Radiation dose escalation for locally advanced unresectable intrahepatic and extrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (IHCC) and extrahepatic cholangiocarcinoma (EHCC) remain challenging diseases to treat. The majority of patients present with advanced disease, and the tumors often cause life-threatening biliary obstruction and vascular compromise of the liver. Local control (LC) of these tumors has the potential to prolong life for patients. While escalated-dose radiation therapy (EDRT) has been demonstrated to be an effective, safe option to achieve LC of IHCC, data for EHCC suggest that EDRT with current techniques has limitations, often due to dose-limiting bowel structures in close proximity to the extrahepatic biliary system. Here we review the results of EDRT for IHCC and EHCC and point to potential directions to combine radiotherapy with novel agents. The molecular characterization of cholangiocarcinoma has particularly opened new avenues for clinical investigations of targeted therapies with EDRT and may point to ways to achieve both systemic and LC benefits for patients.