索拉非尼治疗失败后序贯局部治疗延长仑伐替尼治疗进展期肝癌患者的生存时间。

Subsequent locoregional therapy prolongs survival in progressive hepatocellular carcinoma patients under lenvatinib treatment.

机构信息

Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taiwan.

Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; College of Medicine, Chang Gung University, Taiwan.

出版信息

J Formos Med Assoc. 2024 Jul;123(7):788-795. doi: 10.1016/j.jfma.2024.01.031. Epub 2024 Feb 2.

DOI:10.1016/j.jfma.2024.01.031

PMID:38310071

Abstract

BACKGROUND

Locoregional therapy and multi-kinase inhibitor agent have been the backbone of treatment for hepatocellular carcinoma (HCC) patients. However, the effect of combination or sequential use of locoregional therapy on HCC patients receiving multi-kinase inhibitor remain uncertain. Therefore, we aim to explore whether the subsequent locoregional therapy provides better survival in HCC patients under lenvatinib treatment.

METHODS

From March 2018 to April 2020, a total of 78 unresectable HCC patients receiving lenvatinib were recruited. Image response was evaluated by dynamic image using the modified RECIST criteria. Among patients with tumor progression under lenvatinib treatment, whether receiving subsequent locoregional therapy or not were documented. Overall survival between two groups and the predictors for tumor progression were also analyzed.

RESULTS

Among the 78 patients receiving lenvatinib, the median age was 67.8 years old, and 69.2 % were male. Forty-four patients (56.4 %) experienced tumor progression with time to progression 5.1 months (95 % confidence interval (CI): 4.7-6.8) months. In multivariable Cox regression analysis, albumin-bilirubin (ALBI) grade II (adjusted HR: 2.883, P = 0.0104), and treatment duration less than three months (adjusted HR: 3.801, P = 0.0014) were the independent predictive factors for tumor progression, while patients achieving objective response under lenvatinib treatment within 12 weeks was the independent protective factor for tumor progression (adjusted HR: 0.144, P = 0.0020). Among the 44 patients with tumor progression, twenty-six (59.1 %) patients received subsequent locoregional therapy after tumor progression. Comparing to those with tumor progression without locoregional treatment, patients who received subsequent locoregional therapy had significantly better survival (1st year cumulative survival rate 70 % vs 27 %, log-rank P = 0.003).

CONCLUSION

ALBI grade, treatment duration of lenvatinib, and achieving objective image response within twelve weeks were the independent predictive factors for tumor progression. Furthermore, longer overall survival was observed in tumor progression patients with subsequent locoregional therapy and with better liver preserved function.

摘要

背景

局部区域治疗和多激酶抑制剂一直是肝细胞癌（HCC）患者治疗的核心。然而，局部区域治疗的联合或序贯应用对接受多激酶抑制剂治疗的 HCC 患者的效果仍不确定。因此，我们旨在探讨索拉非尼治疗后局部区域治疗是否能为 HCC 患者提供更好的生存。

方法

从 2018 年 3 月至 2020 年 4 月，共招募了 78 例不可切除的 HCC 患者接受仑伐替尼治疗。采用改良 RECIST 标准的动态图像评估图像反应。在接受仑伐替尼治疗的患者中，如果肿瘤进展，记录是否接受后续局部区域治疗。分析两组的总生存率和肿瘤进展的预测因素。

结果

在接受仑伐替尼治疗的 78 例患者中，中位年龄为 67.8 岁，69.2%为男性。44 例（56.4%）患者发生肿瘤进展，无进展生存期为 5.1 个月（95%置信区间：4.7-6.8）。多变量 Cox 回归分析显示，白蛋白-胆红素（ALBI）分级 II 级（调整 HR：2.883，P=0.0104）和治疗时间小于 3 个月（调整 HR：3.801，P=0.0014）是肿瘤进展的独立预测因素，而仑伐替尼治疗 12 周内达到客观缓解的患者是肿瘤进展的独立保护因素（调整 HR：0.144，P=0.0020）。在 44 例肿瘤进展的患者中，26 例（59.1%）患者在肿瘤进展后接受了后续局部区域治疗。与未接受局部区域治疗的肿瘤进展患者相比，接受后续局部区域治疗的患者生存明显更好（1 年累积生存率 70% vs 27%，log-rank P=0.003）。