External Beam Radiation Therapy for Intrahepatic Cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive primary liver malignancy with rising incidence and poor outcomes. Most patients present with unresectable disease, with mortality frequently driven by intrahepatic tumor burden and liver failure, making local control (LC) a central treatment goal. External beam radiation therapy (EBRT) plays an expanding role in multidisciplinary care, enabled by modern planning, image guidance, and motion management techniques that permit safe dose escalation. Across definitive EBRT series, a consistent dose–response relationship is observed. Higher biologically effective doses (BED) have been associated with improved outcomes, with BED > 80.5 Gy achieving superior 3-year LC and overall survival (OS) compared with lower-dose regimens. Dose-escalated approaches have reported 2-year LC rates of 80–90% and median OS approaching 20–30 months in selected patients. Advanced technologies such as proton beam therapy and MR-guided radiotherapy may further improve the therapeutic ratio, with reported grade 3 or higher toxicity rates below 8% and one- to two-year LC rates exceeding 90% in PBT series. Beyond definitive therapy, EBRT contributes to tumor downstaging, enabling surgical resection in approximately 10–30% of initially unresectable patients, and may improve survival in selected metastatic or liver-dominant disease. Early-phase data combining EBRT with immune checkpoint inhibition are emerging and warrant prospective validation.