Background: Epidermal growth factor receptor (EGFR)-based targeted therapy improves the survival of patients with advanced lung adenocarcinoma harboring EGFR mutations. However, factors including treatment or heterogeneity partly contribute to EGFR genetic status alteration between baseline and disease progresses (PD). The aim of this study is to compare difference of EGFR mutations between biopsy and rebiopsy in real world.
Methods: Data from 61 paired specimens performed EGFR testing in Jilin Provincial Cancer Hospital between January 2015 and December 2017 were collected and analyzed. The specimens were collected at baseline and PD, confirmed by histology or cytology and categorized as tumor tissue, malignant pleural effusion or plasma. All patients were naive and received chemotherapy or targeted therapy as first-line treatment. Amplification Refractory Mutation System (ARMS) was used to detect EGFR mutations.
Results: EGFR mutation rate in tumor tissue, pleural effusion or blood was 90.2% vs 88.5%, 6.6% vs 6.6% and 3.2% vs 4.9% at baseline or PD respectively and discrepancy was 72% and 36.3% for the same (n=50) or different (n=11) type of specimens. The EGFR mutation rate was 95.1% and 91.8% in patients before and after treatment, and the discrepancy was 63.9%, among which, 69.2% and 92.3% in chemotherapy-treated patients (n=13) with discrepancy to 46.1% (6/13), and 100.0% and 91.7% in EGFR-TKI-treated patients (n=48) with discrepancy to 70.8%. There were four types of alterations in terms of EGFR mutations: wild type turned into mutation (4.9%), mutation disappeared (8.2%), sensitive mutations transformed (1.6%), and new mutations appeared (49.1%).
Conclusions: In real world, the EGFR mutation status in advanced non-small cell lung cancer (NSCLC) patients altered significantly, due to tissue resources and therapeutic approaches, implying the importance of rebiopsy and real-time detection of EGFR mutation, in order to provide data to guide precise strategy in the following treatment.
【中文题目：晚期肺腺癌患者一线治疗前后EGFR基因突变差异性分析】 【中文摘要：背景与目的 表皮生长因子受体（epidermal growth factor receptor, EGFR）靶向治疗能够显著提高EGFR突变的晚期肺腺癌患者预后生存，但治疗及异质性等因素可导致初次和疾病进展时EGFR基因状态发生改变。为了探讨真实世界中EGFR基因突变在疾病进展和基线时的差异，我们开展了此项研究。方法 收集2015年1月-2017年12月在吉林省肿瘤医院进行EGFR基因检测的61例配对标本数据并进行分析。标本取材时间为治疗前和疾病进展时，所有标本均经病理学或细胞学证实，标本来源为肿瘤组织﹑恶性胸腔积液和血浆，患者为初治，一线接受化疗或靶向治疗，采用扩增阻滞突变系统法（Amplification Refractory Mutation System, ARMS）对29种EGFR基因突变进行检测。结果 初次和再次活检相比（n=61），肿瘤组织、恶性胸腔积液和血浆标本所占的比例分别为90.2% vs 88.5%、6.6% vs 6.6%和3.2% vs 4.9%，其中标本类型前后一致的患者（n=50）EGFR突变差异率为72.0%，标本类型不一致患者（n=11）为36.3%；治疗前EGFR突变率为95.1%，治疗后为91.8%，二者的差异率为63.9%；化疗患者（n=13）治疗前EGFR突变率为69.2%，治疗后为92.3%，二者差异率为46.1%；靶向治疗患者（n=48）治疗前EGFR突变率为100%，治疗后为91.7%，二者差异率为70.8%。EGFR基因变化类型有4类：野生型变为突变型（4.9%）、突变消失（8.2%）、敏感突变类型互变（1.6%）和突变种类增加（49.1%）。结论 临床实践中，晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者由于标本取材部位和类型及治疗的影响，治疗前后EGFR基因突变具有较大差异性，动态检测并明确EGFR基因状态，可以为临床医生选择精准的后续靶向治疗方案提供参考。】 【中文关键词：肺肿瘤；再次活检；EGFR检测】.
Keywords: EGFR testing; Lung neoplasms; Rebiopsy.