靶向联合免疫方案结合或不结合TACE/放疗在中晚期肝细胞癌转化治疗中的应用

Application of targeted immunotherapy combined with or without TACE/radiotherapy in the conversion therapy for intermediate-to-advanced hepatocellular carcinoma

摘要

目的: 评估靶向联合免疫方案结合或不结合经导管动脉化疗栓塞术(transcatheter arterial chemoembolization，TACE)/放疗对初始不可切除中晚期肝细胞癌(hepatocellular carcinoma，HCC)的有效性及安全性。方法: 回顾性分析20例巴塞罗那临床肝癌(Barcelona clinic liver cancer，BCLC)分期B/C期HCC患者资料，所有患者均接受靶向联合免疫治疗。19例联合TACE，其中4例加用放疗。评价指标包括客观缓解率(objective response rate，ORR)、显微镜下切缘阴性(microscopic margin-negative，R0)率及安全性。结果: 总体ORR为55%，疾病控制率为85%。4例(20%)成功实施R0切除，术后病理显示2例达到主要病理缓解。3级不良事件发生率为20%，多为免疫相关性肝损伤，安全性可控。全组中位随访18.3个月。4例手术患者中，3例在术后12个月无复发生存。结论: 以靶向联合免疫为核心的多模式方案对中晚期HCC具有显著的降期能力，R0切除率达20%，病理缓解显著且安全性可控。

Abstract

Objective: To evaluate the efficacy and safety of targeted therapy plus immunotherapy ± transcatheter arterial chemoembolization(TACE)/radiotherapy for conversion therapy in initially unresectable intermediate-to-advanced hepatocellular carcinoma(HCC). Methods: We retrospectively analyzed 20 patients with Barcelona clinic liver cancer(BCLC)stage B/C HCC treated with targeted therapy and immunotherapy；19 received concurrent TACE，and 4 received radiotherapy among them. The evaluation indicators include objective response rate(ORR)，microscopic margin-negative(R0)resection rate and safety. Results: The overall ORR and the disease control rate were 55% and 85%，respectively. Four patients(20%)successfully underwent R0 resection，with 2 achieving major pathological response. The incidence of grade ≥3 adverse events was 20%，primarily immune-related liver injury. At a median follow-up of 18.3 months，3 of the 4 resected patients remained recurrence-free 12 months post-surgery. Conclusion: The multimodal approach centered on targeted combined immunotherapy has a significant ability to downstage advanced HCC. The R0 resection rate is 20%，and the pathological remission is remarkable with controllable safety.

关键词

肝细胞癌 / 转化治疗 / 靶向联合免疫 / 经导管动脉化疗拴塞术 / 放疗

Key words

hepatocellular carcinoma / conversion therapy / targeted therapy combined with immunotherapy / transcatheter arterial chemoembolization / radiotherapy

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基金资助

国家自然科学基金(81972768)