Proton Beam Therapy in Managing Unresectable Hepatocellular Carcinoma with Bile Duct Invasion

SIMPLE SUMMARY: Hepatocellular carcinoma with bile duct invasion is well known for its poor survival outcome, and no definite treatment guideline has been suggested. This study analyzed the treatment outcome and toxicity of proton beam therapy in managing patients with unresectable hepatocellular carcinoma with bile duct invasion. After a median follow-up of 19.9 months, proton beam therapy provided an optimal in-field control rate for these patients. The overall survival results were comparable with surgical series. This study concluded that proton beam therapy offers desirable treatment outcomes with acceptable toxicities. Based on the results, proton beam therapy provides patients with another optimal alternative for treating this notorious subtype of hepatocellular carcinoma. ABSTRACT: Hepatocellular carcinoma (HCC) with bile duct invasion is a rare and notorious subtype of HCC. This study included patients that had unresectable HCC with bile duct invasion and proton beam therapy between November 2015 and February 2021. Twenty patients fit the inclusion criteria. The median tumor size was 6.3 cm. Nine patients (45.0%) had major vascular invasions. All included patients received the radiation dose of 72.6 gray relative biological effectiveness due to the proximity of porta hepatis and tumor. The median follow-up time was 19.9 months. The median overall survival was 19.9 months among deceased patients. The 1-year cumulative local recurrence rates were 5.3%, with only two patients developing in-field failure. The 1-year and 2-year overall survival rates were 79.4% and 53.3%. The 1-year progression-free survival was 58.9%. Four patients developed radiation-induced liver disease. The 1-year cholangitis-free survival was 55.0%. Skin toxicity was the most common acute toxicity and rarely severe. Eight patients developed ≤ grade 3 gastrointestinal ulcers. Proton beam therapy offers desirable survival outcomes for unresectable HCC patients with bile duct invasion. Optimal local tumor control could also be obtained within acceptable toxicities.