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放射治疗联合乐伐替尼与放射治疗联合索拉非尼治疗伴门静脉癌栓的肝细胞癌:一项回顾性研究

Radiotherapy plus lenvatinib versus radiotherapy plus sorafenib for hepatocellular carcinoma with portal vein tumor thrombus: a retrospective study.

作者信息

Zhang Min, Zheng Zhuangzhuang, Ding Qiuhui, Su Jing, Xin Ying, Jiang Xin

机构信息

Jilin Provincial Key Laboratory of Radiation Oncology and Therapy, The First Hospital of Jilin University and College of Basic Medical Science, Jilin University, Changchun, China.

Department of Radiation Oncology, the First Hospital of Jilin University, Changchun, China.

出版信息

Front Pharmacol. 2024 Oct 15;15:1458819. doi: 10.3389/fphar.2024.1458819. eCollection 2024.

Abstract

BACKGROUND AND AIMS

Portal vein tumor thrombus (PVTT) occurs frequently in hepatocellular carcinoma (HCC) patients. However, there is currently no satisfactory treatment. Radiotherapy (RT) and tyrosine kinase inhibitors (TKI) are currently commonly used. However, whether their combined use provides a survival benefit is debatable. This retrospective study compared the efficacy and safety between radiotherapy plus lenvatinib (RT + L) and radiotherapy plus sorafenib (RT + S) in the treatment of hepatocellular carcinoma with portal vein tumor thrombus (PVTT).

METHODS

Among patients with PVTT who received RT + L or RT + S between March 2017 and September 2022, the primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and incidence of treatment-related adverse effects. The prognostic factors were also assessed.

RESULTS

The analysis included 152 patients (RT + L: 48; RL: 25; RT + S: 55; S: 24). Compared with the RT + S group, the RT + L group had a longer OS and PFS. Among patients with type I/II PVTT, the median OS times were 19.8 months and 13.5 months ( = 0.047) and the median PFS was 12.3 months and 7.3 months ( = 0.042), respectively. And the median OS of the patients with type I/II PVTT were 14.4 months and 8.3 months ( = 0.030) and the median PFS was 8.3 months and 6.2 months ( = 0.026). ORR and DCR in RT + L group (25.0% and 75.0%) were also little higher than those in RT + S group (20.0% and 70.9%), but not statistically significant. In univariate analysis, etiology, Type of PVTT, alpha-fetoprotein (AFP) level, Child-Pugh score, and treatment method influenced OS. Multivariate analysis confirmed that treatment method, etiology, alpha-fetoprotein (AFP) level, and Child-Pugh score were independent prognostic factors for OS. Similar safety profiles were observed in the RT + L and RT + S groups. The most common adverse events were myelosuppression, decreased liver function, fatigue, diarrhea, nausea, and vomiting. Most adverse reactions were grade 1-2.

CONCLUSION

The side effects of radiotherapy plus lenvatinib were acceptable. Compared to RT + S, RT + L had good efficacy in the treatment of hepatocellular carcinoma with PVTT. Validation is needed in prospective studies with larger sample sizes.

摘要

背景与目的

门静脉癌栓(PVTT)在肝细胞癌(HCC)患者中频繁出现。然而,目前尚无令人满意的治疗方法。放射治疗(RT)和酪氨酸激酶抑制剂(TKI)是目前常用的治疗手段。然而,它们联合使用是否能带来生存获益仍存在争议。本回顾性研究比较了放射治疗联合乐伐替尼(RT + L)与放射治疗联合索拉非尼(RT + S)治疗伴有门静脉癌栓(PVTT)的肝细胞癌的疗效和安全性。

方法

在2017年3月至2022年9月期间接受RT + L或RT + S治疗的PVTT患者中,主要终点为总生存期(OS)和无进展生存期(PFS)。次要终点为客观缓解率(ORR)、疾病控制率(DCR)以及治疗相关不良反应的发生率。同时评估了预后因素。

结果

分析纳入152例患者(RT + L组:48例;RL组:25例;RT + S组:55例;S组:24例)。与RT + S组相比,RT + L组的OS和PFS更长。在I/II型PVTT患者中,中位OS时间分别为19.8个月和13.5个月(P = 0.047),中位PFS分别为12.3个月和7.3个月(P = 0.042)。I/II型PVTT患者的中位OS分别为14.4个月和8.3个月(P = 0.030),中位PFS分别为8.3个月和6.2个月(P = 0.026)。RT + L组的ORR和DCR(分别为25.0%和75.0%)也略高于RT + S组(分别为20.0%和70.9%),但差异无统计学意义。单因素分析显示,病因、PVTT类型、甲胎蛋白(AFP)水平、Child-Pugh评分和治疗方法影响OS。多因素分析证实,治疗方法、病因、甲胎蛋白(AFP)水平和Child-Pugh评分是OS的独立预后因素。RT + L组和RT + S组的安全性特征相似。最常见的不良事件为骨髓抑制、肝功能下降、疲劳、腹泻、恶心和呕吐。大多数不良反应为1 - 2级。

结论

放射治疗联合乐伐替尼的副作用可接受。与RT + S相比,RT + L治疗伴有PVTT的肝细胞癌疗效良好。需要在更大样本量的前瞻性研究中进行验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9dff/11518791/ed159887ff04/fphar-15-1458819-g001.jpg

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