Temperature-sensitive liquid embolic agent transarterial chemoembolization versus drug-eluting bead transarterial chemoembolization for BCLC Stage B/C hepatocellular carcinoma: a multicenter real-world study and spatial transcriptomics profiling (CHANCE 2515).

Transarterial chemoembolization (TACE) remains a cornerstone therapy for intermediate-to-advanced hepatocellular carcinoma (HCC); however, the optimal embolic platform remains uncertain. This multicenter, retrospective, real-world study (Clinical trial registration number: ChiCTR2500113198) conducted across China compared a novel temperature-sensitive liquid embolic agent, TempSLE-TACE (T-TACE), with conventional drug-eluting bead TACE (D-TACE) in 328 patients with Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC. Following inverse probability of treatment weighting (IPTW), T-TACE achieved significantly superior objective response rates (ORRs) compared with D-TACE according to both RECIST 1.1 criteria (54.11% vs. 27.78%, P < 0.001) and mRECIST criteria (73.56% vs. 54.93%, P = 0.002). T-TACE was additionally associated with significantly prolonged progression-free survival (median PFS: 12.0 vs. 9.0 months; HR = 0.67, P = 0.001) and overall survival (median OS, 24.0 vs. 15.0 months; HR = 0.49, P < 0.001). Moreover, T-TACE demonstrated a favorable safety profile, with lower incidences of hepatic and gastrointestinal toxicities, including any-grade alanine aminotransferase elevation and hyperbilirubinemia. Subgroup analyses further demonstrated consistent OS, PFS, and ORR benefits across major clinical subgroups, with effect sizes remaining significantly favorable in high-risk populations, including advanced portal vein tumor thrombosis type Vp4, baseline AFP > 1000 ng/mL, and PIVKA-II > 2000 mAU/mL. Exploratory histo-molecular and spatial transcriptomic analyses suggested that T-TACE may promote immune microenvironment remodeling through enhanced Th17-cell infiltration and CD8⁺ T-cell activation, whereas incomplete embolization after D-TACE was more frequently associated with residual intermediate-state tumor cells and an immunosuppressive microenvironment. Collectively, these findings provide preliminary evidence supporting T-TACE as a promising real-world therapeutic strategy for intermediate-to-advanced HCC.