Definitive liver radiotherapy for intrahepatic cholangiocarcinoma with extrahepatic metastases

Introduction: Tumor-related liver failure (TRLF) is the most common cause of death in patients with intrahepatic cholangiocarcinoma (ICC). Though we previously showed that liver radiotherapy (L-RT) for locally advanced ICC is associated with less frequent TRLF and longer overall survival (OS), the role of L-RT for patients with extrahepatic metastatic disease (M1) remains undefined. We sought to compare outcomes for M1 ICC patients treated with and without L-RT. Methods: We reviewed ICC patients found to have M1 disease at initial diagnosis at a single institution between 2010 and 2021 who received L-RT, matching them with an institutional cohort by propensity score and a National Cancer Database (NCDB) cohort by frequency technique. The median biologically effective dose (BED10) was 98 Gy (interquartile range [IQR] 80.5-97.9 Gy) for L-RT. Patients treated with other local therapies or supportive care alone were excluded. We analyzed survival with Cox proportional hazards modeling. Results: We identified 61 patients who received L-RT and 220 who received chemotherapy alone. At median follow up of 11 months after diagnosis, median OS was 9 months (95% confidence interval [CI] 8-11) and 21 months (CI 17-26) for patients receiving chemotherapy alone and L-RT, respectively. TRLF was the cause of death more often in the patients who received chemotherapy alone compared to those who received L-RT (82% vs. 47%; P=0.001). On multivariable propensity-score matched analysis, associations with lower risk of death included duration of upfront chemotherapy (hazard ratio [HR] 0.82; P=0.005) and receipt of L-RT (HR 0.40; P=0.002). The median OS from diagnosis for NCDB chemotherapy alone cohort was shorter than that of the institutional L-RT cohort (9 vs. 22 months; P<0.001). Discussion/Conclusion: For M1 ICC, L-RT associated with a lower rate of death due to TRLF and longer OS vs. those treated with chemotherapy alone. Prospective studies of L-RT in this setting are warranted.