胆道恶性肿瘤合并高危复发因素患者术后辅助靶向联合免疫治疗的安全性及有效性分析

Safety and efficacy analysis of postoperative adjuvant targeted therapy combined with immunotherapy in patients of biliary tract carcinoma with high-risk factors for recurrence

摘要

目的：探讨术后辅助靶向联合免疫治疗在合并高危复发因素的胆道恶性肿瘤患者中的安全性与有效性。方法：回顾性分析2023年1—12月于南京医科大学第一附属医院接受手术切除后不愿接受辅助化疗、自愿选择靶向联合免疫治疗的24例胆道恶性肿瘤合并高危复发因素患者的临床资料。记录患者临床病理特征、无复发生存期（relapse-free survival，RFS）、总生存期（overall survival，OS）及不良反应（adverse event，AE）发生情况。采用Kaplan-Meier法进行生存分析，Cox比例风险回归分析影响RFS的因素。结果：24例患者随访期间，12例（50.00%）患者复发，7例（29.17%）患者死亡，中位RFS为12个月，中位OS未达到。其中，R0切除合并高危复发因素患者的中位RFS、中位OS均未达到，R1切除患者的中位RFS为8个月，中位OS未达到。R0切除合并高危复发因素患者的RFS率、OS率均显著高于R1切除患者。预后因素分析显示，年龄<60岁、肿瘤单发、R0切除、无淋巴结转移、无血管侵犯、单一复发高危因素为影响患者RFS的因素（P均<0.05）。安全性方面，AE发生率为79.17%（19/24），3级AE发生率为8.33%（2/24），无治疗相关死亡事件发生。结论：术后辅助靶向联合免疫治疗在合并高危复发因素的胆道恶性肿瘤患者中显示出一定的疗效，且安全性可控。年龄<60岁、肿瘤单发、R0切除、无淋巴结转移、无血管侵犯、单一复发危险因素为本研究中影响患者RFS的因素。

Abstract

Objective：To explore the safety and efficacy of postoperative adjuvant targeted therapy combined with immunotherapy in patients of biliary tract carcinoma with high-risk factors for recurrence. Methods：A retrospective analysis was performed on the clinical data of 24 patients with biliary tract carcinoma complicated with high-risk factors for recurrence，who underwent surgical resection in the First Affiliated Hospital of Nanjing Medical University from January to December 2023，declined adjuvant chemotherapy，and voluntarily opted for targeted therapy combined with immunotherapy. The clinicopathological characteristics，relapse-free survival（RFS），overall survival（OS），and incidence of adverse events（AE）of the enrolled patients were recorded. Survival analysis was performed using the Kaplan-Meier method，and the Cox proportional hazards regression model was used to analyze the factors affecting RFS. Results：During the follow-up of the 24 patients，12 patients（50.00%）developed recurrence and 7 patients（29.17%）died. The median RFS was 12 months，and the median OS was not reached. Among them，the median RFS and median OS were not reached in patients with R0 resection and high-risk factors for recurrence，while the median RFS was 8 months and the median OS was not reached in patients with R1 resection. The RFS rate and OS rate of patients with R0 resection and high-risk factors for recurrence were significantly higher than those of patients with R1 resection. Prognostic factor analysis showed that age <60 years，single tumor，R0 resection，no lymph node metastasis，no vascular invasion，and single high-risk recurrence factor were prognostic factors affecting RFS（all P < 0.05）. In terms of safety，the incidence of all-grade AE was 79.17%（19/24），and the incidence of grade 3 AE was 8.33%（2/24）. No treatment-related death occurred. Conclusion：Postoperative adjuvant targeted therapy combined with immunotherapy shows certain efficacy and controllable safety in biliary tract carcinoma patients with high-risk factors for recurrence. Age <60 years，single tumor，R0 resection，no lymph node metastasis，no vascular invasion，and single high-risk recurrence factor are prognostic factors affecting RFS in this research.

关键词

胆道恶性肿瘤 / 高危复发因素 / 靶向治疗 / 免疫治疗 / 有效性 / 安全性

Key words

biliary tract carcinoma / high-risk factors for recurrence / targeted therapy / immunotherapy / efficacy / safety

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基金资助

北京陈菊梅公益基金会(L2025070182)