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免疫检查点抑制剂在老年原发性肝癌患者中的疗效和安全性:一项回顾性、多中心、真实世界队列研究。

Efficacy and safety of immune checkpoint inhibitors in elderly patients with primary liver cancer: a retrospective, multicenter, real-world cohort study.

机构信息

Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.

出版信息

Cancer Immunol Immunother. 2023 Jul;72(7):2299-2308. doi: 10.1007/s00262-023-03417-3. Epub 2023 Mar 8.

Abstract

BACKGROUND

There is still no specific real-world data regarding the clinical activity of immune checkpoint inhibitors in the elderly with liver cancer. Our study aimed to compare the efficacy and safety of immune checkpoint inhibitors between patients aged ≥ 65 years and the younger group, while exploring their differences in genomic background and tumor microenvironment.

METHODS

This retrospective study was conducted at two hospitals in China and included 540 patients treated with immune checkpoint inhibitors for primary liver cancer between January 2018 and December 2021. Patients' medical records were reviewed for clinical and radiological data and oncologic outcomes. The genomic and clinical data of patients with primary liver cancer were extracted and analyzed from TCGA-LIHC, GSE14520, and GSE140901 datasets.

RESULTS

Ninety-two patients were classified as elderly and showed better progression-free survival (P = 0.027) and disease control rate (P = 0.014). No difference was observed in overall survival (P = 0.69) or objective response rate (P = 0.423) between the two age groups. No significant difference was reported concerning the number (P = 0.824) and severity (P = 0.421) of adverse events. The enrichment analyses indicated that the elderly group was linked to lower expression of oncogenic pathways, such as PI3K-Akt, Wnt, and IL-17. The elderly had a higher tumor mutation burden than younger patients.

CONCLUSIONS

Our results indicated that immune checkpoint inhibitors might exhibit better efficacy in the elderly with primary liver cancer, with no increased adverse events. Differences in genomic characteristics and tumor mutation burden may partially explain these results.

摘要

背景

目前尚无关于肝癌老年患者免疫检查点抑制剂临床活性的具体真实世界数据。本研究旨在比较≥65 岁患者和年轻组患者接受免疫检查点抑制剂治疗的疗效和安全性,同时探索其基因组背景和肿瘤微环境的差异。

方法

本回顾性研究在中国的两家医院进行,纳入 2018 年 1 月至 2021 年 12 月期间接受免疫检查点抑制剂治疗原发性肝癌的 540 例患者。回顾患者的临床和影像学数据及肿瘤学结局。从 TCGA-LIHC、GSE14520 和 GSE140901 数据集提取原发性肝癌患者的基因组和临床数据并进行分析。

结果

92 例患者被归类为老年患者,其无进展生存期(P=0.027)和疾病控制率(P=0.014)更好。两组间总生存期(P=0.69)或客观缓解率(P=0.423)无差异。两组不良事件的数量(P=0.824)和严重程度(P=0.421)无显著差异。富集分析表明,老年组与 PI3K-Akt、Wnt 和 IL-17 等致癌途径的低表达相关。老年患者的肿瘤突变负荷高于年轻患者。

结论

我们的结果表明,免疫检查点抑制剂在原发性肝癌老年患者中可能具有更好的疗效,且不良事件发生率未增加。基因组特征和肿瘤突变负荷的差异可能部分解释了这些结果。

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