Integration of radiotherapy with anti-PD-1 antibody for the treatment of intrahepatic or hilar cholangiocarcinoma: reflection from four cases.

Cholangiocarcinoma (CCA) represents a clinically challenging disease with a dismal prognosis. A therapeutic plateau has been reached with traditional treatments. However, with immunotherapy advances in cancer therapy, integration of stereotactic body radiotherapy (SBRT) with anti-PD-1 antibody shows a synergistic effect and high clinical efficacy in many cancer types. This combination may represent a breakthrough in the treatment of this fatal malignancy. Here, we report four cases of refractory advanced intrahepatic or hilar cholangiocarcinoma that were successfully controlled with anti-PD-1 antibody following or concurrent with SBRT. Furthermore, one case was initially unresectable; however, following this novel combined therapy, it became operable. We discuss the challenges of developing predictive biomarkers for anti-PD-1 antibody responsiveness. We also consider the regulatory effect of SBRT on the tumor microenvironment and the potential advantages of this therapy combination for treatment of intrahepatic or hilar cholangiocarcinoma. These are important considerations and provide direction for future clinical trial designs.