Objectives: To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC) and to identify patients who may benefit from it. Methods: The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 at 13 hospitals in China were collected retrospectively. According to the inclusion and exclusion criteria,455 patients were included in this study,including 69 patients (15.2%) who received adjuvant chemotherapy and 386 patients (84.8%) who did not receive adjuvant chemotherapy. There were 278 males and 177 females,with age of 59 (16) years (M(IQR))(range:23 to 88 years). Propensity score matching (PSM) method was used to balance the difference between adjuvant chemotherapy group and non-adjuvant chemotherapy group. Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS) and recurrence free survival(RFS)between the two groups. Univariate analysis was used to determine prognostic factors for OS. Multivariate Cox proportional hazards models were then performed for prognostic factors with P<0.10 to identify potential independent risk factors. The study population were stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy. Results: After 1∶1 PSM matching,69 patients were obtained in each group. There was no significant difference in baseline data between the two groups (all P>0.05). After PSM,Cox multivariate analysis showed that lymph node metastasis (HR=3.06,95%CI:1.52 to 6.16,P=0.039),width of resection margin (HR=0.56,95%CI:0.32 to 0.99,P=0.044) and adjuvant chemotherapy (HR=0.51,95%CI:0.29 to 0.91,P=0.022) were independent prognostic factors for OS. Kaplan-Meier analysis showed that the median OS time of adjuvant chemotherapy group was significantly longer than that of non-adjuvant chemotherapy group (P<0.05). There was no significant difference in RFS time between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group (P>0.05). Subgroup analysis showed that,the OS of female patients,without HBV infection,carcinoembryonic antigen<9.6 μg/L,CA19-9≥200 U/ml,intraoperative bleeding<400 ml,tumor diameter>5 cm,microvascular invasion negative,without lymph node metastasis,and AJCC stage Ⅲ patients could benefit from adjuvant chemotherapy (all P<0.05). Conclusion: Adjuvant chemotherapy can prolong the OS of patients with ICC after radical resection,and patients with tumor diameter>5 cm,without lymph node metastasis,AJCC stage Ⅲ,and microvascular invasion negative are more likely to benefit from adjuvant chemotherapy.
目的： 探讨术后辅助化疗对肝内胆管癌（ICC）患者根治性切除的影响及辅助化疗的可能获益人群。 方法： 回顾性收集2011年12月至2017年12月中国13家医院654例术后病理学诊断为ICC的患者的临床和病理学资料。根据纳入及排除标准，共纳入455例患者，男性278例，女性177例；年龄［M（IQR）］59（16）岁（范围：23~88岁）。其中接受术后辅助化疗69例（化疗组），未接受术后辅助化疗386例（未化疗组）。采用倾向性评分匹配（PSM）法对化疗组和未化疗组的组间差异进行均衡，采用Kaplan-Meier法绘制PSM前后的生存曲线，并使用Log-rank检验比较组间总体生存（OS）与无复发生存（RFS）的差异。采用Cox单因素分析确定根治性切除术后ICC患者OS的预后因素。然后对P<0.10的预后因素进行多变量Cox比例风险模型分析，以确定潜在的独立预后因素。根据纳入的研究变量及AJCC分期系统对人群进行分层，并使用Kaplan-Meier法进行亚组分析，探讨辅助化疗的可能获益人群。 结果： 经1∶1 PSM后，两组均得到69例患者，组间基线资料的差异无统计学意义（P值均>0.05）。PSM后Cox多因素分析结果显示，淋巴结是否转移（HR=3.06，95%CI：1.52~6.16，P=0.039）、切缘宽度（HR=0.56，95%CI：0.32~0.99，P=0.044）及是否接受辅助化疗（HR=0.51，95%CI：0.29~0.91，P=0.022）是影响ICC患者OS的独立预后因素。Kaplan-Meier 法分析结果显示，化疗组较未化疗组的OS时间更长（P<0.05）；而化疗组及未化疗组RFS时间的差异无统计学意义（P>0.05）。亚组分析结果显示，女性、无乙肝病毒感染、癌胚抗原<9.6 μg/L、CA19-9≥200 U/ml、术中出血量<400 ml、肿瘤最大径>5 cm、无微血管侵犯、淋巴结转移阳性、AJCC Ⅲ期的患者可从辅助化疗中获益（P值均<0.05）。 结论： 辅助化疗能延长ICC患者根治性切除术后的OS时间，肿瘤最大径>5 cm、淋巴结转移阳性、AJCC Ⅲ期、无微血管侵犯的患者更可能从辅助化疗中获益。.