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    Original Investigation
    September 13, 2019

    Association of Liver-Directed Local Therapy With Overall Survival in Adults With Metastatic Intrahepatic Cholangiocarcinoma

    Author Affiliations
    • 1Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus
    • 2Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus
    • 3Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus
    • 4Division of Surgical Oncology, Department of Surgery, The Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus
    JAMA Netw Open. 2019;2(9):e1911154. doi:10.1001/jamanetworkopen.2019.11154
    Key Points español 中文 (chinese)

    Question  Is the addition of liver-directed local therapy to chemotherapy associated with an improvement to overall survival for patients with metastatic intrahepatic cholangiocarcinoma?

    Findings  This cohort study, using data from 2201 patients with metastatic intrahepatic cholangiocarcinoma from the National Cancer Database, found statistically significant higher overall survival in patients treated with chemotherapy and liver-directed surgery or irradiation vs patients treated with chemotherapy alone.

    Meaning  The findings suggest that patients with metastatic intrahepatic cholangiocarcinoma who receive chemotherapy, definitive treatment to the primary liver tumor in the form of surgery or radiation is associated with improved overall survival.


    Importance  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.

    Objective  To compare the overall survival of patients with metastatic intrahepatic cholangiocarcinoma treated with chemotherapy alone vs chemotherapy with definitive liver-directed local therapy.

    Design, Setting, and Participants  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.

    Exposures  Chemotherapy alone and chemotherapy with liver-directed surgery or radiation.

    Main Outcomes and Measures  Overall survival.

    Results  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).

    Conclusions and Relevance  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.