Hepatic Arterial Infusion Chemotherapy Group Research Articles

Combining immune checkpoint inhibitors and molecular-targeted agents with hepatic arterial infusion chemotherapy for hepatocellular carcinoma with inferior vena cava and/or right atrium tumor thrombus.

e16177 Background: Patients with hepatocellular carcinoma and inferior vena cava and/or right atrium tumor thrombus (HCC-IVC/RATT) have a poor prognosis and lack evidence for standard first-line systemic treatment due to its low incidence. This study aims to evaluate the effectiveness and safety of three treatments in HCC-IVC/RATT patients: immune checkpoint inhibitors plus molecular-targeted agents (ICI-MTA), hepatic arterial infusion chemotherapy (HAIC), and their combination (ICI-MTA-HAIC). Methods: This multicenter retrospective cohort study included consecutive HCC-IVC/RATT patients who received ICI-MTA, HAIC, or ICI-MTA-HAIC from June 1, 2014, to December 31, 2022. The propensity score matching (PSM) was used to balance baseline characteristics. Survival analysis was conducted using Kaplan-Meier curves and compared using the log-rank test. Results: A total of 243 HCC-IVC/RATT patients were included, with 144 receiving ICI-MTA-HAIC, 29 receiving ICI-MTA, and 70 receiving HAIC. Before PSM, the ICI-MTA-HAIC group had significantly superior median overall survival (OS) of 16.5 months, progression-free survival (PFS) of 8.0 months, and objective response rate (ORR) of 47.9%, in comparison to both the ICI-MTA (OS: 7.7 months, P < 0.001; PFS: 3.5 months, P = 0.001; ORR: 24.1%, P = 0.019) and HAIC groups (OS: 9.1 months, P = 0.003; PFS: 4.9 months, P = 0.007; ORR: 25.7%, P = 0.002) among HCC-IVC/RATT patients based on RECIST v1.1 criteria. The ICI-MTA and HAIC groups didn’t exhibit significant differences in OS, PFS, or ORR ( P = 0.061, 0.043, 0.869, respectively). After PSM, similar results were obtained across the three groups. All adverse reactions were manageable, and no unexpected adverse reactions or treatment-related deaths were observed among the three groups. Conclusions: ICI-MTA-HAIC was a safe and effective therapy that prolonged the survival of HCC-IVC/RATT patients compared to ICI-MTA or HAIC.

Combining immune checkpoint inhibitors and molecular-targeted agents with hepatic arterial infusion chemotherapy for hepatocellular carcinoma with inferior vena cava and/or right atrium tumor thrombus.

e16177 Background: Patients with hepatocellular carcinoma and inferior vena cava and/or right atrium tumor thrombus (HCC-IVC/RATT) have a poor prognosis and lack evidence for standard first-line systemic treatment due to its low incidence. This study aims to evaluate the effectiveness and safety of three treatments in HCC-IVC/RATT patients: immune checkpoint inhibitors plus molecular-targeted agents (ICI-MTA), hepatic arterial infusion chemotherapy (HAIC), and their combination (ICI-MTA-HAIC). Methods: This multicenter retrospective cohort study included consecutive HCC-IVC/RATT patients who received ICI-MTA, HAIC, or ICI-MTA-HAIC from June 1, 2014, to December 31, 2022. The propensity score matching (PSM) was used to balance baseline characteristics. Survival analysis was conducted using Kaplan-Meier curves and compared using the log-rank test. Results: A total of 243 HCC-IVC/RATT patients were included, with 144 receiving ICI-MTA-HAIC, 29 receiving ICI-MTA, and 70 receiving HAIC. Before PSM, the ICI-MTA-HAIC group had significantly superior median overall survival (OS) of 16.5 months, progression-free survival (PFS) of 8.0 months, and objective response rate (ORR) of 47.9%, in comparison to both the ICI-MTA (OS: 7.7 months, P < 0.001; PFS: 3.5 months, P = 0.001; ORR: 24.1%, P = 0.019) and HAIC groups (OS: 9.1 months, P = 0.003; PFS: 4.9 months, P = 0.007; ORR: 25.7%, P = 0.002) among HCC-IVC/RATT patients based on RECIST v1.1 criteria. The ICI-MTA and HAIC groups didn’t exhibit significant differences in OS, PFS, or ORR ( P = 0.061, 0.043, 0.869, respectively). After PSM, similar results were obtained across the three groups. All adverse reactions were manageable, and no unexpected adverse reactions or treatment-related deaths were observed among the three groups. Conclusions: ICI-MTA-HAIC was a safe and effective therapy that prolonged the survival of HCC-IVC/RATT patients compared to ICI-MTA or HAIC.

Higher objective responses by hepatic arterial infusion chemotherapy following atezolizumab and bevacizumab failure than when used as initial therapy in hepatocellular carcinoma: a retrospective study.

Atezolizumab/bevacizumab (atezo-bev) is the first-line chemotherapy for patients with unresectable hepatocellular carcinoma (HCC). However, hepatic artery infusion chemotherapy (HAIC) can be used as an alternative. Our aim was to compare the prognosis of HAIC treatment between newly diagnosed patients and patients treated after failure of atezo-bev. We retrospectively assessed 73 patients with HCC treated with HAIC between January 2022 and September 2023. Fifty-seven patients were treated with HAIC at initial diagnosis, while 16 were treated with HAIC after first-line atezo-bev combination chemotherapy. We evaluated tumor responses, such as overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). No significant difference was observed in either OS or PFS between patients with HCC treated with HAIC at the initial diagnosis and those treated after atezo-bev treatment failure. However, the ORR of the initial HAIC group was 19.6% and that of the HAIC group after atezo-bev therapy failure was 43.6%, which was a statistically significantly difference. Although no significant difference was observed for OS and PFS, the ORR of patients in the HAIC group after the failure of atezo-bev therapy was superior to that of newly diagnosed patients. HAIC may prolong survival in patients with HCC after atezo-bev treatment failure.

High-Risk Hepatocellular Carcinoma: Hepatic Arterial Infusion Chemotherapy versus Transarterial Chemoembolization.

To compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with transarterial chemoembolization (TACE) for the treatment of high-risk hepatocellular carcinoma (hHCC) patients. Between January 2014 and August 2022, a total of 1765 consecutive patients with hHCC who underwent initial intra-arterial therapies were reviewed and divided into a TACE group (n, 507) and a HAIC group (n, 426). The study used propensity score matching (PSM) to reduce selectivity bias. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan‒Meier curves with the Log rank test. The objective response rate (ORR), conversion surgery rate (CSR) adverse event (AE) comparison and subgroup analysis were performed between the two groups. After PSM 1:1, 444 patients were divided into two groups. The patients with hHCC who received HAIC had higher median PFS (6.1 vs 3.3 months, P < 0.001) and OS (10.3 vs 8.2 months, P=0.303) than TACE. Higher ORR (24.8% vs 11.7%) and CSR (15.5% vs 8.9%) were found in the HAIC group than in the TACE group (both P < 0.05). The incidence of grade 3/4 AE was 23.9% and 8.1% in the TACE and HAIC groups, respectively. The subgroup analysis suggest that HAIC appeared to particularly benefit patients with tumor diameter of more than 10 centimeters (hazard ratio [HR], 0.6; 95% CI, 0.47-0.77; p, 0.00) and PVTT Vp4 (HR, 0.56; 95% CI, 0.39-0.8; P, 0.01) for PFS outperforming TACE. HAIC can provide better disease control for hHCC than cTACE, with a comparable long-term OS and safety.

Comparative study on the efficacy and safety of transarterial chemoembolization combined with hepatic arterial infusion chemotherapy for large unresectable hepatocellular carcinoma.

Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) are two new treatments for hepatocellular carcinoma (HCC). Previous studies had reported that TACE combined with HAIC conferred better survival benefit than TACE alone. The study was to evaluate the availability and safety of TACE combined with HAIC for the treatment of large HCC. Patients with unresectable large HCC who underwent TACE combined with HAIC (TACE-HAIC group) and HAIC alone (HAIC group) at the Department of Interventional Radiology between August 2018 and September 2022 were retrospectively enrolled in this study. Overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) were used to evaluate the efficacy and safety of the two groups by using log-rank test. The independent factors of OS of large HCC patients were investigated by Cox regression model. A total of 73 patients (mean age, 59.8±8.8; 60 men) with unresectable large HCC were finally screened in the current study, including 32 who received TACE combined with HAIC and 41 who received HAIC alone. Compared with patients in HAIC group, TACE-HAIC group had higher median OS (37.1 vs. 14.9 months, P=0.0014). Similarly, PFS in the TACE-HAIC group was longer than that in the HAIC group (16.5 vs. 6.9 months, P=0.0037). The objective response rate (ORR) was 65.6% vs. 53.7% and the disease control rate (DCR) was 90.6% vs. 78.0% in the two groups, neither was statistically significant (P=0.345 and 0.208, respectively). All AEs related to therapy were manageable, and there were no significant differences in the incidence of any grade and grade 3/4 AEs between the two groups (P>0.05). TACE combined with HAIC yielded a promising prognosis in treating patients with large HCC compared with HAIC alone, with tolerable toxicity.

Efficiency and safety of hepatic arterial infusion chemotherapy (HAIC) combined with anti-PD1 therapy versus HAIC monotherapy for advanced hepatocellular carcinoma: A multicenter propensity score matching analysis.

To investigate the clinical efficacy and safety of combination therapy of hepatic arterial infusion chemotherapy (HAIC) and anti-programmed cell death protein-1 (PD-1) therapy in the treatment of advanced hepatocellular carcinoma (HCC). In this retrospective clinical research, from March 2018 to December 2019, 1158 HCC patients categorized as BCLC stage C were reviewed for eligibility. We utilized propensity score matching (PSM) to mitigate initial disparities between the groups. The evaluation of the best tumor response was conducted in accordance with mRECIST 1.1 criteria. The difference in survival outcomes including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) between groups were compared. Following the eligibility review, 453 patients underwent a combined treatment of HAIC with PD1 inhibitors (HAIC-PD1 group), while 221 patients received HAIC monotherapy (HAIC group) met the inclusion criteria and were finally enrolled in this study. In the entire cohort, the HAIC-PD1 group exhibited significantly prolonged overall survival (median overall survival: 40.4 months vs. 9.7 months, p < 0.001) and progression-free survival (median progression-free survival: 22.1 months vs. 5.8 months, p < 0.001). By propensity score, patients were matched according to baseline differences, resulting in all 442 patients in group HAIC-PD1 (n = 221) and group HAIC (n = 221). After PSM adjustment, as well, the survival of the HAIC-PD1 group was still distinctly longer than the HAIC group (median overall survival time, 40.4 months vs 9.7 months, p < 0.001; median progression-free survival, 22.1 months vs 5.7 months, p < 0.001). Univariate and multivariable analysis demonstrated that AFP level, metastasis, and therapeutic schedule were independent predictive factors for overall survival. The combination therapy of HAIC and PD1 inhibitors successfully extended OS to advanced HCC patients and could be a better choice than HAIC monotherapy.

Efficacy and Safety of HepaSphere Drug-Eluting Bead Transarterial Chemoembolization Combined with Hepatic Arterial Infusion Chemotherapy as the Second-Line Treatment in Advanced Hepatocellular Carcinoma.

Recently, hepatic arterial infusion chemotherapy (HAIC) has also gained popularity for hepatocellular carcinoma (HCC). Several studies have compared HAIC and Transarterial chemoembolization (TACE). However, comparisons between TACE plus HAIC and HAIC are rarely reported. Here, we evaluated the performance of HepaSphere DEB-TACE combined with HAIC (Hepa-HAIC) compared to HAIC in patients with advanced HCC. In this retrospective study, we enrolled 167 patients diagnosed with advanced HCC and treated at Peking University Cancer Hospital from May 2018 to May 2022. The cohort comprised 74 patients who received HepaSphere DEB-TACE combined with HAIC-FOLFOX (Hepa-HAIC) and 93 patients who received HAIC-FOLFOX. Over 60% of patients received prior treatments. To avoid selection bias, propensity score matching was applied to the efficacy and safety analyses. The primary endpoints are progression-free survival (PFS) and overall survival (OS); the secondary endpoints include objective response rate (ORR), disease control rate (DCR), and safety. Propensity-matching yielded 48 pairs, and group baselines were almost equal after matching. Median PFS and median OS were both higher in the matched Hepa-HAIC cohort (median PFS: 8.9 vs 5.8 months, p = 0.035; median OS: 22.4 vs 9.5 months, p = 0.027), which was consistent with pre-matching analysis. The ORR in the Hepa-HAIC and HAIC cohorts was 75.0% and 37.5%, respectively; the DCR was 93.8% after Hepa-HAIC and 81.3% after HAIC. There was no treatment-related death. Grade 3-4 ALT elevation was more frequent in the Hepa-HAIC group (33.3% vs 8.3%, p = 0.003), while vomiting was more frequent in the HAIC group (29.2% vs 12.5%, p = 0.084). The Hepa-HAIC group is superior to the HAIC group in metrics of PFS, OS, ORR, and DCR, which indicates the combination of HepaSphere DEB-TACE and HAIC may lead to improved outcomes with a comparable safety profile in advanced HCC.

Similar Efficacy Between Atezolizumab Plus Bevacizumab Versus Hepatic Arterial Infusion Chemotherapy For Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Retrospective Cohort Study.

The landscape of treatments for hepatocellular carcinoma (HCC), including immune checkpoint inhibitors, has expanded significantly. However, unresectable HCC patients with portal vein tumor thrombus (PVTT) continue to face a poor prognosis. This investigation examined the survival outcomes and determinants influencing survival rates in advanced HCC patients with PVTT undergoing treatment with atezolizumab plus bevacizumab (ATZ+BEV) or hepatic arterial infusion chemotherapy (HAIC). Between December 2003 and June 2023, 48 advanced HCC with PVTT underwent treatment with either ATZ+BEV (16 patients) or HAIC (32 patients). The analysis revealed no significant disparities in overall survival (OS) or treatment efficacy between the ATZ+BEV and HAIC groups (ATZ+BEV: 10.0 months, HAIC: 15.3 months). Treatment with either ATZ+BEV or HAIC resulted in minimal alterations in the ALBI score and preserved hepatic function. Independent prognostic factors for OS, identified via multivariate logistic regression, included serum α-fetoprotein levels >400 ng/ml [hazard ratio (HR)=1.94; p=0.001], the existence of more than five tumors (HR=1.55; p=0.043), and the Child-Pugh score (HR=2.53; p=0.002). This investigation revealed no significant variance in OS and response rates between patients receiving ATZ+BEV and those treated with HAIC. The survival of advanced HCC patients with PVTT is intricately linked to the preservation of liver function, emphasizing the necessity for additional research to enhance treatment approaches for this patient population.

Systemic Chemotherapy with or without Hepatic Arterial Infusion Chemotherapy for Intrahepatic Cholangiocarcinoma with Extrahepatic Oligometastasis: A Propensity Score–Matched Analysis

PurposeTo compare the effectiveness of hepatic arterial infusion chemotherapy (HAIC) plus systemic chemotherapy (SYS) with that of SYS alone in patients with intrahepatic cholangiocarcinoma (ICC) with extrahepatic oligometastasis in terms of overall survival (OS) and mortality related to liver failure. Materials and MethodsConsecutive patients diagnosed with ICC with extrahepatic oligometastasis who received either HAIC plus SYS or SYS alone between January 2019 and January 2021 were included in this retrospective cohort study. Propensity score matching (PSM) analysis was performed to address potential confounding factors. OS, progression-free survival (PFS), and intrahepatic progression–free survival (IPFS) were analyzed. The occurrence of death due to liver failure was also assessed. ResultsThe study included a total of 179 patients, with 96 receiving SYS alone and 83 receiving HAIC plus SYS. After PSM, 83 pairs were included for further analysis. The median OS and IPFS were significantly longer in the HAIC plus SYS group compared to the SYS alone group (OS: 15.8 months vs 12.7 months; P = .023; IPFS: 9.7 vs 6.1 months; P < .001). No difference was found in PFS between the 2 groups. The HAIC plus SYS group had a significantly lower rate of mortality due to liver failure compared to the SYS alone group (42% vs 72%; P = .002). ConclusionsHAIC plus SYS is a promising treatment approach for patients with ICC and extrahepatic oligometastasis with improved OS, IPFS, and freedom from liver failure mortality compared with SYS alone.

Study on the comparison of postoperative liver injury caused by hepatic arterial perfusion chemotherapy combined with targeted immunotherapy with hepatic arterial chemoembolization combined with targeted immunotherapy for intermediate-and advanced-stage liver cancer

Objective: To compare the postoperative liver function injury condition in patients with intermediate-and advanced-stage hepatocellular carcinoma (HCC) treated with hepatic artery infusion chemotherapy (HAIC) and hepatic artery chemoembolization (TACE) combined with immune checkpoint inhibitors (ICIs) and multi-target tyrosine kinase inhibitors (TKIs). Methods: Patients with intermediate-and advanced-stage HCC who were admitted and treated with HAIC/TACE+ICIs+TKIs therapy at Nanfang Hospital of Southern Medical University from January 2019 to November 2021, with follow-up up to July 2023, were retrospectively enrolled. The results of liver function tests within one week before interventional surgery and on the first day after surgery were recorded. The degree of postoperative liver injury was graded according to the common terminology criteria for adverse events 5.0 (CTCAE 5.0). The treatment efficacy was evaluated according to RECIST 1.1 criteria. Measurement data were compared between groups using a t-test or a non-parametric rank sum test. Enumeration data were compared between the groups using the χ(2) test or Fisher's exact probability method. The survival condition differences were analyzed by the log-rank method. Results: This study included 82 and 77 cases in the HAIC and TACE groups. There were no statistically significant differences between the two groups of patients in terms of gender, age, physical condition score, number of tumors, presence or absence of liver cirrhosis, Child-Pugh grade, albumin-bilirubin (ALBI) grade, and combined ICIs and TKIs . The HAIC group had later tumor staging, a greater tumor burden, poorer liver reserve function, and a larger proportion of patients in stage C (81.7% vs. 63.6%), χ(2)=6.573, P = 0.01). There were 53 cases (64.6% vs. 32.5%) with a maximum tumor diameter of ≥ 10cm, χ(2)=16.441, P < 0.001), and more patients had a retention rate of ≥ 10% for indocyanine green (ICG) at 15 minutes (68.3% vs. 51.9%, P = 0.035). The postoperative incidence rate of increased levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin was significantly lower in the HAIC group than that in the TACE group (28.0% vs. 63.6%, χ(2)=20.298, P < 0.001, 54.9% vs. 85.7%, χ(2)=17.917, P < 0.001;40.2% vs. 55.8%, χ(2)=3.873, P = 0.049). The number of patients with postoperative ALBI grade 3 was significantly lower in the HAIC group than that in the TACE group (6.1% vs. 16.9%, χ(2)=4.601, P = 0.032). There was no statistically significant difference in the incidence rate of postoperative hypoalbuminemia, activated partial thromboplastin time, or increased international standardized ratio between the two groups of patients. There was no statistically significant difference in median progression-free survival (7.3 months vs. 8.2 months, P = 0.296) or median overall survival (16.5 months vs. 21.9 months, P = 0.678) between the two groups of patients. Conclusion: The incidence rate of postoperative liver injury is higher in patients with intermediate-and advanced-stage HCC treated with TACE combined with ICIs and TKIs than in patients with HAIC combined with ICIs and TKIs.

Comparison of hepatic arterial infusion chemotherapy with mFOLFOX vs. first-line systemic chemotherapy in patients with unresectable intrahepatic cholangiocarcinoma.

Background: Systemic chemotherapy (SC) remains the only first-line treatment for unresectable intrahepatic cholangiocarcinoma (iCCA). Hepatic arterial infusion chemotherapy (HAIC) has been recently proven to be effective in managing hepatocellular carcinoma (HCC). Hence, our study aims to investigate the safety and efficacy of HAIC in treating unresectable iCCA patients. Methods: We reviewed 146 patients with unresectable iCCA who had received HAIC or SC between March 2016 and March 2022 in a retrospective manner. Outcomes of patients and safety were compared between the HAIC and SC groups. Results: There were 75 and 71 patients in the HAIC and SC groups, respectively. The median OS in the HAIC and SC groups was 18.0 and 17.8 months (p = 0.84), respectively. The median PFS in the HAIC and SC groups was 10.8 and 11.4months (p = 0.59), respectively. However, the HAIC group had significantly longer intrahepatic progression-free survival (IPFS) than the SC group (p = 0.035). The median IPFS in the HAIC and SC groups was 13.7 and 11.4months, respectively. According to the OS (p = 0.047) and PFS (p = 0.009), single-tumor patients in the HAIC group appeared to benefit more. In addition, the overall incidence of adverse events (AEs) was lower in the HAIC group than that in the SC group. Conclusion: Our study revealed that HAIC was a safe and effective therapeutic regimen for unresectable iCCA with better intrahepatic tumor control when compared to SC. Meanwhile, patients with single tumor were more likely to benefit from HAIC than SC.

Efficacy of Lenvatinib Combined with Transcatheter Intra-Arterial Therapies for Patients with Advanced-Stage of Hepatocellular Carcinoma: A Propensity Score Matching.

This study aimed to evaluate the effect of lenvatinib (LEN) combined with transcatheter intra-arterial therapy (TIT) for advanced-stage hepatocellular carcinoma (HCC) after propensity score matching (PSM). This retrospective study enrolled 115 patients with advanced-stage HCC who received LEN treatment. The patients were categorized into the LEN combined with TIT group (n = 30) or the LEN monotherapy group (n = 85). After PSM, 38 patients (LEN + TIT group, n = 19; LEN monotherapy group, n = 19) were analyzed. The median overall survival (OS) in the LEN + TIT group was significantly higher than that in the LEN monotherapy group (median survival time (MST): 28.1 months vs. 11.6 months, p = 0.014). The OS in the LEN combined with transcatheter arterial chemoembolization and LEN combined with hepatic arterial infusion chemotherapy groups was significantly higher than that in the LEN monotherapy group (MST 20.0 vs. 11.6 months, 30.2 vs. 11.6 months, p = 0.048, and p = 0.029, respectively). Independent factors associated with OS were alpha-fetoprotein and LEN combined with TIT. The indications for LEN combined with TIT were age <75 years and modified albumin bilirubin (m-ALBI) grade 1. We concluded that LEN combined with TIT may improve prognosis compared with LEN monotherapy in patients with advanced-stage HCC.

Pseudo-capsulated Hepatocellular Carcinoma: Hepatic Arterial Infusion Chemotherapy Versus Transcatheter Arterial Chemoembolization

The effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) or transarterial chemoembolization (TACE) for cases with single pseudo-capsuled hepatocellular carcinoma (pHCC), as well as their survival outcomes, were investigated. A total of 196 cases with single pHCC (diameter >5cm) receiving initial HAIC (n=92) and TACE (n=104) were enrolled. The propensity score match (PSM) approach based on Cox models was employed to tune any possible imbalance in treatment assignment. The overall survival (OS), objective response rate (ORR), progression-free survival (PFS), and partial response rate (PRR) of the subjects were investigated using the log-rank test. The independent risk factors for outcomes were investigated by univariate and multivariate analyses, and the results were analyzed using the Cox regression model. The median follow-up of the subjects was 22.3 months. After PSM, no significant difference was found in the OS of the HAIC and TACE groups (OS, 12.0 vs. 16.8 months; P=.267), while the median PFS of the TACE group was prolonged compared with the HAIC group (PFS, 5.7 vs. 2.8 months; P=.003). Moreover, PRR and ORR of the TACE group were prolonged compared with the HAIC group (PRR, 34.6% vs. 21.7%; P=.046; ORR, 35.6% vs. 21.7%; P=.033). The nomogram model showed high predictive accuracy and significant discrimination. TACE therapy could delay tumor progression compared with HAIC for cases with a single pHCC.

Efficacy and safety of HepaSphere drug-eluting bead transarterial chemoembolization combined with hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma.

4122 Background: Transarterial chemoembolization (TACE) is widely applied and shows good efficacy in advanced hepatocellular carcinoma (HCC). Recently, hepatic arterial infusion chemotherapy (HAIC) has also gained popularity in the treatment of HCC. Several studies have described the comparison between HAIC and TACE or TACE combined with HAIC. However, the evaluation between TACE plus HAIC and HAIC is rarely reported. Here, we observed the performance of HepaSphere DEB-TACE combined with HAIC (Hepa-HAIC) comparing to HAIC in patients with advanced HCC. Methods: 167 patients diagnosed as advanced HCC and treated in Peking University Cancer Hospital from May 2018 to May 2022 were enrolled in this retrospective study, composed of 74 patients received HepaSphere DEB-TACE combined with HAIC-FOLFOX (Hepa-HAIC) and 93 patients received HAIC-FOLFOX. More than 60% patients experienced other treatments before the enrollment. To avoid the selection bias, propensity score matching (PSM) was conducted and applied for the efficacy and safety analysis between these two cohorts. The primary endpoints are progression-free survival (PFS) and overall survival (OS); the secondary endpoint includes objective response rate (ORR), disease control rate (DCR) and safety. Results: Propensity-matching yielded 48 pairs and the baselines were almost equal in Hepa-HAIC and HAIC cohorts after matching. Median PFS and median OS were both higher in matched Hepa-HAIC cohort (median PFS:8.9 vs. 5.8 months, P=0.035; median OS:22.4 vs. 9.5 months, P=0.027), which were consistent with pre-matching analysis. The ORR in Hepa-HAIC and HAIC cohorts was 75.0% and 37.5%, respectively; DCR was 93.8% after Hepa-HAIC and 81.3% after HAIC. There was no treatment-related death. Serious adverse events were similar in these two groups, except alanine aminotransferase (ALT) and vomiting. There was more frequency of Grade 3–4 ALT elevation in Hepa-HAIC (33.3% vs. 8.3%, P=0.003) while more incidence of vomiting in HAIC group (29.2% vs. 12.5%, P=0.044). Conclusions: All of the observed PFS, OS, ORR and DCR in Hepa-HAIC group are superior to HAIC group, which indicates the combination of HepaSphere DEB-TACE and HAIC may lead to improved outcomes with comparable safety profile in advanced HCC. [Table: see text]

Hepatic arterial infusion chemotherapy versus sorafenib for advanced hepatocellular carcinoma with portal vein tumor thrombus: An updated meta-analysis and systematic review.

Sorafenib was the first drug approved for advanced hepatocellular carcinoma (HCC). However, it is limited by poor efficacy for HCC with portal vein tumor thrombus (PVTT). Some studies suggested that hepatic artery infusion chemotherapy (HAIC) could provide survival benefits to patients with advanced HCC with PVTT. The study aimed to compare the efficacy of HAIC versus sorafenib in patients with HCC accompanied by PVTT. The PubMed, Embase, and Cochrane Library databases were searched for studies published until September 2022. Statistical analyses were performed using Stata SE 15 software. Eight studies with 672 patients, 403 in the HAIC group and 269 in the sorafenib group, were included in the meta-analysis. The rates of complete response (RR=3.88, 95%CI:1.35-11.16, P=0.01), partial response (RR=3.46, 95%CI:1.94-6.18, P<0.0001), objective response rate (RR=4.21, 95%CI:2.44-7.28, P<0.00001) and disease control rate (RR=1.73, 95%CI:1.28-2.35, P=0.0004) were significantly higher in the HAIC group compared to the sorafenib group, whereas the progressive disease rate (RR=0.57, 95%CI:0.40-0.80, P=0.02) was significantly lower in the former. In contrast, the stable disease rate (RR=1.10, 95%CI (0.69-1.76), P=0.68) was similar in both groups. The overall survival (HR=0.50, 95%CI:0.40-0.63, P<0.05) and progression-free survival (HR=0.49, 95%CI:0.35-0.67, P<0.05) rates were significantly higher in the HAIC group compared to the sorafenib group. HAIC has better efficacy against HCC with PVTT than sorafenib and may be considered an alternative to the latter. However, more high-quality randomized control trials and longer follow-ups are needed to verify our findings.

Analysis on Efficacy of Hepatic Artery Infusion Chemotherapy with or without Lenvatinib for Unresectable Hepatocellular Carcinoma

Introduction: For patients with advanced hepatocellular carcinoma (HCC), hepatic artery infusion chemotherapy (HAIC) is a common and mature treatment, but the safety and efficacy of HAIC combined with lenvatinib for advanced HCC patient treatment remains unclear. Therefore, this study compared the safety and efficacy of HAIC with or without lenvatinib in unresectable HCC patients. Methods: We retrospectively analyzed 13 unresectable advanced HCC patients who received HAIC monotherapy or combination therapy of HAIC and lenvatinib. Overall survival (OS), disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), incidence of adverse events (AEs), and changes in liver function were compared between the two groups. We applied a Cox regression analysis to evaluate the independent risk factors affecting survival outcomes. Results: The ORR in the HAIC+lenvatinib group was markedly increased compared to the HAIC group (p < 0.05), while the DCR in the HAIC group was higher (p > 0.05). No notable difference was found between the two groups in median OS and PFS (p > 0.05). Compared to the HAIC+lenvatinib group, more patients had improved liver function in the HAIC group after treatment, but the difference was not dramatical (p > 0.05). The AEs incidence was 100.00% in both groups, which was relieved with corresponding treatment. Besides, Cox regression analysis did not identify independent risk factors related to OS and PFS. Conclusion: Combination therapy of HAIC and lenvatinib notably performed better than the HAIC monotherapy in patients with unresectable HCC in terms of ORR and was well tolerated, which deserves further investigation with large-scale clinical trials.

HAIC versus TACE for patients with unresectable hepatocellular carcinoma: A systematic review and meta-analysis.

Hepatic arterial infusion chemotherapy (HAIC) and Transarterial chemoembolization (TACE) both showed good local efficacy in advanced or unresectable hepatocellular carcinoma (HCC). We performed a systematic review and meta-analysis to compare the effect of HAIC with TACE in patients with unresectable HCC. Clinical trials, which were about HAIC or TACE in Patients with unresectable HCC, were identified by searching PubMed, Medline, and EMBASE from January 2010 to March 2022. A meta-analysis was performed to analyze HAIC in comparison with TACE. Treatment response, 1-year overall survival (OS), 2-year OS and serious adverse events were evaluated in this meta-analysis. This meta-analysis included 6 studies. Objective response rate or Partial response in the HAIC group was significantly more than that in the TACE group (P < .05). But, stable disease showed no difference between the 2 groups (P = .52). Disease control rate in the HAIC group was better than that in the TACE group (P < .05). Progressive disease in the HAIC group was less than that in the TACE group (P < .05). In 1-year OS, there was no significant deterioration between the 2 groups (P = .53). There was not significant difference in 2-year OS between the 2 groups (P = .05). serious adverse events in the HAIC group was significantly less than that in the TACE group (P < .05). To some degree, HAIC may be a better therapeutic method in patients with unresectable HCC than TACE.

Hepatic arterial infusion chemotherapy and sequential ablation treatment in large hepatocellular carcinoma

Aim To investigate the individualized survival benefit of hepatic arterial infusion chemotherapy (HAIC) and sequential ablation treatment in large hepatocellular carcinoma (HCC) patients. Methods Between February 2016 and December 2020, a total of 228 HCC patients (diameter > 5 cm) who underwent HAIC alone (HAIC group, n = 135) or HAIC and sequential ablation (HAIC-ablation group, n = 93) treatment were reviewed. We applied the inverse probability of treatment weighting (IPTW) to adjust for potential bias of two treatment groups. The overall survival (OS) and progression-free survival (PFS) were compared with Kaplan–Meier curves. The Cox regression model was used to identify independent prognostic factors. And a prediction nomogram based on these independent prognostic factors was built, aiming to make probabilistic survival predictions and estimate personalized ablation benefits. Results After a median follow-up of 17.9 months, HCC patients in the HAIC-ablation group have longer significantly OS and PFS than those in the HAIC alone group (median OS: 22.2 months vs. 14.5 months; median PFS: 8.5 months vs. 4.6 months; both, p < 0.001). The IPTW-adjusted analysis revealed similar findings (both, p < 0.001). Tumor size, tumor number, and treatment modality were identified as independent prognostic factors for OS. The nomogram based on these factors showed favorable discrimination and well calibration. Conclusions HAIC and sequential ablation provided significant survival benefits in patients with large HCC. The nomogram could help predict individual survival probabilities and estimate personalized sequential ablation benefits.

Comparison of Arterial Infusion Chemotherapy and Chemoembolization for Locally Advanced Hepatocellular Carcinoma: a Multicenter Retrospective Study

BackgroundUnresectable hepatocellular carcinoma (HCC) has a poor prognosis. We aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) for locally advanced HCC compared to transcatheter arterial chemoembolization (TACE). MethodsA propensity score–matched cohort study was performed in patients with locally advanced HCC with ≥ 4 tumors or portal vein tumor thrombosis (PVTT) who underwent either HAIC using oxaliplatin plus raltitrexed or TACE at three institutions between June 2015 and December 2021. Overall survival (OS), progression-free survival (PFS), objective response rates (ORR), and adverse events (AEs) were compared between the groups. ResultsAfter propensity score matching, 62 pairs of patients were evaluated. The HAIC group had longer OS (15.0 [95% CI: 12.1–17.9] vs. 9.0 [95% CI: 5.1–12.9] months; P = 0.034), better PFS (6.7 [95% CI: 5.1–8.3] vs. 4.0 [95% CI: 2.6–5.4] months; P = 0.020), and a higher ORR (RECIST 1.1: 54.8% vs. 11.3%; P < 0.001) than the TACE group in the intention-to-treat population. Compared with the TACE group, Grade 1–2 nausea and vomiting occurred significantly more frequently in the HAIC group. ConclusionCompared to TACE, HAIC significantly increased the ORR of locally advanced HCC with multiple tumors or portal invasion and prolonged survival without causing a significant increase in severe AEs.

Hepatic arterial infusion oxaliplatin plus raltitrexedand chemoembolization in hepatocellular carcinoma with portal vein invasion: A propensity score-matching cohort study.

About 55% of hepatocellular carcinoma (HCC) cases in China are advanced HCC at the initial diagnosis. We aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) for HCC with portal vein tumor thrombosis (PVTT) compared to transcatheter arterial chemoembolization (TACE) after propensity score matching (PSM). A propensity score-matched cohort study was performed in patients with advanced HCC with PVTT who underwent either HAIC using oxaliplatin plus raltitrexed or TACE at three institutions between January 2016 and January 2021. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events were compared between the groups. After PSM, 44 pairs of patients were assessed. The HAIC group had longer OS (11.2 [95% confidence interval [CI]: 9.9-12.5] vs. 9.0 [95% CI: 5.3-12.7] months; p = 0.010), better PFS (5.6 [95% CI: 3.7-7.9] vs. 2.0 [95% CI: 1.3-2.7] months; p = 0.006), and a higher ORR (Response Evaluation Criteria in Solid Tumors [version 1.1]: 56.8% vs. 18.2%; p < 0.001) than the TACE group. In multivariate analysis, HAIC was identified as an independent favorable prognostic factor for survival. Compared to TACE, HAIC significantly increased the ORR of HCC with portal invasion and prolonged survival without causing a significant increase in severe adverse events.