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.

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.

Hydrochloric acid enhanced radiofrequency ablation for treatment of large hepatocellular carcinoma in the caudate lobe:Report of three cases

BACKGROUND To report on the use of percutaneous hydrochloric acid(HCl) enhanced radiofrequency ablation(HRFA) for the treatment of large(maximum diameter ≥5 cm) hepatocellular carcinoma(HCC) in the caudate lobe.CASE SUMMARY Between August 2013 and June 2016, three patients with a large HCC(maximum diameter: 5.0, 5.7, and 8.1 cm) in the caudate lobe were treated by transarterial chemoembolization followed by computer tomography(CT) guided RFA using a monopolar perfusion RF electrode, which was enhanced by local infusion of 10%HCl at 0.2 mL/min(total volume, 3 to 12 mL). The output power of HRFA reached 100 W, and the average ablation time was 39 min(range, 15 to 60 min).Two patients each underwent one session of HRFA and one patient two sessions.After treatment, CT/magnetic resonance imaging showed that all the three lesions were completely ablated. There was no major complication. Two patients had asymptomatic bile duct dilatation. One patient died of tongue cancer 24 mo after ablation. The remaining two patients were alive and no area of enhancement is detected in the caudate lobe at 28 and 60 mo after ablation, respectively.CONCLUSION Percutaneous CT-guided HRFA is safe and efficacious in treating large HCC in the caudate lobe.

Camrelizumab (a PD-1 inhibitor) plus apatinib (an VEGFR-2 inhibitor) and hepatic artery infusion chemotherapy for hepatocellular carcinoma in Barcelona Clinic Liver Cancer stage C (TRIPLET): a phase Ⅱ study

Hepatic arterial infusion chemotherapy(HAIC)using a combination of oxaliplatin,fluorouracil,and leucovorin(FOLFOX)has shown promise for hepatocellular carcinoma(HCC)patients classified under Barcelona Clinic Liver Cancer(BCLC)stage C.In China,the combined therapy of camrelizumab and apatinib is now an approved first-line approach for inoperable HCC.This study(NCT04191889)evaluated the benefit of combining camrelizumab and apatinib with HAIC-FOLFOX for HCC patients in BCLC stage C.Eligible patients were given a maximum of six cycles of HAIC-FOLFOX,along with camrelizumab and apatinib,until either disease progression or intolerable toxicities emerged.The primary outcome measured was the objective response rate(ORR)based on the Response Evaluation Criteria in Solid Tumors(RECIST)v1.1.Thirty-five patients were enrolled.Based on RECIST v1.1 criteria,the confirmed ORR stood at 77.1%(95%CI:59.9%to 89.6%),with a disease control rate of 97.1%(95%CI:85.1%to 99.9%).The median progression-free survival was 10.38 months(95%CI:7.79 to 12.45).Patient quality of life had a transient deterioration within four cycles of treatment,and generally recovered thereafter.The most frequent grade≥3 or above treatment-related adverse events included reduced lymphocyte count(37.1%)and diminished neutrophil count(34.3%).The combination of camrelizumab,apatinib,and HAIC demonstrated encouraging results and manageable safety concerns for HCC at BCLC stage C.