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Molecular profiling of endometrial cancer subsets: <i>Pole</i> hotspot mutations, mismatch repair status, microsatellite instability, TP53 mutation.

e17642 Background: Molecular characterization of endometrial cancer (EC) is essential for therapeutic stratification and prognostic assessment. 1/3 EC cases are mismatch repair deficient (dMMR) in the MLH1, MSH2, MSH6, or PMS2 genes. 10 % EC harbor pathogenic variants within exonuclease domain of DNA polymerase epsilon ( POLE ). Generally, dMMR and POLE mut ECs exhibit favorable survival outcomes due to responsiveness to immune checkpoint inhibitors (ICIs). However, chemotherapy resistance to ICIs has been reported in dMMR and POLEmut subsets,and attributed to potential molecular heterogeneity. The aim of the present study; delineate potential molecular differences among EC subsets. Methods: 214 ECs submitted for routine clinical testing for MMR status and p53 by immunohistochemistry (IHC). POLE hotspot mutations tested via Sanger Sequencing. Comprehensive targeted Next Generation Sequencing (NGS) for microsatellite instability (MSI), tumor mutation burden (TMB), and EC oncogenic mutations. Results: 214 ECs: 30.8% dMMR and 69.2% pMMR. 5.6 % POLE mut cases. 33 samples were selected (11 POLE mut and 22 POLE neg) for comprehensive NGS testing. Herein preliminary findings: 1) POLE mut: all were pMMR. 9 microsatellite stable (MS-S) and 2 microsatellite instability-high (MSI-H). p53 IHC: 3 of 9 MSS p53 aberrant and 6 p53 wt. 2 MSI-H cases p53 aberrant. All p53 IHC results consistent with TP53 mutation. TMB very high in POLE mut (500 Mut/Mb MSI-H, 315 MSS/p53 aberrant, and 201 MSS/p53 wt). All harbor PTEN mutations 2) POLE neg: 8 pMMR and 14 dMMR. Among dMMR, 11 MSI-H, 3 MSS. p53 IHC consistent with TP53 NGS in 3 MSS and 7 out of 8 cases of MSI-H (p53 wt). But p53 IHC and TP53 NGS diverged in 1 of the 8 MSI-H/p53 wt and in MSI-H/p53 aberrant. For pMMR, all 8 cases MSS. However, overall p53 IHC not consistent with TP53 NGS: whereas all 8 cases p53 aberrant, 7 out of the 8 noTP53 mutation. In contrast to POLE mut, TMB in POLE neg significantly lower (avg = 28Mut/Mb), lowest in POLE neg/pMMR (8Mut/Mb). POLE neg/pMMR mostly harbor ARID1A mutations. Conclusions: Cohort demonstrates remarkable molecular heterogeneity among EC cases. In present study, we established molecular classification based on current NCCN guidelines for EC into two main groups based on POLEmut . We further subdivided these two groups based on MMR and microsatellite instability. Then, correlated p53 IHC results with NGS TP53 mutation. Previous studies have associated POLE mut, microsatellite instability (MSI-H), and dMMR with favorable prognosis. These preliminary findings clearly show the presence of additional EC subsets POLE mut/TP53-positive and POLE neg/pMMR/TP53-negative which may point to a poor prognosis (TP53 mutation). We demonstrated the inconsistencies in IHC assay. Taken together, there is necessity for comprehensive and robust molecular testing for accurate prognosis and clinical management.

Evaluation of a tissue-free genome-wide methylome enrichment assay for detecting molecular residual disease (MRD) in patients with head and neck squamous cell carcinoma (HNSCC).

6084 Background: Squamous cell carcinomas comprise ~90% of head and neck cancers (HNCs). Although ~80% of patients with HNSCC are eligible for curative therapy, an estimated 20% to 35% will develop recurrence, typically within 2 years. Recurrence is associated with poor survival, but early detection may enable salvage therapy. We previously reported clinical validation of a tissue-free, genome-wide methylome enrichment MRD assay for recurrence detection in HNC. Here we present performance of an updated classifier in a subset of patients with HNSCC. Methods: Test performance was evaluated using blood samples collected at ~3 (landmark), 12, and 24 mo after curative-intent treatment from patients with stage I-IVb HNSCC. MRD testing was performed using an assay based on cell-free methylated DNA immunoprecipitation and high throughput sequencing (cfMeDIP-seq) as previously described (Liu et al. Ann Oncol . 2025;36(1):108-117). To improve test performance and clinical actionability, we evaluated the effect of defining an indeterminate test category near the classifier threshold. An updated classifier defining 5% of training samples as indeterminate was analyzed in a training set, followed by a pre-specified clinical validation analysis. The primary endpoint was recurrence-free survival (RFS), comparing patients with MRD detected vs not detected. RFS was estimated using the Kaplan-Meier method, with differences assessed by the 2-sided log-rank test. Hazard ratios (HR) were estimated using the Cox proportional hazards model. Results: Among 117 patients in the validation set, median follow-up was 65.3 mo. MRD detection during surveillance was strongly associated with inferior RFS (HR, 54.5 [95% CI, 18.4-161.2]), an improvement over the previously reported HR of 35.7. Lead time between MRD detection and clinical recurrence was up to 10.8 mo (mean, 3.3 mo). MRD detection was also prognostic for OS (HR, 89.3 [11.8-676.4]). The updated classifier showed improved performance, with a sensitivity of 86.7% (26/30) and a specificity of 97.7% (85/87) for recurrence detection. Positive predictive value was 92.9% (26/28); negative predictive value was 95.5% (85/89). Performance was similar ( P =0.24) among patients with HPV-positive oropharyngeal carcinoma (n=52) vs HPV-negative disease (n=65), patients with stage I-II (n=72) vs stage III-IVb (n=45) disease ( P =0.20), and patients with surgery (n=34) vs non-surgical (n=83) definitive treatment ( P =0.37). Conclusions: This study demonstrates that tissue-free, blood-based MRD testing using a genome-wide methylome enrichment platform is prognostic for recurrence in patients with HNSCC treated with curative intent, regardless of stage, HPV status, or treatment modality. The platform offers a robust, sensitive approach for early detection of recurrence in a broad patient population.

A late-phase randomized open-label multi-cohort trial to evaluate immune-related adverse events with different standard-of-care dosing strategies of standard-of-care immunotherapies: ImmuRAd trial.

TPS12172 Background: Programmed cell death-1 (PD-1) inhibitors, such as nivolumab and pembrolizumab, are widely used in treating solid tumors. These inhibitors have multiple FDA-approved dosing schedules. Extended-interval, higher-dose regimens offer patient convenience and health-system efficiencies. However, there is limited comparative prospective data evaluating immune-related adverse events (irAEs) across different dosing strategies. Our study aims to evaluate this important safety question in routine clinical practice. Methods: ImmuRAd is an investigator-initiated, open-label, randomized late phase trial. Adults (≥18 years) with histologically or cytologically confirmed solid tumor malignancies who are scheduled to receive standard-of-care PD-1 inhibitor-based therapy in any disease setting or line of therapy are eligible for the study. Participants are randomly assigned to one of two pre-defined standard dosing strategies based on their physician-selected PD-1 inhibitor cohort. In the nivolumab cohort, patients are randomized 1:1 to receive nivolumab 240 mg every 2 weeks or nivolumab 480 mg every 4 weeks. In the pembrolizumab cohort, patients are randomized 1:1 to receive pembrolizumab 200 mg every 3 weeks or pembrolizumab 400 mg every 6 weeks. Route of administration is at the discretion of the investigator and can be given intravenous or subcutaneous. After completing 12 weeks of therapy, patients meeting predefined treatment-tolerance criteria may transition to extended-interval dosing at the discretion of the treating investigator. The primary objective is to determine the proportion of patients experiencing grade ≥3 immune-related adverse events (CTCAE v5.0) in each dosing arm within each cohort. Secondary endpoints include the incidence of all-grade immune-related adverse events, the time to resolution of these adverse events, treatment discontinuation due to immune-related adverse events, the overall response rate (for patients with measurable disease), progression-free or disease-free survival, and overall survival. Exploratory analyses will investigate the associations between immune-related adverse events and factors such as tumor type, treatment setting, microsatellite instability status, tumor mutational burden, and NGS biomarker profiles. The planned sample size is 192 evaluable patients (96 per cohort and 48 per arm). The study will enroll patients over a period of 24 months and will have a follow-up period of up to 2 years. In this IRB approved clinical trial, safety oversight will be provided by the institutional Data Safety Monitoring Committee. Trial Status: The study is actively enrolling at The University of Kansas Cancer Center and affiliated network sites. Clinical trial information: NCT07174453 .

Impact of AI-based risk stratification integrating routine laboratory data with age on screening volume and multi-cancer early detection yield.

10538 Background: Early cancer detection improves survival, yet population-wide screening remains costly and logistically challenging. Traditional cancer risk models, such as lifestyle-based assessments and polygenic risk scores, offer limited predictive performance. Routine laboratory tests (complete blood count, urinalysis, and biochemical panels) are performed in primary care and may harbor latent cancer signals. We developed an AI-based cancer risk assessment (CRA) model using routine laboratory data to enrich cancer cases and improve the cost-effectiveness of downstream multi-cancer early detection (MCED) testing. Methods: Routine laboratory data from 7,672 individuals (1,245 cancer; 6,427 non-cancer) across two hospitals were retrospectively collected and used to develop a random forest based CRA model incorporating 56 selected routine laboratory features. Among them, 5,392 (70.3%) also underwent OncoSeek test, a validated MCED assay based on seven protein tumor markers (e.g., AFP, CEA). OncoSeek screening performance was estimated under two enrichment strategies: (1) age-based enrichment (≥50 years), and (2) risk-stratified enrichment using a joint CRA–age model. A two-dimensional CRA–age risk landscape was used to estimate cancer incidence across strata. Strata with a modeled cancer incidence ≥0.57%, corresponding to the overall cancer incidence among Chinese adults (GLOBOCAN 2017), were classified as high risk. Performance metrics from both strategies were applied to simulate OncoSeek screening outcomes in a hypothetical cohort of 1,000,000 adults aged ≥20 years. Results: In the simulated cohort with an overall cancer incidence of 0.57%, direct OncoSeek screening detected 2,450 cancers with a PPV of 5.6%. Age-based screening (≥50 years) required screening 536,206 individuals (−46.4%), increased cancer incidence to 0.92%, and detected 2,327 cancers. In contrast, CRA–age risk-stratified screening reduced the screened population to 178,660 individuals (−82.1%), enriched cancer incidence to 2.69%, and detected 2,402 cancers. Compared with age-based screening, CRA–age stratification improved PPV from 7.6% to 15.9%, reduced false positives by 55.2% and lowered the cost per cancer detected from $18,436 to $5,950 (−67.7%), while preserving overall cancer detection. Conclusions: AI-based CRA–age risk stratification enables efficient population-level cancer screening by restricting downstream MCED testing to a high-risk subset comprising approximately one-fifth of the population, while preserving overall cancer detection. This strategy substantially improves PPV, reduces false positives, and lowers the cost per cancer detected. These findings support a risk-stratified MCED screening paradigm as a scalable and economically sustainable alternative to population-wide or age-based population screening.

A single-arm, phase 2 study of neoadjuvant mirvetuximab soravtansine and carboplatin for FRα-expressing advanced-stage serous epithelial ovarian, fallopian tube, or primary peritoneal cancer (M25-231; NCT06890338; GOG-3115).

TPS5633 Background: Folate receptor alpha (FRα) has limited expression on normal tissues but is highly expressed in most high-grade serous epithelial ovarian cancers (EOC), making it an attractive therapeutic target. Mirvetuximab soravtansine (MIRV), an antibody-drug conjugate targeting FRα, has demonstrated efficacy and manageable safety in recurrent, FRα-expressing EOC when used as monotherapy. Additionally, a phase 1b/2 study (IMGN853-0402) of MIRV + carboplatin showed promising clinical activity in patients with platinum-sensitive ovarian cancer who had tumor recurrence after platinum-based chemotherapy. The safety and efficacy of neoadjuvant MIRV + carboplatin in newly diagnosed, advanced-stage FRα-expressing high-grade serous ovarian cancer (HGSOC) remains unknown. Methods: This single-arm phase 2 trial will evaluate the safety and efficacy of MIRV + carboplatin in newly diagnosed patients with advanced-stage (Stage III/IV), FRα-expressing (≥75% tumor cells with ≥2+ membrane intensity per the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay [Roche Diagnostics]) HGSOC. Approximately 140 patients (aged ≥18 years) will be enrolled; 5 patients were enrolled as of January 23, 2026. Patients will receive ≤6 cycles of MIRV (6 mg/kg adjusted ideal body weight) and carboplatin (AUC 5) intravenously every three weeks before interval debulking surgery (IDS), with a total of ≤9 cycles pre- and post-IDS. IDS suitability will be evaluated radiologically, and all eligible patients, including those with progressive disease (PD), will undergo IDS after Cycle 3 Day 1. IDS-ineligible patients may receive ≤3 additional cycles and undergo repeat imaging to assess IDS suitability. Patients with complete response (CR), partial response (PR), or stable disease will resume MIRV + carboplatin 3–6 weeks post-IDS following radiologic assessment. At the treating physician’s discretion, bevacizumab may be added post-IDS and standard-of-care maintenance therapy may begin ≥21 days after MIRV + carboplatin ± bevacizumab completion. Imaging will occur every 9 weeks after IDS (for those who undergo IDS) or last radiologic tumor assessment (for those who do not) until 1 year from the first dose of study treatment and then every 12 weeks until PD, death, or withdrawal of consent. The primary endpoint is objective response (OR), defined as best overall response of radiographic CR or PR assessed by Independent Central Review (ICR) per Response Evaluation Criteria in Solid Tumors v1.1 prior to initiation of subsequent anticancer therapy (including IDS). Secondary endpoints include OR by investigator (INV), disease control by ICR and INV, IDS, extent of cytoreduction at the time of IDS, cancer antigen 125 response, progression-free survival by INV, and patient-reported outcomes (NFOSI-18). Clinical trial information: NCT06890338 .

Clinicopathologic profile and comparative performance of limited next-generation sequencing and qPCR for detection of <i>RAS/RAF</i> mutations in stage IV colorectal cancer (mCRC).

e15576 Background: The implications of limited next-generation sequencing (NGS) compared with quantitative/real-time PCR (qPCR) in metastatic colorectal cancer (mCRC) remain unclear in resource-constrained settings. Our study explores correlations between genetic alterations and patient demographics, and compares the sensitivity, specificity, and concordance rate of KRAS, NRAS, and BRAF mutation analysis detected by NGS with qPCR in mCRC. Methods: A prospective analysis was conducted on stage IV colorectal cancer patients diagnosed at a tertiary academic institute in Eastern India, from September 2023 to March 2024. Data on age, gender, tumour grade, tumour location, mismatch repair (MMR) status by immunohistochemistry, and mutations in TP53 , KRAS , NRAS , BRAF , PIK3CA , and HER2, detected by NGS on formalin-fixed, paraffin-embedded tumour tissue blocks, were collected. Post-NGS paraffin blocks with adequate tumour tissue remaining were taken up for qPCR analysis of KRAS, NRAS, and BRAF mutations. Statistical analysis was done using SPSS Statistics (version 27). Results: A total of 90 patients (male-50, 55.6%; female-40, 44.4%; median age 51 years) were included in the study. The Majority had left-sided tumours (63.3%), with rectum being the most common (MC) site (33.3%). MC mutation was TP53 [more in left-sided tumours (p = 0.042)]. BRAF mutations were more common in males (p = 0.034) and grade 3 histology (p = 0.006). Younger patients (15–39 years) had higher-grade tumours (p = 0.007), KRAS mutations (p = 0.084) and deficient MMR (dMMR) (p = 0.047). Only 39 patients were eligible for evaluation of BRAF mutation by qPCR post-NGS, for which the sensitivity, specificity, and concordance rate were 100%, 97.29% &amp; 97.43%, respectively. 34 and 28 patients were eligible for evaluation of KRAS and NRAS mutations by qPCR post-NGS. The sensitivity, specificity, and concordance rate for KRAS and NRAS detection were 100%, 87.5% &amp; 85.29%, while for NRAS, they were 100%, 96.29% &amp; 96.42%, respectively. The marginally lower specificity observed for KRAS and NRAS was attributable to additional variants ( BRAF D594G; KRAS G13C, G12V, R68M; NRAS G12D) uniquely identified by NGS. Conclusions: In low-and middle-income country settings, where access to comprehensive NGS remains limited by cost and infrastructure, our findings provide important evidence that targeted qPCR can reliably identify key actionable mutations required for standard-of-care treatment decisions in mCRC. A stepwise testing strategy, employing limited NGS or qPCR initially followed by comprehensive NGS only in highly selected patients, can optimize resource utilization, reduce diagnostic delays, and expand equitable access to precision oncology.

Treatment of localized pulmonary pleomorphic adenocarcinoma: A systematic review and meta-analysis.

e20040 Background: Pulmonary pleomorphic adenocarcinoma (PPADC) is a rare, aggressive subtype of non-small cell lung cancer (NSCLC) classified under pulmonary pleomorphic carcinoma (PPC), defined as NSCLC with ≥10% spindle or giant cell components or entirely sarcomatoid elements. Optimal treatment for localized disease remains undefined, with surgical resection as the mainstay and uncertain benefits from perioperative chemotherapy or radiotherapy. Methods: A systematic search of PubMed, Cochrane, and ClinicalTrials.gov was conducted in accordance with PRISMA guidelines, identifying five studies on localized PPADC treatment. Inter-study heterogeneity was evaluated using the DerSimonian-Laird estimator. Pooled analyses with 95% confidence intervals (CIs) were conducted via the 'meta' package in R (version 4.16-2). Results: Across five retrospective studies (2007-2018), 162 patients with localized PPADC were analyzed. Median age was 64.7 years (range, 35-90); 85% (n=138) were male. Disease distribution: stage I, 40% (n=66); stage II, 40% (n=64); stage III, 20% (n=32). Tumors were predominantly upper-lobe (70%, n=123) and peripheral (31%, n=51), with a median size of 49 mm (range, 11-100). Median follow-up was 32 months (range, 5-120). Neoadjuvant chemotherapy was rare (n=2/162, 1.2%; poor response). All underwent curative-intent resection; adjuvant chemotherapy/radiation was inconsistent. Pooled 5-year overall survival (OS) was 41.7% (95% CI, 32.3-51.4; I²=91%; P&lt;0.01; n=107); disease-free survival (DFS), 46.7% (95% CI, 32.3-61.3; I²=70%; P=0.07; n=47). Pooled 1-year recurrence rate was 40% (95% CI, 30.2-50.1; I²=0%; P=0.40; n=95). Reported adverse events (Ji et al.): atrial fibrillation (7%, n=4/60), prolonged air leak (5%, n=3), infection (3%, n=2), hemothorax requiring reoperation (2%, n=1), hoarseness (2%, n=1). Conclusions: Localized PPADC is associated with poor long-term outcomes despite curative resection. Evidence is constrained by small retrospective series and variable perioperative therapy use. Prospective trials are essential for refining strategies and improving patient selection.

Safety, efficacy, and immunogenicity of adjuvant therapy with personalized cancer vaccine (PCV) RGL-270 in combination with adebrelimab and mFOLFIRINOX in resectable pancreatic ductal adenocarcinoma (PDAC).

4231 Background: Tumor specific neoantigens are peptides carrying somatic mutations presented by HLA molecules and recognized by T cells, which subsequently induce specific immune response (IR). The IR could be further boosted when in combination with PD-1/L1 inhibitor. RGL-270 is a lipid nanoparticle (LNP)-encapsulated, mRNA-based PCV, encoding tumor specific neoantigens screened via a proprietary algorithm to induce patient specific IR. This investigator-initiated, open-label, dose escalation and expansion clinical trial was conducted in China, to evaluate the safety, efficacy and immunogenicity of RGL-270 in combination with adebrelimab (anti-PD-L1 mAb) in patients with resectable PDAC. Methods: PDAC patients with R0/R1 surgical margins were enrolled. After surgery, RGL-270 was administrated up to 9 cycles, in combination with adebrelimab and followed by modified FOLFIRINOX chemotherapy. The key endpoints included safety, efficacy assessment with recurrence-free survival (RFS), overall survival (OS), 18-month RFS rate, and PCV specific IR evaluation by ELISpot. Results: As of 01/15/2026, 16 patients in the dose escalation (n = 7) and expansion (n = 9 at expansion dose level) stage received RGL-270 combo with adebrelimab therapy. Up to date, all dose levels were safe and well tolerated. The most common treatment-related adverse events (TRAEs) were fever, influenza-like illness and injection-site reactions. All TRAEs were CTCAE grade 1~2 and no treatment-related SAE or DLT was reported. Currently, the median follow-up is 18.0 months, with median RFS and OS not reached yet, and the 18-month RFS rate is 100%.The PCV-specific IR positive rate was 100%. Interestingly, IR was also detected in patients who had undergone prior splenectomy (5/16). The primary IR emerged as early as 2 cycles after the first PCV administration, with the best of response (BoR) observed 2~4 cycles post-baseline and, in most cases, persisting until cycle 9, the booster cycle. To date, no dose-dependent manner for IR has been observed. Additionally, concordance between the predicted and immunogenic neoantigens was analyzed, and the resulting insights were fed back to improve the neoantigen screening algorithm. Furthermore, bulk T-cell receptor sequencing was performed to further characterize the PCV specific IR. Conclusions: Based on proprietary LNP delivery systems, algorithms for neoantigen identification and immunogenicity prediction, the combination treatment of RGL-270 and adebrelimab demonstrated a favorable safety profile, promising efficacy, and robust immunogenicity. This preliminary result guarantees the further development of PCV-based anti-tumor therapy in the adjuvant setting for PDAC. Clinical trial information: NCT06156267 .

Proglumide, gemcitabine (GEM), and nab-paclitaxel (NAB-P) in patients (pts) with pancreatic ductal adenocarcinoma (PDAC): Results of the phase 1 PROGEM trial.

4202 Background: PDAC has a poor prognosis and resistance to therapy due to its desmoplastic and immunosuppressive tumor microenvironment (TME). In animal models of PDAC, the cholecystokinin-B receptor (CCK-BR) antagonist, proglumide, was shown to decrease tumoral fibrosis, alter the tumor immune cell signature, and increase chemotherapy uptake and T-cell infiltration into tumors, resulting in decreased metastases and improved survival. We sought to evaluate the safety of proglumide with GEM/NAB-P chemotherapy in pts with metastatic PDAC (mPDAC). Using tumor biopsies and a blood biomarker assay, we also studied the combined effects of proglumide with GEM/NAB-P on the TME. Methods: The PROGEM study was a phase 1 trial of proglumide 1200 mg PO daily, GEM 1000 mg/m2 IV, and NAB-P 125 mg/m2 IV days 1, 8, and 15 every 28 days in GEM-naïve pts with mPDAC (NCT05827055). The primary endpoints were safety and determination of the recommended phase 2 dose (RP2D). Safety was assessed with adverse events (AEs) according to CTCAE v. 5 criteria. Tumor biopsies were obtained pre-treatment and at 8 weeks on-treatment and analyzed by histology and multiplex immunohistochemistry for changes in the TME. A liquid biopsy serum sample was collected at baseline, week 8, and end-of-treatment (EOT) for analysis of a microRNA biomarker panel reflecting changes in the TME. McGill pain surveys were done at baseline, week 8, and at EOT. Results: Six pts were enrolled. Three pts were treatment-naïve, and 3 had had prior mFOLFIRINOX. No AEs related to proglumide were reported. Five pts had stable disease, and 1 pt had disease progression as the best response, for a disease control rate of 83%. Median progression-free survival was 4 months, and median overall survival was 8.5 months. Compared to baseline, on-treatment biopsies showed an 81% decrease in Ki67+ cells; a 75% decrease in M2-polarized tumor-associated macrophages; a 42% decrease in tumor collagen content, and a 13-fold increase in CD8 T-cells. Pre- and on-treatment blood biomarkers showed changes correlated with histology and clinical course. Anti-fibrosis markers (miR185, miR346, and miR378) and inhibitors of epithelial to mesenchymal transition (miR200 and miR205) increased with therapy. MiR122, which regulates cell cycle and growth, decreased initially but increased at the time of progression. Pain scores showed improved pain at week 24 or EOT. Conclusions: Proglumide is safe in pts with mPDAC, and the RP2D is 1200 mg PO daily with standard dose GEM/NAB-P. Proglumide remodels the TME by decreasing fibrosis and immunosuppression while increasing T-cell infiltration. Changes in circulating microRNAs offer a promising non-invasive biomarker panel for monitoring treatment response. These results support further investigation of proglumide with GEM/NAB-P in a phase 2 clinical trial and future immunotherapy combinations. Clinical trial information: NCT05827055 .

Failure-to-rescue following acute hepatic decompensation in hospitalized patients with hepatocellular carcinoma in the United States, 2018–2022.

e23119 Background: In hospitalized oncology populations, mortality may be influenced by failure to rescue after acute deterioration. Hepatocellular carcinoma (HCC) is frequently complicated by hepatic decompensation, yet national data describing failure-to-rescue patterns in this population remain limited. Methods: A serial cross-sectional analysis was conducted using the 2018–2022 Healthcare Cost and Utilization Project National Inpatient Sample. Adult hospitalizations with a principal diagnosis of hepatocellular carcinoma were identified. Acute hepatic decompensation was defined using secondary diagnosis codes for ascites, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, or spontaneous bacterial peritonitis. Failure-to-rescue was defined as in-hospital mortality among hospitalizations with hepatic decompensation. Outcomes included in-hospital mortality, length of stay (LOS), and hospitalization cost estimated using cost-charge ratios. National estimates accounted for survey weighting, clustering, and stratification. Stratified analyses evaluated outcomes by hospital teaching status, bed size, region, and patient urban–rural residence. Survey-weighted multivariable logistic regression, restricted to decompensated hospitalizations, identified factors independently associated with in-hospital mortality. Results: From 2018–2022, 22,531 unweighted HCC hospitalizations represented an estimated 112,655 hospitalizations nationally. Acute hepatic decompensation occurred in 41.1% of hospitalizations. Overall in-hospital mortality was 7.6%, increasing to 12.8% among hospitalizations complicated by hepatic decompensation, compared with 1.4% among non-decompensated admissions. Decompensated hospitalizations were associated with longer LOS (7.51 vs 5.66 days) and higher costs ($31,941 vs $25,644). Failure-to-rescue varied across hospital settings, with lower mortality at teaching and large hospitals despite similar decompensation incidence. In adjusted analyses restricted to decompensated hospitalizations, admission to a teaching hospital was associated with lower odds of mortality (adjusted odds ratio 0.39, 95% CI 0.26–0.59). Increasing age, non-private insurance, and Black race were independently associated with higher mortality, while hospital bed size and region remained significant. Conclusions: Among HCC hospitalizations, hepatic decompensation was common and associated with higher inpatient mortality, longer length of stay, and higher costs. Although decompensation incidence was similar across settings, failure-to-rescue varied by hospital characteristics and region. These findings provide benchmarking data for rescue outcomes following acute hepatic decompensation in hospitalized patients with HCC.

Don’t ask, don’t tell: Missing ECOGS and anticancer treatment, neutrophil-to-lymphocyte ratios, and outcomes in hospitalized patients with solid tumors.

e24071 Background: ASCO’s Choosing Wisely campaign has recommended avoiding cancer-directed therapy for patients with ECOG performance status (PS) 3–4. Hospitalized patients with solid tumor patients frequently have poor PS, yet ECOG documentation is often missing, potentially contributing to non-beneficial treatment. Caregiver-reported ECOG may offer a pragmatic alternative source of functional status information. Methods: We are enrolling hospitalized patients with solid tumors and their personal caregivers from a NYPresbyterian-affiliated (Weill, Queens, Brooklyn Methodist) Hospital (preliminary analyses on the first 21). Caregivers (e.g., spouses/partners) completed ECOG PS and sarcopenia assessments at baseline. Medical charts were reviewed for ECOG documentation, anticancer treatments, and neutrophil-to-lymphocyte ratio (NLR) values closest to baseline and 3-month follow-up. Caregiver expectations were assessed at baseline and patient survival and quality-of-life at 3 months. Results: ECOG PS was undocumented in 88% of charts within 48 hours of baseline. Caregivers rated 70% of patients as ECOG &gt; 2. Over 80% had NLR &gt; 4 (indicating significant inflammation). Patient sarcopenia assessments were completed by 88% of caregivers (vs. 22% of patients). Caregiver-rated patient functional impairment was substantial: 56% could not lift 10 lbs., 61% could not walk, and 41% could not transfer independently. Despite poor PS and high NLR, more than half were receiving anticancer therapy; most were offered at least one modality (chemotherapy 75%, immunotherapy 25%, targeted therapy 17%, radiation 32%, surgery 17%). Caregivers strongly endorsed treatment, with 65% wanting inpatient chemotherapy and most believing it would improve quality of life (71%) and 3-month survival (69%). At follow-up, 58% of patients had died; among survivors, 66% continued to have NLR &gt; 4. Conclusions: Hospitalized patients with solid tumors in this cohort were acutely ill, yet ECOG PS was rarely documented. Caregivers provided feasible and clinically plausible assessments of ECOG and sarcopenia. Despite caregiver-identified poor PS and high NLR, most patients were offered and received anticancer therapy; the majority died within 3 months. Caregiver-reported ECOG may represent a scalable, underutilized clinical signal to guide more treatment decisions for hospitalized patients with solid tumor cancers.

Temporal and demographic trends in mortality from multiple myeloma with coexisting mental and behavioral disorders in U.S. adults, 1999–2023.

e22592 Background: Multiple myeloma is a plasma cell malignancy with a persistently high mortality rate; when it occurs in patients with mental and behavioral disorders, it negatively affects treatment adherence, disease management, and survival outcomes. In this study, we aimed to discuss the temporal and demographic trends of this comorbidity among the adult population in the United States. Understanding these temporal trends is crucial for identifying vulnerable subgroups, guiding policy, and informing integrated oncologic and mental health care. Methods: Mortality data was obtained from the Centers for Disease Control and Prevention (CDC) WONDER website. International Classification of Disease (ICD-10) code used for multiple myeloma was C90.0 and F01-99 for mental and behavioral disorders. Data were obtained for adults aged 25 years and above. Joinpoint regression was used to calculate APC (Annual Percent Change) and AAPC (Average Annual Percent Change) values per 100,000 population. A p value of less than 0.05 was considered statistically significant. Results: Between 1999 and 2023, multiple myeloma mental and behavioural disorders among adults ≥25 years led to 20,414 deaths, with the most deaths being recorded at medical facilities (31.90%). The AAMR rose from 0.09 in 1999 to 0.49 in 2023 with an associated AAPC of 6.4675* (p &lt; 0.000001). In 1999, men had an AAMR of 0.13, while women had an AAMR of 0.07. This almost increased 5 times in 2023, where men had an AAMR of 0.67 (AAPC: 7.06 p &lt; 0.000001), while women had an AAMR of 0.37 (AAPC: 4.88; p &lt; 0.000001). Black or African American individuals had an AAMR of 1.01 in 2023 (AAPC: 5.1949*, p &lt; 0.000001), which was almost twice as high as the AAMR of White individuals, who experienced an AAMR of 0.46 (AAPC: 6.5591*, p &lt; 0.000001) in 2023. States with the highest AAMRs included Vermont (0.67), Oregon (0.65) and North Dakota (0.63); states with the lowest AAMRs included California (0.17), Alabama (0.18) and Nevada (0.19). Geographically, the Midwest had the highest AAMR of 0.56 in 2023 (AAPC: 8.1007*; p &lt; 0.000001), followed by the South with an AAMR of 0.54 (AAPC: 5.4181*; p &lt; 0.000001), then the Northeast with an AAMR of 0.41 (AAPC: 7.3614*; p &lt; 0.000001) and the West with an AAMR of 0.41 (AAPC: 4.4606*; p &lt; 0.000001). Conclusions: Multiple myeloma mortality among adults with coexisting mental and behavioral disorders has increased significantly in the United States over the past two decades. Pronounced disparities, with the highest burden among males, Black individuals, and residents of the Midwest. These findings highlight vulnerable populations experiencing a disproportionate mortality burden. Targeted, integrated oncologic and mental health interventions are needed to reduce disparities and improve survival outcomes.

Antibiofilm efficacy of biosynthesized silver nanoparticles against ampicillin-resistant Staphylococcus aureus: Inhibition on AgNP-coated urinary catheters

Orbital Electrowetting: From Continuous Droplet Transport to Programmable Microfluidics

ABSTRACT Droplet transport on solid surfaces underpins applications in microfluidics, thermal management, and water harvesting. Conventional electrowetting (CEW) has enabled digital droplet control, but reliance on numerous individually addressed electrodes, complex driving circuitry, and step‐wise motion has limited scalability and practical deployment. Orbital electrowetting (OEW) has recently been introduced as a complementary paradigm, where asymmetric electrowetting forces and electrostatic energy gradients drive droplets into continuous, high‐speed motion along predefined orbital pathways using only a minimal number of electrodes and simple global excitation. In this perspective, the physical mechanisms of OEW are summarized, with emphasis on how surface wettability, electric field distribution, and orbital geometry govern droplet speed, stability, and confinement. Key challenges are identified, including the current lack of robust bidirectional and position‐resolved control in complex networks. Future directions and application opportunities for OEW‐enabled platforms are outlined, such as programmable microfluidics with low overhead wiring, defogging and self‐cleaning of photovoltaic modules, enhancement of condensation heat transfer, and atmospheric water harvesting when combined with passive radiative cooling surfaces. It is argued that, as these challenges are addressed, OEW will substantially expand the electrowetting toolbox for next‐generation droplet manipulation and water‐energy technologies.

EU-OPEN: A novel approach for generating European oncology real-world evidence at scale.

11161 Background: The European Oncology Platform for Evidence Needs (EU-OPEN) is a strategic initiative to generate high-quality oncology real-world evidence (RWE) in Europe. It focuses on establishing multi-study partnerships with access to clinically rich data, regional medical expertise and to enable adoption of novel approaches to conduct research on cohorts of interest efficiently at scale. Methods: For each tumor area (e.g., EU-OPEN Breast) , master protocols aligned to specific patient populations (e.g., ER+/HER2- earlier stage breast cancer or triple negative metastatic breast cancer) are developed alongside a fit-for-purpose data assessment at prospective data partners (primarily hospital sites and registries). Data partners are selected based on their data availability, data quality and operational aspects of collaboration. After finalizing the master protocol, supporting documentation (including common data models and statistical analysis plans) are prepared and shared with partner sites for consistent execution. Data partners then curate, harmonize and analyze data in accordance with the study requirements. Studies and patient cohorts can be efficiently refreshed to capture longer-term outcomes. Results: The initiative began in 2024 with a multi-tumor assessment of prospective data partners and an early breast cancer pilot study (completed and published in 2025). EU-OPEN has since expanded to metastatic breast, endometrial, ovarian and esophageal cancers. Collectively these studies encompass 11 cohorts and plan to include &gt; 2,200 patients. Future plans include expanding to additional tumor areas and data partner types, adopting advanced capabilities such as natural language processing (NLP) to maintain ‘live cohorts’ for rapid analyses, and strengthening governance through clinical and data committees across partners. Conclusions: EU-OPEN demonstrates a scalable, efficient approach to generating research-grade European Oncology RWE at scale. As the initiative grows, adoption of novel technologies and deeper collaboration with data and clinical experts will further accelerate insight generation.

The prognostic impact of epilepsy in glioblastoma: Insights from a systematic review and meta-analysis.

e14038 Background: Epilepsy is a common comorbidity in patients with glioblastoma (GBM) and significantly impacts quality of life and clinical management. Whether epilepsy itself or the choice of antiepileptic drugs (AEDs) influences overall survival remains controversial, with conflicting results reported across observational and interventional studies. Methods: Following PRISMA 2020 guidelines, a systematic review and meta-analysis were performed across PubMed, Cochrane Library, Google Scholar, Mendeley, and Open Evidence (January 2015 - December 2025). Eligible studies included adults (≥18 years) with histologically confirmed GBM reporting seizure incidence, clinical features, or treatment outcomes. Data extraction and bias assessment were independently conducted by four reviewers. Results: Thirty-four studies were included, comprising 28 primary studies and 6 prior systematic reviews. Across high-quality pooled and registry-based analyses, no consistent survival advantage was associated with the use of specific AEDs, including valproic acid or levetiracetam, after adjustment for molecular and clinical confounders. Levetiracetam demonstrated equivalent or superior seizure control with a more favorable safety profile compared with valproic acid. IDH mutation status and MGMT promoter methylation emerged as the strongest independent prognostic factors for both survival and seizure-related outcomes. Conclusions: Epilepsy in GBM is associated with favorable molecular subtypes and improved survival, likely reflecting less aggressive tumor biology. Levetiracetam remains the preferred agent for tumor-related epilepsy management in glioblastoma. Quality assessment of observational studies (Newcastle-Ottawa Scale). Study Selection (Max 4) Comparability (Max 2) Outcome (Max 3) Total Score (Max 9) Overall Quality Knudsen-Baas et al. (2016) 4 2 3 9 Very Low Risk Chen et al. (2017) 4 2 2 8 Low Risk Watanabe et al. (2017) 4 1 3 8 Low Risk Toledo et al. (2017) 3 2 3 8 Low Risk Salvati et al. (2018) 3 2 3 8 Low Risk Pallud et al. (2024) 3 2 3 8 Low Risk Bianconi et al. (2024) 3 2 3 8 Low Risk Cardona et al. (2017) 3 2 3 8 Low Risk Yu et al. (2018) 3 2 3 8 Low Risk Happold et al. (2016) 3 2 3 8 Low Risk Salvati et al. (2020) 3 2 2 7 Low Risk Feyissa et al. (2019) 3 2 2 7 Low Risk Li et al. (2021) 3 2 2 7 Low Risk Bushara et al. (2021) 3 2 2 7 Low Risk Ollila &amp; Roivainen (2025) 3 1 3 7 Low Risk Al-Dorzi et al. (2023) 3 2 2 7 Low Risk Ryu et al. (2019) 3 2 2 7 Low Risk Tinchon et al. (2015) 3 2 2 7 Low Risk Yang et al. (2023) 4 1 2 7 Low Risk Hattori et al. (2023) 3 2 2 7 Low Risk van der Meer et al. (2023) 3 2 2 7 Low Risk Królicki et al. (2018) 3 0 3 6 Moderate Risk Sughrue et al. (2015) 3 1 2 6 Moderate Risk Casas Parera et al. (2019) 3 0 3 6 Moderate Risk Maschio et al. (2017) 2 0 2 4 Moderate Risk Rades et al. (SURF-ROGG) 1 0 1 2 High Risk

Frameworks for improving comprehensive biomarker testing in NSCLC: A multi-stakeholder consensus.

e23121 Background: Despite the availability of numerous targeted therapies for NSCLC, significant barriers persist in ensuring timely comprehensive biomarker testing, leading to suboptimal patient outcomes and inequitable care. To better understand system-level barriers and develop actionable solutions, multidisciplinary experts from four stakeholder perspectives were convened in a structured two-day workshop in the United States: clinicians (oncology, pathology, surgery), laboratory diagnostics, payers, and manufacturers. Methods: A validated, stepwise consensus process with 30 experts was conducted to qualitatively and quantitatively identify barriers and solutions across the NSCLC patient journey. World Café-style small group discussions were used, with participants rotating across thematic care-stage tables (diagnosis through survivorship). Synthesized results were prioritized via iterative digital voting based on impact, relevance, and feasibility. Prioritized solutions were consolidated into idea profiles and translated through a standardized concept development process into pilot-ready concepts. Results: Key barriers to comprehensive biomarker testing in NSCLC included delayed or inconsistent NGS testing and result reporting, tissue inadequacy, non-standardized biomarker reporting, payer coverage and authorization barriers, and fragmented multispecialty care coordination. A total of 26 solutions were generated and consolidated into 8 idea profiles. Expert voting prioritized 3 of these profiles (Table 1), which informed development of 2 minimum viable products (MVPs) addressing upstream and downstream gaps in comprehensive biomarker testing and treatment initiation. MVP 1 focuses on accelerating availability of biomarker results through automated, concurrent reflex NGS testing using tissue and plasma (ctDNA) at diagnosis, supported by standardized pathology workflows. MVP 2 addresses downstream delays by integrating molecular results with therapy authorization and payer approval within a single digital workflow, reducing administrative friction and enabling timely guideline-based treatment decisions. Conclusions: This structured, multi-stakeholder consensus process identified key cross-system barriers to timely and comprehensive biomarker testing in NSCLC and generated feasible, high-impact solutions, including automated reflex testing and integrated access workflows. These findings highlight actionable opportunities to improve delivery of the right therapy to the right patient at the right time, with potential applicability beyond NSCLC. Selected Top 3 Idea Profiles Mean Rank Votes (clinician / payer / lab / manufacturer)* Reflex Biomarker Testing Pathway 1.7 2.2; 2.3; 1.0; 1.2 PA Fast-Track &amp; Coverage Clarity 3.1 4.0; 1.7; 2.5; 4.2 Value-Based Testing &amp; Therapy Bundle 3.9 5.1; 3.0; 4.5; 3.0 *Scale 1 (highest) – 8 (lowest).

The effects of specialized сardio-oncological care on the duration of TKI therapy.

e24030 Background: tyrosine kinase inhibitors (TKIs) often cause arterial hypertension (AH) that leads to dose reduction/withdrawal of them, but studies of effects on prognosis of goal blood pressure achievement are lacking. Methods: patients (n = 54, 78% men, median age 67 yrs) with metastatic renal cell carcinoma were divided into 2 groups before starting TKI treatment: in the control group, patients were observed during TKI-therapy by GP at local clinic, in the intervention group patients attended the cardio-oncological center (multicomponent antihypertensive therapy with rapid dose titration using telemedicine technologies). At the end of the study, the time to withdrawal/dose reduction of TKI (months) due to progression or intolerable toxicity, as well as overall survival (OS) and progression-free survival (PFS) in the groups were analyzed using the Kaplan-Mayer method and the median time to withdrawal/dose reduction of TKI/progression/death/ in the groups according to the Mann-Whitney criterion were compared in groups. Results: in the intervention group, 28 out of 38 patients stopped treatment with the prescribed TKI at the initial dose, the median time to TKI withdrawal was 9.7 months (95%CI = 4-15.5). During the study, 12 patients died, and the median OS was 15.8 months (95%CI = 0-38.2). Progression occurred in 23 patients, and the median PFS was 13.3 months (95%CI = 3.4-23.2). In the control group, 14 out of 16 patients stopped treatment with the prescribed TKI at the initial dose, the median time to TKI withdrawal was 2.7 months (95%CI = 1.3-4.1). During the study, 14 patients died, with a median OS of 9.8 months (95%CI = 7.6-12.1). Progression occurred in 11 patients, and the median PFS was 6.4 months (95% = 1.3-11.5). Statistically significant differences in the control and intervention groups according to the Mann-Whitney criterion were observed only in the time before the withdrawal of TKI (p = 0.001). Differences in OS and PFS were not statistically significant (p = 0.085 and p = 0.06, respectively). Conclusions: observation in cardio-oncological center has advantage over local clinics. The small sample size suggests further studies to assess the impact of specialized cardio-oncological care on prognosis with antiangiogenic therapy.

Spatial mapping of human colorectal cancer cell states to identify co-targeting opportunities and determinants of drug response.

3140 Background: Colorectal cancer (CRC) progression relies on multiple mechanistically distinct proliferative and survival programs differing in lineage dependence, plasticity, and environmental sensitivity. LGR5-driven proliferation represents a stem-like program, whereas non-LGR5 modes—including progenitor, KRAS/MAPK, AP-1, and YAP-driven proliferation—reflect inflammatory and adaptive states that may confer therapeutic resistance. Single-cell studies revealed these programs, but technical barriers have restricted their quantitative and spatial analysis in human tumors, limiting translation to drug development and patient stratification. Methods: We integrated single-cell RNA sequencing (81 CRC patients) with spatial transcriptomics (Xenium; 16 matched primary CRC samples) to quantify epithelial cell states and tissue organization. Analyses focused on proliferative programs defined by LGR5, CDX2, ANXA1, and MKI67, stratified by KRAS genotype and intratumoral location, with extended spatial annotation of immune and stromal niches. Results: CRC tumors showed high compositional heterogeneity across subgroups (mean normalized Shannon entropy &gt;0.6). On average, 36% of tumor epithelial cells were proliferative; only 50% expressed LGR5, with substantial inter-patient variability and genotype dependence. 14% of proliferating cells expressed ANXA1 alone, corresponding to inflammatory, YAP-high states with potential cytotoxic implications. LGR5-driven proliferation was enriched in KRAS-mutant tumors, contrasting with mouse models suggesting KRAS-mediated suppression and potentially indicating reduced sensitivity to KRAS inhibition. EGFR–LGR5 double-positive cells were abundant, identifying additional targetable niches. Spatial analyses revealed regions with high TGFβ signaling and co-localization with SPP1⁺ macrophages consistent with TGFβ-driven immunosuppressive niches described in complementary studies. These niches associate with reduced PD-1/PD-L1 blockade response, coincide with states responsive to combined TGFβ and PD-1 inhibition, and are not captured by genotype alone. Conclusions: Spatial transcriptomics provides quantitative, systems-level resolution of tissue architecture, revealing opportunities for rational co-targeting to disrupt tumor homeostasis and enhance immunotherapy efficacy. Ongoing analyses of neoadjuvant-treated tumors and paired primary–metastatic samples will extend this framework to capture therapy-induced and naturally evolving tumor states.

Apatinib combined with adebrelimab and GEMOX regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: A multicenter, open-label, single-arm, phase II trial.

e16202 Background: Immune checkpoint inhibitor combined with chemotherapy have shown improved prognosis compared with chemotherapy alone in patients with advanced intrahepatic cholangiocarcinoma (ICC). However, whether adding tyrosine kinase inhibitor (TKI) could further provide more survival benefits remains unclear. This study aims to evaluate the efficacy and safety of apatinib (a VEGFR2-targeted TKI) combined with adebrelimab (PD-L1 inhibitor) and GEMOX chemotherapy as first-line treatment for advanced ICC. Methods: This study (ACADEMY) enrolled adults aged ≤75 years with pathologically confirmed advanced ICC. All patients received apatinib (250 mg daily) combined with adebrelimab (1200 mg, day 1) and GEMOX chemotherapy (Gemcitabine 1000 mg/m 2 , day 1 and day 8; Oxaliplatin 85 mg/m 2 , day 1) per 21-day cycle. Tumor response was assessed using both RECIST 1.1 and mRECIST criteria. Survival outcomes were analyzed using Kaplan-Meier methods. The primary endpoint was objective response rate (ORR) accessed by RECIST 1.1 criteria. The secondary endpoints included progression free survival (PFS), overall survival (OS), disease control rate (DCR) and treatment-related adverse events (TRAEs). A Simon’s two -stage Optimum design was adopted in this study. If a response is observed in over 3 out of the initial 13 evaluated patients during the first phase, an additional 21 patients would be recruited for the study. Results: As of January 4, 2026, a total of 22 patients were recruited (median age 58.9 years; 59.1% female; 27.2% HBV-positive), with 19 included in efficacy analysis. Baseline characteristics: median tumor size 7.2 cm, median tumor number 3.5, 95.5% with TNM stage III-IV, 45.5% with macrovascular invasion. The ORR was 31.6% (RECIST 1.1) and 63.2% (mRECIST), and DCR was 100% (RECIST 1.1 and mRECIST criteria). With a median follow-up time of 7.9 months, the estimated median PFS was 6.2 months (95% CI: 5.4-NR), the 6-month OS rate was 100%, and the median OS was not reached. 21.1% (4/19) patients underwent radical surgical resection after tumor downstaging. In the respect of safety evaluation, TRAEs were observed in all enrolled patients, 50.0% with grade 3-4, and no grade 5 TRAE occurred. The most frequent AEs were hypoalbuminemia (68.2%), fatigue (59.1%) and liver damage (36.4%). Conclusions: Apatinib combined with adebrelimab and GEMOX regimen demonstrates promising efficacy and acceptable safety profile as first-line treatment for advanced ICC, supporting its potential as a preferred therapeutic option. Clinical trial information: NCT06925516 .