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Dynamics analysis of disturbance propagation in ecosystem with proportional migration based on epidemic model

In order to investigate the propagation dynamics of ecological disturbances within ecological networks, we conceptualize ecological disturbances as infectious diseases and employ complex network theory to analyze ecosystems. In this approach, the transmission process of ecological interference is abstracted as the spread of infectious diseases on complex networks. Based on the principles of infectious disease models, a disturbance propagation model for ecological networks is constructed and analyzed. In this paper, species within the ecosystem are abstracted as nodes in a complex network, where connections between nodes signify predator-prey relationships. When the ecosystem is under attack, a small number of species are initially disturbed, and this disturbance spreads among the ecosystem through the food chain. Given that species possess self-recovery capabilities, some species will return to a stable state over time after being disturbed. Consequently, any species within the ecosystem can be in one of three states at a given time: undisturbed, disturbed, or recovered. By establishing and analyzing the disturbance propagation dynamics, we determine the basic reproduction number and its influencing factors, and assess the stability of the disease-free equilibrium and the endemic equilibrium. The results demonstrate that when the basic reproduction number is less than 1, the system exhibits only a disease-free equilibrium, which is globally stable. When the basic reproduction number exceeds 1, an endemic equilibrium exists, the disease-free equilibrium becomes unstable, while the endemic equilibrium is globally stable. The basic reproduction number is associated with the topological structure of the food web, the probability of disturbance propagation, and the probability of species recovery. Subsequently, we validate the conclusions of the theorem using the actual food web data of 85 species from a pine forest in Otago, New Zealand. Finally, we consider protection measures for species from a human-intervention perspective, treating species protection as species immunity. Through theoretical derivation and numerical simulation, we find that the active immunization strategy is the most effective. This is because it effectively targets and protects neighbor nodes with medium and high degrees (i.e., highly connected species), thereby inhibiting the cascade of disturbance more efficiently than random or targeted strategies.

Energy flux and kinetic energy analysis of MHD natural convection of Ag–MgO/water hybrid nanofluid in a porous trapezoidal enclosure with an internal heated obstacle

Helical Photonic Confinement of Metal Clusters Enables Switching and Imaging of Near‐Infrared Circularly Polarized Light

ABSTRACT Near‐infrared (NIR) circularly polarized luminescent (CPL) materials are highly desirable for optical communication, bioimaging, night‐vision applications, and chiral encrypted information transfer, yet their practical use is limited by extremely low luminescence asymmetry factors ( g lum ). Here, we establish a helical photonic confinement strategy by embedding NIR‐emissive Au 13 nanoclusters into chiral nematic mesoporous silica (CNMS). Precise matching between the chiral photonic bandgap and cluster emission yields strongly enhanced NIR‐CPL with a g lum of −0.4, enabling direct discrimination of left‐ and right‐handed circularly polarized emission in the NIR region. This system realizes the first high‐contrast, CPL‐resolved near‐infrared (night‐vision) imaging based on intrinsic cluster emission, without external polarization optics. The Au 13 clusters undergo reversible assembly‐disassembly within helical nanochannels, allowing controllable NIR‐CPL switching and handedness inversion. Mechanistic studies confirm that the CPL enhancement originates from chiral photonic propagation modulation rather than intrinsic emitter chirality. This helical‐confinement principle is extendable to multicolor metal clusters, offering a general route toward high‐efficiency CPL materials.

Research on length deformation control of high-altitude linear engineering based on the ellipsoid expansion method

Abstract In engineering control surveys, the problem of length distortion arising from the reduction of field-measured distances to the Gauss plane has long posed challenges in practical applications, particularly in high-altitude linear engineering projects where such distortions are more pronounced. Effective methods for controlling this distortion remain unclear. This paper systematically analyzes the deformation patterns of ground survey distances reduced to the ellipsoid and then projected onto the Gauss plane. It also evaluates and compares the effectiveness of four ellipsoid expansion methods—mean curvature radius method, prime vertical curvature radius method, planar analytical method, and generalized differential calculus method—in establishing engineering ellipsoids for distortion control. The results demonstrate that the engineering ellipsoid constructed via the generalized differential calculus method achieves optimal control over length distortion, with a maximum distortion of only 11.4 mm, well below the specified tolerance limit (± 37.9 mm). The findings confirm that this method provides a reliable technical basis for establishing coordinate systems in linear engineering projects located in high-altitude regions.

Highly branched complex-type N-glycans on integrin β1 in extracellular vesicles enhance the binding of sEVs to laminin on recipient cells

Sex-specific trends and outcomes in small cell lung cancer (SCLC) in Spain: Insights from the CLARISSE study (2019–2024).

8092 Background: SCLC is an aggressive malignancy with poor prognosis. Although overall incidence is declining, cases among women are increasing. European projections show decreasing mortality in men but stable rates in women—except in Spain, where a +2.4% rise is expected—highlighting the need to examine sex-specific trends. Methods: CLARISSE is a multicenter, retrospective, observational real-world study conducted in Spain. Data were collected from 29 oncology departments across the country and included adult patients (≥18 years) with histologically confirmed SCLC diagnosed between January 2019 and December 2024. Baseline characteristics, treatment patterns, and survival outcomes were analyzed by sex. Results: Among 3,488 SCLC patients, 1,177 (33.8%) were women. The annual distribution of included SCLC cases remained stable over time (15.1%–17.7%), while the proportion of women increased from 29.3% to 39.2% over 6 years. Women were diagnosed at a younger age (mean 64.5 vs. 67.8 years). Active smoking was more frequent in women (68.0% vs. 54.7%, p<0.001), whereas men showed longer smoking and greater cumulative exposure, with median durations of 45 vs. 43 years (p=0.02) and median pack-years of 50 vs. 44 (p<0.001), respectively At diagnosis, 27% had limited-stage (LS) disease, more often in women (29.6% vs. 25.7%, p=0.015). Most LS patients received platinum–etoposide plus thoracic radiotherapy. In this population, 1-year overall survival (OS) was 67.9% (95%CI, 64.8-71.0%), with a median OS of 22 months (95%CI, 19.3-24.6 months); women had longer survival than men (Table 1). Systemic first-line (1L) treatment for extensive-stage (ES) consisted predominantly of platinum-based chemotherapy (95.6%; carboplatin 83.0% and cisplatin 12.6%) combined with etoposide (92.1%). Since its approval in September 2021, immunotherapy has been given to 66.3% of patients, more often to women (70.6% vs . 63.9%, p=0.013). In the population receiving 1L therapy, 1-year OS was 34.0% (95%CI, 32.1–35.9%), and median OS was 8.5 months (95%CI, 8.1–8.8). Women had longer survival (Table 1). Patients who received 1L immunotherapy had longer OS than those who did not: 10.1 months (95%CI, 9.4–10.7 months) vs. 7.2 months (95%CI, 6.6–7.7 months). Conclusions: This large multicenter SCLC cohort shows marked sex-related differences in epidemiology, stage distribution, treatment patterns and survival in Spain. Women were increasingly represented over time, diagnosed younger, and experienced longer survival in both LS and ES disease. These results support the importance of integrating sex-specific perspectives in SCLC management and research. Survival outcomes (CLARISSE study). LS-SCLC ES-SCLC Women Men Women Men 1-year OS(95% CI) 78.1%(73.1-83.1) 62.1%(58.1-66.1) 38.3%(34.9-41.7) 31.7%(29.7-33.7) Median OS (95% CI) (months) 30.1(25.4-34.7) 17.3(14.4-20.3) 9.1(8.2-9.9) 8.0(7.6-8.5)

Prognostic value of circulating tumor DNA in muscle-invasive bladder cancer treated with radical cystectomy: A systematic review and meta-analysis.

e16611 Background: Muscle-invasive bladder cancer (MIBC) is an aggressive disease that carries a high risk of disease recurrence. While traditional prognostic factors have been well established, circulating tumor DNA (ctDNA) has emerged as a biomarker for minimal residual disease (MRTD) in many malignancies, including MIBC.Various trials have evaluated the role of ctDNA in determining post-cystectomy adjuvant therapy, but pooled evaluation of survival outcomes based on ctDNA status remains unknown. Our meta-analysis compare disease-free survival (DFS) and overall survival (OS) based on ctDNA status in MIBC patients. Methods: A systematic literature search was conducted in PubMed, the Cochrane Library, and clinicaltrials.gov through January 2026, and we identified 216 studies evaluating ctDNA in MIBC. Studies reporting DFS and OS according to Signatera-based ctDNA for MRTD after radical cystectomy were evaluated. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted and pooled using a random-effects model. Statistical heterogeneity was assessed using I² statistic. The primary endpoints of our analysis were DFS and OS. Results: After screening, 7 studies met our selection criteria. Our pooled analysis had 1434 patients with a median age of 65 (60-69) years and a median follow-up of 53.6 (34-68) months. Patients with a ctDNA positive (ctDNA+ve) had a higher risk of mortality compared to ctDNA-negative (ctDNA-ve) (HR 4.51, 95% CI 2.44–8.33), with substantial heterogeneity (I² = 79.3%). Similarly, ctDNA+ve patients had an increased risk of disease recurrence (HR 8.87,95% CI 4.19–18.78; I² = 87.2%). In ctDNA+ve patients, adjuvant immunotherapy (AI) provided better OS compared to placebo (HR 0.56, 95% CI 0.44-0.72). However, in the ctDNA-ve patients, AI provided limited DFS benefit (HR 0.84, 0.50-1.41). Conclusions: Our meta-analysis demonstrates that patients with ctDNA+ve had inferior DFS and OS compared to those with ctDNA-ve status, irrespective of treatment across diverse study settings. There was no survival benefit with AI in patients with ctDNA-ve status. Post-surgery ctDNA status is a strong prognostic marker and should be incorporated into risk stratification and adjuvant therapy decision-making. Pooled hazards ratios for OS and DFS based on ctDNA. Study HR OS ctDNA+ve HR DFS ctDNA +ve HR DFS within ctDNA-ve HR OS within ctDNA+ve CheckMate 274 2.3 (1.3-4.0) 3.3 (2.1-5.6) 0.99 (0.51-1.93) 0.41 (0.20-0.84) IMVigor010 8.0 (4.9-12.9) 6.3 (4.5-8.9) 1.14 (0.81-1.62) 0.59 (0.42-0.83) NIAGRA 2.4 (1.7-3.3) 11.1 (5.7-20) 0.49 (0.28-0.84) - Nordentoft. 4.0 (1.8-8.8) - - - Lindskrog (NAC) 19.5 (6.9-54.6) 37.7 (8.5-167.1) - - Lindskrog (No NAC) 17.8 (3.9-81.2) 17.8 (3.9-81.2) - - TOMBOLA 2.3 (1.2-4.5) 2.3 (1.2-4.5) - - IMVigor011 - - 0.59 (0.39-0.90) Pooled Results 4.33 (2.58-7.28) 7.11 (3.35-15.07) 0.84 (0.50-1.41) 0.56 (0.44-0.72)

Clinicopathologic features of invasive lobular breast carcinoma in Syria: An epidemiological analysis from the country’s main cancer center in 2025.

e13032 Background: Invasive lobular carcinoma (ILC) is a distinct histological subtype of breast cancer that arises from the lobules. ILC accounts for approximately 10–15 % of all invasive breast cancers worldwide. Global epidemiological data on ILC indicates increased incidence rates over recent decades, likely influenced by improved detection methods. However, comprehensive population-based data on ILC in Syria and similar conflict-affected health systems remain limited. Methods: This retrospective study analyzed data from Al-Bairouni University Hospital, Syria’s main cancer center. It serves 65-70% cases nationwide. We included all patients diagnosed with primary Invasive Lobular Carcinoma in the Breast between January 1 and December 31, 2025. Abstracted variables included demographics (age, governorate of residence) and tumor data (stage, grade). Institutional ethical approval was obtained prior to data collection. Results: A total of 189 patients were diagnosed with ILC of the breast during 2025 (Table 1). The average age at diagnosis was 54.1 years, 3.7% of patients were Male, and 22.7% were smokers. At presentation, 81% were high grade, and 28.7% of all cases had advanced/metastatic disease. Ki-67 testing was unavailable in approximately 40% of cases. The highest patient load originated from Damascus (48.1%) and Rural Damascus (9%), followed by the central governorates of Homs and Hama (10%). Notably, patients from more distant and underserved governorates such as Deir ez-Zor (3.2%), Aleppo (8%), and Al-Hasakeh with Raqqa (8%) accounted for a significant proportion of the cancers presenting to our center. Analysis revealed significant differences in advanced disease rates at diagnosis across molecular subtypes (χ²(3) = 8.65, p = 0.034), with a linear trend of increasing metastatic presentation from Luminal A (18%) to Triple Negative (40%) (p = 0.012). No significant differences were observed in age, gender distribution, smoking rates, or tumor grade across subtypes. Caution is warranted in interpreting Triple Negative results due to the small sample size (n = 10). Conclusions: This study represents the first comprehensive analysis of invasive lobular carcinoma in Syria. Notably, a high prevalence of high-grade tumors was observed, which may reflect diagnostic limitations. In addition to lack of long-term follow-up which makes it difficult to assess overall and disease-free survival, underscoring the need for improved oncologic infrastructure and cancer registries in resource-limited settings. Disease characteristics. Diagnosis 2025 Cases Male cases Average Age Smokers (%) High grade (2,3 grade) Advanced/Metastatic at diagnosis Luminal A 72 3 53.1 25% 84.3% 18% Luminal B 73 3 54.5 23.2% 79% 24.3% HER2 Enriched 34 1 55.6 17.7% 81% 32.3% Triple Negative 10 0 52.2 20% 80% 40%

Early results from the first-in-human phase 1 study of WEE1 inhibitor APR-1051 in patients with advanced solid tumors (ACESOT-1051).

3107 Background: WEE1 tyrosine kinase regulates cell cycle checkpoints (G1-S, G2-M) and DNA damage responses. Inhibiting WEE1 can force premature mitotic entry and subsequent apoptosis. APR-1051 is a highly potent, orally bioavailable WEE1 inhibitor (WEE1i) with in vivo anti-proliferative activity. Low off-target inhibition of APR-1051 on PLK kinases (PLK1, PLK2, PLK3) differentiates it from other WEE1i’s and may confer improved safety. Methods: This open-label dose escalation (BOIN) and dose selection optimization study is evaluating APR-1051 using a once-daily (QD) regimen. The study is currently enrolling at 220 mg at three US sites (NCT06260514). Primary study objectives are to characterize the safety, dose-limiting toxicity (DLT), maximum tolerated dose/maximum administered dose, and recommended phase 2 dose of APR-1051. Secondary objectives include evaluating APR-1051 pharmacokinetic properties and preliminary efficacy (RECIST v1.1; PCWG3 criteria for mCRPC). Key inclusion criteria are age ≥ 18 years with advanced solid tumor and cancer-associated gene alterations, prior standard-of-care systemic treatment, and ECOG PS 0 or 1. Key exclusion criteria are prior WEE1i use, CNS metastases/unstable involvement, secondary malignancies requiring therapy, and concomitant moderate/strong inhibitors/inducers of CYP3A4/5, MDR1, or BCRP. Results: As of January 16, 2026, 22 patients (median age 62 years [range: 40–86]; have been enrolled up to the 220 mg dose level. Most (n=13, 59%) cases were colorectal cancers (colon [n=9, 41%], rectal [n=4, 18%]) followed by uterine (n=3, 14%), pancreatic (n=2, 9%), and breast, gastric, oropharyngeal, and soft tissue cancer (each n=1, 5%). The median prior lines of treatments was 3. Any grade adverse event (AE) was report in 21 (95%) patients. Treatment-related AEs were reported in 12 (55%) patients; 10 (45%) patients had non-serious gastrointestinal events. Twelve (55%) patients had 18 unique serious AEs, including one death on treatment unrelated to APR-1051 and one DLT of grade 3 elevated liver enzymes (AST, ALT) probably related to APR-1051 (n=1, 5%). Antitumor activity was observed in one (5%) patient with uterine serous carcinoma treated with APR-1051 150 mg who had an unconfirmed partial response—50% reduction in target lesion size (RECIST v1.1) and > 90% reduction in CA-125 tumor marker—at per protocol 8-week assessment. Five (23%) patients had stable disease: oropharyngeal cancer (APR-1051 70 mg [n=1, 5%]); colon, rectal, uterine cancer (100 mg [n=3, 14%]); colon cancer (150 mg [n=1, 5%]). A dose proportional increase in exposure was observed. Conclusions: In the ongoing trial, continuous, oral APR-1051 QD has a manageable safety profile with preliminary signals of antitumor activity in patients with pretreated advanced solid tumors. Clinical trial information: NCT06260514 .

Pancreatic cancer risk and metastatic outcomes in patients with metabolic dysfunction–associated steatotic liver disease.

e16440 Background: Pancreatic cancer (PC) is a malignancy with poor survival outcomes. Metabolic dysfunction–associated steatotic liver disease (MASLD) may influence PC risk and progression; however, its association with incidence, metastatic patterns, and clinical outcomes is unclear. Methods: We conducted a retrospective cohort study using the TriNetX Research Network from 2010 to 2026, including adults with MASLD and PC. Patients with other chronic liver diseases were excluded. First, two cohorts were established: patients with MASLD and patients without MASLD. Incidence rates of PC were calculated for each cohort. The MASLD and non-MASLD cohorts were then propensity score–matched in a 1:1 ratio to evaluate the risk of developing PC after 5 years. Subsequently, among patients diagnosed with PC, individuals were stratified into MASLD and non-MASLD groups and again matched 1:1 to compare metastatic outcomes after 1 and 2 years. Analyses were performed using Cox proportional hazards regression models and hazard ratios (HRs) with 95% confidence intervals. Results: 65,857 patients with MASLD and 333,116 without MASLD were included. The incidence of PC was 520 cases per 100,000 in the MASLD cohort compared with 250 cases per 100,000 in the non-MASLD cohort, with incidence rates of 4.3×10⁻⁴ and 2.4×10⁻⁴ cases per person-year, respectively. After matching 62,941 patients per group, MASLD was associated with a higher risk of PC compared with non-MASLD individuals (HR, 1.47; 95% CI, 1.17–1.86; p = 0.001). Among patients with PC, 10,526 patients with MASLD were matched 1:1 to non-MASLD patients. MASLD was associated with a higher risk of metastatic disease within 1 year (HR, 1.06; 95% CI, 1.01–1.11; p = 0.024), with an increased risk of peritoneal carcinomatosis (HR, 1.15; 95% CI, 1.03–1.28; p = 0.010). Risks were similar for liver metastasis (HR, 1.00; 95% CI, 0.94–1.07; p = 0.93), lung metastasis (HR, 1.07; 95% CI, 0.96–1.20; p = 0.25), bone metastasis (HR, 0.87; 95% CI, 0.75–1.00; p = 0.05), and brain metastasis (HR, 0.85; 95% CI, 0.65–1.13; p = 0.25). Over 2 years, MASLD remained associated with higher rates of peritoneal carcinomatosis (HR, 1.22; 95% CI, 1.10–1.35; p < 0.0001) and lung metastasis (HR, 1.13; 95% CI, 1.02–1.24; p = 0.02). Liver metastasis (HR, 1.04; 95% CI, 0.98–1.10; p = 0.17), bone metastasis (HR, 0.92; 95% CI, 0.81–1.05; p = 0.21), and brain metastasis (HR, 0.85; 95% CI, 0.66–1.10; p = 0.23) were similar between groups. Conclusions: MASLD is associated with a higher risk of incident PC and with an increased metastatic burden, particularly involving peritoneal and lung spread. These findings highlight MASLD as an important risk in PC and underscore the need for further mechanistic and prospective studies to clarify its role in pancreatic carcinogenesis and disease progression.

User-centered design of a COPD care pathway embedded in oncology care for patients receiving immune checkpoint inhibitors.

1566 Background: Chronic obstructive pulmonary disease (COPD) is one of the most common comorbidities among patients treated with an immune checkpoint inhibitor (ICI) for cancer, and it is often underdiagnosed and undertreated. We aimed to assess COPD treatment burden among patients with cancer and design a scalable intervention. Methods: This mixed-methods study enrolled (1) patients with confirmed/suspected COPD and ICI-treated cancer, and (2) clinicians providing ambulatory cancer or COPD care. Semi-structured surveys assessed treatment burden, self-confidence in COPD care, and barriers. Interviews, guided tours, and focus groups informed the user-centered design of a novel COPD care pathway, and the primary endpoint was participant-perceived feasibility. Qualitative analysis used a matrix approach informed by interview-guide constructs and emergent concepts, with quotations synthesized iteratively. Results: Between Feb-Dec 2025, the study team screened 478 individuals to enroll the planned cohort of 100 participants, including 20 patients and 80 clinicians. Nearly all participants completed a survey (n = 96), and 36 completed either an interview, tour, or focus group. Most patients reported their diagnosis of COPD had been confirmed (90%), and all were ≥50 years old. Clinicians were nurses (47%), physicians (44%), or APPs (6%); 41% practiced at a community oncology clinic. Most patients would use COPD-related services if integrated into oncology visits (75%) and 65% felt they had effective treatment options for both cancer and COPD. Nearly all clinicians (97%) agreed that COPD increased the risk of complications during cancer treatments, and 59% agreed that COPD care should be addressed within oncology clinics. Although most reported feeling confident in managing COPD in patients with cancer (80%), many reported a lack of skills to do so (e.g., teaching inhaler technique, 34%). Commonly cited barriers were insufficient time (63%), limited availability of COPD providers (65%), and COPD medication costs (50%). Qualitative analysis identified key themes: limited awareness of COPD guidance in oncology; resource constraints in community clinics; reliance on specialist referrals; conditional willingness to implement a COPD pathway if it did not detract from cancer care; and needs for educational materials and interoperable electronic medical records. These integrated datasets informed the design of a COPD care pathway to be embedded within oncology infusion visits using flowchart-based decision support to stratify COPD control (green/yellow/red) and support self-management and targeted clinician education at the point of care. Conclusions: COPD imposes a substantial treatment burden on patients with cancer, but there are actionable opportunities for care delivery. A user-centered COPD care pathway was designed for feasibility in community oncology settings.

Tumor-associated macrophage (TAM) score as an independent predictor of recurrence in residual disease after neoadjuvant chemotherapy and for identification of high-risk patients for adjuvant escalation.

522 Background: Tumor-associated macrophages (TAMs) drive immune evasion and chemotherapy resistance in breast cancer through tumor microenvironment reprogramming. We developed a composite TAM score integrating transcriptional programs with spatial IHC polarization markers to stratify recurrence risk and enrich macrophage-modulating trials, hypothesizing it would improve prognostic accuracy in treatment-naïve disease and predict neoadjuvant chemotherapy (NACT) response. Methods: TAM score was derived from scRNA-seq atlases (n=4), filtering survival-associated genes in METABRIC/TCGA (n=2,509), and weighting IHC markers CD163/CD206 normalized to CD68/CSF1R via Cox coefficients. Validation: treatment-naïve invasive carcinomas (n=83; follow-up 57 months; 24 events). Primary endpoint: recurrence-free survival (RFS); multivariable Cox adjusted for age, tumor size, nodal status, grade, subtype, treatment. Predictive utility assessed in matched primary/post-NACT residual tumors (n=45) correlating TAM dynamics with RCB. Results: High TAM score (≥median) independently predicted worse RFS (HR 3.8, 95% CI 1.6-9.1, p<0.05) and outperformed CD163/CD68 alone (HR 2.1, p<0.05); 5-year RFS was 68% vs 91% (TAM-high vs TAM-low). Prognostic value persisted in node-negative (HR 4.2, p=0.02) and luminal B (HR 3.5, p=0.01) subsets. In the NACT cohort, baseline TAM score inversely correlated with pCR (12% vs 38%, p=0.04). Among residual disease (RCB-II/III, n=34), persistent TAM-high post-NACT identified 3-year RFS 52% vs 85% in TAM-low/normalized cases (HR 4.1, p=0.01), independent of RCB; CD163+/CD206+ expansion occurred in 76% of RCB-III vs 29% of RCB-I (p=0.008). Conclusions: This TAM score predicts recurrence from pre-treatment tissue and identifies macrophage-driven resistance persisting post-NACT, nominating TAM-high residual disease for macrophage-modulating trials. Translational evidence supports this: CSF1R inhibition reduced immunosuppressive TAMs, increased M1-like programs, decreased PD-L1/PD-L2, and enhanced anti-PD-1 efficacy preclinically with ex vivo confirmation. Early-phase data (rebastinib plus chemotherapy in HER2-negative metastatic disease) demonstrate feasibility, supporting prioritization of TAM-high patients with residual disease for trials combining TAM modulation with checkpoint therapy. TAM score performance in treatment-naïve and NACT cohorts. Endpoint TAM-High TAM-Low HR scores (95% CI) p-value Treatment Naïve cohort 5 year RFS (Overall) 68% 91% 3.8 (1.6-9.1) <0.05 RFS (node-negative) 4.0 0.02 RFS (luminal B)-- 3.5 0.01 CD163/CD68 alone 2.1 <0.05 NACT Cohort (n=45) Baseline pCR rate 12% 38%- 0.04 3-year RFS(RCB-II/III n=34) 52% 85% 4.1 0.01 CD163+/CD206+ expansion 76% (RCB-III) 29%(RCB-I)- 0.008

Real-world second-line treatment patterns and outcomes by platinum sensitivity in extensive-stage small cell lung cancer in the post-immunotherapy era.

8083 Background: Platinum-based chemotherapy (PBC) with checkpoint inhibitor (CPI) is standard first-line (1L) treatment for extensive-stage small cell lung cancer (ES-SCLC), though relapse is common. Second-line (2L) treatment selection is determined by platinum sensitivity status, with guidelines based on pre-CPI data, and the benefit of any CPI continuation is unknown. This study examined treatment patterns and real-world (rw) outcomes for patients following 1L PBC +/- CPI among platinum-sensitive (PS) patients, including the impact of continuing a CPI with platinum rechallenge. Methods: This retrospective study used EHR-derived US Flatiron Health Research Database. Eligible patients were diagnosed with ES-SCLC between January 1, 2018, and September 9, 2025, received 2L treatment following 1L PBC with a calculable platinum sensitivity and had a minimum potential follow up of 120 days. Platinum sensitivity was defined by a chemotherapy-free interval of ≥ 180 days, based on the last order or administration of 1L PBC to first real-world progression event prior to 2L initiation. Real-world response rate (rwRR), progression free survival (rwPFS) and overall survival (rwOS) were described based on 2L regimen class for patients with PS disease, and were compared via HR for platinum rechallenge with CPI continuation versus without. Time-to-event outcomes were analyzed using Kaplan-Meier methods, with medians and 95% CI reported for the overall cohort and subgroups of interest. Results: Among 5,126 eligible patients, 884 (17%) had PS and 4,242 (83%) had platinum refractory (PR) disease. Most patients (73%) received CPI with PBC in 1L. Patients with PR had worse outcomes than PS (rwPFS, 2.7 [95% CI, 2.6-2.8] vs 5.5 [95% CI, 5.3-5.7] mo; rwOS, 4.7 [95% CI, 4.5-4.9] vs 11.2 [95% CI, 10.6-12.4] mo). Among PS patients with 1L CPI exposure (n=666), 48% received 2L PBC, and 41% of 2L PBC continued a CPI. Clinical characteristics in PS disease were similar across classes of 2L regimen. Of patients with PS disease who had 1L CPI exposure, 81% had at least 1 response assessment during the study period. Of PBC patients, rwRR was 52% among CPI treated and 58% without CPI. 2L rwPFS and rwOS were similar regardless of CPI continuation (Table). Conclusions: In this large real-world study, nearly half of patients with PS disease were rechallenged with PBC in 2L, and CPI continuation was common despite limited evidence. CPI continuation did not improve response, progression, or survival, suggesting no additional benefit and highlighting the need for prospective data to guide post-CPI treatment in PS ES-SCLC. Outcome 2L rwPFS median, mo (95% CI) Unadjusted HR (95% CI) P value 2L rwOS median, mo (95% CI) Unadjusted HR (95% CI) P value PBC with CPI (n=112) 5.6 (5.4-6.2) - - 12.3 (11.0-15.9) - - PBC without CPI (n=149) 6.0 (5.6-6.6) 0.97(0.76, 1.25) 0.80 12.9 (11.0-15.3) 1.04 (0.80, 1.35) 0.80

Synthetic lethality–informed neoantigen prioritisation to support mechanism-specific therapeutic strategies across human cancers.

2510 Background: Personalised neoantigen vaccines can elicit strong tumour-specific T cell responses, yet tumours may evade immune pressure by deleting or silencing the targeted gene. Current selection pipelines treat gene-based escape as an unpredictable failure. For tumour suppressor genes, however, loss of the target can create predictable synthetic lethal (SL) dependencies. We present a framework that classifies tumour suppressor mutations by their therapeutic implications. We hypothesised that hypomorphic mutations, which generate immunogenic neoantigens while retaining partial function, may be suited to sequential therapy, where vaccination selects for complete loss and exposes druggable vulnerabilities. In contrast, null mutations with pre-existing SL dependencies may benefit from upfront vaccine–drug combinations. Methods: We analysed 9,953 tumours across 32 cancer types from TCGA. Tumour suppressor mutations were assessed for neoantigen potential using NetMHCpan-4.2, MHCflurry 2.0, and PRIME 2.0 (%rank < 2%), with filtering for clonality, expression (TPM > 1), and multi-allele HLA presentation. Functional status was assigned using gene-specific annotations, including TP53 transactivation scores. SL relationships were curated from DepMap, SynLethDB 2.0, and published clinical evidence, restricted to partners with approved or Phase II+ inhibitors. Results: 7.4% of patients (n = 741) harboured tumour suppressor neoantigens with matched SL vulnerabilities, which segregated into two distinct groups. The first group (4.6%, n = 458) carried hypomorphic mutations that generated immunogenic neoantigens while retaining partial gene activity, consistent with candidacy for sequential vaccination followed by SL inhibition upon escape. TP53 missense mutations predominated (58%), with progression to null status predicted to confer WEE1 or CHK1 vulnerability. Additional recurrent pairings included PTEN–AKT (14%), ATM–ATR or PARP (11%), KMT2D–EZH2 (9%), and BRCA2–PARP (8%). The second group (2.8%, n = 283) carried functionally null mutations with SL dependencies present at diagnosis, nominating these patients for upfront vaccine–drug combinations. Endometrial (12.1%) and colorectal (9.8%) cancers were enriched for both patterns, whereas high-grade serous ovarian cancer was dominated by hypomorphic mutations. Conclusions: This framework reframes immune escape from neoantigen vaccination, conventionally viewed as treatment failure, as a predictable and potentially exploitable therapeutic event. Functional classification of tumour suppressor neoantigens provides a rationale for distinguishing sequential from upfront vaccine–SL inhibitor strategies. Prospective trials with longitudinal monitoring will be required to determine whether vaccination-induced gene loss consistently exposes the predicted vulnerabilities.

GEMINI-NSCLC: Multiomics and single-cell spatial profiling to benchmark, back-translate, and build digital twins of IO response.

8533 Background: Response to first-line standard-of-care (SoC) chemo-immunotherapy (IO) for patients with NSCLC without targetable mutations is heterogeneous, highlighting the need for predictive biomarkers. GEMINI (NCT05236114) integrates real-world outcomes, whole exome sequencing (WES), single-cell spatial transcriptomics (SpTx), and AI-pathology to establish a benchmarking resource and patient-level digital twins, enabling back-translation into testable hypotheses. With >4 million cells from 53 biopsies, GEMINI is one of the largest single-cell spatial datasets linked to IO outcomes. Methods: Patients with metastatic NSCLC were analyzed for outcome associations. Progression-free survival (PFS) was defined from IO start to progression, next regimen, last follow-up, or 2 years. Patients were classified as fast progressors (<3 months PFS) or slow progressors (>3 months PFS). Baseline biopsies (n=53) underwent WES and SpTx. Neural networks traced single-cell boundaries on H&E to quantify gene expression; cells were annotated via clustering and LLM-assisted labeling. AI-, manual-, and digital-pathology (DSP) defined tumor, immune, and stroma regions. Cohort-level benchmarking was integrated into patient-level digital twins to back-translate spatial-genomic features into individualized risk and mechanism hypotheses. Results: WES revealed expected mutation frequencies: STK11 15%, TP53 73%, KEAP1 21%, KRAS 46%, supporting cohort representativeness. Stroma-associated TIL counts were higher in slow versus fast progressors by AI-path (p=0.034) and manual-path (p=0.014). DSP showed immune aggregates in slow progressors were lymphocyte-diverse, whereas fast progressors were enriched for five macrophage subtypes consistent with immunosuppressive niches. Spatial proximity of lymphocytes and stroma to a tumor subcluster (C2) predicted progression (p<0.01). Immunoglobulin light-chain expression localized to the tumor core in slow progressors, suggesting tumor–B cell interactions with disease arrest. Differential expression identified 14 EMT/ECM genes overexpressed in fast-progressor stroma, implicating stromal barrier/ECM remodeling in IO resistance. Digital twins captured these spatial-omic signatures to forecast risk and generate patient-specific, testable hypotheses. Conclusions: GEMINI provides a large single-cell spatial transcriptomic benchmark linked to IO outcomes for patients with NSCLC and enables AI-driven digital twins for clinical decision support. Fast progressors show stromal EMT/ECM programs and immunosuppressive myeloid niches; slow progressors exhibit lymphocyte diversity and tumor–B cell interactions near subcluster C2. Findings support multimodal risk stratification and nominate stromal EMT/ECM targeting to overcome IO resistance, with prospective validation via digital-twin biomarkers. Clinical trial information: NCT05236114 .

National patterns of hospitalization, mortality, and resource utilization in Merkel cell carcinoma in the United States, 2018–2022.

e21574 Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with limited contemporary national data describing inpatient utilization and outcomes. National benchmarking of MCC-related hospitalizations may inform care delivery and resource planning. Methods: A serial cross-sectional analysis of the 2018–2022 Healthcare Cost and Utilization Project National Inpatient Sample was performed. Adult (≥18 years) hospitalizations with a principal diagnosis of MCC (ICD-10-CM C4A) were included; all analyses were conducted at the hospitalization level. National estimates incorporated discharge-level survey weights (DISCWT) with stratification by hospital stratum (NIS_STRATUM) and clustering by hospital (HOSP_NIS). Outcomes included hospitalization volume, admission type (elective vs non-elective), in-hospital mortality, length of stay (LOS), inflation-unadjusted hospitalization cost estimated using HCUP cost-to-charge ratios, hospital location/teaching status, and primary payer. Survey-weighted analyses accounted for the complex sampling design. Results: From 2018–2022, 308 unweighted MCC hospitalizations corresponded to an estimated 1,535 weighted hospitalizations nationally. Elective admissions accounted for 66.4% of hospitalizations, while 33.6% were non-elective. Overall in-hospital mortality was 5.3% and was higher among non-elective compared with elective admissions (8.7% vs 0.5%). Inpatient care was highly centralized, with 90.9% of hospitalizations occurring at urban teaching hospitals. Medicare was the predominant payer (74.9%), followed by private insurance (18.2%). Mean LOS was 4.8 days, and mean hospitalization cost was $20,524. Conclusions: In this contemporary national sample, MCC principal hospitalizations were uncommon but associated with meaningful inpatient mortality and resource utilization. Non-elective admissions were associated with higher in-hospital mortality, and care was predominantly delivered at urban teaching hospitals with substantial reliance on Medicare coverage. These findings provide national benchmarks for inpatient MCC care and support evaluation of care delivery patterns and resource planning for this rare cutaneous malignancy.

Iparomlimab and tuvonralimab combined with paclitaxel and cisplatin as neoadjuvant therapy for cervical cancer: A phase II umbrella trial.

TPS5629 Background: There is an urgent need to improve neoadjuvant therapy for locally advanced cervical cancer (LACC) and fertility-preserving neoadjuvant therapy for early-stage cervical cancer patients. However, there is no study evaluating the efficacy and safety of PD-1 and CTLA-4 dual blockade-based therapy for above clinical scenarios. The present study aims to assess QL1706 combined with paclitaxel and cisplatin as neoadjuvant therapy for LACC and early-stage cervical cancer patients for fertility-preservation respectively. Methods: Trial design: For Arm 1 (LACC), patients aged 18-75 years, with FIGO 2018 stages IB3, IIA2, IIB, or IIICr (lesion ≥4 cm, confirmed by MRI), histologically confirmed as cervical squamous cell carcinoma, cervical adenocarcinoma, or cervical adenosquamous carcinoma will be included. For Arm 2 (fertility preservation), patients aged 18-45 years old, who have a strong desire to preserve fertility, with FIGO 2018 stages IB2, IB3 (lesion ≤6 cm), IIA1, or IIA2 (lesion ≤6 cm) and histologically confirmed as cervical squamous cell carcinoma, cervical adenocarcinoma, or cervical adenosquamous carcinoma, will be included. All participants will be given 3 cycles of neoadjuvant treatment with QL1706 (5 mg/kg), paclitaxel (135-175 mg/m 2 ) and cisplatin (75-80 mg/m 2 ) per 21 days. Patients in Arm 1 (LACC) who achieve CR/PR will undergo radical hysterectomy plus lymphadenectomy after 3 cycles of neoadjuvant therapy whereas patients in Arm 2 (fertility preservation) who achieve CR/PR will undergo fertility-preserving surgery. For IB1/IB2 patients, conization or simple trachelectomy plus lymphadenectomy will be performed. For IIA1/IIA2 patients, radical trachelectomy plus lymphadenectomy will be performed. Patients achieve PD/SD will be given standard treatment according to the current NCCN guideline. The primary endpoints consist of objective response rate (ORR), pathological complete response (pCR) and changes in tumor-related biomarkers (ctDNA, etc). Secondary endpoints include 2-year overall survival (OS), 2-year disease-free survival (DFS) and adverse events. Other endpoints are 2-year pregnancy rate and infant survival rate for Arm 2. Sample size is 20 for Arm 1 and 15 for Arm 2. Clinical trial identification: NCT06878222. Clinical trial information: NCT06878222 .

Disparities in pancreatic cancer incidence and shifting survival trends in the United States (1999–2021).

e16432 Background: Pancreatic cancer remains among the most lethal malignancies in the United States, withpersistently high mortality despite incremental therapeutic advances. Evaluating long-term trendsin incidence, mortality, and mortality-to-incidence rate ratios (MIRRs) is essential for assessingpopulation-level survival gains and identifying demographic and geographic disparities. Methods: We analyzed U.S. pancreatic cancer trends from 1999 to 2021 using the CDC WONDERdatabase. Age-adjusted incidence rates (AAIRs) were obtained from the United States CancerStatistics Incidence dataset, standardized to the 2000 U.S. population. Age-adjusted mortalityrates (AAMRs) and MIRRs were extracted from the 1999–2021 Mortality- Incidence Rate Ratiosdataset. Temporal trends were assessed using Joinpoint regression to estimate average annualpercent changes (AAPCs) with 95% confidence intervals (CIs). Results: From 1999 to 2021, 854,937 pancreatic cancer deaths and 977,683 new cases were reported inthe United States. The age-adjusted incidence rate increased from 10.91 to 13.41 per 100,000(AAPC: 0.90%, 95% CI: 0.82 to 0.98), and the age-adjusted mortality rate increased by 5.7%,from 10.60 to 11.24 per 100,000 (AAPC: 0.29%, 95% CI: 0.24 to 0.36). Despite rising absolutenumbers, the MIRR declined from 0.97 to 0.84 (AAPC: –0.62%, 95% CI: –0.72 to –0.57),indicating modest improvement in survival.By sex, incidence remained higher in males, increasing from 12.47 to 15.25 per 100,000 (AAPC:0.86%, 95% CI: 0.80 to 0.95), compared to 9.61 to 11.85 per 100,000 in females (AAPC: 0.90%,95% CI: 0.83 to 1.00). By race, Black individuals had the highest incidence (14.52 to 15.59 per100,000), followed by White (10.61 to 13.20), Asian/Pacific Islander (8.52 to 9.70), andAmerican Indian/Alaska Native populations (7.95 to 9.21). Incidence among Black individualspeaked at 17.06 in 2018. At the state level, the District of Columbia recorded the highest averageage-adjusted incidence rate at 14.78, and Wyoming had the lowest average rate at 10.33. By age,incidence increased sharply with advancing age. The highest rates were seen among individualsaged ≥85 years (average: 95.54; peak: 100.86), followed by 80–84 (avg: 89.40), 75–79 (77.02),and 70–74 (61.00). Incidence remained below 3 per 100,000 among those under 45. Conclusions: Pancreatic cancer incidence and mortality have continued to rise in the United States, withincidence increasing more rapidly than mortality. Although declining MIRRs indicate limitedsurvival gains, pronounced disparities by sex, race, age, and geography persist. These findings highlight the need for targeted prevention strategies, earlier detection efforts, and equitableaccess to emerging therapies.

Impact of chronic kidney disease on adverse event topography and economic burden in CAR T-cell therapy for DLBCL: A national analysis.

e19054 Background: Chronic kidney disease (CKD) may potentiate toxicity and impair organ resilience in recipients of chimeric antigen receptor (CAR) T-cell therapy for diffuse large B-cell lymphoma (DLBCL). While cytokine response syndrome (CRS) and immune cell effector neurotoxicity syndrome (ICANS) have been reported with CKD, the cardiac, infectious, and economic sequelae are insufficiently described. We evaluated these outcomes across CKD strata from a national database. Methods: Using the National Inpatient Sample (2017–2022), we identified adult DLBCL hospitalizations receiving CAR T-cell therapy. ESRD patients were excluded. CKD was examined in two frameworks: CKD3a+ (eGFR <60 mL/min) versus no/CKD1–2, and CKD3b+ (eGFR <45 mL/min) versus no–CKD3a. Outcomes included in-hospital mortality, CRS (2021–2022), ICANS (2022), cardiac events, infections, acute kidney injury (AKI), renal replacement therapy and total hospitalization costs (calculated using TOTCHG variable and adjusted cost to charge ratio) and comparative analyses was done using chi-square testing. Multivariable models adjusted for demographics, comorbidities, and hospital characteristics. Results: In a cohort of 5,400 hospitalized DLBCL patients receiving CAR-T, those with CKD stage 3a or higher (CKD3a+; n=165; 3.1%) had higher rates of AKI (33.3% vs 11.6%; p<0.001) and renal replacement therapy (6.1% vs 1.4%; p=0.040) compared to no/CKD1–2 (n=5,235. Total hospitalization cost was higher (USD 456,198 vs 365,182; p=0.024) and grade 4 ICANS occurred more frequently (10.0% vs 1.4%; p=0.046). Mortality (6.1% vs 2.8%; p=0.259), pneumonia (12.1% vs 6.1%; p=0.246) and cardiac arrhythmias (33.3% vs 21.2%; p=0.094) were increased numerically. After multivariable adjustment, most differences diminished (mortality odds ratio [OR] 1.8, p=0.617; AKI OR 1.2, p=0.735). Among patients with CKD stage 3b or higher (CKD3b+; n=80; 1.5%), complications were more pronounced. In-hospital mortality was substantially higher (12.5% vs 2.7%; p=0.017), along with grade 4 CRS (7.7% vs 1.0%; p=0.011), acute myocardial infarction (6.3% vs 0.7%; p=0.007) and AKI (50.0% vs 11.7%; p<0.001). The cost of hospitalization (USD 446,074 vs 366,826; p=0.197) trended higher. Adjusted models confirmed markedly increased mortality (OR 10.2, 1.5–67.8; p=0.016) but other outcomes were not significant. Conclusions: CKD3b+ is associated with substantially higher mortality with signal of augmented high-grade CRS and cardiac events, whereas CKD3a+ exhibited worsening in renal outcomes and higher cost that attenuated after adjustment. These findings position pre-existing renal dysfunction especially CKD3b+ as a clinically salient risk substrate warranting pre-emptive risk stratification, vigilant cardiac monitoring and proactive organ-support pathways to mitigate downstream morbidity and mortality.

Role of FNDC1 and Gβ2 in suppression of the β-catenin destruction complex and promotion of gastric cancer malignancy.

e16478 Background: Gastric cancer (GC) is a leading cause of cancer-related deaths with high recurrence rates. Fibronectin domain-containing protein 1 (FNDC1) is implicated in GC progression, but its molecular mechanisms remain unclear. Methods: Multi-omics analyses (TCGA, GEO datasets) were used to assess FNDC1 expression and clinical correlation. In vitro (cell proliferation, invasion, EMT markers) and in vivo (xenograft) experiments, combined with molecular assays (Co-IP, WB, ChIP), explored FNDC1’s function and mechanism. Results: FNDC1 was significantly upregulated in GC, correlating with advanced clinicopathological features and poor prognosis. Knockdown of FNDC1 suppressed GC cell proliferation, invasion, and metastasis by inhibiting EMT and Wnt/β-catenin signaling. Mechanistically, FNDC1 competitively bound the WD5 domain (residues 224-254) of Gβ2, disrupting Gβγ-Dvl1 interaction. This prevented Dvl1 degradation, promoted Axin1 ubiquitination, and destabilized the β-catenin destruction complex (GSK3β-APC-Axin1), leading to β-catenin accumulation and Wnt pathway activation. Conclusions: FNDC1 drives GC malignancy by targeting the Gβ2-Dvl1 axis to activate Wnt/β-catenin signaling, suggesting FNDC1 as a novel prognostic biomarker and therapeutic target.