在基因檢測指導下非小細胞肺癌患者接受表皮生長因子受體酪氨酸激酶抑制劑治療臨床療效比較

王黎銘　尹俊　劉書琴　偰燕燕　范鈺

【摘要】 目的：探討病理組織切片和外周血檢測基因突變的一致性，不同EGFR敏感突變類型NSCLC患者一線接受EGFR-酪氨酸激酶抑制劑（EGFR-TKIs）治療的療效和預后。方法：回顧性分析2016年1月-2017年2月收治的接受EGFR基因檢測的晚期NSCLC患者62例的臨床資料。比較應用病理組織片和外周血檢測基因突變結果的一致性，比較EGFR基因突變組與野生組的臨床特征及2種EGFR基因型突變患者EGFR-TKIs治療的近期療效和中位無進展生存時間（PFS）。結果：病理組織切片和外周血檢測EGFR基因的一致性達0.8（P<0.05）。兩組病理類型和吸煙史比較，差異均有統計學意義（P<0.05）；而兩組性別、年齡、TNM分期、體力評分（ECOG）比較，差異均無統計學意義（P>0.05）。19del組和L858R組的客觀有效率（ORR）和疾病控制率（DCR）比較，差異均無統計學意義（P>0.05）；而19del組的中位PFS優于L858R組（P<0.05）。10例患者進行基因捕獲與高通量測序法（NGS）檢測發現，3例EGFR-TKIs治療無效的患者中，存在PIK3CA突變2例。結論：病理組織切片和外周血EGFR基因檢測結果一致性較好，外周血基因檢測可以成為臨床無法取得病理組織標本患者的替代選擇。EGFR-TKIs治療EGFR突變，19del基因型患者預后可能好于L858R基因型，而下游基因如PIK3CA基因突變可能會引起EGFR-TKIs藥物耐藥，影響療效。

【關鍵詞】 肺癌； 基因檢測； 表皮生長因子； 酪氨酸酶抑制劑

Clinical Efficacy of EGFR-TKIs Treatment Non-small Cell Lung Cancer under Guidance of Gene Sequencing/WANG Liming，YIN Jun，LIU Shuqin，et al.//Medical Innovation of China，2017，14（32）：005-009

【Abstract】 Objective：To investigated the consistency of gene sequencing of histopathologic slide and peripheral blood，and evaluated the curative effect and prognosis of different types of EGFR sensitive mutant NSCLC patients received first-line EGFR-TKIs treatment.Method：The clinical data of 62 cases of advanced NSCLC who received EGFR gene sequencing from January 2016 to February 2017 were retrospectively analyzed.The consistency test gene by histopathologic slide and peripheral blood of mutation results were compared，the clinical features of EGFR gene mutation group and wild group were compared，and short term efficacy and median progression free survival（PFS） of two kinds of EGFR gene mutation in patients treated with EGFR-TKIs were compared.Result：The consistency of detection of EGFR gene in pathological tissue and peripheral blood reached 0.8（P<0.05）.The pathological types and smoking history of two groups were compared，the differences were statistically significant（P<0.05），and the gender，age，TNM stage and physical strength score（ECOG） of two groups were compared，the differences were not statistically significant（P>0.05）.The objective response rate（ORR） and disease control rate（DCR） between 19del group and L858R group were compared，the differences were not statistically significant（P>0.05）.The median PFS of 19del group was better than that of L858R group（P<0.05）.10 patients were detected with next generation sequencing（NGS），and 2 cases of PIK3CA mutation were found in 3 cases of ineffective EGFR-TKIs treatment.Conclusion：Histopathologic slide and peripheral blood of EGFR gene detection results are good agreement，and the detection of peripheral blood gene can become a clinical pathological specimen of patients unable to obtain alternative choice.In EGFR mutation treated with EGFR-TKI，the prognosis of 19del genotype may be better than that of L858R genotype，while the downstream genes such as PIK3CA gene mutations may cause drug resistance EGFR-TKIs，influence curative effect.endprint

【Key words】 Lung cancer； Gene sequencing； Epidermal growth factor receptor； Tyrosine kinase inhibitors

First-authors address：Zhenjiang First Peoples Hospital，Zhenjiang 212002，China

doi：10.3969/j.issn.1674-4985.2017.32.002

肺癌是目前我國發病率和死亡率最高的惡性腫瘤[1]，根據病理分型分為非小細胞肺癌（NSCLC）和小細胞肺癌（SCLC），其中85%為NSCLC[2]。目前晚期NSCLC推薦組織標本分子檢測，根據分子分型指導治療[3]。對于組織標本不足或難以取得的患者，推薦通過血漿游離DNA檢測確定分子型[4]。表皮生長因子受體（Epidermal growth factor receptor，EGFR）突變和間變性淋巴瘤激酶（Anaplastic lymphoma kinase，ALK）重排是NSCLC主要的兩種癌驅動基因[5-6]，而ROS1，RET等基因突變也被發現存在于NSCLC中，但其作用機制尚未被闡明[7]。本研究回顧性分析了接受病理組織切片和外周血基因檢測的患者資料，比較病理組織切片和外周血基因檢測結果的一致性，EGFR突變陽性患者一線接受EGFR-酪氨酸激酶抑制劑（Tyrosine kinase inhibitor，TKI）治療療效和不同突變類型的相關性，并探討了其他基因突變對于EGFR-TKIs療效的影響。現報……