突变类型和丰度与接受一线酪氨酸激酶抑制剂治疗的晚期肺腺癌患者的总生存期相关。
mutation types and abundance were associated with the overall survival of advanced lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors.
作者信息
Liu Yang, Wang Hongyan, Yang Sen, Yang Yuanyuan, Wu Yufeng, He Zhen, Ma Shuxiang, Mo Yuqing, Chen Haiyang, Wang Qiming, Ge Hong
机构信息
Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Department of Internal Medicine, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
出版信息
J Thorac Dis. 2022 Jun;14(6):2254-2267. doi: 10.21037/jtd-22-755.
BACKGROUND
Epidermal growth factor receptor tyrosine kinases inhibitors (EGFR-TKIs) are currently recognized as the standard treatment for advanced non-small cell lung cancer (NSCLC) patients with mutations. Clinically found patients with different mutational status have different prognosis.
METHODS
A retrospective cohort study was performed to explore the relationship between mutations and abundance with patient survival by using patient data from the Affiliated Cancer Hospital of Zhengzhou University between January 2013 and November 2016. All patients involved in the present study had sensitive mutations [either exon 19 deletion (DEL) or exon 21 L858R] and treated by EGFR-TKIs. They were followed up every three months until lost or dead. Mutation abundance was calculated as the copies of mutation divided by copies of locus, and the cut-off values for 19DEL and L858R were 4.9% and 9.5%, respectively.
RESULTS
Total of 236 patients were included, comprising 116 (49.2%) patients with 19DEL mutation and 120 (50.8%) patients with L858R mutation. The median follow-up duration was 23.2 months (95% CI: 14.9-26.7 months). Overall survival (OS) was significantly longer in patients with 19DEL mutation (20.9 months, 95% CI: 17.7-24.1 months versus 17.0 months, 95% CI: 14.4-19.6 months in patients with L858R; P0.008) and in patients with high mutation abundance (20.9 months, 95% CI: 18.3-23.5 months versus 13.0 months, 95% CI: 10.3-15.7 months in patients with low mutation abundance; P0.001). Multivariate Cox regression including age, performance status and tumor stage revealed that longer OS was independently associated with 19DEL mutation (HR: 0.48, 95% CI: 0.39-0.67, P0.033) and high mutation abundance (HR: 0.62, 95% CI: 0.50-0.79, P=0.027).
CONCLUSIONS
mutation types and abundance was associated with the patients' survival which might be used to predict the efficacy of targeted therapy by EGFR-TKIs.
背景
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）目前被认为是晚期非小细胞肺癌（NSCLC）伴有 突变患者的标准治疗方法。临床上发现，具有不同 突变状态的患者预后不同。
方法
采用回顾性队列研究，利用郑州大学附属肿瘤医院2013年1月至2016年11月的患者数据，探讨 突变和丰度与患者生存之间的关系。本研究纳入的所有患者均有敏感的 突变[外显子19缺失（DEL）或外显子21 L858R]，并接受了EGFR-TKIs治疗。每三个月对他们进行随访，直至失访或死亡。突变丰度计算为 突变拷贝数除以 基因座拷贝数，19DEL和L858R的截断值分别为4.9%和9.5%。
结果
共纳入236例患者，其中116例（49.2%）为19DEL突变患者，120例（50.8%）为L858R突变患者。中位随访时间为23.2个月（95%CI：14.9 - 26.7个月）。19DEL突变患者的总生存期（OS）显著更长（20.9个月，95%CI：17.7 - 24.1个月，而L858R突变患者为17.0个月，95%CI：14.4 - 19.6个月；P<0.008），高突变丰度患者的总生存期也显著更长（20.9个月，95%CI：18.3 - 23.5个月，而低突变丰度患者为13.0个月，95%CI：10.3 - 15.7个月；P<0.001）。多因素Cox回归分析包括年龄、体能状态和肿瘤分期，结果显示，更长的总生存期与19DEL突变（HR：0.48，95%CI：0.39 - 0.67，P<0.033）和高突变丰度（HR：0.62，95%CI：0.50 - 0.79，P = 0.027）独立相关。
结论
突变类型和丰度与患者生存相关，这可能用于预测EGFR-TKIs靶向治疗的疗效。
Zotero 插件