Citations

Background: Transanal total mesorectal excision (taTME) facilitates sphincter preservation in low rectal cancer. Preliminary results and functional outcomes from the North American multicenter phase II taTME trial (NCT03144765) have been published. Three-year outcomes are reported. Methods: Patients with stage I to III rectal adenocarcinoma were enrolled across 11 centers (2017–2022). Endpoints included TME grade, 3-year overall survival, disease-free survival, cancer-specific survival, recurrence, late (beyond 90 d) complications, and stoma-free survival. Surveillance followed National Comprehensive Cancer Network guidelines, with pelvic magnetic resonance imaging (MRI) at 3 years to assess for pelvic sidewall recurrence when possible. Kaplan–Meier analysis assessed oncologic outcomes. Results: One hundred patients underwent taTME for tumors at a median of 5.8 cm from the anal verge, with intersphincteric resection in 36% and handsewn anastomosis in 54%. Median follow-up was 50.9 months. Late complications occurred in 32 patients, including 21 severe (Clavien-Dindo ≥3). Late anastomotic complications occurred in 5 patients; one required surgical revision. Estimated 3-year overall survival, cancer-specific survival, and disease-free survival were 93.7%, 96.6%, and 84.6%, respectively. Distant recurrence occurred in 15 patients (median: 17.6 months), most commonly in the lung and liver. Locoregional recurrence occurred in 2 patients. Preoperative N stage, lymph node yield, tumor deposits, and perineural invasion were associated with recurrence. Among 100 patients diverted at taTME, 97% were stoma-free at 3 years; 4 patients later underwent secondary diversion. Conclusions: Three-year outcomes of this multicenter trial support the safety and efficacy of taTME in resectable mid and low rectal tumors, with outcomes comparable to contemporary studies. Longer-term oncologic and functional outcomes are needed.

Abstract Introduction Combat casualty care requires standardized proficiency criteria to ensure readiness in austere environments, yet gaps persist in defining performance thresholds for critical trauma skills. The Combat Medical Skills Sustainment Consortium (CMSSC), a novel military-civilian collaboration, aimed to validate competency thresholds for 21 Department of Defense-identified trauma skills. Materials and Methods A prospective cohort study (2022-2025) enrolled 1,495 military and civilian personnel across five academic centers, stratified by experience (novice, intermediate, expert). Skills, including cricothyroidotomy, whole blood transfusion, and ultrasound-guided vascular access, were assessed using validated checklists in Role 2-congruent simulations. Statistical analysis compared checklist performance against participant experience with a priori checklist scores estimated at 40% (novices) and 90% (experts). Results Competency thresholds were established, ranging from 77% (mechanical ventilation) to 100% (handoff). Experts achieved 85%-98% proficiency across most skills, with novices at 34%-97%. A ceiling effect was observed for less complex skills consistent with the power law of practice. Conclusion The Combat Medical Skills Sustainment Consortium validated standardized assessment tools, with potential to address readiness gaps through military-civilian synergy. Findings support consortium-guided curriculum development and highlight the need for longitudinal skill decay studies. Impact This study sets a benchmark for trauma care skills assessment, facilitating rapid adoption across military and civilian settings.

Cancer stem cells (CSCs) are increasingly recognized as central drivers of tumorigenesis, therapeutic resistance, and recurrence across diverse malignancies. This review synthesizes our current understanding of CSC biology across CNS tumors, with a focus on glioblastoma, where stem-like cells are sustained by specialized and overlapping tumor microenvironmental niches. Perivascular, hypoxic, invasive, immunosuppressive, and extracellular matrix-associated niches cooperatively enforce stemness, metabolic adaptability, immune evasion, and phenotypic plasticity, enabling CSC persistence despite maximal surgical resection and standard-of-care therapy. Notably, CSCs extend beyond radiographically defined tumor margins and populate peritumoral regions, providing a biological basis for near-universal recurrence. Advances in multiparametric imaging, stem cell-based ex vivo and in vivo models, and single-cell and spatial profiling have refined insight into CSC heterogeneity, niche dependence, and treatment resistance. Together, these findings reframe therapeutic strategies, highlighting the need for function-preserving maximal resection and multimodal therapies that target both CSC-intrinsic pathways and their supportive microenvironments.

Background Effective leadership is critical to the success of complex multidisciplinary healthcare organisations. As the organisation emerged from the global pandemic, Mayo Clinic recognised a need to transform its traditional, linear care model into a dynamic, platform-based approach to support its strategy. This required a new leadership model that could support and equip leaders with the skills needed to drive patient-centred healthcare transformation from within. Objective To develop and validate a new leadership competency framework capable of supporting future-ready leadership. Methods A multiphase, evidence-based approach was employed: (1) a visionary interview, goal setting and literature review; (2) focus groups with 23 leaders from across the organisation; (3) iterative competency framework development; and (4) a validation study involving a stratified sample of 129 physician leaders who rated competencies on importance and differentiation, and a qualitative verification by key stakeholders. Results Five core competencies with 23 behaviours were identified. The validation analysis established all behaviours as important for differentiating leadership performance. Stakeholder review confirmed the competencies were actionable and applicable across leadership roles at all levels. Conclusion The Leads Self, Leads Others, Inspires Others, Forward Thinking and Engages Others (abbreviated LLIFE) competency model positions a healthcare organisation to advance leadership excellence in a rapidly evolving healthcare environment that requires comprehensive transformation. It aligns with strategic goals, embeds values-based behaviours and supports continuous development, establishing a model that other healthcare institutions may learn from and adapt.

Abstract Objectives: In the RadComp randomized trial, we compared radiation dose to cardiac substructures in patients treated with proton versus photon radiation therapy (RT) ; evaluated changes in cardiac-specific health-related quality of life (HRQOL) outcomes from baseline to 6 months following RT; and determined associations between radiation dose volume histogram (DVH) parameters and changes in cardiac-specific HRQOL. Methods: The study cohort included patients with locally advanced breast cancer enrolled on RadComp who completed treatment per protocol, had available radiation DVH metrics for all cardiac substructures, and completed both the baseline and at least one follow-up cardiac-specific HRQOL over the 6 months post-RT. Cardiac-specific HRQOL measures included PROMIS fatigue, PRO-CTCAE shortness of breath (SOB) (severity and interference with daily activities), and PRO-CTCAE chest pain, chest tightness, and angina (frequency, severity, and interference). Detailed dose volume histograms (DVH) for cardiac substructures included the whole heart, left ventricle (LV), right ventricle (RV), left atrium (LA), right atrium (RA), and left anterior descending artery (LAD) were derived. The Wilcoxon rank-sum test was used to compare dose distributions between photon and proton RT. Associations between DVH metrics and HRQOL outcomes were evaluated using repeated-measures linear regression via generalized estimating equations with an independent working correlation structure. All models were adjusted for RT type, age, cardiovascular risk factors, surgery type, laterality, ethnicity, education, timepoint, and race. Additional stratified analyses was performed according to laterality (right versus left + bilateral). Results: Across 1160 RadComp participants, RT exposure to cardiac substructures differed significantly between proton and photon RT and by laterality. Median mean heart dose was lower with protons, 0.9 Gy (Q1, Q3 0.49, 1.46), compared to photons 2.83 Gy (Q1, Q3 1.49, 4.52) (p< 0.001), and lower for right-sided disease, 0.91 Gy (Q1, Q3 0.44, 1.55), compared to left and bilateral 1.99 Gy (Q1, Q3 1.11, 3.63) (p<0.001). Similarly, for the LAD, LA, LV, and RA, mean proton dose was significantly lower (p<0.001). However, for the whole heart, RA, and RV, maximum doses to small-volume parameters and dose to 0.03cc were higher with proton RT. PRO-CTCAE measures of HRQOL were generally favorable at all timepoints across all participants, and grade ≥3 toxicity was rare (≤5.5%) for all measures. The PROMIS Fatigue T-Score increased from baseline (median 49 [Q1, Q3 46, 57]) to end of RT (55 [Q1, Q3 49, 63]), and returned to baseline levels at 6 months (p<0.001). While there were no significant differences in PRO-CTCAE SOB severity (p=0.24) and interference (p=0.11) over time, PRO-CTCAE chest pain worsened compared to pre-RT with respect to frequency (p<0.001), severity (p<0.001), and interference (p=0.008). However, the absolute changes were small. No DVH metrics were significantly associated with any cardiac-specific HRQOL outcomes. Stratification by laterality yielded similar results. Conclusions: Proton RT generally conferred significantly lower doses to the heart and cardiac substructures compared to photon RT. HRQOL outcomes were favorable across all participants, with fatigue returning to baseline, no change in SOB parameters, and a slight worsening of chest pain outcomes over 6 months following RT. Cardiac-specific HRQOLs appear not to be significantly affected by RT dose to cardiac substructures within the first 6 months post-RT. Other organs at risk that could also impact cardiac HRQOL endpoints, longer follow-up, and major cardiac events will be evaluated in future analyses. Citation Format: J. L. Wright, K. Ko, W. Kenworthy, W. Bosch, L. Braunstein, G. Freedman, E. Gillespie, R. Jimenez, S. Pugh, H. Lu, M. Pankuch, N. Remmes, W. Straube, W. Zou, E. Berlin, L. Fang, S. MacDonald, N. Taunk, J. Kim, A. Thukral, A. Taghian, M. Mishra, R. Mutter, V. Croog, D. Boggs, J. Urbanic, N. Ohri, A. Chawla, T. Meier, L. Rosen, M. Fegundes, O. Cahlon, K. Hoffman, A. Ferriozzi, J. Bekelman, A. Lin, B. Ky. Associations Between Cardiac Radiation Dose Volume Metrics and Cardiac Specific Health Related Quality of Life for Patients with Breast Cancer Randomized to Proton versus Photon Radiation on the RadComp Trial [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 RF6-04.

Abstract Background: Invasive lobular carcinoma (ILC) accounts for up to 15% of breast cancer (BC) cases and has distinct clinical and biological features compared to invasive carcinoma of no special type (IBC-NST). Prior studies, including PENELOPE-B, suggested greater benefit from adjuvant palbociclib (palbo) in ILC. We assessed the prognostic and predictive value of histology in patients (pts) treated with endocrine therapy (ET) ± palbo. Methods: PALLAS is a global, phase III trial in which pts with stage II-III, HR+/HER2− BC were randomized to 2 years (y) of adjuvant palbo + ET or ET alone. Pts with IBC-NST or pure ILC per local pathology assessment were included. Endpoints included invasive disease-free (IDFS; primary), distant recurrence-free (DRFS), locoregional recurrence-free (LRRFS), and overall survival (OS). Prognostic value was assessed using univariable and multivariate Cox models adjusted for age, T and N stage, grade, and progesterone receptor. Predictive value was assessed using histology-by-treatment interactions. Results: Among 5,748 pts in the ITT population, 4,982 (87%) were included (3,838 IBC-NST [67%], 1,144 ILC [20%]); median follow-up 6.9y. Compared with IBC-NST, ILC was associated with older age (median 54 vs 51 y), higher T stage (T3/T4: 41.7% vs 20.4%), fewer grade 3 tumors (12.7% vs 33.5%), higher mastectomy rates (74.5% vs 58.4%), less (neo)adjuvant chemotherapy (72.2% vs 86.2%), and less tamoxifen as initial ET (28.8% vs 34.5%) (all p<0.001). ILC prevalence varied by country: lower in Asia (Japan 10.5%, Korea 0%, Taiwan 2.8%) and higher in Europe (23.1%) and North America (24.0%). When evaluating the predictive value, palbo appeared to confer greater benefit in ILC for all endpoints (HRs ranging from 0.41 to 0.86) and not in IBC-NST (HRs ranging from 0.97 to 1.01), although the histology-by-treatment interaction was significant only for LRRFS (Table). In the overall population, 7-year IDFS was 79.3% for IBC-NST and 75.8% for ILC. While the difference was significant in univariable analysis (HR 1.17, 95% CI 1.01-1.35), it was not in multivariable analysis (HR 1.06, 0.91-1.24). Notably, the proportional hazards assumption was violated, and time-dependent modeling demonstrated that worse outcomes for ILC on IDFS, DRFS, and other endpoints emerged predominantly beyond 3 years. Conclusions: In this large, randomized dataset of pts with early HR+/HER2− breast cancer with long-term follow-up, ILC demonstrated distinct clinicopathologic features and geographic distribution. While ILC was not an independent prognostic factor over the entire follow-up, time-dependent modeling revealed worse long-term outcomes which only emerged after 3 years. Palbo appeared to be associated with more favorable outcomes in ILC than in IBC-NST across endpoints. These findings suggest a potential benefit of palbo in ILC that warrants further investigation in other adjuvant trials evaluating CDK4/6 inhibitors. Citation Format: G. Nader-Marta, C. Desmedt, D. Hlauschek, A. DeMichele, G. Zoppoli, E. Blondeaux, E. de Azambuja, M. Bellet-Ezquerra, O. Metzger-Filho, J. M. Suga, G. Pfeiler, M. P. Goetz, M. Ruiz-Borrego, S. Loibl, J. Meisel, A. Ring, K. Van Baelen, E. P. Mamounas, N. Zdenkowski, E. Agostinetto, M. Lambertini, E. Gauthier, L. Soelkner, A. C. Dueck, M. Gnant, E. L. Mayer. Long-term prognostic and predictive value of lobular histology in the PALLAS trial [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 PS3-11-06.

Purpose: The ASPiration to Improve Renal Calculi Removal Effectiveness study showed steerable ureteroscopic renal evacuation (SURE) with CVAC that significantly reduced residual stone volume at 30 days vs standard ureteroscopy (URS). This report presents 2-year health care consumption and stone events (SE) and their link to residual stone volume and other variables ( n = 101 at primary end point; n = 93 at 2 years). Materials and Methods: Logistic regression identified predictors of health care consumption events (HCEs), that is, emergency department visits, hospitalization, surgical retreatment, and SE across the study population. Incidence was compared between the treatment groups with Kaplan–Meier survival analysis. Results: At 2 years, residual stone volume was significantly associated with both HCEs and SE. For every 100 mm 3 increase in residual stone volume, the HCE risk increased by 50% to 54%, and the SE risk increased by 70%. Stone-free rate, the number of residual fragments (RFs), and RF total stone burden (based on diameter) were not predictors. Significantly fewer HCEs occurred in the SURE group (3 vs 20 events, p = 0.0004). Survival analysis confirmed this (4.3% vs 20%, log-rank p = 0.02), with a 73% risk reduction (hazard ratio 0.27, 95% Cl 0.09–0.80, p = 0.02). Fewer SE occurred in the SURE group, although not statistically significant. These subjects also had longer event-free survival. Conclusion: High-quality volumetric analysis supports evaluation of stone removal therapies, as residual stone volume predicts HCEs and SE. SURE significantly reduces the downstream incidence and risk of HCEs compared with standard URS.