Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus.
Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus.
JAMA Netw Open. 2019 Sep 4;2(9):e1911154. doi: 10.1001/jamanetworkopen.2019.11154.
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.
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.
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.
重要性：肝内胆管细胞癌是一种侵袭性肝胆恶性肿瘤，其特征为局部进展和频繁转移。转移性肝内胆管细胞癌患者采用肝脏局部定向确定性治疗可能会改善总体生存率。
目的：比较单独化疗与化疗联合肝脏局部定向确定性治疗转移性肝内胆管细胞癌患者的总生存率。
设计、设置和参与者：本队列研究使用国家癌症数据库，确定了 2004 年 1 月至 2014 年 12 月期间诊断为转移性肝内胆管细胞癌的 2201 例患者，这些患者接受了化疗联合或不联合肝脏手术或外照射治疗，剂量达到 45Gy 或更高。采用多重插补、Cox 比例风险、倾向评分匹配和里程碑分析来调整混杂变量。分析于 2018 年 9 月至 2019 年 2 月进行。
暴露：单独化疗和化疗联合肝脏定向手术或放疗。
主要结果和测量：总生存率。
结果：共纳入 2201 例患者（1131 例[51.4%]为男性；中位[四分位间距]年龄为 63[5571]岁），其中 2097 例（95.3%）接受单独化疗，104 例（4.7%）接受化疗联合肝脏局部定向治疗（手术治疗 76 例[73.1%]，放疗 28 例[26.9%]）。单独化疗组患者的原发肿瘤大小中位数（四分位间距）更大[7.0（4.410.0）cm 比 5.6（4.08.3）cm；P=0.048]，肺转移频率更高[383 例（25.9%）比 7 例（6.7%）；P=0.004]。接受肝脏定向局部治疗的患者远处淋巴结转移频率更高[34 例（32.7%）比 528 例（25.2%）；P=0.045]。多变量分析显示，与单独化疗相比，肝脏定向局部治疗与更高的总生存率相关（风险比[HR]，0.60；95%CI，0.480.74；P<0.001）。对单独化疗的 208 例患者进行倾向评分匹配，与接受化疗联合肝脏定向局部治疗的 104 例患者进行匹配。肝脏定向局部治疗仍与更高的总生存率相关（HR，0.57；95%CI，0.440.74；P<0.001），在 3 个月（HR，0.61；95%CI，0.470.79；对数秩 P<0.001）、6 个月（HR，0.68；95%CI，0.500.92；对数秩 P=0.01）和 12 个月（HR，0.68；95%CI，0.470.98；对数秩 P=0.04）的里程碑分析中也保持一致。
结论和相关性：在这项研究中，与单独化疗相比，在转移性肝内胆管细胞癌患者中，化疗联合肝脏手术或放疗可提高总生存率。鉴于这种疾病的可用数据有限，这些发现可能具有重要价值，应该在独立队列或前瞻性研究中得到验证。
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