Safety and efficacy of liver-directed radiotherapy after chemoimmunotherapy for advanced cholangiocarcinoma: an early report from a large tertiary cancer center

Background: Recent randomized controlled trials have established chemoimmunotherapy as the standard of care for patients with advanced biliary cancers with a median overall survival (OS) of about thirteen months. No data exist to demonstrate the safety and efficacy of liver-directed radiotherapy (RT) for extrahepatic and intrahepatic cholangiocarcinoma (CCA) in the era of chemoimmunotherapy. The purpose of this study is to report our early experience treating patients with CCA using RT and chemoimmunotherapy. Methods: Twenty-eight patients with CCA who received chemoimmunotherapy sequentially and/or concurrently with RT were retrospectively analyzed. The median biologic equivalent dose (BED) of RT was 84.0 [interquartile range (IQR) 81.4–98.0] Gy. For each patient, we tabulated demographic, disease, and treatment characteristics, including kinetic assessment of laboratory values. The primary goal was to assess acute and late toxicities. Secondary goals were to measure OS using the Kaplan-Meier method and local control using cumulative incidence curves, considering death as a competing risk for local failure. We explored clinical and pathological associations with outcomes. Results: Most patients (89%) experienced acute low-grade RT toxicities. There were no grade three acute toxicities. Two patients experienced late toxicities potentially attributable to RT. One patient experienced grade two hepatic impairment and another patient experienced grade three pneumonitis. The median OS measured from time of RT completion to death was 17.4 months, and the cumulative incidence of local failure for our patient population was 11% [95% confidence interval (CI): 2.7–26%] at six months, 24% (95% CI: 9.3–43%) at 12 months, and 30% (95% CI: 12–50%) at 24 months. Exploratory analyses indicated that patients whose absolute lymphocyte count recovered faster three months after RT had better survival outcomes [hazard ratio (HR) 0.11 (95% CI: 0.021–0.56, P=0.02)]. Presence of portal vein thrombus (P=0.04) and evidence of liver dysfunction on laboratory values [e.g., increased aspartate aminotransferase (AST) (P=0.005), direct bilirubin (P<0.001), and total bilirubin (P<0.001)] associated with worse OS. Conclusions: RT appears safe for patients with CCA who receive chemoimmunotherapy, with promising survival outcomes. Immune kinetics and other standard clinicopathological features may identify important prognostic differences amongst patients and help guide management decisions.