EGFR 19/21位点突变与597例非小细胞肺癌患者中发生脑转移的关联分析
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摘要
目的表皮生长因子受体(epidermal growth factor receptor,EGFR)敏感突变型非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的脑转移发生率较高,本研究进一步探讨NSCLC患者EGFR突变亚型之间脑转移发生率的差异。方法收集2014-03-03-2017-12-31山东省肿瘤医院收治的597例EGFR 19号外显子突变(n=286)和21号外显子L858R位点突变(n=311)阳性的NSCLC患者。其中,男214例,女383例;年龄30～89岁,中位年龄59岁;无吸烟史患者476例,有吸烟史患者121例;KPS评分≤80者311例,>80者286例。采用χ~2检验、Fisher精确概率法和多因素Logistic回归模型,分析EGFR突变亚型之间脑转移发生率的差异。结果 194例患者发生脑转移,其中19号外显子突变患者81例,L858R位点突变患者113例,EGFR 19号外显子突变患者的脑转移发生率(28.3%)低于L858R位点突变患者(36.3%),差异有统计学意义,χ~2=4.361,P=0.037。多因素Logistic关联分析显示,年龄、淋巴结转移和EGFR突变亚型是影响脑转移发生率的危险因素,均P<0.05。结论 NSCLC患者EGFR突变亚型与脑转移发生有关,EGFR21号外显子L858R位点突变的NSCLC患者脑转移发生率比EGFR19号外显子突变者高。
OBJECTIVE Epidermal growth factor receptor(EGFR)sensitive mutant non-small cell lung cancer(NSCLC)patients have a higher incidence of brain metastasis.This study aimed to further explore the difference between EGFR mutant subtypes and the incidence of brain metastasis patients with NSCLC.METHODS A total of 597 NSCLC patients with positive EGFR 19 exon mutation(n=286)and exon 21 L858 Rsite mutation(n=311)were collected in Shandong Cancer Hospital.There were 214 males and 383 females;age from 30 to 89,with a median age of 59;476 patients without smoking history and 121 patients with smoking history;311 patients with KPS(Karnofsky)score≤80 and286 patients>80.The statistical analysis methods includedχ~2 test,Fisher exact probability method and multivariate logistic regression model analysis.RESULTS Among 194 patients with brain metastasis,81 patients with exon 19 mutation and 113 patients with locus L858 R mutation had brain metastasis rate(28.3%)significantly lower than that of patients with locus L858 Rmutation(36.3%),and the difference was statistically significant(P=0.037).Multivariate Logistic regression analysis showed that age,lymph node metastasis and EGFR mutant subtype were all related factors affecting the incidence of brain metastasis,all P<0.05.CONCLUSIONS EGFR mutant subtypes are associated with brain metastasis in NSCLC patients.The incidence of brain metastasis in NSCLC patients with EGFR 21 exon L858 Rlocus mutation was higher than that with EGFR19 exon mutation in NSCLC patients.
OBJECTIVE Epidermal growth factor receptor(EGFR)sensitive mutant non-small cell lung cancer(NSCLC)patients have a higher incidence of brain metastasis.This study aimed to further explore the difference between EGFR mutant subtypes and the incidence of brain metastasis patients with NSCLC.METHODS A total of 597 NSCLC patients with positive EGFR 19 exon mutation(n=286)and exon 21 L858 Rsite mutation(n=311)were collected in Shandong Cancer Hospital.There were 214 males and 383 females;age from 30 to 89,with a median age of 59;476 patients without smoking history and 121 patients with smoking history;311 patients with KPS(Karnofsky)score≤80 and286 patients>80.The statistical analysis methods includedχ~2 test,Fisher exact probability method and multivariate logistic regression model analysis.RESULTS Among 194 patients with brain metastasis,81 patients with exon 19 mutation and 113 patients with locus L858 R mutation had brain metastasis rate(28.3%)significantly lower than that of patients with locus L858 Rmutation(36.3%),and the difference was statistically significant(P=0.037).Multivariate Logistic regression analysis showed that age,lymph node metastasis and EGFR mutant subtype were all related factors affecting the incidence of brain metastasis,all P<0.05.CONCLUSIONS EGFR mutant subtypes are associated with brain metastasis in NSCLC patients.The incidence of brain metastasis in NSCLC patients with EGFR 21 exon L858 Rlocus mutation was higher than that with EGFR19 exon mutation in NSCLC patients.
引文
[1] Shin DY,Na II,Kim CH,et al.EGFR mutation and brain metastasis in pulmonary adenocarcinomas[J].J Thorac Oncol,2014,9(2):195-199.
[2] Wu YL,Lee JS,Thongprasert S,et al.Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer(FASTACT-2):a randomised,doubleblind trial[J].Lancet Oncol,2013,14(8):777-786.
[3]邹传伟,王小拍,周丽霞.非小细胞肺癌171例患者EGFR基因突变分析[J].广东医学,2017,38(13):2015-2018.
[4] Qin BM,Chen X,Zhu JD,et al.Identification of EGFR kinase domain mutations among lung cancer patients in China:implication for targeted cancer therapy[J].Cell Res,2005,15(3):212-217.
[5] Burel-Vandenbos F,Ambrosetti D,Coutts M,et al.EGFR mutation status in brain metastases of non-small cell lung carcinoma[J].J Neurooncol,2013,111(1):1-10.
[6] Fujimoto D,Ueda H,Shimizu R,et al.Features and prognostic impact of distant metastasis in patients with stageⅣlung adenocarcinoma harboring EGFR mutations:importance of bone metastasis[J].Clin Exp Metastasis,2014,31(5):543-551.
[7] Guan J,Chen M,Xiao N,et al.EGFR mutations are associated with higher incidence of distant metastases and smaller tumor size in patients with non-small-cell lung cancer based on PET/CT scan[J].Med Oncol,2016,33(1):1.
[8]李博,孙锁柱,陈秀丽,等.非小细胞肺癌EGFR不同突变状态的脑转移发生特点及治疗[J].中华肿瘤防治杂志,2017,24(5):328-331.
[9]孙晓远,刘斌,蒋捍东,等.不同EGFR突变位点晚期非小细胞肺癌的临床特征及对靶向药物治疗反应分析[J].中华肺部疾病杂志(电子版),2018,11(3):289-294.
[10] Hubbs JL,Boyd JA,Hollis D,et al.Factors associated with the development of brain metastases:analysis of 975patients with early stage nonsmall cell lung cancer[J].Cancer,2010,116(21):5038-5046.
[11] Jacobs RH,Awan A,Bitran JD,et al.Prophylactic cranial irradiation in adenocarcinoma of the lung.A possible role[J].Cancer,1987,59(12):2016-2019.
[12] Wang SY,Ye X,Ou W,et al.Risk of cerebral metastases for postoperative locally advanced non-small-cell lung cancer[J].Lung Cancer,2009,64(2):238-243.
[13] Dimitropoulos C,Hillas G,Nikolakopoulou S,et al.Prophylactic cranial irradiation in non-small cell lung cancer patients:who might be the candidates[J].Cancer Manag Res,2011,3:287-294.
[14]张永芹,孙秀锦,左云,等.肺癌脑转移患者中不同EGFR突变状态下的临床及影像学特点[J].临床神经外科杂志,2018,15(3):179-183.
[15] Petrovic M,Ilic N,Loncarevic O,et al.Risk factors for brain metastases in surgically stagedⅢA non-small cell lung cancer patients treated with surgery,radiotherapy and chemotherapy[J].Vojnosanit Pregl,2011,68(8):643-649.
[16] Pottgen C,Eberhardt W,Grannass A,et al.Prophylactic cranial irradiation in operable stageⅢA non small-cell lung cancer treated with neoadjuvant chemoradiotherapy:results from a German multicenter randomized trial[J].J Clin Oncol,2007,25(31):4987.
[2] Wu YL,Lee JS,Thongprasert S,et al.Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer(FASTACT-2):a randomised,doubleblind trial[J].Lancet Oncol,2013,14(8):777-786.
[3]邹传伟,王小拍,周丽霞.非小细胞肺癌171例患者EGFR基因突变分析[J].广东医学,2017,38(13):2015-2018.
[4] Qin BM,Chen X,Zhu JD,et al.Identification of EGFR kinase domain mutations among lung cancer patients in China:implication for targeted cancer therapy[J].Cell Res,2005,15(3):212-217.
[5] Burel-Vandenbos F,Ambrosetti D,Coutts M,et al.EGFR mutation status in brain metastases of non-small cell lung carcinoma[J].J Neurooncol,2013,111(1):1-10.
[6] Fujimoto D,Ueda H,Shimizu R,et al.Features and prognostic impact of distant metastasis in patients with stageⅣlung adenocarcinoma harboring EGFR mutations:importance of bone metastasis[J].Clin Exp Metastasis,2014,31(5):543-551.
[7] Guan J,Chen M,Xiao N,et al.EGFR mutations are associated with higher incidence of distant metastases and smaller tumor size in patients with non-small-cell lung cancer based on PET/CT scan[J].Med Oncol,2016,33(1):1.
[8]李博,孙锁柱,陈秀丽,等.非小细胞肺癌EGFR不同突变状态的脑转移发生特点及治疗[J].中华肿瘤防治杂志,2017,24(5):328-331.
[9]孙晓远,刘斌,蒋捍东,等.不同EGFR突变位点晚期非小细胞肺癌的临床特征及对靶向药物治疗反应分析[J].中华肺部疾病杂志(电子版),2018,11(3):289-294.
[10] Hubbs JL,Boyd JA,Hollis D,et al.Factors associated with the development of brain metastases:analysis of 975patients with early stage nonsmall cell lung cancer[J].Cancer,2010,116(21):5038-5046.
[11] Jacobs RH,Awan A,Bitran JD,et al.Prophylactic cranial irradiation in adenocarcinoma of the lung.A possible role[J].Cancer,1987,59(12):2016-2019.
[12] Wang SY,Ye X,Ou W,et al.Risk of cerebral metastases for postoperative locally advanced non-small-cell lung cancer[J].Lung Cancer,2009,64(2):238-243.
[13] Dimitropoulos C,Hillas G,Nikolakopoulou S,et al.Prophylactic cranial irradiation in non-small cell lung cancer patients:who might be the candidates[J].Cancer Manag Res,2011,3:287-294.
[14]张永芹,孙秀锦,左云,等.肺癌脑转移患者中不同EGFR突变状态下的临床及影像学特点[J].临床神经外科杂志,2018,15(3):179-183.
[15] Petrovic M,Ilic N,Loncarevic O,et al.Risk factors for brain metastases in surgically stagedⅢA non-small cell lung cancer patients treated with surgery,radiotherapy and chemotherapy[J].Vojnosanit Pregl,2011,68(8):643-649.
[16] Pottgen C,Eberhardt W,Grannass A,et al.Prophylactic cranial irradiation in operable stageⅢA non small-cell lung cancer treated with neoadjuvant chemoradiotherapy:results from a German multicenter randomized trial[J].J Clin Oncol,2007,25(31):4987.