Observation Of The Efficacy,adverse Events And Changes Of Inflammatory Markers Of TACE Combined With Immune Checkpoint Inhibitor Plus Tyrosine Kinase Inhibitors For The Treatment Of Hepatocellular Carcinoma

Objective:To observe the therapeutic effect,adverse events,and changes of blood inflammatory markers of TACE(transarterial chemoembolization)combined with Immune Checkpoint Inhibitor(Camrelizumab)plus Tyrosine Kinase Inhibitors(Sorafenib or Lenvatinib or Apatinib)for the treatment of Hepatocellular Carcinoma.Methods:We retrospectively analyzed patients with HCC who had received TACE+ICI+TKI or ICI+TKI treatment in First Affiliated Hospital of Gannan Medical University from August 2019 to March 2021,and case data were collected from 54 patients.The modified Response Evaluation Criteria in Solid Tumors(m RECIST)criteria were used for efficacy evaluation in terms of CR(complete response),PR(partial response),SD(stable disease),PD(progressive disease),confirmed the ORR(objective response rate)and DCR(disease control rate),and the progression-free survival(PFS),overall survival(OS),treatment‐related adverse events(TRAEs)were recorded.Blood inflammatory markers were collected within 1 week before TACE and immunotherapy and after 2 cycles of PD-1,including NLR(neutrophils to lymphocytes ratio),PLR(platelet lymphocyte ratio),MLR(monocyte to lymphocyte ratio),SII(neutrophils multiply with platelet to lymphocyte ratio),d NLR(derive neutrophil-to-lymphocyte ratio)and PNI(prognostic nutritional index).The curative effect and the incidence of adverse reactions during the treatment were compared between the two groups(the TACE+ICI+TKI group(n=31)and the ICI+TKI group(n=23)).Univariate and multivariate analyses were performed using logistic regression models to identify independent influencing factors of ORR.The PFS and OS curves were drawn by the Kaplan-Meier method.The Log-rank test was used for univariate analysis of PFS and OS,and the multivariate Cox proportional hazards regression model was used to determine the independent influencing factors of PFS and OS.The changes of blood inflammatory markers in the TACE+ICI+TKI group were observed before treatment,after TACE,and after two cycles of systemic treatment(ICI+TKI).Results:1.For short-term efficacy,compared with ICI + TKI,the ORR of TACE + ICI +TKI for patients with HCC after 2 courses of ICI was 58.1%: 17.4%(P<0.05),and the ORR after 4 courses of ICI was 67.7%: 39.1 %(P < 0.05)with 6.5% of patients achieved CR,and the DCR was 90.3% and 73.9%(P = 0.218),respectively.First TACE treatment was an independent protective factor for ORR.2.For long-term efficacy,median PFS was 9.7 months for TACE + ICI + TKI and 3.7 months for ICI + TKI(P =0.001),median OS was not reached for TACE +ICI + TKI,and 11.6 months for ICI + TKI(P=0.009).First TACE treatment was an independent protective factor for PFS.First TACE treatment and hepatitis B virus infection are independent prognostic factors for OS in patients with HCC.3.In terms of TRAEs,the overall adverse reactions of the two groups were mainly graded 1/2.The TACE+ICI+TKI group was significantly higher than the ICI+TKI group in terms of ALT(alanine aminotransferase)elevation and AST(aspartate transaminase)elevation,and the differences of other adverse reactions were not statistically significant(P values were all greater than 0.05).The adverse reaction rash was significantly associated with ORR(P<0.05).4.Blood inflammatory markers NLR,MLR,SII,NLR,and PNI decreased after TACE treatment compared with pre-treatment(P<0.05);PLR and SII still decreased significantly after two cycles of systemic treatment compared with pre-treatment.Conclusion:1.Both TACE+ICI+TKI and ICI+TKI regimens are effective and safe treatment methods for HCC,and the TACE+ICI+TKI regimen has more advantages than the ICI+TKI regimen;2.The TACE+ICI+TKI regimen can increase the short-term and long-term efficacy of patients with HCC,suggesting that the first TACE treatment has a synergistic effect in the treatment of HCC with the ICI+TKI regimen;3.The adverse reaction rash may be related to the short-term efficacy of TACE combined with ICI plus TKI regimen in the treatment of HCC;4.HBV infection may be related to the long-term efficacy of TACE combined with ICI+TKI regimen in the treatment of HCC;5.TACE treatment may have the effect of improving blood inflammatory markers in HCC.