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The cost of cancer care in Singapore: A population-based analysis of healthcare expenditures and survivorship.
e23397 Background: Cancer is the leading cause of death in Singapore and advances in diagnostics and therapeutics have increased healthcare expenditure. However, population-level studies examining rising costs and survival gains across cancer types remains limited. We aim to quantify the direct medical costs of cancer care in Singapore and evaluate how changes in expenditure relate to survival gains across cancer types, disease stages, and phases of care. Methods: This population-based study included 103,243 individuals diagnosed with 1 of the 15 common cancers in Singapore between January 1, 2005, and December 31, 2016. Data were obtained from the national cancer registries and linked administrative healthcare databases through the Trusted Research and Real-World Data Utilisation and Sharing (TRUST) platform. Patients were followed through December 31, 2020. Direct medical costs were estimated from a health system perspective and inflation-adjusted to 2020 Singapore dollars (SGD). Costs were analysed by cancer type, phase of care and disease stage. Survival was assessed using restricted mean survival time (RMST). We assessed change in cost per discounted life-year gained across two time periods (modified ICERs). Results: Total first-year cancer expenditures increased from SGD 135.3 million (mil) in 2005 to SGD 400.4 mil in 2016, while cumulative five-year costs rose from SGD 195.0 mil to SGD 672.0 mil. Mean per-patient first-year costs increased from SGD 20,600 to SGD 36,200 and five-year costs more than doubled from SGD 29,700 to SGD 60,800. Initial treatment accounted for the largest share (50.4%; SGD 2.32 billion), followed by end-of-life care (35.4%; SGD 1.60 billion). Mean per-patient initial-phase costs were highest for myeloid cancer (SGD 70,900), lymphoid cancer (SGD 66,700), and pancreatic cancer (SGD 48,800). Inpatient services constituted the largest percentage of five-year expenditures, with per-patient inpatient costs increasing from SGD 25,600 in 2005–2008 to SGD 35,800 in 2013–2016 (compound annual growth rate (CAGR), 3.66%). Outpatient expenditures grew most rapidly from SGD 18,600 to SGD 41,200 per patient (CAGR, 7.48%). Stage IV cancers had the fastest cost growth (CAGR, 8.8%), exceeding stage I (2.4%), stage II (6.0%), and stage III (6.0%) disease. Survival gains varied across cancers, with RMST increase from 0.04 to 0.34 years. Corresponding modified ICERs ranged from SGD 750 per dLYG for myeloid cancers to SGD 94,450 per dLYG for prostate cancer. Conclusions: Cancer care in Singapore has become more resource intensive with wide variation in the value across cancer types. While survival outcomes have improved, gains have not consistently matched rising expenditures. These findings highlight the need for value-based cancer policies that align resource allocation with measurable clinical benefit to ensure sustainable cancer care delivery.
Impact of MASLD in-hospital mortality in patients with cholangiocarcinoma: A nationwide analysis.
e16217 Background: Cholangiocarcinoma is an aggressive hepatobiliary malignancy frequently requiring hospitalization due to advanced disease and treatment-related complications. Metabolic dysfunction–associated steatotic liver disease (MASLD) is a common chronic liver condition and a recognized risk factor for hepatobiliary cancers, characterized by metabolic and inflammatory disturbances that may influence short-term inpatient outcomes. However, the impact of MASLD on hospitalization outcomes in cholangiocarcinoma remains poorly defined. Using a nationally representative database, we evaluated the association between MASLD and in-hospital mortality, complications, and healthcare utilization among patients hospitalized with cholangiocarcinoma. Methods: A retrospective cohort study was conducted using the 2019–2023 National Inpatient Sample (NIS) database. Adult patients (≥18 years) hospitalized with cholangiocarcinoma were identified using ICD-10 codes and stratified based on the presence of MASLD. The primary outcome was in-hospital mortality, and secondary outcomes included race, length of stay (LOS), hospital charges, infections and gastrointestinal complications, and other clinical outcomes. Results: A total of 189,820 hospitalized patients with cholangiocarcinoma were identified, of whom 6,425 (3.4%) had MASLD. Affected patients were younger (mean age 66 vs 68 years; Coefficient: -1.8; P < 0.001), predominantly White (n = 4,498; 70%) with equal sex distribution (50% Female). Compared with non-MASLD, patients with MASLD were associated with significantly lower in-hospital mortality (5% vs 7%; OR: 0.72; P < 0.05) but higher gastrointestinal adverse events (27% vs 23%; OR: 1.29; P < 0.001), including acute pancreatitis (6% vs 4%; OR: 1.5; P < 0.05), peptic ulcer diseases (4% vs 2%; OR: 1.5; P < 0.001), and hepatic failure (8% vs 5%; OR: 1.5; P < 0.001). No significant differences were observed in GI bleed, diarrhea, or nausea. Hospital charger costs were higher among MASLD patients ($106,994 vs $95,531; Coefficient: 11,462; P < 0.05), while LOS did not differ significantly between groups (Coefficient: 0.212 days; P = 0.260). Conclusions: MASLD was associated with lower in-hospital mortality despite higher hospital charges and increased gastrointestinal adverse events. MASLD patients had higher rates of acute pancreatitis, peptic ulcer disease, and hepatic failure, while no differences were observed in gastrointestinal bleeding, diarrhea, or nausea. Length of stay was similar between groups. These findings indicate a heterogeneous association between metabolic liver disease and short-term inpatient outcomes in cholangiocarcinoma and support the need for further investigation.
Immunotherapy access disruptions in Mexico: Real-world delivery irregularities at a public cancer referral center.
1511 Background: Immunotherapy improves outcomes in selected cancers, but access in middle-income countries may be limited by cost and supply instability. We quantified eligibility, initiation, and delivery disruptions attributable to drug unavailability at a public cancer referral center in Mexico. Methods: Retrospective cohort of adults with a first oncology consultation at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (Mexico City) between January 2023 and March 2025. Records were reviewed to identify standard indications for immunotherapy per NCCN/ESMO/ASCO guidelines current at evaluation. Among eligible patients, we assessed initiation and delivery fidelity. Deviations were defined as delay to initiation >30 days, regimen modification, or temporary/permanent suspension due to drug shortages. Results: Among 1,201 first-time consultations, 228 (18.9%) had an immunotherapy indication; 114/228 (50.0%) initiated immunotherapy. Among eligible patients who did not initiate (n=114), medication unavailability was the most frequent reason (48, 42.1%). Among treated patients (n=114), delivery disruptions were common: 42 (36.8%) had treatment suspensions due to shortages, 9 (7.9%) received regimens deviating from approved protocols, and 8 (7.0%) started with >30-day delay. Overall, only 55/228 (24.1%) immunotherapy-eligible patients received treatment as recommended by international guidelines. Conclusions: In this public Mexican referral center, only half of immunotherapy-eligible patients initiated treatment, and over half of treated patients experienced delivery disruptions linked to drug unavailability. These findings support urgent procurement and supply-chain strategies to ensure timely, uninterrupted access to high-impact cancer therapies in publicly funded systems. Extent of immunotherapy eligibility, initiation, and delivery disruptions attributable to drug unavailability. Measure Value First-time oncology consultations 1201 Immunotherapy indication 228 (18.9%) Initiated immunotherapy 114/228 (50.0%) Non-initiation due to medication unavailability 48/114 (42.1%) Any delivery irregularity among treated patients 59/114 (51.8%) Suspension due to drug shortages 42/114 (36.8%) Regimen deviation due to unavailability 9/114 (7.9%) Initiation delay >30 days 8/114 (7.0%) Guideline-concordant immunotherapy among eligible patients 55/228 (24.1%) Values are n (%) unless otherwise indicated. Delivery irregularities include initiation delay >30 days, regimen modification, or temporary/permanent treatment suspension due to drug shortages. Percentages are calculated using the denominators specified in each row.
Immune infiltration features relative to cancer cell clumps as predictors of survival in triple-negative breast cancer.
1134 Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. While immune infiltration and abundance have been established as prognostic indicators, we examine how immune spatial organization and tumor geometry jointly influence survival. Methods: Whole-slide H&E images from 125 TNBC TCGA cases were analyzed using pathology instance learning models to generate tile-based predictions, which were reconstructed into polygon annotations for tumor epithelium, tumor-infiltrating lymphocytes (TILs), and tertiary lymphoid structures (TLS). From these annotations, we extracted novel spatial features describing abundance, fragmentation, dispersion, shape, and boundary properties of immune and tumor regions, as well as immune–tumor distances, overlap gradients, and boundary engagement. Associations with disease-specific survival (DSS) were assessed using univariate Cox models, and significant features were incorporated into a multivariate Cox model. Kaplan–Meier and correlation analyses were performed for dichotomized features. Results: Among all spatial features analyzed, global immune dispersion emerged as a strong indicator of survival. This metric, quantified by the radius of gyration of immune islands, was significantly associated with worse disease-specific survival (DSS) (HR per SD = 1.90; p = 0.03) and demonstrated clear Kaplan–Meier separation (log-rank p = 0.028). Increased tumor boundary complexity, measured by edge density normalized to tissue area, was also associated with poorer DSS (HR per SD = 1.77; p = 0.007). Kaplan–Meier analysis for edge density showed only modest separation (log-rank p = 0.071), consistent with a gradual, continuous risk effect rather than a discrete threshold. Similarly, greater intratumoral immune area correlated with adverse DSS (HR per SD = 1.26; p = 0.020), supporting the interpretation of intratumoral immune accumulation as a marker of ineffective or dysfunctional immune infiltration rather than protective immunity. In a multivariable Cox model, immune dispersion, tumor boundary complexity, and intratumoral immune area retained concordant effect directions and jointly achieved strong discrimination (C-index ≈ 0.74). Correlation analysis confirmed that the dominant spatial features were non-redundant, with minimal multicollinearity (all variance inflation factors < 1.2). Conclusions: In TNBC, survival is not solely dependent on immune abundance and proximity to the tumor region, but on the immune spatial dispersion, aggressive tumor boundaries, and ineffective immune accumulation in the intratumoral space. Novel spatial biomarkers examined here may refine risk stratification beyond conventional metrics.
Integrated transcriptomic profiling and explainable machine learning to reveal functional reprogramming and biomarker candidates in pancreatic ductal adenocarcinoma.
e16002 Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive and lethal malignancies of the digestive tract, with a five-year survival rate below 5%. Late diagnosis, high tumour heterogeneity, and limited therapeutic efficacy highlight the urgent need to identify molecular biomarkers and therapeutic targets. This study combines transcriptomic analysis with interpretable machine learning to characterise key functional alterations in PDAC. Methods: Gene expression data from 146 pancreatic tissue samples (72 normal and 74 tumour) were obtained from the Pan-Cancer Atlas (TCGA). Differential expression analysis was performed using DESeq2, followed by functional enrichment analysis via GO and KEGG. A classification model was built using the XGBoost algorithm and evaluated with 500 bootstrapping iterations. Model interpretability was assessed through SHAP (SHapley Additive exPlanations) values to identify genes with the highest predictive contribution, which were then cross-referenced with differentially expressed genes. Results: A comprehensive transcriptomic analysis revealed significant dysregulation of multiple genes between normal and tumor pancreatic tissues. Genes such as GJB3, S100A2, MSLN, and SLC2A1 were notably overexpressed, whereas DEFA6, APOB, and RBP2 exhibited marked downregulation, indicative of impaired exocrine function and aberrant epithelial reprogramming. The XGBoost classification model achieved an average area under the curve (AUC) of 0.9868 and an overall accuracy of 98.6%. SHAP (SHapley Additive exPlanations) analysis identified GJB3, LINC02086, and TSPAN1 as key predictive features. Six genes were concurrently identified as differentially expressed and highly influential within the model, supporting their potential utility as robust biomarkers for pancreatic tumor characterization. Conclusions: Pancreatic ductal adenocarcinoma is marked by extensive transcriptomic reprogramming. The integration of differential gene expression analysis with interpretable machine learning enabled the identification of a molecular signature with potential diagnostic and therapeutic relevance.
First-in-human study of SYS6043, a novel B7-H3–targeting antibody-drug conjugate, in patients with advanced pan-tumor malignancies.
3002 Background: B7-H3, a tumor-associated immune checkpoint, is broadly overexpressed in multiple solid tumors and associated with aggressive disease biology and treatment resistance. SYS6043, a novel ADC targeting B7-H3, is designed to selectively deliver a cytotoxic payload to B7-H3 expressing tumors. Preclinical trials showed potent antitumor activity across diverse solid tumor models. Here, we report safety and efficacy results from a phase 1/2 trial of SYS6043 in patients with advanced solid tumors. Methods: Eligible patients (18–75 years) had advanced solid tumors refractory to or progressing after standard therapies. The study included a phases 1 dose-escalation and PK expansion phase, followed by a phase 2 cohort expansion. Phase 1 used a BOIN design to evaluate SYS6043 at a dose of 1.2-10.0 mg/kg Q3W and 4.0-6.0 mg/kg Q2W, with PK expansion at selected doses. Phase 2 evaluated SYS6043 at 8.0 mg/kg Q3W and 6.0 mg/kg Q3W and Q2W across tumor-specific cohorts. Primary endpoints were safety, tolerability, and determination of the RP2D in Phase 1, and objective response rate (ORR) in Phase 2. Results: As of November 28 2025, 502 patients were enrolled, including ovarian cancer (OC, n = 68), small cell lung cancer (SCLC, n = 57), breast cancer (BC, n = 55), cervical cancer (CC, n = 42), nasopharyngeal carcinoma (NPC, n = 40), non-squamous non-small lung cancer (nsq-NSCLC, n = 34), endometrial cancer (EC, n = 21), and other solid tumors ( n = 185). Dose-limiting toxicities (grade 3 gastrointestinal disease, and grade 4 febrile neutropenia) occurred at 10.0 mg/kg Q3W. Treatment-related adverse events (TRAEs) occurred in 94.2% of patients, with ≥grade 3 TRAEs in 28.5%. The most common TRAEs were anemia (52.0%), nausea (44.4%), fragile (42.8%), leukemia (41.6%), neutropenia (36.9%), decreased appetite (35.3%), and hypoalbuminemia (25.3%). Efficacy analyses focused on Q3W cohorts. SYS6043 demonstrated rapid and deep antitumor activity across multiple tumor types. In heavily pretreated SCLC ( n = 50), ORR was 64.0% (95% CI, 49.2-77.1) with DCR of 92.0% (95% CI, 80.8-97.8). At 6 mg/kg Q3W ( n = 28), ORR reached 75.0% (95% CI, 55.1-89.3), including one complete response. In OC, ORR and DCR were 46.2% and 87.2%, respectively with median PFS of 5.6 months at 6 mg/kg Q3W. Notably high response rates were also observed in BC (ORR 83.8%, DCR 100%), nsq-NSCLC (ORR, 57.1%), CC (ORR, 38.5%), NPC (ORR, 37.9%), and EC (ORR, 30.0%), indicating broad and consistent antitumor activity. Conclusions: SYS6043 demonstrated a manageable safety profile and robust, cross-tumor antitumor activity in a large population of patients with advanced solid tumors. The magnitude and consistency of responses across multiple histologies, including treatment-refractory tumors such as SCLC, support SYS6043 as a promising therapeutic candidate warranting further clinical and translational investigation. Clinical trial information: ChiCTR2400094683.
Sepsis-related 30- and 90-day readmissions among patients with pancreatic cancer: A nationwide readmissions database analysis.
e23240 Background: Pancreatic cancer is associated with high morbidity, frequent hospitalizations, and limited physiologic reserve. Sepsis is a common and life-threatening complication, often occurring in the setting of advanced disease, cancer-directed therapy, and biliary or gastrointestinal infections. While outcomes during index sepsis hospitalizations have been described, national data on short- and intermediate-term sepsis-related readmissions and their clinical and economic burden among patients with pancreatic cancer remain limited. Methods: We conducted a retrospective cohort study using the 2021–2022 Nationwide Readmissions Database (NRD). Adult, non-elective hospitalizations with a primary diagnosis of sepsis and secondary pancreatic cancer were identified using ICD-10 codes. December discharges were excluded for 30-day analyses, and October–December discharges were excluded for 90-day analyses to ensure complete follow-up. Index admissions were defined using a validated NRD algorithm. Sepsis-related readmissions were identified by ICD-10 sepsis codes during rehospitalization within 30 or 90 days, with only the first qualifying readmission counted. Primary outcomes were 30- and 90-day sepsis-related readmission rates; secondary outcomes included in-hospital mortality, length of stay (LOS), and total hospital charges. Results: For 30-day analyses, 26,534 weighted index hospitalizations were identified, of which 21,211 (80.0%) survived to discharge. The 30-day sepsis readmission rate was 8.2% (95% CI, 7.7–8.8). Mean age was 69 years, 55.8% were female, and 77.8% were treated at urban teaching hospitals. In-hospital mortality was 20.0% during index admissions and 16.3% among 30-day readmissions. Thirty-day readmissions accounted for 13,025 inpatient days (mean LOS 7.1 days) and $178 million in charges (95% CI, $157M–$198M). For 90-day analyses, 25,846 weighted index hospitalizations were identified, with 16,661 (64.4%) survivors eligible for follow-up. The 90-day sepsis readmission rate was 15.9% (95% CI, 14.6–17.2). Mortality among 90-day sepsis readmissions was 15.6% (95% CI, 13.7–17.6). These readmissions accounted for 18,682 inpatient days (mean LOS 7.0 days) and $253 million in charges (95% CI, $226M–$279M). Conclusions: Patients with pancreatic cancer hospitalized for sepsis experience substantial 30- and 90-day sepsis-related readmission rates, with high mortality, prolonged hospital stays, and significant healthcare costs. Nearly one in six patients surviving the index hospitalization was readmitted with sepsis within 90 days. These findings highlight vulnerability after sepsis hospitalization and underscore the need for improved post-discharge care coordination, infection surveillance, and transitional care strategies to reduce recurrent sepsis and readmissions.
PRO results from the Beamion LUNG-1 trial in treatment-naïve patients with <i>HER2</i> -mutant advanced NSCLC.
8616 Background: Zongertinib is an irreversible tyrosine kinase inhibitor that selectively inhibits HER2 while sparing wild-type EGFR, thereby minimizing associated toxicities. Here, we report patient-reported outcomes (PROs) on NSCLC-related symptoms, physical functioning, symptomatic adverse events (AEs) and their burden, from patients who were given 120 mg zongertinib QD as first-line in Cohort 2 of the Phase Ib Beamion LUNG-1 trial (NCT04886804). Methods: EORTC QLQ-C30 physical functioning scale, NSCLC-SAQ (domains: cough, dyspnea, pain, fatigue and poor appetite), EORTC IL46 (overall side effect burden) and nine PRO-CTCAE symptoms (mouth and/or throat sores, taste changes, nausea, vomiting, diarrhea, rash, skin dryness, itching, and numbness/tingling) were collected at cycle 1: days 1, 8 and 15, and day 1 of cycles 2, 3, 5, 7 and 9, each cycle being 21 days. Change from baseline (CFB) in EORTC QLQ-C30 physical functioning and NSCLC-SAQ total score were analyzed using mixed model repeated measures. The proportion of patients regarded as responders was defined as patients meeting within-patient meaningful improvements in PRO score or maintaining low levels of baseline symptomatology/high functioning. EORTC IL46 (1 = ‘Not at all’, 4 = ‘Very much’) and PRO-CTCAE (for frequency/severity/interference items: 0 “Never”/ “None”/ “Not at all” to 4 “Almost Constantly”/ “Very Severe”/ “Very much”) were analyzed descriptively. Results: The PRO analysis set included 71 patients. High completion rates were observed, over 85% up to cycle 7. Patients had low levels of symptomatology and high levels of physical functioning at baseline. Mean CFB analysis showed patients reported rapid within-patient improvements in EORTC QLQ-C30 physical functioning and NSCLC-SAQ total score after the first week of treatment (from cycle 1, day 8), which were sustained over time. A high proportion of patients responded to treatment in terms of their PRO score; at cycle 5, 70% of patients were responders for physical functioning, and 47% of patients for NSCLC-SAQ total score. There was low side-effect burden; at any post-baseline timepoint a maximum of 8.4% of patients [n=6] reported being troubled with side-effects of treatment ‘Quite a bit’ or worse; supported by low proportions of patients reporting symptomatic adverse events via PRO-CTCAE. Conclusions: Patients treated with first-line zongertinib reported a rapid improvement followed by stability in physical functioning and NSCLC-SAQ total score, with high proportions of patients qualifying as PRO responders. Zongertinib was well tolerated, as reflected by the low overall side effect burden and the low incidence and mild nature of patient-reported symptomatic adverse events. Clinical trial information: NCT04886804 .
QL1706 (PD-1/CTLA-4 bispecific antibody) plus bevacizumab specific for patients with hepatocellular carcinoma combined with lung metastasis: A secondary analysis of a prospective, single-arm, phase Ib/II study.
4114 Background: Hepatocellular carcinoma (HCC) with lung metastasis carries a dismal prognosis, and effective systemic treatments remain limited. Bispecific antibodies targeting multiple immune checkpoints have emerged as promising therapeutic strategies. This study assessed the efficacy and safety of QL1706, a PD-1/CTLA-4 bispecific antibody, in combination with bevacizumab in patients with HCC and lung metastases. Methods: This was a secondary analysis of a multicenter, phase Ib/II clinical trial. Eligible patients with unresectable, advanced HCC and confirmed lung metastases received QL1706 (5.0 or 7.5 mg/kg, cohort A) or QL1604 (PD-1 antibody, 200 mg, cohort B) plus bevacizumab every three weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: In cohort A, 15 patients were included in this analysis. At a median follow-up of 19.2 months, the ORR was 53.3% (95% CI, 26.6–78.7) and the DCR was 73.3% (95% CI, 44.9–92.2). Median PFS was 9.9 months (IQR, 1.6–NE), with a 1-year PFS rate of 46.7%, and the 2-year OS was 66.7%. Among the 7 patients with measurable lung target lesions, the ORR was 71.4% (95% CI, 29.0–96.3), including 2 complete responses. In cohort B, 5 patients were included, with a median follow-up of 23.7 months. The ORR was 20.0% (95% CI, 0.5–71.6) and the DCR was 60.0% (95% CI, 14.7–94.7). Treatment-related adverse events occurred in 93.3% of patients in cohort A and 100.0% in cohort B, with grade ≥3 TRAEs observed in 53.3% and 40.0% of patients, respectively. Most adverse events were manageable, and no treatment-related deaths were reported. Conclusions: QL1706 plus bevacizumab demonstrated promising antitumor activity and a manageable safety profile in patients with HCC and lung metastases. The high response rate observed in lung lesions highlights the potential of intensified immunotherapy combined with anti-VEGF therapy for this subgroup, warranting further validation in phase III trials. Clinical trial information: NCT05603039 . Treatment-emergent adverse events of QL1706 / QL1604 and bevacizumab. All grades Grade ≥ 3 Cohort A (N = 15) Cohort B (N = 5) Cohort A (N = 15) Cohort B (N = 5) TEAEs 15 (100.0) 5 (100.0) 10 (66.7) 4 (80.0) irAEs 11 (73.3) 0 2 (13.3) 0 TRAEs 14 (93.3) 5 (100.0) 8 (53.3) 2 (40.0) Associated with QL1706 / QL1604 14 (93.3) 5 (100.0) 6 (40.0) 2 (40.0) Associated with bevacizumab 14 (93.3) 5 (100.0) 8 (53.3) 3 (60.0)
Genomic determinants of cisplatin resistance in germ cell tumors.
5027 Background: Cisplatin-based chemotherapy achieves complete remission in 70-80% of patients with germ cell tumors (GCTs), but a subset are cisplatin-resistant and progress after first-line therapy. Prior studies have linked TP53 and MDM2 alterations and chromosome 3p25.3 gain to cisplatin resistance and worse outcomes in GCT. We sought to validate this and identify additional genomic determinants of cisplatin response in a large GCT cohort. Methods: Patients who received first-line cisplatin-based chemotherapy for GCT of any primary site with genomic analysis of the tumor were eligible. Cisplatin resistance was defined as: (1) incomplete response to chemotherapy, (2) non-teratomatous progression after chemotherapy, or (3) viable non-teratomatous GCT at post-chemotherapy surgery; all other patients were considered sensitive. Next-generation sequencing was performed using the MSK-IMPACT assay and association between genomic alterations and resistance was assessed using Fisher’s exact test. Cytoband analysis was completed using the FACETS algorithm to calculate chromosomal alterations, with a required cytoband coverage of 75%. The association between cytoband alterations and resistance was assessed using relative risk with a robust variance estimator. Results: The cohort of 556 patients included 79% testicular, 15% mediastinal, 4% ovarian, and 1.5% tumors of other primary site. 79% were nonseminomatous germ cell tumors and 21% pure seminoma. Among these, 336 (60%) were cisplatin-resistant. TP53 mutations were more common in resistant than sensitive tumors (16% vs 2%), as were MDM2 and CRKL amplifications (7% vs 1% and 4% vs < 1%, respectively). KIT was more frequently mutated in cisplatin-sensitive tumors (5% in resistant vs 14% in sensitive) (Table 1). TP53 mutations occurred predominantly in mediastinal primary tumors (89%) whereas MDM2 alterations were confined to testicular primaries. Of 472 patients who underwent cytoband 3p25.3 analysis, chromosome 3p25.3 gain was associated with cisplatin resistance (relative risk 1.23; 95% CI: 1.00, 1.49; p = 0.04). Conclusions: In this large GCT cohort, TP53 and MDM2 alterations and chromosome 3p25.3 gains were associated with cisplatin resistance, consistent with prior reports. We also found that CRKL amplifications were associated with cisplatin resistance whereas KIT mutations were associated with cisplatin sensitivity. These latter findings are the first reports of the association of these genes with cisplatin response and warrant further mechanistic investigation to define how these alterations influence cisplatin sensitivity. Genomic alterations corresponding to cisplatin response in GCT. Alteration Resistant (n=336) Sensitive (n=220) p-value TP53 mutations 53 (16%) 4 (2%) <0.01 KIT mutations 16 (5%) 31 (14%) <0.01 MDM2 amplifications 23 (7%) 2 (1%) <0.01 CRKL amplifications 14 (4%) 1 (<1%) <0.01
Reducing avoidable observation stays in cancer patients requiring procedural interventions through standardized ED pathways.
e23289 Background: Patients with cancer frequently present to the emergency department (ED) with symptomatic malignant pleural effusions, malignant ascites, or complications related to indwelling devices such as gastrostomy or nephrostomy tubes. These conditions often require procedures that are not routinely performed outside of regular working hours, resulting in potentially avoidable overnight hospital observation stays. The purpose of this Quality Improvement (QI) project was to reduce unnecessary observation admissions for such patients. Our specific aim was to achieve a 10% reduction in ED-to-observation unit admissions for patients awaiting these procedures. Methods: Through interdisciplinary collaboration, existing workflows for arranging procedures for ED patients were reviewed and standardized clinical pathways were developed. These pathways enabled eligible patients to be discharged from the ED with arrangements for completion of selected procedures within 48 hours. Inclusion and exclusion criteria were defined to ensure appropriate patient selection, and safety measures were incorporated through structured notification and follow-up processes. A retrospective chart review was conducted for eligible encounters before and after pathway implementation, applying consistent inclusion and exclusion criteria across both periods. Included cases were independently reviewed by two reviewers to determine whether patients could have been safely discharged if outpatient procedures had been arranged within 48 hours. Discrepancies were resolved by a third independent reviewer. Results: A total of 332 encounters were included. In the baseline period (n = 268), 76 encounters (29.7%) were deemed appropriate for discharge rather than observation. In the intervention period (n = 61), 15 encounters (34.8%) were judged to have involved avoidable observation stays. Among all encounters considered safe for discharge, a significantly higher proportion of patients were discharged during the intervention period. The mean time from discharge to procedure completion did not differ significantly between periods. Conclusions: Interdisciplinary collaboration enabled the development and implementation of feasible and effective clinical pathways that reduced avoidable observation stays. In addition to alleviating ED and hospital crowding, these workflows may confer financial, physical, and psychological benefits to patients. This model may be adaptable to other procedures and care pathways to further optimize resource utilization.
Overall survival by genomic profile in HER2-positive (HER2+) metastatic breast cancer (mBC): A large US clinico-genomic database study.
1045 Background: Over the past few years, the landscape of treatment for HER2+ breast cancer has evolved significantly. Multiple active 1L treatment options have emerged, including T-DXd plus pertuzumab, maintenance palbociclib or tucatinib, providing an opportunity to tailor treatment according to the disease profile. This study aims to describe real-world treatment patterns and evaluate overall survival (OS) in a modern cohort of patients with HER2+ mBC, with sub-analysis by genetic profile of the disease. Methods: This retrospective study used the Flatiron Clinico-Genomic database (CGDB), where each patient received at least one Foundation Medicine next generation sequencing (NGS) test along the course of disease. Adults (≥18 years) diagnosed with HER2+ mBC between 1 January 2018 and 31 March 2024 (one year prior to the data cutoff) were included. OS was examined using the Kaplan-Meier method, with descriptive analyses by genetic alteration. Results: Among 7,933 mBC patients who underwent NGS profiling, 732 (9.2%) patients with HER2+ mBC were included. The median age at diagnosis was 59 years (range: 23-85); 68.3% had hormone receptor positive disease, and 37% had de novo mBC. Patients received a median of 3 lines of therapy (range: 1–14). The use of anti-HER2 antibodies ranged from 59.4% to 33.6% across 1L through 5L. Trastuzumab deruxtecan was prescribed more often in later lines (23.9% for 3L, 19.6% for 4L, and 23.0% for 5L) compared to 2L and 1L (11.3% and 4.2%). Similarly, the use of anti-HER2 tyrosine kinase inhibitors increased in later lines. The median (95% CI) OS for the entire population was 48 (41.6-53.1) months, with notable differences based on the detection of key genetic alterations. Patients with mutations in DNMT3A (14.2%), ARID1A (11.9%), MLL2 (10.9%), and CHEK2 (9%) had numerically longer mOS (64 [49.5-NE], 51.4 [35.8-69.4], 51.4 [36.1-68.9], 51.4 [40.1-NE] months, respectively) while patients with mutations in BRCA1 (6.6%), CDH1 (10.9%), BRCA2 (10.9%), PIK3CA (37.4%), TP53 (59.6%), ERBB2 (11.5%), and ATM (12.7%) experienced numerically shorter mOS (36 [25.0-56.3], 40.1 [28.0-70.1], 40.1 [34.1-62.5], 40.1 [35.2-46.9], 40.6 [35.9-48.7], 43.3 [36.2-58.9], 44.3 [36.5-62.8] months, respectively). Conclusions: The present study provides key insights into clinico-genomic characteristics, modern treatment patterns and OS for HER2+ mBC patients in the US. Although survival was 4 years in the overall cohort, patients with mutations in key DNA repair genes (BRCA1, BRCA2, ATM, TP53), in CDH1, PIK3CA or ERBB2 experienced a numerically worse prognosis, representing key unmet needs for drug development.
Impact of malnutrition and morbid obesity on inpatient mortality among patients with hematologic malignancies: A National Inpatient Sample analysis.
e23091 Background: Nutrition is a critical yet frequently under-recognized determinant of clinical outcomes in patients with cancer. Malnutrition and morbid obesity have been linked to adverse outcomes. Despite advances in the management of hematologic malignancies, patients with poor nutritional status remain particularly susceptible to complications during hospitalization, including increased mortality. This study examined national-level data on the association of malnutrition and morbid obesity with inpatient mortality among patients with hematologic malignancies, an area in which existing data remain limited. Methods: We conducted a cross-sectional study using the 2021–2022 National Inpatient Sample database. Adults with hematologic malignancies were identified via ICD-10 codes. Nutritional status was defined by the codes for malnutrition and morbid obesity. The primary outcome was inpatient mortality. Sociodemographic variables included age, sex, race, payer, and median household income. To adjust for illness severity, a composite variable was created based on sepsis, respiratory failure, ventilation, or dialysis-requiring AKI. Multivariable logistic regression assessed factors linked to inpatient mortality. Results: A total of 1,202,329 hospitalizations were included. The median age was 69 years, and 33.8% of patients were aged ≥75 years. Patients were predominantly male (57.2%) and White (68.7%); 11.7% were Black and 10.9% Hispanic. Medicare was the most common payer (58.1%). Non-Hodgkin lymphoma (34.6%) and multiple myeloma (19.7%) were the most frequent malignancies. Malnutrition was present in 15.2% of hospitalizations, and 4.8% had morbid obesity. Overall, 29.4% met criteria for critical illness, and inpatient mortality was 6.1%. After adjustment, malnutrition was independently associated with increased inpatient mortality (adjusted OR 1.56, p < 0.001), whereas morbid obesity was associated with lower mortality (adjusted OR 0.93, p < 0.001). Critical illness was the strongest predictor of mortality (adjusted OR 5.29, p < 0.001). Older age, male sex, racial and ethnic minority status, lower neighborhood income, non-Medicare insurance, and acute myeloid leukemia were also associated with higher mortality. Conclusions: Among hospitalized patients with hematologic malignancies, malnutrition is a strong independent predictor of inpatient mortality, while morbid obesity is associated with lower mortality. Persistent sociodemographic disparities highlight the ongoing impact of nutritional and socioeconomic vulnerability on inpatient outcomes.
Impact of adherence to interstitial lung disease (ILD)/pneumonitis toxicity management guidelines (TMGs) on ILD/pneumonitis outcomes: A retrospective analysis of patients (pts) treated with trastuzumab deruxtecan (T-DXd) in DESTINY-Breast06 (DB-06).
1063 Background: DB-06 (NCT04494425) showed a progression-free survival benefit with T-DXd vs physician’s choice of chemotherapy for pts with hormone receptor–positive, HER2-low/-ultralow metastatic breast cancer, with no new safety signals. We report adherence rates to ILD/pneumonitis TMGs and their impact on ILD/pneumonitis outcomes. Methods: We retrospectively analyzed pts who received ≥1 dose of 5.4 mg/kg T-DXd and had adjudicated drug-related ILD/pneumonitis by the Mar 18, 2024 data cutoff. Adherence criteria were defined by ILD/pneumonitis severity at diagnosis (per investigator assessment) and associated TMGs (Table); adherence was classified as complete (CA), partial (PA), or non-adherence (NA) by TMG criteria met (all, ≥1 but not all, or none, respectively). Investigator-reported ILD/pneumonitis outcomes were ‘recovered’ (± sequelae), ‘recovering’, ‘not recovered’, and ‘fatal’. Results: Of 49 pts with adjudicated drug-related ILD/pneumonitis, respective rates of CA, PA, and NA were 73.5% (n=36), 14.3% (n=7), and 12.2% (n=6). By Mar 24, 2025, 66.7% (n=24) of pts with CA and 71.4% (n=5) with PA had an outcome of recovered ± sequelae, with no fatalities. Of pts with NA, 50% (n=3) did not recover, including one fatality. At diagnosis, 31 (63.3%), 15 (30.6%), and 3 (6.1%) pts had Grade (Gr) 1, 2, and 3 ILD/pneumonitis, respectively. Across all cases, 38.8% (n=19) progressed to a worse grade after diagnosis; progression from Gr 1 to Gr 2 represented 84.2% of progressions. Of 25 pts with Gr 1 ILD/pneumonitis and CA (optional steroid use), 16 received steroids and 9 did not; recovery rates were comparable (68.8% with steroids vs 66.7% without). For pts with Gr ≥2 ILD/pneumonitis and CA or PA (n=18), steroid use as recommended was associated with improved recovery rates (66.7% with steroids vs 33.3% without). Two pts with Gr 1 ILD/pneumonitis at diagnosis were rechallenged with 4.4 mg/kg T-DXd; both had recurrent Gr 1 ILD/pneumonitis but recovered. Conclusions: Adherence to ILD/pneumonitis TMGs was associated with improved ILD/pneumonitis outcomes in this small subset of pts. Steroid use as recommended for Gr ≥2 cases was associated with improved recovery. While further investigation of patient-level determinants of recovery is needed, these data demonstrate that adhering to ILD/pneumonitis TMGs may optimize ILD/pneumonitis outcomes. Clinical trial information: NCT04494425 . Adherence criteria by ILD/pneumonitis grade at diagnosis. Gr 1 Gr 2 Gr ≥3 T-DXd interrupted after AE onset Yes – – T-DXd discontinued after AE onset – Yes Yes 500–1000 mg/day methylprednisolone for 3 days – – Yes ≥1 mg/kg/day prednisone* – Yes Yes Steroid duration ≥14 days – Yes Yes ≥4-week taper – Yes Yes If no improvement 5 days from AE onset, switched to 2 mg/kg/day IV prednisone* – Yes Yes *Or equivalent; AE, adverse event.
TP53 co-mutations and survival outcomes in patients (pts) with NSCLC bearing uncommon EGFR alterations.
e20721 Background: Pts with NSCLC bearing uncommon EGFR alterations experienced inferior survival with tyrosine kinase inhibitors (TKIs) vs. those with sensitizing exon 19 deletions or L858R in prior studies. While TP53 co-mutations are well-recognized to be associated with poorer outcomes in sensitizing EGFR-mutant NSCLC, no research to our knowledge has examined the contribution of this adverse co-mutation to the inferior survival observed in pts with uncommon EGFR alterations receiving front-line TKIs. Methods: The Flatiron Health-Foundation Medicine clinical-genomic database (~800 sites of care) was used to evaluate pts (N = 108) with advanced NSCLC (Stage IIIB/IV) bearing uncommon EGFR alterations receiving front-line osimertinib or afatinib from 6/2014 – 9/2024. Kaplan-Meier methods (accounted for left truncation) estimated real-world progression-free survival (rwPFS) and overall survival (OS) in months (m). Comparisons by presence of TP53 co-mutations vs. wild-type were assessed using multivariable Cox regression after adjusting for the covariates gender, age, smoking history, performance status, presence of brain and liver metastases, EGFR subtype (e.g. G917X, L861Q, compound), and TKI received. Results: Of the 108 pts, 30 (27.8%) had G719X, 30 (27.8%) had L861Q, 3 (2.8%) had S768I, 3 (2.8%) had E709X, 2 (1.9%) had L747X, and 40 (37.0%) had compound mutations made-up of ˃ 1 EGFR alteration. Seventy-six (70.4%) pts had a TP53 co-mutation, which is higher than the rate reported for pts with sensitizing EGFR-mutant NSCLC in prior studies. Sixty-nine pts (63.9%) received osimertinib and 39 (36.1%) received afatinib as a front-line TKI. Pts with TP53 co-mutations had a shorter median rwPFS (5.9 m vs. 15.7 m, HR 1.9, 95% CI 1.1-3.3, P = 0.017) and OS (11.0 m vs. 24.7 m, HR 2.4, 95% CI 1.4-4.4, P = 0.003) with front-line TKIs as compared to wildtype pts after adjusting for relevant covariates. In our multivariable model, the TKI received (i.e. osimertinib vs. afatinib) did not alter survival. However, having L861Q correlated with a poorer OS (HR 2.5, 95% CI 1.3-4.7, P = 0.006) and having G719X predicted inferior rwPFS (HR 2.5, 95% CI 1.3-4.5, P = 0.004) and OS (HR 2.3, 95% CI 1.2-4.5, P = 0.016) as compared to pts with compound EGFR mutations. Conclusions: This is the first study to demonstrate that the occurrence of a TP53 co-mutation is a significant predictor of inferior rwPFS and OS in pts with NSCLC bearing uncommon EGFR alterations. Although conventional thought is that pts with uncommon EGFR alterations derive less benefit from TKIs, our analysis suggests TP53-wildtype pts experience survival comparable to that of pts with sensitizing EGFR alterations in the real-world. Pts possessing uncommon EGFR alterations with a TP53 co-mutation critically need more effective therapies. Emerging strategies that target mutant p53 may benefit this high-risk subgroup.
Quality-driven medical oversight in global oncology trials: Standardizing immune-related AE management to enhance patient safety.
e23311 Background: Immune-based therapies have transformed the treatment landscape across multiple malignancies; however, they are associated with a distinct spectrum of immune-related adverse effects. If not adequately managed, these toxicities may affect multiple organ systems, resulting in treatment interruptions or discontinuation. In global oncology trials, variability in site-level operational practices may contribute to inconsistent immune-related adverse event (ir-AE) documentation and management, potentially impacting patient safety and data integrity. A standardized, quality-driven operational framework was implemented to support consistent identification, documentation, and oversight of irAEs across diverse trial settings. Methods: A retrospective analysis was conducted across four global oncology clinical trials evaluating immune-therapy–based regimens delivered under a standardized medical oversight framework. Predefined MedDRA preferred terms within the safety database, were used to identify irAEs. Adverse event severity was summarized using CTCAE grading. Patterns of AE grading consistency, treatment impact (dose interruption, delay, or discontinuation), and use of concomitant medications for irAE management, including corticosteroids and immunosuppressive agents, were assessed on aggregated data. Results: Evaluation of AE data identified delayed or inconsistent AE grading and recurring patterns in irAE documentation across the four trials. Analysis of trends of AE severity, treatment impact, and concomitant medication use, highlighted frequently observed and clinically complex irAEs. Review of aggregated safety data demonstrated variation in the timing of AE reporting and protocol deviation identification with a median 3-week difference in time to detection of underreported AEs and a 20% difference in time from protocol deviation occurrence to identification across studies. Pre-established irAE management guidelines, aligned with published consensus recommendations, were consistently applied across global trial sites. Conclusions: A structured, quality-driven medical oversight framework enhanced consistency in monitoring and reporting of irAEs across global oncology trials. Standardization of safety oversight enabled earlier identification of documentation issues, reduced variability in irAE management practices, and strengthened the reliability and integrity of safety data, supporting effective centralized medical oversight in immune-oncology clinical development.
Association of immune checkpoint inhibitors with increased pancreatitis risk in gastrointestinal cancers: A propensity-matched real-world analysis.
e16498 Background: Immune checkpoint inhibitors (ICIs) are widely used in gastrointestinal (GI) malignancies but are associated with immune-related toxicities, including pancreatitis. Comparative real-world data evaluating pancreatitis risk following ICIs versus chemotherapy are limited. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network (2015–2025) including adults with GI malignancies treated with ICIs or chemotherapy. Patients with non–treatment-related pancreatitis were excluded. The primary outcome was acute pancreatitis at 3 months, 6 months, and 1 year. Secondary outcomes included mortality, ICU admission, pneumonia, colitis, and gastrointestinal surgery at 1 year. Propensity score matching was applied. Results: After matching, 34,021 patients were included in each cohort. ICI therapy was associated with a significantly higher risk of acute pancreatitis at 3 months (0.4% vs 0.2%; RR 1.67), 6 months (0.6% vs 0.3%; RR 1.70), and 1 year (0.9% vs 0.5%; RR 1.65; all p < 0.001). At 1 year, ICIs were also associated with higher mortality (35.1% vs 23.8%; HR 1.66) and higher gastrointestinal surgery rates (13.5% vs 9.8%; RR 1.39), but lower ICU admission (RR 0.82), pneumonia (RR 0.94), and coded noninfectious colitis (RR 0.86). Conclusions: In this large real-world analysis, ICIs were associated with a significantly increased and persistent risk of acute pancreatitis compared with chemotherapy, along with higher mortality and GI surgical burden. These findings support pancreatitis as a clinically relevant immune-related adverse event and underscore the need for vigilant pancreatic monitoring in GI cancer patients receiving ICIs.
Early-onset gastrointestinal cancers: Racial disparities in stage and survival from large-scale community oncology data.
1653 Background: Research on early-onset (EO) gastrointestinal (GI) cancers has focused predominantly on colorectal cancer, leaving knowledge gaps regarding racial variations across other GI malignancies. We used real-world data from a large, nationally representative community oncology network to assess age-of-onset differences in clinical characteristics and survival for colorectal, gastric, and esophageal cancers across key social determinants. Methods: This was a retrospective cohort of patients with colorectal, gastric and esophageal cancers treated within the U.S. Oncology Network and non-Network practices from 2000–2025. Patients were categorized as EO (<50 years) or average-onset (AO) (≥50 years) at diagnosis. Characteristics including demographics, stage at diagnosis (I–II, III–IV, or unknown), and distress level (NCCN Distress Thermometer) were sourced from iKnowMed. Overall survival (OS) was assessed from diagnosis using Kaplan–Meier methods, stratified by race/ethnicity and stage. Results: Among 195,624 patients with GI cancers, 23,244 (11.9%) had EO disease. In the EO cohort, 20,203 (87%) had colorectal, 1,693 (7%) gastric, and 1,348 (6%) esophageal cancers. EO disease occurred in a more racially and ethnically diverse population, with higher representation of Hispanic/Latino (10.3% vs 6.7%), Black (8.2% vs 6.6%), and Indigenous/Native (1.3% vs 0.8%) patients, and higher female representation (46.4% vs 43.9%), versus AO disease. Advanced-stage (III–IV) disease at diagnosis was more common in EO vs AO disease across colorectal (41% vs 32%), esophageal (41% vs 31%), and gastric (37% vs 29%) cancers. Among EO patients, stage III/IV disease at diagnosis was higher in Black (75.3%) and Asian (73.1%) versus White patients (64.9%), whereas among AO patients advanced stage was more balanced across racial groups (66.2%, 64.9%, 62.9%, respectively). Within EO advanced-stage disease, median OS was 8.1 m shorter in Black vs White patients (51.0 vs 59.1 m), compared with only a 1.6 m difference in AO disease (35.0 vs 36.6 m). Among patients with available distress data (N=3,426), distress was higher in EO versus AO patients (median 4 vs 3) but did not differ by race, sex or ethnicity. Conclusions: This study represents one of the largest real-world characterizations of EO GI cancers, revealing that EO patients more often present with advanced-stage and higher distress than AO counterparts. While racial disparities in stage were relatively balanced in AO disease, they were exacerbated in EO disease, with Black and Asian patients presenting with substantially higher rates of advanced disease. The resulting survival gap between Black and White EO patients underscores a widening disparity less pronounced in older patients. A precision–public health approach is needed to address biological and socioeconomic drivers of outcomes in young, diverse GI cancer populations.
Preliminary efficacy and safety of first-line anlotinib plus carboplatin/paclitaxel induction therapy followed by anlotinib maintenance in advanced ovarian cancer: Results from the ALTER-GO-010 phase II multicenter trial.
5576 Background: Several studies have shown that antiangiogenic drugs combined with chemotherapy as first-line treatment, followed by maintenance therapy with antiangiogenic agents, significantly improve outcomes for ovarian cancer patients. Anlotinib, a highly effective multi-target tyrosine kinase inhibitor targeting VEGFRs, FGFRs, PDGFRs, and c-Kit, has been approved for multiple tumor types in China. The ALTER-GO-010 study is a single-arm, multicenter phase II trial designed to assess the efficacy and safety of anlotinib in combination with carboplatin/paclitaxel as first-line induction therapy, followed by anlotinib maintenance, in patients with newly diagnosed advanced ovarian cancer. Methods: Eligible patients with newly diagnosed FIGO stage III–IV primary epithelial ovarian, fallopian tube, or primary peritoneal cancer (ECOG PS 0–1) who have undergone primary or interval debulking surgery will receive 6-8 cycles of chemotherapy (paclitaxel 175 mg/m² + carboplatin AUC 5 every 3 weeks) combined with anlotinib (12 mg orally once daily on days 1–14, 21-day cycle; omitted during the first cycle to prevent delayed wound healing). Following chemotherapy completion, anlotinib will be continued as maintenance monotherapy until disease progression, unacceptable toxicity, or death. Exclusion criteria include prior anti-angiogenic therapy or major surgery within 28 days before anlotinib initiation. The primary endpoint is progression-free survival (PFS). Key secondary endpoints include overall survival, and safety profile. Results: As of the data cutoff date (November 30, 2025), 54 patients had received at least one dose of the study drug and were included in the analysis. The median age was 56 years, 98.11% had high-grade serous carcinoma and 1.89% had endometrioid carcinoma. 96.23% had FIGO stage III and 3.77% had stage IV. The data maturity for PFS analysis was 40.7%. The median PFS was 20.76 months (95% CI: 11.58-29.95). Patients without prior history of neoadjuvant therapy had longer mPFS than those with prior therapy. The median OS was not reached. The most common all-grade treatment emergent adverse events (TEAEs) were white blood cell deceased, anemia, neutrophil count decreased, platelet count decreased and lymphocyte count decreased. Grade ≥3 TEAEs occurred in 75.5% of patients during the chemotherapy phase and 22.7% during maintenance. No treatment-related deaths were reported. Conclusions: The preliminary efficacy and safety data suggest that anlotinib plus carboplatin/paclitaxel induction therapy, followed by anlotinib maintenance, is a promising regimen for newly diagnosed advanced ovarian cancer, with a median PFS of 20.76 months and a favorable safety profile. Clinical trial information: NCT04807166 .
A novel syngeneic immunocompetent mouse model of GBC to reveal CXCL5-mediated early tumor progression and demonstrate chemotherapeutic sensitivity.
e16264 Background: Gallbladder cancer (GBC) is a highly lethal malignancy with a poor prognosis. Research progress has been critically hampered by the lack of experimental models in immunocompetent hosts, which limits the study of tumor-immune interactions and preclinical therapeutic evaluation. We aimed to establish a novel, immunocompetent mouse model of GBC that recapitulates key features of the human disease, and to utilize it for identifying early drivers of tumorigenesis and assessing therapeutic responses. Methods: We engineered a murine GBC cell line (mGBC1-ZH) from normal gallbladder organoids stably expressing oncogenic Kras and Trp53 mutations. Syngeneic tumor models were established via subcutaneous and orthotopic implantation of mGBC1-ZH cells into immunocompetent C57BL/6J mice. Genomic and transcriptomic profiling was performed to characterize chromosomal stability and transcriptional similarity to human GBC. CXCL5 expression was analyzed in early-stage human GBC tissues. Functional assays included in vitro cell proliferation and migration assays, as well as in vivo tumor growth and metastasis monitoring. Neutrophil infiltration was evaluated via immunophenotyping. Therapeutic sensitivity was assessed by treating tumor-bearing mice with frontline chemotherapy (gemcitabine plus cisplatin), with tumor regression measured as the primary endpoint. Results: The mGBC1-ZH syngeneic model supported robust subcutaneous and orthotopic tumor growth in C57BL/6J mice, recapitulating key hallmark features of human GBC: biliary epithelial differentiation, aggressive histopathological characteristics, and an immunosuppressive tumor microenvironment. Genomic analysis revealed recurrent chromosomal instability, and transcriptomic profiling demonstrated a profound transcriptional resemblance to human GBC. CXCL5 was identified as a key factor significantly upregulated in the early stage of human GBC. Functional studies confirmed that CXCL5 promoted tumor cell proliferation and metastasis in vitro, and enhanced tumor growth and neutrophil infiltration in vivo. Additionally, the model exhibited therapeutic responsiveness to gemcitabine plus cisplatin combination chemotherapy, with treatment inducing significant tumor regression compared to control groups. Conclusions: We have established a novel, immunocompetent syngeneic mouse model of GBC that closely mimics the human disease. This model revealed CXCL5 as a critical mediator of early tumor progression and neutrophil recruitment. It also serves as a robust platform for investigating tumor microenvironment interactions and advancing preclinical therapeutic development.