NSCLC脑转移磁共振影像特征评价EGFR突变的研究
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摘要
目的分析EGFR突变与临床非小细胞肺癌(non-small cell lung cancer,NSCLC)脑转移磁共振(magnetic resonance imaging,MRI)影像特征的关系,探讨脑转移MRI特征评价EGFR突变的价值。方法收集本院2011年1月至2017年1月116例NSCLC脑转移患者临床资料,应用扩增阻滞突变系统方法检测肺癌EGFR突变;回顾性分析患者MRI特征,脑转移瘤个数、大小、部位、强化方式、最大病灶瘤周水肿大小及瘤周水肿指数与EGFR突变相关性。结果 116例NSCLC脑转移患者中,EGFR突变型50例(43.1%);与年龄>60岁患者相比,年龄<60岁患者19 Del突变比例较高(25.4%vs 10.2%,P=0.040),但L858R突变比例较低(16.4%vs 34.7%,P=0.023)。在所测的201个脑转移灶中,野生型组瘤周水肿直径显著高于19缺失突变组(中位值:2.87 vs 1.54,P=0.008);L858R突变组瘤周水肿直径亦显著高于19缺失突变组(中位值:3.31 vs 1.54,P=0.034)。然而瘤周水肿指数仅在野生型组中显著高于19缺失突变组(中位值:0.979 vs 0.413,P=0.012)。构建年龄、瘤周水肿直径和水肿指数的EGFR 19缺失突变预测模型,ROC曲线分析显示该模型预测效能为0.733(95%CI=0.625～0.842)。结论 NSCLC脑转移临床特征及MRI影像可预测EGFR基因突变,为医学上无法进行EGFR突变检测的患者选用EGFR-TKI靶向治疗提供了理论依据。
Objective To investigate the correlation between brain metastatic MRI features and EGFR mutation status in the patient with non-small cell lung cancer(NSCLC) and explore the value of radiographic characteristics of MRI for evaluation of EGFR mutation. Methods Clinical data of 116 patients diagnosed with brain metastases from NSCLC admitted in our hospital during January 2011 and January 2017 were collected. Their EGFR mutation status in pulmonary primary tumors and metastatic tissues was detected by amplification block mutation system(ARMS). The features of MR images were analyzed for the correlation of EGFR mutation status with number, size, location of the metastatic brain tumors, strengthen approaches, size of peritumoral brain edema of the largest lesion and peritumoral brain edema index. Results Among the 116 patients with brain metastasis of NSCLC, 50 patients had EGFR mutation, at a mutation rate of 43.1%. The patients younger than 60 years had significantly higher ratio of EGFR 19 Del mutation(25.4% vs 10.2%, P=0.040) and lower ratio of L858 R mutation(16.4% vs 34.7%, P=0.023) when compared with those older than 60 years. Of the 201 brain metastatic lesions measured, the diameter of peripheral edema were significantly larger in the patients with EGFR wild type than those harboring EGFR 19 Del mutation(median: 2.87 vs 1.54, P=0.008), and in those with L858 R mutation than those with 19 Del mutation(median: 3.31 vs 1.54, P=0.034). However, the index of peripheral edema in the patients with EGFR wild type was obviously higher than those harboring EGFR 19 Del mutation(median: 0.979 vs 0.413, P=0.012). The predictive model for EGFR 19 deletion mutation was developed based on age, diameter and index of peripheral edema of metastatic tumor, and the capacity of this model was 0.733(95%CI=0.625～0.842) by ROC analysis. Conclusion Clinical features and MRI radiographic characteristics of brain metastatic lesions of NSCLC can be used to predict EGFR mutation status. Our study provides theoretical evidence for selecting subpopulation benefiting from EGFR-TKI from the patients who can't detect the mutation of EGFR medically.
Objective To investigate the correlation between brain metastatic MRI features and EGFR mutation status in the patient with non-small cell lung cancer(NSCLC) and explore the value of radiographic characteristics of MRI for evaluation of EGFR mutation. Methods Clinical data of 116 patients diagnosed with brain metastases from NSCLC admitted in our hospital during January 2011 and January 2017 were collected. Their EGFR mutation status in pulmonary primary tumors and metastatic tissues was detected by amplification block mutation system(ARMS). The features of MR images were analyzed for the correlation of EGFR mutation status with number, size, location of the metastatic brain tumors, strengthen approaches, size of peritumoral brain edema of the largest lesion and peritumoral brain edema index. Results Among the 116 patients with brain metastasis of NSCLC, 50 patients had EGFR mutation, at a mutation rate of 43.1%. The patients younger than 60 years had significantly higher ratio of EGFR 19 Del mutation(25.4% vs 10.2%, P=0.040) and lower ratio of L858 R mutation(16.4% vs 34.7%, P=0.023) when compared with those older than 60 years. Of the 201 brain metastatic lesions measured, the diameter of peripheral edema were significantly larger in the patients with EGFR wild type than those harboring EGFR 19 Del mutation(median: 2.87 vs 1.54, P=0.008), and in those with L858 R mutation than those with 19 Del mutation(median: 3.31 vs 1.54, P=0.034). However, the index of peripheral edema in the patients with EGFR wild type was obviously higher than those harboring EGFR 19 Del mutation(median: 0.979 vs 0.413, P=0.012). The predictive model for EGFR 19 deletion mutation was developed based on age, diameter and index of peripheral edema of metastatic tumor, and the capacity of this model was 0.733(95%CI=0.625～0.842) by ROC analysis. Conclusion Clinical features and MRI radiographic characteristics of brain metastatic lesions of NSCLC can be used to predict EGFR mutation status. Our study provides theoretical evidence for selecting subpopulation benefiting from EGFR-TKI from the patients who can't detect the mutation of EGFR medically.
引文
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[10] LI Q, DENG M, XI M, et al. Characteristics and treatment of brain metastases from esophageal squamous cell carcinoma[J]. J Cancer, 2018,9(5):901-905. DOI: 10.7150/jca.21511.
[11] LIM S O, LI C W, XIA W, et al. EGFR signaling enhances aerobic glycolysis in triple-negative breast cancer cells to promote tumor growth and immune escape[J]. Cancer Res, 2016, 76(5):1284-1296. DOI: 10.1158/0008-5472. CAN-15-2478.
[12] CHEN N, FANG W, ZHAN J, et al. Upregulation of PD-L1 by EGFR activation mediates the immune escape in EGFR-driven NSCLC: implication for optional immune targeted therapy for nsclc patients with EGFR mutation[J]. J Thorac Oncol, 2015, 10(6):910-923. DOI: 10.1097/JTO.0000000000000500.
[13] HSIAO S H, CHOU Y T, LIN S E, et al. Brain metastases in patients with non-small cell lung cancer: the role of mutated-EGFRs with an exon 19 deletion or L858R point mutation in cancer cell dissemination[J]. Oncotarget, 2017, 8(32):53405-53418. DOI: 10.18632/oncotarget.18509.
[14] SHI Z, ZHENG X, SHI R, et al. Radiological and clinical features associated with epidermal growth factor receptor mutation status of exon 19 and 21 in lung adenocarcinoma[J]. Sci Rep, 2017, 7(1):364. DOI: 10.1038/s41598-017-00511-2.
[15] LIU Y, KIM J, QU F, et al. CT Features associated with epidermal growth factor receptor mutation status in patients with lung adenocarcinoma[J]. Radiology, 2016, 280(1):271-280. DOI: 10.1148/radiol.2016151455.
[16] CHO A, HUR J, MOON YW, et al. Correlation between EGFR gene mutation, cytologic tumor markers, 18F-FDG uptake in non-small cell lung cancer[J]. BMC Cancer, 2016, 16: 224. DOI: 10.1186/s12885-016-2251-z.
[17] SEKINE A, KATO T, HAGIWARA E, et al. Metastatic brain tumors from non-small cell lung cancer with EGFR mutations: distinguishing influence of exon 19 deletion on radiographic features[J]. Lung Cancer, 2012, 77(1):64-69. DOI: 10.1016/j.lungcan.2011.12.017.
[2] OLMEZ I, DONAHUE B R, BUTLER J S, et al. Clinical outcomes in extracranial tumor sites and unusual toxicities with concurrent whole brain radiation(WBRT) and Erlotinib treatment in patients with non-small cell lung cancer(NSCLC) with brain metastasis[J]. Lung Cancer, 2010, 70(2):174-179. DOI:10.1016/j.lungcan.2010.01.018.
[3] STARK A M, ST?HRING C, HEDDERICH J, et al. Surgical treatment for brain metastases: Prognostic factors and survival in 309 patients with regard to patient age[J]. J Clin Neurosci, 2011, 18(1):34-38. DOI:10.1016/j.jocn.2010.03.046.
[4] LA SALVIA A, ROSSI A, GALETTA D, et al. Intercalated chemotherapy and epidermal growth factor receptor inhibitors for patients with advanced non-small-cell lung cancer: a systematic review and meta-analysis[J]. Clin Lung Cancer, 2017, 18(1):23-33.e1. DOI: 10.1016/j.cllc.2016.08.006.
[5] 任广, 陈爽, 耿道颖. 脑肿瘤瘤周水肿MSCT灌注成像的定量研究[J]. 放射学实践, 2011, 26(5):483-487. REN G, CHEN S, GENG D Y. The quantitative evaluation of multislice CT perfusion imaging in peritumoral brain edema[J]. Radiol Prac, 2011, 26(5):483-487.
[6] MAEMONDO M, INOUE A, KOBAYASHI K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR[J]. N Engl J Med, 2010, 362(25):2380-2388. DOI: 10.1056/NEJMoa0909530.
[7] ZHAO X, HAN R B, ZHAO J, et al. Comparison of epidermal growth factor receptor mutation statuses in tissue and plasma in stage I-IV non-small cell lung cancer patients[J]. Respiration, 2013, 85(2):119-125. DOI: 10.1159/000338790.
[8] ZHUO Y, GUO Q, SONG P, et al. Correlation study and significance of the EGFR expression in serum, lymph nodes and tumor tissue of NSCLC[J]. Thorac Cancer, 2014, 5(1):31-37. DOI: 10.1111/1759-7714.12048.
[9] 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. DOI: 10.1007/s11060-012-0990-5.
[10] LI Q, DENG M, XI M, et al. Characteristics and treatment of brain metastases from esophageal squamous cell carcinoma[J]. J Cancer, 2018,9(5):901-905. DOI: 10.7150/jca.21511.
[11] LIM S O, LI C W, XIA W, et al. EGFR signaling enhances aerobic glycolysis in triple-negative breast cancer cells to promote tumor growth and immune escape[J]. Cancer Res, 2016, 76(5):1284-1296. DOI: 10.1158/0008-5472. CAN-15-2478.
[12] CHEN N, FANG W, ZHAN J, et al. Upregulation of PD-L1 by EGFR activation mediates the immune escape in EGFR-driven NSCLC: implication for optional immune targeted therapy for nsclc patients with EGFR mutation[J]. J Thorac Oncol, 2015, 10(6):910-923. DOI: 10.1097/JTO.0000000000000500.
[13] HSIAO S H, CHOU Y T, LIN S E, et al. Brain metastases in patients with non-small cell lung cancer: the role of mutated-EGFRs with an exon 19 deletion or L858R point mutation in cancer cell dissemination[J]. Oncotarget, 2017, 8(32):53405-53418. DOI: 10.18632/oncotarget.18509.
[14] SHI Z, ZHENG X, SHI R, et al. Radiological and clinical features associated with epidermal growth factor receptor mutation status of exon 19 and 21 in lung adenocarcinoma[J]. Sci Rep, 2017, 7(1):364. DOI: 10.1038/s41598-017-00511-2.
[15] LIU Y, KIM J, QU F, et al. CT Features associated with epidermal growth factor receptor mutation status in patients with lung adenocarcinoma[J]. Radiology, 2016, 280(1):271-280. DOI: 10.1148/radiol.2016151455.
[16] CHO A, HUR J, MOON YW, et al. Correlation between EGFR gene mutation, cytologic tumor markers, 18F-FDG uptake in non-small cell lung cancer[J]. BMC Cancer, 2016, 16: 224. DOI: 10.1186/s12885-016-2251-z.
[17] SEKINE A, KATO T, HAGIWARA E, et al. Metastatic brain tumors from non-small cell lung cancer with EGFR mutations: distinguishing influence of exon 19 deletion on radiographic features[J]. Lung Cancer, 2012, 77(1):64-69. DOI: 10.1016/j.lungcan.2011.12.017.