Study On Predictive Factors Of Clinical Efficacy Of Targeted And Immunization Combined Interventional Therapy For Primary Hepatic Carcinoma And Observation Of Adverse Reactions

Objective:The clinical outcomes of patients with primary hepatic carcinoma(PHC)treated with targeted therapy and immunotherapy combined with interventional therapy were analyzed,and the predictive value of conventional laboratory indices and inflammation-related indices and their change values at baseline and during treatment on the prognosis of patients with hepatocellular carcinoma treated with targeted therapy and immunotherapy combined with interventional therapy was investigated.The adverse reactions that occurred during the treatment were also followed up and observed.Methods:Patients with primary hepatic carcinoma treated in Taizhou People’s Hospital from January 2018 to July 2022 were retrospectively studied.Patients who were treated with targeted and/or immune combined with TACE(transhepatic artery chemoembolization)and TACE alone were selected.The indexes of blood routine examination,liver function,tumor markers and liver imaging were reexamined every 2 months(±2 weeks),and the adverse reactions during the course of treatment were recorded until December 31,2022.The baseline data of the patients,the changes of tumor markers and inflammation-related indexes and the clinical efficacy of 8 weeks,16 weeks,24 weeks,32 weeks and 40 weeks of treatment were analyzed.The patients with combined treatment regimen were divided into high OS group and low OS group according to their median OS(overall survival time).Univariate analysis and logistic multivariate regression analysis were used to screen out the relevant factors affecting OS,and the predictive efficiency was evaluated by ROC curve.The patients were divided into groups according to the cutoff values of predictive factors obtained by AUC(area under ROC curve).The 1 year and 3 year cumulative survival rates were estimated by Kaplan-Meier survival curve,and Log-rank logarithmic rank test was used to compare the differences between groups.The difference was statistically significant(P < 0.05).Results:1 A total of 134 patients with primary hepatic carcinoma were included,including 81 in the combination group and 53 in the interventional group.The efficacy analysis showed objective remission rates of 35% vs 13%,disease control rates of 60% vs 29%,and overall survival rates of 75.3% vs 62.1% and 46.5% vs 21.8% at 1 and 3 years in the combined and interventional groups,and all these differences were statistically significant.2 The combined group was divided into a high OS group(36 cases)and a low OS group(45 cases)according to the median OS of their cohort(18.0 months).Analysis of baseline data showed statistically significant differences in Child-Pugh classification and CNLC staging between the two groups,and the low OS group had higher NLR,PLR(platelet lymphocyte ratio),MLR(monocyte lymphocyte ratio),SII(systemic immunoinflammatory index),and SIRI(systemic inflammatory response index)than the high OS group,and lower PNI(prognostic nutritional index)than the high OS group,all with P values <0.05.3 During the course of treatment,AFP(alpha-fetoprotein),PIVKA II(protein induced by vitamin k absence or antagonist II),NLR,PLR,MLR,SII,SIRI,and PNI indexes in the high-OS and low-OS groups showed a dynamic decline compared to baseline levels.At 16 weeks of treatment,there was a statistically significant difference in the decrease in AFP and PNI between the two groups.4 Logistic multivariate regression analysis showed that baseline NLR(P=0.013),baseline SIRI(P=0.004),decrease in PNI at 16 weeks of treatment(P=0.016),CNLC stage(P=0.025)and number of tumors(P=0.032)were independently associated with OS.The AUCs for baseline NLR,baseline SIRI,and decrease in PNI at 16 weeks of treatment to predict OS were 0.841,0.817,and 0.786,respectively,with optimal cutoff of 2.60,0.60×109/L,and 14.14%,respectively.Comparing the overall survival rate of the groups with baseline NLR ≤2.60 and NLR >2.60,the groups with baseline SIRI ≤0.60×109/L and SIRI >0.60×109/L,the groups with PNI decrease ≤14.14% and decrease >14.14% at 16 weeks of treatment,the CNLC stage grouping,and the groups with tumor number <3 and tumor number ≥3,the differences were statistically significant.5 Among the adverse events that occurred during treatment,the highest rate of hematologic toxicity [58 cases(40.8%)] was followed by gastrointestinal reactions [34 cases(23.9%)],and the rest were elevated transaminases [18 cases(12.7%)],hypothyroidism [11cases(7.7%)],rash [8 cases(5.6%)],elevated blood pressure [8 cases(5.6%)] and fever [5cases(3.5%)].The highest rates of rash [4 cases(10.3%)] and elevated blood pressure [3cases(7.7%)] occurred in the targeted combined intervention group,and the highest rates of gastrointestinal reactions [15 cases35.7%)],fever [2 cases(4.8%)],hematologic toxicity[22 cases(52.4%)],elevated transaminases [8 cases(19.0%)],and hypothyroidism [6 cases(14.3%)] occurred in the targeted immune combined intervention group.No serious adverse events occurred.Conclusion:1 The clinical efficacy and overall survival rate of primary hepatic carcinoma patients treated with targeted immunotherapy combined with TACE were much higher than those of patients treated with TACE alone.2 Among primary hepatic carcinoma patients receiving targeted immunotherapy,the more advanced the CNLC stage and the higher the number of tumors,the worse the OS.3 Baseline NLR of 2.60,SIRI of 0.60×109/L and PNI decrease of 14.14% at 16 weeks of treatment can be used as cut-off values to predict the prognosis of patients with primary hepatic carcinoma,and those above the critical values suggest poor prognosis.4 Baseline NLR combined with baseline SIRI can be used as a prognostic assessment indicator for patients with primary hepatic carcinoma.5 The safety and tolerability of targeted immunotherapy combined with TACE in patients with primary hepatic carcinoma were good.