Efficacy And Safety Of Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors For The Treatment Of Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

Objective: To retrospectively compare the effectiveness of transarterial chemoembolization(TACE)combined with immune checkpoint inhibitors(ICIs),(here-after,TACE-ICIs)and TACE monotherapy in the treatment for the hepatocellular carcinoma(HCC)patients with portal vein tumor thrombus(PVTT)and absence of lymph nodes and distant metastasis,and assess the safety of TACE-ICIs treatment method.Methods: This study retrospectively collected and sorted the medical data of patients with HCC and PVTT that received TACE-ICIs or TACE monotherapy from June 2015 to February 2022 in two hospitals.After screening,patients who received TACE combined with immune checkpoint inhibitors were included in the TACE-ICIs group,and patients who only received TACE treatment were included in the TACE group.The administration of ICIs started within 2 weeks after the initial TACE operation.The short-term tumor response of the two groups was reflected by objective response rate(ORR)at three months and disease control rate(DCR)at three months evaluated by the modified evaluation criteria for the efficacy of solid tumors(m RECIST).Overall survival(OS)and progression-free survival(PFS)of the patients who received TACE-ICIs were compared with that of the patients who received TACE monotherapy.Then Univariate and multivariate COX regression analysis were applied to explore the factors affecting the OS prognosis of patients.We assessed the patient data of patients in TACE-ICIs group and conduct telephone follow-up to evaluate their adverse events.Propensity score matching(PSM)with a ratio of 1:1 and a matching tolerance of 0.01 was used to balance the potential baseline difference of the two groups of patients.Results: 46 patients in TACE-ICIs group and 292 patients in TACE group were enrolled.Before PSM,patients in the TACE-ICIs group survived the patients in the TACE group(median OS,17.1 vs 10.3 months,p < 0.001,HR =0.362).There were 45 patients in the TACE-ICIs group and 45 patients in the TACE group who were matched by PSM.After PSM,the ORR of TACE-ICIs group and TACE group were 37.3% and 8.9%(p=0.001),and the DCR were88.9% and 60.0%(p=0.002),respectively.Patients in the TACE-ICIs group also survived the patients in the TACE group after PSM(median OS,17.1 vs11.7 months,p = 0.005,HR = 0.290).In the subgroup analysis after PSM,TACE combined with ICIs showed a better advantage in prolonging OS than TACE alone in the patients with PVTT type I and II(median OS,17.1 vs 12.5months,p = 0.036),also with PVTT type III and VI(median OS,15.8 vs 8.3months,p = 0.034).The PFS of the patients in the TACE-ICIs group and TACE group were 7.0 months and 5.0 months(p = 0.003).We found that Child-Pugh class B and blood AFP level ≥ 400ng/m L were risk factors affecting OS of patients,and blood leukocyte count ≥ 100 × 109/L was a protective factor for OS prognosis.The adverse effects of patients in TACE-ICIs group mainly included bilirubin elevation,reactive cutaneous capillary endothelial proliferation,abdominal pain,liver enzyme elevation,fever,rash,etc.There were no grade 4 adverse events.The adverse effects of TACE-ICIs were relieved after symptomatic support treatment.Conclusion: TACE combined with ICIs may be superior to TACE monotherapy in prolonging the survival time and delaying the progression of tumor for patients with HCC and PVTT,with controllable side effects and satisfactory safety.