Efficacy And Safety Analysis Of Interventional Therapy Combined With Targeted Therapy And Immunotherapy Compared With Interventional Therapy Alone In Unresectable Hepatocellular Carcinoma

Purpose:The conversion therapy for unresectable hepatocellular carcinoma(u HCC)is currently a hot topic in the field of hepatocellular carcinoma research,but there is no standardized conversion therapy protocol.As there are different anti-tumors mechanisms between interventional therapy,targeted therapy and immunotherapy,this study aims to investigate the clinical efficacy of interventional therapy combined with targeted therapy and immunotherapy compared with interventional therapy alone in patients with u HCC.Method:From October 2020 to October 2022,patients with unresectable hepatocellular carcinoma who received interventional therapy combined with targeted therapy and immunotherapy or interventional therapy alone in the First Affiliated Hospital of Nanchang University were retrospectively analyzed.According to the inclusion and exclusion criteria,a total of 130 patients with unresectable hepatocellular carcinoma were included,of whom 70 patients received combined therapy and 60 patients underwent interventional therapy alone.General information,imaging examinations,laboratory tests,drug efficacy and adverse reactions of patients were collected and recorded.The efficacy response after treatment was assessed according to the modified solid tumor evaluation criteria(m RECIST),and the conversion rate after treatment was calculated;survival curves were plotted by Kaplan-Meier method,and progression-free survival(PFS)were calculated for all included patients;Cox regression analysis was used to find the factors that may affect patients’ m PFS;adverse reactions were determined by the Common Terminology Criteria for Adverse Events Version 5.0(CTCAE 5.0).Differences were considered statistically significant at P< 0.05.Result:Follow-up ended on 31 January 2023,with a median follow-up of 9.4 months(IQR=11.2).In terms of efficacy,referring to m RECIST standard,9(12.86%)of all included patients achieved complete response,29(41.43%)had partial response among 70 patients receiving combined therapy.The ORR was 54.29 % and 34 patients underwent successful surgical resection after conversion therapy,with a conversion rate of 48.57%.On the 60 patients who received only interventional treatment,2(3.33%)achieved complete response,19(31.67%)had partial response.The ORR was 35.00% and 14 patients underwent successful surgical resection after conversion therapy,with a conversion rate of 23.33%.The difference in ORR(P=0.028)and conversion rate(P=0.003)between the two groups was statistically significant.By the last follow-up date,41 patients in the combined treatment group had disease progression,and the m PFS was 10.38 months(95% CI:8.59-12.14),while in the interventional treatment group,34 patients had disease progression,and the m PFS was 7.87 months(95% CI: 3.07-12.66),and the difference in m PFS between the two groups was statistically significant(P=0.013).The factors that may affect m PFS were analyzed.Cox regression analysis of factors that may affect m PFS showed that vascular invasion and treatment modality were independent risk factors for m PFS in patients.Patients without vascular invasion(HR=0.55,95%CI: 0.34-0.90,P=0.017)and those treated with combined therapy(HR=0.57,95% CI:0.36-0.90,P=0.017)had a better m PFS.In terms of adverse reactions,the most common adverse reactions are elevated transaminases,abdominal pain,thrombocytopenia,leukopenia,fever,weight loss,etc.,but most of them are mild to moderate.And comparison between groups showed no statistical difference in the occurrence of most adverse reactions between the two groups.Patients with grade 3adverse reactions improved after drug reduction,discontinuation and symptomatic treatment.No Grade 4 adverse reactions were observed and no adverse reaction related deaths were observed.Conclusion:Interventional therapy combined with targeted therapy and immunotherapy is a safe and feasible treatment strategy for patients with primary unresectable hepatocellular carcinoma.This strategy is more effective than interventional therapy alone and has controllable adverse effects.