晚期非小细胞肺癌原发灶和转移灶ROS1融合基因表达差异分析

目的分析ROS1(c-ros oncogene 1,receptor tyrosine kinase)融合基因在晚期非小细胞肺癌原发灶和转移灶中的差异表达。方法选取非小细胞肺癌原发灶162例,其中配对转移灶139例。采用实时荧光定量PCR检测ROS1融合基因的表达,并分析其在晚期非小细胞肺癌原发灶和转移灶中的表达差异。结果晚期非小细胞肺癌原发灶ROS1融合基因表达阳性率4.3%(7/162),配对原发灶ROS1融合基因表达阳性率2.6%(5/139),配对转移灶融合基因表达阳性率2.2%(3/139);原发灶较转移灶ROS1融合基因检出阳性率显著增高,差异具统计学意义(χ~2=13.517,P=0.000);ROS1融合基因阳性表达在原发灶和转移灶一致性好(κ=0.479,P=0.000)。非小细胞肺癌原发灶中ROS1融合基因表达与病理类型存在密切关系(χ~2=5.195,P=0.031),与患者性别、年龄等不存在明显相关性(P>0.05)。非小细胞肺癌配对原发灶以及转移灶中ROS1融合基因表达与患者性别、年龄、吸烟以及病理类型不存在明显相关性(P>0.05)。结论晚期非小细胞肺癌ROS1融合基因的阳性表达在原发灶中与病理类型有关,其在配对原发灶和转移灶中阳性表达一致性较好,可作为检测ROS1融合基因的备选手段。     

伴微乳头成分的肺腺癌EGFR KRAS基因突变和临床病理学特征相关研究

  目的   探讨伴微乳头成分的肺腺癌(pulmonary adenocarcinoma with a micropapillary pattern, MPPAC) EGFR、KRAS基因突变情况及其临床病理学特征。   方法   根据2011年的肺腺癌新分类诊断标准, 以是否伴有微小乳头状结构(micropapillary pat tern, MPP), 将144例肺腺癌病例分为MPP阳性组77例和MPP阴性组77例。MPP阳性组中又按MPP所占比例分为(+、++、+++) 三亚组。RT-PCR法检测两组EGFR、KRAS基因突变情况。   结果   在144例肺腺癌病例中EGFR突变62例(43.1%), KRAS突变9例(6.25%), EGFR突变与性别(P=0.018) 和肿瘤体积(P=0.016) 有关。MPP阳性组EGFR突变率高于MPP阴性组(P < 0.001);KRAS突变率低于MPP阴性组(P=0.016)。EGFR基因突变频率在MPP三亚组中无明显不同(P=0.932)。   结论   伴微乳头结构的肺腺癌EGFR突变频率高于肺腺癌其它亚型, KRAS突变频率低于肺腺癌其它亚型, 说明其有独特的分子生物学特点。      

let-7前体、K-ras基因在肺腺癌的表达及其相关性研究

目的 探讨let-7前体、K-ras基因在肺腺癌中的表达及其意义。方法 以GAPDH为内参,采用RT-PCR检测31例肺腺癌患者癌组织和正常组织中let-7前体、K-ras基因在肺腺癌中的表达。结果 31例肺腺癌患者中let-7前体61.29%为低表达,K-ras基因67.74%为高表达,差异有统计学意义。let-7前体与K-ras基因在肿瘤组织表达具有显著相关性。结论 let-7前体低表达与K-ras基因高表达在肺腺癌的发生、发展过程中可能具有某种协同作用。     

完全手术切除Ⅰ期肺腺癌病理亚型的预后意义

目的:本研究旨在分析完全手术切除Ⅰ期肺腺癌患者的病理亚型,及其对预后的影响.方法:2001年1月-2004年12月接受完全手术切除的Ⅰ期肺腺癌153例,按WHO 2004年版肺癌病理分类标准进行亚型分类,并对患者进行随访,分析病理亚型与生存之间的关系.结果:153例Ⅰ期肺腺癌以腺癌混合亚型最多见,占53.59%(82例);腺癌单一亚型占39.87%(61例),按所占比例高低依次为乳头样腺癌、腺泡样腺癌、细支气管肺泡癌(bronchoalveolar carcinoma,BAC)和实性腺癌伴黏液形成(solid adenocarcinoma with mucin,SACM),分别占27.45%(42例)、5.88%(9例)、3.92%(6例)和2.61%(4例);还有10例变异型腺癌,包括9例黏液性腺癌(5.88%)和1例胎儿型腺癌(0.65%).术后3年生存率以BAC和胎儿型腺癌最高(100%),SACM最低(45%),但差异无统计学意义(P=0.330).含SACM成分(9例)与不含SACM成分(144例)腺癌组患者的肿瘤大小、胸膜侵犯和T分期无明显差异,但含SACM成分的肺腺癌术后3年生存率(54.55%)要低于含SACM成分的肺腺癌(79.22%),差异有统计学意义(P=0.048).结论:肿瘤组织中含有SACM成分是Ⅰ期肺腺癌患者预后不良的预测因素.     

最新国际肺腺癌分类方法回顾性分析具有细支气管肺泡癌特征的肺腺癌209例

  目的   探讨最新国际肺腺癌分类中肺腺癌各组织学亚型与预后的相关性。  方法   收集天津医科大学附属肿瘤医院2000年1月至2005年12月间经手术切除、病理诊断为细支气管肺泡癌(bronchioloalveolar carcinoma, BAC)或伴有BAC成分的腺癌209例。按照肺癌新分类, 对所有病例组织学切片进行复习和分类, 同时进行临床资料的收集和随访。  结果   原诊断BAC的209例病例中原位腺癌(adenocarcinoma in situ, AIS)20例, 微小浸润性腺癌(minimally invasive adenocarcinoma, MIA)13例, 鳞屑样生长方式为主型腺癌(Lepidic predominant adenocarcinoma, LPA)82例, 乳头状和腺泡状为主型55例, 实性型和微乳头为主型39例。随访发现, 腺癌的组织学亚型与5年生存率有显著的相关性, AIS和MIA两组患者的5年生存率均为100%, 且均无淋巴结转移; LPA患者5年生存率为54.5%;腺泡型和乳头型腺癌的患者比AIS、MIA、LPA三组预后差, 而实性型和微乳头型的病例预后最差。  结论   肺腺癌中AIS和MIA有独特的临床病理特征及较好的预后。对具有细支气管肺泡癌特征的肺腺癌, 严格按照最新国际肺腺癌分类标准进行亚型分型, 对指导临床治疗及预测预后有重要意义。      

浸润性肺腺癌不同病理亚型的研究进展

肺癌是全球致死率最高的恶性肿瘤,长久以来严重威胁着人们的生命健康。其中肺腺癌的发病率逐年上升,目前已超过肺鳞癌成为肺癌中最常见的组织学类型。2015年世界卫生组织(WHO)发布了新版肺癌组织分型,根据组织学特点将肺腺癌分为腺泡状为主型、乳头状为主型、微乳头状为主型、贴壁状为主型、实体为主伴黏液分泌型5种病理亚型。很多研究表明这5种不同的肺腺癌病理亚型在组织学、细胞学及分子学方面具有相似之处,但又具有其独特的组织结构和临床特点,它们拥有不同的基因状态和淋巴结转移情况,且对肺癌患者预后的影响也不尽相同。在如今的临床工作中,充分了解不同肺腺癌病理亚型的临床特点对肺腺癌患者的辅助诊断、治疗方案的选择及疾病复发、进展等预后情况的判断具有至关重要的作用。本文就浸润性肺腺癌不同病理亚型的研究进展作一综述。     

非小细胞肺癌驱动基因检测及其与临床病理特征的相关性

目的:探讨非小细胞肺癌(NSCLC)驱动基因的变化情况及其与临床病理特征的相关性。方法:回顾性分析我院2016年01月至2020年07月NSCLC患者607例临床及病理学特征资料,采用扩增阻滞突变系统(ARMS)荧光PCR法检测EGFR突变,RT-PCR法检测ALK、ROS1基因融合,荧光原位杂交法（FISH）检测MET基因扩增。结果:607例NSCLC组织中325例(53.5%,325/607)检测到基因改变,分别为EGFR突变（45.5%,276/607）、ALK融合（5.1%,31/607）、ROS1融合（1.3%,8/607）和MET扩增（2.8%,17/607）,EGFR双位点突变15例（2.5%,15/607）,双驱动基因改变7例（1.2%,7/607）,其中EGFR突变与ALK融合阳性共存3例,EGFR突变与ROS1融合阳性共存2例,EGFR突变与MET扩增阳性共存2例。EGFR在女性、非吸烟、腺癌患者中突变率更高（P＜0.05）,EGFR突变更容易发生在以贴壁为主型、腺泡为主型、乳头为主型、微乳头为主型腺癌中（P＜0.05）;ALK融合多见于女性、年轻、非吸烟、实性为主型的腺癌患者（P＜0.05）;MET基因扩增在老年男性患者中发生率更高（P＜0.05）。结论:在NSCLC中EGFR突变率较高,驱动基因联合突变不容忽视,基因分型对临床治疗具有重要指导意义。     

伴微乳头结构的肺腺癌恶性潜能机制研究

  目的  探讨伴微乳头成分的肺腺癌(pulmonary adenocarcinoma with a micropapillary pattern, MPPAC)上皮间质转化和增殖调亡特征, 为临床评价其恶性潜能提供理论依据。  方法  根据2011年发表的肺腺癌新分类诊断标准, 以是否伴有微小乳头状结构(micropapillary pattern, MPP)将120例肺腺癌病例分为64例MPP阳性组, 56例MPP阴性组。免疫组织化学法检测Vimentin、E-cadherin、Capase-3、pEGFR的表达。  结果  120例肺腺癌病例中pECFR在女性(P=0.035)、非吸烟(P=0.017)患者中高表达。Vimentin在MPP阳性组的表达(28.1%)高于MPP阴性组(16.1%)并且其多表达于微乳头结构腔内散落的细胞; Caspase-3在MPP阳性组高表达(P=0.001)。  结论  微乳头结构的腔内散落细胞表现间质表型有利于癌细胞浸润转移, 伴乳头结构的肺腺癌有其独特的分子生物学特征。      

二代测序对比增强免疫组化检测非小细胞肺癌ROS1基因探索

目的:比较增强免疫组化（Ventana immunohistochemistry,Ventana IHC）检测非小细胞肺癌（non-small cell lung cancer,NSCLC）C-ros原癌基因1-受体酪氨酸激酶（C-ros oncogene 1 receptor tyrosine kinase,ROS1）蛋白表达和二代测序（next-generation sequencing,NGS）技术检测ROS1基因融合突变的一致性。方法:应用NGS技术在DNA层面检测966例NSCLC患者标本ROS1基因融合突变情况,同时应用Ventana IHC检测其中732例标本ROS1蛋白的表达情况。结果:NGS检测结果显示966例NSCLC患者的ROS1基因融合突变率为1.0%（10/966）,阳性样本病理类型为肺腺癌。Ventana IHC检测结果显示ROS1蛋白表达阳性率为17.6%（129/732）,阳性样本病理类型主要为肺腺癌。Ventana IHC和NGS两种方法检测结果的一致性为83.6%(612/732),kappa=0.110（P＜0.001）。两种方法检测ROS1基因差异具有统计学意义（P＜0.001）。结论:作为ROS1基因的检测方法,Ventana IHC法比NGS法更灵敏,两种方法检测结果的一致性较差,两者差异具有统计学意义。Ventana IHC筛查出ROS1阳性样本,可采用NGS进行验证。     

中国新疆维吾尔族人群中肺癌驱动基因的表达

背景与目的：肺癌的发病率和肿瘤相关死亡率居当前世界各地恶性肿瘤的首位。肺癌亦存在多种驱动基因。各民族间的差异反映出肺癌的不同基因突变存在差异。该研究旨在探讨新疆维吾尔族患者中肺癌驱动基因的表达状况。方法：收集维吾尔族肺癌患者组织标本43例,采用扩增受阻突变系统(amplification refractory mutation system,ARMS)检测EGFR基因表达,采用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)检测K-ras、ALK、ROS1、BRAF及PIK3CA基因表达,分析肺癌驱动基因突变与新疆维吾尔族肺癌患者临床病理特征之间的相关性。结果：43例标本中,EGFR基因突变率为11.63%,其中腺癌及鳞癌EGFR基因突变检出率分别为26.67%和4.76%;大细胞癌、腺鳞癌及小细胞肺癌均未测出EGFR基因突变。肺腺癌患者EGFR基因突变率为26.67%,明显高于非腺癌者的3.57%,差异有统计学意义(P=0.024)。K-ras12/13杂合突变6例,突变检出率为16.28%(6/43);PIK3CA杂合突变2例,突变检出率为4.65%(2/43)。1例发生EGFR基因与K-ras基因同时突变。维吾尔族肺癌患者EGFR基因突变与年龄、性别、吸烟状况、TNM分期、ECOG评分均无关。43例标本中均未见ALK、ROS1融合基因及BRAF基因突变。结论：与亚洲人群相比,新疆维吾尔族肺癌患者EGFR突变率较低,K-ras突变率高,类似于欧美高加索人群的突变特点。     

KIF5B/RET fusion gene in surgically-treated adenocarcinoma of the lung

Recently, a novel fusion gene resulting from a linkage between the kinesin family member 5B gene (KIF5B; 10p11.22) and the rearranged during transfection gene (RET; 10q11.21) was identified in non-small cell lung cancer (NSCLC). However, the correlation between the KIF5B/RET fusion gene status and the clinicopathological features of surgically-treated lung cancer has not been well characterized. In this study, we have independently investigated the KIF5B/RET fusion gene status in 371?surgically-treated NSCLCs (270 were adenocarcinomas and 101 were squamous cell carcinomas), 60 breast cancers, 11?metastatic lung cancers from colon cancers and thyroid papillary adenocarcinoma cases at the Nagoya City University Hospital. The fusion gene status was analyzed by an RT-PCR-based assay and by using direct sequencing. We detected 3 of 270 cases of KIF5B/RET fusion genes in adenocarcinomas (1.1%) consisting of female and never smokers with mixed subtype adenocarcinomas. The fusion genes were detected exclusively with other mutations, such as EGFR, Kras, Braf, erbB2 mutations, and EML4/ALK fusion. KIF5B/RET fusion was not detected in the cases with squamous cell carcinoma or other types of cancers. From the 3?cases, 2?were KIF5B (exon 15); RET (exon 12) fusions with papillary dominant and 1?case was KIF5B (exon 22); RET (exon?12) fusion with solid dominant adenocarcinoma. The matched normal lung tissues did not display translocation. We reported KIF5B/RET fusion genes as a driver somatic mutation of lung adenocarcinomas. The cinicopathological backgrounds of the KIF5B/RET fusion-positive patients were similar with those of the EML4/ALK fusion-positive patients. The chimeric oncogene may be a promising molecular target for the personalized diagnosis and treatment of NSCLC.     

Detection of Novel NRG1, EGFR,and MET Fusions in Lung Adenocarcinomas in the Chinese Population

IntroductionMultiple oncogene fusions beyond ALK receptor tyrosine kinase (ALK), RET, and ROS1 fusion has been described in lung cancer, especially in lung adenocarcinomas without common oncogenic mutations. Molecular inhibitors have been developed and proved effective for patients whose tumors harbor these novel alterations.MethodsA consecutive series of surgically resected lung adenocarcinomas were collected and profiled using an enrichment strategy to detect nine common oncogenic driver mutations and fusions concerning EGFR, KRAS, HER2, BRAF, MET, ALK, RET, ROS1, and FGFR. Driver-negative cases were further analyzed by a comprehensive RNA-based next-generation sequencing (NGS) fusion assay for novel fusions.ResultsIn total, we profiled 1681 lung adenocarcinomas, among which 255 cases were common driver–negative. One hundred seventy-seven cases had sufficient tissue for NGS fusions screening, which identified eight novel fusions. NRG1 fusions occurred in 0.36% of all lung adenocarcinoma cases (6 of 1681 cases), including 4 CD74-NRG1–positive cases, 1 RBPMS-NRG1–positive case, and 1 novel ITGB1-NRG1–positive case. Furthermore, another 2 novel fusions were also detected, including 1 EGFR-SHC1 fusion and 1 CD47-MET fusion, both of which were in-frame and retained the functional domain of the corresponding kinases. No fusion event was detected for NTRK, KRAS, BRAF or HER2 genes in this cohort. Detailed clinicopathologic data showed that invasive mucous adenocarcinoma (three of eight cases) and acinar-predominant adenocarcinoma (three of eight cases) were the most prevalent pathologic subtypes among novel fusions.ConclusionsFusions affecting NRG1, EGFR, and MET were detected in 0.48% of unselected lung adenocarcinomas, and NRG1 fusions ranked the most prevalent fusions in common driver-negative lung adenocarcinomas from Chinese population. RNA-based NGS fusion assay was an optional method for screening actionable fusions in common driver-negative cases.     

The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis

Purpose. The RET fusion gene is a novel oncogene observed in a subset of NSCLC in recent years. Nevertheless, the results of epidemiological studies concerning the gene remain unclear. Thus, a meta-analysis was conducted to evaluate the correlation of RET fusion gene with demographic and clinicopathological features of NSCLC. Methods. PubMed, Embase, and Web of Science databases were searched to identify eligible studies. The association of RET fusion gene occurrence with gender, age, smoking status, histology type and tumor stage were analyzed in meta-analysis. Subgroup analysis according to patients'' location (Asian and non-Asian) was also conducted. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the correlation. Results. Nine studies with a total of 6,899 NSCLC patients met the inclusion criteria. A total of 84 patients with RET fusion gene were detected. The RET fusion gene was identified at significantly higher frequencies in female (OR = 0.55, 95%CI = 0.35–0.85) than male patients and in young (<60 ) patients (OR = 0.43, 95%CI = 0.19–0.99) than old patients (≤60 ), particularly in patients from Asian. A significant higher frequency was also identified in non-smokers (OR = 0.28, 95% CI = 0.16–0.49), and in patients with lung adenocarcinomas (OR = 3.59, 95%CI = 1.50–8.56). Additionally, no association between RET fusion gene and the TNM stage of tumor was observed. Conclusion. RET fusion gene occurred predominantly in Asian females with younger age, in non-smokers, and in lung adenocarcinomas patients. This subset of NSCLC patients might be good candidates for personalized diagnostic and therapeutic approaches.     

RET-Rearranged Lung Adenocarcinomas with Lymphangitic Spread,Psammoma Bodies,and Clinical Responses to Cabozantinib

Oncogenic rearrangements of the RET gene have recently been described in 1% to 2% of lung adenocarcinomas. We report five cases of RET-rearranged lung adenocarcinoma with an unusual constellation of clinical and histologic features that has not previously been described in tumors with this genomic alteration. The age at diagnosis of the five patients (4F, 1M) ranged from 44 to 77 years. All were never-smokers. Radiologically, four tumors showed lymphangitic spread within the lungs at presentation; three of these had multiple bilateral lung nodules. Histology showed psammoma bodies within the tumor in four of five cases. Molecular testing for activating EGFR mutations by standard genotyping and ALK expression by immunohistochemistry was negative in all cases. Additional molecular analysis was prompted by the clinical profile in that all five patients were never-smokers with metastatic, relapsed, and/or refractory disease; and also by unusual histologic findings in two cases. Comprehensive genomic profiling performed by means of a clinical grade cancer gene panel next-generation sequencing assay demonstrated a KIF5B-RET fusion in three; and fluorescence in-situ hybridization documented a RET rearrangement in two. Three of the patients were treated with the RET inhibitor cabozantinib. By Response Evaluation Criteria In Solid Tumors (RECIST) criteria, two had a confirmed partial response (at 6 weeks and 4 weeks) and one had stable disease. Our findings suggest that the combination of lymphangitic spread and psammoma bodies may be characteristic of a subset of advanced stage RET-rearranged lung adenocarcinomas. These findings should prompt additional molecular testing for RET translocations, particularly in never-smokers with EGFR- and ALK-negative lung adenocarcinoma.     

RET fusion gene: Translation to personalized lung cancer therapy

Development of lung adenocarcinoma (LADC), the most frequent histological type of lung cancer, depends in many cases on the activation of “driver” oncogenes such as KRAS, epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK). Inhibitors that target the EGFR and ALK tyrosine kinases show therapeutic effects against LADCs containing EGFR gene mutations and ALK gene fusions, respectively. Recently, we and others identified the RET fusion gene as a new targetable driver gene in LADC. The RET fusions occur in 1–2% of LADCs. Existing US Food and Drug Administration‐approved inhibitors of RET tyrosine kinase show promising therapeutic effects both in vitro and in vivo, as well as in a few patients. Clinical trials are underway to investigate the therapeutic effects of RET tyrosine kinase inhibitors, such as vandetanib (ZD6474) and cabozantinib (XL184), in patients with RET fusion‐positive non‐small‐cell lung cancer.     

Entrectinib in children and young adults with solid or primary CNS tumors harboring NTRK,ROS1, or ALK aberrations (STARTRK-NG)

BackgroundEntrectinib is a TRKA/B/C, ROS1, ALK tyrosine kinase inhibitor approved for the treatment of adults and children aged ≥12 years with NTRK fusion-positive solid tumors and adults with ROS1 fusion-positive non–small-cell lung cancer. We report an analysis of the STARTRK-NG trial, investigating the recommended phase 2 dose (RP2D) and activity of entrectinib in pediatric patients with solid tumors including primary central nervous system tumors.MethodsSTARTRK-NG ({"type":"clinical-trial","attrs":{"text":"NCT02650401","term_id":"NCT02650401"}}NCT02650401) is a phase 1/2 trial. Phase 1, dose-escalation of oral, once-daily entrectinib, enrolled patients aged <22 years with solid tumors with/without target NTRK1/2/3, ROS1, or ALK fusions. Phase 2, basket trial at the RP2D, enrolled patients with intracranial or extracranial solid tumors harboring target fusions or neuroblastoma. Primary endpoints: phase 1, RP2D based on toxicity; phase 2, objective response rate (ORR) in patients harboring target fusions. Safety-evaluable patients: ≥1 dose of entrectinib; response-evaluable patients: measurable/evaluable baseline disease and ≥1 dose at RP2D.ResultsAt data cutoff, 43 patients, median age of 7 years, were response-evaluable. In phase 1, 4 patients experienced dose-limiting toxicities. The most common treatment-related adverse event was weight gain (48.8%). Nine patients experienced bone fractures (20.9%). In patients with fusion-positive tumors, ORR was 57.7% (95% CI 36.9-76.7), median duration of response was not reached, and median (interquartile range) duration of treatment was 10.6 months (4.2-18.4).ConclusionsEntrectinib resulted in rapid and durable responses in pediatric patients with solid tumors harboring NTRK1/2/3 or ROS1 fusions.     

ALK基因状态与晚期肺腺癌患者一线培美曲塞化疗疗效的关系

背景与目的 间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)是非小细胞肺癌(non-small cell lung cancer,NSCLC)的重要驱动基因之一,多项研究显示培美曲塞在ALK阳性肺癌中的疗效存在争议.本研究旨在继续探索以培美曲塞为基础的化疗在ALK阳性和阴性肺腺癌患者中的疗效.方法 回顾性分析郑州大学第一附属医院2015年1月-2016年4月经组织病理学证实的98例表皮生长因子受体(epidermal growth factor receptor,EGFR)、鼠类肉瘤病毒癌基因(kirsten rat sarcoma viral oncogene,KRAS)、鼠类肉瘤滤过性毒菌致癌同源体B1(V-rafmurine sarcoma viral oncogene homolog B1,BRAF)均为阴性的晚期肺腺癌患者的临床资料.分析ALK基因状态、临床特征、化疗疗效及无疾病进展生存期(progression-free survival,PFS)之间的关系.结果 98例患者均进行了ALK基因检测,ALK基因断裂融合34例(34.7%),未发生断裂融合64例(65.3%).全部患者均接受一线培美曲塞联合铂类的化疗,客观缓解率(objective response rate,ORR)为21.4%,疾病控制率(disease control rate,DCR)为84.7%.ALK阳性肺腺癌患者的ORR和DCR均高于阴性患者(41.2%vs 10.9%,χ2=23.389,P<0.001;91.2%vs 81.3%,χ2=4.153,P=0.042),差异有统计学意义.ALK基因状态与年龄、性别、吸烟史、临床分期均无明显关系.ALK阳性肺腺癌的中位PFS为7.1个月(95%CI:6.1-8.1),阴性4.7个月(95%CI:3.818-5.582),二者的PFS差异有统计学意义(χ2=13.269,P<0.001).Cox回归多因素分析显示:培美曲塞联合铂类化疗的PFS与性别、年龄、吸烟、分期、与铂类药物的种类均无明显关系,ALK基因断裂融合是PFS相关的唯一变量(HR=0.392,95%CI:0.243-0.634,P<0.001).结论 ALK阳性相比ALK阴性肺腺癌患者一线应用以培美曲塞为基础的化疗有更大的临床获益.