Establishment A Prognostic Score Model For Predicting The Prognosis Of Patients With Unresectable Hepatocellular Carcinoma Undergoing Hepatic Arterial Infusion Chemotherapy

BackgroundTransarterial chemoembolization(TACE),which can effectively control tumor and improve the survival time of patients with hepatocellular carcinoma(HCC),is a commonly used treatment for patients with unresectable HCC.Recently,hepatic artery infusion chemotherapy(HAIC)using fluorouracil,leucovorin,and oxaliplatin is administered by continuous infusion,improving a high sustained concentration of chemotherapeutic agents in the hepatic tumors.It is reported that HAIC is characterized of higher tumor response and lower toxicities,and has been widely applied in the treatment of unresectable HCC in China.However,due to the large heterogeneity of unresectable HCC,the prognosis for those patients undergoing HAIC is of great variation.Additionally,the survival benefits of HAIC versus TACE for the treatment of unresectable HCC remain controversial.Aimsi)To establish a simple and effective prognostic score for predicting the prognosis of patients with unresectable HCC undergoing HAIC.ii)To compare the efficacy and safety of TACE and HAIC for patients with unresectable HCC.Methods1.Between January 2018 and December 2020,136 consecutive patients with unresectable HCC,who were treated with HAIC at Nanfang Hospital,Southern Medical University,were retrospectively enrolled in this study and defined as a training cohort.An external validation cohort including of 94 patients with unresectable HCC who were treated with HAIC at the Seventh Affiliated Hospital,Sun Yat-sen University were collected.2.Univariate and multivariate COX regression analysis were performed in the training cohort to explore the clinical factors independently correlated with overall survival(OS).A prognostic socre was then developed,validated using the external cohort,and compared the predictive ability with other current commonly used scoring/staging systems on liver cancer,including BCLC,CNLC,Okuda,CLIP and AJCC.3.An additional dataset of 289 patients with unresectable HCC who were treated with TACE at the same two centers were collected to compare the efficacy and safety with HAIC.4.Tumor response rate to HAIC and TACE assessed by RECIST and mRECIST,respectively,were compared.OS,progression-free survival(PFS),and safety were compared.Results1.In the multivariate analysis,tumor number,tumor capsule,a-fetoprotein and extension of portal vein tumor thrombus(PVTT)were identified as key factors associated with OS.2.These factors were used to establish a Hepatoma arterial chemotherapy prognostic socre(HAP socre,range from 0 to 8).The HAP score was well correlated with OS,the median survival was decrease as the HAP score increased.Patients were stratified into a very low-risk group(HAP-A,0 points),low-risk group(HAP-B,1-3 points),intermediate-risk group(HAP-C,4-5 pionts),and high-risk group(HAP-D,>5 points).The median survival for the four risk groups HAP-A,B,C,and D was 38 months,22 months,14 months,and 6 months,respectively(P<0.001).The external cohort validated well with the HAP score and showed better performance than other scoring/staging systems.3.The tumor response to HAIC and TACE was 39.5%and 33.6%,respectively(P=0.169).The median OS was 12 months and 10 months in the HAIC and TACE cohort,respectively(P=0.222).The median PFS was 4 months and 3 months in the HAIC and TACE cohort,respectively(P=0.010).4.Subgroup survival analysis showed the median OS for HCC patients with major PVTT(VP3-4)who received HAIC was superior to those who underwent TACE(9 vs.6 months,P<0.001).The differences on OS between the two treatments among other subgroups were not significant.5.The adverse events related to HAIC were lower than TACE,and the incidence rate of grade 3-4 was 11.7%vs.18.7%(P=0.030).Conclusions1.The proposed HAP socre can accurately predicts the outcomes of patients with unresectable HCC treated with HAIC.2.The patients with unresectable HCC who treated with HAIC had a comparable OS compared with those treated with TACE,but with a lower incidence rate of adverse events.3.Given patients with major PVTT,HAIC treatment might achieve a longer OS compared with TACE treatment.