AbstractObjective To explore the association between epidermal growth factor receptor (EGFR) mutation subtypes and the prognosis of brain metastasis in patients with lung adenocarcinoma. Methods A retrospective analysis was performed on the clinical data of 256 patients who were admitted to our hospital and confirmed with brain metastases of lung adenocarcinoma by EGFR mutation detection from 2010 to 2015. The prognostic factors for brain metastases were analyzed. The survival rate was calculated by the Kaplan-Meier method and analyzed by the log-rank test. The univariate and multivariate prognostic analyses were performed by the log-rank test and the Cox proportional hazards model. Results The median survival time was 10.13 months in all patients. The univariate analysis showed that sex,EGFR mutation status,exon 19 deletion,the Karnofsky Performance Status (KPS) score of brain metastases,and targeted therapy were prognostic predictors (P=0.006,0.001,0.010,0.000,0.003). The multivariate analysis showed that the KPS score and exon 19 deletion were prognostic factors for brain metastases (P=0.000,0.045). When grouped into the recursive partitioning analysis classes,all the patients were split into three subgroups with significantly different prognosis (P=0.000). Conclusions Exon 19 deletion is a prognostic predictor of brain metastases in patients with lung adenocarcinoma,which can be integrated into the prognosis scoring system for brain metastases of lung adenocarcinoma. EGFR tyrosine kinase inhibitors improve the survival in patients with brain metastases of lung adenocarcinoma and EGFR mutation,particularly,in those with exon 19 deletion.
Corresponding Authors:
Li Hongwei,Email:3420010@163.com
Cite this article:
Zhou Wei,Zhang Jie,Jia Haixia et al. Association between epidermal growth factor receptor mutation subtypes and the prognosis of brain metastases in patients with lung adenocarcinoma[J]. Chinese Journal of Radiation Oncology, 2017, 26(2): 144-149.
Zhou Wei,Zhang Jie,Jia Haixia et al. Association between epidermal growth factor receptor mutation subtypes and the prognosis of brain metastases in patients with lung adenocarcinoma[J]. Chinese Journal of Radiation Oncology, 2017, 26(2): 144-149.
[1] Soon YY,Leong CN,Koh WY,et al. EGFR tyrosine kinase inhibitors versus cranial radiation therapy for EGFR mutant non-small cell lung cancer with brain metastases:a systematic review and meta-analysis[J].Radiother Oncol,2015,114(2):167-172.DOI:10.1016/j.radonc.2014.12.011. [2] Nayak L,Lee EQ,Wen PY,et al. Epidemiology of brain metastases[J].Curr Oncol Rep,2012,14(1):48-54.DOI:10.1007/s11912-011-0203-y. [3] Sperduto PW,Berkey B,Gaspar LE,et al. A new prognostic index and comparison to three other indices for patients with brain metastases:an analysis of 1,960 patients in the RTOG database[J].Int J Radiat Oncol Biol Phys,2008,70(2):510-514.DOI:10.1016/j.ijrobp.2007.06.074. [4] Chang DB,Yang PC,Luh KT,et al. Late survival of non-small cell lung cancer patients with brain metastases:influence of treatment[J].Chest,1992,101(5):1293-1297.DOI:10.1378/chest.101.5.1293. [5] Gaspar L,Scott C,Rotman M,et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials[J].Int J Radiat Oncol Biol Phys,1997,37(4):745-751.DOI:10.1016/S0360-3016(96)00619-0. [6] McHaffie DR,Chabot P,Dagnault A,et al. Safety and feasibility of motexafin gadolinium administration with whole brain radiation therapy and stereotactic radiosurgery boost in the treatment of ≤6 brain metastases:a multi-institutional phase Ⅱ trial[J].J Neurooncol,2011,105(2):301-308.DOI:10.1007/s11060-011-0590-9. [7] Li B,Sun SZ,Yang M,et al. The correlation between EGFR mutation status and the risk of brain metastasis in patients with lung adenocarcinoma[J].J Neurooncol,2015,124(1):79-85.DOI:10.1007/s11060-015-1776-3. [8] Zeng YD,Zhang L,Liao H,et al. Gefitinib alone or with concomitant whole brain radiotherapy for patients with brain metastasis from non-small-cell lung cancer:a retrospective study[J].Asian Pac J Cancer Prev,2012,13(3):909-914.DOI:10.7314/APJCP.2012.13.3.909. [9] Park SJ,Kim HT,Lee DH,et al. Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in non-small cell lung cancer patients harboring either exon 19 or 21 mutation[J].Lung Cancer,2012,77(3):556-560.DOI:10.1016/j.lungcan.2012.05.092. [10] Wu YL,Zhou C,Cheng Y,et al. Erlotinib as second-line treatment in patients with advanced non-small-cell lung cancer and asymptomatic brain metastases:a phase Ⅱ study (CTONG-0803)[J].Ann Oncol,2013,24(4):993-999.DOI:10.1093/annonc/mds529. [11] Eichler AF,Kahle KT,Wang DL,et al. EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer[J].Neuro Oncol,2010,12(11):1193-1199.DOI:10.1093/neuonc/noq076. [12] Hsiao SH,Lin HC,Chou YT,et al. Impact of epidermal growth factor receptor mutations on intracranial treatment response and survival after brain metastases in lung adenocarcinoma patients[J].Lung Cancer,2013,81(3):455-461.DOI:10.1016/j.lungcan.2013.06.004. [13] Lee DW,Shin DY,Kim JW,et al. Additional prognostic role of EGFR activating mutations in lung adenocarcinoma patients with brain metastasis:integrating with lung specific GPA score[J].Lung Cancer,2014,86(3):363-368.DOI:10.1016/j.lungcan.2014.10.001. [14] Gow CH,Chien CR,Chang YL,et al. Radiotherapy in lung adenocarcinoma with brain metastases:effects of activating epidermal growth factor receptor mutations on clinical response[J].Clin Cancer Res,2008,14(1):162-168.DOI:10.1158/1078-0432.CCR-07-1468. [15] Luo DD,Ye X,Hu Z,et al. EGFR mutation status and its impact on survival of Chinese non-small cell lung cancer patients with brain metastases[J].Tumor Biol,2014,35(3):2437-2444.DOI:10.1007/s13277-013-1323-9. [16] Yang JCH,Wu YL,Schuler M,et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6):analysis of overall survival data from two randomised,phase 3 trials[J].Lancet Oncol,2015,16(2):141-151.DOI:10.1016/S1470-2045(14)71173-8. [17] Sekine A,Satoh H,Iwasawa T,et al. Prognostic factors for brain metastases from non-small cell lung cancer with EGFR mutation:influence of stable extracranial disease and erlotinib therapy[J].Med Oncol,2014,31:228.DOI:10.1007/s12032-014-0228-9. [18] Welsh JW,Komaki R,Amini A,et al. Phase Ⅱ trial of erlotinib plus concurrent whole-brain radiation therapy for patients with brain metastases from non-small-cell lung cancer[J].J Clin Oncol,2013,31(7):895-902. [19] Jiang T,Min WJ,Li YN,et al. Radiotherapy plus EGFR TKIs in non-small cell lung cancer patients with brain metastases:an update meta-analysis[J].Cancer Med,2016,5(6):1055-1065.DOI:10.1002/cam4.673. [20] Sperduto PW,Wang MH,Robins HI,et al. A phase 3 trial of whole brain radiation therapy and stereotactic radiosurgery alone versus WBRT and SRS with temozolomide or erlotinib for non-small cell lung cancer and 1 to 3 brain metastases:radiation therapy oncology group 0320[J].Int J Radiat Oncol Biol Phys,2013,85(5):1312-1318.DOI:10.1016/j.ijrobp.2012.11.042.