The Study Of Efficacy And Safety Of Robotic Stereotactic Body Radiation Therapy For Locally Hepatocellular Carcinoma Patients:A Multi-institutional,Single-arm Phase Ⅱ Trial

Objective 1.The primary objective of the phase II trial was to evaluate the efficacy and safety of stereotactic body radiation therapy(SBRT)in treatment of the patients with locally primary hepatocellular carcinoma(HCC).2.To investigate the safety of robotic stereotactic body radiation therapy(SBRT)for hepatocellular carcinoma patients and its related factors.Methods 1.There were 74 patients with locally primary HCC treated by SBRT with 3 fractions of 45 Gy in 3 days.The primary endpoint is overall survival(OS),progression-free survival(PFS),local control rates(LC rates)and hepatic toxicity after SBRT.The Kaplan-Meier method was used to calculate overall survival(OS),progression-free survival(PFS)and local control rates(LC rates).Analyses were based on intention-to-treat.A p of 0.05 was considered the level of statistical significance.2.Seventy-four hepatocellular carcinoma(HCC)patients with Child-Turcotte-Pugh(CTP)Class A were included in a multi-institutional,single-arm phase II trial(NCT 02363218)between February 2013 and October 2016.All patients received SBRT treatment at a dose of 45 Gy/3f.The liver function was compared before and after SBRT treatment by the analysis of adverse hepatic reactions as well as changes in CTP classification.Results 1.Seventy-four patients were included in this study,median follow-up was 17.1 months(1.22-41.9 months).The median GTV volume was 25.17ml(2.1-123.6ml).The median time to OS was 16.0 months(1.22–41.95 months).The 1 and 2-year OS were 93.8% and 91.5%,respectively.The median time to progression was 13.5 months(1.22–41.95 months).The 1 year PFS was 89.4% and 2 year PFS was 71.3%.The median time to LC was 14.7 months(1.22–41.95 months).The 1 and 2-year LC rates were 97.2% and 84.3%,respectively.Among the 74 patients,24(32.4%)patients showed a complete response(CR),26(35.1%)patients showed a partial response(PR),20(27.0%)patients showed a stable disease(SD),4(5.4%)patients showed a progression disease(PD),and effective rate in the trial group(CR+PR)was 67.5%.There were 1 patient(1.4%)had Child-Pugh class from A to C due to SBRT,7(15.9%)patients had Child-Pugh class from A to B due to SBRT and improvement after therapy,Child-Pugh class returned to A in 6 months after SBRT in all patientsr.2.After SBRT treatment,8 patients presented with decreases in CTP classification,and 13 patients presented with > grade 2 hepatic adverse reactions.For patients presenting with > grade 2 hepatic adverse reactions,the total liver volume≤1162 ml and a normal liver volume(total liver volume-GTV)≤1148 ml were found to be independent risk factors and statistically significant(p<0.05).Conclusion 1.SBRT achieved high local control and with mild adverse reactions for the locally primary hepatocellular carcinoma(HCC).The results showed SBRT a safe and effective method in the treatment of HCC in inoperable Child-Pugh A patients.2.The total liver volume and normal liver volume are associated with the occurrence of > grade 2 hepatic adverse reactions after SBRT treatment on HCC patients.Therefore,if the fractionated scheme of 45 Gy/3f is applied in SBRT for HCC patients,a total liver volume>1162 ml and a normal liver volume>1148 ml should be ensured to improve therapeutic safety.