High Rate of Local Control Reported With High-Dose Hypofractionated Proton Beam Therapy in Liver Cancers


Key Points

  • The local control rate at 2 years was 94.8% in patients with hepatocellular carcinoma and 94.1% in patients with intrahepatic cholangiocarcinoma, according to the findings of a phase II study.
  • Overall survival was 76.5% and 69.7% at 1 year and 63.2% and 46.5% at 2 years. 

High-dose hypofractionated proton beam therapy produced a high rate of local control in patients with localized unresectable hepatocellular carcinoma or intrahepatic cholangiocarcinoma, according to a phase II study reported in the Journal of Clinical Oncology by Hong et al.

Study Details

In the study, 83 evaluable patients from Massachusetts General Hospital, MD Anderson Cancer Center, or University of Pennsylvania with Child-Turcotte-Pugh scores of A or B, no extrahepatic disease, and no prior radiation received proton therapy in 15 fractions, to a maximum total dose of 67.5 Gy equivalent. In total, 44 patients had hepatocellular carcinoma, 37 had intrahepatic cholangiocarcinoma, and 2 had mixed hepatocellular carcinoma/intrahepatic cholangiocarcinoma (included in the intrahepatic cholangiocarcinoma group). A total of 80% had a Child-Turcotte-Pugh score of A; 96% had an Eastern Cooperative Oncology Group performance status of 0 or 1; 4.8% had no cirrhosis; and prior treatment had been received by 32% of those with hepatocellular carcinoma and 62% of those with intrahepatic cholangiocarcinoma. The median maximum tumor dimension was 5.0 cm for hepatocellular carcinoma and 6.0 cm for intrahepatic cholangiocarcinoma; 27% and 13% had multiple tumors; and 30% and 28% had tumor vascular thrombosis.


The median proton therapy dose delivered was 58.0 Gy in both patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma. At a median follow-up of 19.5 months among survivors, the local control rate at 2 years was 94.8% in those with hepatocellular carcinoma and 94.1% in those with intrahepatic cholangiocarcinoma. Median progression-free survival was 13.9 and 8.4 months; progression-free survival was 56.1% and 41.4% at 1 year and 39.9% and 25.7% at 2 years. Median overall survival was 49.9 and 22.5 months; overall survival was 76.5% and 69.7% at 1 year and 63.2% and 46.5% at 2 years.

Grade 3 radiation-related toxicity occurred in four patients (5%), consisting of thrombocytopenia in one patient with intrahepatic cholangiocarcinoma and liver failure and ascites, stomach ulcer, and elevated bilirubin in three patients with intrahepatic cholangiocarcinoma. No grade ≥ 4 radiation-related toxicity was observed. Worsening of Child-Turcotte-Pugh score occurred in three patients (4%).

The investigators concluded: “High-dose hypofractionated proton therapy demonstrated high [local control] rates for hepatocellular carcinoma and intrahepatic cholangiocarcinoma safely, supporting ongoing phase III trials of radiation in hepatocellular carcinoma and intrahepatic cholangiocarcinoma.”

The study was supported by the National Institutes of Health and the National Cancer Institute.

Theodore S. Hong, MD, of Massachusetts General Hospital, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.