Exploration Of Response-related Factors For Hepatic Arterial Infusion Of FOLFOX Regime In Patients With Advanced Hepatocellular Carcinoma

Background:Hepatocellular carcinoma（HCC）is one of the most common cancer in China.Most patients with hepatocellular carcinoma are diagnosed with advanced stage and lost the opportunity for radical treatment due to the insidious onset.At present,these patients are mainly treated with molecular targeted therapy such as sorafenib and lenvatinib.However,the objective response rate,disease control rate,and overall survival are not satisfactory for patients with advanced HCC.What’s more,dose reductions or dose interruptions were happened in some patients because severe adverse events.Recently,several clinical trials had confirmed that hepatic arterial infusion chemotherapy of FOLFOX（HAIF）is effective and well tolerated for patients with advanced hepatocellular carcinoma.Nevertheless,the individual efficacy for patients receiving HAIF differs significantly.Therefore,reliable factors that can predict the efficacy of HAIF are needed to clarifiedPurpose:To explore the predictors related to the efficacy of patients with advanced hepatocellular carcinoma who received HAIF in order to improve the clinical value of this treatment.Methods:We retrospectively evaluated 96 patients with advanced HCC treated with HAIF between December 2017 and April 2019.The primary endpoint was overall survival（OS）.Age,gender,tumor burden,portal tumor thrombus,extrahepatic metastasis and AFP,Child-pugh class,Neutrophil-to-lymphocyte ratio,Lymphocyte subset count,HMGB1 that before and three weeks after HAIF treatment were evaluated to predict prognosis.In addition,the role of DNA damage repair（DDR）gene mutations as predictive biomarker was analyzed in 33 patients received Next Generation Sequencing.Results:Median OS for all patients was 11.2 months（95%CI:9.7-12.7 months）,and the best tumor response of CR/PR/SD/PD were 0/41.7%/29.2%/29.2%（RECIST1.1）and 3.1%/41.7%/26%/29.2%（mRECIST）,respectively.The objective response rate were 41.7%（RECIST1.1）and 44.8%（mRECIST）,respectively.Logistics regression showed that patients with AFP<200 ng/ml（OR=0.904,95%CI=0.8920.938,P=0.04）,NLR<2.77 at baseline（OR=0.117,95%CI=0.032-0.421,P=0.001）,HMGB1<13.9ng/ml in three weeks（OR=0.916,95%CI=0.843-0.995,P=0.04）,Child-pugh A class（OR=0.674,95%CI=0.451-0.879,P=0.02）were more likely to objective response after HAIF treatment.Furthermore,DDR gene mutations present was also a predictor for higher objective response rate.Multivariate analysis identified that Child-pugh B class（HR=2.14,1.27-3.62,P=0.004）,AFP≥200ng/ml（HR=2.08,1.21-3.35）.P=0.01),NLR≥2.77 at baseline（HR=2.57,1.45-3.96,P=0.001）,HMGB1≥13.9 ng/ml in three weeks（HR=2.03,1.13-3.21,P=0.02）,onset The 3-week Treg≥5.8%（HR=1.82,1.07-3.11,P=0.03）is an independent predictors of poor overall survival in HAIF treatment,objective response after treatment（HR=0.12,0.05-2.89,P<0.001）is an independent predictor associated with improved OS.Conclusion:These results suggested that AFP<200 ng/ml,NLR<2.77 at baseline,Child-pugh A class,DDR pathway gene mutations present,HMGB1<13.9ng/ml in three weeks were associated with better objective response rate in HCC patients treated with HAIF.Child-pugh B grade,AFP≥200ng/ml,NLR≥2.77 at baseline,HMGB1≥13.9 ng/ml,three weeks,Treg≥5.8%in three weeks were associated with poor overall survival.The results of this study was helpful to improve the clinical value of HAIF for advanced HCC patients.