Abstract
Intrahepatic cholangiocarcinoma is an aggressive hepatobiliary malignant neoplasm characterized by local progression and frequent metastasis. Definitive local therapy to the liver in the setting of metastatic intrahepatic cholangiocarcinoma may improve overall survival. To compare the overall survival of patients with metastatic intrahepatic cholangiocarcinoma treated with chemotherapy alone vs chemotherapy with definitive liver-directed local therapy. This cohort study used the National Cancer Database to identify 2201 patients with metastatic intrahepatic cholangiocarcinoma diagnosed between January 2004 and December 2014 who received chemotherapy with or without hepatic surgery or external beam radiation to a dose 45 Gy or higher. Multiple imputation, Cox proportional hazards, propensity score matching, and landmark analysis were used to adjust for confounding variables. Analyses were performed between September 2018 and February 2019. Chemotherapy alone and chemotherapy with liver-directed surgery or radiation. Overall survival. A total of 2201 patients (1131 [51.4%] male; median [interquartile range] age, 63 [55-71] years) who received chemotherapy alone (2097 [95.3%]) or chemotherapy with liver-directed local therapy (total, 104 [4.7%]; surgery, 76 [73.1%]; radiation, 28 [26.9%]) were identified. Patients treated with chemotherapy alone had larger median (interquartile range) primary tumor size (7.0 [4.4-10.0] cm vs 5.6 [4.0-8.3] cm; P = .048) and higher frequency of lung metastases (383 [25.9%] vs 7 [6.7%]; P = .004). Patients treated with liver-directed local therapy had higher frequency of distant lymph node metastases (34 [32.7%] vs 528 [25.2%]; P = .045). Liver-directed local therapy was associated with higher overall survival compared with chemotherapy alone on multivariable analysis (hazard ratio [HR], 0.60; 95% CI, 0.48-0.74; P < .001). A total of 208 patients treated with chemotherapy alone were propensity score matched with 104 patients treated with chemotherapy plus liver-directed local therapy. Liver-directed local therapy continued to be associated with higher overall survival (HR, 0.57; 95% CI, 0.44-0.74; P < .001), which persisted on landmark analysis at 3 months (HR, 0.61; 95% CI, 0.47-0.79; log-rank P < .001), 6 months (HR, 0.68; 95% CI, 0.50-0.92; log-rank P = .01), and 12 months (HR, 0.68; 95% CI, 0.47-0.98; log-rank P = .04). In this study, the addition of hepatic surgery or irradiation to chemotherapy was associated with higher overall survival when compared with chemotherapy alone in patients with metastatic intrahepatic cholangiocarcinoma. These findings may be valuable given the paucity of available data for this disease and should be validated in an independent cohort or prospective study.
Highlights
Cholangiocarcinoma is the most common biliary malignant neoplasm and second most common primary hepatic malignant neoplasm in the United States, and its incidence continues to increase globally.[1,2] Primary therapy for localized intrahepatic cholangiocarcinoma (ICC), which is anatomically and biologically distinct from extrahepatic perihilar and distal cholangiocarcinomas, entails hepatic resection with or without adjuvant chemotherapy and hepatic irradiation
Liver-directed local therapy was associated with higher overall survival compared with chemotherapy alone on multivariable analysis
A total of 208 patients treated with chemotherapy alone were propensity score matched with 104 patients treated with chemotherapy plus liver-directed local therapy
Summary
Cholangiocarcinoma is the most common biliary malignant neoplasm and second most common primary hepatic malignant neoplasm in the United States, and its incidence continues to increase globally.[1,2] Primary therapy for localized intrahepatic cholangiocarcinoma (ICC), which is anatomically and biologically distinct from extrahepatic perihilar and distal cholangiocarcinomas, entails hepatic resection with or without adjuvant chemotherapy and hepatic irradiation. Given the rarity of ICC, observational studies leveraging national databases are beneficial for evaluating patterns of care and survival. To this end, we sought to evaluate the overall survival of patients with metastatic ICC treated with chemotherapy with local treatment to the liver, in the form of hepatic resection or definitive irradiation, using the National Cancer Database (NCDB), a nationwide hospital-based registry encompassing 70% of newly diagnosed malignant neoplasms in the United States
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