To determine the safety and efficacy of transarterial chemoembolization (TACE) combined with sorafenib (hereafter, TACE-sorafenib) in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). This study was approved by the institutional review board, and the requirement for informed consent was waived. The medical records of consecutive patients with HCC and PVTT who underwent TACE-sorafenib or TACE alone from January 2010 to December 2012 were retrospectively evaluated. Sorafenib (400 mg) was administered twice daily. Outcomes of patients who underwent TACE-sorafenib were compared with outcomes of patients who underwent TACE by using the Kaplan-Meier method according to types of PVTT: PVTT in the main portal vein (type A), PVTT in the first-order portal vein branch (type B), and PVTT in second- or lower-order portal vein branches (type C). Ninety-one patients were included in the analysis; 46 patients underwent TACE-sorafenib and 45 underwent TACE. TACE-sorafenib showed significant survival benefits compared with TACE in patients with type B (median survival, 13 months vs 6 months; P = .002) or type C (median survival, 15 months vs 10 months; P = .003) PVTT. TACE-sorafenib and main PVTT were the independent prognostic factors for survival at uni- and multivariate analysis. Liver function after TACE-sorafenib worsened only in patients with main PVTT. Sorafenib-related adverse events of grade 3 or higher occurred in 16 patients (35%). TACE-sorafenib side effects were acceptable, and this treatment may improve overall survival in patients with HCC with first-order or lower-branch PVTT when compared with patients who underwent TACE alone.

This retrospective study showed that the combination of sorafenib with transarterial chemoembolization and radiofrequency ablation resulted in a significant survival benefit in patients with medium or large hepatocellular carcinoma when compared with results in patients who underwent only transarterial chemoembolization and radiofrequency ablation. Purpose To determine the safety and efficacy of sorafenib combined with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, S-TACE-RFA) in patients with medium or large (range, 3.1–7.0 cm in diameter) hepatocellular carcinoma (HCC). Materials and Methods This retrospective study evaluated the medical records of consecutive patients with medium or large HCC who underwent S-TACE-RFA or combined TACE and RFA (hereafter, TACE-RFA) from January 2010 to December 2014. Sorafenib was started 3–5 days after TACE, and RFA was performed 1–2 weeks after TACE. Treatment complications, recurrence-free survival (RFS), and overall survival (OS) in patients who underwent S-TACE-RFA were compared with those in patients who underwent TACE-RFA. Results Of the 174 patients who underwent S-TACE-RFA or TACE-RFA, 106 who met the eligibility criteria were included in this study. Among them, 40 underwent S-TACE-RFA and 66 underwent TACE-RFA. The patients who underwent S-TACE-RFA had longer RFS (med...

Hepatocellular carcinoma (HCC) is one of the most common malignancies imposing a serious threat to human health worldwide. To date, the effect of HCC chemotherapy has been limited due to drug resistance. Combination therapy of chemotherapeutic drugs and siRNA represents an emerging strategy that may improve anticancer effects by synergistic actions. The current study was aimed at achieving better HCC treatment via combination therapy, in which PEI-modified liposomes prepared by a thin-film hydration method were used to codeliver sorafenib (SF) and siRNA targeting GPC3 gene (siGPC3). Under optimized experimental conditions, SF and siGPC3 were effectively loaded into liposomes (SF-PL/siGPC3). SF-PL/siGPC3 with selected sizes and zeta potentials effectively accumulated at tumor sites and entered HCC cells. The two codelivered therapeutic agents exerted good anticancer effects by jointly suppressing the expression of the anti-apoptotic GPC3 gene and the proliferative cyclin D1 gene in HCC. Consequently, the intravenous injection of SF-PL/siGPC3 into nude mice bearing subcutaneous human HepG2 xenografts effectively inhibited tumor growth and also increased the survival rates of animals. These results revealed the great potential of the PEI-modified liposomal nanomedicine carrying SF and siGPC3 to improve HCC treatment.

To evaluate the safety and efficacy of regorafenib combined with anti-PD-1 antibody sintilimab (rego-sintilimab) as a second-line treatment for advanced hepatocellular carcinoma (HCC). This multicenter retrospective study evaluated consecutive patients with advanced HCC who received rego-sintilimab (rego-sintilimab group) or regorafenib alone (regorafenib group) as a second-line treatment from January 2019 to December 2020. Adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Uni- and multi-variable analyses of prognostic factors for OS and PFS were performed using Cox proportional hazard regression models. In total, 113 patients were included in the study: 58 received rego-sintilimab and 55 received regorafenib. The rego-sintilimab group had higher ORR (36.2% vs 16.4%, P = 0.017), longer PFS (median 5.6 vs 4.0 months; P = 0.045), and better OS (median 13.4 vs 9.9 months; P = 0.023) than the regorafenib group. Regorafenib alone, Child-Pugh B, and neutrophil-to-lymphocyte ratio (NLR) > 3.6 were independent prognostic factors for poor OS. Regorafenib alone, α-fetoprotein level, and NLR > 3.6 were independent prognostic factors for poor PFS. Subgroup analyses showed a survival benefit of rego-sintilimab in patients with NLR ≤ 3.6 (hazard ratio 0.518 [95% CI, 0.257–0.955]) but not in those with NLR > 3.6 (0.852 [0.461–1.572]); P = 0.002 for interaction. The difference in incidence of grade 3/4 adverse events between the two groups was not statistically significant (39.7% vs 30.9%; P = 0.331). Rego-sintilimab was tolerated and led to better OS than regorafenib as a second-line treatment for advanced HCC patients, especially in those with NLR ≤ 3.6.

Sorafenib (SF) is the first drug demonstrated to improve the survival of patients diagnosed with advanced-stage hepatocellular carcinoma (HCC). However, its clinical application is limited by the poor oral bioavailability and severe side effects. In this study, a multifunctional micellar nanodrug was developed for simultaneous HCC-targeted delivery of SF and tumor detection with magnetic resonance imaging (MRI). The micellar nanodrug incorporating SF and superparamagnetic iron oxide nanoparticles (SPIONs) was prepared from a diblock copolymer of monomethoxyl poly(ethylene glycol) and poly(N-(2-aminoethanethiol-co-2-aminoethyldiisopropylamine) aspartamide) and then decorated with anti-glypican-3 antibody (Ab_GPC3). Owing to the small size, weak positive charge and Ab_GPC3-mediated active targeting to HCC cells, the nanodrug exhibited an easy cellular uptake and enhanced tumor accumulation. The prominent reduction and pH dual-sensitivity allowed the nanodrug to rapidly release SF inside cancer cells via responding to the cytoplasmic glutathione and lysosomal acidity. The nanodrug not only significantly improved the anticancer effects of SF in hepatoma treatment but also facilitated a noninvasive tumor detection and monitoring of in vivo drug delivery by MRI, which revealed its great potential as a promising theranostic system.