Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma:A network meta-analysis

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.AIM 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.CONCLUSION 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.

Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.

Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma

Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy varies.This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications.As of October 25,2023,51 articles have been retrieved based on keyword predictions and HAIC.Sixteen eligible articles were selected for inclusion in this study.Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing,gene testing,and imaging testing.The above indicators and their combined forms showed excellent predictive effects in retrospective studies.This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC,analyzed each marker's ability to predict HAIC efficacy,and provided a reference for the clinical application of the prediction system.

Current efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma

Newer systemic therapies for hepatocellular carcinoma(HCC)have led to growing interest in combining hepatic arterial infusion chemotherapy(HAIC)with systemic treatments.To evaluate the effectiveness and safety of HAIC and combination therapies in treating advanced HCC,a network meta-analysis was conducted by Zhou et al.The study included data from 44 articles.HAIC was superior in overall survival(OS),progression-free survival(PFS),and response rates compared to transarterial chemoembolization and sorafenib.Moreover,combinations of HAIC with other treatments and single agents(e.g.,lenvatinib,ablation,anti-programmed cell death 1 therapy,radiotherapy)provided better OS and PFS outcomes than HAIC alone.In this editorial,we will discuss the study findings,the strengths and weaknesses of the metanalysis,and future advances in the field of HAIC for advanced HCC.

Advancing hepatocellular carcinoma treatment with hepatic arterial infusion chemotherapy

Hepatocellular carcinoma(HCC)remains a major challenge in oncology,being a leading cause of cancer-related mortality worldwide.Early-stage HCC is typically treated with surgical resection,transplantation,or ablation,while advanced-stage HCC relies on systemic therapies like sorafenib and newer combinations such as atezolizumab-bevacizumab.Despite these advancements,there is still a need for effective treatments for unresectable HCC,especially in cases with macroscopic vascular invasion.Hepatic arterial infusion chemotherapy(HAIC)has demonstrated promising outcomes in Asia for the treatment of unresectable HCC,yet its application in Western countries has been relatively limited.This letter reviews the recent meta-analysis by Zhou et al published in the World Journal of Gastrointestinal Oncology,which demonstrates the efficacy and safety of HAIC vs sorafenib.The analysis includes 9 randomized controlled trials and 35 cohort studies,highlighting significant improvements in overall survival,progressionfree survival,and objective response rates with HAIC and its combinations.The editorial explores the reasons behind the limited use of HAIC in Western countries.It underscores the potential of HAIC to enhance treatment outcomes for advanced HCC and calls for more research and broader adoption of HAIC in clinical practice globally.

Camrelizumab,apatinib and hepatic artery infusion chemotherapy combined with microwave ablation for advanced hepatocellular carcinoma

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.AIM To compare the efficacy and safety of TRIPLET alone(T-A)vs TRIPLET-MWA(TM)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).CONCLUSION T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma:a prospective non.randomized study

Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on large(> 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy(HAIC)might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX(mFOLFOX) regimen and those ofTACE in patients with massive unresectable HCC.Methods: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen(oxaliplatin, 85 mg/m^2 intra-arterial infusion; leucovorin,400 mg/m^2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m^2 continuous infusion)every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression(TTP), and safety were assessed.Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group(52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months(hazard radio[HR] = 2.35,95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection(10 vs. 3,P = 0.033). The proportions of grade 3-4 adverse events(AE) and serious adverse events(SAE) were lower in the HAIC group than in the TACE group(grade 3-4 AEs: 13 vs. 27, P = 0.007;SAEs: 6 vs. 15,p = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent(10 vs. 2,P = 0.026).Conclusions: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.

Transarterial embolization and low-dose continuous hepatic arterial infusion chemotherapy with oxaliplatin and raltitrexed for hepatocellular carcinoma with major portal vein tumor thrombus

AIM To determine the efficacy and safety of transarterial embolization and low-dose continuous hepatic arterial infusion chemotherapy with oxaliplatin and raltitrexed in hepatocellular carcinoma(HCC) with major portal vein tumor thrombus(MPVTT).METHODS eighty-six patients with MPVTT accepted routine embolization. The catheter was kept in the hepatic artery and oxaliplatin(50 mg in 250 m L of glucose) was infused by pump for 4 h,followed by raltitrexed(2 mg in 100 m L of 0.9% saline) infusion by pump for the next 1 h. The efficacy and safety were evaluated afterthe transarterial chemoembolization(TACe).RESULTS Full or partial embolization was achieved in 86 cases,where all the cases received low dose continuous hepatic arterial infusion chemotherapy. Complete responses(CRs),partial responses(PRs),stable disease(SD),and disease progression(PD) for intrahepatic disease were observed in 0,45,20,and 21 patients,respectively. The 1-,2-and 3-year overall survival rates of the 86 patients were 40.7%,22.1%,and 8.1% respectively,and the median survival time was 8.7 mo. Complication was limited. CONCLUSION TACE with low dose continuous hepatic arterial infusion of oxaliplatin and raltitrexed could be an option in MPVTT patient; it was shown to be effective in patients with advanced HCC with MPVTT with less toxicity.

Safety and efficacy of hepatic arterial infusion chemotherapy with raltitrexed and oxaliplatin post-transarterial chemoembolization for unresectable hepatocellular carcinoma

Objective:To investigate the safety,efficacy,and prognostic factors of hepatic arterial infusion chemotherapy(HAIC)with raltitrexed and oxaliplatin post-transarterial chemoembolization(TACE)for unresectable hepatocellular carcinoma(uHCC).Methods:Thirty-seven patients with uHCC who received HAIC with raltitrexed and oxaliplatin post-TACE between June 2014 and December 2016 at our hospital were recruited.The primary endpoint was overall survival(OS),and secondary endpoint was progression-free survival(PFS).The overall response rate(ORR)was evaluated using the modified Response Evaluation Criteria in Solid Tumors.Toxicity was assessed according to the Common Terminology Criteria for Adverse Events(v4.0).The OS and prognostic factors were analyzed using the Kaplan-Meier method,log-rank test,and Cox regression models.Results:Three(8.1%)patients achieved complete response,17(46.0%)patients achieved partial response,and the ORR was54.0%.The median OS and median PFS were 19.0 months and 12.0 months,respectively.The common toxicities included grade 3-4 increased aspartate aminotransferase levels(8/37,21.6%),grade 1-2 hyperbilirubinemia(75.7%,28/37),nonspecific abdominal pain and fever,and grade 2-3 thrombocytopenia(18.9%,7/37);no patients developed grade 3-4 neutropenia.Univariate analysis showed that the tumor diameter(≤50 mm,p=0.028),Barcelona Clinic Liver Cancer(BCLC)stage(p=0.012),hepatitis B virus DNA level(p=0.033),and derived neutrophil-to-lymphocyte ratio(dNLR;derived neutrophils/leukocytes minus neutrophils)(p=0.003)were predictive factors for prognosis.Multivariate analysis showed that patients with BCLC stage B disease(p=0.029)and dNLR<2 before therapy(p=0.004)had better prognosis.Conclusions:HAIC with raltitrexed and oxaliplatin post-TACE is a safe and efficacious therapy for patients with uHCC;in particular,those with BCLC stage B and dNLR<2 have better prognosis.

Effect of double platinum agents, combination of miriplatintransarterial oily chemoembolization and cisplatinhepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases

Hepatocellular carcinoma(HCC) is one of the most common cancers and the third highest cause of cancerassociated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization(TOCE), and hepatic arterial infusion chemotherapy(HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.

Prognostic factors for transarterial chemoembolization combined with sustained oxaliplatin-based hepatic arterial infusion chemotherapy of colorectal cancer liver metastasis

Objective： To investigate the prognostic factors in chemorefractory colorectal cancer liver metastasis（CRCLM）patients treated by transarterial chemoembolization（TACE） and sustained hepatic arterial infusion chemotherapy（HAIC）.Methods： Between 2006 and 2015, 162 patients who underwent 763 TACE and HAIC in total were enrolled in this retrospective study, including 110 males and 52 females, with a median age of 60（range, 26–83） years.Prognostic factors were assessed with Log-rank test, Cox univariate and multivariate analyses.Results： The median survival time（MST） and median progression-free survival（PFS） of the 162 patients from first TACE/HAIC were 15.6 months and 5.5 months respectively. Normal serum carbohydrate antigen 19-9（CA19-9, 〈37 U/m L）（P〈0.001） and carbohydrate antigen 72-4（CA72-4, 〈6.7 U/m L）（P=0.026）, combination with other local treatment（liver radiotherapy or liver radiofrequency ablation）（P=0.034） and response to TACE/HAIC（P〈0.001） were significant factors related to survival after TACE/HAIC in univariate analysis. A multivariate analysis revealed that normal serum CA19-9（P〈0.001）, response to TACE/HAIC（P〈0.001） and combination with other local treatment（P=0.001） were independent factors among them.Conclusions： Our findings indicate that serum CA19-9 〈37 U/m L and response to TACE/HAIC are significant prognostic indicators for this combined treatment, and treated with other local treatment could reach a considerable survival benefit for CRCLM. This could be useful for making decisions regarding the treatment of CRCLM.

Sorafenib combined with embolization plus hepatic arterial infusion chemotherapy for inoperable hepatocellular carcinoma

BACKGROUND There is little evidence of combining sorafenib with hepatic arterial infusion chemotherapy(HAIC)after transarterial chemoembolization(TACE)for intermediate and advanced hepatocellular carcinoma(HCC).It is important to identify that patients with intermediate and advanced HCC are most likely to benefit from this combination therapy.AIM To investigate the safety and clinical outcomes of sorafenib combined with HAIC with folinic acid,5-fluorouracil(5-FU),and oxaliplatin(FOLFOX)after TACE for intermediate and advanced HCC.METHODS This prospective phase II study enrolled patients with intermediate and advanced HCC who underwent treatment with sorafenib combined with TACEHAIC.All patients initially received the standard 400 mg dose of sorafenib twice daily before TACE-HAIC.Participants at our institute with intermediate and advanced HCC underwent routine TACE.Then,the catheter used for embolization was kept in place in the hepatic artery,and oxaliplatin was intraarterially administered for 6 h,followed by 5-FU for 18 h,and folinic acid was intravenously administered for 2 h.The primary endpoints were safety,as evaluated by the Common Terminology and Criteria for Adverse Events version 4.0,and 12-mo progression-free survival(PFS),as analyzed by the Kaplan-Meier method.As secondary endpoints,the objective response rate(ORR)was evaluated by the modified Response Evaluation Criteria for Solid Tumors,and survival time[overall survival(OS)]was analyzed by the Kaplan-Meier method.RESULTS Sixty-six participants at our institute with intermediate and advanced HCC were enrolled in this prospective study(mean age,53.3±11.7 years).Approximately 56.1%of participants had Barcelona Clinic Liver Cancer(BCLC)stage C disease,and 43.9%had BCLC stage B disease.The ORR was 42.4%.The disease control rate was 87.9%.The grade 3-4 toxicities consisted of thrombocytopenia(4.5%),neutropenia(3.0%),and elevated aspartate aminotransferase(12.2%).Hand-foot skin reaction was also observed(40.9%).The median PFS was 13.1 mo(13.5 mo in the BCLC stage B participants and 9.4 mo in the BCLC stage C participants).The 6-mo,12-mo,and 24-mo PFS rates were 75.0%,54.7%,and 30.0%,respectively.The median OS was 21.8 mo.CONCLUSION Sorafenib combined with HAIC(FOLFOX)after TACE may be a feasible treatment choice for intermediate and advanced HCC because this treatment met the prespecified endpoint of a 6-mo PFS rate exceeding 50%and had good patient tolerance.Prospective randomized controlled trials are needed to confirm the effect of this combination therapy.

Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?

AIM:To evaluate the effectiveness of hepatic arterial infusion chemotherapy(HAIC) for advanced hepatocellular carcinoma(HCC) resistant to transarterial chemoembolization(TACE).METHODS:This study was conducted on 42 patients who received HAIC for advanced HCC between 2001and 2010 at our hospital.5-fluorouracil(5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir.Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU.The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010(written in Japanese);one group of patients who did not fulfill the criteria for TACE resistance(group A,n = 23),and another group who fulfilled the criteria for TACE resistance(group B,n = 19).We compared the outcomes in terms of the response and survival rates between the two groups.RESULTS:Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B(response rate:48% vs 16%,P = 0.028,tumor suppression rate:87% vs 53%,P = 0.014).Furthermore,both the progression-free survival rate and survival time were significantly superior in group A than in group B(3-,6-,12-,and 24-mo = 83%,70%,29% and 20% vs 63%,42%,16% and 0%,respectively,P = 0.040,and 9.8 mo vs 6.2 mo,P = 0.040).A multivariate analysis(Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival(P = 0.007).CONCLUSION:HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE.Other tools for treatment,i.e.,molecular-targeting agents may be considered for these cases.

Transarterial chemoembolization with hepatic arterial infusion chemotherapy plus S-1 for hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization(TACE)and hepatic arterial infusion chemotherapy(HAIC)have shown promising local benefits for advanced hepatocellular carcinoma(HCC).S-1,a composite preparation of a 5-fluorouracil prodrug,has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC.AIM To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced HCC.METHODS In this single-center,open-label,prospective,randomized controlled trial,117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with(TACE/HAIC+S-1,n=56)or without(TACE/HAIC,n=61)oral S-1 between December 2013 and September 2017.Two participants were excluded from final analysis for withdrawing consent.The primary endpoint was progression-free survival(PFS)and secondary endpoints included overall survival(OS),objective response rate,disease control rate and safety.RESULTS In total,115 participants(100 males and 15 females;mean age,57.7 years±11.9)were analyzed.The median PFS and OS were 5.0 mo(0.4–58.6 mo)(95%confidence interval(CI):3.82 to 6.18)vs 4.4 mo(1.1–54.4 mo)(95%CI:2.54 to 6.26;P=0.585)and 8.4 mo(0.4–58.6 mo)(95%CI:6.88 to 9.92)vs 8.3 mo(1.4–54.4 m)(95%CI:5.71 to 10.96;P=0.985)in the TACE/HAIC+S-1 and TACE/HAIC groups,respectively.The objective response rate and disease control rate were 30.9%vs 18.4%and 72.7%vs 56.7%in the TACE/HAIC+S-1 and TACE/HAIC groups,respectively.Grade 3/4 adverse events had a similar frequency in both treatment groups.CONCLUSION No improvements in tumor response rates,PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced HCC.Both treatment regimens had a similar safety profile.

Efficacy of 5-Fluorouracil and High-Concentration Cisplatin Suspended in Lipiodol by Short-Term Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

Background: Since advanced hepatocellular carcinoma (HCC) is potentially fatal, and patients’ quality of life (QOL) often deteriorates during their treatment, improving the prognosis and QOL of patients given chemotherapy is very important. In addition, cost-effective treatments are highly desirable when chemotherapy must be given repeatedly. The aim of this study was to evaluate the efficacy and usefulness of 5-fluorouracil (5-FU) and high-concentration cisplatin by short-term hepatic arterial infusion chemotherapy (3-day FPL) in advanced HCC patients. Methods: Thirty patients with unresectable advanced HCC were enrolled. The patients underwent hepatic arterial infusion chemotherapy via the implanted port system with 5-FU on days 1 - 3 and a fine-powder formulation of cisplatin in suspended pre-warmed lipiodol on day 2 every 4 to 10 weeks. Tumor response was assessed one month later with CT. Results: All patients had evidence of portal vein invasion (Vp2-4). Four patients achieved a complete response (CR), 8 patients achieved a partial response (PR), and 7 patients had stable disease (SD). The median progression-free survival (PFS) and overall survival (OS) were 198 days and 452 days, respectively. The OS was significantly longer in the successful disease control group (CR, PR, and SD) than in the progressive disease group (P < 0.005). Conclusions: Three-day FPL was effective and tolerable in advanced HCC patients due to its shorter time of administration than conventional FP therapy. Therefore, repetitive 3-day FPL appears useful and contributes to improving the prognosis and QOL of patients with advanced HCC. In addition, this protocol is a cost-effective treatment.

Retrograde embolization technique of the right gastric artery during the implantation of port-catheter system for hepatic arterial infusion chemotherapy

Objective:This study aimed to introduce and evaluate a new embolization technique for the right gastric artery(RGA) during percutaneous implantation of a port-catheter system for hepatic arterial infusion chemotherapy(HAIC).Methods:From January 2013 to January 2017,159 patients with unresectable advanced liver cancer underwent percutaneous implantation of a port-catheter system.In 86 of these patients(56 men;aged 28-88 years;mean:60.6±12.0 years),in whom the RGA was obvious on arteriography,embolization of RGA was attempted using microcoils to protect the gastric mucosa during HAIC.In the first phase(first three years),antegrade embolization of the RGA using a 2.7 Fr microcatheter was performed in 55 patients.In the second phase(next two years),embolization of the RGA was attempted by combining antegrade embolization and retrograde embolization through the left gastric artery(LGA) in 31 patients.The success rates and the incidence of acute gastroduodenal mucosal toxicity(AGMT) in these two groups were compared.Results:The total success rate of the RGA embolization was 70.9%.The success rate was 83.9% in 31 patients who underwent combined antegrade and retrograde embolization,which was significantly higher than that of antegrade embolization alone(63.6%) performed in 55 patients(p=0.047).No complications related to embolization of RGA were documented.The incidence of AGMT was 29.1%(16/55) in patients in the first phase,which was significantly higher than that in the patients in the second phase(9.7%,3/31)(p=0.037).Conclusion: A combination of retrograde embolization via LGA could increase the success rates of RGA embolization and reduce the incidence of AGMT after HAIC.

Treatment strategies for advanced hepatocellular carcinoma:Sorafenib vs hepatic arterial infusion chemotherapy

Sorafenib is used worldwide as a first-line standardsystemic agent for advanced hepatocellular carcinoma(HCC) on the basis of the results of two large-scale Phase Ⅲ trials. Conversely,hepatic arterial infusion chemotherapy(HAIC) is one of the most recommended treatments in Japan. Although there have been no randomized controlled trials comparing sorafenib with HAIC,several retrospective analyses have shown no significant differences in survival between the two therapies. Outcomes are favorable for HCC patients exhibiting macroscopic vascular invasion when treated with HAIC rather than sorafenib,whereas in HCC patients exhibiting extrahepatic spread or resistance to transcatheter arterial chemoembolization,good outcomes are achieved by treatment with sorafenib rather than HAIC. Additionally,sorafenib is generally used to treat patients with Child-Pugh A,while HAIC is indicated for those with either Child-Pugh A or B. Based on these findings,we reviewed treatment strategies for advanced HCC. We propose that sorafenib might be used as a first-line treatment for advanced HCC patients without macroscopic vascular invasion or Child-Pugh A,while HAIC is recommended for those with macroscopic vascular invasion or Child-Pugh A or B. Additional research is required to determine the best second-line treatment for HAIC non-responders with Child-Pugh B through future clinical trials.

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. METHODS: Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m 2 epirubicin on day 1, 60 mg/m 2 cisplatin for 2 h on day 2, and 500 mg/m 2 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. RESULTS: Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD).The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm 3 (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-Ⅱ (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. CONCLUSION: HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm 3 and good prognostic factors.

Sorafenib plus hepatic arterial infusion chemotherapy with oxaliplatin versus sorafenib alone for advanced hepatocellular carcinoma

Objective:To compare the efficacy of sorafenib plus hepatic arterial infusion chemotherapy(HAIC)with oxaliplatin to that of sorafenib alone in patients with advanced hepatocellular carcinoma(HCC).Methods:This was a retrospective,single-center trial.Between April 3,2017 and July 2,2018,104 patients with Child-Pugh A and advanced HCC received either 400 mg of sorafenib orally twice daily plus HAIC with oxaliplatin(oxaliplatin 85 mg/m^2,every 3 weeks via repetitive catheterization)(n=46,soraOXA group)or 400 mg of only sorafenib orally twice daily(n=58,sorafenib group).Overall survival,progression-free survival,objective response rate,and treatment-related adverse events were compared.Results:The median overall survival was 9.37 months(95%CI,7.05-11.68)in the soraOXA group versus 4.8 months(95%CI,2.98-6.62)in the sorafenib group(HR 0.46[95%CI,0.29-0.72];P<0.001).The soraOXA group also showed a higher objective response rate(16[34.8%]vs 1[1.7%];P<0.001)and a longer progressionfree survival rate(5.5 months[95%CI,2.32-8.68]vs 2.4 months[95%CI,1.65-3.15],HR 0.54[95%CI,0.36-0.81],P=0.003)than the sorafenib group.There was no significant difference in the overall incidence of any grade adverse events,grade 3/4 adverse events,serious adverse events,or incidence of treatment termination due to adverse events between the two groups.Conclusion:Compared with sorafenib alone,sorafenib plus HAIC with oxaliplatin showed favorable treatment outcomes in patients with advanced HCC.The merits of this approach need to be established with a prospective trial.