Adjuvant Radiotherapy On Resection Margin To Prevent Local Recurrence In Hepatocellular Carcinoma With Inadequate Margin And Microvascular Invasion

Backgrounds and Objective: Hepatocellular carcinoma(HCC)is the fifth most common malignant tumor in the world,and the second leading cause of death.China is a country with high incidence of HCC,and the total number of cases accounts for more than half of the global annual incidence.The main cause is chronic hepatitis B infection and subsequent hepatitis and cirrhosis.At present,the main treatment methods for HCC include surgical resection,transarterial chemo-embolizaiton(TACE),biological targeting therapy,radiotherapy,systemic chemotherapy,etc.At present,the main group of patients treated by hepatic surgery is early small hepatocellular carcinoma.Surgical treatment is the preferred treatment.The main reason affecting the long-term prognosis of HCC is recurrence after operation.Anti-recurrence therapy after HCC is one of the keys to improve the curative effect of surgery,but there is no effective local adjuvant therapy.In order to find appropriate adjuvant therapy after HCC resection,it is necessary to identify the risk factors of recurrence after HCC resection,so as to explore effective interventions to inhibit the growth of cancer cells.Research Methods: In the first part,171 patients who underwent resection of hepatocellular carcinoma in the liver transplantation Department of Shanghai Eastern Hepatobiliary Surgery Hospital from July 2014 to December 2016 were collected.The surgical methods,incision margin status and micrometastasis of these patients were retrospectively analyzed.The surgical methods were divided into anatomical resection and non-anatomical resection groups.The incision margin status was based on the internal incision margin width of the resected specimens.The degree of micrometastasis was divided into wide and narrow incision margins.Micrometastasis was assessed according to whether there was microvascular invasion and/or pericancerous lesions reported by pathology.All the patients were followed up to compare the survival time without recurrence and the total survival time.The second part of the study recruited clinical and imaging data of 262 patients with BCLC-0/A stage receiving hepatectomies,analyzed the related factors of m VI by logistic multivariate regression,and established a prediction model of m VI,which was presented as a nomogram.The third part is a prospective randomized controlled study.According to the admission criteria,patients were enrolled in the study from August 2015 to December 2016.Three weeks after HCC resection,they were treated with gamma-ray external radiotherapy.The non-recurrence survival time,total survival time and side effects of radiotherapy were observed and compared with the control group.Research Results: The retrospective analysis showed that there was no significant difference in RFS and OS between anatomical and non-anatomical resection in patients with small hepatocellular carcinoma(P= 0.089 and 0.068 respectively);RFS in wide incision margin group was higher than that in narrow incision margin group(P = 0.003),OS had no obvious advantage(P = 0.175);RFS and OS in m VI positive group were lower than those in m VI negative group(P < 0.001 and < 0.001 respectively);The RFS and OS of sexual patients were lower than those of negative patients(P 0.002 and < 0.001,respectively).The results of stratified analysis showed that RFS and OS could be improved by anatomical excision when m VI was positive(P 0.005 and 0.019,respectively).Anatomical excision could improve RFS and OS when pericancerous lesions were present(P 0.005 and 0.007,respectively).COX regression analysis showed that m VI and pericancerous lesions were independent risk factors for prognosis of patients in this group.In the second part,logistic regression analysis showed that splenic enlargement,abnormal prothrombin elevation,incomplete tumor envelope,tumor diameter?5cm,and multinodular fusion tumors were of great significance in preoperative prediction of m VI.The optimal total score cut-off value of Nomogram was 350 points,and the area under the ROC curve reached 0.8758 and 0.8661 in the training group and the validation group,respectively.When the cumulative score reached more than 220 points,the model predicted that the positive rate of m VI would reach more than 80%.Thirdly,a prospective randomized controlled study showed that RFS in the radiotherapy group was better than that in the control group(P =0.027),and there was no significant difference in OS(P =0.297).There was no radiotherapy-related liver disease in the radiotherapy group,and all the side effects of radiotherapy could be alleviated by symptomatic treatment.Conclusions: Pericancerous micrometastasis is the main cause of short-term recurrence of small hepatocellular carcinoma after operation.Regular resection and wide resection margin can improve the surgical effect of such patients.Anti-recurrence therapy like external radiotherapy targeting the resection marginal liver tissue can improve the surgical effect of such patients.It is an effective supplementary treatment for patients with hepatocellular carcinoma who can not achieve anatomical resection and ensure a certain width of resection margin.