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经动脉化疗栓塞术(TACE)-肝动脉灌注化疗(HAIC)联合PD-1抑制剂加乐伐替尼作为非转移性晚期肝细胞癌的术前转化治疗:单中心经验

Transarterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC) combined with PD-1 inhibitors plus lenvatinib as a preoperative conversion therapy for nonmetastatic advanced hepatocellular carcinoma: a single center experience.

作者信息

Zhao Wenchao, Liu Che, Wu Yintao, Yao Zhiyuan, Dou Qi, Li Wenping, Zhao Xiangfei, Xia Nianxin

机构信息

Faculty of Hepato-Pancreato-Biliary Surgery, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Medical School of Chinese PLA, Beijing, China.

出版信息

Transl Cancer Res. 2024 May 31;13(5):2315-2331. doi: 10.21037/tcr-24-93. Epub 2024 May 29.

Abstract

BACKGROUND

The preoperative conversion therapy for advanced hepatocellular carcinoma (HCC) is still being explored. This study reported the potential of combination of transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), programmed cell death protein-1 (PD-1) inhibitors and lenvatinib as preoperative conversion therapy for nonmetastatic advanced HCC.

METHODS

This retrospective study gathered data on patients with nonmetastatic advanced HCC who received this combination therapy. We used drug-eluting bead (DEB) instead of conventional iodized oil in TACE. The clinical data, conversion rate, adverse events (AEs) and short-term survival were summarized. A stratified analysis based on whether or not the patient received surgery was conducted.

RESULTS

A total of 28 patients were included in the analysis. No grade 4 AEs were observed. The overall objective response rate (ORR) was 64.3%. Ten (35.7%) patients eventually received R0 resection after 2 cycles of combination therapy. Patients succeeding to resection (surgery group) had significantly higher ORR (90.0% 50.0%, P=0.048). The proportion of patients with alpha-fetoprotein (AFP) >1,000 µg/L was significantly lower in surgery group (10.0% 66.7%, P=0.006). After combination therapy, more patients in surgery group experienced significant reduction of >90% in AFP levels (75.0% 23.1%, P=0.03), as well as standardized uptake value (SUV) of F-fluorodeoxyglucose (F-FDG) both in primary tumors and portal vein tumor thrombosis (PVTT) (60.0% 5.6%, P=0.003; 57.1% 8.3%, P=0.04). Of note, 85.7% of PVTT exhibited major pathological response (MPR) in pathological examination although only 28.6% achieved downstage in preoperative imaging examination. MPR was more commonly observed in PVTT than in main tumors (85.7% 20.0%). In non-surgery group, the median overall survival (OS) was 7 months with a 1-year survival rate of 27.8%, while in surgery group, the median OS was not reached and 1-year survival rate was 60.0%.

CONCLUSIONS

The combination of TACE-HAIC, PD-1 inhibitors and lenvatinib showed its benefit as a preoperative conversion therapy for nonmetastatic advanced HCC. In addition to imaging evaluation, significant reduction of F-FDG uptake and AFP can be used as predictors of successful conversion, especially for PVTT.

摘要

背景

晚期肝细胞癌(HCC)的术前转化治疗仍在探索中。本研究报告了经动脉化疗栓塞(TACE)、肝动脉灌注化疗(HAIC)、程序性细胞死亡蛋白-1(PD-1)抑制剂和乐伐替尼联合作为非转移性晚期HCC术前转化治疗的潜力。

方法

这项回顾性研究收集了接受这种联合治疗的非转移性晚期HCC患者的数据。我们在TACE中使用药物洗脱微球(DEB)代替传统的碘化油。总结了临床数据、转化率、不良事件(AE)和短期生存情况。根据患者是否接受手术进行分层分析。

结果

共有28例患者纳入分析。未观察到4级AE。总体客观缓解率(ORR)为64.3%。10例(35.7%)患者在2个周期的联合治疗后最终接受了R0切除。成功切除的患者(手术组)的ORR显著更高(90.0%对50.0%,P=0.048)。手术组中α-甲胎蛋白(AFP)>1000μg/L的患者比例显著更低(10.0%对66.7%,P=0.006)。联合治疗后,手术组更多患者的AFP水平显著降低>90%(75.0%对23.1%,P=0.03),以及原发肿瘤和门静脉癌栓(PVTT)的18F-氟脱氧葡萄糖(18F-FDG)标准化摄取值(SUV)也显著降低(60.0%对5.6%,P=0.003;57.1%对8.3%,P=0.04)。值得注意的是,85.7%的PVTT在病理检查中表现出主要病理反应(MPR),尽管术前影像学检查中只有28.6%实现降期。MPR在PVTT中比在主要肿瘤中更常见(85.7%对20.0%)。在非手术组中,中位总生存期(OS)为7个月,1年生存率为27.8%,而在手术组中,中位OS未达到,1年生存率为60.0%。

结论

TACE-HAIC、PD-1抑制剂和乐伐替尼联合作为非转移性晚期HCC的术前转化治疗显示出其益处。除了影像学评估外,18F-FDG摄取和AFP的显著降低可作为成功转化的预测指标,尤其是对于PVTT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/715d/11170507/b2333814aec1/tcr-13-05-2315-f1.jpg

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