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Breaking the stromal barrier in bladder tumor with a urea-powered platelet nanomotor for potentiated BCG immunotherapy.

e16604 Background: Intravesical Bacillus Calmette-Guérin (BCG) therapy for bladder cancer is severely limited by poor tumor penetration and an immunosuppressive tumor microenvironment. We identified death-associated protein like 1 (DAPL1) as a critical regulator of BCG resistance: low DAPL1 expression in bladder cancer promotes pathological extracellular matrix (ECM) stiffening and immune exclusion, driving a BCG-refractory phenotype. This prompted the development of a targeted delivery strategy to overcome this stromal barrier. Methods: DAPL1’s role in BCG resistance was validated via bioinformatics, immunohistochemistry, transcriptomic/proteomic profiling, and in vitro/in vivo functional assays. We engineered a platelet-derived nanomotor (BCG@PLTm) that encapsulated BCG and harnessed urine urea decomposition for autonomous propulsion, enabling active tumor penetration. Nanomotor properties were characterized via microscopy and 3D tumor models; therapeutic efficacy and biosafety were evaluated in orthotopic bladder cancer mouse models using live imaging, flow cytometry, and histology. Results: DAPL1 was downregulated in bladder cancer tissues, where its deficiency drove ECM barrier and immune desert. In vivo and in vitro, BCG@PLTm significantly restored DAPL1 expression, reversed pathological ECM remodeling, and reactivated intratumoral cytotoxic T-cell infiltration. These effects translated to potent tumor suppression (tumor growth inhibition rate > 90%) with a favorable safety profile, as no overt toxicity was observed in major organs. Conclusions: Our findings established the DAPL1-ECM-immune exclusion axis as a targetable driver of BCG resistance. The urea-powered BCG@PLTm represented an autonomously propelled delivery platform to reprogram stromal-rich bladder tumors, providing a translatable therapeutic strategy for immunotherapy-refractory bladder cancer.

Targeting cellular senescence to enhance skeletal muscle recovery in survivors of breast cancer: An ancillary study of the phase II randomized PROFFi clinical trial.

TPS12168 Background: Postmenopausal survivors of breast cancer frequently experience persistent physical function decline after chemotherapy. A key contributor is skeletal muscle dysfunction, leading to weakness, fatigue, and reduced physical activity. One potentially targetable mechanism of chemotherapy-induced skeletal muscle dysfunction is cellular senescence. Senescence is a state of terminal growth arrest that leads to a senescence-associated secretory phenotype marked by the secretion of pro-inflammatory cytokines. These cytokines worsen muscle dysfunction by impairing calcium handling and muscle fiber contractility. Emerging evidence suggests senolytics and exercise may reduce senescent cell (SnC) burden. Senolytics are agents that selectively eliminate Sncs and can improve physical function in non-cancer populations. Exercise not only enhances physical function but also reduces blood markers of senescence. Preclinical studies demonstrate a synergistic effect of senolytics and exercise on SnC reduction. However, no human studies have examined the independent or combined effects of senolytics and exercise on skeletal muscle function and senescence in cancer survivors. We hypothesize that fisetin plus exercise will produce independent and synergistic effects that enhance skeletal muscle recovery in survivors of breast cancer. Methods: This site-specific ancillary mechanistic study at UCLA is embedded within PROFFi (Prevention of Frailty with Fisetin), an ongoing phase II multicenter, randomized, placebo-controlled clinical trial evaluating fisetin and exercise in postmenopausal survivors of breast cancer. Eligible participants are within 12 months of completing neo/adjuvant chemotherapy and have reduced physical function as measured by a 6-minute walk distance of 400-480 meters. PROFFi uses a 2x2 factorial design, randomizing 200 participants 1:1:1:1 to exercise plus fisetin, exercise alone, fisetin alone, or placebo for 16 weeks. Fisetin is administered orally at 20mg/kg/day on days 1-3 every 14 days. Exercise is individually tailored and remotely supervised by an exercise physiologist and includes aerobic and resistance exercises. The ancillary study will enroll 84 of the 200 participants (21 per arm) to undergo additional muscle-specific assessments including Biodex strength testing, thigh magnetic resonance imaging (MRI), and vastus lateralis muscle biopsies. The primary objectives of the ancillary study are to evaluate the effects of fisetin and/or exercise on muscle strength (Biodex peak torque), muscle volume (on MRI), and muscle mitochondrial function (oxidative phosphorylation capacity). Secondary objectives include assessing changes in blood and muscle-specific markers of senescence from baseline to end of study. Enrollment to this study began July 2024 and is ongoing (NCT06113016). Clinical trial information: NCT06113016 .

A sensitivity study on the measurement of urban polycentricity in chinese cities: Center definition, indicator selection, and their interaction effects

Research on urban polycentricity has long been hampered by fragmented case studies, inconsistent standardized criteria, and methodological misuse, complicating cross-study comparisons and limiting a nuanced understanding of complex spatial structures. To systematically reveal the combined effects of center definition methods and measurement indicators on polycentricity assessment, this study takes Hangzhou, Wuhan, and Nanning as comparative cases. We integrate four employment center identification methods and five polycentricity measurement indicators to conduct a comprehensive assessment from both morphological and functional dimensions. A Linear Mixed-effects Model (LMM) is employed to quantify the influence of method choices, indicator properties, and their interactions on the measurement results. The findings indicate that: (1) There are systematic differences between morphological and functional polycentricity. Morphological polycentricity is insensitive to the choice of center definition methods, whereas functional polycentricity is significantly constrained by the identification method used. (2) A significant “method-indicator” interaction effect exists in functional polycentricity. The LMM reveals that specific “method-indicator” combinations systematically lead to substantial variations in measurement results, suggesting that functional polycentricity is a “dynamic process” co-constructed by methodological choices rather than a purely objective reality. (3) Inter-city comparisons reveal diverse pathways of polycentric development: Hangzhou exhibits a “mature-type” structure characterized by the synergy between morphological and functional polycentricity; Wuhan demonstrates a transitional pattern of “morphologically monocentric but functionally networked”; while Nanning represents a policy-driven emerging polycentric city. This study argues that methodological choices profoundly shape the conclusions of polycentricity research. Future studies and practices should emphasize methodological transparency and sensitivity analysis, promoting a paradigm shift from “seeking the single truth” to “understanding sources of uncertainty,” thereby providing more reliable foundations for scientific urban planning.

A comprehensive review on various synthesis approaches and application of inorganic and carbon quantum dots

Machine learning based prediction of diesel engine emissions and performance using hemp biodiesel enriched with nano additives

Abstract The present study was focused on the experimental and machine learning approach to evaluate the diesel engine parameters behavior with hemp biodiesel blends enriched with nano additives (Al 2 O 3 , TiO 2 and MWCNT’s) at different loads. The Hemp biodiesel was characterized by using FTIR and GC-MS analysis. The nano additives were examined through a SEM and XRD analysis for identifying the morphological structure and crystalline phases. The experimental results revealed that HMBD20 + MWCN100 fuel shows higher BTE (5.60%) and lower BSFC (18.58%) compared to HMBD20 fuel. The CO and HC pollutants for HMBD20 + TINP100 fuel were diminished by 22.24% and 16.12% but NOx emissions were enhanced by 13.7% than HMBD20 fuel at peak load. For predictive modelling, Decision Tree (DT), Support Vector Machine (SVM) and Artificial Neural Network (ANN) were employed using the engine load and fuel type as input features. The DT model exhibits a higher prediction accuracy of R 2 0.9899 & 0.998 and lowest RMSE of 1.085 & 0.0264 for BTE and BSFC data. The greater accuracy of R 2 of 0.9865, 0.9899 and 0.9975 were achieved by DT model for CO, HC and Smoke emissions but NOx emissions were predicted by 0.9997 by using ANN model. The optimal condition was recorded for HMBD20 + 100 ppm MWCNT fuel at 75% load, achieving BTE (32.56%), BSFC (0.30 kg/kWhr), CO (0.12%), HC (42 ppm), NOx (980 ppm), Smoke opacity (35.2 HSU) and CO 2 (7.48%) which confirms the strong potential of nano additive hemp biodiesel for efficient and cleaner operation of a diesel engine.

Lipid transfer proteins and PI4KIIα generate a phosphoinositide-linked proteome

Arrhythmia phenotype and 30-day readmission in selected cancers: Propensity-matched NRD study.

11180 Background: Cardiac arrhythmias are common in oncology and may increase rehospitalization and resource use, but arrhythmia-type and cancer-specific readmission risk is incompletely characterized. Methods: Retrospective cohort of adult index hospitalizations for colorectal, breast, lung, prostate, kidney, or melanoma in the HCUP Nationwide Readmissions Database. Arrhythmias coded during the index stay (atrial fibrillation [AF], atrial flutter [AFL], ventricular tachycardia [VT], supraventricular tachycardia [SVT]) were identified using ICD-10-CM codes. Primary outcome was all-cause 30-day readmission. For each phenotype, propensity-score matching (caliper 0.05) created arrhythmia and no-arrhythmia cohorts balanced on demographics, payer, income quartile, and comorbidity. Multilevel logistic regression with hospital clustering estimated adjusted odds ratios (aOR) with 95% CI and tested arrhythmia-by-cancer interactions. Secondary outcomes were index length of stay (LOS) and total charges, analyzed with mixed-effects models; results are reported as adjusted mean differences (days) and incremental charges (USD). Two-sided p < 0.05 was significant. Results: Among 1,562,919 index hospitalizations, AF was present in 214,475 (13.7%), AFL 27,545 (1.8%), VT 5,184 (0.3%), and SVT 25,714 (1.6%). After matching/adjustment, AFL was associated with higher 30-day readmission (aOR 1.095, 95% CI 1.03-1.17; p = 0.005). AF (aOR 1.001, 0.98-1.03; p = 0.940), VT (aOR 1.128, 0.99-1.29; p = 0.078), and SVT (aOR 1.018, 0.95-1.09; p = 0.598) were not significant overall. AF demonstrated cancer-specific heterogeneity: lung aOR 1.092 (1.043-1.144; p < 0.001) and melanoma aOR 1.143 (1.019-1.283; p = 0.023), while breast was not increased (aOR 0.964, 0.908-1.025; p = 0.242). In the AF model, older age was inversely associated with readmission (aOR 0.974 per year, 95% CI 0.972-0.976; p < 0.001). In the AF model, highest income quartile was associated with higher readmission (aOR 1.409, 95% CI 1.275-1.557; p < 0.001). AF/VT/SVT increased LOS: AF +0.658 days, VT +1.419 days, SVT +1.146 days (p < = 0.001); charges increased: AF +$12,399 (95% CI 8,231-16,569), VT +$48,114 (36,846-59,382), SVT +$26,656 (19,822-33,489) (all p < 0.001). Conclusions: In selected cancers, AFL was independently associated with higher 30-day readmission, while AF readmission risk varied by cancer type. AF/VT/SVT were linked to increased LOS and charges, with the largest resource impact in VT. Prospective studies incorporating cancer stage and therapy exposures should test phenotype-guided cardio-oncology transitional care to reduce readmissions and costs. Limitations include ICD-coded phenotyping, inability to distinguish incident vs prevalent arrhythmias, and unavailable outpatient therapy/anticoagulation; residual confounding is possible. Misclassification may bias estimates toward null, particularly for VT.

Time to treatment for primary melanoma in an integrated healthcare system.

e21577 Background: Delayed treatment intervention for primary melanoma may negatively impact prognosis. This study investigated the relationship between the time from diagnosis to treatment (TTT) and overall survival (OS) in a large cohort of patients with primary melanoma. Methods: We analyzed data from a cohort of primary melanoma patients, stratifying them into three groups based on their TTT: 0-29 days (early treatment),30-59 days (intermediate delay), and more than 60 days (significant delay). Overall Survival (OS) was assessed using Kaplan-Meier analysis, and differences in survival were visually represented. Results: A total of 14,570 patients were included. The majority of patients (84%, 12,265) received treatment within 30 days. The proportion of patients with intermediate and significant delays were 13% (1901) and 3% (404), respectively. The overall survival was 113 months when their TTT was less than 30 days, 105 months for TTT 30-60 days and 91 months for patients more than 60 days ( p<.001 ). However, further analysis revealed that the TTT > 60 days group was significantly enriched for aggressive clinicopathological features, including male sex, older age, non-Caucasian race, advanced stage at diagnosis, and high-risk histology/location. After adjusting for these potent prognostic factors in the multivariate model, the apparent association between TTT and OS was substantially attenuated, suggesting that the observed decreased OS in the delayed group primarily serves as a proxy for inherently aggressive tumor biology and patient characteristics (p<.001). Conclusions: A significant treatment delay (> 60 days) in our integrated system is associated with a raw reduction in OS. Crucially, this delay appears to be a surrogate marker for existing, aggressive clinicopathological factors, rather than an independent cause of decreased survival. This finding suggests that patient and tumor characteristics, rather than system-level TTT alone, may drive the observed survival differences.

REJOICE-Ovarian01: Phase 3 part of a phase 2/3 study evaluating raludotatug deruxtecan (R-DXd) versus treatment of physician’s choice in patients with platinum-resistant ovarian cancer.

TPS5637 Background: Platinum-resistant ovarian cancer (PROC) is associated with poor outcomes. Standard-of-care single-agent non-platinum therapies, with or without bevacizumab, have demonstrated only modest activity in PROC, while targeted therapies remain limited to specific biomarker-defined patient populations. Cadherin-6 (CDH6), a mediator of cell–cell adhesion, is aberrantly expressed in up to 94% of epithelial ovarian cancer tumors. R-DXd is an antibody–drug conjugate comprising a humanized CDH6 antibody covalently linked to a topoisomerase I inhibitor payload (DXd) via a tumor-selective cleavable linker. REJOICE-Ovarian01 is a Phase 2/3 study of R-DXd monotherapy in patients with PROC. Among patients who had completed ≥18 weeks of follow-up or discontinued treatment in the Phase 2 dose-optimization part, the objective response rate (ORR) by blinded independent central review (BICR) was 44.4% (16/36) at 4.8 mg/kg, 50.0% (18/36) at 5.6 mg/kg, and 57.1% (20/35) at 6.4 mg/kg, including three complete responses overall. Clinically meaningful tumor responses were observed irrespective of tumor CDH6 expression, and the safety profile of R-DXd was manageable. R-DXd 5.6 mg/kg was identified as the optimal dose for further evaluation in the Phase 3 part of REJOICE-Ovarian01, which is described here. Methods: The Phase 3 part of REJOICE-Ovarian01 (NCT06161025) is a global, randomized, open-label study of R-DXd in patients with platinum-resistant, high-grade serous or high-grade endometroid ovarian, primary peritoneal, or fallopian tube cancer. Patients must have received 1–4 prior lines of therapy (LOT), including bevacizumab (unless ineligible) and mirvetuximab soravtansine for folate receptor α–positive disease (unless not available locally). Patients are not selected based on tumor CDH6 expression. Approximately 600 patients will be randomized 1:1 to receive either R-DXd 5.6 mg/kg intravenously every 3 weeks until disease progression per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), lost to follow-up, death, or other reason per protocol, or treatment of physician’s choice (TPC; weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan) per local guidelines. Randomization will be stratified by number of prior LOT, tumor CDH6 expression, and by TPC. The primary endpoint is progression-free survival (PFS) by BICR per RECIST 1.1. Key secondary endpoints include overall survival (OS) and quality of life. Stratified log-rank tests will be used to compare PFS and OS between treatment groups. Stratified Cox regression models will be fitted to estimate the hazard ratios for PFS and OS. Enrollment in Phase 3 began in December 2025. Clinical trial information: NCT06161025 .

Trends and disparities in prostate cancer and tobacco use–related mortality among adults aged ≥55 years in the United States, 1999-2024: A CDC WONDER analysis.

e17082 Background: Prostate cancer (PC) is one of the leading causes of death among men in the United States and represents a major public health burden. Tobacco use contributes to PC through carcinogen-induced DNA damage, chronic inflammation, and oxidative stress, particularly among men aged ≥55 years bearing the highest mortality burden. Existing literature is only focused on the mortality due to PC but the major contributing factor such as tobacco addiction needs to be addressed; therefore, this study aims to analyze the national mortality trends due to PC and tobacco use. Methods: National mortality trends involving prostate cancer (C61) and tobacco use (F17, T65.2) were examined using data from the Centers for Disease Control and Prevention WONDER database. Age-adjusted mortality rates (AAMR) per 1 million of adults aged ≥55 years, and temporal changes were quantified using Joinpoint regression to evaluate Average Annual Percentage Change (AAPC) and 95% confidence interval (CI). Results: Between 1999 and 2024, 65,035 deaths were attributed to prostate cancer with concurrent tobacco use, with a sustained overall increase in mortality (AAPC: 10.1; 95% CI: 4.8–15.8). Rising trends were observed across racial groups, including Non-Hispanic (NH) Black/African American (AAPC: 11.7; 95% CI: 8.1–15.3) and NH White populations (AAPC: 12.0; 95% CI: 10.0–14.1). Mortality increased across all census regions, with the steepest incline in the Northeast (AAPC: 13.9; 95% CI: 11.1–16.7), followed by the South (AAPC: 12.0; 95% CI: 8.9–15.2), Midwest (AAPC: 11.1; 95% CI: 9.2–13.0), and West (AAPC: 9.3; 95% CI: 7.6–11.0). Urban–rural differences were evident, with mortality increasing in both metropolitan (AAPC: 13.8; 95% CI: 11.3–16.4) and non-metropolitan areas (AAPC: 14.6; 95% CI: 11.6–17.6). Age-specific analysis demonstrated the most profound increase in mortality among older individuals aged 75–85+ years bearing the burden of 42,178 deaths with a persistent increase (AAPC: 12.2; 95% CI: 10.3–14.2) followed by the individuals aged 55–74 years with 22,857 deaths (AAPC: 9.1; 95% CI: 4.2–14.3). Conclusions: Mortality involving PC and tobacco use has increased substantially over the past two decades, with consistently increasing trends across geo-demographic variables. Older adults (75-85+ years) experience both a higher prevalence of tobacco use and an increased risk of PC, contributing to elevated mortality, underscoring the need for effective population-level tobacco control interventions according to the WHO Framework Convention on Tobacco Control. There is also a need to integrate the tobacco addiction management into targeted prevention strategies including tobacco cessation services, age-specific screening initiatives, and advancements in diagnostic and treatment modalities to mitigate the risk of PC associated mortality.

Real-world cumulative exposure of various endocrine-disrupting chemicals and association with breast cancer risk via common carcinogenic pathway.

630 Background: Convergent evidence suggests carcinogenicity of endocrine disrupting chemicals (EDCs). But there is a lack of large-scale epidemiological evidence concerning real-world EDCs mixture exposure and breast cancer (BC). A dataset of emerging knowledge of toxic pathways provides a valuable toolkit to infer the carcinogenicity of chemicals, but current studies of this thus filed are rare. We test whether real-world EDCs exposure, independently or in mixture, increases BC risk in the population, through carcinogenic toxic pathways. Methods: A total of 234,273 women from the UK Biobank cohort were followed for a median of 13.85 years. The annual monitoring record from UK Water Quality Sampling Harmonised was used to estimate the exposure to 13 EDCs (e.g., lead and chlorpyrifos-methyl) for each woman by Kriging interpolation model. The association between EDCs and breast cancer was analyzed by Cox proportional hazard model (for single EDC) and weighted quantile sum (WQS) regression (for mixture). The EDCs were also added to the modified Gail model to test their additional contribution. Twenty-seven Olink proteins were selected via EDC-BC toxic pathway dataset and BC genetic propensity score model to examine their correlation with EDCs. Interaction between EDCs and these proteins and SNPs within their sequence were analyzed by multiplicative model. Results: During the follow-up period, 9,282 women developed BC, 984 of whom died. All the 13 EDCs showed association with increased BC risk. Each unit increase of the 13-EDC mixture was associated with 2.15 fold (95% CI, 2.01-2.31) of BC risk and 4.18 fold of BC-related mortality (95% CI, 3.39-5.17), and 34.38 % of total morbidity and 59.6% of BC-related mortality in the population were attributable to EDC mixture. The risk of hormone receptor-positive BC was higher than that of hormone receptor-negative BC (HR: 2.87 vs HR: 2.03, p = 0.002). The EDCs provided 2.1 % improvement to the modified Gail model of BC prediction. For the 27 Olink proteins referring to BC toxic pathway and genetic propensity score, 26 (96.3%) correlated with at least one EDC (average number ≥8), among which NACC1 protein mediated up to 98.8% (chlorpyrifos-methyl) of the individual EDC’s effect on BC. The EDC mixture showed interaction with multiple proteins, including NACC1 and estrogen receptor 1, on BC-related mortality. Conclusions: Various EDCs in the real world may increase BC morbidity and mortality via common carcinogenic pathways. Future policies of novel EDC emission and safety evaluations must consider the cumulative EDC stressor in the environment because they may act as a whole.

Advancing breast cancer diagnosis in rural Kenya: Bridging histopathological gaps toward Global Breast Cancer Initiative (GBCI) goals.

e12717 Background: Breast cancer disproportionately impacts low-middle income countries such as Kenya. In Kisumu over 75% of cases present with advanced disease due to high diagnostic costs, limited access, low awareness, and systemic delays. The WHO Global Breast Cancer Initiative targets diagnosis within 60 days; Kenya’s National Cancer Control Strategy (2023–2028) emphasizes equitable diagnostic access. We are implementing an accelerated breast cancer histopathological diagnostic project to reduce delays and improve access to diagnosis at Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH) through subsidized breast core needle biopsy (CNB), histopathology, and immunohistochemistry (IHC) with patient navigation. Methods: Collaboration between JOOTRH, Africa Cancer Foundation, and Tiba Foundation (Jan– December 2025) identified 158 patients presenting with breast masses for subsidized CNB, histology, IHC, and navigation. Diagnostic turnaround times (TAT) and patient-level data were tracked. Results: 104 patients with invasive breast carcinoma were included; contact-to-biopsy TAT averaged 0.22 days (100% met < 2-day target). Average laboratory TAT for histopathology and IHC were 21.4 days (8.65% met 10 day target) and 11.3 days (32.69% met 10-day target), respectively. Mean patient age was 50.11 (±15.4) years, with 48.08% being premenopausal, with a mean of 36.7 (±7.5) years. Most were rural (84.2%), unemployed/informally employed (82.40%), faced median 8-month pre-diagnostic delays, visited multiple hospitals before diagnosis (mean 3.79 hospitals/hospital visits), and reported financial barriers (75%). 48.8% of patients were hormone receptor positive, 14.4% were HER2 amplified, and 28.85% were triple negative breast cancer (TNBC). The median duration of symptoms was 11.5 months (IQR 20.0), and 92.31% presented after more than 3 months of symptomatology. Self-reported barriers to diagnosis were household delays (78.85%) and hospital diagnostic delays (88.46%). 17 (16.35%) women have died; the median duration of follow-up before mortality was 86.1 days. Conclusions: Access to breast cancer diagnosis remains a challenge in Western Kenya. Importantly, receptor status was unknown compared to Western populations. The project has established baseline data on breast cancer in the region: patients are younger, present with more advanced and aggressive disease, and experience higher mortality rates compared to high income countries. Critical to designing a comprehensive cancer approach was understanding that rates of Her2/TNBC comprised almost 50% of patients. This data has enabled targeted planning to shorten histopathology TAT, strengthen referral pathways, and secure sustainable financing for diagnostic services and infrastructure to reduce the mortality burden and to meet the WHO and National Cancer Control program targets.

Sex-associated differences in osimertinib pharmacokinetics among Asian patients with non-small cell lung cancer.

3094 Background: Osimertinib is an oral, third-generation tyrosine kinase inhibitor (TKI) used in the treatment of epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancers (NSCLC). However, therein lies a high interindividual variability in osimertinib trough concentrations at steady state, which may in turn affect clinical outcomes. The study aimed to evaluate factors influencing osimertinib exposure and their potential impact on treatment response. Methods: This was a prospective single-institution study of Asian NSCLC patients receiving once daily 80mg osimertinib. Plasma concentrations of osimertinib and its metabolites, AZ5104 and AZ7550 were quantified at steady state using a validated LC-MS/MS method. Pharmacogenetic analysis was conducted using commercially available Taqman SNP genotyping assays. Results: A total of 177 Asian patients with Stage I-IV NSCLC tumors were enrolled. Median age was 65 (35-84) years old. Majority of patients were Chinese (90%), female (59%) and non-smokers (82%). Exon 19 deletions were present in 45% of patients. Subgroup analysis of 72 patients with available pharmacokinetic data showed no significant genotypic-phenotypic associations between CYP3A5*3, ABCB1 1236C>T, ABCB1 3435C>T, ABCB1 2677G>T/A and ABCG2 421C>A and osimertinib pharmacokinetics parameters. Sex was significantly associated with trough osimertinib levels and clearance, with females exhibiting 28% higher osimertinib levels and lower clearance compared with males ( P =0.0098). Similar trends were observed with AZ5104 and AZ7550 and osimertinib clearance ( P <0.001). No significant differences in overall survival and progression-free survival were observed between sexes. Analysis of best overall response showed that males were more likely to PD compared with females (OR=1.88, 95% CI; 0.54- 6.3) but this was not statistically significant ( P = 0.489). Conclusions: Our study showed that sex influences osimertinib pharmacokinetics, with females showing higher trough levels and lower clearance. These differences did not, however, translate into significant differences in survival or treatment response between males and females.

Efficacy and safety of a temperature-controlled oral cryotherapy device in preventing oral mucositis among patients receiving high-risk anticancer regimens.

12154 Background: Oral mucositis (OM) is a severe dose-limiting toxicity in cancer patients receiving intensive chemotherapy or novel antibody-drug conjugates (ADCs). Recent clinical data indicate that the incidence of OM with Sacituzumab Tirumotecan (sac-TMT) is as high as 54.1%, with approximately 11.1% of patients experiencing severe (Grade≥3) events. For Liposomal Doxorubicin, reported OM incidence is approximately 22%. Established therapies such as Docetaxel, Paclitaxel plus Carboplatin, and Sacituzumab Govitecan exhibit OM rates ranging from 10% to 30%. Severe OM frequently leads to excruciating pain, nutritional compromise, and treatment delays. This study evaluated the efficacy of a specialized oral cryotherapy (OC) device in preventing treatment-induced OM across these high-risk regimens. Methods: In this prospective trial, patients scheduled for high-risk regimens including Sacituzumab Tirumotecan, Sacituzumab Govitecan, Liposomal Doxorubicin, Docetaxel, or Taxane plus Carboplatin were enrolled. The intervention group received continuous OC using 8°C purified water, delivered via safe, non-toxic intraoral molds regulated by a temperature-controlled device. The protocol was administered 15 minutes prior to, throughout, and 30 minutes post-infusion. Primary endpoints included time to first OM onset, OM incidence, and WHO severity grading. Results: From September, 2025 to January, 2026, 116 patients were enrolled, with the most frequent user completing 13 OC sessions. The overall incidence of OM was only 6.9% (8/116), and all cases were Grade 1, with no interference with oral intake. In the Sacituzumab Tirumotecan (sac-TMT) subgroup (n = 26), the OM incidence was 11.5% (3/26)occurring at C2D1 (n = 2) and C4D8 (n = 1). Other subgroup incidences were as follows: Sacituzumab Govitecan, 50.0% (1/2) occurring at C2D1; Liposomal Doxorubicin, 4.2% (1/24) occurring at C2D1; Taxanes, 7.1% (2/28) both occurring at C2D8; and Epirubicin, 5.6% (1/18) occurring in C3D1. Notably, zero Grade ≥ 2 OM events were observed across all cohorts. No serious adverse events related to the temperature-controlled device were reported, and patient compliance with the OC protocol was high. Conclusions: Regulated oral cryotherapy using a temperature-controlled device and intraoral molds is a simple, cost-effective, and well-tolerated intervention that significantly reduces the incidence and severity of treatment-induced oral mucositis. Particularly for patients receiving high-risk ADCs such as Sacituzumab Tirumotecan, this standardized OC protocol should be considered a standard prophylactic measure to improve clinical outcomes and treatment adherence.

Circulating extracellular vesicles carrying PD-1, PD-L1, and CTLA-4 to inform resistance to immunotherapy in HCC.

2567 Background: First-line immune checkpoint inhibitor (ICI) therapy has contributed to improved outcomes in hepatocellular carcinoma (HCC). However, only around 30% of patients respond, highlighting the need for biomarker driven patient selection. Considering the lack of tissue acquirement in HCC in clinical routine, liquid biopsy holds great promise. In this study, we aimed at profiling immune checkpoints (IC) on circulating extracellular vesicles (EVs) as potential liquid biopsy-based biomarkers for prediction of treatment response. Methods: Three distinct cohorts were analyzed in this study: (1) HCC Explorer Cohort (n=40), testing the presence of membrane-bound ICs on EVs; (2) early-stage HCC Cohort (n=37 with paired blood and tissue), assessing the interplay between EV and tissue ICs alongside clinicopathological parameters and (3) Treatment Cohort (n=161 with 548 sequential blood samples), comprising a training (n=79,n=402 sequential samples) and a validation group (n=82, n=146 sequential samples), to identify predictors of immunotherapy response through IC profiling of circulating EVs via multiplex immunoassay. Results: PD-1, PD-L1 and CTLA-4 were enriched in EVs compared to EV-depleted serum. Baseline and early dynamics in EV-IC levels significantly discriminated between responders and non-responders in the training and validation cohort, while simultaneously predicting PFS and OS. In addition, dynamic changes of EV-IC levels during therapy in patients with initial response predicted acquired therapeutic resistance, approximately 36-42 weeks before progression was traceable on imaging. High serum EV-IC levels correlated with “cold” tumor features on paired tissue samples and single-EV profiling revealed various cells of origin of our EV-IC, e.g., PD-L1+ EV mainly derived from hepatocyte/HCC cells and antigen presenting cells, and PD-1+ EV mainly from T-cells and macrophages, as expected. Conclusions: EVs carrying PD-1, PD-L1 and CTLA-4 represent readily quantifiable, non-invasive biomarkers to predict response and survival in advanced HCC patients undergoing ICI therapy and serve to identify biological ICI resistance much earlier than current standards with imaging. Dataset on diverse clinical endpoints in training and validation cohorts. Biomarker Cohort Objective Response p-value mPFS High vs Low (months) mOS High vs Low (months) EV-PD-L1 Training 0.022 2.8 vs 10.8 (p<0.001) 13.7 vs 25.7 (p=0.021) Validation <0.001 3.1 vs 5.8 (p=0.008) 10.4 vs 12.5 (p=0.97) EV-PD-1 Training <0.001 2.9 vs 15.9 (p<0.001) 6.4 vs 25.7 (p=0.002) Validation <0.001 2.9 vs 8.4 (p=0.001) 7.3 vs 12.7 (p=0.056) EV-CTLA-4 Training <0.001 3.3 vs 16.1 (p<0.001) 20.2 vs 21.9 (p=0.081) Validation <0.001 2.9 vs 9.0 (p<0.001) 8.8 vs 16.3 (p=0.003) High vs low -> based on ideal cut-off. NR = not reached.

The effect of adjuvant therapy on survival in gastric cancer patients achieving pathologic complete response after neoadjuvant immunochemotherapy.

e16120 Background: Perioperative immunotherapy has significantly increased pathologic complete response (pCR) rates in locally advanced gastric cancer (LAGC). Whether adjuvant therapy provides additional survival benefit for patients (pts) with LAGC who achieve pCR after neoadjuvant immunochemotherapy remains unclear. We evaluated the association between adjuvant therapy and survival in this population. Methods: We prospectively collected clinicopathologic data on 65 consecutive pts who were diagnosed with cT3-4bN0-3M0 LAGC and were treated at Nanfang Hospital from October 2019 to May 2025. All received neoadjuvant immunochemotherapy, underwent gastrectomy, and achieved pCR (ypT0N0). Neoadjuvant regimens consisted of immunochemotherapy, with trastuzumab for HER2-positive tumors. Neoadjuvant therapy comprised 2-6 cycles. Adjuvant therapy was defined as ≥2 cycles after surgery. Pts were grouped into the adjuvant therapy group (TG, n = 44) and the no adjuvant therapy group (nTG, n = 21) according to receipt of adjuvant therapy. Survival was compared between the groups. The final follow-up was conducted on January 14, 2026, with one pt lost to follow-up. Results: Clinical stage was III in 49 pts (75.4%) and IVA in 16 (24.6%). 23.8% (15/63) of pts were dMMR, 66.7% (42/63) had PD-L1 CPS ≥5, 20.0% (12/60) were HER2-positive, and 5.5% (3/55) were EBV-positive. Overall, 85.7% (54/63) were biomarker-positive (dMMR and/or PD-L1 CPS ≥5 and/or HER2-positive and/or EBV-positive). The median number of neoadjuvant cycles was 4 (range, 2-6). In TG, immunochemotherapy was the predominant adjuvant regimen (65.9%), with a median of 4 adjuvant cycles (range, 2-6). In nTG, adjuvant therapy was not administered due to severe surgery- or treatment-related adverse events or comorbidities (8 pts, 38.1%) or refusal (13 pts, 61.9%). No significant differences were detected between the two groups in baseline clinicopathologic or neoadjuvant treatment-related characteristics. After a median follow-up of 32.0 months (IQR, 22.0-48.5), one pt in TG (CPS = 5, HER2- and EBV-negative, pMMR) relapsed at 38 months from initiation of neoadjuvant therapy and died at 40 months with extensive peritoneal metastases and massive ascites. Two additional pts in TG died of non-cancer causes (aspiration [OS, 15 months]; cardiac disease [OS, 26 months]). No recurrences were observed in nTG, and one pt died of pneumonia-related respiratory failure (OS, 30 months). No significant differences were observed between TG and nTG in 3-year EFS (93.3% vs 92.9%; log-rank p = 0.718), 3-year OS (93.8% vs 92.9%; log-rank p = 0.747), and 3-year cancer-specific survival (100% vs 100%; log-rank p = 0.552). Conclusions: In this small-sample cohort of LAGC pts achieving pCR after neoadjuvant immunochemotherapy, the recurrence rate was low, and the survival benefit observed with adjuvant therapy appeared limited.

Empowering patients with multiple myeloma through the INSIST! program: Outcomes of biomarker testing education.

e19545 Background: Multiple myeloma is a biologically complex hematologic malignancy in which biomarker testing is essential to risk stratification, treatment selection, and disease monitoring over time. Cytogenetic, molecular, and genomic testing inform prognosis and guide personalized treatment strategies; however, many patients report limited understanding of these tests and their implications for care decisions, particularly at relapse or disease progression. To address this gap, the Patient Empowerment Network developed the INSIST! Multiple Myeloma program to improve patient understanding of biomarker testing and support informed engagement in care. Methods: Since the program began in 2020, the INSIST! Multiple Myeloma program has delivered national patient education through virtual expert-led sessions, digital educational content, and downloadable resource materials. Educational topics included the role of biomarker and cytogenetic testing in treatment planning, frequency of monitoring, and strategies for effective patient-provider communication. Program reach and engagement metrics were analyzed, and participant feedback was reviewed to assess perceived changes in knowledge and confidence related to testing and treatment discussions. Results: The INSIST! Multiple Myeloma program demonstrated strong engagement and positive patient-reported outcomes. Since the program began in 2020, it has reached 27,868 patients and care partners nationwide. Participants engaged most frequently with expert-led educational content focused on biomarker testing, treatment decision making, and research updates, as well as downloadable patient resources designed to support informed discussions with healthcare professionals. Post-program survey responses indicated a strong positive impact on patient understanding and confidence. 94% of respondents reported increased understanding of multiple myeloma and health equity considerations. 89% percent indicated that the program gave them the knowledge and confidence to play a more active role in treatment decisions. 90% reported improved understanding of research and clinical trials, and 93% reported a stronger understanding of available treatment options. Conclusions: Patient-focused education programs centered on biomarker testing can meaningfully improve understanding and engagement among individuals living with multiple myeloma. The INSIST! Multiple Myeloma program supports patient activation as a critical component of precision oncology and aligns with ASCO’s emphasis on equitable access to personalized cancer care. Mikhael, J., et al. Treatment of multiple myeloma: ASCO and CCO joint clinical practice guideline. Journal of Clinical Oncology , 37(14), 2019.

Efficacy and safety of mixed formulation aprepitant and palonosetron (QLM2010) for prevention of cisplatin-based highly emetogenic chemotherapy-induced nausea and vomiting: A multicenter, randomized, double-blind, double-dummy, positive-controlled phase III study.

12147 Background: QLM2010, a novel fixed-dose intravenous antiemetic combination of aprepitant and palonosetron (PALO), can simultaneously antagonize 5-hydroxytryptamine-3 and neurokinin-1 receptors. This study aimed to assess the efficacy and safety of QLM2010 plus dexamethasone (DEX) versus fosaprepitant (FAPR) combined with PALO and DEX for preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC). Methods: This was a multicenter, randomized, double-blind, double-dummy, positive-controlled Phase III trial. Chemotherapy-naïve patients with solid tumors were randomly assigned 1:1 to receive QLM2010 (Day 1) or FAPR + PALO (Day 1) prior to cisplatin-based HEC, together with oral DEX (Days 1–4). The primary efficacy endpoint was complete response (CR: no emesis/no rescue medication) during the overall (0–120 hours) phase. Results: Baseline demographic and clinical characteristics were well-balanced between the two groups (QLM2010 group: n = 329; FAPR+PALO group: n = 331). The overall CR rate was 82.67% versus 80.97% (risk difference, 1.65%; 95% CI, −4.21–7.50%), confirming the non-inferiority of QLM2010 + DEX to FAPR + PALO + DEX. CR rates in both the acute (0–24 hours) and delayed (24–120 hours) phases were comparable between groups. Across all phases, the QLM2010 group showed similar rates to the FAPR+PALO group for no emesis, no nausea, no significant nausea, no rescue therapy, and complete protection (all P > 0.05). Notably, QLM2010 + DEX showed greater proportions of patients reporting no impact on daily life on Day 2 after treatment compared with FAPR + PALO + DEX (P = 0.0279). A single injection-site reaction (0.30 %) was confined to the FAPR+PALO group; none was observed in the QLM2010 group. The incidence of hiccups was numerically lower in the QLM2010 group compared with the FAPR+PALO group (8.2% vs. 15.1%). Conclusions: QLM2010 + DEX was non-inferior to FAPR + PALO + DEX for preventing CINV in cisplatin-based HEC patients and well tolerated, with the potential to reduce the impact of CINV on daily life. QLM2010 furnishes a novel, more convenient therapeutic alternative for the clinical management of CINV. Clinical trial information: NCT07081256 .

Association between intratumoral <i>Fusobacterium nucleatum</i> levels and clinical outcomes in esophageal squamous cell carcinoma: A comprehensive systematic review.

e16081 Background: Intratumoral Fusobacterium nucleatum (F. nuc) is a key microbial participant in gastrointestinal malignancy progression. In esophageal squamous cell carcinoma (ESCC), the link between bacterial colonization and metastatic potential requires characterization. This systematic review synthesizes evidence from independent cohorts to define the relationship between bacterial DNA load, molecular pathways driving metastasis, and survival. Methods: PubMed, EMBASE, and Cochrane databases were searched for studies till January 2026 evaluating F. nuc and ESCC prognosis using quantitative DNA-based assays (qPCR or 16S rRNA sequencing). Multivariate-adjusted hazard ratios (HR) for cancer-specific survival (CSS) and disease recurrence were pooled using a Random Effects Model; heterogeneity was assessed by I^2. Synthesis identified technical/geographic consistencies and correlations with pathological markers of tumor invasion and lymph node spread. Results: Eight studies from China and Japan met inclusion criteria. High intratumoral F. nuc load was a significant independent prognostic factor. Elevated DNA load was a robust predictor of poor outcomes, specifically associated with a CSS HR of 1.78 (95% CI 1.06-2.65). Recurrence risk was similarly elevated, yielding a pooled Relapse-Free Survival (RFS) HR of 1.71 (95% CI 1.27-2.30,I^2 = 0).Findings remained stable across multicenter registries in Japan and China, likely due to standardized qPCR targeting nusG or 16S rRNA genes. Qualitatively, high DNA load correlated with advanced pT stage and lymph node metastasis. This phenotype is mediated by TLR4/NF-κB and NOD1/RIPK2 signaling, which drive epithelial-mesenchymal transition (EMT) and foster an immunosuppressive "cold" tumor microenvironment characterized by M2-like macrophage and regulatory T-cell recruitment. Conclusions: Intratumoral F. nuc DNA quantification identifies a high-risk biological subtype of ESCC. Consistency across regional cohorts indicates F. nuc is a universal driver of metastatic progression in squamous cell pathology. Standardized microbial DNA quantification may serve as a high-fidelity biomarker to refine risk stratification and guide microbiota-targeted neoadjuvant strategies to mitigate metastatic spread in ESCC.

Oral mucositis as a predictor of differential long-term adverse events and mortality in breast cancer patients treated with monoclonal antibody-drug conjugates: Evidence from a propensity score-matched cohort comparison using real-world data from 88 U.S Healthcare organizations.

e12752 Background: Monoclonal antibody-drug conjugates (mADCs) are a cornerstone of advanced breast cancer treatment, but oral mucositis as an adverse effect may contribute to long-term systemic complications and mortality, even after balancing for confounders. Methods: We conducted a retrospective cohort study using the TriNetX federated network, accessing electronic medical records from 88 healthcare organizations. Adults with breast cancer treated with mADCs were identified. Before matching, 61,279 patients without mucositis and 1,766 patients with mucositis were included. Propensity score matching balanced cohorts on age, sex, race, ethnicity, and comorbidities, yielding 1,766 matched patients per cohort. Outcomes were assessed from one day after the index event ( breast cancer diagnosis for non mucositis patients; breast cancer diagnosis plus mADC therapy with mucositis for mucositis patients) excluding &gt; 20-year-old events. Post propensity score matching (PSM) risks of volume depletion, fluid and electrolyte disorders, respiratory infection, circulatory diseases, malaise/fatigue, pain, dysphagia, and mortality were assessed using measures of association, Kaplan-Meier survival, and event frequency. Results: After PSM, mucositis patients (Cohort 2) had higher risks for most outcomes. Volume depletion: risk 0.210 vs 0.170; P &lt; 0.001, Hazard ratio(HR) 0.702 (95% CI, 0.612-0.805; P &lt; 0.001, fluid/electrolyte disorders: 0.375 vs 0.300; P &lt; 0.001; HR 0.680, respiratory infections: 0.460 vs 0.370; P &lt; 0.001; HR 0.650, circulatory diseases: 0.610 vs 0.470; P &lt; 0.001; HR 0.560, malaise/fatigue: 0.290 vs 0.250; P = 0.005; HR 0.780, pain: 0.150 vs 0.100 ; P &lt; 0.001; HR 0.560, dysphagia: 0.100 vs 0.070; P = 0.002; HR 0.670, mortality: 0.250 vs 0.210; P &lt; 0.001; HR 0.710. Mean instances showed no differences (e.g., 3.5 vs 3.2 for volume depletion; P = 0.45). Associations attenuated slightly post-PSM but remained significant. Conclusions: Even after PSM, oral mucositis in mADC-treated breast cancer patients is linked to increased long-term risks, underscoring the importance of preventive strategies to enhance patient outcomes.