With the rise of anti-vascular endothelial growth factor antibody and programmed cell death-ligand 1 (PD-L1) regimens, particularly bevacizumab and atezolizumab, as first-line treatments for advanced hepatocellular carcinoma (HCC), there is a need to explore PD-L1 and programmed cell death 1 inhibitors in combination therapies for unresectable HCC (uHCC). Integrating systemic therapies with locoregional approaches is also emerging as a potent strategy. This study compares the outcomes of atezolizumab (PD-L1 inhibitor) and sintilimab (programmed cell death 1 inhibitor) with bevacizumab or its biosimilar, combined with hepatic arterial interventional therapies (HAIT) in uHCC patients. From January 2020 to September 2023, a retrospective analysis was conducted on 138 uHCC patients at Sun Yat-sen University Cancer Center. The cohort included 69 patients treated with atezolizumab with bevacizumab (Bev/Ate) and 69 with bevacizumab biosimilar with sintilimab (Bio/Sin), combined with HAIT. The propensity score matching was also employed to further explore the efficacy and safety. The median progression-free survival (mPFS) was 13.8 months for the Bev/Ate group and 10.0 months for the Bio/Sin group (p = 0.188). The Bev/Ate group showed significantly longer intrahepatic mPFS (HR 0.381; 95% confidence interval 0.176-0.824; p = .018) and higher overall response rates compared with the Bio/Sin group (60.87% vs. 31.88%, p = .001; 69.57% vs. 49.28%, p = .024) based on Response Evaluation Criteria in Solid Tumors v1.1 and modified Response Evaluation Criteria in Solid Tumors criteria. Treatment-related adverse events were similar between groups (p > .050). Combining atezolizumab or sintilimab with bevacizumab or its biosimilar alongside HAIT provided similar overall PFS in uHCC patients. However, the atezolizumab-bevacizumab combination with HAIT showed superior intrahepatic PFS and control rates, warranting further validation.

 Combining local interventions with tyrosine kinase inhibitors (TKIs) plus anti-PD-1 antibodies in a triple therapy has demonstrated remarkable anti-tumor efficacy and facilitated conversion resection in patients with initially unresectable hepatocellular carcinoma (HCC). However, the long-term survival outcomes remain largely unexplored. This study focused on a cohort of consecutive patients who underwent triple therapy for initially unresectable HCC at the authors' hospital between January 2020 and December 2022. Specifically, patients who exhibited a positive response to triple therapy and fulfilled the criteria for hepatectomy were selected for liver resection. Additionally, investigation assessed association between clinical factors and successful achievement of conversion resection, as well as postoperative recurrence. The study cohort comprised 79 patients, among whom 20 individuals (25.3%) underwent R0 resection subsequent to the initiation of triple therapy. Notably, patients without extrahepatic disease and those who exhibited a radiographic response to triple therapy were more likely to be eligible for curative resection. Importantly, hepatectomy independently associated with a favorable overall survival (HR, 0.388; 95% CI, 0.177-0.847; P = 0.017). Other independent risk factors related to overall survival contained extrahepatic metastasis (HR, 2.152; 95% CI, 1.076-4.302; P = 0.030), tumor number ≥ 4 (HR, 2.058; 95% CI, 1.001-4.234; P = 0.049) and radiological remission (HR, 0.233; 95% CI, 0.071-0.768; P = 0.017). For the 20 patients who underwent surgery, 12-month recurrence-free survival and overall survival rates were respectively 43.3% and 66.6%. The triple therapy demonstrated favorable prognostic outcomes and manageable safety profiles in patients with initially unresectable HCC.

This study aimed to evaluate the effectiveness of combining hepatic arterial infusion chemotherapy (HAIC) with lenvatinib and programmed cell death protein 1 (PD-1) inhibitors in the treatment of advanced, unresectable hepatocellular carcinoma (HCC).

A comprehensive search across multiple databases was conducted to identify relevant studies published up to May 2024. This search focused on clinical trials investigating the combination of HAIC with lenvatinib and PD-1 inhibitors for the treatment of advanced HCC. Data from these trials were analyzed using either fixed-effects or random-effects models, with results reported as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). To evaluate the robustness of the findings, trial sequential analysis was employed.

A total of 8 cohort studies encompassing 1073 patients with unresectable HCC were included. Compared with other treatment regimens, the combined use of HAIC, lenvatinib, and PD-1 inhibitors significantly improved overall survival (OS) (HR=0.53 [95% CI 0.45, 0.63], P<0.00001), progression-free survival (PFS) (HR 0.56 [95% CI 0.46, 0.61], P<0.0001), the objective response rate (ORR) (RR=1.82 [95% CI 1.52, 2.18], P<0.00001), and the disease control rate (DCR) (RR=1.24 [95% CI 1.16, 1.33], P<0.00001). Trial sequential analysis (TSA) results indicated that the existing data were sufficient for making quantitative conclusions about the ORR and DCR.

Combining HAIC with lenvatinib and PD-1 inhibitors enhances the effectiveness of treatment for unresectable HCC. This approach is particularly beneficial for patients who have a high tumor burden or those who are refractory to transarterial chemoembolization (TACE), providing a more effective solution for these challenging cases.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024575853, identifier CRD42024575853.

Local treatment may function synergistically with immunotherapy and targeted agents. This study aimed to assess the effectiveness and safety of transcatheter arterial chemoembolization (TACE) and hepatic artery infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and programmed death-1 (PD-1) inhibitors in patients with initially unresectable hepatocellular carcinoma (uHCC).

A retrospective study was conducted on patients diagnosed with initially uHCC who received combined treatment of TACE-HAIC combined with TKIs and PD-1 inhibitors from July 2020 to February 2023. The primary endpoints were overall survival (OS) and progression free survival (PFS) and adverse events (AEs). Objective response rate (ORR), disease control rate (DCR) and conversion surgery rate (CSR), whereas the secondary endpoints.

After screening, a total of 62 patients were selected for this study. The overall median OS was 18.2 (95% CI 16.24-20.16) months and median PFS was 9.2 (95% CI 7.24-11.16) months. Based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and RECIST v1.1 criteria, ORR was 67.7% (42/62), and the DCR was 90.3% (56/62), the CSR was 27.4% (17/62). The most common treatment-emergent adverse events (TEAEs) were transaminitis (56.4%, 35/62), nausea and vomiting (43.5%, 27/62), thrombocytopenia (37.1%, 23/62), abdominal pain (33.9%, 21/62), and fever (33.9%, 21/62).

TKIs combined with PD-1 inhibitors plus TACE-HAIC therapy represents an effective and tolerable treatment option in patients with uHCC. Patients undergoing surgery after combination therapy may have survival benefits.

Systemic conversion therapy provides patients with initially unresectable hepatocellular carcinoma (HCC) the chance to salvage radical liver resection and superior survival outcomes, but the optimal conversion strategy is unclear.

A systematic literature search was conducted on PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library between 2007 and 2024 focusing on studies reporting conversion therapy for HCC. The treatment groups were divided into Tyrosine kinase inhibitors (TKI), TKI plus loco-regional therapy (LRT), TKI plus anti-PD-1 therapy (TKI + PD-1), TKI + PD-1 + LRT, immune checkpoint inhibitors (ICI) plus LRT, and Atezolizumab plus bevacizumab (A + T) groups. The conversion to surgery rate (CSR), objective response rate (ORR), grade ≥ 3 treatment-related adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were analyzed.

38 studies and 4,042 patients were included. The pooled CSR were 8% (95% CI, 5-12%) in TKI group, 13% (95% CI, 8-19%) in TKI + LRT group, 28% (95% CI, 19-37%) in TKI + PD-1 group, 33% (95% CI, 25-41%) in TKI + PD-1 + LRT group, 23% (95% CI, 1-46%) in ICI + LRT group, and 5% (95% CI, 3-8%) in A + T group, respectively. The pooled HR for OS (0.45, 95% CI, 0.35-0.60) and PFS (0.49, 95% CI, 0.35-0.70) favored survival benefit of conversion surgery. Subgroup analysis revealed that lenvatinib + PD-1 + LRT conferred higher CSR of 35% (95% CI, 26-44%) and increased ORR of 70% (95% CI, 56-83%).

The current study indicates that TKI + PD-1 + LRT, especially lenvatinib + PD-1 + LRT, may be the superior conversion therapy with a manageable safety profile for patients with initially unresectable HCC. The successful conversion therapy favors the superior OS and PFS compared with systemic treatment alone.

International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289).

This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab.

A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a >20% decrease in AFP within 4 weeks, and AFP response as a >75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated.

The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p<0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p<0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333-6.585, p=0.008, and HR 6.182, 95% CI 1.780-21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107-4.318, p=0.024, and HR 3.078, 95% CI 1.407-6.730, p=0.005), serving as significant prognostic values.

Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.

Comparing the efficacy and safety of programmed cell death protein-1 (PD-1) inhibitors combined with tyrosine kinase inhibitors (TKIs) with or without hepatic artery infusion chemotherapy (HAIC) in HBV-related advanced HCC and exploring prognostic predictors of the combined regimen.

A total of 194 patients diagnosed with HBV-related advanced HCC between 2020 and 2022 were included in the study, including 99 in the HAIC combined with PD-1 inhibitors plus TKIs (HPT group) and 95 in the PD-1 inhibitors plus TKIs (PT group). The efficacy was evaluated according to the tumor response rate and survival, and the safety was evaluated according to the adverse events.

The HPT group showed higher overall response rate and disease control rate than the PT group. The median overall survival (OS) of the HPT group and the PT group were 18.10 months and 12.57 months, respectively, and the difference was statistically significant (hazard ratio (HR) = 0.519, 95% confidence interval (CI): 0.374-0.722, P < 0.001). The median progression-free survival (PFS) was 9.20 months in the HPT group and 6.33 months in the PT group (HR = 0.632, 95% CI: 0.470-0.851, P = 0.002). In addition, albumin bilirubin (ALBI) and systemic inflammatory response index (SIRI) are independent prognostic factors affecting HAIC combined with targeted immunotherapy and can be used as prognostic predictors. Almost all patients included in the study experienced treatment-related adverse events (TRAEs) of varying degrees of severity, with grade 1-2 adverse events predominating.

The HPT group had better OS and PFS than the PT group in patients with HBV-related advanced HCC. In addition, high ALBI and high SIRI were associated with poor prognosis in the HAIC combined group.

Combination therapy is the primary treatment for unresectable hepatocellular carcinoma (u-HCC). The hepatic functional reserve is also critical in the treatment of HCC. In this study, u-HCC was treated with combined hepatic arterial infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKIs), and programmed cell death protein-1 (PD-1) inhibitors to analyze the therapeutic response, progression-free survival (PFS), and safety.

One hundred sixty-two (162) patients with u-HCC were treated by combination therapy of HAIC, TKIs, and PD-1 inhibitors. PFS was assessed by Child-Pugh (CP) classification subgroups and the change in the CP score during treatment.

The median PFS was 11.7 and 5.1 months for patients with CP class A (CPA) and CP class B (CPB), respectively (p = 0.013), with respective objective response rates of 61.1 and 27.8% (p = 0.002) and conversion rates of 16 and 0% (p = 0.078). During treatment, the CP scores in patients with CPA worsened less in those with complete and partial response than in those with stable and progressive disease. In the CP score 5, patients with an unchanged CP score had longer PFS than those with a worsened score (Not reached vs. 7.9 months, p = 0.018). CPB was an independent factor negatively affecting treatment response and PFS. Patients with CPA responded better to the combination therapy and had fewer adverse events (AEs) than those with CPB.

Thus, triple therapy is more beneficial in patients with good liver function, and it is crucial to maintain liver function during treatment.

Patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) present a poor prognosis. Current systemic therapies offer limited benefits. Hepatic artery infusion chemotherapy (HAIC) is a local regional treatment for advanced HCC, particularly in selected patients such as patients with PVTT or high intrahepatic tumor burden.

The purpose of this study is to retrospectively evaluate the efficacy and safety of HAIC combined with anti-PD-1 immunotherapy for HCC patients with PVTT, and explore factors related to survival prognosis, providing clues for treatment decisions for HCC patients.

This is a single-center retrospective study conducted over 2 years on consecutive PVTT patients receiving HAIC combined anti-PD-1 antibodies.

The primary endpoint was overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors affecting OS. Treatment-associated adverse events were evaluated as well.

A total of 119 patients were analyzed. The median OS and PFS were 14.9 months and 6.9 months. A total of 31.1% of grade 3-4 adverse events were reported, with elevated transaminase and total bilirubin being the most common. The independent variables correlated with survival include treatment-related alpha-fetoprotein (AFP) response, the presence of extrahepatic organ metastasis, absolute value of platelet (PLT), neutrophil-to-lymphocyte ratio, and combined usage of tyrosine kinase inhibitors (TKIs).

In HCC patients with PVTT, combination therapy with HAIC and anti-PD-1 antibodies might be a promising therapy. The efficacy and safety of this combination protocol on patients with HCC complicated by PVTT warrants further investigation prospectively, especially in combination with TKIs.

Research has shown that locoregional and/or systemic treatments can reduce the tumor stage, enabling radical surgical resection in patients with initially unresectable hepatocellular carcinoma. This is referred to as conversion therapy. Patients who undergo conversion therapy followed by curative surgery experience a significant survival benefit compared to those who receive chemotherapy alone, those who are successfully downstaged with conversion therapy but not treated with surgery, or those who are treated with upfront surgery. Several treatments have been studied as conversion therapy. However, the success rate of conversion varies greatly, ranging from 0.8% to 60%. Combined locoregional plus systemic conversion therapy has demonstrated significant clinical advantages, with a conversion rate of up to 60%, an objective remission rate of 96% for patients, and a disease control rate of up to 100%. However, patients who underwent conversion therapy experienced significantly more complications than those who underwent direct LR without conversion therapy. Conversion therapy can cause hepatotoxicity, bone marrow suppression, local adhesions, increased fragility of blood vessels and liver tissues, and hepatic edema, which can increase the difficulty of surgery. In addition, criteria need to be established to evaluate the efficacy of conversion therapy and subsequent treatment. Further clinical evidence in this area is urgently needed.

To assess the effectiveness and safety of transarterial chemoembolization (TACE) in combination with hepatic artery infusion chemotherapy (HAIC)、PD-1 inhibitors, and tyrosine kinase inhibitors(TKI) for unresectable hepatocellular carcinoma (HCC).

A retrospective analysis was performed on 158 unresectable HCC patients admitted to the First Affiliated Hospital of Nanchang University between May 2019 and October 2022. The patients were split into two groups based on the type of treatment they received: TACE combined with HAIC,PD-1 and TKI group (THPK) and TACE combined with PD-1 and TKI group (TPK). The response was evaluated using modified solid tumor Efficacy Assessment Criteria (mRECIST). Kaplan-Meier curves were used to analyze the overall survival (OS). OS-influencing factors were identified using the Cox proportional risk regression model.

Finally, 63 patients who received THPK treatment and 60 patients who had TPK treatment were included. The THPK group had higher DCR (77.78% vs. 55.00%, P=0.007) and ORR (20.63% vs. 13.34%, P=0.282) than the TPK group did. The survival analysis curve also showed that the median OS was substantially longer in the THPK group than in the TPK group (OS: 21 months vs. 14 months, P=0.039). After multivariate Cox regression-corrected analysis, extrahepatic metastases (P=0.002) and methemoglobin >400 (P=0.041) were adverse influences on OS, but the THPK group (relative to the TPK group) was an independent favorable prognostic factor for OS (P=0.027). The results of the subgroup analysis showed that the addition of HAIC therapy to TPK treatment in patients with BCLC stage C, age ≦60 years, ECOG grade 0 and lobular distribution of tumors prolonged overall survival time and improved prognosis. Except for nausea, there was no difference in the adverse events between the two groups.

In patients with unresectable HCC, the THPK group had a longer OS and similar adverse events compared to the TPK group. In the future, TACE-HAIC in combination with targeted and immunotherapy may be a more effective therapeutic option for hepatocellular carcinoma that cannot be surgically removed.

Triple combination conversion therapy, involving transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), has shown an encouraging objective response rate (ORR) and successful conversion surgery rate in initially unresectable hepatocellular carcinoma (HCC). However, the safety and long-term survival outcomes of subsequent liver resection after successful conversion still remain to be validated. From February 2019 to February 2023, 726 patients were enrolled in this retrospective study (75 patients received hepatectomy after conversion therapy [CLR group], and 651 patients underwent pure hepatectomy [LR group]). Propensity score matching (PSM) was used to balance the preoperative baseline characteristics. After PSM, 68 patients in the CLR group and 124 patients in the LR group were analyzed, and all the matching variables were well-balanced. Compared with the LR group, the CLR group experienced longer Pringle maneuver time, longer operation time, and longer hospital stays. In addition, the CLR group had significantly higher incidence rates of intra-abdominal bleeding, biliary leakage, post-hepatectomy liver failure (PHLF), and Clavien-Dindo grade IIIa complications than the LR group. There were no significant statistical differences in overall survival (OS) (hazard ratio [HR] 0.724; 95% confidence interval [CI] 0.356-1.474; p = 0.374) and recurrence-free survival (RFS) (HR 1.249; 95% CI 0.807-1.934; p = 0.374) between the two groups. Liver resection following triple combination conversion therapy in initially unresectable HCC may achieve favorable survival outcomes with manageable safety profiles; presenting as a promising treatment option for initially unresectable HCC.

To investigate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with PD-(L)1 inhibitors and molecular targeted therapies (MTT) for intermediate and advanced HCC that are unsuitable for transarterial chemoembolization (TACE).

We conducted a retrospective analysis of data from patients with TACE-unsuitable HCC who were receiving triple therapy from January 2020 to December 2021 at two medical centers. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS), objective response rates (ORR), disease control rates (DCR), and incidence of adverse events (AEs).

A total of 55 patients were enrolled in the study with median treatment periods of 4 and 6 for HAIC and PD-(L)1 inhibitors, respectively. The median OS and PFS were 15.0 and 10.0 months, respectively, with a median follow-up of 11.0 months (range: 4.0-27.5 months). According to the mRECIST criteria, the optimal ORR was 43.6% (24/55) and the DCR was 61.8% (34/55). The incidence of AEs was 58.2%, with grade 3 and above accounting for 20.0%; elevated AST (18.2%), hyperbilirubinemia (16.4%), and thrombocytopenia (16.4%) were most common. There were no treatment-related fatalities and all AEs were effectively managed. Multifactorial analysis showed that NLR > 3.82 (HR 2.380, 95% CI 1.116-2-5.079, P = 0.025), ECOG 1 (HR 2.906, 95% CI 1.373-6.154, P = 0.005), and extrahepatic metastases (HR 8.373, 95% CI 3.492-20.078, P < 0.001) were associated with the median OS.

Triple therapy with HAIC, PD-(L)1 inhibitors, and MTT was safe and effective for patients with intermediate and advanced HCC for TACE-unsuitability.

At present, hepatic arterial infusion chemotherapy (HAIC) for the treatment of hepatocellular carcinoma (HCC) is often applied to patients who are not suitable or are unwilling to undergo surgical treatment. However, to the best of our knowledge, the efficacy and safety of HAIC combined with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in HCC have not been fully demonstrated. Published studies involving the treatment of patients with HCC with HAIC, ICIs and TKIs were searched from public databases, including PubMed, Embase, the Cochrane Library and Sinomed. Efficacy and safety data for each study, including progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were collected. The present study included 17 treatment groups from 15 studies, including 1,987 patients with HCC in the systematic review. The target population was dominated by those unsuitable for surgical treatment, with Barcelona Clinic Liver Cancer stage B or C, Eastern Cooperative Oncology Group performance status ≤2 and Child-Pugh score A or B. The results showed that the longest estimated median PFS (95% CI) in the HAIC + ICI/TKI therapy group (group C) was 9.37 months (95% CI, 6.81-11.93); in the HAIC therapy group (group B) was 7.45 months (95% CI, 6.45-8.46); and in the ICIs + other systemic therapies group (group A) was 5.92 months (95% CI, 5.31-6.54). There was no significant difference in the expected OS among the three groups, which may be because OS events were not reached in numerous studies during the follow-up time. The incidence of treatment-related adverse effects, such as increased AST [14/221 (6.33%)], increased ALT [13/221 (5.88%)], and decreased platelet count [13/221 (5.88%)], was not significantly increased in group C when compared with groups A or B (P>0.05). In conclusion, the effectiveness of HAIC + ICI/TKI for the treatment of advanced HCC was better than that of ICIs + other systemic therapies or HAIC alone. In addition, the incidence of AEs above grade 3 was not significantly higher compared with that in the other treatment groups, and the safety profile was good.

This study aimed to assess the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with unresectable hepatocellular carcinoma (u-HCC) treated with hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab.

We conducted a retrospective cohort study involving patients diagnosed with u-HCC who underwent HAIC combined with lenvatinib and camrelizumab. Patients were stratified into two cohorts using the median NLR as the cutoff point. We then assessed treatment response, overall survival (OS), progression-free survival (PFS), and adverse events in these patient groups.

Between October 2020 and April 2022, a total of 88 patients were enrolled in the study. The overall cohort exhibited a median PFS of 7.9 months, while the median OS was not reached, and a median NLR of 3.46. Notably, the group with NLR<3.46 demonstrated significantly superior OS (not reached vs 9.6 months, p = 0.017) and PFS (18.3 vs 5.3 months, p = 0.0015) compared to the NLR≥3.46 group. Furthermore, multivariate analysis revealed that an alpha-fetoprotein (AFP) ≥ 400 ng/mL [hazard ratio (HR), 2.133; 95% confidence interval (CI), 1.102-4.126; p = 0.024], Barcelona Clinical Hepatocellular Carcinoma (BCLC) stage C (HR, 2.319; 95% CI, 1.128-4.764; p = 0.022), and NLR ≥3.46 (HR, 2.35; 95% CI, 1.239-4.494; p = 0.009) were identified as independent risk factors for OS. Additionally, multivariate analysis demonstrated that AFP ≥ 400 ng/mL, BCLC stage C, and NLR ≥ 3.46 were independent negative factors of PFS.

NLR can be associated with outcomes in patients with u-HCC treated with HAIC combined with lenvatinib and camrelizumab.

The triple combination of hepatic arterial infusion chemotherapy (HAIC) with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) plus tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitors (ICIs) is expected to have a synergistic anticancer effect in HCC. We conducted this meta-analysis to evaluate the efficacy and safety of the triple combination treatment in advanced HCC patients.

PubMed, Embase, Cochrane Library, Web of Science databases were systematically searched for relevant studies from the inception of each database to May 10, 2023. All articles focusing the triple combination treatment of HAIC-FO plus TKI and ICIs for advanced HCC were eligible. The meta-analysis was conducted following the PRISMA guidelines. The risk of bias was assessed using the Joanna Briggs Institute (JBI) for case series and Newcastle-Ottawa Scale (NOS) for cohort studies. The primary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). The secondary results were adverse events. Further meta-analysis of control studies demonstrated the superiority of the triple combination modality to TKI plus ICIs, and TKI alone.

Nine articles (four cohort studies and five one-arm studies) involving 777 advanced HCC patients were included in this meta-analysis. In terms of survival analysis, the pooled median PFS was 11 months (95% CI: 10.1-12.0 months) with low heterogeneity (I2 = 0%, p = 0.97). With regard to tumor response, the pooled ORR and DCR was 61.6% (I2=0%, p = 0.71) and 87.9% (I2 = 13%, p = 0.33) with low heterogeneity, respectively. As compared with TKIs plus ICIs, and TKIs alone, the triple combination thrapy was associated with improved median OS (HR=0.51, 95%CI 0.41-0.62) with low heterogeneity across studies (I2 = 0%, p = 0.47), median PFS (HR=0.51, 95%CI 0.41-0.64) with low heterogeneity across studies (I2 = 0%, p = 0.41), ORR (RR = 0.56, 95% CI: 0.42-0.74) with high heterogeneity across studies (I2 = 69%, p = 0.02), and DCR (RR = 0.38, 95%CI 0.27-0.54) with low heterogeneity across studies (I2 = 14%, p = 0.32). The most common 3/4 AEs were elevated ALT and AST, thrombocytopenia, hypertension, nausea and vomiting in this meta-analysis.

The triple combination therapy of HAIC-FO plus TKI and ICIs showed promising efficacy and safety in patients with advanced HCC.

The protocol was registered with PROSPERO (ID:CRD42023424281).

In the translational therapy of giant hepatocellular carcinoma (HCC), hepatic arterial infusion chemotherapy (HAIC) combined with anti-PD-1 immunotherapy and tyrosine kinase inhibitors (TKI) after laparoscopic portal vein ligation (PVL) is extremely rare. This is a dual conversion therapy that combines surgery and oncology. Here, we report two cases of successful surgical completion after dual conversion therapy.

We report that a 54-year-old man and a 69-year-old woman were diagnosed with primary HCC combined with hepatitis B cirrhosis (case 2 also combined with fatty liver) on physical examination. Due to the insufficient residual liver volume assessed before surgery, laparoscopic right PVL was performed, followed by HAIC combined with anti-PD-1 immunotherapy and TKI. Finally, surgical resection was successfully completed, and pathology confirmed that the tumor was mostly necrotic (90%) in one case, and no live tumor tissue was found in the other case.

In the process of surgical transformation, our treatment plan takes into account the control and transformation of oncology at the same time, which is expected to provide more opportunities for radical hepatectomy and improve the prognosis of patients with large liver cancer.

Advanced-stage hepatocellular carcinoma (HCC), especially huge HCC or portal vein tumour thrombus (PVTT), is difficult to treat, and the prognosis is poor. The advantages of hepatic artery infusion chemotherapy (HAIC) combined with targeted therapy and immunotherapy for this complex disease are gradually becoming apparent. However, HAIC still has some inevitable disadvantages, such as arterial perfusion therapy requiring a long time, which results in many patients having difficulty completing the procedure. Modified HAIC (mHAIC)-based oxaliplatin and S-1 is a new treatment option for huge HCC or PVTT that can reduce complications and improve patient compliance. We report two cases of huge HCC or PVTT that were successfully treated with mHAIC combined with lenvatinib and camrelizumab. The clinical presentations, treatment strategies, and outcomes of these cases are presented.

Case 1: A 52-year-old female was found to have a huge HCC with a size of 14×11 cm. She was treated with one cycle of mHAIC combined with transcatheter arterial chemoembolization (TACE), lenvatinib and camrelizumab and 3 cycles of mHAIC in combination with lenvatinib and camrelizumab. The patient's follow-up maintenance therapy with lenvatinib and camrelizumab has been evaluated for efficacy in achieving complete response (CR). Case 2: A 57-year-old man was diagnosed with advanced HCC in combination with PVTT. He achieved partial remission (PR) after four cycles of mHAIC combined with lenvatinib and camrelizumab. This was followed by treatment with lenvatinib and camrelizumab with an efficacy assessment for CR, and progression-free survival (PFS) was 7 months.

For advanced HCC with a large mass or PVTT, mHAIC combined with lenvatinib and camrelizumab is a safe and effective treatment with good patient compliance.

To understand the proportion of uHCC (unresectable hepatocellular carcinoma) patients who achieve successful conversion resection in a high-volume setting with state of the art treatment options.

We retrospectively reviewed all HCC patients hospitalized to our center from June 1^st, 2019 to June 1^st, 2022. Conversion rate, clinicopathological features, response to systemic and/or loco-regional therapy and surgical outcomes were analyzed.

A total of 1,904 HCC patients were identified, with 1672 patients receiving anti-HCC treatment. 328 patients were considered up-front resectable. Of the remaining 1344 uHCC patients, 311 received loco-regional treatment, 224 received systemic treatment, and the remainder (809) received combination systemic plus loco-regional treatment. Following treatment, one patient from the systemic group and 25 patients from the combination group were considered to have resectable disease. A high objective response rate (ORR) was observed in these converted patients (42.3% under RECIST v1.1 and 76.9% under mRECIST criteria). The disease control rate (DCR) reached 100%. 23 patients underwent curative hepatectomy. Major post-operative morbidity was equivalent in the both groups (P=0.76). Pathologic complete response (pCR) was 39.1%. During conversion treatment, grade 3 or higher treatment-related adverse events (TRAEs) were observed in 50% of patients. The median follow-up time was 12.9 months (range, 3.9~40.6) from index diagnosis and 11.4 months (range, 0.9~26.9) from resection. Three patients experienced disease recurrence following conversion surgery.

By intensive treatment, a small sub-group of uHCC patients (2%) may potentially be converted to curative resection. Loco-regional combined with systemic modality was relative safe and effective in the conversion therapy. Short-term outcomes are encouraging, but long-term follow-up in a larger patient population are required to fully understand the utility of this approach.