| Objective:Researching the diffirence of the efficacy and safety of HAIC combined with targeted and immunological therapy and HAIC combined with targeted therapy and HAIC combined with immunological therapy compared for the treatment of advanced liver cancer.Meanwhile,analyzing the influencing factors of efficacy among the three different therapies,to provide a reference for the selection of clinical treatment of advanced liver cancer.Methods:1.Retrospectively collected 60 patients diagnosed with intermediate and advanced liver malignancy complicated by hepatic arterial infusion chemotherapy(HAIC)from the First Affiliated Hospital of Kunming Medical University from September 2020 to August 2022,and were divided into HAIC combined with targeted and immunological therapy group(30 cases),HAIC combined with targeted therapy group(14 cases),and HAIC combined immunological therapy group(16 cases).2.Collected the basic data of patients before surgery,including demographic data(age,sex,BMI,etiology),imaging data(tumor capsule,number of tumors,tumor maximum diameter,portal vein cancer thrombus and classification,extrahepatic metastasis),laboratory tests(serum AFP,PIVKA-II,HBV DNA load,etc.).3.Tumor response was evaluated 1,3,and 6 months after treatment,using the American Association For The Study Of Liver Diseases(AASLD)revised the efficacy evaluation criteria for solid tumors(m RECIST),through the patient’s imaging examination data(abdominal enhanced MR assessment is preferred,if MR is not available,abdominal enhanced CT is used to evaluate)to evaluate the efficacy,The efficacy evaluation was specifically divided into:complete response(CR),Partial response(PR),Stable disease(SD),Progressive disease(PD).4.Recorded the complications and survival of patients after surgery and during treatment,the primary observation endpoints of the study were objective response rate(ORR)and disease control rate(DCR)6 months after surgery,and the secondary observation endpoints were overall survival(OS),progression-free survival(progression-free survival,PFS).ORR is defined as the proportion of CR plus PR cases,and DCR is defined as the proportion of CR plus PR plus SD cases.OS is defined as the time from the start of the first HAIC treatment to death for any cause or the cut-off of follow-up,PFS as the time from the start of the first HAIC treatment to the first occurrence of disease progression or death from any cause or the cut-off time for follow-up,and if the patient is lost to follow-up before death,the time of their last follow-up is counted as the time to death.Follow-up was until December 2022.5.Multivariate analysis of risk factors affecting OS and PFS.6.Evaluation of treatment-related adverse events using the Standard Common Terminology for Adverse Events(CTCAE-Version 5.0).Results:The baseline data of HAIC plus targeted and immunological therapy group,HAIC plus targeted therapy group and HAIC plus immunological therapy were not statistically different.The ORR and DCR of the three groups at 1 month after treatment were not statistically different(ORR:73.3%vs 71.4%vs 62.5%,X~2=0.690,P>0.05;DCR:100.0%vs 100.0%vs 93.8%,X~2=2.472,P>0.05).There was no significant difference in ORR and DCR among the three groups at 3 months after treatment(ORR:80%vs 64.3%vs 62.5%,X~2=2.064,P>0.05;DCR:96.7%vs 92.9%vs 93.8%,X~2=0.955,P>0.05).After 6 months of treatment,the ORR and DCR of the three groups were significantly different(ORR:80%vs 57.1%vs 43.8%,X~2=6.523,P<0.05;DCR:96.7%vs 78.6%vs 75.0%,X~2=5.637,P<0.05).The ORR and DCR of the three groups were further compared by chi-square test,and the ORR of HAIC plus target immunological therapy group was better than that of HAIC plus immunological therapy group(P<0.05).However,there was no significant difference in ORR between HAIC plus targeted and immunological therapy group and HAIC plus targeted therapy group after 6 months of treatment,and between HAIC plus targeted therapy group and HAIC plus immunological therapy group(P>0.05).After 6 months of treatment,there was no significant difference in DCR between HAIC plus targeted and immunological therapy group and HAIC plus targeted therapy group,HAIC plus targeted and immunological therapy group and HAIC plus immunological therapy group,HAIC plus targeted therapy group and HAIC plus immunological therapy group(all P>0.05).There were significant differences in AFP and PIVKA-Ⅱbetween the three groups after combined treatment and before treatment(P<0.005),indicating that the AFP and PIVKA-II after treatment were significantly lower than those before treatment.Survival analysis showed that the follow-up time ranged from 6 months to24 months,and the number of deaths during the follow-up period was 6 in HAIC plus targeted and immunological therapy group,5 in HAIC plus targeted therapy group,and 4 in HAIC plus immunological therapy group.There was no significant difference in median progression-free survival(m PFS)among the three groups(5.0 months vs6.0 months vs 6.0 months,X~2=0.109,P=0.947).The median overall survival(m OS)of the three groups was statistically significant(11.0 months vs 7.0 months vs 6.0months,X~2=8.701,P=0.013).Further pairwise chi-square test of subgroups showed that the m OS of HAIC plus targeted and immunological therapy group was better than that of HAIC plus targeted therapy group,and the m OS of HAIC plus targeted and immunological therapy group was better than that of HAIC plus immunological therapy group(all P<0.05).There was no significant difference in m OS between HAIC plus targeted therapy group and HAIC plus immunological therapy group(P>0.05).Cox univariate and multivariate analysis showed that hepatic artery-portal vein fistula was an independent risk factor for PFS,and the maximum tumor diameter>10cm may be a risk factor for PFS.Combined treatment and Child-Pugh grade B are independent risk factors for OS,and portal vein invasion may be a risk factor for OS.No treatment-related death occurred in the three groups.Most of the treatment-related adverse reactions were grade 1-2,and very few were grade 3-4.The incidence of hypertension in HAIC+target immunization group and HAIC plus targeted therapy group was significantly higher than that in HAIC plus immunological therapy group(43.3%vs 42.9%vs 0%,X~2=11.959,P=0.003),and there was no significant difference in other adverse reactions between the two groups(P>0.05).Conclusion:In the treatment of advanced liver cancer,HAIC combined with targeted and immunological therapy showed better ORR than HAIC alone combined with immunological therapy after 6 months of treatment.HAIC plus targeted and immuno-logical therapy have longer m OS than HAIC combined with targeted therapy or HAIC combined with immunological therapy,respectively,suggesting better overall survival benefits.Compared with HAIC alone combined with targeted therapy and HAIC alone combined with immunological therapy,HAIC alone combined with immunolo-gical therapy did not occur more serious treatment-related adverse reactions.HAIC combined with targeted therapy and immunological therapy has good tumor control effect and controllable treatment-related adverse reactions in the treatment of advanced liver cancer,which is worthy of further promotion and application. |
