BackgroundLocoregional therapy combined with systemic therapy can further improve the prognoses for HCC. However, the efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown.PurposeTo identify the efficacy of TACE+ICIs+TKIs for unresectable hepatocellular carcinoma (uHCC) and its effect on systemic immunity.Materials and MethodsThis single-center retrospective study was approved by the Institutional Review Board. From August 1, 2019, to March 30, 2021, patients with uHCC who received the combination therapy of TACE+ICIs+TKIs were included. Peripheral blood samples were collected at baseline and once a month for 4 months after treatment. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The dynamic change trend of circulating parameters was tested using simple linear regression.ResultsFifty-three patients with a mean age of 59 ± 10.6 years were included. TTP was 8.0 months (95% CI, 5.5–10.5) and PFS was 8.5 months (95% CI, 5.4–11.5). ORR was 52.8% and DCR was 81.1%. Twenty patients had completed analysis of biomarkers in peripheral blood. For cellular immune response, the level of circulating CD8+, CD3+ T cells and NK cells increased, the frequency of CD4+T cells and the CD4+/CD8+ ratio decreased, and among them, CD8+ T cells increased significantly. For humoral immune response, there was a significant decrease in B cells and a significant increase in Ig G, Ig κ, and Ig λ. Moreover, Ig G, Ig κ, and Ig λ were related to tumor response.ConclusionTACE+ICIs+TKIs showed considerable efficacy in patients with uHCC. This triple therapy activated not only cell immune but also humoral immune activation. Circulating Ig G, Ig λ, and Ig κ can serve as potential biomarkers.

Objective: To compare the outcomes of transarterial chemoembolization (TACE) combined with sorafenib versus TACE alone for treating patients with unresectable hepatocellular carcinoma (HCC). Methods: This retrospective analysis included all patients receiving either TACE plus sorafenib therapy or TACE alone for unresectable HCC between February 2008 and August 2015 at the First Affiliated Hospital of Soochow University, China. Propensity score matching (PSM) was carried out to reduce bias due to confounding variables. The primary outcome was overall survival (OS), calculated from the date of the first TACE treatment until the date of death of any cause. A multivariate Cox proportional hazards analysis was conducted to examine determinants of OS. Results: A total of 308 patients were included in the study: 61 receiving TACE plus sorafenib treatment and 247 receiving TACE monotherapy. The PSM cohort included 61 subjects receiving TACE plus sorafenib and 122 subjects receiving TACE alone. In the overall analysis that included all patients, the median OS in the combination group was significantly longer than that in the monotherapy group (29.0 ± 7.2 vs. 14.9 ± 1.1 months; P = 0.008). In the PCM cohort, the median OS was also significantly longer in the combination group (29.0 ± 7.2 vs. 14.9 ± 1.5 months; P = 0.018). Subgroup analysis revealed longer OS in patients receiving combination treatment in both the BCLC-B and BCLC-C subgroups (P < 0.05 for both). Multivariate analyses in the PSM cohort revealed that treatment methods (P = 0.003), number of nodules (P = 0.010), tumor size (P = 0.012), vascular invasion (P = 0.005), and number of TACE (P = 0.029) were independent prognostic factors of OS. The most common adverse events were hand-foot skin reaction (75.4%) and diarrhea (47.5%) in the combination group, and fatigue (19.0%) and liver dysfunction (18.2%) in the monotherapy group. There were no treatment-related deaths in either group. Conclusion: The combined use of TACE and sorafenib is generally well tolerated and could significantly increase OS of patients with unresectable HCC.

PurposeTo explore the safety and efficacy of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of unresectable hepatocellular carcinoma (uHCC).Materials and MethodsFrom August 2019 to July 2020, patients who received TACE combined with ICIs and TKIs were retrospectively analyzed. Treatment-related adverse events (AEs) were recorded. The Kaplan–Meier method was used to estimate time to progression (TTP) and progression-free survival (PFS).ResultsIn total, 31 patients with uHCC were included. Eleven patients were classified as BCLC-C. Nineteen patients had multiple lesions, and the cumulative targeted lesions were 69 mm (range, 21-170 mm) according to mRECIST. Twenty-nine (93%) patients experienced at least one AE during the treatment. Four (12.9%) patients developed AEs of higher grade (grade≥3). The objective response rate (ORR) and disease control rate (DCR) were 64.5% and 77.4%, respectively. The median time to response was 7 weeks (range, 4-30 w), and the duration of response was 17.5 weeks (range, 2-46 w). From the first ICIs, TTP and PFS were 6.5 months (95% CI, 3.5-11) and 8.5 months (95% CI, 3.5-NE), respectively.ConclusionsTACE combined with ICIs and TKIs shows an acceptable safety profile and considerable efficacy in patients with HCC.

Objective This study aimed to evaluate the effectiveness and safety of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) plus tyrosine kinase inhibitors (TKIs) (TACE+IT) versus ICIs plus TKIs (IT) for advanced hepatocellular carcinoma (HCC). Materials and Methods Data of consecutive advanced HCC patients receiving TACE+IT or IT between January 2019 and December 2021 were included and were retrospectively analyzed. Propensity score matching (PSM) was performed to reduce bias due to confounding variables. The primary outcome of the study was overall survival (OS). The secondary outcomes were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs), respectively. Results Sixty-four patients were enrolled in the study, among which 24 and 40 received TACE+IT and IT, respectively. The PSM cohort included 24 patients receiving TACE+IT (TACE+IT group) and 24 patients receiving IT (IT group) alone. During a median follow-up of 23 months, patients in TACE+IT group had significantly longer OS (median, 17.3 vs 11.8 months, P = 0.023), better ORR (41.7% vs 12.5%, P = 0.023) and DCR (79.2% vs 50.0%, P = 0.035) than those in the IT group, whereas a non-significant trend in PFS (median, 7.4 vs 6.7 months, P = 0.23) was observed. According to multivariable cox regression analysis, it was found that treatment modality was the only independent risk factor for OS (HR = 0.404, 95% CI = 0.179–0.911, P < 0.05). There were no remarkable differences in AEs associated with ICIs and TKIs between the two groups, with the exception of gastrointestinal reaction. Conclusion TACE combined with ICIs plus TKIs significantly improved OS, ORR, and DCR and showed a relatively longer PFS trend over ICIs combined with TKIs for advanced HCC.

No abstract