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Trinity Cooperative Electrode as a High‐Performance Electrocatalytic Host for Ultra‐Stable, High‐Rate Zinc–Halogen Batteries

ABSTRACT Aqueous zinc–halogen batteries (ZHBs) offer safety and low cost but are hindered by halogen dissolution, shuttle effects, and sluggish interfacial kinetics. We present a trinity cooperative electrode (TCE) that integrates a conductive polymer, a supramolecular solvent matrix, and an elastic polymer network to simultaneously enhance electronic conductivity, mechanical/solvent stability, and halogen immobilization. The iodine conversion pathway is elucidated by in situ/ex situ characterizations and molecular dynamics simulations. In ZnI 2 + Zn(CF 3 SO 3 ) 2 electrolytes, TCE‐based cells deliver 255 mAh g −1 at 1 A g −1 , retain 150 mAh g −1 at 50 A g −1 for > 50 000 cycles, and operate reliably at −10°C. The TCE also catalyzes Br − /Br 2 conversion in Zn(CF 3 SO 3 ) 2 + ZnBr 2 and enables sequential multielectron reactions in a ternary Zn(CF 3 SO 3 ) 2 + ZnI 2 + ZnBr 2 electrolyte, achieving ∼200 mAh g −1 at 30 A g −1 for > 22 000 cycles. This approach advances high‐energy, long‐life ZHBs through pseudocapacitive interfacial chemistry.

Nanoparticles in the fight against antimicrobial challenges: A comprehensive review

Cell surface SRC flags tumours

Digital Light Processing of Three‐dimensional Liquid Metal Hydrogels

ABSTRACT Liquid metal (LM) hydrogels emerge as promising materials for flexible electronics and soft robotics, but they are challenged by simplistic structure, limited precision, and insufficient functional designability. Herein, we demonstrate the first digital light processing of three‐dimensional (3D) LM hydrogels with micrometer precision (10 µm) and arbitrarily elaborated architectures. A universal strategy is developed for photo‐curable LM‐based various resins by encapsulation of LM droplets with sodium alginate (SA). The SA coating not only prevents the ink from sedimentation and self‐polymerization by forming hydrogen and ionic bonds, but also ensures uniformly dispersed ink with maintained photo‐curing properties. As a result, the photo‐cured 3D LM hydrogels illustrate enhanced tensile stretchability (2000%) and cycling stability (800 cycles at 500% strain), which outperforms most previously reported 3D hydrogels. The 3D LM hydrogel also shows enhanced sensitivity and tunable photothermal responsivity, demonstrating promising applications in strain sensors, object grasping robotics, remote‐controlled devices, and anti‐counterfeiting systems.

Energy-aware flexible job shop scheduling under time-of-use pricing with renewable, battery storage and preventive maintenance

Exclusive neoadjuvant chemotherapy with the FLOT regimen protocol in resectable gastric cancer: A retrospective cohort study in a Brazilian reference center.

e16118 Background: Perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is currently considered the standard of care for patients with resectable gastric and esophagogastric junction adenocarcinoma. However, completion of postoperative chemotherapy remains a major challenge, particularly in real-world and public healthcare settings. In this context, some centers have adopted an exclusive neoadjuvant approach, delivering all eight cycles before surgery. This study aimed to evaluate the feasibility, safety, and oncologic outcomes of this exclusive neoadjuvant strategy. Methods: We retrospectively analyzed 32 consecutive patients with resectable gastric or esophagogastric junction adenocarcinoma (≥cT2 and/or cN+) treated between 2019 and 2024 with neoadjuvant FLOT followed by surgery at a Brazilian reference center. Patients were grouped according to the number of neoadjuvant cycles received (≤4 vs > 4). Clinical, pathological, and survival outcomes were assessed. Overall survival (OS) was calculated from diagnosis and disease-free survival (DFS) from curative-intent surgery. Survival analyses were performed using Kaplan-Meier estimates and the log-rank test. Results: Twenty-one patients (65.6%) completed all eight neoadjuvant cycles, and 84.3% received more than four cycles. Dose reductions were required in 50% of cases. Curative-intent surgery was performed in 87.5%, with a mean of 25 lymph nodes retrieved. The R0 resection rate was 75%. Pathological complete response occurred in 9.4%, and pathological downstaging in 25%. Postoperative complications occurred in 18.8%, with no perioperative mortality. Mean OS estimate was 45.3 months in patients receiving more than four cycles versus 18.7 months in those receiving four or fewer cycles (p = 0.0096). Mean DFS estimate was 41.1 versus 18.6 months, respectively (p = 0.028). Toxicity was manageable, although 50% required dose adjustments. Conclusions: Delivering all eight cycles of FLOT exclusively in the neoadjuvant setting was feasible and safe in this Brazilian real-world cohort, with high adherence and encouraging survival outcomes. This strategy may represent a pragmatic alternative in scenarios of low compliance with adjuvant treatment or limited access to postoperative chemotherapy, warranting prospective validation. Treatment delivery, surgical feasibility, and oncologic outcomes. Variable Result Patients, n 32 Completed all 8 neoadjuvant cycles 21 (65.6%) Received >4 neoadjuvant cycles 27 (84.3%) Dose reduction required 16 (50%) Mean lymph nodes retrieved 24.9 ± 12.0 Pathological complete response (ypT0N0) 3 (9.4%) Pathological downstaging 8 (25%) Mean OS, months (>4 vs ≤4 cycles) 45.29 vs 18.71 Mean OS, months (dose reduction yes vs no) 30.83 vs 54.43

Incidence of malignancy in dermatomyositis vs polymyositis: A systematic review and meta-analysis.

e22578 Background: Dermatomyositis (DM) and Polymyositis (PM) are the two major subtypes of idiopathic inflammatory myopathies (IIMs) having different cancer incidences. DM is clinically recognized to have a strong cancer link than PM, but the comparative incidence of malignancy between DM and PM including sex stratified patterns, trends of malignancies, and tumor specific risk remains unquantified. We conducted a meta-analysis to evaluate incidence of malignancies in DM and PM. Methods: We performed PRISMA based searches across three databases (PubMed, Google Scholar, and ScienceDirect) for retrospective studies which reported malignancies in adult DM and PM patients after myositis onset were included. Due to variable follow up durations, malignancies were pooled as post diagnosis events. Trend analyses were performed to determine whether the DM–PM malignancy association was consistent overall and across subgroups stratified by sex and cancer type. We applied random effects model and estimated Pooled Risk Ratios with 95% confidence intervals. Subgroup analyses evaluating sex specific risk, cancer spectrum, and trends relative to myositis cohorts was performed. We assessed statistical heterogeneity using I² statistics. Results: Twelve studies which included 10,870 patients were analyzed in this meta-analysis which met the eligibility criteria. The primary outcome, comprised of 9 studies (10,230 patients; 5,063 DM and 5,167 PM patients), was incidence of malignancy which was diagnosed after myositis onset during follow up. DM showed higher malignancy incidence than PM (RR 1.79; 95% CI 1.54–2.08; I²=21%; p<0.000001). The trend analysis showed consistent greater malignancy in DM across overall and in subgroups than PM, but some cancer types (e.g. prostate and colorectal cancer) favored PM, and some (lung and ovarian cancer) favored DM while non-Hodgkin lymphoma showed equal trend. Gender specific analysis showed male gender to have higher incidence in DM and modestly higher in PM than females. In direct subtype comparison, DM carried higher incidence in both sexes. However, tumor specific cancer incidence differed :lung cancer (RR 3.14; 95% CI 1.94–5.08; I²=0%), ovarian cancer (RR 3.86; 95% CI 1.36–10.94; I²=7%), prostate cancer (RR 0.86; 95% CI 0.27–2.75; I²=19%), non-Hodgkin lymphoma (RR 1.06; 95% CI 0.38–2.93; I²=0%) , and colorectal cancer (RR 1.57; 95% CI 0.58–4.25; I²=53%). Conclusions: It concluded that DM has higher incidence of malignancy than PM overall and across all subgroup analyses. PM patients had increased risk of malignancy than general population but lower than DM. Trend analyses showed that malignancy remained consistent in DM, but some cancer types favored DM and some PM. These results provide a clear and quantitative overview about subtype, sex specific, tumor specific, and malignancy patterns showing an overall distribution of cancer incidence in myositis.

Decision regret and toxicity perception following adjuvant pembrolizumab in renal cell carcinoma.

4512 Background: Adjuvant pembrolizumab (pembro) is standard of care in renal cell carcinoma (RCC). We explored whether patients retrospectively regret their decision to receive adjuvant pembro and hypothesised that this is related to long-term toxicity that is not adequately captured by CTCAE criteria. To address this we developed a patient-informed tool, co-designed with patients, focusing specifically on long-term toxicity. Methods: Patients with RCC who received adjuvant pembro across three tertiary cancer centres in London between June 2022-Dec 2024 were invited to participate. Eligible patients completed the validated Ottawa Decision Regret Scale (DRS) and a complementary questionnaire exploring factors influencing regret including toxicity and disease recurrence. CTCAE-graded immune-related adverse events (irAEs) were collected and correlated with decision regret (DR). In parallel, patients categorised irAEs as life-changing, significant or non-significant and these were correlated with DR. DRS > 25 was defined as moderate-high regret. Appropriate ethical approval was obtained. Results: 104 patients were included post adjuvant pembro (88% pT3N0, 4% pT3N1 and 8% M1 NED). Median follow up was 30 months. 14% patients have relapsed. CTCAE ≥G3 irAEs occurred in 18%. 28% and 11% reported toxicity as significant (S) or life changing (LC) respectively. Patient reported S and LC toxicity did not correlate with ≥G3 CTCAE ( p = 0.11), with 33% CTCAE G1-2 events reported as significant. Mean DR score was 14.9 (95% CI 8.5-21.3) with 13% expressing regret. 1/14 patients who had disease recurrence expressed regret (mean DRS = 10.3 [1.4-19.3]). Patients that reported LC & S toxicity expressed more regret (26.9 LC v 26.1 S v 2.1 NS, p = 0.0021). There was no difference in regret between patients that sustained CTCAE G1-2 versus G3-4 irAE (14.9 vs 15.1, p = 0.23). DR was highest with permanent endocrine (n = 24) or musculoskeletal (n = 22) irAEs (endo: DRS 28.8 v 9.5, p = 0.003; MSK: DRS 25.1 v 12.8, p = 0.042). Lower baseline expectations of toxicity correlated with greater DR ( p = 0.002). Conclusions: DR after adjuvant pembro is driven by long-term, low-grade toxicity rather than disease recurrence. Novel patient-informed tools that capture life-changing or permanent toxicities outperform CTCAE in identifying patients at risk of regret. Improved baseline education on long-term risks may reduce decision regret and improve shared decision-making.

BL0175, a novel nano-mediated polypeptide conjugate of protein degrader, in patients (pts) with locally advanced/metastatic HR+/HER2− breast cancer (HR+, HER2- LA/mBC): Initial results from a phase 1 study.

1078 Background: BL0175 is a novel nano-conjugate (~10 nm) composed of PEG-modified poly (amino acid), enzyme-responsive peptide linkers, and the protein-degrader payload fulvestrant. It accumulates in the tumor microenvironment (TME), where enzymatic cleavage releases fulvestrant continuously. The released fulvestrant penetrates tumor cells, effectively inducing cell death. Nonclinical studies demonstrated that BL0175 provides superior tumor distribution of fulvestrant, enhanced tumor growth inhibition, and greater progesterone receptor suppression compared with conventional fulvestrant injection at equivalent doses. This first-in-human Phase I study reports preliminary safety, efficacy, and pharmacokinetic (PK) data for BL0175. Methods: Postmenopausal pts with HR+, HER2- LA/mBC received intramuscular BL0175 (Cycle 1: Days 1, 15; thereafter every 4 weeks) at doses ranging from 50 mg to 500 mg. Data are summarized across all cohorts unless otherwise specified. Results: As of January 14, 2026, 22 pts were treated (50 mg: n=1; 100, 200, 300, 400, 500 mg: n=3 each; 250 mg: n=6). The median number of prior lines of therapy was 3 (range: 1–7). Safety: Adverse events (AEs) and treatment-related AEs (TRAEs) occurred in 64% of pts (14/22). All AEs were Grade 1–2, with no dose-dependent trends or unexpected safety signals. Efficacy: Eleven pts had post-baseline tumor assessments (50 mg & 300 mg: n=1 each; 100, 200, 400 mg: n=3 each). Disease control rate (DCR) was 100% in cohorts receiving ≥200 mg. Three partial responses (PR) were observed in cohorts ≥200 mg, yielding an objective response rate (ORR) of 42.9% (3/7). The pts who achieved PR comprised individuals with prior progression on standard CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (aromatase inhibitor or fulvestrant injection), as well as those presenting with brain metastases at baseline. These data suggest that 200 mg may be an effective therapeutic dose. Pharmacokinetics: PK exposure (C max and AUC 0–336h ) of both released and total fulvestrant increased dose-proportionally. BL0175 was stable in systemic circulation (release rate ≤0.03% across doses). Notably, in two pts (50 mg and 100 mg cohorts), released fulvestrant concentrations in tumor tissue were 9-fold and 18-fold higher, respectively, than in plasma, confirming tumor-specific enrichment. Conclusions: BL0175 demonstrated promising efficacy in pts with HR+, HER2- LA/mBC, including those with prior progression on fulvestrant injection and CDK4/6i-based therapy and in brain metastases. The preliminary results validate BL0175's design rationale, supporting its tumor-targeted delivery and potential for enhanced efficacy at lower doses. These findings warrant further investigation of BL0175 in this patient population. Clinical trial information: NCT06738966 .

Factors influencing early readmission among breast, lung, and colorectal cancer patients admitted for febrile neutropenia: A Nationwide Readmissions Database (NRD) analysis.

e13105 Background: Febrile neutropenia accounts for some of the highest mortality among oncology patients. Several patient and treatment related factors contribute to these outcomes. However, there remains a gap in the literature regarding readmissions among patients after recovery from febrile neutropenia admissions in the setting of cancer and its treatment. Through this analysis, we aim to identify statistically significant factors associated with higher healthcare utilization and frequent readmissions in this population. Methods: We conducted a retrospective analysis of the 2022 Nationwide Readmissions Database (NRD), part of the Healthcare Cost and Utilization Project (HCUP). Hospitalizations for febrile neutropenia among patients with diagnosed breast, lung, and colorectal cancer were identified and categorized as index admissions, those discharged alive were followed for 90 day readmissions. Survey weighted logistic, linear, and Cox proportional hazards regression models were used to compare clinical and hospital-level characteristics and to identify predictors of 90 day readmission. Results: A total of 5,336.169 weighted patients met eligibility criteria and were categorized as index admissions. Among these, 1,341.106 patients experienced at least one readmission within 90 days. There were 311.33 deaths during index admissions. Resource utilization for index admissions versus 90-day readmissions was as follows: mean length of stay 6.37 vs 6.79 days, mean total charges 66,507.09 vs 74,039.91 USD, and mean total costs 17,845.69 vs 19,526.61. Cumulative LOS was 34,007.78 vs 9,113.21 days, with cumulative charges 353.0M vs 99.1M and cumulative costs 94.7M vs 26.1M. Patients with a higher comorbidity burden (Charlson category 3 vs 1) had increased hazards of readmission (adjusted hazard ratio [aHR] 1.44, p = 0.001). In addition, longer index length of stay showed statistically significant increase in readmission hazard per additional hospital day (aHR 1.01, p = 0.020). Conclusions: Approximately 25% of patients were readmitted within 90 days, and readmissions were associated with higher resource utilization and substantial system-level burden. Higher comorbidity burden and longer index length of stay independently predicted readmission. Infectious etiologies and treatment-related toxicities were leading causes, highlighting key targets to improve care and reduce healthcare burden Leading principal causes of 90-day readmissions (Weighted Patient Counts). Principal Diagnosis Weighted Patient Count Sepsis 306.68 Neutropenia / agranulocytosis 203.81 Pneumonia 79.96 Secondary malignant neoplasms 38.54 Encounter for antineoplastic chemotherapy 38.50 Acute kidney failure 37.37 Respiratory Failure 32.38 Neoplasm-related pain 26.83 C. difficile enterocolitis 20.16

Trends in leukemia-related mortality with heart failure as a contributing cause among U.S. adults aged ≥55 years, 1999–2023.

e24001 Background: Advances in leukemia therapy have improved survival, but cardiotoxic exposures and aging-related comorbidity may increase heart failure (HF) involvement in leukemia-related deaths. Trends in HF involvement are not well described. We examined national temporal trends in leukemia-related mortality involving HF among U.S. adults aged ≥55 years. Population-level HF trends can guide cardio-oncology risk mitigation and survivorship care. Methods: We used CDC WONDER Multiple Cause of Death data (1999–2023)—with bridged-race data through 2020 and single-race data for 2021–2023—to identify decedents aged ≥55 years with leukemia (ICD-10 C91–C95) as the underlying cause of death and heart failure (ICD-10 I50.x) listed as a contributing (multiple) cause. We calculated age-adjusted mortality rates (AAMR) per 100,000 population (2000 U.S. standard) overall and by sex and race/ethnicity, and age-specific crude mortality rates for adults aged ≥85 years. Temporal trends were modeled using weighted log-linear regression of ln(rate) by year, with standard errors derived from CDC WONDER 95% CIs to estimate annual percent change (APC) and 95% CIs. We report APCs to quantify rate-based change independent of population growth. Results: We identified 25,373 leukemia-related deaths with HF as a contributing cause among adults aged ≥55 years from 1999–2023 (14,311 male; 11,062 female). Overall AAMR was stable (1.6 per 100,000 in 1999 and 2023; APC 0.01%/year, 95% CI −0.74 to 0.76), while deaths increased from 946 (1999) to 1,459 (2023). Rising counts despite stable rates are consistent with population aging and growth. Male AAMR remained higher than female AAMR (2.2 to 2.3 vs 1.3 to 1.1), with no significant change over time (males: APC 0.48%/year, 95% CI −0.16 to 1.12; females: APC −0.41%/year, 95% CI −1.00 to 0.19). Rates were stable for NH White adults (1.7 to 1.8; APC 0.55%/year, 95% CI −0.17 to 1.28) and NH Black adults (1.1 to 1.0; APC 0.16%/year, 95% CI −0.77 to 1.10). Hispanic/Latino rates were low and stable in reliable years (0.8 in 2001 to 0.7 in 2023; APC 0.03%/year, 95% CI −1.28 to 1.36). Adults aged ≥85 years had higher age-specific crude mortality (8.1 to 7.8 per 100,000; APC 0.17%/year, 95% CI −0.45 to 0.79), with 484 deaths in 2023. Adults ≥85 accounted for a substantial share of HF-involved leukemia deaths, indicating concentrated risk. Conclusions: From 1999–2023, leukemia-related mortality with HF as a contributing cause was stable, despite rising death counts, with persistent differences by sex and race/ethnicity and a high burden among adults aged ≥85 years. These findings support integrating HF risk assessment, cardiotoxicity mitigation, and longitudinal HF monitoring into leukemia care and survivorship, particularly for older adults and other high-burden groups. Future work should evaluate treatment- and subtype-specific contributors to HF involvement.

Temporal trends in lung cancer stage at diagnosis and pre-treatment staging in United States, 2004-2022.

e20118 Background: Major advances in lung cancer detection and staging have occurred over the past two decades, including widespread adoption of endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA), navigational bronchoscopy, and low-dose CT (LDCT) screening. The population-level impact of these advances on stage at diagnosis and completeness of pretreatment staging remains uncertain. We evaluated national trends in lung cancer stage distribution to characterize changes in diagnostic patterns and staging over time. Methods: We conducted a population-based analysis of Surveillance, Epidemiology, and End Results (SEER) data from 2004–2022, calculating age-adjusted lung cancer incidence stratified by stage at diagnosis (localized, regional, distant, unstaged). Temporal changes in stage-specific incidence rates and proportions were compared between 2004–2006 and 2020–2022. Five-year relative survival was assessed for cases diagnosed between 2000 and 2022. Results: Marked shifts in stage distribution were observed over the study period. Age-adjusted incidence of localized-stage lung cancer increased from 10.8 to 13.4 per 100,000 (+24%; p < 0.001), while distant-stage incidence declined from 33.1 to 20.4 per 100,000 (−38%; p < 0.001). The incidence of unstaged disease decreased by 60%, from 6.8 to 2.7 per 100,000 ( p < 0.001). Correspondingly, the proportion of patients diagnosed with localized disease increased from 17.0% in 2004–2006 to 28.2% in 2020–2022, whereas the proportion diagnosed with distant-stage disease declined from 50.9% to 45.8%. Over the same period, five-year relative survival improved from 15.1% among cases diagnosed in 2000 to 27.9% among those diagnosed in 2017, representing an 85% relative increase. Conclusions: Between 2004 and 2022, lung cancer staging in the United States improved markedly, with a substantial decline in unstaged disease and a shift toward earlier-stage diagnosis, reflecting more complete pretreatment evaluation. These changes coincided with the widespread adoption of modern staging technologies and low-dose CT screening. Prospective, patient-level studies linking specific diagnostic modalities to staging completeness, treatment selection, and outcomes will be required to confirm causality. Stage distribution at diagnosis: Before and after comparision. Stage 2004-2006Early Period 2020-2022Recent Period Localized 16.7% 29.5% Regional 22.5% 19.3% Distant 51.2% 44.9% Unstaged 9.6% 6.3%

Assessing the effects of USP10 on pancreatic ductal adenocarcinoma metastasis via deubiquitinating and stabilizing RIOK3 to induce cytoskeleton remodeling.

e16408 Background: Metastasis is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and a primary driver of its lethal nature. While Ubiquitin-Specific Protease 10 (USP10) is implicated in various cancers, its specific role and molecular mechanism in PDAC metastasis remain elusive. This study investigates the clinical significance, biological function, and downstream regulatory network of USP10 in PDAC. Methods: USP10 expression and prognostic value were analyzed using TCGA data and tissue microarrays (TMAs) from two independent cohorts (n = 136). Stable cell lines were established to assess invasion and metastasis via Transwell, wound healing assays, and a tail-vein injection lung metastasis mouse model. Interactions between USP10 and downstream targets were identified using LC-MS/MS, Co-IP, structural modeling, and domain mapping. Deubiquitination assays, cycloheximide (CHX) chase assays, and immunofluorescence were employed to dissect the molecular mechanism. A prognostic nomogram was constructed based on clinical data. Results: Clinical analysis revealed that USP10 is significantly upregulated in PDAC tissues and correlates with poor overall survival (OS). Functionally, USP10 overexpression markedly enhanced PDAC cell invasion in vitro and lung metastasis in vivo. Mechanistically, USP10 interacts with RIOK3 in the cytoplasm, specifically binding to the RIOK3 NAT domain. We demonstrated that USP10 functions as a deubiquitinase that removes K48-linked polyubiquitin chains from RIOK3, thereby stabilizing RIOK3 protein levels. This USP10-RIOK3 axis upregulates Rho and RAC1 expression, promoting F-actin cytoskeleton remodeling and a mesenchymal-like morphology; notably, RIOK3 knockdown abolished USP10-induced metastatic phenotypes. Clinically, a significant positive correlation between USP10 and RIOK3 expression was validated in both cohorts. Patients with dual high expression of USP10 and RIOK3 exhibited the worst prognosis. A nomogram incorporating the USP10-RIOK3 signature demonstrated high predictive accuracy for patient survival. Conclusions: Our findings characterize USP10 as a critical driver of PDAC metastasis through the USP10-RIOK3-Rho/RAC1 axis, which orchestrates cytoskeleton remodeling. The USP10-RIOK3 complex serves as a novel prognostic biomarker and suggests that targeting this deubiquitination axis could offer a promising therapeutic strategy for metastatic PDAC.

Safety and efficacy of PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone in esophageal squamous cell carcinoma: A systematic review and meta-analysis.

e16024 Background: Patients with advanced esophageal squamous cell carcinoma (ESCC) continue to have poor outcomes with chemotherapy alone. The addition of PD-L1 inhibitors to first-line chemotherapy has shown encouraging results in individual trials, but the overall magnitude and consistency of benefit across key clinical endpoints have not been fully clarified. To better understand the effects of PD-L1 inhibitors used in combination with chemotherapy, we performed a systematic review and meta-analysis to compare the efficacy and safety of PD-L1-based combination therapies to chemotherapy alone in patients with advanced or metastatic ESCC. Methods: A systematic search of PubMed, Embase, and Scopus identified randomized controlled trials comparing PD-L1 inhibitor plus chemotherapy versus chemotherapy alone in patients with advanced or metastatic ESCC. Three eligible studies met inclusion criteria. We calculated pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS); and pooled risk ratios (RRs) for objective response rate (ORR) and Grade 3-5 treatment-related adverse events (TRAEs) using random effects models. We quantified the heterogeneity among studies using the I² test. Results: Across three randomized trials, the addition of a PD-L1 inhibitor to chemotherapy resulted in a statistically significant and highly consistent survival advantage. OS was longer with combination therapy (HR 0.67, 95% CI 0.60–0.76; p < 0.00001), representing a 33% reduction in the risk of death, with no heterogeneity across studies (I² = 0%). Similarly, PFS was prolonged with combination therapy (HR 0.61, 95% CI 0.55–0.68; p < 0.00001; I² = 0%), corresponding to a 39% reduction in the risk of disease progression or death. Tumor responses occurred at higher frequencies in patients who received PD-L1 inhibitor-based therapy than in patients who received chemotherapy alone (RR = 1.49, 95% CI = 1.35-1.63; p < .00001; I² = 0%). The increased efficacy observed with combination therapy was not accompanied by an increase in severe toxicities. The rates of Grade 3-5 TRAEs were similar between the two groups (RR = 1.06, 95% CI = 0.99-1.13; p = 0.09; I² = 0%). Conclusions: Based on evidence from three randomized trials, the addition of PD-L1 inhibitors to standard chemotherapy improves both survival and response rates in patients with advanced ESCC without an increase in severe treatment related adverse events. Therefore, PD-L1-based combination therapies represent a promising new therapeutic option for patients with advanced ESCC.

Immune-related adverse events in patients with mismatch repair–deficient gynecologic malignancies.

e17534 Background: Immune checkpoint inhibitors (ICIs) have shown clinical efficacy in treating tumors that harbor mismatch repair deficiencies (dMMR). However, despite their clinical efficacy, these treatments carry a risk of immune-related adverse events (irAEs). In all patients with a gynecologic malignancy being treated with an ICI, the risk of adverse event of any grade is around 30-50%, with risk of a grade 3 or 4 event around 5-11%. We hypothesize that the rate of irAE may differ in frequency and severity among dMMR patients compared to those who are mismatch repair proficient. Methods: A retrospective review was conducted of patients with gynecologic malignancies harboring mismatch repair deficiency who received immune checkpoint inhibitor therapy at Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University Hospital and its affiliated sites. Patients who received their first dose of therapy between January 2020 and August 2025 were eligible. The primary outcome was the incidence and grade of immune-related adverse events. Secondary outcomes included progression-free survival (PFS) and overall survival (OS). Event rates in this cohort were descriptively compared with published literature reporting outcomes in patients with gynecologic malignancies irrespective of mismatch repair status. Results: A total of 89 patients were screened, and 52 met inclusion criteria. Among these 52 patients, 35 (67.3%) experienced at least one immune-related adverse event (irAE) of any grade. In total, 57 irAEs were reported, with 12 of the 35 affected patients (34%) experiencing involvement of more than one organ system. The most frequently affected organ systems were endocrine (31.6% of reported irAEs) and gastrointestinal (22.8%). Grade 3 or 4 events accounted for only 7% of all reported adverse events. No statistically significant differences in age or race were observed among patients who experienced adverse events. Median PFS and OS were not reached. Conclusions: The incidence of immune-related adverse events was higher in patients with dMMR gynecologic cancers than in gynecologic cancer patients overall, independent of mutational status; the frequency of grade 3 or 4 events was similar.

Real-world healthcare resource utilization (HCRU) following chimeric antigen receptor (CAR) T-cell therapy in US patients treated in new authorized treatment centers (ATCs) without FACT accreditation.

e19515 Background: CAR T-cell therapy offers improved outcomes in lymphoid malignancies and multiple myeloma (MM), yet access is suboptimal due to a limited number of ATCs. In recent years, US expansion has included the launch of new ATCs, many opening without Foundation for the Accreditation of Cellular Therapy (FACT) accreditation. Real-world HCRU at these sites remain understudied. We examined post-infusion HCRU among patients treated at new US ATCs without FACT accreditation at the time of analysis. Methods: We conducted a retrospective analysis of HealthVerity Marketplace open claims (Jul 2023–Sep 2025). Adults (≥18 years) with CAR T-cell infusion at new ATCs without FACT accreditation were included, identified using procedure and billing codes. Outcomes assessed ≤30 days post-infusion were hospitalization length of stay (LOS), emergency department (ED) visits, 30-day readmission rates, and outpatient HCRU. Analyses were descriptive and limited to DLBCL and MM; other indications were included in the cohort but excluded from analyses due to small sample sizes. Results: A total of 55 patients across all indications received CAR T at 6 new ATCs. The cohort included 26 patients with diffuse large B-Cell lymphoma (DLBCL) (17/26 received axi-cel), 22 with MM (14/22 received ide-cel), and 7 with other hematologic cancers. Use of CAR T at new non-FACT ATCs increased over time (<11 patients in 2023; 16 in 2024; 34 in the first half of 2025). Mean age was 69.0 (DLBCL) and 68.5 (MM), and most patients were male. Infusion-related hospitalization, readmissions, and 30-day outpatient HCRU are summarized in the table. Conclusions: Delivery of CAR T at newly established, non-FACT accredited ATCs has increased over time, expanding patient access. Post-infusion HCRU appears consistent with prior reports, suggesting manageable resource needs. These early findings support the feasibility of expanding CAR T delivery to improve access even without FACT accreditation, with further evaluation of clinical outcomes and costs warranted. Utilization Category DLBCL & MM (n=48)Mean (SD)/Median (Range) DLBCL subgroup (n=26)Mean (SD)/Median (Range) MM subgroup (n=22)Mean (SD)/Median (Range) Initial hospitalization LOS (days) 16.0 (12.0) / 12 (7-81) 19.0 (15.2) / 15 (7-81) 11.6 (4.0) / 10.5 (7-22) Readmissions (≤ 30 days post-infusion) Number of inpatient readmissions 0.2 (0.4) / 0 (0-2) 0.2 (0.5) / 0 (0-2) 0.1 (0.3) / 0 (0-1) Readmission LOS (days; among readmitted) 7.5 (5.9) / 5.5 (2-19) 8.5 (6.6) / 7 (2-19) 4.5 (2.1) / 4.5 (3-6) Outpatient utilization (≤ 30 days post-infusion) Number of physician visits 0.4 (0.7) / 0 (0-3) 0.3 (0.7) / 0 (0-3) 0.6 (0.6) / 1 (0-2) Number of ED visits <0.1 (0.1) / 0 (0-1) <0.1 (0.2) / 0 (0-1) 0 (0) / 0 (0-0) Number of outpatient services (e.g. lab, imaging) 1.7 (1.8) / 1 (0-7) 0.9 (1.3) / 0 (0-5) 2.6 (1.9) / 2 (0-7)

Costs per avoided event (CPAE) in adjuvant CDK4/6 inhibitor therapy: A comparative analysis of subgroups from monarchE and NATALEE trials.

e12542 Background: Assessing the economic efficiency of high-cost therapies like adjuvant CDK4/6 inhibitors for HR+/HER2- early breast cancer (EBC) is crucial. The Costs per avoided event (CPAE), based on the Number Needed to Treat (NNT), is a powerful metric indicating the investment required to prevent one disease recurrence. This study uses CPAE analysis to compare the economic efficiency across key subgroups from the monarchE (abemaciclib) and NATALEE (ribociclib) trials, aiming to inform value-based decision-making in Brazil. Methods: Invasive Disease-free Survival (iDFS) data (Hazard Ratio) for ITT and subgroups were derived from monarchE and NATALEE analyses. The NNT was calculated as the inverse of the Absolute Risk Reduction (1/ARR). monarchE enrolled: Cohort 1 (high-risk features) and Cohort 2 (Ki-67≥20%). NATALEE included a broader population, adding intermediate-risk patients. Treatment costs were based on 24 (abemaciclib) and 36 (ribociclib) cycles, using the factory price established by CMED (Brazil's drug regulation chamber) and applying an 18% ICMS tax rate. The CPAE for each subgroup was then calculated by multiplying its specific NNT by the total treatment cost. Results: Efficacy and economic metrics varied substantially across all analyzed subgroups, underscoring the critical impact of baseline risk on clinical and economic value (Table 1). In monarchE, the CPAE value was more favorable in high-risk subgroups, such as Cohort 1 with high Ki-67 (BRL 6.3MM), but escalated dramatically in the lower-risk, lower-benefit Cohort 2 (BRL 23.6MM). Similarly, in NATALEE, the CPAE was more favorable for higher-risk stage III patients (BRL 9.2MM) compared to stage II patients (BRL 13.8MM). These disparities demonstrate that the economic value of treatment is highly dependent on the baseline risk of the patient subgroup. Conclusions: Risk stratification can significantly optimize treatment costs and is a critical driver of cost-effectiveness. These findings underscore the importance of precise patient selection for the sustainable implementation of therapies in the Brazilian healthcare system. Clinical efficacy and economic efficiency of adjuvant CDK4/6 inhibitors for HR+/HER2- EBC. Study & Subgroup HR (iDFS) ARR (%) NNT CPAE (BRL MM) monarchE (ITT) 0.73 5% 20 10.5 monarchE (C1, Ki-67 high) 0.64 9% 12 6.3 monarchE (C2, Ki-67 high) 0.83 2% 45 23.6 NATALEE (ITT) 0.72 4.5% 23 11.3 NATALEE (Stage III) 0.70 5.6% 18 9.2 NATALEE (Stage II) 0.76 3.7% 27 13.8 NATALEE (N+) 0.71 4.4% 23 11.8 NATALEE (N0) 0.63 5.7% 18 9.2

Evaluation of GATA6 expression as a biomarker in advanced pancreatic cancer: Real-world evidence study.

e16393 Background: Pancreatic adenocarcinoma is an aggressive disease and ranks as the fourth leading cause of cancer-related deaths worldwide. Recent studies have linked pancreatic malignancy closely to GATA6 expression. Indicating more favorable prognosis and better outcome with chemotherapy in tumors with high GATA6 expression. Methods: Between 2017 and 2023, we had a total of 175 patients with locally advanced pancreatic cancer. Based on immunohistochemical (IHC) analysis, the eligible patients were divided into two groups according to their GATA6 expression: high and low GATA6 expression. The primary endpoint was overall survival (OS) between the two groups, and the secondary endpoint included progression-free survival (PFS) and response to chemotherapy. The Kaplan-Meier method was used to assess OS, PFS and response to chemotherapy. Results: out of the175 medical records reviewed, 41 patients were eligible for the study. The patients were stratified according to their GATA6 expression into high and low based on IHC results. Among these, 15 patients had high GATA6 expression while 26 patients had low GATA6 expression. Median follow up time was 14 months. The median OS was 18 months in the high GATA6 group compared to 13 months in the low GATA6 group, (95% CI, 9.7 to 18.2) with P value of 0.20. Median PFS was 13 months in the high GATA6 group and 11 months in the low GATA6 group, (95% CI, 9 to 14.9) with P Value of 0.92. Treatment response was observed in 13 patients (68.4%) in the high GATA6 expression group compared with 12 patients (54.5%) in the low GATA6 expression group with P value of 0.34. Conclusions: Patients with high GATA 6 expression demonestrated a trend toward improved survival, and a more favorable response to chemotherapy; however, these differences did not reach statistical significance, highlights the need for further investigations in larger, well-powered studies.

Automated discovery and curation of public spatial transcriptomic datasets across multiple cancer indications.

e15010 Background: Public spatial transcriptomic datasets provide critical insights into tumor architecture and the tumor microenvironment, which is central to target discovery, biomarker identification and patient stratification. However, their integration for oncology research is limited by fragmentation across repositories, platforms, and inconsistent metadata and molecular data across studies. Scalable approaches are needed to systematically identify and organize these datasets across cancer indications. Methods: The Rancho Data Crawler, an automated discovery tool, was used to systematically identify publicly available spatial transcriptomic studies across seven thoracic and gastrointestinal oncologic indications. Searches were conducted across GEO, EGA, dbGaP, ArrayExpress, SRA, and Zenodo. Initial discovery focused on 10x Genomics Visium and Xenium platforms, with NanoString GeoMx and CosMx technologies incorporated to expand coverage. Candidate studies underwent manual review, followed by harmonized study-, donor-, and sample-level metadata curation and quality control. Raw and author-processed data were downloaded and delivered using a standardized cloud-based structure. Results: Automated crawling enabled large-scale, systematic identification of spatial transcriptomic studies across the targeted cancer indications, from which 25 studies were prioritized for detailed curation. The curated dataset was enriched for thoracic and aerodigestive tissues, with lung and head-and-neck samples comprising the largest tissue groups, alongside substantial representation of liver, pancreas, colorectum, and stomach. Samples were predominantly derived from malignant tumors, with a notable proportion representing advanced and metastatic disease. Tumor-proximal and immune-relevant tissues, including lymph node and peritoneal samples, were also captured. Data delivery comprised 27 datasets totaling approximately 4 TB and more than 8,500 files, organized with manifest files to support traceability and data integrity. Conclusions: Automated discovery using the Rancho Data Crawler, combined with rigorous metadata harmonization, enables scalable access to spatial transcriptomic datasets enriched for clinically and translationally relevant tumor tissues and disease states, supporting downstream translational oncology research.

Temporal trends, sociodemographic factors, and healthcare utilization of immune-related adverse events in hospitalized cancer patients: A national analysis, 2016-2020.

e13606 Background: Immune checkpoint inhibitors have transformed cancer treatment, but immune-related adverse events (irAEs) present significant clinical and economic challenges. We characterized temporal trends, risk factors, and healthcare utilization of irAE-related hospitalizations. Methods: Using the National Inpatient Sample (2016-2020), we identified adult patients hospitalized with adverse effects of antineoplastic/immunosuppressive drugs (ICD-10: T45.1X5) and concurrent cancer diagnoses (lung, melanoma, renal, bladder, head/neck). We classified irAE subtypes (colitis, pneumonitis, thyroiditis, hepatotoxicity, rash) and analyzed temporal trends, predictors, and clinical outcomes. Multivariable regression models adjusted for baseline comorbidity burden using the Elixhauser Comorbidity Index. Results: We identified 40,700 hospitalizations for irAEs. Mean age was 66.8 years; 53.7% were male; mean Elixhauser comorbidity score was 4.2. Lung cancer (76.1%) was most common, followed by bladder (9.5%), renal (6.6%), melanoma (5.2%), and head & neck (3.4%). Colitis was the most frequent irAE (7.89%), followed by rash (1.98%), pneumonitis (0.69%), hepatotoxicity (0.54%), and thyroiditis (0.13%). Annual irAE hospitalizations increased 14.5% from 7,133 (2016) to 8,171 (2020). Colitis prevalence increased from 6.73% to 8.82% (p < 0.001), and pneumonitis increased more than 4-fold from 0.22% to 0.97% (p < 0.001). Mean total hospital charges increased significantly from $54,520 (2016) to $66,814 (2020), representing a $3,044 annual increase (p < 0.001). Mean length of stay (LOS) remained stable at 6.0 days. After adjusting for baseline comorbidities, pneumonitis conferred the highest clinical burden with significantly longer LOS (8.2 vs 6.0 days, p < 0.001) and higher charges ($78,719 vs $60,748, p < 0.001). Paradoxically, colitis patients had $8,444 lower charges (p < 0.001) despite similar LOS. Significant racial differences were observed across multiple irAE subtypes. Black patients had 26% lower odds of colitis (OR = 0.74, p < 0.001) and 54% lower odds of rash (OR = 0.46, p < 0.001) compared to White patients. Conversely, Asian patients had lower odds of colitis (OR = 0.61, p = 0.003) but significantly higher rates of pneumonitis (OR = 1.98, p = 0.039), hepatotoxicity (OR = 2.07, p = 0.037), and rash (OR = 1.83, p = 0.002). Conclusions: As immunotherapy becomes standard of care across multiple malignancies, irAE hospitalizations increased 14.5% (2016-2020), with pneumonitis rising 4-fold. With expanding ICI utilization, healthcare systems must prepare for growing irAE burden. Notable racial differences in irAE patterns warrant further investigation to inform care delivery. These findings inform risk stratification, resource allocation, and cost projections for the growing population of ICI-treated patients.