Department of Oncology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, China.
Graduate School Peking Union Medical College, Beijing, 100730, China.
J Cancer Res Clin Oncol. 2023 Sep;149(11):8993-9006. doi: 10.1007/s00432-023-04792-1. Epub 2023 May 10.
Older patients with cancer are underrepresented in pivotal trials of immune checkpoint inhibitors (ICIs). This study aimed to investigate immune-related adverse events (irAEs) that occur in older patients with lung cancer treated with ICIs, and explore predictors of the occurrence of irAEs.
A prospective analysis was performed on older patients with lung cancer aged ≥ 65 years who were treated with anti-programmed cell death-1/-ligand 1 (PD-1/PD-L1) inhibitors in Beijing Hospital from January 2018 to December 2022. The incidence and risk factors of irAEs were estimated by the Chi-square test or Wilcoxon rank-sum tests. The predictive power of Geriatric-8 (G-8) for irAEs was tested by receiver operating characteristic (ROC) curve analysis. Lymphocyte counts were measured by flow cytometry. Cytokine levels were tested by Enzyme-linked immunosorbent assay, respectively. Kaplan-Meier method was used to calculated progression-free survival (PFS) curves, and the log-rank test was used to evaluate differences.
A total of 201 older patients aged ≥ 65 years with lung cancer were enrolled in this study. The most common irAEs were interstitial pneumonia, dermatological toxicity and hypothyroidism, with rates of 17.2%, 16.1% and 5.6%, respectively. ROC showed that G-8 could predict the occurrence of irAEs in patients aged 65-71 years (≥ G2 irAEs: AUC = 0.757, p < 0.001; ≥ G3 irAEs: AUC = 0.862, p < 0.001), but not for patients aged ≥ 71 years. NLR, LMR, PNI, hypertension and diabetes were associated with irAEs. Lower CD4 + T cells and B cells, and lower levels of IL-10 were associated with the development of irAEs.
Our study confirmed the accuracy of G-8 for predicting irAEs in older patients. We also identified several predictors of irAEs in older patients with lung cancer.
在免疫检查点抑制剂(ICI)的关键试验中,癌症老年患者代表性不足。本研究旨在调查接受 ICI 治疗的老年肺癌患者发生的免疫相关不良事件(irAE),并探讨 irAE 发生的预测因素。
对 2018 年 1 月至 2022 年 12 月在北京医院接受抗程序性细胞死亡蛋白-1/配体 1(PD-1/PD-L1)抑制剂治疗的年龄≥65 岁的老年肺癌患者进行前瞻性分析。采用卡方检验或 Wilcoxon 秩和检验估计 irAE 的发生率和危险因素。通过受试者工作特征(ROC)曲线分析评估老年 8 项(G-8)预测 irAE 的能力。通过流式细胞术测量淋巴细胞计数,通过酶联免疫吸附试验(ELISA)分别检测细胞因子水平。采用 Kaplan-Meier 法计算无进展生存期(PFS)曲线,采用对数秩检验评估差异。
本研究共纳入 201 名年龄≥65 岁的老年肺癌患者。最常见的 irAE 是间质性肺炎、皮肤毒性和甲状腺功能减退症,发生率分别为 17.2%、16.1%和 5.6%。ROC 显示,G-8 可预测 65-71 岁患者(≥G2 irAE:AUC=0.757,p<0.001;≥G3 irAE:AUC=0.862,p<0.001)发生 irAE,但对年龄≥71 岁患者则不行。NLR、LMR、PNI、高血压和糖尿病与 irAE 相关。较低的 CD4+T 细胞和 B 细胞以及较低的 IL-10 水平与 irAE 的发生相关。
本研究证实了 G-8 对预测老年患者 irAE 的准确性,同时还确定了老年肺癌患者 irAE 的几个预测因素。