Srinivasan, Gurunathan

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.

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.

e15091 Background: Early identification of patients likely to benefit from immune checkpoint inhibitors (ICIs) remains a major challenge across solid tumors. Circulating tumor DNA (ctDNA) kinetics have emerged as a promising noninvasive biomarker, yet results across studies are heterogeneous. We conducted a systematic review and meta-analysis to evaluate the prognostic and predictive value of early ctDNA reduction in patients receiving ICIs. Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane Library was conducted from inception through March 2025 following PRISMA guidelines. Studies evaluating early ctDNA dynamics (≤8 weeks after ICI initiation) in adult patients with solid tumors were included. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included objective response rate (ORR). Random-effects models were used to pool hazard ratios (HRs) and odds ratios (ORs). Heterogeneity was assessed using I² statistics, and publication bias was evaluated with funnel plots and Egger’s test. Results: A total of 27 studies encompassing 3,842 patients across lung, melanoma, breast, gastrointestinal, and genitourinary malignancies met inclusion criteria. Early ctDNA reduction (defined as ≥50–90% decline or complete clearance, study-specific) was associated with significantly improved PFS (pooled HR 0.45; 95% CI 0.38–0.53; I² = 41%) and OS (pooled HR 0.40; 95% CI 0.32–0.49; I² = 36%). Patients demonstrating early ctDNA reduction had a markedly higher ORR (pooled OR 4.92; 95% CI 3.71–6.53; I² = 29%). Subgroup analyses showed consistent benefit across tumor types and ICI regimens. Early ctDNA dynamics outperformed baseline PD-L1 expression and tumor mutational burden in predicting treatment response. No significant publication bias was detected. Conclusions: Early ctDNA kinetics are a robust, tumor-agnostic biomarker associated with improved survival and treatment response in patients receiving ICIs. These findings support the integration of ctDNA monitoring into early treatment assessment and clinical trial design. Prospective trials are warranted to validate ctDNA-guided immunotherapy strategies.