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.

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.

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.

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.

Combined treatment of hepatocellular carcinoma with partial splenic embolization and transcatheter hepatic arterial chemoembolization

AIM: To prospectively evaluate the effi cacy and safety of partial splenic embolization (PSE) combined with transcatheter hepatic arterial chemoembolization (TACE) in treatment of hepatocellular carcinoma (HCC). METHODS: Fifty patients suffering from primary HCC associated with hypersplenism caused by cirrhosis were randomly assigned to 2 groups: group A receiving PSE combined with TACE (n = 26) and group B receiving TACE alone (n = 24). Follow-up examinations included calculation of peripheral blood cells (leukcytes, platelets and red blood cells) and treatment-associated complications. RESULTS: Prior to treatment, there was no signifi cant difference in sex, age, Child-Pugh grade, tumor diameter, mass pathology type and peripheral blood cell counts between the 2 groups. After treatment, leukocyte and platelet counts were significantly higher in group A during the 3-mo follow-up period (P < 0.05), but lower in group B (P < 0.05). Severe complications occurred in 3 patients (11.5%) of group A and in 19 patients (79.2%) of group B (P < 0.05), and there was no significant difference in symptoms of post-embolization syndrome, including abdominal pain, fever, mild nausea and vomiting between the 2 groups (P > 0.05). CONCLUSION: PSE combined with TACE is more effective and safe than TACE alone for patients with HCC associated with hypersplenism caused by cirrhosis.

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.

Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma

AIM:To investigate the efficacy of hepatic arterial infusion chemotherapy(HAIC) using floxuridine(FUDR) in patients with advanced hepatocellular carcinoma(HCC) confined to the liver.METHODS:Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at ourhospital between March 2005 and May 2008.Among the 34 patients,9 patients were classified as Child class C,and 18 patients had portal vein tumor thrombus(PVTT).One course of chemotherapy consisted of continuous infusion of FUDR(0.3 mg/kg during day 1-14) and dexamethasone(10 mg on day 1,4,7 and 11),and this treatment was repeated every 28 d.RESULTS:Two patients(5.9%) displayed a complete response,and 12 patients(35.3%) had a partial response.The tumor control rate was 61.8%.The median overall survival times were 15.3 mo,12.4 mo and 4.3 mo for the patients who were classified as Child class A,Child class B and Child class C,respectively(P = 0.0392).The progression-free survival was 12.9 mo,7.7 mo and 2.6 mo for the patients who were classified as Child class A,Child class B and Child class C,respectively(P = 0.0443).The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT.In addition to hepatic reserve capacity and PVTT,the extent of HCC was an independent factor in determining a poor prognosis.The most common adverse reactions to HAIC were mucositis,diarrhea and peptic ulcer disease,but most of these complications were improved by medical treatment and/or a delay of HAIC.CONCLUSION:The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities,even in patients with advanced cirrhosis.

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.

Angiographic embolization in the treatment of intrahepatic arterial bleeding in patients with blunt abdominal trauma

BACKGROUND: Angiographic embolization (AE) as an adjunct non-operative treatment of intrahepatic arterial bleeding has been widely used. The present study aimed to evaluate the efficacy of selective AE in patients with hepatic trauma.METHODS: Seventy patients with intrahepatic arterial bleeding after blunt abdominal trauma who had undergone selective AE in 10 years at this institution were retrospectively reviewed.The criteria for selective AE included active extravasation on contrast-enhanced CT, an episode of hypotension or a decrease in hemoglobin level during the non-operative treatment. The data of the patients included demographics,grade of liver injuries, mechanism of blunt abdominal trauma,associated intra-abdominal injuries, indications for AE,angiographic findings, type of AE, and AE-related hepatobiliary complications. RESULTS: In the 70 patients, 32 (45.71%) had high-grade liver injuries. Extravazation during the early arterial phase mainly involved the right hepatic segments. Thirteen (18.57%) patients underwent embolization of intrahepatic branches and the extrahepatic trunk and these patients all developed AE-related hepatobiliary complications. In 19 patients with AE-related complications, 14 received minimally invasive treatment and recovered without severe sequelae. CONCLUSIONS: AE is an adjunct treatment for liver injuries.Selective and/or super-selective AE should be advocated to decrease the incidence and severity of AE-related hepatobiliary complications.

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.

Study of hepatic arterial infusion of Endostar combined with TACE on advanced hepatocellular carcinoma

Objective:To study the efficacy and safety of hepatic arterial infusion of Endostatin(YH-16,Endostar),combined with transcatheter arterial chemoembolization(TACE) on advanced hepatocellular carcinoma.Methods:Thirty patients with advanced hepatocellular carcinoma were enrolled in the study.The patients received hepatic arterial infusion of Endostar combined with TACE.The efficacy was evaluated strictly after 1-2 cycles according to RECIST criteria and the value of AFP;quality of life(QOL) was evaluated according to Karnofsky scores.Adverse effects were evaluated too.Results:29 cases' efficacy was evaluated among the total 30 cases.The KPS were significantly increased after the treatment(80.39 ± 8.37 vs 73.93 ± 9.22,P = 0.002).Compared with control group,the objective response rate(CR and PR) and the rate of AFP negative changed were significantly higher(P = 0.021,P = 0.046).The adverse effects were not obvious.Conclusion:The QOL and preliminary efficiency of patients of advanced hepatocellular carcinoma may be improved by hepatic arterial infusion of Endostar combined with TACE,the rate of AFP negative changed were significantly higher too,and there are little of adverse effects.It is worthy to clinical generalization and further clinical observation.

Tumor-feeding artery diameter reduction is associated with improved short-term effect of hepatic arterial infusion chemotherapy plus lenvatinib treatment

BACKGROUND Recently,hepatic arterial infusion chemotherapy(HAIC)plus lenvatinib has been frequently used to treat unresectable hepatocellular carcinoma(uHCC)in China.In the clinic,the hepatic arteries of some patients shrink significantly during this treatment,leading to improved short-term efficacy.AIM To investigate the relationship between the shrinkage of hepatic arteries and the short-term effect of HAIC plus lenvatinib treatment.METHODS Sixty-seven participants with uHCC were enrolled in this retrospective study.The patients received HAIC every 3 wk,followed by oral lenvatinib after the first HAIC course.Hepatic artery diameters were measured on CT before treatment and after 1 and 2 mo of treatment.Meanwhile,the changes in tumor capillaries were also examined on pathological specimens before and after 1 mo of treatment.The antitumor response after 1,3,and 6 mo of treatment was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST).The relationship between the changes in vessel diameters and the short-term effect of the combination treatment was evaluated by receiver-operating characteristic and logistic regression analyses.RESULTS The hepatic artery diameters were all significantly decreased after 1 and 2 mo of treatment(P<0.001),but there was no difference in the vessel diameters between 1 and 2 mo(P>0.05).The microvessel density in the tumor lesions decreased significantly after 1 mo of combination treatment(P<0.001).According to mRECIST,46,41,and 24 patients had complete or partial responses after 1,3,and 6 mo of treatment,respectively,whereas 21,21,and 32 patients had a stable or progressive disease at these times,respectively.Shrinkage of the tumor-feeding artery was significantly associated with the tumor response after 1,3,and 6 mo of treatment(P<0.001,P=0.004,and P=0.023,respectively);however,changes in other hepatic arteries were not significantly associated with the tumor response.Furthermore,shrinkage of the tumor-feeding artery was an independent factor for treatment efficacy(P=0.001,P=0.001,and P=0.002 and 1,3,and 6 mo,respectively).CONCLUSION The hepatic arteries shrank rapidly after treatment with HAIC plus lenvatinib,and shrinkage of the tumor-feeding artery diameter was closely related to improved short-term efficacy.

Resection of a locally advanced hilar tumor and the hepatic artery after stepwise hepatic arterial embolization: A case report

We herein report a case of a hilar tumor with extensive invasion to the proper hepatic artery, which was successfully treated with a radical resection in a 57-year-old female patient after a stepwise hepatic arterial embolization. She underwent right colectomy and partial hepatectomy for advanced colon cancer two years ago and radiofrequency ablation therapy for a liver metastasis one year ago, respectively. A recurrent tumor was noted around the proper hepatic artery with invasion to the left hepatic duct and right hepatic artery 7 mo previously. We planned a radical resection for the patient 5 mo after the absence of tumor progression was confirmed while he was undergoing chemotherapy. To avoid surgery-related liver failure, we tried to promote the formation of collateral hepatic arteries after stepwise arterial embolizationof the posterior and anterior hepatic arteries two weeks apart. Finally, the proper hepatic artery was occluded after formation of collateral flow from the inferior phrenic and superior mesenteric arteries was confirmed. One month later, a left hepatectomy with hepatic arterial resection was successfully performed without any major complications.

Efficacy comparison between hepatic arterial infusion chemotherapy plus systemic chemotherapy used as first-line and non-first-line treatments for the patients of colorectal cancers with unresectable hepatic metastases

Objective: The combination of hepatic arterial chemotherapy(HAIC) and systemic chemotherapy(SYC) has potential effect on colorectal cancer(CRC) patients with unresectable hepatic metastasis. The aim of this retrospective study was to investigate the efficacy and safety of this combined therapeutic regimen on Chinese patients based on single institute experiences. Methods: All 54 patients of this retrospective analysis were diagnosed with CRC with unresectable liver metastasis and received combined HAIC and SYC. Among the patients, 23 of them received HAIC plus SYC when they developed liver metastases as first-line treatment(Group 1), and 31 patients received HAIC plus SYC as non-first-line treatment(Group 2). The different efficacy in two groups was analyzed by SPSS 19.0. Results: The overall response rate(ORR) were 52.2% and 25.8% respectively in Groups 1 and 2(P = 0.047), and the disease control rate(DCR) were 65.2% and 35.5% respectively in Groups 1 and 2(P = 0.031). The median progression-free survival(PFS) were 6.8 and 3.3 months(P = 0.002), the median hepatic progression-free survival(H-PFS) were 8.8 and 3.7 months(P = 0.001), and the median overall survival(OS) were 18.8 and 13.7 months(P = 0.121) in Groups 1 and 2, respectively. No fatal reaction was observed and no significant difference of adverse reaction was found in two groups. Grade 3/4 toxic effects included neutropenia(9.7% in Group 2 only), gastrointestinal reaction(8.7% in Group 1 and 6.5% in Group 2), stomatitis(6.5% in Group 2 only) and hyperbilirubinemia(4.3% in Group 1 only). Conclusion: HAIC combined with SYC showed promising efficacy and safe profiles on CRC patients with unresectable liver metastases.

Influence of hepatic arterial blockage on blood perfusion and VEGF,MMP-1 expression of implanted lver cancer in rats

AIM: To investigate the influence of hepatic arterial blockage on blood perfusion of transplanted cancer in rat liver and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-1 (MMP-1), and to explore the mechanisms involved in transarterial embolization (TAE)-induced metastasis of liver cancer preliminarily. METHODS: Walker 256 carcinosarcoma was transplanted into rat liver to establish the liver cancer model. Hepatic arterial ligation (HAL) was used to block the hepatic arterial blood supply and simulate TAE. Blood perfusion of tumor in control, laparotomy control, and HAL group was analyzed by Hoechst 33342 labeling assay, the serum VEGF level was assayed by ELISA, the expression of VEGF and MMP-1 mRNA was detected by in situ hybridization. RESULTS: Two days after HAL, the number of Hoechst 33342 labeled cells which represent the blood perfusion of tumor directly and hypoxia of tumor indirectly in HAL group decreased significantly compared with that in control group (329+/-29 vs 384+/-19, P【0.01). The serum VEGF level in the HAL group increased significantly as against that of the control group (93 ng.L(-1)+/-44 ng.L(-1) vs 55 ng.L(-1)+/-19 ng.L(-1), P【0.05). The expression of VEGF and MMP-1 mRNA in the tumor tissue of the HAL group increased significantly compared with that of the control and the laparotomy control groups (P【0.05). The blood perfusion data of the tumor, represented by the number of Hoechst 33342 labeled cells, showed a good linear inverse correlation with the serum VEGF level (r=-0.606, P【0.05) and the expression of VEGF mRNA in the tumor tissue ( r =-0.338, P【0.01). CONCLUSION: Blockage of hepatic arterial blood supply results in decreased blood perfusion and increased expression of metastasis-associated genes VEGF and MMP-1 of transplanted liver cancer in rats. Decreased blood perfusion and hypoxia may be the major cause of up-regulated expression of VEGF.

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.

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.

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.