Wang Yuyan, Duan Jianchun, Chen Hanxiao, Bai Hua, An Tongtong, Zhao Jun, Wang Zhijie, Zhuo Minglei, Wang Shuhang, Wang Jie
The Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Medical Oncology, Beijing Institute of Cancer Research, Beijing 100142, P.R. China.
Oncol Lett. 2017 Apr;13(4):2425-2431. doi: 10.3892/ol.2017.5740. Epub 2017 Feb 14.
The detection of mutations in the epidermal growth factor receptor () gene in tumor tissues has been established as the gold standard for predicting the efficacy of treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small-cell lung cancer (NSCLC). The current study aimed to investigate whether the presence of co-existing EGFR mutations in tumor tissue and in cell-free tumor DNA (ctDNA) in the plasma predicts a more favorable outcome of EGFR-TKI treatment in advanced NSCLC. A total of 287 NSCLC patients who had undergone EGFR-TKI treatment were enrolled and stratified into four subgroups: Wild-type EGFR in plasma and tissue specimens (B-/T-); mutated EGFR in plasma and tissue specimens (B+/T+); mutated EGFR in only in plasma samples (B+/T-); or mutated EGFR in only tissue specimens (B-/T+). EGFR mutations were tested using denaturing high-performance liquid chromatography and confirmed by amplification-refractory mutation system analysis. Of the 287 patients, 101 had mutations in both tissue and plasma samples and 103 had mutation in either tissue (n=65) or plasma (n=38). The median progression-free survival (mPFS) times were 9.2 and 2.0 months in the B+/T+ and B-/T- groups, respectively. The mPFS times were 7.9 months in the B-/T+ group and 11.9 months in the B+/T-group (P=0.001). Among the 187 patients with available pre-EGFR-TKI plasma samples, 70 received first-line EGFR-TKI treatment, and the mPFS in the B+/T+ group was longer than in the B-/T+ or B+/T- groups (18.8 vs. 9.4 vs. 6.9 months; P=0.003). In second-line setting of EGFR-TKI therapy, the groups of patients with EGFR mutation in ctDNA, regardless of the mutation status in the tissues, exhibited longer mPFS times compared with the B-/T+ group (10.0 vs. 5.8 months; P=0.044). The results suggest that co-existence of EGFR mutations in tissue and ctDNA predict longer PFS times for NSCLC patients who receive first-line EGFR-TKI therapy. In addition, real-time detection in ctDNA is an excellent predictor for the efficacy of second- or higher line EGFR-TKI therapy.
肿瘤组织中表皮生长因子受体（EGFR）基因突变的检测已被确立为预测晚期非小细胞肺癌（NSCLC）患者接受EGFR酪氨酸激酶抑制剂（EGFR-TKIs）治疗疗效的金标准。本研究旨在探讨肿瘤组织和血浆中游离肿瘤DNA（ctDNA）中同时存在EGFR突变是否预示晚期NSCLC患者接受EGFR-TKI治疗会有更良好的预后。共有287例接受EGFR-TKI治疗的NSCLC患者入组，并分为四个亚组：血浆和组织标本中EGFR野生型（B-/T-）；血浆和组织标本中EGFR突变型（B+/T+）；仅血浆样本中EGFR突变型（B+/T-）；或仅组织标本中EGFR突变型（B-/T+）。使用变性高效液相色谱法检测EGFR突变，并通过扩增阻滞突变系统分析进行确认。在287例患者中，101例在组织和血浆样本中均有突变，103例在组织（n = 65）或血浆（n = 38）中存在突变。B+/T+组和B-/T-组的中位无进展生存期（mPFS）分别为9.2个月和2.0个月。B-/T+组的mPFS为7.9个月，B+/T-组为11.9个月（P = 0.001）。在187例有EGFR-TKI治疗前血浆样本的患者中，70例接受一线EGFR-TKI治疗，B+/T+组的mPFS长于B-/T+组或B+/T-组（18.8个月对9.4个月对6.9个月；P = 0.003）。在EGFR-TKI治疗的二线治疗中，ctDNA中存在EGFR突变的患者组，无论组织中的突变状态如何，与B-/T+组相比，mPFS更长（10.0个月对5.8个月；P = 0.044）。结果表明，组织和ctDNA中EGFR突变的共存预示接受一线EGFR-TKI治疗的NSCLC患者的PFS更长。此外，ctDNA中的实时检测是二线或更高线EGFR-TKI治疗疗效的优秀预测指标。
