Phase II Study of Concurrent Sorafenib and Radiotherapy for Advanced Hepatocellular Carcinoma With Portal Vein and/or Hepatic Vein Tumor Thrombosis

Abstract

<h3>Purpose/Objective(s)</h3> Portal vein or hepatic vein tumor thrombosis is a leading predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). We conduct this phase II clinical trial to investigate the efficacy and safety of concurrent sorafenib and radiotherapy for advanced HCC with portal vein and/or hepatic vein tumor thrombosis. <h3>Materials/Methods</h3> We designed a single-arm, prospective phase II trial to evaluate median survival time (MST), overall response rate (ORR), time to progression (TTP) and toxicities in patients of HCC with portal vein and/or hepatic vein tumor thrombosis receiving concurrent sorafenib and radiotherapy. Eligibility criteria included the following: clinical or histologic diagnosis of HCC with portal vein or hepatic vein tumor thrombosis; liver-GTV > 700ml; and ECOG performance status score of 0 or 1 <b>etc</b>. Eligibility patients would receive radiotherapy to hepatic primary tumor and vein tumor thrombosis with concurrently sorafenib with a dose of 400mg twice daily. Prescription of radiotherapy would be a conventional fraction dose of 2-2.6Gy to a total dose of 40 to 65Gy to tumor. Sorafenib will be maintained with a dose of 400mg twice daily after radiotherapy until disease progression, or unacceptable adverse events. <h3>Results</h3> Between April 2018 and January 2020, a total of 86 eligible patients were enrolled. Seventy patients were with portal vein thrombosis, 5 patients were with hepatic vein tumor thrombosis, and 11 patients were with portal vein and hepatic vein tumor thrombosis. For portal vein thrombosis, 87.5% patients involved main trunk or first branches of portal vein. For hepatic vein tumor thrombosis, 43.8% patients involved inferior vena cava, and 2 patients involved right atrium. The median dose of radiotherapy was 54Gy (40-65Gy). ORR was 53.4% and disease control rate (DCR) was 76.6%. With a median follow-up of 24 months for living patients, MST and TTP was 16.8 months and 7.1 months, respectively. The 2-year local control rate for hepatic primary tumor and tumor thrombosis were 83.0% and 90.7%, respectively. Out-field recurrence in liver and distance metastasis were the main failure pattern. The 2-year out-field recurrence rate in liver and distance metastasis rate were 43.6% and 45.7%. Concurrent sorafenib and radiotherapy was well tolerated by patients. All patients were able to complete radiotherapy as planned. And 87.2% patients could complete concurrent sorafenib as a dose of 400mg twice daily. The most common grade 3 toxicities were thrombocytopenia (23.3%), leukopenia (14.0%), dermatitis (4.7%), anemia (3.5%), hand-foot syndrome (2.3%) and elevated alanine aminotransferase (2.3%). Classical or non-classical radiation-induced liver disease was not noted. <h3>Conclusion</h3> Concurrent sorafenib and radiotherapy is an effective, well tolerated and promising treatment in HCC patients with portal vein and/or hepatic vein tumor thrombosis. This trial was registered at ClinicalTrials.gov (number NCT03535259).