breast lesion and lymph node. CONCLUSION: Although this study is limited in patient number, it demonstrates safety of this technique and its reliability in guiding the surgeon directly to the lesion(s) of concern.

Axillary management in breast cancer after neoadjuvant chemotherapy in the modern era: A national cancer database analysis.

BACKGROUND: Axillary management for node-positive breast cancer continues to evolve. Data further supporting targeted axillary dissection after neoadjuvant chemotherapy was published in 2016 and may have induced changes in practice. METHODS: Patients included in the National Cancer Database from 2014 to 2017 with clinical T1 to T4 and node-positive disease who underwent neoadjuvant chemotherapy before surgical axillary management were evaluated. Patients were divided into the following 3 groups: selective axillary dissection, minimal axillary dissection, and maximal axillary dissection, according to surgical axillary management and pathological node status. RESULTS: Patients who underwent selective axillary dissection were younger (52.4 years ± 12.4, P < .0001) compared to maximal axillary dissection (55.1 ± 12.7) and minimal axillary dissection (54.6 ± 12.7). Patients with higher clinical stage more frequently underwent maximal axillary dissection, and those with lower tumor grade more frequently underwent minimal axillary dissection (P < .0001). Community cancer programs were more likely to perform maximal axillary dissection compared to all other types of programs and had the slowest rate of adoption of selective axillary dissection. Integrated Network Cancer Programs had the lowest proportion of maximal axillary dissection performed and the highest proportion of selective axillary dissection. Uninsured patients were more likely to receive maximal axillary dissection, and those with private insurance were more likely to undergo selective axillary dissection (P < .0001). Selective axillary dissection rates increased from 29.8% of procedures in 2016 to 41.5% in 2017, and MaxAD rates decreased from 62.4% in 2016 to 47.9% in 2017. CONCLUSION: Utilization of selective axillary dissection has increased since 2016; however, discrepancies in surgical axillary management after neoadjuvant chemotherapy still exist.

Incidence and predictors of neuropathic pain following breast surgery.

PURPOSE: Neuropathic pain (NPP) following breast surgery extends morbidity in the postoperative period. The incidence and etiology of postoperative NPP remains unclear and under-reported in literature. This study aims to define the incidence of neuropathic pain following breast surgery and to identify patient characteristics that are predictors for developing postoperative NPP. METHODS: Consecutive female patients undergoing breast resection surgery over a 5-year period (2008-2012) with 1-year minimum follow-up were included in this single-center study. Retrospective chart review was performed to identify patient specific characteristics including the development of post-operative NPP. Data was analyzed using univariate and multivariate logistic regression. RESULTS: A total of 470 patients were identified for study inclusion. The incidence of postoperative NPP was 14.7 % (69 of 470). Significant predictors for the development of postoperative NPP in the univariate analyses included history of diabetes mellitus, diabetic neuropathy, or fibromyalgia, concomitant axillary surgery, axillary node dissection, and taxane-based chemotherapy regimen. Multivariate analysis identified African American race [odds ratio (OR) = 1.78; 95 % CI = 1.01-3.17; p = 0.05), history of diabetes mellitus (OR = 1.98; 95 % CI = 1.0-3.74; p = 0.01) or fibromyalgia (OR = 2.75; 95 % CI = 1.13-6.69; p = 0.03), and taxane-based chemotherapy regimen (OR = 2.85; 95 % CI = 1.23-6.58; p = 0.01) as being independently associated with the development of postoperative NPP. CONCLUSIONS: NPP is a significant risk following breast surgery. African American race, history of either diabetes mellitus or fibromyalgia, and treatment with taxane-based chemotherapy regimens are all associated with an increased risk of NPP.

The Factors That Influence Chemotherapy Exposure Among Nurses: An Integrative Review.

BACKGROUND: Exposure to chemotherapy is an occupational hazard predisposing nurses to severe health effects. The purpose of this integrative review was to identify the recent literature describing the risk factors for occupational exposure to chemotherapy among nurses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology was employed to conduct the review. The databases searched were Scopus, PubMed, and CINAHL using the search terms "chemotherapy," "drugs," "exposure," and "nurses." Included articles were published between January 2010 and February 2022, published in peer-reviewed journals for research conducted in the United States, and written in English language. Excluded articles were studies that did not involve nurses in their samples. Review articles, books, theses, and dissertations were excluded as well. The Johns Hopkins Nursing Evidence-Based Practice Model was used to assess the level of evidence from the reviewed studies. FINDINGS: Fourteen studies were included in this review. Ten studies were rated on Evidence Level III, two on Evidence Level II, one on Evidence Level I, and one on Evidence Level V. The main risk factors for occupational exposure were nurses' knowledge of chemotherapy handling guidelines, nurses' adherence to using the personal protective equipment, nurses' health beliefs regarding chemotherapy exposure, and workplace-related factors such as workload and managerial support. CONCLUSION: Addressing the identified risk factors would protect nurses from chemotherapy exposure. More research on nurses' health beliefs regarding chemotherapy exposure and the cues to adhere to chemotherapy handling guidelines in the work environment is needed.

Psychometric Testing of the Oncology Nurses Health Behaviors Determinants Scale: A Cross-Sectional Study.

OBJECTIVES: Adherence by oncology nurses to chemotherapy safe handling guidelines is essential to prevent hazards of chemotherapy exposure. A review of the literature revealed the need for an instrument with evidence of reliability and validity to measure factors influencing adherence to safe chemotherapy-handling guidelines among oncology nurses. The purpose of this study was to psychometrically test the Oncology Nurses' Health Behaviors Determinants Scale (HBDS-ON) that measures the mentioned factors. DATA SOURCES: Methodological research of a quantitative cross-sectional survey design was used. The study surveys were administered by email to a sample of 108 oncology nurses. Cronbach alpha, item analysis, exploratory factor analysis using principal axis factoring, and convergence validity testing were used to test reliability and validity. CONCLUSION: Factor analysis yielded six subscales, each having acceptable internal consistency reliability (Cronbach alpha between 0.70 and 0.88). The subscales included four oncology nurse health beliefs (perceived threat, benefits, barriers, and self-efficacy), cues to action, and personal protective equipment availability and accessibility. Convergence validity testing results support the Oncology Nurses Health Behaviors Determinant Scale (HBDS-ON) construct validity. Oncology nurses' self-efficacy to adherence to chemotherapy-handling guidelines, the perceived barriers to adhere to chemotherapy-handling guidelines, and cues to action are associated with adherence to chemotherapy-handling guidelines. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses' health beliefs, the cues to action, and personal protection equipment availability and accessibility are important determinants of nurses' adherence to chemotherapy-handling guidelines. The HBDS-ON is an instrument that has evidence of reliability and validity and could be used in practice to measure these determinants.

Lessons from other fields of medicine, Part 1: Breast cancer.

Through the understanding of multiple etiologies, pathologies, and disease progression trajectories, breast cancer shifted historically from a singular malignancy of the breast to a complex of molecular/biological entities, translating into individualized disease-modifying treatments. As a result, this led to various de-escalations of treatment compared with the gold standard in the era preceding systems biology: radical mastectomy. Targeted therapies have minimized morbidity from the treatments and mortality from the disease. Biomarkers further individualized tumor genetics and molecular biology to optimize treatments targeting specific cancer cells. Landmark discoveries in breast cancer management have evolved through histology, hormone receptors, human epidermal growth factor, single-gene prognostic markers, and multigene prognostic markers. Relevant to the reliance on histopathology in neurodegenerative disorders, histopathology evaluation in breast cancer can serve as a marker of overall prognosis rather than predict response to therapies. This chapter reviews the successes and failures of breast cancer research through history, with focus on the transition from a universal approach for all patients to divergent biomarker development and individualized targeted therapies, discussing future areas of growth in the field that may apply to neurodegenerative disorders.

Outcomes of a pilot virtual mentorship program for medical students interested in surgery.

BACKGROUND: Lack of mentorship may deter medical students who identify as underrepresented minorities (URM) from entering academic surgery. METHODS: 30 mentor-medical student pairs from the AWS 2020 virtual mentorship pilot-program were surveyed pre-and post-program to explore 1) feasibility of meetings, and, 2) program's perceived efficacy in fostering professional development skills. Participants responded using a 5-point Likert scale (1 = not at all; 5 = completely). Proportions of participants in each category were compared. RESULTS: Proportion of participants perceiving monthly meetings to be completely feasible did not differ from pre-to post-program surveys for mentees (75%(21/28) vs. 71%(12/17); p = 0.743) or mentors (71%(17/24) vs 71%(13/18); p = 1.00). Compared to pre-program responses, mentees endorsed "completely" (Likert scale 5) improving with regard to their elevator speech (p = 0.001), developing their curriculum vitae (p = 0.003), ability to network (p = 0.021), and acquiring skills for career advancement (p = 0.003). CONCLUSION: Virtual mentorship may be a feasible and effective means of increasing access to mentors for URM medical students.

Exploiting the advantages of a wireless seed localization system that differentiates between the seeds: Breast cancer resection following neoadjuvant chemotherapy.

BACKGROUND: Most wireless localization methods utilize only one means of detection for the surgeon, sufficient to localize a single small breast lesion for excision. Complex cases requiring bracketing of a larger lesion or localization of two or more close lesions can superimpose the signal from separate "seeds" with such methods. The lack of discernment between the localization "seeds" can disorient the surgeon, risking a missed lesion on excision and longer operative times. with the use of neoadjuvant chemotherapy prior to breast surgery, the necessity of localizing both a breast lesion and an axillary lymph node previously biopsied is becoming frequent. CASE: A 44 year-old woman underwent neoadjuvant chmotherapy for a breast cancer the did not express estrogen receptor, progesterone receptor, or HER2 receptor. In establishing the extent of disease, a suspicious ipsilateral lymph node was biopsied and found to contain metastatic disease. She had an excellent response to the chemotherapy, with decreased size of the primary tumor and the previously biopsied lymph node. The patient desired breast conservation. The primary tumor and associated calcifications were bracketed using two different Smartclips™, with a third localizing the lymph node biopsied. CONCLUSION: This report illustrates how the use of three SmartClips™, within the EnVisioTM system, allowed for separate tracking of each "seed" throughout a complex surgery in a patient following neoadjuvant chemotherapy. This resulted in successful resection of both the tumor and the tagged lymph node.