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A strong organizational culture begins with leadership who create systems and structures to support safety and well-being of staff. The purpose of this article is to provide direction for nursing leaders on resources and actionable items to support staff who have been involved in challenging encounters with patient behavior. Staff needs are impacted not only by the situation but also by available on-the-job support and leadership respect for staff’s individual judgment. Postsituation support from both leaders and peers offer a protective effect against negative outcomes from adverse experiences. Ultimately, staff preferences for specific resources are individual and best determined through private conversation with their leadership. Given the unique nature of each situation, taking into account patient intentions and staff perceptions, it is important to offer flexible and actionable measures for staff managing challenging patient behaviors.

Importance Total thyroidectomy is the established surgical standard for hereditary and sporadic medullary thyroid cancer (sMTC). However, for unilateral sporadic tumors, its benefit over lobectomy remains uncertain. Objective To compare oncologic outcomes between total thyroidectomy and lobectomy in patients with sMTC. Data Sources and Study Selection MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials were searched from inception to December 2025 to identify comparative studies on patients with sMTC who underwent total thyroidectomy or lobectomy. Data Extraction and Synthesis Reviewers working independently and in duplicate screened titles, abstracts, and full-text articles for eligibility using standardized instructions. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( PRISMA ) and Meta-Analysis of Observational Studies in Epidemiology ( MOOSE ) guidelines were used for reporting. Main Outcomes and Measures Primary outcomes were mortality, overall survival, structural recurrence, biochemical cure, and distant metastasis development. The secondary outcome was postoperative complications. Effect measures were calculated as odds ratios (ORs) or relative risks (RRs) with 95% CIs using a random-effects model. The risk of bias was assessed using the Newcastle-Ottawa Scale. Results Nine retrospective studies met inclusion criteria and comprised 1371 patients (295 of 397 patients [74.3%] with documented sex were female, and median age ranged from 45.0 to 58.2 years). A total of 531 patients (38.7%) underwent lobectomy and 840 (61.3%) underwent total thyroidectomy. Of 341 tumors, 280 (82.1%) lacked extrathyroidal extension, 284 of 401 tumors (70.8%) measured smaller than 2 cm (70.8%), and 197 of 343 tumors (57.4%) were node negative; central neck dissection was performed in 445 of 492 patients (90.4%). Multifocal disease was uncommon and reported in 30 of 330 patients (9.1%). Mortality did not differ at 5 years (RR, 0.30; 95% CI, 0.07-1.35) or beyond (RR, 1.00; 95% CI, 0.40-2.47). Overall survival at 5 years was similar (RR, 1.02; 95% CI, 0.94-1.11). Total thyroidectomy was not associated with lower structural recurrence rates at 5 years (OR, 0.45; 95% CI, 0.14-1.49), but it was associated beyond 5 years (OR, 7.26; 95% CI, 1.07-49.21). No differences were observed for biochemical cure at 5 years (OR, 0.86; 95% CI, 0.47-1.56) or beyond 5 years (OR, 0.87; 95% CI, 0.26-2.89). Distant metastasis development did not differ at 5 years (OR, 1.64; 95% CI, 0.09-31.52). Sensitivity analyses revealed no differences across any outcomes. Postoperative complications were more common in total thyroidectomy. Risk of bias was high in 4 studies, moderate in 4, and low in 1. Conclusions and Relevance Findings in this systematic review and meta-analysis, based on data from retrospective studies, suggest that thyroid lobectomy may be associated with oncologic outcomes comparable to total thyroidectomy in selected patients with sMTC.

PURPOSE The continuous development of new imaging approaches, molecular phenotyping, genetic subtypes, prognosis assessments, and effective therapies across a range of disease states has created a need to redefine terminology and best practices for clinical trial conduct in patients with advanced prostate cancer. Methods We convened an international expert committee of diverse working groups, the Prostate Cancer Working Group 4 (PCWG4), between 2016 and 2025. Our objective was to formulate updated criteria based on emerging evidence and clinical trial data in a biomarker context to provide guidance for clinical trial design, eligibility, and end point assessments for patients with advanced prostate cancer. RESULTS PCWG4 redefines terminology around the disease state and previous therapies in a patient-centric context and terminology focused on androgen pathway modulation. We consider imaging, with a particular focus on positron emission tomography (PET)–defined disease. New recommendations are provided for disease state terminology, defining eligibility criteria, response and delay/prevent end points, intervals for reassessments including imaging, and patient-reported outcome determination. We provide recommendations in a biomarker-based context of use for the intended indication, reflective of patient benefit for specific interventions. We emphasize the need for development of validated PET imaging and molecular and phenotypic criteria as well as trial designs to appropriately risk stratify patients, predict and assess benefit, and measure post-treatment outcomes reliably in a trial framework. CONCLUSION PCWG4 updates recommendations on patient and tumor characterization, therapy development, and imaging criteria and extends guidance into earlier androgen pathway modulator–naïve/sensitive disease states to reflect an evolving, heterogeneous, and diverse patient population to optimize treatment benefits for all patients.

BACKGROUND: Guidelines acknowledge that discordant low-gradient (LG) aortic stenosis (AS) may be severe, but verifying this can be challenging. Right heart catheterization during exercise is considered the gold standard for evaluating ventricular hemodynamics. No invasive studies have compared the hemodynamic response of discordant LG and severe AS during exercise. The aim of this observational study was to describe exercise hemodynamics in patients with asymptomatic discordant AS and left ventricular ejection fraction ≥50%. METHODS: Patients with aortic valve area ≤1.5 cm 2 underwent right heart catheterization at rest and during maximal exercise, measuring pulmonary capillary wedge pressure (PCWP), cardiac output (CO), and the PCWP/CO-slope. Patients were stratified into 3 groups: discordant LG AS (aortic valve area ≤1.0 cm 2 and mean gradient <40 mm Hg); moderate AS (aortic valve area >1.0 cm 2 ); and high-gradient (HG) severe AS (aortic valve area ≤1.0 cm 2 and mean gradient ≥40 mm Hg). RESULTS: Among 86 patients, 17 (20%) had discordant LG, 49 (57%) moderate, and 20 (23%) HG severe AS. The median PCWP/CO-slope was significantly steeper in discordant LG (3.3 [interquartile range, 2.1–4.3] mm Hg/L/min) and HG severe AS (2.7 [1.9–3.4] mm Hg/L per minute) compared with moderate AS (1.9 [0.7–2.8] mm Hg/L per minute), P =0.004. In a regression model adjusted for age, sex, and rest PCWP, systemic arterial compliance and AS severity were significantly associated with the PCWP/CO-slope. Furthermore, patients with discordant LG AS had a leftward-upward shift in the PCWP/CO-curve. CONCLUSIONS: Discordant LG and HG severe AS had similar hemodynamic responses to exercise with steeper PCWP/CO-slope than in moderate AS, suggesting that discordant LG AS is a severe form of AS. In addition, the left upwards shift in PCWP/CO-curve for discordant LG compared with HG severe AS indicates that this group also has heart failure with preserved ejection fraction physiology. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04913870 and NCT02395107.

Background: Blood-based biomarker panels, including GALAD, have been proposed as an alternative to abdominal ultrasound for hepatocellular carcinoma (HCC) surveillance. Studies suggest longitudinal evaluation of biomarkers can improve test performance; however, no large studies have validated these findings. Methods: We leveraged the HCC Early Detection Strategy (HEDS) study (n=1019 patients with cirrhosis; 99 incident HCC) and Texas HCC Consortium (THCCC) (n=2345 patients with cirrhosis; 126 incident HCC) to compare the performance of fixed-threshold GALAD (cutoff of −1.36), and 4 longitudinal algorithms: longitudinal GALAD, PALAD, mFB-ALAD, and mPEB-ALAD. The HEDS cohort was used to derive longitudinal algorithms, and external validation was performed in THCCC. Patient-level sensitivity and test-level false-positive rate (FPR) were examined overall and across subgroups by age, sex, and cirrhosis etiology. Results: In THCCC, fixed-threshold GALAD had higher sensitivity in the 6 months before HCC diagnosis (71.4%, 95% CI: 62.9%–81.7%) than longitudinal GALAD (55.1%, 95% CI: 49.3–66.4), PALAD (55.1%, 95% CI: 50.0%–70.5%), mPEB-ALAD (53.1%, 95% CI: 43.6%–62.0%), and mFB-ALAD (42.9%, 95% CI: 32.3–48.5). However, fixed-threshold GALAD had a higher FPR (25.4%, 95% CI: 23.7%–26.9%) compared with longitudinal GALAD (15.0%, 95% CI: 12.8%–15.8%), PALAD (13.0%, 95% CI: 10.2%–14.6%), and mFB-ALAD (11.2%, 95% CI: 9.6%–12.1%) but comparable to mPEB-ALAD (22.9%, 95% CI: 21.2%–23.8%). In subgroup analyses, fixed-threshold GALAD had the highest FPR in males (35.6%) and those aged ≥65 (43.5%); longitudinal algorithms had significantly lower FPRs in subgroups but with lower sensitivity for HCC. Conclusions: Improvements in FPRs with longitudinal GALAD algorithms, as compared with fixed-threshold GALAD, are offset by significantly decreased sensitivity for HCC detection.

Abstract Introduction Cancer clinical trials have historically faced challenges in achieving fully representative trial population, particularly in terms of including patients from diverse ethnic and racial groups, those with low socioeconomic status, and those living in rural regions. This has contributed to inequities in access to novel therapeutic options. Background The I-SPY adaptive platform trials have prioritized diversity since inception, consistently enrolling in &gt;10% of trial patients being Black and/or Hispanic individuals. The majority of participating institutions in the I-SPY 2.2 study are academic or large well-resourced health systems. In 2023, the I-SPY ACCESS (Achieving Cancer Clinical Trial Equity in Socioeconomically Diverse Sites) Initiative was launched to enhance representation by engaging and involving nontraditional trial sites- such as safety-net hospitals, community cancer centers, and rural cancer centers- that serve historically excluded patient populations. Methods The I-SPY ACCESS Initiative offers customized and personalized tailored support to under-resourced sites. This includes comprehensive feasibility and readiness assessments, onboarding guidance, enhanced site-specific training, centralized institutional review board (IRB) navigation, site peer mentorship, and educational materials for both patient and provider. Additionally, patients gain access to I-SPY advocate peer trial navigators. Sites are provided culturally responsive patient education tools- including multilingual brochures, a dedicated patient website, and content co-developed with community partners. A Clinical Trial Navigator supports both patients and sites, helping to locate logistical, social, and trial specific resources.Tools such as virtual Clinical Research Coordinators (vCRC's) and OneSource technology are deployed strategically based on assessed site need and resource availability. OneSource is an innovative platform that enables direct extraction of clinical data from electronic health records into trial databases, reducing site workload and improving data quality. Funding models are currently being explored to extend OneSource and vCRC services across more ACCESS sites. In the future, there are plans to pilot financial navigation services and integrative care resources for all patients enrolled in I-SPY with particular focus on those enrolled at ACCESS sites. Results and Progress As of June 2025, seven sites have been assessed as ACCESS sites for I-SPY 2.2, with two sites having successfully completed activation and currently enrolling participants. Beginning in mid-2024, one DCIS RECAST ACCESS site has been activated and 11 additional sites are in the onboarding process. The modest pace of I-SPY 2.2 activation reflects the complexity and operational demands associated with resource-intensive platform trial. In contrast, the DCIS RECAST protocol was designed with a lower burden, facilitating easier implementation by under-resourced sites, reflected by increased interest in the study among ACCESS sites. The ACCESS framework is being explored for potential future application in the Pre I-SPY Phase 1 platform trial, particularly considering the historical underrepresentation of such sites in the early-phase clinical research. Conclusion and Future Goals The I-SPY ACCESS initiative demonstrates that investing in thoughtful, innovative, and effective means for trial delivery, as well as incorporating community-based support, can strengthen representation in complex, adaptive breast cancer trials. The initiative offers a flexible, equity-driven framework that is impactful now and scalable for future innovation in oncology research. Citation Format: S. L. Horton, D. A. Idossa, K. C. Hewitt, J. Perlmutter, L. Van't Veer, N. Hylton, A. Borowsky, F. Symmans, D. Yee, C. Yau, P. Pohlmann, J. Boughey, L. Esserman. Expanding Diversity through Innovation: Development of the I-SPY ACCESS Initiative for the I-SPY2.2 and DCIS RECAST Clinical Trials [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-09-08.

Abstract Background: The Breast Cancer Index (BCI) is clinically validated to stratify patients with hormone receptor-positive (HR+), early-stage BC based on the risk of overall (0-10 years [y]) and late (5-10 y) distant recurrence (DR) with N0/N1 lymph node involvement. Validation of BCI in patients with HR+ HER2+ BC has been limited, especially in patients treated with adjuvant trastuzumab-based chemotherapy. The HOXB13 and IL17BR genes constitute the predictive component of BCI and are known to exhibit an ER-dependent correlation pattern with HER2. We evaluated the prognostic performance of BCI in patients with HR+ HER2+ disease enrolled in the NCCTG N9831 (Alliance) trial treated with the combination of chemotherapy and trastuzumab. Methods: All available tumor specimens from patients with HR+ HER2+ N0/N1 BC in arms B (sequential trastuzumab) and C (concurrent trastuzumab) of the trial were included. BCI testing was performed blinded to clinical outcomes. The primary endpoint was distant recurrence-free interval (DRFI). BCI (N0) and BCIN+ (N1) risk groups were calculated based on prespecified cut points. Kaplan-Meier analysis and log-rank testing were used to assess the prognostic significance of BCI/BCIN+ risk groups based on DR. Cox proportional hazard models with and without clinical covariates were used to estimate hazard ratios (HRs), and the associated 95% confidence intervals (CIs). Results: A total of 454 HR+ patients (234 arm B, 220 arm C), including 69 N0 and 385 N1 patients, were analyzed (median age was 47 y, 85% N1, 55% T2, 63% G3). BCIN+ scores were available for 378 of the 385 N1 patients due to missing tumor grade for 7 patients. The median follow-up was 12.7 years. In the overall cohort, BCI/BCIN+ stratified 51 (11%), 24 (5%) and 372 (83%) patients as low-, intermediate- and high-risk with 10-y DRFI rates of 96% (95% CI: 84-99%), 100% (100-100%) and 89% (86-92%), respectively. Since the low and intermediate risk groups had few patients and a similar risk of 10-y DRFI, they are combined into a single low-risk group hereafter. Thus, for overall 10-y DR, 75 (17%) and 372 (83%) of patients were classified by BCI/BCIN+ as low and high risk with 10-y DRFI rates of 97% (95% CI: 89-99%) and 89% (95% CI: 86-92%), respectively (HR=4.50, 95% CI: 1.09-18.61; p = 0.038). BCI/BCIN+ remained statistically significant in the multivariable analysis, adjusting for age, treatment, and nodal status (HR=7.54, 95% CI: 1.34-42.64; p = 0.022). For 69 N0 patients, BCI stratified 54 (78%) and 15 (22%) patients as low and high risk with 10-y DRFI rates of 100% (95% CI, 100-100%) and 77% (95% CI, 44-92%), respectively (p = 0.012). For 378 N1 patients, BCIN+ stratified 21 (6%) and 357 (94%) of patients as low and high risk with 10-y DRFI of 90% (95% CI, 66-97%) and 90% (95% CI, 86-93%), respectively (p = 0.07). Of the 21 patients classified as BCIN+ low-risk, two had BCIN+ scores of 6.75 and 6.73 in close proximity to the cut point (6.93) and experienced DR after 5 years, resulting in the same 10-y DRFI for both BCIN+ low- and high-risk patients. Conclusions: BCI is significantly prognostic for the risk of overall DR (0-10 y) in patients with HR+ HER2+ disease treated with adjuvant trastuzumab-based chemotherapy. Optimization of BCI cut points may further improve prognostic performance in HR+ HER2+. Additional validation in other HR+ HER2+ cohorts treated in the modern setting with anti-HER2-based therapy is warranted, given the small sample size of N0 patients and relatively low DR rate in the late recurrence cohort. In summary, these results provide further evidence of BCI’s utility to support clinical decision-making for adjuvant endocrine therapies for HR+ HER2+ BC. Support: U10CA180821, U10CA180882, U24CA196171, Genentech; Clinicaltrials.gov Id: NCT00005970; https://acknowledgments.alliancefound.org. Citation Format: S. Chumsri, E. Liu, K. Edwards, Y. Wen, Y. Zhang, A. K. Anderson, A. H. Partridge, L. Carey, K. Ballman, E. Perez, K. Treuner, M. Goetz, E. Thompson. Prognostic performance of Breast Cancer Index in patients with early-stage HR+ HER2+ breast cancer (BC) treated with adjuvant trastuzumab: NCCTG N9831 (Alliance) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-08-08.

Abstract Background: Women younger than 40 generally fall outside the routine screening population for breast cancer (BC). We aimed to understand factors influencing diagnosis and treatment delays in these patients, and the impact of delays on disease-free survival (DFS). Methods: We included women aged ≤ 40 years at diagnosis of stage 0-IV BC enrolled in the Young Women’s BC Study from 2006-2016. Sociodemographics, initial BC symptoms, and disease status were collected via annual surveys. Medical record review was used to capture tumor characteristics and recurrence status. We used logistic regression to estimate associations between patient and tumor factors and three delay types: (1) self-delay (≥ 90 days from first symptom to presentation to a provider), (2) diagnosis delay (≥ 90 days from healthcare visit to diagnosis), and (3) treatment delay (≥ 60 days from diagnosis to first treatment). Odds ratios (OR) and 95 % confidence intervals (CI) were estimated in multivariable models after choosing factors via backwards selection (p≤0.05 retained). Hazard ratios (HR) and 95% CIs for the association between delays and DFS, overall and by stage, were estimated via Cox proportional hazard models, adjusted for tumor and treatment factors. Time to event was measured from diagnosis or treatment to recurrence, death, or last follow-up, whichever occurred first. Results: Of 1,297 patients, 1,071 who completed the long-form baseline survey were included. Median time from first symptom to presentation was 14 days (interquartile range (IQR)=2-45), presentation to diagnosis was 14 days (IQR=7-30), and diagnosis to treatment was 41 days (IQR=25-57). Overall, 14% (n=153) had a self-delay and 11% (n=120) had a diagnosis delay. Of 839 patients with self-detected tumors, 18% had a self-delay and 13% had a diagnosis delay. Among those with Stage 1-3 BC (N=928), 22% (n=205) had a treatment delay. In univariable models, income &lt;50K (p=0.01), lower financial comfort (p=0.01), and not living with a partner (p=0.03) were associated with higher odds of self-delay, while pregnancy within 1 year pre-diagnosis (p=0.05) and first-degree family history of any cancer (p=0.04) or BC (p=0.03) were associated with lower odds. Self-delays were more likely for women diagnosed with stage 4 BC (p=0.004) or with HER2+ tumors (p=0.03) and less likely for those with triple negative (TN) BC (p&lt;0.001). In the multivariable model, family history of BC (OR=0.40, 95% CI=0.17-0.80), income &lt;50K (OR=1.97, 95% CI=1.22-3.13) and TN subtype (OR v. luminal A=0.30, 95% CI=0.13-0.60) remained associated. Odds of diagnosis delay were higher among women who were younger (p=0.01) or with Stage 4 BC (p=0.004), and lower for those with luminal B (p=0.04), TN (p=0.01), or high grade tumors (p=0.03). In the multivariable model, younger age (OR per 1-year=0.94, 95% CI=0.89-0.99), and subtype (luminal B v. A OR=0.60, 95% CI=0.38-0.95; TN v. luminal A OR=0.35, 95% CI=0.16-0.70) remained associated. Multivariable models for self-and diagnosis delays remained similar when restricted to self-detected patients.Treatment delays were less likely among unemployed individuals (p=0.001), and women with a positive germline BC risk variant (p=0.002), luminal B (p=0.005) or TN (p&lt;0.001) subtypes, and high-grade tumors (p=0.03). Only tumor factors remained significant in the multivariable model, including subtype (luminal B v. A OR=0.59, 95% CI=0.41-0.86, TN v. luminal A OR=0.25, 95% CI=0.13-0.43), and stage (stage 3 v. 1 OR=0.37, 95% CI=0.20-0.65). Overall and by stage at diagnosis, delays were not statistically significantly associated with DFS before or after adjusting for tumor and treatment factors. Conclusions: Delays in breast cancer care are influenced by multiple psychosocial and clinical factors, and disparities exist by socioeconomic status. It is critical to decrease self- and diagnosis delays to prevent stage 4 breast cancer. Citation Format: B. X. Zhang, T. Sella, Y. Zheng, G. J. Kirkner, K. J. Ruddy, S. M. Rosenberg, V. F. Borges, L. Schapira, S. E. Come, J. Peppercorn, A. H. Partridge, K. D. Brantley. Delays in breast cancer diagnosis and treatment in young women [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-02-16.