Browse Articles

Pharmacogenetic (PGx) markers of cardiovascular side effects (CVSEs) in allogeneic hematopoietic cell transplant (HCT) patients receiving post-transplant cyclophosphamide (PTCy).

6559 Background: PTCy is used to prevent graft versus host disease (GVHD) post-HCT. CVSEs can be observed with Cy. We previously showed 16% of PTCy-treated patients experienced CVSEs within 30 days post-HCT. PGx determinants of Cy metabolism have been explored, but data are lacking on the impact of PGx on PTCy-related CVSEs. This study aims to identify PGx markers of CVSE risk in adult patients undergoing HCT. Methods: This is a retrospective PGx study of patients who underwent HCT between January 2014 and July 2024. Germline DNA was extracted from buccal swabs, and genotyping was performed using the Illumina Global Diversity Array with Enhanced PGx. The analysis focused on 99 single nucleotide polymorphisms (SNPs) in 13 candidate genes involved in Cy metabolism: GSTM1, GSTA1, GSTP1, GSTT1, CYP3A5, CYP3A4, CYP2C9, CYP2C8, CYP2C19, CYP2A6, CYP2B6, ALDH1A1, and ALDH3A1. The primary endpoint was time to CVSE occurrence at 90 days, 180 days, and 5 years post-HCT, including acute or chronic ischemic heart disease, acute myocardial infarction, angina pectoris, atrial fibrillation or flutter, other arrhythmias, cardiomyopathy, heart failure, hypertensive heart disease, pericardial effusion, pericarditis, peripheral vascular disease, and pulmonary edema. Covariates included age, sex, ancestral variation, diabetes, dyslipidemia, hypertension, atherosclerosis, and CVSEs within 2 years prior to HCT. Using an additive genetic model, a Cox proportional hazards model was generated to evaluate the association between each SNP and time to CVSE, adjusting for covariates. A CVSE risk score was developed using the total number of risk alleles from statistically significant SNPs and tested for association with time to CVSE using a Cox proportional hazards model. Results: Of 86 evaluable patients, the median age was 60 (range 24-78), 78% were male, 77% White, and 20% Black; 54% received haploidentical and 24.4% matched related donor HCT. The incidence of CVSEs was 27% at 90 days post-HCT, 31% at 180 days, and 58% at 5 years. The table describes three SNPs significantly associated with time to CVSE (p<0.05). The CVSE risk score (n=19 for low risk, 0-1 risk alleles; n=49 for intermediate, 2-3 risk alleles; n=18 for high, 4-6 risk alleles) was significantly associated with time to CVSE (HR 2.30, 95% CI 1.43-3.71, p=0.0006). Conclusions: PTCy-related CVSEs were common post-HCT. Single nucleotide polymorphisms in CYP2A6, GSTT1, and ALDH1A1 may influence CVSE risk post-HCT. These findings require further validation in independent datasets and may be used to develop a clinicogenomic risk model for CVSE post-HCT. SNP Gene Risk allele frequency Hazard ratio (95% CI) p value rs1137115 CYP2A6 0.215 2.78 (1.48-5.23) 0.0015 rs1007888 GSTT1 0.494 1.78 (1.13-2.81) 0.0129 rs1330283 ALDH1A1 0.506 1.82 (1.06-3.12) 0.0301

Time to response with HMA/venetoclax as a predictor of survival in acute myeloid leukemia: Analysis of 1- vs 2-cycle responders.

6548 Background: Hypomethylating agents (HMA) with venetoclax are the standard of care for patients with AML ineligible for intensive chemotherapy. However, the prognostic significance of time to response and the optimal duration of venetoclax, often modified in real-world practice due to myelosuppression, remain unclear. Methods: We conducted a retrospective analysis of adults with AML achieving CR/CRi with HMA/venetoclax at University of Kentucky from 2016-2025. Patients were stratified by cycle of response: 1 vs 2 cycles, using ELN 2022 response criteria. These groups were compared by demographics, cytogenetic and mutational profiles, and allogeneic HSCT. RFS and OS were estimated using Kaplan-Meier methods and compared with log-rank tests. Cox models evaluated associations between cycle of response, response type (CR vs CRi), and survival outcomes. Results: Eighty-six responding patients were included, with 69 (80%) achieving response after 1 cycle and 17 (20%) achieving response after 2 cycles. Median age was 66.7 vs. 67.1 years, male sex was 58% vs. 76%, and ELN risk distribution was similar: favorable 25% vs. 18% and adverse 64% vs. 65% (p=0.671). Frequent cytogenetic profiles included normal karyotype (44% vs. 41%) and complex karyotype (27% vs. 24%), and common mutations included IDH1/2 (23% vs. 18%), DNMT3A (19% vs. 24%), and NPM1 (22% vs. 12%). Overall, baseline demographics and cytogenetic/mutational profile were similar between 1-cycle and 2-cycle responders, supporting comparability of these groups for outcome analyses. With a median follow-up of 23.8 months, relapse occurred in 36% of 1-cycle responders vs. 82% of 2-cycle responders (p=0.002). Inferior RFS was noted in 2-cycle responders (HR 3.04, p=0.002), which remained after adjusting for total venetoclax exposure (HR 3.26, p=0.002). Median OS was 22.8 months (95% CI 14.0–NR) for 1-cycle responders and 12.7 months (95% CI 7.2–NR) for 2-cycle responders (p=0.01). In Cox models, 2-cycle response was associated with significantly inferior OS (HR 2.33, p=0.012), which persisted after adjusting for venetoclax exposure (HR 2.26, p=0.018). Hematologic recovery at time of CR was assessed and was not significantly associated with cycle of response or survival outcomes. Increased venetoclax exposure was associated with improved OS (HR 0.82 per day; p=0.049). When venetoclax exposure was dichotomized, receipt of ≤14 days was associated with inferior OS (HR 2.49; p=0.028). In this cohort, 6% of 1-cycle responders and 18% of 2-cycle responders proceeded to allogeneic HSCT (p=0.14). Conclusions: Delayed response beyond 1 cycle in patients receiving HMA/venetoclax identifies AML patients at higher risk of relapse and inferior survival. Time to response can inform early risk-adapted strategies, including venetoclax optimization.

Targeting nitrogen metabolism in hepatocellular carcinoma.

e15101 Background: Hepatocellular carcinoma (HCC) commonly develops in patients with cirrhosis, a condition associated with impaired hepatic ammonia clearance and systemic hyperammonemia. Although ammonia has traditionally been considered a byproduct of liver dysfunction, its direct role in tumor biology remains incompletely understood. We hypothesized that ammonia functions as an active metabolic substrate that promotes HCC aggressiveness through tumor-intrinsic mechanisms. Methods: Metabolic, molecular, and functional assays were performed in human and murine HCC models to evaluate ammonia uptake, downstream metabolic utilization, and effects on cancer stem cell phenotypes. Nitrogen isotope tracing was used to define the metabolic fate of ammonia-derived nitrogen. Genetic and pharmacologic approaches were employed to disrupt ammonia transport and metabolism. Clinical relevance was assessed using multivariable analyses of a large, clinically annotated HCC cohort with adjustment for liver function. Results: Ammonia was actively imported into HCC cells via the transporter SLC4A11 and utilized as a nitrogen source to support tumor metabolism. Ammonia uptake promoted cancer stem cell properties, including enhanced sphere formation, tumor initiation, and growth in vivo. Isotope tracing demonstrated incorporation of ammonia-derived nitrogen into downstream amino acid and nucleotide metabolic pathways. Disruption of ammonia transport or metabolism suppressed stemness and tumor growth. Clinically, elevated serum ammonia levels were independently associated with worse overall survival in HCC patients, even after controlling for liver function and disease stage. Conclusions: These findings redefine ammonia from a consequence of cirrhosis to an active, tumor-intrinsic metabolic driver of HCC progression. Ammonia import and utilization sustain cancer stem cell phenotypes and aggressive tumor behavior, identifying ammonia metabolism as a previously unrecognized and therapeutically actionable vulnerability in HCC. Given the availability of clinically approved ammonia-lowering agents, targeting ammonia may offer a novel strategy to improve outcomes in patients with HCC.

In-person versus telehealth outpatient palliative care visits in oncology: A multicenter study.

12056 Background: As telehealth becomes integral to outpatient palliative care delivery in oncology, evidence comparing consultation duration and time allocation between in-person and remote visits remains limited, especially in low- and middle-income countries. We compared consultation duration and time composition between in-person and telehealth visits after adjustment for visit type and clinical complexity. Methods: This observational study evaluated outpatient oncological palliative care consultations conducted between February and May 2025 across seven practices in Brazil. Total consultation time and predefined time components were recorded. Multivariable linear regression models estimated adjusted differences in consultation duration according to care modality, controlling for visit type (first appointment, follow-up, family meeting), performance status (ECOG), quality-of-life (IPOS), and number of participants. Results: A total of 269 consultations were analyzed, including 171 in-person and 98 telehealth visits. Care modality was associated with consultation type (p < 0.001): telehealth was less frequently used for first consultations (15% vs. 35%) and more frequently used for follow-up visits (76% vs. 63%) and family meetings (9% vs. 3%). Telehealth visits involved patients with worse performance status (ECOG 3-4: 36% vs. 17%; p=0.007) and poorer quality of life (higher IPOS distribution; p=0.037). In unadjusted analyses, telehealth consultations were shorter than in-person visits, particularly for follow-up visits. After multivariable adjustment, telehealth visits remained independently and significantly shorter by a mean of 10.5 minutes (95% confidence interval [CI] -15.6 to -5.4; p<0.001). Follow-up consultations were consistently shorter than first consultations by 19.4 minutes (95% CI -24.9 to -14.0; p<0.001), regardless of care modality, while family meetings showed no difference in duration compared with first consultations (95% CI -13.8 to 8.9; p=0.70). Each additional healthcare provider was associated with a 2.9 minute increase in consultation time (95% CI 0.1 to 5.6; p=0.04). ECOG was not independently associated with total consultation duration. Conclusions: After accounting for visit type and clinical context, differences in consultation duration between telehealth and in-person are modest. Telehealth was preferentially used for follow-up care and among patients with poorer functional status and quality of life, while preserving consultation complexity when clinically indicated. These findings support telehealth as a viable modality for outpatient palliative care delivery in resource-limited settings.

Burden of bladder cancer across Asia: Insights from the Global Burden of Disease (1999–2023).

e16617 Background: Bladder cancer is a malignant neoplasm arising from uncontrolled growth of the urothelial lining and represents an increasing global health concern. This study examines long-term trends in disability-adjusted life years (DALYs) and mortality due to bladder cancer across Asia from 1990 to 2023. Methods: Age-standardized bladder cancer data were obtained from the Global Burden of Disease (GBD) database. Mortality was reported as age-standardized death rates (ASDRs) per 100,000 population. Temporal trends were assessed using joinpoint regression to estimate annual percentage change (APC) and average annual percentage change (AAPC). Results: From 1990 to 2023, age-standardized DALYs declined across most Asian regions. East Asia carried the highest burden but showed a marked reduction, with DALYs decreasing from 70.38 to 40.42 (AAPC −1.59%; 95% CI −2.27 to −0.90; p < 0.001). Significant declines were also observed in Central Asia (57.34 to 40.10; AAPC −1.10%; p = 0.020) and High-income Asia Pacific (49.51 to 43.00; AAPC −0.44%; p < 0.001). South Asia demonstrated only a modest decrease (31.78 to 30.68; AAPC −0.17%; p = 0.042), while Southeast Asia remained relatively stable (26.30 to 28.60; AAPC 0.24%; p = 0.16). ASDRs showed similar patterns. East Asia had the highest mortality rates, declining from 3.20 to 2.03 per 100,000 (AAPC −1.03%; p < 0.001). Central Asia and High-income Asia Pacific also experienced significant reductions, whereas South and Southeast Asia exhibited largely stable trends. Conclusions: Although bladder cancer burden has declined across much of Asia, mortality and DALYs remain substantial. Strengthening early detection, risk-factor control, and preventive strategies remains essential to further reduce disease impact. Trends in bladder cancer burden across Asia (1990–2023). Region DALYs 1990 DALYs 2023 AAPC (%) ASDR trend East Asia 70.38 40.42 −1.59 ↓ Central Asia 57.34 40.10 −1.10 ↓ High-income Asia Pacific 49.51 43.00 −0.44 ↓ South Asia 31.78 30.68 −0.17 ↔ Southeast Asia 26.30 28.60 +0.24 ↔ DALYs and ASDRs are age-standardized per GBD 2023. ↓ indicates significant decline; ↔ indicates stable trend.

Melanoma stage as influenced by 31-GEP risk prediction.

e21604 Background: 31-gene expression profiling (31-GEP) has demonstrated the ability to predict the risk of recurrence (ROR) of cutaneous melanoma. The 31-GEP assay identifies high-risk patients (Class 2A/2B) who have recurrence rates higher than what is expected based on AJCC stage alone. This study details use of 31-GEP testing in a single center to identify patients at high ROR to guide risk-aligned management to improve patient outcomes. Methods: Patients with cutaneous melanoma who underwent 31-GEP testing on the primary tumor and were found to have Class 2A/2B results (n = 20 stage I, 52 stage II, and 28 stage III) were included in this study. They were offered follow-up quarterly physical examination and biannual cross-sectional imaging with yearly brain MRI and were followed by a single physician longitudinally. Oncology consultation for immunotherapy was routine. IRB approval was granted for review of patient outcomes. Results: Median patient age was 64 (range: 32-84); more than 50% of patients had more than 5 years follow-up. Median tumor depth was 2.9mm (0.4-12.0mm). Seventy-three patients were alive and 17 died from melanoma. The entire study population had a 41% recurrence rate. Seventy-one percent (22/31) of patients with metastatic recurrence were salvaged with immunotherapy. Two patients died of treatment complications and one of intracranial bleeding. All 7 patients with metastases not treated with immunotherapy died from their disease. Twenty percent (4/20) of stage I patients recurred, with 2 deaths and one patient alive with disease (AWD). Thirty-eight percent (20/52) of stage II patients recurred and 14/20 were disease-free (NED) or AWD after multidisciplinary treatment for a salvage rate of 70%. All 4 patients who received adjuvant immunotherapy for stage II, class 2B lesions were alive at time of last follow-up. Thirteen percent (7/52) died of metastatic disease. Twenty-eight patients had stage III disease. Forty-six percent (13/28) of patients recurred. Twenty-nine percent (n = 8) died of metastatic disease and 15 were NED. More patients who had regular clinical exams and imaging were NED at follow-up than those who refused imaging (55/73 vs 12/17, respectively). Conclusions: Patients with elevated 31-GEP melanoma have substantial ROR and death regardless of AJCC stage. Even "low risk, node-negative" patients had substantial ROR when found to have high 31-GEP scores. Nearly 75% of patients with recurrence were NED if followed closely and treated with immunotherapy. 31-GEP should augment AJCC staging to improve patient outcomes.

Role of ATM as a prognostic biomarker in breast cancer: A systematic review and meta-analysis.

e12705 Background: Breast cancer is the most common malignancy among women worldwide and remains a leading cause of cancer related mortality. Prognostic biomarkers are essential for risk stratification and personalized treatment. The ataxia-telangiectasia mutated (ATM) gene is a key regulator of the DNA damage response, and its altered expression has been linked to tumor progression and therapeutic resistance. However, the prognostic significance of ATM expression in breast cancer remains inconsistent. This study aimed to evaluate the prognostic role of ATM expression in breast cancer through a systematic review and meta analysis. Methods: This systematic review and meta-analysis was conducted according to PRISMA 2020 guidelines and prospectively registered on PROSPERO. PubMed, Scopus, Web of Science, Embase, and the Cochrane Library were searched from inception to July 2025 for cohort studies assessing the association between ATM expression and breast cancer prognosis. Eligible studies reported hazard ratios (HRs) with 95% confidence intervals (CIs). Study quality was assessed using the modified Newcastle Ottawa Scale. Pooled HRs for disease free survival (DFS), breast cancer specific survival (BCSS), and disease-specific survival (DSS) were calculated using a random effects model. Results: Five cohort studies met the inclusion criteria and were included in the quantitative synthesis. Low ATM expression was significantly associated with poorer disease free survival (HR 1.69; 95% CI, 1.12–2.22; p = 0.01; I² = 0%) and breast cancer specific survival (HR 1.51; 95% CI, 1.03–2.20; p = 0.04; I² = 53%). No statistically significant association was observed between ATM expression and disease specific survival (HR 3.13; 95% CI, 0.77–12.77; p = 0.11), with substantial heterogeneity (I² = 79%). Conclusions: Low ATM expression is associated with adverse prognostic outcomes in breast cancer, particularly reduced disease free and breast cancer specific survival. ATM may represent a clinically relevant prognostic biomarker; however, further large scale prospective studies are required to validate its prognostic utility and guide biomarker driven therapeutic strategies.

Real-world safety of elranatamab in low-weight patients: Findings from the SUMMIT study.

e23364 Background: Elranatamab is the first BCMA bispecific antibody approved in Japan for treatment of patients with heavily pre-treated multiple myeloma (MM). Although prior clinical work supports the safety of elranatamab’s fixed dose formulation (Elmeliegy 2025), assessing its tolerability across different patient weights in a real-world (RW) context is important, especially in typically lower weight Asian populations. This study aimed to characterize the safety of elranatamab among RW patients with MM by weight in Japan. Methods: SUMMIT is a retrospective cohort study using deidentified administrative claims data from the Japan Medical Data Vision database. Adult patients with a diagnosis of MM who first received elranatamab from March 26, 2024, to March 31, 2025 outside of clinical trials, were included in the study. Five subgroups were created using baseline weight quartiles and a ≤40kg very low-weight (VLW) group. Baseline characteristics and elranatamab administration patterns were reported descriptively. The incidence of adverse events including CRS (Cytokine Release Syndrome), ICANS (Immune Effector Cell-Associated Neurotoxicity Syndrome), and cytopenia (encompassing anemia, leukopenia, lymphopenia, neutropenia, pancytopenia, and thrombocytopenia), was estimated among at-risk patients who had no prior history of the respective events within the preceding 30 days using disease codes following elranatamab initiation (14 days [d], cytopenia only: 8d, 30d). Results: Results for n = 258 elranatamab patients are summarized in Table 1. Safety outcomes were similar across all weight groups, with CRS (14d) ranging 45.5-50.8%. Cytopenia (30d) was similar across quartiles (23.2-28.3%) but differed in the VLW group (43.8%). Conclusions: Safety outcomes and elranatamab administration patterns were comparable for Japanese patients by weight. Further investigation in larger samples of this population is warranted. Baseline characteristics, elranatamab administration and incidence of safety outcomes by weight for RW Japanese patients. VLW≤40.0 kgn=22 Q1≤48.0 kgn=66 Q2>48.0-54.6 kgn=63 Q3>54.6-62.0 kgn=66 Q4>62.0-96.1 kgn=63 Age (median[IQR]) 76.5(69.0-82.0) 74.0(70.0-80.0) 76.0(69.0-79.0) 74.5(68.0-78.0) 72.0(64.0-76.0) Female, n(%) 22 (100.0) 59 (89.4) 43 (68.3) 24 (36.4) 12 (19.0) Time to first full dose, d (median[IQR]) 9.0(7.0-14.0) 8.0(7.0-14.0) 10.0(7.0-13.0) 7.0(7.0-10.0) 7.0(7.0-8.0) CRS (14d), n(%*) 10 (45.5) 30 (45.5) 32 (50.8) 32 (49.2) 29 (46.0) ICANS (14d), n(%*) 0 (0.0) 0 (0.0) 4 (6.3) 3 (4.5) 2 (3.2) Cytopenia (8d), n(%*) 3 (16.7) 6 (10.5) 13 (22.8) 10 (16.7) 11 (19.3) Cytopenia (14d), n(%*) 4 (23.5) 8 (14.5) 14 (25.0) 12 (20.7) 11 (20.0) Cytopenia (30d), n(%*) 7 (43.8) 15 (28.3) 14 (25.9) 13 (23.2) 13 (24.5) *Percentages are calculated based on the at-risk population, not the total cohort.

Prognostic significance of STK11, KEAP1, and NFE2L2- mutations in lung squamous cell carcinoma treated with immunotherapy with or without chemotherapy.

e20635 Background: Mutations in STK11 and KEAP1 are consistently associated with poor prognosis in NSCLC. In the lung squamous cell carcinoma (LSCC) subtype, KEAP1 and NFE2L2 mutations converge on constitutive activation of NRF2, a key oncogenic driver of tumor progression. Although KEAP1 and NFE2L2 are among the most frequently mutated genes in LSCC, their combined prognostic significance along with STK11 in LSCC remains poorly characterized. Methods: This multicenter retrospective study enrolled patients with LSCC treated at Dana-Farber Cancer Institute, Memorial Sloan Ketting Cancer Center, and MD Anderson Cancer Center. Genomic and clinicopathologic data were collected for all patients. Eligible patients received immunotherapy, and with or without chemotherapy. Baseline characteristics and clinical outcomes were systematically assessed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared between groups using the log-rank test. Results: Across the three combined cohorts, a total of 407 patients were included, 99 (24.3%) harbored mutations in at least one of the three genes of interest. The median age was 68 years; 75.4% (n = 307) were male, and 89.9% (n = 366) had a history of smoking. Among mutation carriers, 42 had STK11 mutations, 33 had KEAP1 mutations, and 32 had NFE2L2 mutations, with 8 patients exhibiting co-occurring mutations. Baseline clinicopathologic features were generally well balanced between patients with versus without STK11/KEAP1/NFE2L2 mutations. However tumor mutational burden was higher among STK11/KEAP1/NFE2L2 mutant compared wild-type cases (harmonized TMB 0.35 vs -0.03, p < 0.01). In the pooled cohort, the presence of STK11/KEAP1/NFE2L2 was not associated with response rate (37.4% vs 26.9%, p = 0.06) progression-free survival (PFS HR 1.22; p = 0.10) or overall survival (OS HR 1.09; p = 0.57). When stratified by individual gene (STK11, KEAP1 and NFE2L2), none demonstrated a statistically significant association with, ORR, PFS or OS. Conclusions: STK11, KEAP1, and NFE2L2 mutations, alone or in combination, were not associated with inferior outcomes in patients treated with immunotherapy with or without chemotherapy in LSCC. Unlike non-squamous NSCLC, these alterations appear to have limited clinical impact in LSCC, with important implications for clinical decision-making and for the interpretation and design of future trials.

A study on the application of metaproteomic and serum metabolomic integration analysis in TACE combined with targeted immunotherapy for unresectable hepatocellular carcinoma.

e16207 Background: TACE combined with targeted therapy and immunotherapy represents a potentially effective therapy for uHCC. By evaluating the predictive value of gut microbiota-derived proteins and metabolites for treatment efficacy and prognostic outcomes, this study aims to provide evidence for prognostic stratification in patients in uHCC which received TACE combined targeted and immunotherapy in the real world. Methods: Prospective data of patients (pts) with uHCC who received TACE combined with targeted and immunotherapy were collected, and pts were grouped by therapeutic effect. The primary endpoint was integrated proteomics and metabolomics analysis based on plasma, urine, tumor tissue and faeces were conducted to evaluate the candidate biomarkers for prediction of prognostic outcomes in pts before treatment. Results: As of Jan 16, 2026, a total of 47 pts eligible for HCC were enrolled and 41 were evaluable, 13 (31.7%) had ECOG PS 1, 15 (36.6%) were BCLC C. The results show ORR was 43.9%, and DCR was 80.5%, mOS was 29.0m(95% CI, 22.7-35.3), No grade 5 AEs. The responders (CR+PR) had a longer OS (NR vs 20.6 m, p = 0.006) compared to non-responders (SD+PD). In proteomics analysis, our study indicated both plasma and urine proteomes can reflect the functional difference in tumor tissue between responder and non- responder groups. In serum, proteins associated with growth factor receptor, kinase activity, and programmed cell death exhibited differential expression. In urine, proteins related to metabolic processes demonstrate varying levels of expression. In the metabolomic analysis, all plasma, urine, and faeces can serve as indicators of functional difference in tumor tissue between the two groups. The differential metabolites were associated with amino acid metabolism in plasma, caffeine, ascorbate and aldarate metabolism in urine, and both amino acid and ascorbate/ aldarate metabolism in faeces. A panel including 4 plasma biomarkers and a panel containing 4 urine biomarkers could robustly predict responder group and non- responder group before treatment, with AUC = 0.89 and 0.95 respectively. Metabolites biomarker/biomarker panels in plasma, urine and faeces also demonstrated acceptable predictive performance (AUC = 0.768–0.821). Conclusions: The combination regimen is expected to be a effective treatment for uHCC. Biofluids and faeces multi-omics could reflect the functional differences in tumor tissues between the responder and non-responder pts, and could provide a non-invasive approach to predict treatment responsiveness. Clinical trial information: NCT06540508 . Baseline characteristics. n CR+PR (18) SD+PD (23) P Age (years) 62.2 (9.16) 62.0 (10.24) 0.950 Number of tumors 1 2 (11.1) 1 (4.35) 0.708 2-5 7 (38.9) 12 (52.2) ＞5 9 (50.0) 10 (43.5) Maximum tumor diameter (cm) 8.61 (3.68) 6.38 (4.47) 0.088 PVTT YES 8 (44.4) 6 (26.1) 0.369 NO 10 (55.6) 17 (73.9)

A dual-interface load transfer model for precast concrete-cored cemented soil piles considering progressive damage

Precast concrete-cored cemented soil piles (PCCS) are widely used to improve the bearing capacity of soft ground. However, existing design models usually assume perfect bonding between the concrete core and cemented soil shell, ignoring progressive interface damage under external loads, which leads to inaccuracies in bearing capacity predictions. This study proposes a dual-interface load transfer model that explicitly simulates progressive interface damage. Its innovation lies in the coupling of an exponential damage constitutive model for the inner concrete–cemented soil interface calibrated by direct shear tests with an elastoplastic model for the outer cemented soil–surrounding soil interface, along with a convergent iterative algorithm for solving the governing equations. Verified by field measurements of the test pile in Jiangxi Province, China, the model shows strong agreement with measured data R 2 = 0 . 9746 . Quantitative analysis shows that the concrete core bears more than 90% of the pile-head load, and the cemented soil shows a distinctive C-shaped axial force distribution along the pile shaft. The model captures the coupled evolution of load sharing and skin friction at both interfaces, providing theoretical support for the refined design and safety assessment of PCCS foundations.

Unimolecular Organic Afterglow Luminophore With Anti‐Kasha/Kasha Emission for in Vivo Activatable Imaging

ABSTRACT Afterglow luminescence holds great promise for biomedical imaging by eliminating tissue autofluorescence. Unimolecular afterglow systems avoid the need for nanoencapsulation, providing enhanced simplicity and structure flexibility as well as in vivo stability over common nanoparticle‐based designs. However, rational design remains challenging, and only a few unimolecular systems have been reported. These systems often exhibit low signal intensity, which restricts their biomedical applications. To resolve it, we design a hemicyanine‐based unimolecular organic afterglow platform (CyIA) with high afterglow brightness and structural tunability for in vivo activatable imaging. CyIA displays anti‐Kasha/Kasha dual‐emission with bright afterglow signal in aqueous solution, up to 10 8 p/s/cm 2 /sr, which is nearly three orders of magnitude higher than previously reported unimolecular organic afterglow probes. Leveraging the structural flexibility, a butyrylcholinesterase (BChE)‐activatable afterglow probe (CyIAB‐T) is fabricated. This probe enables a specific and sensitive detection of BChE in Alzheimer's disease (AD) model mice with higher contrast relative to fluorescence imaging. Importantly, this probe permits dynamic tracking of the age‐dependent upregulation of BChE during AD progression. Therefore, this study establishes a versatile unimolecular organic afterglow scaffold with high intensity and structural flexibility for developing activatable afterglow probes for high‐contrast biomedical imaging.

Synergistic 2D/2D g-C3N4/RGO heterojunction coatings for Sustainable textiles: Mechanistic insights into UV protection, self-cleaning, and antimicrobial activity

A multi objective framework with an interactive dashboard for cost optimal infectious disease management

Ngt-1: A glycosyltransferase that confers resistance to three distinct antibiotic classes

External validation of a MMAI model for prognosis and chemotherapy benefit prediction in postmenopausal, node-positive, hormone receptor–positive breast cancer patients: Analysis of SWOG S8814.

107 Background: Despite effective endocrine therapy, the absolute benefit of adjuvant chemotherapy varies widely in node-positive HR+ disease, particularly among patients with 1-3 positive nodes. Prognostic tools for these patients often rely on genomic assays, which are costly, timely, or inaccessible in many clinical settings. We present a multimodal artificial intelligence (MMAI) model that integrates clinical and histopathological data to quickly stratify risk of distant metastasis and inform therapeutic decisions. Developed in six phase III randomized clinical and validated for chemotherapy benefit in N0 patients, MMAI offers an accessible alternative to genomic tools. Here, we validated MMAI for prognosis and prediction of chemotherapy benefit in SWOG S8814 – a randomized phase III trial of tamoxifen ± chemotherapy (CT) in postmenopausal women with node-positive (N+) HR+ breast cancer. Methods: Patients with digitized baseline H&E- stained diagnostic slides and clinical data (age, tumor size, nodal status) were analyzed (N = 413). The locked MMAI generated a continuous risk score and categorical risk groups (low, high). Associations with disease-free survival (DFS; 168 events) and overall survival (OS; 125 events) were assessed using univariable and multivariable Cox Proportional Hazard models. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated. Differential CT benefit was evaluated by estimating relative risk reduction by MMAI risk groups. Results: MMAI was prognostic for DFS (HR per SD 1.73, 95% CI 1.48–2.03; p < 0.001) and OS (HR per SD 1.93, 95% CI 1.60–2.32; p < 0.001), remaining significant after adjustment for age, tumor size, and nodal burden. In the subset of patients with 1–3 positive nodes (n = 253), MMAI identified differential CT benefit: high-risk patients (56% of the patients) demonstrated a 26.3% relative reduction in 10-year DFS risk with CAF-T+TAM versus TAM alone, while low-risk patients (44% of the patients) derived minimal benefit (1.8% relative reduction in 10-year DFS risk). Additionally, the addition of CT resulted in DFS HRs of 1.21 (95% CI: 0.51-2.83) and 0.85 (95% CI: 0.55-1.23) in low- and high-risk patients, respectively. Conclusions: In SWOG S8814, a locked MMAI model using routinely available pathology and clinical data independently stratified prognosis and identified node-positive HR+ patients most likely to benefit from adjuvant CT, with minimal benefit among MMAI low-risk patients with 1–3 nodes. These findings support the use of MMAI as a fast (hours instead of weeks), scalable, cost-effective, and non-tissue consumptive alternative to genomic testing to inform adjuvant decisions in HR+ N+ EBC patients.

Association of high baseline thymidine kinase 1 activity with poor prognosis in breast cancer patients across different molecular subtypes and treatments.

e13093 Background: Despite advances in diagnostics, there is an unmet need of biomarkers able to foresee breast cancer prognosis, particularly in metastatic tumors. Thymidine kinase 1 (TK1) is a surrogate marker of cell proliferation and potentially a prognostic biomarker. We aimed to investigate if the baseline TK1 activity measurement in blood is associated with prognostic end-points. Methods: An electronic database search was done and studies were screened for eligibility. Data extraction was performed for study characteristics, patient demographics, clinicopathological and biomarker measurements, and prognostic end-points. The included studies were evaluated for statistical associations between TK1 activity and various end-points. Results: Altogether, 17 studies were included and comprised of over 4,700 early to metastatic breast cancer patients of different molecular subtypes and treatments. High baseline TK1 activity was associated with increased recurrence and progression, shorter time to progression, shorter progression-free survival, recurrence-free survival, event-free survival, and overall survival. Few studies showed fall in activity in subsequent dosing time points being associated with favorable prognosis. Conclusions: Baseline and prospective measurement of TK1 activity while treating breast cancer of any molecular subtype and treatments can predict prognosis. However, there is an unmet need of standardization of assay, appropriate cut-off and reference ranges so as to facilitate the clinical use of TK1 activity in breast cancer management.

Temporal changes in mortality among adults with breast cancer and diabetes mellitus in the United States.

1116 Background: Breast cancer and diabetes mellitus represent major and intersecting public health challenges in the United States. Although breast cancer mortality has declined over recent decades, the growing prevalence of metabolic comorbidities, particularly diabetes, may offset these gains. National patterns of mortality among individuals with both conditions remain incompletely defined. We evaluated long-term trends and demographic disparities in breast cancer--and diabetes-associated mortality from 1999 to 2023. Methods: We conducted a retrospective population-based analysis using the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) Multiple Cause of Death database (1999–2023). Decedents aged 45–85+ years with breast cancer (ICD-10: C50) and diabetes mellitus (ICD-10: E10–E14) listed as underlying or contributing causes of death were included. Age-adjusted mortality rates (AAMRs) were calculated using the 2000 U.S. standard population. Trends were evaluated using Joinpoint regression to estimate annual percent change (APC) with 95% confidence intervals (CI). Analyses were stratified by age, sex, race/ethnicity, census region, and urbanization. Results: Between 1999 and 2023, 78,253 deaths occurred among adults aged 45–85+ years with breast cancer and diabetes mellitus (1.6% male, 98.4% female). Overall AAMRs increased modestly from 2.64 to 2.84. Females consistently exhibited higher mortality than males (5.00 vs 0.13 in 2023). Non-Hispanic Black individuals had the highest AAMRs (5.61), whereas non-Hispanic American Indian/Alaska Native, Asian, and Native Hawaiian/Pacific Islander populations had the lowest (2.05). Mortality counts were greatest in the Southern region and lowest in the Northeast. Nationally, AAMRs declined from 2004 to 2018 (APC −1.82%; 95% CI, −2.12 to −1.51; P<0.001), followed by a sharp increase from 2018 to 2021 (APC 12.30%; 95% CI, 6.64 to 18.25; P<0.001), with subsequent stabilization. In contrast, males demonstrated a steady increase throughout the study period. Conclusions: Breast cancer– and diabetes-associated mortality declined for more than a decade but reversed sharply after 2018, highlighting the vulnerability of patients with metabolic comorbidity. Persistently higher mortality among women and non-Hispanic Black individuals and the disproportionate burden in the Southern United States underscore important disparities. These findings emphasize the need for integrated oncologic and metabolic risk management strategies and renewed attention to chronic disease control in breast cancer survivorship.

Cumulative barriers to access: An AI-driven analysis of eligibility restrictions, clinical setting, and molecular gatekeeping in 509 interventional glioblastoma trials (2016-2025).

e14065 Background: The 2021 WHO Classification redefined glioblastoma (GBM) via strict molecular parameters. It is unclear how this shift influenced the accessibility of clinical trials and the prevalence of molecular subtypes in study protocols. We utilized a large language model (LLM) to quantify the evolution of eligibility complexity, clinical setting allocation, and biomarker mandates (BM) from 2016-2025. Methods: Glioblastoma trials were extracted from ClinicalTrials.gov (Jan 2016–Dec 2025). An LLM (Gemini 2.5-Flash) parsed unstructured eligibility text from 573 unique protocols (excluding IDH-mutant). Trials were classified as "therapeutic" (disease-modifying intent) or “supportive." Therapeutic protocols were further stratified by clinical setting (newly diagnosed [ND], recurrent restricted, or recurrent open) and BM (requiring biomarkers beyond diagnosis, e.g., MGMT, EGFR). Accuracy was validated via manual review of 30 randomly sampled trials, yielding 93% agreement on clinical setting and 90% on biomarker mandates. Results: 509 (88.7%) of the 573 protocols were classified as therapeutic. Across the decade, protocol complexity remained static (mean exclusion criteria: 13.4, P=0.40). 1) Front-Line Allocation: Clinical settings showed a substantial allocation to the ND population, with 38.3% (n=195) of all therapeutic trials restricted to the front-line setting. 2) Recurrence & Salvage: Among the remaining 314 trials accessible at recurrence, 12.1% (n=38) were restricted to first recurrence only. While 54.2% (n=276) of the therapeutic trials permitted salvage (2nd+ line) entry, 21.4% (n=59) of these enforced additional BM. 3) Molecular Gatekeeping: 24.8% (n=126) of therapeutic trials enforced BM. This proportion fluctuated between 12.8% (2016) and 30.4% (2025) without a statistically significant upward trend (P=0.08). Conclusions: Our AI-driven analysis reveals that while most trials allow salvage entry, access is obstructed by cumulative barriers. Patients face a landscape where 38% of trials are front-loaded to ND disease, and the remaining options are gated by persistent BM and static complexity. This suggests that even trials allowing salvage entry may remain inaccessible to broad patient populations due to these overlapping exclusivity criteria. Comparison of the mean exclusion criteria, biomarker mandates, and clinical setting allocation pre- and post-2021 WHO CNS tumor classification updates. Characteristic 2016-2020 2021-2025 P-Value Total Protocols (N) 235 273 Mean Exclusion Criteria (SD) 14.7 (±7.7) 13.9 (±8.3) 0.25 Biomarker Mandates 53 (22.6%) 72 (26.4%) 0.37 Clinical Setting Allocation 0.53 Newly Diagnosed (Front-line) 87 (37.0%) 107 (39.2%) Recurrent (Restricted/1st Line) 15 (6.4%) 23 (8.4%) Recurrent (Salvage/Open) 133 (56.6%) 143 (52.4%)

Negative effect of malignant pleural effusion on the efficacy of immunotherapy via IL-6–mediated abscopal immunosuppression in advanced non-small cell lung cancer.

12059 Background: The present study is designed to determine the effect and mechanism of malignant pleural effusion (MPE) on the efficacy of immunotherapy in advanced non-small cell lung cancer (NSCLC). Methods: We identified patients with advanced NSCLC who underwent immunotherapy as a first-line or second-line regimen in multiple cohorts. The objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), and overall survival (OS) were analyzed. Using a mouse model with MPE, we determined whether MPE could affect the efficacy of immunotherapy and investigated the mechanism of MPE-related immunosuppression. Results: In a cohort with 269 advanced NSCLC patients who received PD-1 inhibitor alone or combined chemotherapy, MPE occurred in 82 (30.5%) patients. Patients with MPE had a shorter median PFS (4.0 vs. 9.8 months) and OS (21.0 vs. 29.9 months) than those without MPE. MPE was an independent factor affecting PFS (HR:1.87) and OS (HR: 2.73). The ORR for patients with and without MPE was 20% and 34%, respectively. In another cohort with 69 advanced NSCLC patients with MPE who receive PD-1 inhibitor plus chemotherapy plus bevacizumab or PD-1 inhibitor plus chemotherapy, there was no significant difference in median PFS (19.1 vs. 13.2 months) and OS (21.8 vs. 21.6 months), ORR (42.1% vs. 36.8%,), and extrapleural ORR (23.9% vs. 26.3%) between the two groups. In addition, IL-6 levels in serum and pleural effusions were significantly higher in NSCLC patients with MPE. Furthermore, in a mouse tumor MPE model by subcutaneous and pleural injection of lung cancer cells, PD-1 inhibitor did not decrease tumor growth and prolong survival in MPE-bearing mice. Immunohistochemistry and flow cytometry demonstrated the proportion of CD3 + T cells, CD4 + T cells and CD8 + T cells were decreased in the subcutaneous tumors with MPE. Dural blockade with PD-1 inhibitor and IL-6 receptor antibody inhibited tumor growth and prolonged survival of MPE-bearing mice. Conclusions: The occurrence of MPE is negatively correlated with patient outcomes when receiving PD-1 inhibitor or PD-1 inhibitor plus bevacizumab. Elevated IL-6 levels may be responsible for abscopal inhibitory tumor immune microenvironment and reduced efficacy of immunotherapy. Dural blockade of PD-1 and IL-6 could be a promising therapeutic strategy for advanced NSCLC with MPE.