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e16300 Background: Transarterial chemoembolization (TACE) remains the standard of care for intermediate stage hepatocellular carcinoma (HCC), yet long term survival is limited by high rates of recurrence and progression. The addition of immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) with TACE has recently emerged as a promising strategy. This meta-analysis evaluates the efficacy and safety of TACE plus systemic combination therapy compared to TACE alone. Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. Studies evaluating TACE combined with dual systemic therapy (ICI + TKI/VEGF inhibitor) were identified through major databases up to January 2026. Pooled odds ratios (ORs) and Hazards Ratio (HRs) were calculated using fixed effects models as appropriate. Results: Five studies (4 RCTs, 1 cohort) comprising 1964 patients were included. Progression-free survival was significantly longer with TACE combined with dual systemic therapy compared with TACE alone (mean difference 4.12 months, 95% CI 2.86-5.37; p < 0.00001; I² = 73%). The objective response rate was also significantly higher with TACE combination therapy (OR 2.66, 95% CI 2.17-3.26; p < 0.00001), despite substantial heterogeneity (I² = 83%). Grade 3/4 adverse events were significantly more frequent with TACE combination therapy (OR 3.36, 95% CI 2.66-4.25; p < 0.00001; I² = 68%). The most common severe toxicities included Hypertension (16.2%), Immune-mediated Hepatitis (9.6%), and Proteinuria (8.8%). Hypertension occurred significantly more often with TACE combination therapy than with TACE alone (pooled OR 9.52, 95% CI 1.83-49.62; p = 0.007; I² = 51%). Conclusions: The addition of ICI and TKI/VEGF inhibitors to TACE provides consistent, statistically significant and clinically meaningful improvement in disease control for unresectable HCC. This can be explained on the basis of complementary biological mechanisms, including enhanced tumor antigen exposure following TACE, restoration of antitumor T cell activity with ICI, and suppression of TACE induced angiogenesis through VEGF pathway blockade. While the efficacy benefit is robust across trials, safety profiles vary significantly by regimen.The higher rate of grade ¾ adverse effects, especially hypertension and immune-mediated hepatitis, is mainly due to the biological effects of VEGF inhibitors on blood vessels and the increased immune activation caused by immune checkpoint inhibitors. Despite a higher incidence of grade 3/4 toxicities, adverse events were generally manageable with standard supportive care and dose modifications. Overall, these findings support the use of TACE-systemic combinations as a new potential standard of care, with careful patient selection and toxicity monitoring.

e16246 Background: First line systemic therapy for advanced hepatocellular carcinoma (HCC) includes immune checkpoint inhibitor (ICI) combination therapy, with tyrosine kinase inhibitors (TKIs), lenvatinib or cabozantinib, commonly used as second line therapy. However, there is limited data comparing efficacy of TKIs following first line ICI therapy. In the present study, we compared survival and risk of hospitalization in a propensity score matched analysis of patients who received lenvatinib or cabozantinib following progression on first line ICI therapy in patients with advanced HCC. Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. We identified adult patients with a history of HCC who received atezolizumab plus bevacizumab (A+B) or durvalumab plus tremelimumab (D+T) as first line treatment. We then stratified patients by use of lenvatinib or cabozantinib in the subsequent line setting. Propensity score matching (PSM) was conducted between those who received lenvatinib and those who received cabozantinib, matching for demographic factors (age, sex, race), clinical characteristics (history of alcohol use, ascites, esophageal varices, or viral hepatitis), and laboratory parameters [platelets, albumin, bilirubin, INR and alpha-1-fetoprotein (AFP)]. Results: We identified 416 patients who were initially treated with either A+B or D+T, with 327 patients receiving A+B and 89 patients receiving D+T. Of these, 336 patients (80.8%) subsequently received lenvatinib and 80 patients (19.2%) received cabozantinib. Baseline characteristics of demographic factors, clinical characteristics, and laboratory parameters were comparable between patients in the lenvatinib arm and cabozantinib arm with all standardized mean differences (SMD) < 0.10. After PSM, 76 patients were included in the analyses, with all variables adequately balanced. There was no significant difference in the risk of hospitalization between those receiving lenvatinib or cabozantinib at 3 months [31.6% vs 34%, odds ratio (OR) 1.13, 95% confidence interval (CI) 0.57-2.2]. There was also no significant difference in mOS between those receiving lenvatinib and cabozantinib [9.5 vs 9.0 months, hazard ratio (HR) 1.03, 95% CI 0.62-1.7]. Conclusions: In patients with HCC who received lenvatinib or cabozantinib as second-line therapy following first-line ICI combination therapy, we found no significant differences in rate of hospitalization or survival. These findings suggest that either option may be appropriate, and decisions may be based in side effect profile and patient preferences. Prospective studies will be important to further assess differences in patient outcomes.

e16229 Background: Liver cancer is a leading cause of cancer-related mortality worldwide, with rising incidence linked to metabolic disorders. Conditions such as obesity, diabetes mellitus, and metabolic syndrome contribute substantially to non-viral liver carcinogenesis. However, long-term temporal trends and mortality disparities among adults with metabolic disorders in the United States remain incompletely characterized. Methods: Mortality data for liver cancer among adults with metabolic disorders were obtained from the centers for disease control and prevention (CDC) mortality database. Adults aged 25 years and older were included and age-adjusted mortality rates (AAMRs) per 100,000 were calculated. Temporal trends were evaluated using joinpoint regression and average annual percent change (AAPC) with 95% confidence intervals. Results: From 1999–2023, AAMR for liver cancer in adults with metabolic disorders rose from 0.17 to 0.65 per 100,000 in the U.S., with an overall AAPC of 5.95% [95% CI 5.2–6.7]. Men had higher absolute mortality (0.25→0.93; AAPC 5.68%), while women showed a sharper recent rise (0.11→0.41; AAPC 7.08%), peaking at 11.86% annually after 2016. Hispanic/Latino (0.27→0.89; AAPC 6.73%) and Black populations (0.15→0.75; AAPC 6.15%) experienced steady increases, whereas White mortality accelerated post-2011 (AAPC 9.37%). Regionally, the West had highest rates, the South showed highest growth, and Northeast/Midwest had sharp recent increases. Rural mortality overtook urban by 2020 (0.50 vs. 0.48). Most deaths occurred in medical facilities (48.2%) or home (33.1%), with highest state rates in Hawaii (0.56), Texas (0.47), and Rhode Island (0.47). Conclusions: Mortality from liver cancer in adults with metabolic disorders rose sharply in the U.S. since 1999, with accelerating trends and marked disparities by sex, race/ethnicity, region, and urbanization. These findings highlight an urgent need for targeted metabolic risk reduction and equity-focused prevention strategies. Trends in Age-Adjusted Mortality Rates (AAMR) from 1999 to 2023 by demographic and geographic variables. Variable AAMR 1999 (per 100,000) AAMR 2023 (per 100,000) AAPC (95% CI) Overall 0.16 0.64 5.94* (5.22 – 6.67) Males 0.25 0.92 5.67* (4.82 – 6.5) Females 0.11 0.40 7.08* (5.79 – 8.38) White 0.16 0.63 6.12* (5.41 – 6.82) Black 0.15 0.75 6.15* (5.11 – 7.19) Hispanic or Latino 0.27 0.89 6.73* (5.98 – 7.48) Variable AAMR 1999 (per 100,000) AAMR 2020 (per 100,000) AAPC (95% CI) Urban 0.16 0.47 5.38* (4.43 – 6.33) Rural 0.19 0.50 5.73* (4.48 – 6.99) AAPC denotes the average annual percent change; * indicates p < 0.05.

e16159 Background: Pivotal trials established atezolizumab-bevacizumab and durvalumab-tremelimumab as first-line therapies for unresectable hepatocellular carcinoma (HCC). Atezolizumab plus bevacizumab demonstrated superior survival outcomes compared to sorafenib for unresectable HCC in the IMbrave150 trial in 2020, while durvalumab plus tremelimumab showed superior survival in the HIMALAYA trial in 2022. However, data on head-to-head comparison of these two combinations as first-line systemic therapy for the patient with decompensated HCC are limited. This study aims to compare survival outcomes between these two treatment regimens in decompensated HCC patients to address a critical gap in the current literature, as decompensated patients have largely been excluded from clinical trials. Methods: This retrospective study utilized electronic health records from 146 U.S. healthcare organizations within the TriNetX Network. Adults aged ≥21 years diagnosed with decompensated HCC receiving atezolizumab/bevacizumab and durvalumab/tremelimumab from 10/21/2022 to 8/20/2024 were included. The comparison group received atezolizumab/bevacizumab, and the control group received durvalumab/tremelimumab. The primary outcome was all-cause mortality. A 1:1 propensity score matching was conducted to balance baseline characteristics (age, gender, race/ethnicity, lab results including liver function tests, platelet counts, INR, gamma glutamyl transferase, alpha-fetoprotein, and underlying liver diseases). Kaplan–Meier survival analysis and Cox regression was used to estimate the mortality risk. Subgroup analysis was stratified by HCC etiology. Results: A total of 302 and 664 patients received durvalumab/tremelimumab, atezolizumab/bevacizumab, respectively. After propensity matching, 253 patients per group were included. Median OS was 283 days with durvalumab/tremelimumab and 391 days with atezolizumab/bevacizumab. The two treatment regimens showed no significant difference in survival (hazard ratio [HR]: 0.875, 95% confidence intervals [CI] 0.696–1.101, p=0.254). Subgroup analyses demonstrated no significant differences in survival between the two groups of patients in MASLD (HR: 0.698, 95% CI: 0.468–1.040), alcohol associated liver disease (HR: 0.821, 95% CI: 0.603–1.118), and chronic viral hepatitis (HR: 0.852, 95% CI: 0.596–1.219). Conclusions: There was no statistically significant difference in survival outcomes between atezolizumab plus bevacizumab and durvalumab plus tremelimumab in patients with decompensated advanced HCC. These results support current real-world practice in which both regimens may be considered viable first-line treatment options in this high-risk population with liver decompensation.

e16157 Background: Liver cancer mortality remains a major public health burden in the United States despite advances in prevention and treatment. Psychoactive substance use disorder (PSUD) is an increasingly prevalent comorbidity; however, national trends and disparities in liver cancer mortality among adults with PSUD remain poorly characterized. Methods: We conducted a retrospective analysis of liver cancer-related deaths among U.S. adults aged 25 years and older with PSUD from 1999 to 2023 using Centers of Disease Control (CDC) Wide Ranging Online Data for Epidemiological Research (WONDER) mortality database. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 population and stratified by census region, state, urban–rural status, sex, and race/ethnicity. Temporal trends were assessed using Joinpoint regression to estimate average annual percent change (AAPC). Statistical significance was determined using p-value (<0.05). Results: Overall liver cancer related AAMR per 100,000 among adults with PSUD significantly increased from 0.15 in 1999 to 1.02 in 2023 (AAPC: 7.47; 95% CI: 6.33 to 8.61; p < 0.000001). The overall mortality burden was higher in males. However, females experienced larger rises in mortality (AAPC: 10.03; 95% CI: 8.85 to 11.24; p < 0.000001) as compared to males (AAPC: 7.30; 95% CI: 5.78 to 8.84; p < 0.000001). Marked racial disparities were observed, with non-Hispanic Black and non-Hispanic White individuals experiencing the highest mortality rates with persistent increases over time, while Hispanic/Latino populations exhibited modest and variable trends. A substantial geographic variability was observed, with the greatest increases in the Midwest and the South. State-level analysis revealed higher mortality rate in Oregon (1.27) followed by Washington (1.12) and Texas (1.06) respectively. Both rural and urban areas experienced a sharp rise in mortality with AAPC being slightly higher in rural areas (AAPC: 10.34) as compared to urban areas (AAPC: 9.67). Conclusions: Liver cancer mortality among U.S. adults with PSUD has risen markedly over the past two decades, with substantial demographic and geographic disparities. These findings highlight the need for integrated liver cancer screening and substance use disorder interventions targeting high-risk populations. Variables AAMR (95% CI) in 2023 AAPC (95% CI) Overall 1.02 (0.98 –1.05) 1999-2023: 7.47* (6.33 – 8.61) Female 0.42 (0.39 – 0.46) 1999-2023: 10.03* (8.85 – 11.24) Men 1.69 (1.62 –1.76) 1999-2023: 7.30* (5.78 – 8.84) White 1.05 (1.0 –1.09) 1999-2023: 9.52* (8.08 – 10.98) Black / African Americans 1.22 (1.09 – 1.35) 1999-2023: 6.59* (5.50 – 7.68) Hispanics / Latinos 0.75 (0.65 – 0.84) 1999-2023: 1.26 (-1.01 – 3.60) AAMR (95% CI) in 2020 AAPC (95% CI) Rural 1.51 (1.39 – 1.62) 1999-2020: 10.34* (5.05 – 15.90) Urban 0.92 (0.82 – 0.95) 1999-2020: 9.67* (7.32 – 12.06)

e16102 Background: Esophageal cancer remains a significant cause of cancer mortality in the United States. While overall trends have been reported, less is known regarding contemporary long-term patterns and specific disparities across demographic and geographic strata. We aimed to characterize esophageal cancer mortality trajectories and identify populations with divergent outcomes by age, race/ethnicity, geographic region, and urbanization status. Methods: We analyzed esophageal cancer mortality data from 1999 to 2023 using the Centers for Disease Control and Prevention (CDC) WONDER database. Age-adjusted mortality rates (AAMRs) were standardized to the 2000 U.S. standard population. Joinpoint regression analysis was utilized to estimate the annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs). Analyses were stratified by age, sex, race/ethnicity, census region, state, and urbanization level. Results: Overall esophageal cancer mortality in the U.S. declined significantly from 1999 to 2023 (AAPC, -0.81%; 95% CI, -0.97% to -0.65%; P < 0.001). Declines were observed across most age groups, with the steepest reductions among adults aged 45-54 years (AAPC, -1.68%; 95% CI, -2.01% to -1.35%) and 55-64 years (AAPC, -1.25%; 95% CI, -1.51% to -0.99%). Marked racial and ethnic disparities were identified. Non-Hispanic (NH) Black individuals experienced the most rapid decline (AAPC, -4.07%; 95% CI, -4.42% to -3.72%). Conversely, trends among NH White individuals remained stable overall (AAPC, -0.05%; P = 0.59), characterized by an initial increase from 1999 to 2005 (APC, 1.14%; P = 0.002) followed by a modest decline from 2005 to 2023 (APC, -0.44%; P < 0.001). Regionally, the West demonstrated the largest decline (AAPC, -1.13%; 95% CI, -1.26% to -0.99%), followed by the Northeast (AAPC, -1.05%). West Virginia was the only state to exhibit a significant increase in mortality (AAPC, 1.01%; 95% CI, 0.38% to 1.64%; P = 0.003). Mortality declined significantly in metropolitan areas (AAPC, -1.09%; P < 0.001), while trends in nonmetropolitan areas remained stagnant (AAPC, 0.48%; P = 0.12). Conclusions: Despite a national decline in esophageal cancer mortality, substantial disparities persist across racial, geographic, and urbanization groups. The dramatic improvement among NH Black populations contrasts with the relative stability in NH White populations and the lack of progress in nonmetropolitan areas. The significant rise in mortality in West Virginia warrants targeted investigation. These findings underscore the critical need for population-tailored strategies to ensure equitable progress in cancer prevention and care.

e16081 Background: Intratumoral Fusobacterium nucleatum (F. nuc) is a key microbial participant in gastrointestinal malignancy progression. In esophageal squamous cell carcinoma (ESCC), the link between bacterial colonization and metastatic potential requires characterization. This systematic review synthesizes evidence from independent cohorts to define the relationship between bacterial DNA load, molecular pathways driving metastasis, and survival. Methods: PubMed, EMBASE, and Cochrane databases were searched for studies till January 2026 evaluating F. nuc and ESCC prognosis using quantitative DNA-based assays (qPCR or 16S rRNA sequencing). Multivariate-adjusted hazard ratios (HR) for cancer-specific survival (CSS) and disease recurrence were pooled using a Random Effects Model; heterogeneity was assessed by I^2. Synthesis identified technical/geographic consistencies and correlations with pathological markers of tumor invasion and lymph node spread. Results: Eight studies from China and Japan met inclusion criteria. High intratumoral F. nuc load was a significant independent prognostic factor. Elevated DNA load was a robust predictor of poor outcomes, specifically associated with a CSS HR of 1.78 (95% CI 1.06-2.65). Recurrence risk was similarly elevated, yielding a pooled Relapse-Free Survival (RFS) HR of 1.71 (95% CI 1.27-2.30,I^2 = 0).Findings remained stable across multicenter registries in Japan and China, likely due to standardized qPCR targeting nusG or 16S rRNA genes. Qualitatively, high DNA load correlated with advanced pT stage and lymph node metastasis. This phenotype is mediated by TLR4/NF-κB and NOD1/RIPK2 signaling, which drive epithelial-mesenchymal transition (EMT) and foster an immunosuppressive "cold" tumor microenvironment characterized by M2-like macrophage and regulatory T-cell recruitment. Conclusions: Intratumoral F. nuc DNA quantification identifies a high-risk biological subtype of ESCC. Consistency across regional cohorts indicates F. nuc is a universal driver of metastatic progression in squamous cell pathology. Standardized microbial DNA quantification may serve as a high-fidelity biomarker to refine risk stratification and guide microbiota-targeted neoadjuvant strategies to mitigate metastatic spread in ESCC.

e16067 Background: Gastric carcinoma remains a significant cause of cancer mortality in the United States. Although overall mortality rates have declined, persistent disparities exist across racial, age, and geographic groups. For cancer patients, sepsis—a life-threatening infection response—is a major fatal complication. Analyzing linked mortality data is crucial for identifying high-risk populations, understanding the burden of cancer-associated infections, and guiding targeted prevention and treatment strategies to improve outcomes and achieve health. Methods: This cross-sectional study used CDC WONDER mortality data from 1999–2020 for adults aged 25 years and older. Causes of death were identified using ICD-10 codes, and age-adjusted mortality rates (AAMRs) were calculated across sex, race/ethnicity, age, census regions, and urban–rural categories. Mortality trends were assessed using Joinpoint regression to estimate average annual percentage changes (AAPC) with 95% confidence intervals (CIs) and statistical significance. Results: From 1999 to 2020, U.S. stomach cancer mortality declined overall, with AAMRs decreasing from 0.29 to 0.22 per 100,000 (AAPC = –0.8%, 95% CI: –1.64 to 0.04). Significant declines occurred among adults aged 65–74 (APC = –1.7%, 95% CI: –2.32 to –1.05), 75–84 (APC = –1.9%, 95% CI: –2.65 to –1.05), and ≥85 years (APC = –3.0%, 95% CI: –4.02 to –1.99). Adults 45–54 years experienced increasing mortality after 2005 (APC = 5.1%, 95% CI: 2.82 to 7.46), while rates among 55–64 years remained stable. Male mortality declined significantly (AAPC = –1.24%, 95% CI: –1.93 to –0.54), whereas female mortality showed no significant long term change (AAPC = –0.93%, 95% CI: –2.44 to 0.60). Black (AAPC = –2.25%, 95% CI: –3.02 to –1.47) and Hispanic/Latino populations (AAPC = –1.50%, 95% CI: –2.26 to –0.74) experienced significant declines. Regionally, the Northeast showed the largest decline (AAPC = –2.30%, 95% CI: –3.52 to –1.07), while the Midwest, South, and West demonstrated no significant long term trends. Metropolitan areas declined from 1999–2011 (APC = –2.80%, 95% CI: –4.44 to –1.14). Conclusions: While overall U.S. gastric cancer mortality declined from 1999–2020, this progress is uneven. Significant increases among adults aged 45–54 and stable rates for those 55–64 highlight an emerging concern. Furthermore, declining trends are concentrated in specific demographic groups and regions, such as the Northeast, revealing persistent disparities. These findings underscore the need for targeted prevention and research focused on younger adults and lagging geographic areas.

e16027 Background: Postoperative oral intake after esophagectomy has traditionally been delayed due to concerns about anastomotic leakage. Although Enhanced Recovery After Surgery (ERAS) pathways increasingly support early feeding, its safety remains debated. This study compared early versus delayed oral feeding following esophagectomy for esophageal cancer. Methods: PubMed, Embase, and Scopus were systematically searched through October 2025 for randomized controlled trials evaluating early oral feeding (postoperative days 0–3) versus delayed feeding (postoperative day ≥5) after esophagectomy. Primary outcomes were anastomotic leakage and pneumonia. Secondary outcomes included postoperative complications, gastrointestinal recovery, length of hospital stay, healthcare costs, and quality of life. Pooled risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% confidence intervals were calculated using Review Manager 5.4. Results: Thirteen trials involving 1,468 patients were included. Early oral feeding was not associated with increased anastomotic leakage (RR: 0.89, 95% CI: 0.55–1.45; I² = 0%) and showed consistent safety across surgical approaches and anastomotic sites. The incidence of pneumonia was significantly reduced (RR: 0.66, 95% CI: 0.47–0.92; p = 0.01). Early feeding accelerated gastrointestinal recovery, including earlier first bowel movement (MD: −0.50 days, p < 0.00001) and passage of flatus (MD: −0.61 days, p = 0.0006). Hospital stay was shortened (MD: −1.89 days, p = 0.002), with lower medical costs (SMD: −1.19, p = 0.009). Quality-of-life measures improved, including global health status, dysphagia, pain, and swallowing function. Conclusions: Early oral feeding after esophagectomy appears safe and beneficial, reducing pulmonary complications and enhancing postoperative recovery. Further high-quality multicenter trials are needed to confirm these findings.

e16024 Background: Patients with advanced esophageal squamous cell carcinoma (ESCC) continue to have poor outcomes with chemotherapy alone. The addition of PD-L1 inhibitors to first-line chemotherapy has shown encouraging results in individual trials, but the overall magnitude and consistency of benefit across key clinical endpoints have not been fully clarified. To better understand the effects of PD-L1 inhibitors used in combination with chemotherapy, we performed a systematic review and meta-analysis to compare the efficacy and safety of PD-L1-based combination therapies to chemotherapy alone in patients with advanced or metastatic ESCC. Methods: A systematic search of PubMed, Embase, and Scopus identified randomized controlled trials comparing PD-L1 inhibitor plus chemotherapy versus chemotherapy alone in patients with advanced or metastatic ESCC. Three eligible studies met inclusion criteria. We calculated pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS); and pooled risk ratios (RRs) for objective response rate (ORR) and Grade 3-5 treatment-related adverse events (TRAEs) using random effects models. We quantified the heterogeneity among studies using the I² test. Results: Across three randomized trials, the addition of a PD-L1 inhibitor to chemotherapy resulted in a statistically significant and highly consistent survival advantage. OS was longer with combination therapy (HR 0.67, 95% CI 0.60–0.76; p < 0.00001), representing a 33% reduction in the risk of death, with no heterogeneity across studies (I² = 0%). Similarly, PFS was prolonged with combination therapy (HR 0.61, 95% CI 0.55–0.68; p < 0.00001; I² = 0%), corresponding to a 39% reduction in the risk of disease progression or death. Tumor responses occurred at higher frequencies in patients who received PD-L1 inhibitor-based therapy than in patients who received chemotherapy alone (RR = 1.49, 95% CI = 1.35-1.63; p < .00001; I² = 0%). The increased efficacy observed with combination therapy was not accompanied by an increase in severe toxicities. The rates of Grade 3-5 TRAEs were similar between the two groups (RR = 1.06, 95% CI = 0.99-1.13; p = 0.09; I² = 0%). Conclusions: Based on evidence from three randomized trials, the addition of PD-L1 inhibitors to standard chemotherapy improves both survival and response rates in patients with advanced ESCC without an increase in severe treatment related adverse events. Therefore, PD-L1-based combination therapies represent a promising new therapeutic option for patients with advanced ESCC.