UNASSIGNED: The prognosis of microsatellite stable (MSS)-colorectal cancer liver metastasis (CRCLM) following failure of multi-line therapy remains dismal. The aim of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus fruquintinib and tislelizumab (HAIC-F-T treatment) for MSS-CRCLM which failed from multiple-line therapy.
UNASSIGNED: From February 2021 to June 2023, 45 patients with MSS-CRCLM after failure of multiple-line therapy who received HAIC combined with fruquintinib and tislelizumab (HAIC-F-T triple treatment) were enrolled. The combination therapy included HAIC regimens with oxaliplatin and 5-fluorouracil or irinotecan, oxaliplatin, and 5-fluorouracil on days 1-2, intravenous tislelizumab (200 mg) before HAIC on day 1, and oral fruquintinb (3 mg/d) on day 3-21, every 4 weeks. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.
UNASSIGNED: The follow-up ended on June 22, 2024, with a median follow-up time of 17.5 months. The objective response rate was 42.2%, and the disease control rate was 82.2%. The median OS was 15.3 months (95% confidence interval [CI]:12.634-17.966), and the median PFS was 7.5 months (95% CI:5.318-9.682). The independent risk factors related to worse OS were previous PD-1 immunotherapy (P = 0.021) and the number of HAIC-F-T triple treatment cycles of ≤ 2 (P = 0.007). The incidence of grade 3 or higher adverse events (AEs) was 20%, with the most frequent grade 3 or higher AEs being abdominal pain (3/45, 6.7%).
UNASSIGNED: HAIC combined with fruquintinib and tislelizumab may be an alternative salvage treatment for patients with MSS-CRCLM following failure of multiple-line therapy.

UNASSIGNED: The prognosis of infiltrative hepatocellular carcinoma (HCC) is dismal. Hepatic arterial infusion chemotherapy (HAIC) plus Lenvatinib (Len) and immune checkpoint inhibitor (ICI) have shown promising results for HCC. However, this three combination therapy on infiltrative HCC is unknown. In this study, we compared HAIC plus lenvatinib (Len) and programmed cell death protein-1 (PD-1) inhibitor with HAIC plus Len for infiltrative HCC.
UNASSIGNED: This multi-center cohort study included patients with infiltrative HCC who received HAIC combined with Len (HAIC+Len group, n = 173) or HAIC combined with Len and PD-1 inhibitor (HAIC+Len+ICI group, n = 128) as the first-line treatment from January 2019 to December 2021. To balance any intergroup differences, one-to-one propensity score matching (PSM) was applied. Overall survival (OS) and progression-free survival (PFS) were compared between the two groups.
UNASSIGNED: After PSM, the median OS was 14.1 ± 1.0 and 16.1 ± 1.4 months in the HAIC+Len and HAIC+Len+ICI groups, respectively. The median PFS was 4.6 ± 0.4 months in the HAIC+Len group and 7.5 ± 0.8 months in the HAIC+Len+ICI group. The HAIC+Len+ICI group showed significantly better OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.90; P = 0.008) and PFS (HR, 0.53; 95% confident index [CI], 0.40-0.70; P < 0.001) compared with the HAIC+Len group. Subgroup analysis revealed that for OS in HCC without metastasis, the addition of PD-1 inhibitor was not significant (HR, 0.68; 95% CI, 0.43-1.07; P = 0.091). No difference was observed in OS between low (2-3 cycles) and high (4-6 cycles) level of HAIC cycles (HR, 0.99; 95% CI, 0.67-1.44; P = 0.938).
UNASSIGNED: The HAIC+Len+ICI group had a longer PFS and OS compared with the HAIC+Len group, demonstrating an acceptable safety profile. This triple combination strategy may be an alternative treatment for infiltrative HCC management.
The evidence of HAIC plus Len and PD-1 inhibitors for infiltrative HCC is limited. There was no study to evaluate the efficacy of HAIC combined with Len and PD-1 inhibitors for infiltrative HCC. In this study, we found that HAIC plus Len and PD-1 inhibitor (HAIC+Len+ICI) was associated with longer progression-free survival and overall survival than HAIC plus Len combination (HAIC+Len) for patient with infiltrative HCC. In addition, OS in patients with metastasis was improved with HAIC+Len+ICI treatment. OS in patients without metastasis, addition of PD-1 inhibitor after HAIC and Len was not beneficial. What’s more, three cycles of HAIC are adequate, especially for patients with high tumor burden, especially with main branch portal vein tumor thrombus (PVTT). Our research provides new evidence that HAIC+Len+ICI treatment significantly improved the OS and PFS of infiltrative HCC patients compared with those who received HAIC+Len treatment. It provides a strong reference for clinical treatment.

OBJECTIVE: This study aimed at ascertaining the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with donafenib versus HAIC alone in the treatment of unresectable hepatocellular carcinoma (HCC).
METHODS: Seventy HCC patients were enrolled for our study, and they were randomized by simple randomization using computer-generated random numbers into two groups: control group and observation group. Regular follow-up reviews were conducted to assess the efficacy of treatments. The levels of apoptotic factors, the levels of hepatic fibrosis indices, the levels of serum tumor vascular factors and tumor markers, and the occurrence of adverse reactions in the two groups were recorded and compared.
RESULTS: Disease control rate, objective response rate, and progression-free survival (PFS) of patients in the observation group were higher in contrast to the control group. After 12 weeks of treatment, lower mRNA expression of c-mesenchymal-epithelial transition factor, telomerase, and Fas Ligand and higher mRNA expression of Fas and Caspase-3 were observed in HCC tissues of the observation group versus the control group (p < 0.05); lower detection values of serum laminin, hyaluronic acid, collage type IV, vascular endothelial growth factor receptor 2, and alpha-fetal protein (AFP) were noted in HCC patients of the observation group in comparison to the control group (p < 0.05); there was no difference in the incidence of adverse reactions between the two groups.
CONCLUSIONS: Donafenib combined with HAIC in the treatment of unresectable HCC patients can notably reduce serum AFP levels, improve hepatic fibrosis, enhance short-term efficacy, prolong PFS, and have a favorable safety profile.

BACKGROUND: With the rapid progress of systematic therapy for hepatocellular carcinoma (HCC), therapeutic strategies combining hepatic arterial infusion chemotherapy (HAIC) with systematic therapy arised increasing concentrations. However, there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.
OBJECTIVE: To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.
METHODS: A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study. The outcomes of interest comprised overall survival (OS), progression-free survival (PFS), tumor response and adverse events. Hazard ratios (HR) and odds ratios (OR) with a 95% confidence interval (CI) were calculated and agents were ranked based on their ranking probability.
RESULTS: HAIC outperformed Sorafenib (HR = 0.55, 95%CI: 0.42-0.72; HR = 0.51, 95%CI: 0.33-0.78; OR = 2.86, 95%CI: 1.37-5.98; OR = 5.45, 95%CI: 3.57-8.30; OR = 7.15, 95%CI: 4.06-12.58; OR = 2.89, 95%CI: 1.99-4.19; OR = 0.48, 95%CI: 0.25-0.92, respectively) and transarterial chemoembolization (TACE) (HR = 0.50, 95%CI: 0.33-0.75; HR = 0.62, 95%CI: 0.39-0.98; OR = 3.08, 95%CI: 1.36-6.98; OR = 2.07, 95%CI: 1.54-2.80; OR = 3.16, 95%CI: 1.71-5.85; OR = 2.67, 95%CI: 1.59-4.50; OR = 0.16, 95%CI: 0.05-0.54, respectively) in terms of efficacy and safety. HAIC + lenvatinib + ablation, HAIC + ablation, HAIC + anti- programmed cell death 1 (PD-1), and HAIC + radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone. HAIC + TACE + S-1, HAIC + lenvatinib, HAIC + PD-1, HAIC + TACE, and HAIC + sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC. HAIC + PD-1, HAIC + TACE + S-1 and HAIC + TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.
CONCLUSIONS: HAIC proved more effective and safer than sorafenib and TACE. Furthermore, combined with other interventions, HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

BACKGROUND: Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib (TRIPLET protocol) is promising for advanced hepatocellular carcinoma (Ad-HCC). However, the usefulness of microwave ablation (MWA) after TRIPLET is still controversial.
OBJECTIVE: To compare the efficacy and safety of TRIPLET alone (T-A) vs TRIPLET-MWA (T-M) for Ad-HCC.
METHODS: From January 2018 to March 2022, 217 Ad-HCC patients were retrospectively enrolled. Among them, 122 were included in the T-A group, and 95 were included in the T-M group. A propensity score matching (PSM) was applied to balance bias. Overall survival (OS) was compared using the Kaplan-Meier curve with the log-rank test. The overall objective response rate (ORR) and major complications were also assessed.
RESULTS: After PSM, 82 patients were included both the T-A group and the T-M group. The ORR (85.4%) in the T-M group was significantly higher than that (65.9%) in the T-A group (P < 0.001). The cumulative 1-, 2-, and 3-year OS rates were 98.7%, 93.4%, and 82.0% in the T-M group and 85.1%, 63.1%, and 55.0% in the T-A group (hazard ratio = 0.22; 95% confidence interval: 0.10-0.49; P < 0.001). The incidence of major complications was 4.9% (6/122) in the T-A group and 5.3% (5/95) in the T-M group, which were not significantly different (P = 1.000).
CONCLUSIONS: T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

UNASSIGNED: This study aims to explore the analgesic effect of lidocaine administered through the hepatic artery during hepatic artery infusion chemotherapy (HAIC) for hepatocellular carcinoma (HCC).
UNASSIGNED: A total of 45 HCC patients were randomly divided into a study group and a control group. Both groups received oxaliplatin (OXA) based FOLFOX protocol via electronic infusion pump. The study group was continuously infused with 100 mg of lidocaine during HAIC, while 5% glucose solution was infused in the same way as described above. Changes in vital signs, visual analogue score (VAS) and general comfort score (GCQ scale) were recorded before surgery (Time point 0), at the end of infusion (Time point 01), 1 h after HAIC (Time point 02), 3 h after HAIC (Time point 03) and 6 h after HAIC (Time point 04).
UNASSIGNED: At each point of time from Time point 0 through Time point 04, the differences in MAP, RR and SPO2 between the two groups were not statistically significant (P > 0.05). At each point of time from Time point 01 through Time point 04, the mean VAS scores in the study group were smaller and GCQ scores were higher than those in the control group, and the differences were both statistically significant (P < 0.05).
UNASSIGNED: Lidocaine infusion through the hepatic artery during HAIC effectively reduces intraoperative and postoperative pain and improves patient satisfaction with pain management, making it a valuable technique for clinical practice.

UNASSIGNED: This study aimed to assess the clinical efficacy and safety of the combined approach involving hepatic arterial infusion chemotherapy (HAIC) and tyrosine kinase inhibitors (TKIs) for the treatment of advanced hepatocellular carcinoma (HCC).
UNASSIGNED: In this multicenter retrospective study conducted from January 2020 to December 2023, we reviewed advanced HCC patients who were treated either with HAIC alone or with a combination of HAIC and TKIs. To address initial disparities between the two groups, we employed propensity score matching (PSM). Tumor response evaluation was performed following RECIST 1.1 criteria. We compared survival outcomes, including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), between the two treatment groups. Safety assessments were conducted for all patients.
UNASSIGNED: Following the eligibility review, 138 patients underwent combined treatment with HAIC and TKIs (HT group), while 198 patients received HAIC monotherapy (HA group) and met the inclusion criteria for enrollment in this study. After PSM, 107 patients were assigned to each group. The HT group exhibited a longer median OS (18.0 versus 8.8 months; hazard ratio [HR], 0.52, p < 0.001) compared to the HA group. Median PFS was also longer in the HT group, although without statistical significance (6.0 versus 4.7 months; HR, 0.85, p = 0.265). The HT group demonstrated a higher ORR (41.1% versus 25.2%; p = 0.020). No significant differences were observed between the two groups in the incidence of all adverse events (AEs) or grade 3/4 AEs (any grade: 81.2% for HT versus 78.8% for HA, p = 0.68; grade 3/4: 18.1% for HT versus 13.6% for HA, p = 0.29). Importantly, all AEs were manageable and acceptable. Notably, no grade 5 AEs occurred in either group.
UNASSIGNED: Combination therapy involving HAIC and TKIs effectively prolonged survival in advanced HCC patients. It represented a preferable alternative to HAIC monotherapy, with manageable safety.

OBJECTIVE: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) in combination with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with large unresectable intrahepatic cholangiocarcinoma (uICC).
METHODS: From November 2019 to December 2022, 21 large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor were retrospectively enrolled. Local tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AEs were evaluated by the common terminology criteria for adverse events (CTCAE) version 5.0.
RESULTS: After a median follow-up duration of 16.0 months (range 5-43.5 months), 17 patients had died. The median OS was 19.5 months (range 9-43.5 months), and the median PFS was 6.0 months (range 2.5-38.5 months). The 1-, 2-, and 3-year OS rates were 71.4 %, 42.9 %, and 19.0 %, respectively. The 1-, 2-, and 3-year PFS rates were 33.3 %, 19.0 %, and 9.5 %, respectively. Complete response, partial response, stable disease, and progressive disease were observed in 0 (0 %), 11 (52.3 %), 5 (23.8 %), and 5 (23.8 %) patients, respectively. The disease control rate and objective response rate were 76.1 % and 52.3 %, respectively. None of the enrolled patients experienced grade 5 AEs.
CONCLUSIONS: GEMOX-HAIC plus GEM-SYS in combination with lenvatinib and PD-1 inhibitor was effective and well tolerated for patients with large uICC.

BACKGROUND: In 2021, the LEOPARD trial reported that the combination of lenvatinib+one-shot cisplatin infusion might contribute to improving the results of conventional advanced hepatocellular carcinoma (HCC) treatment. Thus, combination therapy with lenvatinib and catheterization has emerged as a focal point in treating advanced HCC. Conversely, the New FP regimen consists of low-dose cisplatin (CDDP) combined with 5-fluorouracil (5-FU) and lipiodol via hepatic arterial infusion chemotherapy (HAIC), with a high response rate of approximately 70%. Therefore, lenvatinib+New FP (LEN-New FP) may be a more promising treatment for HCC. Here, we report six patients who were administered LEN+New FP and achieved high therapeutic efficacy. Among them, one case had an interesting clinical course, which has been described in detail.
METHODS: This study included six patients who were administered 12 mg or 8 mg of lenvatinib once daily based on a body weight of ≥60 kg or <60 kg, respectively, along with 50 mg of cisplatin in 5-10 mL lipiodol, and a continuous infusion of 5-FU (1500 mg/5 days) infused every 2-4 weeks. Tumor evaluations were performed 4-8 weeks after the initiation of New FP administration and every 8-12 weeks thereafter.
RESULTS: The median patient age was 65 years. All patients had a history of prior treatment with atezolizumab and bevacizumab and one of the factors associated with poor overall survival for New FP monotherapy, such as a maximum tumor diameter ≥7 cm and bilobular multifocal distribution. Four (67%) patients had severe vascular invasion. The best objective response and disease control rates were 83% and 100%, respectively. The best response of the target lesion was complete remission in four out of six patients.
CONCLUSIONS: The LEN-New FP combination for advanced HCC showed a high response rate and was more effective in high-risk patients with factors associated with poor overall survival than that reported with conventional New FP monotherapy. Additionally, LEN-New FP exhibited extremely high objective response and disease control rates and was well tolerated, including in cases where it was considered second- or third-line systemic chemotherapy for advanced HCC. Thus, LEN-New FP can serve as a breakthrough therapy for advanced HCC based on appropriate case selection.

BACKGROUND: Locoregional treatment with transarterial chemoembolization (TACE) or hepatic artery infusion chemotherapy (HAIC) and systemic targeted immunotherapy with tyrosine kinase inhibitors (TKI) and programmed cell death protein-1 (PD-1) inhibitors in the treatment of unresectable hepatocellular carcinoma (uHCC) have achieved promising efficacy. The retrospective study aimed to evaluate the efficacy and safety of TACE and HAIC plus TKI with or without PD-1 for uHCC.
METHODS: From November 2020 to February 2024, the data of 44 patients who received TACE-HAIC + TKI + PD-1 (THKP group) and 34 patients who received TACE-HAIC + TKI (THK group) were retrospectively analyzed. Primary outcomes were overall survival (OS) and progress-free survival (PFS), and secondary outcomes were objective response rate (ORR), disease control rate (DCR), conversion rates, and adverse events (AEs).
RESULTS: A total of 78 patients were recruited in our single-center study. The patients in THKP group had prolonged median OS [25 months, 95% confidence interval (CI) 24.0-26.0 vs 18 months, 95% CI 16.1-19.9; p = 0.000278], median PFS [16 months, 95% CI 14.1-17.9 vs 12 months 95% CI 9.6-14.4; p = 0.004] and higher ORR (38.6% vs 23.5%, p = 0. 156) and DCR (88.6% vs 64.7%, p = 0.011) compared with those in THK group. Multivariate analysis showed that treatment option and alpha-fetoprotein (AFP) level were independent prognostic factors of OS and PFS. The frequency of AEs were similar between the two groups.
CONCLUSIONS: The THKP group had better efficacy for uHCC than the THK group, with acceptable safety.