Analysis Of Factors Associated With Recurrence After Microwave Ablation For Early-stage Liver Cancer

Background:Hepatocellular carcinoma(HCC)is a highly complex malignant tumor with high incidence and poor prognosis.With the advent of tyrosine-kinase inhibitor and immune checkpoint inhibitors,treatment of patients with advanced liver cancer has become more effective,and they can reduce the burden of disease by controlling disease progression,however,the disease burden of patients with advanced liver cancer is still very heavy.In recent years,with the development of screening for high-risk population,the proportion of patients with early-stage liver cancer is increasing gradually.Although the long-term prognosis is much better than that of middle and late-stage liver cancer,the recurrence and metastasis rate of liver cancer is high,it seriously affects the survival of patients with early liver cancer.Therefore,it is important to analyze the risk factors of postoperative recurrence of early stage liver cancer,monitor the high-risk population closely,give early intervention and reduce the postoperative recurrence rate for the survival of early stage liver cancer patients.According to the clinical liver cancer staging in Barcelona,the treatment methods for early stage liver cancer include surgical resection,liver transplantation and local ablation therapy,considering factors such as lack of donor and tumor progression,the application of liver transplantation is very limited;combined with China’s national conditions,liver cancer patients as a whole are mainly middle-aged and elderly,most of them have underlying chronic liver disease and may not be able to tolerate surgical treatment;local ablation targets the lesion and kills the tumor cells directly,which is less traumatic to the organism Local ablation targets the lesion,kills the tumor cells directly,is less traumatic to the body,is repeatable,and has few complications,and is widely used clinically for the treatment of early stage liver cancer.In addition,microwave ablation enhances immune function while destroying tumor cells,but the high tumor recurrence rate after ablation treatment is its main problem.Tyrosine kinase inhibitors are systemic therapeutic agents that have been applied to intermediate and advanced hepatocellular carcinoma in recent years,mainly by inhibiting tumor angiogenesis and promoting normal anastomosis of tumor vessels,which in turn inhibits tumor growth and significantly improves the survival of patients with intermediate and advanced hepatocellular carcinoma,but the effectiveness of their use in patients with early-stage hepatocellular carcinoma is unclear.Therefore,in order to provide a clinical reference for combining tyrosine kinase inhibitors with microwave ablation in early-stage hepatocellular carcinoma patients,we summarized the data from our center to identify the risk factors for the high recurrence rate of early-stage hepatocellular carcinoma after microwave ablation,to explore whether the combination therapy reduces the recurrence rate and improves survival,and to provide a better clinical study to support early intervention by screening in the high-risk recurrence time period to improve patients’prognosis.The study is expected to improve the prognosis of patients.Aims:1.Exploring the prognosis and risk factors affecting recurrence after microwave ablation of early-stage hepatocellular carcinoma;2.To investigate the prognostic impact of combining TKI after microwave ablation for early-stage hepatocellular carcinoma and to provide a reference for clinical treatment plan.Methods:1.The clinical data of liver cancer patients who underwent microwave ablation in our department from December 2011 to December 2020 were collected,and a total of 167patients with early-stage liver cancer were finally included for retrospective analysis.The follow-up ended on December 31,2021.Continuous variables conforming to normal distribution were expressed by means±standard deviation,non-normally distributed by median(interquartile spacing),and categorical variables were expressed by frequencies as well as percentages;differences between groups for categorical and continuous variables were expressed by chi-square test or Fisher exact test and Mann-Whitney U test,respectively;The disease-free survival rate and overall survival rate of 1 year,2 years,3years and 5 years after microwave ablation of early liver cancer in our center were observed.;Patients with early-stage liver cancer were divided into the early recurrence group(recurrence time interval not more than 2 years)and the late recurrence group,and the differences in indicators between the two groups were compared,and the risk factors affecting patients’early recurrence and late recurrence were analyzed by logistic regression multifactor analysis,and the ratio(OR)and its 95%confidence interval(95%CI).Survival curves at different tumor diameters were plotted by Kaplan-Meier method and tested by Log-rank.2.We collected clinical data of hepatocellular carcinoma patients who underwent microwave ablation in our department from December 2011 to December 2020,and finally included a total of 16 patients with early-stage hepatocellular carcinoma after microwave ablation combined with tyrosine kinase inhibitors,using propensity score matching method to balance baseline characteristics between groups,using the"Match It"package,method"nearest",for 1:2 matching.Results:1.Recurrence and risk factors after microwave ablation for early stage hepatocellular carcinoma1.1 The overall characteristics of patients who underwent microwave ablation at our center at an early stage were described:the majority were male,83.8%had cirrhosis,85.6%had a single tumor,78.4%had a maximum tumor diameter of no more than 3 cm;21.6%had platelets of no more than 50*10~9/L,81.4%had Child-Pugh grade A,and the proportion of patients with Child-Pugh grade A was 81.4%.The proportions of BCLC staged at stage0 or A were 28.1%and 71.9%,respectively,and the proportions of ALBI graded at grade I or II were 44.3%and 54.5%.1.2 In the whole study,57 patients developed postoperative complications after microwave ablation,including 17 patients with postoperative fever,the highest temperature was 38.6°C,which improved after physical cooling;5 patients developed bacterial infection,which improved after antibiotics;33 patients developed right upper abdominal distension,occasionally with back radiating pain,which could be relieved by themselves.2 patients developed transient liver function deterioration after surgery,which improved after hepatoprotective treatment.Two patients had a transient deterioration of liver function after surgery,which improved after hepatoprotective treatment.1.3 The median follow-up time of the whole study was 36.6 months,and the median recurrence time was 25.2 months.The disease-free survival rates of half a year,1 year,2years,3 years and 5 years after microwave ablation were 86.7%,72.0%,53.3%,39.8%and 19.1%,respectively.The median survival time was 85.7 months.The overall survival rates of half a year,1 year,2 years,3 years and 5 years after microwave ablation were 97.0%,94.6%,89.9%,74.1%and 62.8%.1.4 Tumor diameter is a risk factor for recurrence after microwave ablation of early hepatocellular carcinoma;tumor diameter and diabetes mellitus are independent risk factors for recurrence after microwave surgery for early hepatocellular carcinoma.1.5 ALBI grading is a risk factor affecting patients with early recurrence(≤2 years),ALBI grading is an independent risk factor affecting early recurrence.2.Prognostic impact of combining TKI after microwave ablation for early-stage hepatocellular carcinoma2.1 The effects of TKI on recurrence after microwave ablation for hepatocellular carcinoma was not statistically different.2.2 The effect of TKI on long-term survival after microwave ablation of hepatocellular carcinoma was not statistically different.Conclusions:1.Microwave ablation is safe and effective in the treatment of early liver cancer.2.Patients with tumor diameter more than 3cm,and diabetes mellitus are high-risk groups for early postoperative recurrence of early liver cancer.Patients with preoperative ALBI grade II/III are high-risk groups for early postoperative recurrence of early liver cancer.3.The results of the small sample case-control study of combined TKI treatment did not show the effect on the recurrence,disease-free survival and overall survival of early liver cancer after ablation,which needs to be verified in a larger sample size study.