| BackgroundHepatocellular carcinoma(HCC)is the most common pathological types of primary liver cancer and the third leading cause of cancer-related deaths worldwide.At present,there are various treatment options for liver cancer,but the therapeutic effect is closely related to liver cancer staging.China Liver Cancer staging(CNLC)was combined with the characteristics of patients with liver cancer in China and clinical practice to formulate,which is widely recognized by clinicians and is widely used in clinical practice.Transarterial chemoembolization,surgical resection and systemic therapy were used as the main treatment for CNLC stage Ⅱb-Ⅲb HCC.TACE has become an effective treatment method for patients with advanced liver cancer by virtue of its advantages such as small trauma,repeatability,and good curative effect.Drug-eluiting bead(DEB),as an emerging embolization material in recent years,can accurately embolize target blood vessels,and load tumor-sensitive chemotherapeutic drugs which lasts for a long time in the tumor area.It has showed considerable clinical efficacy.However,the single TACE treatment mode still has limitations.After the treatment of TACE,their micro-environment is in a hypoxic and ischemic state,and the expression of VEGF on the surface of stromal cells is up-regulated,which leads to,tumor recurrence or metastasis.In recent years,molecular targeted drugs,such as lenvatinib and sorafenib,can inhibit the expression of VEGF and thus delay tumor progression,and have become the first-line treatment drugs for middle and advanced HCC.In addition,programmed cell death protein-1(PD-1)inhibitors,as a common immune checkpoint inhibitor,can block PD-1 cell signal pathways,and promote the human immune system to kill tumor cells.Studies have shown that the combination of molecular targeted drugs and PD-1 inhibitors can complement each other’s advantages and further improve the efficacy of comprehensive treatment of liver cancer.There are few clinical studies on DEB-TACE combined with lenvatinib or PD-1 in the treatment of HCC at present,The purpose of the study is to investigate the safety and clinical efficacy of lenvatinib and PD-1 inhibitors in the treatment of CNLC Ⅱb-Ⅲb HCC after DEB-TACE,and to analyze the prognostic factors,which provide reference for the selection and improvement of clinical treatment options for advanced liver cancer.Material and MethodsThe clinical data of 85 HCC patients with stage CNLC Ⅱb-Ⅲb between May 2019 to October 2020,who was in the Department of Radiological Intervention at the First Affiliated Hospital of Zhengzhou University and the Affiliated Tumor Hospital of Zhengzhou University,were rertospectively reviewed.All patients were diagnosed by pathological examination or imaging examination.All patients were treated with DEB-TACE after excluding surgical contraindications.According to the patient’ s laboratory examination and recovery,lenvatinib or combination of lenvatinib and PD-1 was recommended,and patients were fully informed of drug efficacy,potential adverse reactions and costs.If patients agreed to the physician’s recommendation,lenvatinid or combination of lenvatinib and PD-1 was administered 5-7 days after the DEB-TACE.Patients who refused the combination therapy underwent DEB-TACE only.According to different treatment regimens,they were divided into DEB-TACE group(Group D),DEB-TACE pius lenvatinib group(Group DL)and DEB-TACE pius lenvatinib pius PD-1 group(Group DLP).Adverse reactions during treatment and follow-up were given symptomatic treatment.The imaging examinations(CT or MRI)of patients before treatment and 1,3,and 6 months after treatment was performed,and the tumor response was evaluated according to Modified Response Evaluation Criteria in Solid Tumors(mRECIST).The survival of each patient was recorded and the survival curves and progression-free survival curves were plotted.Logistic regression was used to analyze the independent influencing factors of overall response rate(ORR)one month after operation,and Cox regression model was used to perform univariate and multivariate analysis to screen the independent influencing factors of the overall survival(OS)and progress free survival(PFS).The three groups were compared and analyzed for statistically significant differences in blood routine,liver and kidney function,coagulation function and tumor markers before surgery,1 week and 1 month after treatment(P<0.05 was considered statistically significant).The serious complications was observed to evaluate safety.ResultA total of 62 patients with HCC were included in this study,with 23 were in the Group D,19 were in the Group DL,and 20 were in the Group DLP.All patients underwent TACE successfully,144 times with an average of 2.32 times and the success rate was 100%.The median follow-up time of patients in the three groups was 8.0(1.0-19.0)months,and no patients were lost to follow up.There was no significant difference in each index among the three groups(P>0.05).Both the ORR and DCR showed trends to be the highest in the Group DLP,followed by the Group DL and then the Group D.OS and PFS were both the highest in the Group DLP,followed by the Group DL and the shortest in the Group D.Multivariate Cox regression analysis showed that treatment methods,gender,GGT and portal vein invasion were independent risk factors for OS in HCC patients with stage CNLC Ⅱb-Ⅲb(P<0.05);treatment methods,TBIL,and hepatic artery fistula were independent prognostic factors for PFS in HCC patients with stage CNLCⅡb-Ⅲb(P<0.05).Compared with preoperative indexes,WBC,ALT and GGT increased and ALB decreased at 1 week after treatment,and there were no significant differences in the other indexes of three groups(P>0.05).There was no significant difference in the incidence of post-embolization syndrome among the three groups(P>0.05).The common adverse reaction in Group DL were hypertension(68.4%vs60.0%)and hand-foot syndrome(47.4%vs45.5%).In addition,there were 4 cases of rash,3 cases of reactive cutaneous capillary endothelial proliferation(RCCEP)and 1 case of immune-associated pneumonia in the Group DLP,all of which is Grade I-II adverse reaction.The symptoms were relieved after administration of glicocorticoid,local treatment or withdrawal of the drug.Conclusion:1.The short-term efficacy of DEB-TACE combined with lenvatinib or PD-1 inhibitor in the treatment of stage CNLC Ⅱb-Ⅲb HCC is more superior than DEB-TACE alone,which can prolong OS and PFS of patients.2.Multivariate Cox regression analysis revealed that treatment methods,GGT and portal vein invasion were independent risk factors for OS in HCC patients with stage CNLC Ⅱb-Ⅲb. |
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