Efficacy and Prognosis of Radiotherapy for Hepatocellular Carcinoma with Tumor Thrombosis in Main Portal Vein or/and Vena Cava

Abstract

To investigate response and survival of radiotherapy (RT) for hepatocellular carcinoma with tumor thrombosis in main portal vein or vena cava, and to analyze prognostic factors. From January 2010 to December 2016, a total of 61 cases of hepatocellular carcinoma with pathological or clinical diagnosis of hepatocellular carcinoma with tumor thrombosis in main portal vein or vena cava were enrolled this study. Main portal vein tumor thrombosis (PVTT) was defined as tumor thrombi was located in main trunk or first branches of portal vein. Fifty-five patients were with PVTT and 4 patients were with venous vein tumor thrombosis alone, respectively. In addition, another 2 patients were with both vein thromboses. All patients had a liver function of Child-Pugh A before radiotherapy. Eighty-five percent of patients (52/61) had a history of hepatitis B, 2% (2/61) had hepatitis C, and 12% (7/61) had no history of hepatitis. Eighty-four percent of patients (51/61) had previously received transcatheter arterial chemoembolization (TACE). Eight patients were treated with concurrent RT and sorafenib. Tumor response was evaluated in one to three months after completion of RT. Survival and prognostic factors were analyzed by Kaplan-Meier method and Cox regression model. The factors included gender, age, history of hepatitis, AFP level before radiotherapy, number of intrahepatic lesions, maximum tumor diameter (MTD), combined TACE, radiotherapy dose were included in analysis of prognosis. All patients were treated with intensity modulated radiotherapy by conventional fraction of 2Gy/f. The median dose was 50Gy (28-66Gy). Response rate (RR, complete response + partial response) was 55.7% when considering all lesions of whole body. In field of RT, RR of the primary tumor was 77.1% and RR of the tumor thrombosis was 83.7%. The 2-year overall survival was 29.9% and median survival time (MST) was 13.6 months. Median time to progression (TTP) was 4.7 months. The 2-year progression free survival of tumor thrombosis was 88.6%. Multivariate analysis showed that the MTD>10cm was an independent poor prognostic factor of TTP (HR, 1.961, 95%CI, 1.034-3.717). TTP in patients with MTD≤10cm and MTD>10cm were 5.0 months and 3.3 months (p=0.026), respectively. However, for MST, combination of TACE (both before or after RT) was an independent favor prognostic factor (HR, 0.184, 95%CI, 0.06-0.565). MST of combination therapy was 15 months, and MST of patients receiving radiotherapy alone was 4 months (p<0.001). Of all patients, grade III or higher liver function damage was 1.6%, and no lethal radiation-induced liver disease occurred. Grade III or higher hematological toxicity was 11.5%. The tumor thrombosis is more sensitive to radiation therapy than the primary tumor. Radiotherapy improves survival by the perfect control of tumor thrombosis. Progression of outside field of RT is primary failure mode for patients with main PVTT. Combination of radiotherapy and TACE is benefit to survivals.