The Impact of EGFR Mutation Status on Outcomes in Patients With Resected Stage I Non-Small Cell Lung Cancers
The Impact of EGFR Mutation Status on Outcomes in Patients With Resected Stage I Non-Small Cell Lung Cancers
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DOI：
10.1016/j.athoracsur.2013.05.091
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发表时间：
2013-09-01
影响因子：
4.6
通讯作者：
Lanuti, Michael
中科院分区：
文献类型：
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作者：
Izar, Benjamin;Sequist, Lecia;Lanuti, Michael
背景表皮生长因子激素受体（EGFR）基因突变与晚期非小细胞肺癌（NSCLC）的治疗反应和预后改善相关。然而，其在早期NSCLC中的预后作用尚未明确。在这项研究中，我们试图确定EGFR突变在未接受辅助治疗的完全切除的I期NSCLC患者中的纯预后作用。使用直接测序或基于多重聚合酶链反应的检测方法，在I期（T1- 2aN 0）NSCLC（2004年至2011年）完全切除的初治患者中检测突变状态。采用Kaplan-Meier方法和考克斯回归模型比较EGFR突变型和野生型患者的复发率、无病生存率和总生存率。307例患者纳入本研究; 62例携带EGFR突变的肿瘤，245例携带野生型EGFR。与野生型肿瘤相比，EGFR突变患者的肿瘤复发率显著降低（9.7% vs 21.6%; p = 0.03），中位无病生存期延长（8.8 vs 7.0年; p = 0.0085），总体5年生存率提高（98% vs 73%; p = 0.003）。肺叶切除术是最常进行的手术，占307例手术中的209例。在这些患者中，EGFR突变与上级总生存率相关（风险比，0.45; 95%置信区间，0.13 - 0.83; p = 0.017），估计5年生存率为98% vs 70%。EGFR突变（p = 0.026）和肿瘤大小小于2 cm（p = 0.04）被确定为无病生存的独立预后标志物，而年龄、性别和吸烟状况则不是。与EGFR野生型患者相比，完全切除的I期EGFR突变阳性NSCLC患者具有显著的生存优势。EGFR基因突变是完全切除的I期NSCLC的阳性预后标志物。(C)2013年由胸外科医师协会
Background. Mutations of the epidermal growth factor hormone receptor (EGFR) gene have been associated with improved treatment response and prognosis in advanced non-small lung cancer (NSCLC). However, their prognostic role in early-stage NSCLC is not well defined. In this study we sought to identify the pure prognostic role of EGFR mutation in patients with completely resected stage I NSCLC who received no adjuvant therapy.Methods. Mutation status was tested in treatment-naive patients who had complete resection of stage I (T1-2aN0) NSCLC (from 2004 to 2011) using direct sequencing or multiplex polymerase chain reaction-based assay. Recurrence rates, disease-free survival, and overall survival were compared between EGFR-mutant and wild-type patients using Kaplan-Meier methods and Cox regression models.Results. Three hundred seven patients were included in this study; 62 harbored tumors with EGFR mutations and 245 had wild-type EGFR. Tumors in patients with EGFR mutations were associated with a significantly lower recurrence rate (9.7% versus 21.6%; p = 0.03), greater median disease-free survival (8.8 versus 7.0 years; p = 0.0085), and improved overall 5-year survival (98% versus 73%; p = 0.003) compared with wild-type tumors. Lobectomy was the most frequently performed procedure, accounting for 209 of 307 operations. Among these patients, EGFR mutation was associated with superior overall survival (hazard ratio, 0.45; 95% confidence interval, 0.13 to 0.83; p = 0.017), with an estimated 5-year survival of 98% versus 70%. The presence of EGFR mutation (p = 0.026) and tumor size less than 2 cm (p = 0.04) were identified as independent prognostic markers for disease-free survival, whereas age, sex, and smoking status were not.Conclusions. Completely resected stage I EGFR mutation-positive NSCLC patients have a significant survival advantage compared with EGFR wild-type patients. Mutation of the EGFR gene is a positive prognostic marker in completely resected stage I NSCLC. (C) 2013 by The Society of Thoracic Surgeons