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A pilot study of a digital, patient-directed consent process for MSK-IMPACT tumor-normal genetic testing in gynecologic cancer.

10604 Background: Although germline and somatic genetic testing is increasingly recommended for many cancers including gynecologic cancers, uptake remains low. Barriers include consenting processes that are time consuming for patients and providers. We sought to test uptake and acceptability of a digital, self-directed genetic testing consent process. Methods: We developed a digital, self-guided consenting process for MSK-IMPACT tumor-normal targeted sequencing called “read and sign” (R&S) that included an educational video and information about genetic testing along with a direct digital consent. We performed a pilot study in gynecologic surgery (GYNS) and medical oncology (GMO) clinics to evaluate the uptake of genetic testing and other metrics including time to consent, clinic time saved, and patient satisfaction. Briefly, adults with gynecologic cancers eligible for MSK-IMPACT were sent R&S consent via electronic health record. Research staff followed up with patients at 2, 7, and 14 days. If patients did not consent after 14 days, the clinical team was notified to follow-up. This study was approved under IRBs 12-245 and X25-012. Results: Between 10/6/2025 and 12/31/2025, we identified 173 patients (122 GYNS and 51 GMO) eligible for MSK-IMPACT and offered them R&S consent. This represented 8% of total MSK-IMPACT consents across the institution during this time. Median age was 61 years. 106 (61%) patients identified as White, 27 (16%) as Asian, 17 (10%) as Black, and 24 (14%) as Hispanic. Most common cancer types were endometrial (n=75, 43%) and ovarian (n=39, 23%). In GYNS, 102/122 (84%) patients consented with R&S, and 59 (58%) consented on the same day the R&S consent was sent. On average, 8 minutes of in-person clinic time per patient was saved using R&S, but 35 (29%) patients had 0 time saved, and 7 (7%) consents were later completed in-person after initial incomplete R&S attempt. One patient who completed the R&S consent later withdrew consent. In GMO, 50/51 (98%) patients consented via R&S, with 38 (76%) consented on the same day. On average, 14 minutes of clinic time per patient was saved, and 4 (8%) patients ultimately required in-person consent. Average time to consent was 3.3 days in GYNS and 1.7 days in GMO. Among 11 patients who completed surveys, 10 (91%) were very/somewhat satisfied with R&S. More in-depth surveys and semi-structured interviews with a subset of patients and staff are ongoing, and data will be forthcoming. Conclusions: A digital, self-guided consent for MSK-IMPACT genetic testing was feasible and acceptable with some differences in workflow between surgical and medical oncology clinics. The R&S consent process empowers patient decision-making and should be scaled to other cancer types.

National trends and disparities in early-onset non-colorectal cancer mortality in the United States, 1999–2023: A population-based analysis of 240,190 deaths.

12106 Background: Early-onset non-colorectal malignancies account for a substantial share of premature cancer mortality in the United States, yet comprehensive national evaluations of long-term trends and disparities remain limited. Methods: We analyzed CDC WONDER Multiple Cause-of-Death data from 1999–2023, identifying deaths among individuals aged 15–54 years with non-colorectal malignancies. Age-adjusted mortality rates (AAMRs) per 1 million population were standardized to the 2000 U.S. standard population. Temporal trends were assessed using Joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC). Results: A total of 240,190 deaths from early-onset non-colorectal malignancies occurred during the study period. Overall AAMRs declined from 61.45 (95% CI 60.22–62.68) in 1999 to 52.76 (95% CI 51.67–53.87) in 2023. Largest proportion of deaths occurred at home (43.4%), followed by inpatient or medical facilities (39.6%). Among women, AAMRs increased steadily from 36.01 (95% CI 35.02–37.04) in 1999 to 39.03 (95% CI 38.03–40.05) in 2023 (AAPC +0.33%, 95% CI 0.20–0.47). In contrast, men exhibited substantially higher but declining mortality, with an accelerated decline after 2012 (APC −2.25%, 95% CI −2.67 to −2.02). Racial and ethnic disparities persisted. Non-Hispanic Black populations showed significant reductions (AAPC −2.25%), Non-Hispanic Asian/Pacific Islander populations experienced the steepest declines (AAPC −2.22%), while Non-Hispanic American Indian/Alaska Native populations exhibited an early surge (APC +9.57%) followed by prolonged plateauing with persistently high rates. Metropolitan areas experienced faster declines (AAPC −0.72%) than non-metropolitan areas. Conclusions: The post-2012 acceleration in mortality reduction suggests progress in cancer management; however, these gains were uneven and masked substantial disparities. Men experienced marked declines but continued to have significantly higher mortality than women, while the steady increase in female mortality raises concern for unaddressed sex-specific risk and disease dynamics. Stagnant trends among individuals aged 15–34 years indicate limited benefit of advances in oncology for the youngest patients. Racial, ethnic, and geographic inequities remained pronounced, with persistently elevated mortality among Non-Hispanic Black and American Indian/Alaska Native populations, slower improvements in non-metropolitan areas, and consistently high rates in several Southern and Appalachian states. Together, these findings indicate that national progress has not translated into equitable outcomes and highlight the urgent need for targeted prevention, earlier diagnosis, and region- and population-specific cancer control strategies to reduce avoidable early-life cancer mortality.

Molecular stratification and actionable genomic alterations in endometrial carcinoma: Real world data from an Indian tertiary oncology centre.

e15174 Background: Endometrial cancer (EC) is the sixth most common malignancy among women worldwide, with over 420,000 new cases annually and a substantial disease burden in India. The 2013 TCGA classification introduced a molecular framework for EC; however, therapeutic advances such as immunotherapy have largely benefited the mismatch repair-deficient (MSI-H/dMMR) subset. Most patients have mismatch repair-proficient (pMMR) disease and continue to face limited treatment options in advanced or recurrent settings. Established biomarkers, including PD-L1, have shown limited predictive value. This study describes the genomic alterations identified in EC using a targeted next-generation sequencing (NGS) panel in a real-world cohort. Methods: This retrospective study included 112 patients with histologically confirmed endometrial carcinoma. Genomic analysis was performed on formalin-fixed paraffin-embedded (FFPE) tumor samples with >20% tumor content. DNA was extracted using IVD manual isolation kits, and samples meeting predefined quality control criteria on the Agilent TapeStation 4200 were selected for library preparation. Sequencing was conducted using a custom 21-gene EC panel validated according to CAP and NABL standards on the MGI DNBSEQ-T7 platform. Somatic variants were annotated and interpreted following ACMG, AMP, and CAP guidelines. Results: Genomic alterations were identified in 73 of 112 cases (65.18%). Most patients presented with primary disease (92.86%), while 7.14% had metastatic disease, most commonly involving lymph nodes (37.5%) and omentum (25%). FIGO staging distribution was stage I (51.79%), stage II (36.61%), stage III (8.04%), and stage IV (3.57%). The most frequently altered genes were PTEN (21.05%), POLE (13.49%), and TP53 (12.83%), followed by ARID1A (8.22%), BRCA2 (5.92%), FGFR2 (4.93%), and BRCA1 (3.29%). Pathogenic alterations in mismatch repair genes were observed across MSH6 (4.28%), MSH2 (3.95%), MLH1 (3.29%), and PMS2 (1.97%). Additional lower-frequency alterations were identified in PIK3CA, POLG2, MUTYH, BRAF, CHEK2, and RET. Conclusions: This real-world genomic profiling study shows that targeted NGS identifies potentially actionable genomic alterations in a substantial proportion of patients with endometrial carcinoma. While mismatch repair gene alterations support immunotherapy use in a subset of cases, the predominance of alterations in pMMR tumors highlights the molecular heterogeneity of EC and the need for further exploration of biomarker-driven treatment strategies. These findings support the role of focused NGS panels in improving molecular characterization and informing personalized treatment considerations in endometrial carcinoma.

Unsupervised clustering of RNA-Seq data to identify molecular subtypes of sarcomas.

11547 Background: Sarcomas are a rare and heterogeneous group of malignancies, which include over 100 histological subtypes. Their histologic diversity present significant diagnostic and therapeutic challenges. This study aimed to define clinically relevant transcriptional subtypes using RNA-Sequencing (RNA-seq) data, and to further characterize the immune and metabolic microenvironment. Methods: This study uses data from the “Cohort to Augment the Understanding of Sarcoma Survivorship Across the Lifespan” (CAUSAL) study, which has enrolled sarcoma patients, treated at VUMC, from 2002-2026 for investigation of health outcomes. We analyzed RNA-seq data from tumor samples of 430 participants representing 42 unique histological sarcoma subtypes. We utilized sparse K-means clustering to identify stable subtypes and developed a classifier using a 310-gene panel. The immune microenvironment was characterized by applying CIBERSORTx deconvolution. Sarcoma subtype reproducibility and prognostic validity were evaluated using the Cancer Genomic Atlas data. Results: Among 430 samples, consensus matrices and diminishing gains in Cumulative Distribution Function (CDF) behavior yielded six distinct sarcoma molecular subtypes (SMS), each demonstrating strong correlation with known sarcoma histologies. SMS1 (labeled as “Cytotoxic-Adaptive”, n=30) and SMS6 (“Interferon-Activated”, n=97) were characterized by robust immune infiltration and interferon signaling, suggesting a potential sensitivity to immune checkpoint blockade. SMS2 (“Myeloid-Dominant”, n=93) primarily grouped undifferentiated pleomorphic sarcoma, giant cell sarcoma, and myxofibrosarcoma, and exhibited an immune-suppressive, macrophage-rich phenotype. SMS3 (“Early-Onset”, n=58) mostly grouped Ewing and synovial sarcoma and comprised mostly fusion-driven tumors with an immune-desert landscape. SMS4 (“EMT-Stromal”, n=107) mostly comprised desmoid and leiomyosarcoma and was defined by epithelial-mesenchymal transition and fibrosis, correlating with the poorest 10-year overall survival ( p=0.022 ). SMS5 (“Metabolic”, n=45) consisted exclusively of Gastrointestinal Stromal Tumors, with distinct metabolic programming and favorable prognosis. Conclusions: Each SMS transcends histological boundaries, grouping tumors based on shared immune, stromal, and metabolic features. This classification highlights distinct vulnerabilities in the tumor microenvironment, offering a functional framework to guide future precision treatment interventions, such as immunotherapy for SMS1/SMS6 and stromal-targeting agents for SMS4.

Association of inpatient outcomes and resource utilization with an ICD-10–defined immune-related adverse event phenotype during U.S. cancer hospitalizations: National Inpatient Sample, 2018–2022.

e23104 Background: Immune checkpoint inhibitor use is rapidly expanding, yet immune-related adverse events (irAEs) are not routinely characterized as an inpatient administrative phenotype with system-level implications during cancer hospitalizations. Methods: A serial cross-sectional, hospitalization-level analysis was performed using the 2018–2022 Healthcare Cost and Utilization Project National Inpatient Sample (NIS). Adult hospitalizations with a principal malignancy were identified using ICD-10-CM codes (C00–C97; D45–D47). An irAE phenotype was defined using any-diagnosis ICD-10-CM codes corresponding to immune-mediated toxicities, including colitis, hepatitis, pneumonitis, myocarditis, hypophysitis, myositis, inflammatory arthritis, and vasculitis. Because the NIS lacks medication and laboratory data, irAEs were analyzed as ICD-defined inpatient phenotypes rather than adjudicated toxicities. Outcomes included in-hospital mortality, mechanical ventilation as an ICU-level care proxy, length of stay (LOS), and hospital cost derived using cost-to-charge ratios. National estimates incorporated NIS discharge weights, hospital clustering, and stratification. Multivariable survey-weighted logistic regression adjusted for demographics, payer, hospital teaching status, and region. Results: Across 2018–2022, an estimated 4.81 million principal malignancy hospitalizations occurred nationally. The irAE phenotype increased from 3.45% in 2018 to 4.19% in 2022, representing approximately 187,020 weighted irAE-associated admissions. The most prevalent irAE categories were colitis (1.74%) and inflammatory arthritis (1.48%). Compared with non-irAE admissions, irAE phenotype hospitalizations had higher in-hospital mortality (5.12% vs 4.35%), greater mechanical ventilation use (2.86% vs 2.58%), longer LOS (10.7 vs 6.7 days), and higher mean costs ($46.9k vs $29.6k; +$17.3k). After adjustment, the irAE phenotype remained associated with increased mortality (adjusted OR 1.06, 95% CI 1.01–1.12). Resource differentials were greatest in urban teaching hospitals and highest-cost regions, where mean costs reached $67.7k among irAE phenotype admissions. Conclusions: An ICD-10–defined irAE phenotype represents an increasingly prevalent and resource-intensive inpatient comorbidity during cancer hospitalizations, associated with higher mortality, ICU-level care, prolonged LOS, and increased costs. Administrative surveillance of irAE phenotypes may support earlier identification of high-resource admissions and inform inpatient resource planning, particularly in teaching centers and high-cost regions.

A phase Ib/II trial of first-line trastuzumab, nivolumab, gemcitabine, and cisplatin in HER2-positive biliary tract cancer (HERBOT): A multi-institutional study from the Korean Cancer Study Group.

4016 Background: Several phase II trials support HER2 as a promising actionable target in advanced biliary tract cancers (BTCs). However, the efficacy of adding anti-HER2 therapy to the current first-line standard-of-care (ICI plus gemcitabine/cisplatin [GemCis]) remains unknown. We report the results of the HERBOT trial evaluating this quadruplet combination. Methods: This multi-institutional, open-label, phase Ib/II study (KCSG-HB23-05; NCT05749900) enrolled treatment-naïve pts with locally advanced/unresectable or metastatic, HER2-positive BTC (defined as centrally confirmed HER2 IHC3+, or IHC2+/ISH+, or ERBB2 gene copy number ≥6.0 by NGS). Pts received trastuzumab 6mg/kg (after 8mg/kg load) D1, nivolumab 360mg D1, cisplatin 25mg/m 2 D1,8, and gemcitabine 1000mg/m 2 (dose level 0) or 800mg/m 2 (dose level -1) D1,8 every 3 weeks. The primary endpoints were recommended phase II dose (RP2D, phase Ib) and ORR per RECIST v1.1 (phase II). Secondary endpoints included PFS, DCR, OS, safety. Exploratory biomarker analyses included AI-powered whole-slide image (WSI) profiling of HER2 expression and immune phenotype assessment. Results: Dose level 0 was established as RP2D with no DLT. Among total of 40 pts, 29 (72.5%) had gallbladder cancer and 26 (62.5%) were HER2 IHC 3+. The primary endpoint was met with an ORR of 55% (95%CI: 38.5 – 70.7; 1 CR, 21 PR) and a DCR of 95% (95%CI: 83.5 – 99.4); median duration of response was 12.6 months (95%CI: 5.7 – NR). With a median follow-up of 17.0 months, median PFS was 10.6 months (95%CI: 7.8 – 17.4) and median OS was not yet reached. Three pts (7.5%) underwent curative-intent conversion surgery. Pts with HER2 IHC 3+ showed a numerically longer PFS compared to IHC 2+/ISH+ (17.4 vs 9.7 months; HR 0.46, 95%CI: 0.20 – 1.07). Common grade ≥3 treatment-related adverse events (TRAEs) included neutropenia (57.5%), anemia (30.0%), and thrombocytopenia (22.5 %). A grade 2 decreased ejection fraction occurred in 1 pt (2.5%); no grade ≥3 immune-related AEs were observed. AI-based WSI analyses revealed that ≥10% HER2 3+ tumor cells proportion was associated with higher ORR (80% vs 36.4%, P = 0.009) and numerically superior PFS (17.4 vs 9.1 months; HR 0.54, 95%CI: 0.23 – 1.28). Pts with inflamed immune phenotype (n = 4) showed durable responses (ORR 75%; mPFS and mOS NR). Conclusions: The HERBOT trial demonstrates that adding trastuzumab to first-line ICI plus GemCis provides robust antitumor activity and manageable safety in HER2-positive BTC. This study is the first to report the efficacy of a HER2-targeted quadruplet regimen in the first-line setting, providing strong clinical rationale for integrating HER2-targeted strategies into first-line treatment and complementing ongoing global phase III trials in this molecularly defined subgroup. Clinical trial information: NCT05749900 .

Using large language models to identify advance care planning in oncology patients who present to the emergency department.

e13642 Background: Large language models (LLMs) can identify advance care planning (ACP) in unstructured notes in a fraction of the time required by human reviewers. When patients with metastatic cancer and poor prognosis present to the emergency department (ED), LLMs may enhance care by providing a quick and accurate method to identify ACP during a clinical crisis. No prior study has examined the efficiency of LLMs to identify ACP documentation at the time of an ED visit, comparing to real-time manual abstraction. Methods: This is a secondary analysis of a prospectively enrolled sample in a feasibility study for an ED-based, ACP intervention. Patients were English-speaking adults aged 50 and older with metastatic solid tumor cancer and a prognosis less than one year. We applied a previously validated LLM (Agaronnik et al. JPSM 2025, Agaronnik et al. JCO-OP 2025) to notes up to 6 months prior to the ED visit, comparing to real-time manual abstraction by trained research assistants. The LLM required output to include source text to support identification of ACP. Output included a hallucination score, which is a measure of the likelihood of an LLM producing false evidence. Qualitative analysis was used to review output. Results: 1262 patients had available notes for application of the LLM. Of 387 patients who had ACP identified by chart review, the LLM identified 363 patients (93.8%) as having ACP. Of 875 patients who were not identified as having ACP with chart review, the LLM found ACP in 551 patients (63.0%) of these patients. Examples of documentation identified by both the LLM and chart review include goals of care (“understands that her prognosis is poor but she states that she ‘is not ready to die yet’”), limitations on life-sustaining therapy (“she reports she would probably not want CPR but would want a breathing tube if it was temporary”), and hospice (“referral to hospice would be reasonable to facilitate safe discharge, especially in light of recent GOC discussions”). The LLM also identified documentation that was missed by chart review but may be relevant to patient care: “her main concern is for her [family] and 'how they will cope' after her eventual passing” and “I know that I am running out of options, but I'm not ready for hospice yet.” A common reason for false positives was statements in notes about health care proxy forms being available in the clinical chart. Average hallucination index for documentation identified by the LLM was low. LLM often found information missed by human reviewers. LLM extraction of ACP required several seconds per patient compared to 1-4 minutes per patient with chart review. Conclusions: LLMs can optimize review of ACP in the ED for patients admitted with serious illness, identifying ACP in a fraction of the time required by human reviewers. LLMs can be used to facilitate faster shared decision-making and accurate delivery of goal-concordant care in emergency settings.

Retrospective evaluation of romiplostim use for patients with chemotherapy-induced thrombocytopenia.

e24161 Background: Chemotherapy-induced thrombocytopenia (CIT) is a frequent complication, resulting in increased bleeding risk, chemotherapy dose reductions, delays or discontinuation. Thrombopoietin receptor agonists (TPO-RA), such as romiplostim (romi), represent a promising therapy for CIT by stimulating platelet production. Methods: Despite National Comprehensive Cancer Network guidance supporting romi or other TPO-RA use in CIT, real-world adoption remains inconsistent across all malignancies. We conducted a retrospective, single-center analysis of romi use for CIT from January 2020 to December 2024. Patients were included if they received romi within 6 months following chemotherapy. This study evaluated achievement of platelet count (×10 9 /L) ≥100 and > 50, time to platelet recovery, dosing patterns, thromboembolic and bleeding events, and chemotherapy dose delay/reductions. Results: Of 121 patients included (median age 58; 69% female), 56% had solid tumors and 44% had hematologic malignancies. The most common chemotherapy regimens prior to the development of thrombocytopenia included carboplatin-based regimens, azacitidine/venetoclax, and FOLFOX-based regimens. Prior to romi initiation, median platelet count was 26. About 12% of patients had a platelet count ≥ 100 prior to romi initiation. After romi initiation, 74% of patients achieved platelets ≥ 100 with a median time of 16 days (patients with a platelet count > 100 were not included in this data point). The median romi dose was 5 mcg/kg during treatment. Dose delays or reductions were avoided in 70% of patients. During romi therapy, bleeding and thrombotic events occurred in 10% and 0.8% respectively. Conclusions: In our study, romi was effective at achieving a platelet goal of > 100 in the majority of our patients. Limitations include a single center study, heterogenous patient population and a lack of comparison to patients who did not receive romi despite similar degrees of thrombocytopenia. Further studies are needed to determine if romi affects overall survival, and to develop an effective dosing strategy for ROMI in CIT as a cost analysis. Outcomes Solid Hematologic Achieved platelets > 100 x 10 9 (n, %) 43, 63.2% 33, 62.3% Achieved platelets > 50 x 10 9 (n, %) 26, 38.2% 36, 68% Not requiring chemotherapy delay or dose reduction (n, %) 48, 70.6% 37, 69.8% Median romi dose during treatment (mcg/kg) 3.5 6.4 Side Effect/Safety Profile Bleeding events recorded during romi (n, %) 6, 8.8% 6, 11.3% Thrombotic events recorded during romi (n, %) 1, 1.5% 0, 0%

Cumulative incidence and risk factors of trastuzumab deruxtecan–related interstitial lung disease in a multicenter real-world cohort.

e15030 Background: Interstitial lung disease (ILD) is a clinically relevant adverse event associated with trastuzumab-deruxtecan (T-DXd). Reported ILD incidence often does not account for competing clinical events, potentially leading to risk overestimation. In parallel, real-world data on patient- and treatment-related risk factors remain limited. We aimed to estimate the cumulative incidence of T-DXd–related ILD using a competing-risk approach and to identify clinical and inflammatory factors associated with increased risk. Methods: We retrospectively collected data from 406 patients with metastatic breast cancer (223 HER2-positive, 162 HER2-low; 21 missing data) treated with T-DXd between October 2024 and January 2026 in 16 Italian Institutions. Competing events included death without ILD and treatment discontinuation due to disease progression or other non-ILD causes. Cumulative incidence functions (CIF) were estimated for each event. For risk factor analysis, 74 candidate variables were evaluated, including 10 clinical characteristics, 20 prior treatment variables, 24 concomitant diseases and drugs, and 20 baseline inflammatory biomarkers. Gray’s test was used for univariable screening, followed by multivariable Fine–Gray regression. Results: Seventy-four patients (18.3%) developed T-DXd–related ILD, with a median time to onset of 5.5 months and a mean of 8.4 months. The CIF of first ILD was 14.5% at 10 months and 16.8% at 20 months, plateauing at 18.8% at 50 months. No significant differences in ILD incidence were observed between HER2-positive and HER2-low disease (Gray test p = 0.83). Disease progression was the most frequent competing event, affecting 47.3% of patients at 10 months and 73.3% at 50 months. In univariate analysis, higher continuous neutrophil-to-lymphocyte ratio (NLR), impaired renal clearance (CLcr), prior lung radiotherapy (RT), smoking, and visceral disease were associated with increased ILD risk, while prior Trastuzumab exposure was protective. No correlation was seen for concomitant disease and drugs. In multivariable analysis, reduced creatinine clearance (sHR 3.53, 95% CI 1.64–7.58; p = 0.001), prior lung radiotherapy (sHR 2.40, 95% CI 1.08–5.33; p = 0.032), and higher baseline neutrophil-to-lymphocyte ratio (sHR 1.14, 95% CI 1.05–1.24; p = 0.002) remained independently associated with increased ILD risk. Conclusions: In this multicenter real-world cohort, the cumulative incidence of T-DXd–related ILD was approximately 19%, accounting for competing risks. The high frequency of competing events underscores the importance of competing-risk methodology for accurate toxicity estimation. Baseline renal impairment, prior lung radiotherapy, and systemic inflammatory status identified patients at increased risk and may support risk-adapted monitoring and earlier clinical intervention during T-DXd treatment.

Trends and disparities in sepsis-related mortality among patients with lung cancer: A 25-year nationwide analysis.

e20682 Background: Lung cancer patients face heightened sepsis susceptibility due to disease-related immune dysfunction and treatment-induced myelosuppression. Despite advances in sepsis management, population trends and disparities in sepsis-related mortality among this population remain poorly characterized. Methods: We conducted a retrospective analysis using the CDC WONDER database (1999-2023) for adults aged ≥25 years where both sepsis (ICD-10: A40-A41) and malignant neoplasm of lung (C34) were listed among the causes of death. Age-adjusted mortality rates (AAMR) per 100,000 population were calculated. Temporal trends were analyzed using Joinpoint regression to determine annual percentage change (APC) and average annual percentage change (AAPC). Results were stratified by sex, age group (25-44, 45-64, ≥65 years), race/ethnicity, urbanization status, census region, and state. Results: From 1999-2023, 104,034 sepsis-related deaths occurred among lung cancer patients. AAMR increased significantly from 1.61 (95% CI: 1.55-1.66) to 2.05 (95% CI: 2.00-2.10), with an overall AAPC of 1.15 (95% CI: 0.20-2.11; p = 0.018). Joinpoint analysis identified significant increases from 1999-2013 (APC: 0.96; 95% CI: 0.56-1.36), followed by attenuation of trends and a non-significant plateau from 2016-2023 (APC: 0.42; 95% CI: -0.51-1.36). Although males had higher AAMR than females (2.48 vs 1.70 in 2023), females demonstrated significantly steeper temporal increases (AAPC: 1.93; 95% CI: 1.73-2.13 vs 0.44; 95% CI: -0.23-1.11). Adults ≥65 years showed significant increases (AAPC: 1.46; 95% CI: 1.31-1.62; p < 0.001). Black or African American individuals had the highest AAMR (2.69 in 2023), followed by Whites (2.18), Asian/Pacific Islanders (1.54), and Hispanics (1.06). Whites exhibited the fastest increase (AAPC: 1.52; 95% CI: 0.75-2.28). Non-metropolitan areas showed significantly higher AAPC (2.40; 95% CI: 1.41-3.41) versus metropolitan areas (0.95; 95% CI: 0.74-1.16), indicating widening rural-urban disparities. Regionally, the South had the highest AAMR (2.38) while the Midwest exhibited the fastest increase (AAPC: 1.78; 95% CI: 1.54-2.02). State-level AAMR ranged from Kentucky (3.08) and West Virginia (3.04) to Utah (0.66) and Wyoming (0.88). The majority of deaths (87.0%) occurred in inpatient medical facilities. Conclusions: This 25-year nationwide analysis reveals a significant rise in sepsis-related mortality among lung cancer patients with pronounced demographic and geographic disparities. Females, rural residents, and populations in Southern and Midwestern states represent vulnerable groups requiring targeted sepsis prevention and early intervention strategies.

Impact of modern systemic and multimodality treatments on post-relapse survival in retroperitoneal soft-tissue sarcoma: A digital-twin target trial emulation study.

11576 Background: We previously observed a significant improvement in post-relapse overall survival (OS) in patients with recurrent retroperitoneal soft-tissue sarcoma (RPS) treated in 2012–2021 compared with 2002–2011. This study aimed to determine whether this survival benefit reflects advances in post-relapse treatment strategies, using digital twins to isolate the impact of systemic therapy and multimodality care. Methods: Adults with resected RPS and first documented recurrence were grouped by era (pre-2012 vs post-2012). Post-recurrence management was modeled as time-dependent multimodal treatment to account for treatment timing and avoid time-related bias, including repeat surgery, radiotherapy, and systemic therapy (up to five sequential lines). Detailed treatment data (surgery, radiotherapy, number of systemic therapy lines, and use of novel agents available since 2012, within or outside clinical trials) were captured. A Cox model for post-relapse survival was fitted in the post-2012 cohort using baseline covariates and time-dependent treatments. This model was used to predict the counterfactual post-relapse survival on the Monte-Carlo simulated digital-twin trajectories for pre-2012 patients under post-2012 management. The effect of post-2012 systemic therapies was isolated and applied to the pre-2012 cohort to estimate their counterfactual impact. Restricted mean survival time (RMST) at 2 and 5 years was standardized to the pre-2012 baseline distribution. Results: Among 872 operated patients, 417 developed recurrence; complete data were available for 86 pre-2012 and 263 post-2012 patients. Post-relapse OS significantly improved over time, with median post-relapse OS of 14.9 months pre-2012 versus 43.8 months post-2012. Observed RMST differences favored the post-2012 cohort by +5.6 months at 2 years, and +18.0 at 5 years (p < 0.001). Counterfactual simulation predicted that applying post-2012 management to pre-2012 patients would increase median OS to 33.8 months and RMST by +4.8 and +12.2 months at 2 and 5 years, respectively. Isolating systemic therapy alone reduced the gain by −2.2, and −5.7 months, indicating a partial but not exclusive contribution of systemic treatment advances (p<0.001). Conclusions: Digital-twin target trial emulation suggests that post-2012 management strategies explain most of the early and a substantial portion of the long-term survival improvement after RPS recurrence. Advances in systemic therapy contribute meaningfully but do not fully explain the observed OS gains, supporting the importance of integrated multimodality post-relapse care.

The overlapping burden of atrial fibrillation and lung cancer: Insights from U.S. mortality data from 1999 to 2023.

e20672 Background: Both lung cancer and atrial fibrillation (AF) are significant causes of morbidity and death in the US, especially in older populations. AF is increasingly associated with poor outcomes in lung cancer patients due to shared risk factors, chronic inflammation, and the cardiotoxic effects of cancer treatments. However, there is still a dearth of national-level information on long-term mortality patterns and demographic differences associated with this overlap. Methods: The U.S. death certificates from CDC WONDER (1999–2023) were analyzed retrospectively. If both AF and lung cancer were identified as underlying or contributory causes, the deaths were counted. We stratified age-adjusted mortality rates (AAMRs) by census area, sex, race/ethnicity, and urban/rural status. Annual percentage changes (APCs) along with their 95% Confidence Intervals (CI) were calculated. And for this purpose, Joinpoint regression program was used. Results: Atrial fibrillation and Lung Cancer were responsible for 101,689 fatalities occurred among adults aged 25 years and older from 1999 to 2023 in the U.S. The information for the location of death was available for 97,739 deaths. Among the total deaths, 42.54% occurred in medical facilities, 31.43% occurred at home. The AAMRs of men were consistently higher than those of women (3.34 vs. 1.96 in 2023). Mortality was greater among non-Hispanics than among Hispanics (AAMR: 2.73 vs. 0.90 in 2023). From 1.08 in 1999 to 3.07 in 2020, the AAMRs of rural people were consistently higher than those of urban groups. Regional variation was marked, with the South showing the highest mortality in 2023 (2.83), followed by the Midwest (2.73), West (2.31), and Northeast (2.17). Conclusions: Lung cancer mortality from AF has gone up, with greater rates in the South, non-Hispanics, men, and rural areas. To overcome these discrepancies, targeted cardio-oncology therapies are required.

CLARITY-GBM: A phase II, multi-centered, open-label, single-arm study to evaluate the safety and efficacy of cetuximab and lomustine (CCNU) in adult patients with recurrent high-grade glioblastoma.

TPS2095 Background: Recurrent glioblastoma (GBM) has a poor prognosis with no universally accepted systemic standard of care. Lomustine (CCNU) remains a commonly used benchmark, achieving 6-month progression-free survival (PFS-6) rates of approximately 20%. Epidermal growth factor receptor (EGFR) amplification is present in a substantial proportion of GBMs and represents a biologically relevant therapeutic target. Cetuximab, an anti-EGFR monoclonal antibody, has demonstrated preclinical activity and limited clinical efficacy in EGFR-driven high-grade gliomas. CLARITY-GBM evaluates the safety and preliminary efficacy of combining cetuximab with lomustine in adults with recurrent high-grade glioblastoma. Methods: CLARITY-GBM is a prospective, open-label, multicenter, single-arm Phase II study conducted at four tertiary cancer centres in India. Eligible patients are adults (≥18 yrs) with histologically confirmed WHO grade 4 glioblastoma at first or second recurrence following standard chemoradiation, ECOG performance status 0–2, and measurable disease per RANO criteria. Participants will receive cetuximab intravenously 500 mg/m² every 2 weeks in combination with oral lomustine 110 mg/m² every 6 weeks. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. Tumour assessments are performed every 6 weeks using MRI and evaluated according to RANO criteria. The study uses an exact single-stage Phase II design testing the null hypothesis that PFS-6 ≤20% versus the alternative hypothesis that PFS-6 ≥40%, with a one-sided alpha of 0.10 and 80% power. A total sample size of 25 patients is planned to ensure 24 evaluable patients for the primary analysis. The regimen will be considered promising if at least 8 patients are progression-free at 6 months. A single interim futility analysis is planned after 15 evaluable patients. The primary endpoint is PFS-6. Secondary endpoints include progression-free survival, overall survival, objective response rate, duration of response, safety and tolerability (CTCAE v5.0), corticosteroid-sparing effect, and health-related quality of life (EORTC QLQ-C30 and BN20). Exploratory analyses evaluate correlations with EGFR amplification, EGFRvIII status, and MGMT promoter methylation. Clinical trial information: CTRI/2026/01/100794. Design and key methodological features of the CLARITY-GBM trial. Characteristic Description Study Design Phase II, open-label, single-arm Population Adults with recurrent WHO grade 4 GBM Sample Size 25 planned (24 evaluable) Treatment Cetuximab q2w + Lomustine q6w Primary Endpoint PFS-6 Statistical Design One-sample exact binomial Null/Alternative PFS-6 ≤20% vs ≥40% Power/Alpha 80%, one-sided 0.10 Interim Analysis After 15 evaluable patients Exploratory Biomarkers EGFR, EGFRvIII, MGMT

Transarterial embolization plus hepatic arterial infusion chemotherapy combined with rivoceranib and camrelizumab for initially unresectable hepatocellular carcinoma with high tumor burden: A single-arm, prospective, multicenter study.

e16156 Background: In recent years, combination treatment strategies incorporating transarterial locoregional therapies with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) for patients with unresectable hepatocellular carcinoma (uHCC) have gained increasing attention. Multiple multicenter retrospective studies have confirmed that treatment regimens combining transarterial chemoembolization plus hepatic arterial infusion chemotherapy (TACE+HAIC) with TKIs and ICIs are associated with significant efficacy and a manageable safety profile. The present study aims to evaluate the efficacy and safety of transarterial embolization plus hepatic arterial infusion chemotherapy (TAE+HAIC) combined with rivoceranib and camrelizumab as a first-line treatment for patients with initially uHCC with high tumor burden (uHTB-HCC). Methods: This single-arm, prospective, multicenter study enrolled patients with initially diagnosed uHTB-HCC who met at least one of the following criteria: (1) a high tumor burden defined as the sum of the number of tumors and the size of the largest tumor exceeding 11, based on criteria 7–11; or (2) the presence of portal vein tumor thrombus classified as VP3–VP4. All enrolled patients received TAE+HAIC, followed by camrelizumab (200 mg every 3 weeks) in combination with rivoceranib (250 mg/day). The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety. This study was registered at ClinicalTrials.gov (NCT06363825). Results: Between April 15, 2024, and August 7, 2025, a total of 51 patients were enrolled across five centers and received the triple-combination therapy (TAE+HAIC+Camrelizumab+Rivoceranib). The cohort comprised 44 men and 7 women, with a mean age of 57.9 ± 9.9 years. Portal vein tumor thrombosis was present in 38 patients (74.5%), and 11 patients (23.5%) had extrahepatic metastases. As of the data cutoff on December 31, 2025, the median follow-up duration was 10.3 months (IQR, 6.1–11.4). According to RECIST1.1 criteria, the ORR was 64.7% and the DCR was 80.4%. Based on mRECIST criteria, the ORR was 78.4% and the DCR remained 80.4%. Notably, 12 patients (23.5%) were successfully converted to surgical resection. The mPFS was 9.2 months (95% CI, 4.0–14.5), while the mOS has not yet been reached. 36 patients (70.5%) had treatment-related adverse event (TRAEs) that were grade 3-5, but no treatment-related deaths were reported. Conclusions: The combination therapy (TAE+HAIC+Camrelizumab+Rivoceranib) significantly improved ORR and PFS in patients with uHTB-HCC, with a manageable safety profile. Further large-scale randomized trials are warranted to validate these findings. Clinical trial information: NCT06363825 .

Antimicrobial activity of sodium dodecyl sulfate-capped silver nanoparticles via green synthesis of continuous wave fiber laser

Post‐Salting‐Out Polymerization Enriching Dynamic Crosslinks for Ultralong High‐Temperature Phosphorescence Hydrogels

ABSTRACT Room‐temperature phosphorescence (RTP) and high‐temperature phosphorescence (HTP) polymer hydrogels hold great photonic applications in 3D printing, bioimaging, etc. Unfortunately, the soft, wet nature of hydrogels fundamentally contradicts the stringent confinement requirements for efficient phosphorescence, making the RTP hydrogels with tens‐of‐seconds afterglow remain underdeveloped, while there is still no report of HTP hydrogels. Herein, we propose a post‐salting‐out polymerization strategy to significantly enrich the dynamic crosslinking network for the compact confinement of HOF‐protected luminogens, leading to remarkable RTP and especially ultralong HTP of hydrogels. Such dynamic hydrogen bonds‐assisted crystallization enhancement synergizes with the orderly HOF structure to significantly restrict molecular vibrations around luminogens and isolate water/oxygen. Consequently, unprecedented RTP lifetime (∼3.3 s) and afterglow (∼45 s) are achieved in hydrogels for the first time. Owing to the good thermo‐stability of HOF and crystallization structures, their HTP lifetime and afterglow are still found to be above 1.3 s and 30 s, even at 100°C, despite the fact that the hydrogen bonds between polymers and HOF rosettes are sensitive to high temperature. Multicolor RTP and HTP performances are further demonstrated by either varying the luminogens or doping commercial dyes into the hydrogel matrix. This study opens new avenues for ultralong HTP hydrogels to broaden their applications.

Temporal trends and racial disparities in anal squamous cell carcinoma outcomes: A population-based study.

e15504 Background: Anal squamous cell carcinoma (SCC) is a relatively uncommon malignancy, accounting for approximately 2% of gastrointestinal tract cancers. Human papillomavirus (HPV) infection is implicated in 80% of cases, and thus key risk factors include immunosuppression and sexual behaviors associated with HPV exposure. This study aimed to characterize current incidence and survival trends in anal SCC using the Surveillance, Epidemiology, and End Results (SEER) Database. Methods: SEER Research Plus Data (17 Registries, 2000-2022) was used to identify cases of primary anal squamous cell carcinoma using ICD-O-3 histology codes 8050-8084 and Primary Site ICD-O-3 C21.0-C21.8 in individuals aged 15 or older. Data were then categorized by era, age group, sex, and race/ethnicity. Multivariable Cox proportional hazards models were used to evaluate associations between overall survival and diagnosis era, age group, sex, race/ethnicity, and stage at diagnosis. Results: A total of 29,584 patients were identified with anal SCC, with registry incidence estimated 2.44 per 100,000 persons. The mean age at diagnosis was 62.0; 64% were female and 36% were male. Non-Hispanic White patients accounted for 78.5% of cases, followed by Black (9.8%), Hispanic (9.2%), Asian/Pacific Islander (A/PI) (1.9%), and American Indian/Alaska Native (AI/AN) patients (0.6%). Over the 23-year study period, incidence increased across all racial and ethnic groups (IRR per year 1.04; p < 0.001). In multivariable Cox proportional hazards model adjusted for age and sex, diagnosis era was independently associated with overall survival (p < 0.001). Compared with patients diagnosed between 2000-2004, those diagnosed between 2010-2014 (HR 0.93, 95% CI 0.88-0.98), 2015–2019 (HR 0.86, 95% CI 0.81-0.91), and 2020–2022 (HR 0.81, 95% CI 0.74-0.88) experienced progressively lower hazards of death. When stratified by race/ethnicity, median overall survival was longest among Hispanic (142 months; 95% CI 128-154) and A/PI patients (140; 95% CI 117-166), followed by White (125; 95% CI 121-130). Median overall survival was poorest in Black (94 months; 95% CI 86-105) and AI/AN patients (90; 95% CI 58-152). Conclusions: In this analysis, the incidence of anal SCC increased substantially over time, while overall survival has improved across successive eras. Despite these survival improvements, significant racial and ethnic disparities remain, with worse outcomes observed among Black and American Indian/Alaska Native patients. Rising incidence and persistent racial disparities suggest ongoing gaps in prevention, early detection, and equitable cancer care. One-year overall survival for anal SCC by race/ethnicity, 2000–2022. Race 2000-2004 2005-2009 2010-2014 2015-2019 2020-2022 White 85.6 86.3 88.3 88.2 88.3 Black 79.3 79.2 85.7 86.6 86 Hispanic 89.3 86.7 90 89.6 89.1 A/PI 90.4 87.3 88.4 91.3 85.6 AI/AN 90.9 90 92.5 84.2 85.9

Neoadjuvant NASOX for pancreatic cancer: A prospective multicenter study.

e16446 Background: Neoadjuvant therapy has become standard practice for selected patients with pancreatic cancer, with proven benefits in improving R0 resection rates and survival outcomes; nevertheless, optimal regimen selection remains poorly defined due to a lack of high-quality evidence. This study evaluated the efficacy and safety of the NASOX regimen—liposomal irinotecan, oxaliplatin, and S-1—as neoadjuvant therapy in patients with high-risk resectable, borderline resectable (BRPC), or locally advanced pancreatic cancer (LAPC). Methods: This ongoing prospective multicenter study enrolled patients with cytologically confirmed pancreatic cancer, an ECOG performance status of 0–2, adequate organ function, and no prior anticancer therapy. Patients received 4-6 cycles of neoadjuvant NASOX (liposomal irinotecan 50 mg/m², oxaliplatin 60 mg/m 2 , S-1 40 mg/m 2 , every 2 weeks), with each cycle defined as 4 weeks and consisting of two administrations. Tumor response was assessed every 2 cycles according to RECIST v1.1, and serum CA19-9 levels were monitored biweekly. The primary endpoint was surgical conversion rate. Secondary end points included R0 resection rate, objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between December 2023 and December 2025, 26 patients were enrolled (median age 58 years (range: 35–75); 34.6% females (n = 9)), including 1 (3.8%) high-risk resectable, 4 (15.4%) BRPC, and 21 (80.8%) LAPC. Among 18 patients with efficacy evaluation result, 8 achieved partial response (PR), 8 had stable disease (SD), and 2 had progressive disease (PD), yielding an ORR of 44.4% (8/18) and a DCR of 88.8% (16/18). Following multidisciplinary team (MDT) discussion, 7 patients were deemed suitable for surgical exploration; 2 declined surgery for non-medical reasons. 5 patients (25.0%) underwent resection, all achieving R0 resection. Median PFS and OS have not yet been reached. Among 16 patients completing planned therapy, median CA19-9 levels decreased from 580.9 U/mL at baseline to 213.5 U/mL; nine patients achieved > 50% reduction, and three normalized CA19-9 levels. Grade ≥3 treatment-related adverse events occurred in 38.5% of patients, most commonly neutropenia (19.2%) and vomiting (11.5%). No treatment-related deaths were observed. Conclusions: Neoadjuvant NASOX demonstrates promising antitumor activity with a manageable safety profile in patients with pancreatic cancer, supporting further prospective evaluation.

Trends in mortality among older diabetic patients with lung cancer in the United States (1999–2023).

e20779 Background: Lung cancer is the leading cause of cancer death in the United States. Diabetes is common in older adults and may worsen outcomes via metabolic, inflammatory, and cardiovascular pathways. Tracking long-term mortality trends in older adults with both conditions is important as survival improves. Methods: We used CDC WONDER death certificates (adults ≥65, 1999–2023) to identify lung cancer (ICD-10 C34.x) and diabetes (E10–E14) as underlying or contributing causes. Age-adjusted and age-specific mortality per 100,000 were calculated; trends evaluated with Joinpoint regression (APC, AAPC) to guide targeted public health interventions nationwide. Results: From 1999–2023, AAMRs among U.S. adults ≥65 years with lung cancer and diabetes showed non-linear trends. Mortality increased in 1999–2003 (APC 3.70%, 95% CI 1.32–6.14), declined in 2009–2018 (APC −2.79%, −3.48 to −2.10), rose in 2018–2021 (APC 7.76%, 1.45–14.46), then declined; overall AAPC was nonsignificant (0.28%). Ages 65–74 declined in 2006–2017 (APC −3.43%), ages 75–84 declined in 2009–2018 (APC −2.65%), while ≥85 years showed a significant long-term increase (AAPC 1.94%) with a sharp rise in 2018–2021 (APC 10.10%). Men (18.95) had higher AAMRs than women (9.17); both declined in 2009–2018 (men −2.75%, women −3.04%). Black individuals had the highest AAMRs (18.30) with increases after 2015 (APC 2.25%), whereas Hispanic (9.41) (APC −1.17%) and Asian/Pacific Islander groups (10.19) (APC −5.06%) showed significant declines. Conclusions: Mortality among older U.S. adults with lung cancer and diabetes followed a non-linear course with mid-period declines and a late resurgence, notably among the oldest adults, men, and Black individuals, underscoring the need for coordinated oncologic, metabolic, and survivorship risk-reduction and targeted public health interventions nationwide.

First-line (1L) cadonilimab plus AK117 and chemotherapy (chemo) in advanced gastric or gastroesophageal junction cancer (GC/GEJC): Updated results from a phase 2 study.

e16040 Background: Cadonilimab (anti-PD-1/CTLA-4 bispecific antibody) plus chemo is approved in China for 1L treatment of advanced GC/GEJC based on the phase 3 COMPASSION-15 study. AK117 is a novel humanized IgG4 monoclonal antibody targeting CD47, a macrophage immune checkpoint enabling tumor cells to evade phagocytic immune destruction. We previously reported preliminary efficacy and safety data from a phase 2 study evaluating cadonilimab + AK117 + chemo in 1L GC/GEJC (Xia et al., ASCO 2023). Herein, we present updated results with extended follow-up. Methods: Eligible patients (pts) with previously untreated, advanced HER2-negative GC/GEJC received cadonilimab (10 mg/kg) and AK117 (45 mg/kg) plus oxaliplatin and capecitabine every 3 weeks. Primary endpoints were safety and objective response rate (ORR). Secondary endpoints included duration of response (DoR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS) and overall survival (OS). Results: As of the data cutoff (October 12, 2025), a total of 41 pts were enrolled, and the median follow-up was 23.8 mo. Median age was 64.5 years (range 39.8-74.8), 82.9% male, 78% ECOG PS 1, 97.6% with metastatic disease (51.2% with liver metastases). Regarding PD-L1 status, 19.5% had CPS ≥ 5 and 43.9% had CPS ≥ 1. In the ITT population, ORR was 75.6% (2 CRs [4.9%]; 29 PRs [70.7%]) and DCR was 95.1%. Median DoR was 9.5 mo (95% CI 4.7-15.1). Median PFS was 8.5 mo (95% CI 5.8-16.1) and median OS was 19.0 mo (95% CI 14.8-NE). PFS and OS outcomes were favorable regardless of PD-L1 expression (Table). In pts with PD-L1 CPS < 5, median PFS and OS were 8.5 mo (95% CI 5.5-10.8) and 18.8 mo (95% CI 12.0-26.6), respectively. In those with PD-L1 CPS ≥ 5, median PFS and OS were not reached, with a 24-mo OS rate of 62.5%. Grade ≥ 3 treatment-related adverse events (TRAEs) were reported in 22 pts (53.7%). The most common TRAEs of grade ≥ 3 were decreased platelet count (24.4%), decreased neutrophil count (12.2%), and anemia (7.3%). No treatment-related deaths were reported. Conclusions: Consistent with prior reports, cadonilimab combined with AK117 and chemo showed encouraging efficacy and manageable safety in first-line treatment of advanced GC/GEJC. Clinical trial information: NCT05235542 . ITT (N=41) CPS < 1(N=21) CPS ≥ 1(N=18) CPS < 5(N=31) CPS ≥ 5(N=8) ORR, % (95% CI) 75.6(59.7-87.6) 71.4(47.8-88.7) 83.3(58.6-96.4) 74.2(55.4-88.1) 87.5(47.3-99.7) DCR, % (95% CI) 95.1(83.5-99.4) 95.2(76.2-99.9) 100(81.5-100) 96.8(83.3-99.9) 100(63.1-100) Median PFS, mo (95% CI) 8.5(5.8-16.1) 8.5(4.6-16.3) 9.6(5.8-NE) 8.5(5.5-10.8) NR(6.1-NE) Median OS, mo (95% CI) 19.0(14.7-NE) 18.8(6.0-NE) 24.7(14.8-NE) 18.8(12.0-26.6) NR(10.0-NE) 24-mo OS rate, % (95% CI) 48.4(32.5-62.6) 41.9(20.9-61.7) 55.6(30.5-74.8) 44.5(26.6-60.9) 62.5(22.9-86.1)