The necessity of EGFR-targeted therapy combined with synchronized whole brain radiotherapy for non-small-cell lung cancer with mutated EGFR and brain metastasis
Su Pengcheng,Cao Jianzhong,Li Hongwei
Cancer Hospital,Shanxi Medical University,Taiyuan 030013,China (Su PC);Department of Radiation Oncology,Shanxi Cancer Hospital,Taiyuan 030013,China (Cao JZH,Li HW)
Abstract：Objective To explore the necessity of EGFR-targeted therapy combined with synchronized whole brain radiotherapy (WBRT) for non-small-cell lung cancer (NSCLC) with mutated EGFR and brain metastasis by comparing the effects on prognosis between WBRT combined with tyrosine kinase inhibitor (TKI) and TKI alone. Methods A retrospective analysis was performed in 43 patients with EGFR mutation-positive NSCLC and brain metastasis. In those patients, 24 patients received WBRT plus TKI and 19 patients TKI alone. Results The overall response rate (RR) and 6-month intracranial disease control rate (CR) were significantly higher in the WBRT+TKI group than in the TKI group (79% vs. 37%, P=0.002;79% vs. 63%, P=0.008). The median intracranial progression-free survival (IPFS) time was significantly longer in the WBRT+TKI group than in the TKI group (23.7 vs. 8.3 months, P=0.025). The multivariate analysis indicated that the control of lung cancer, WBRT+TKI, and single brain metastasis were favorable factors for substantially longer IPFS time (P=0.033,0.019,0.019). In 23 patients with exon 19 deletion, 12 patients received WBRT+TKI and 11 patients TKI alone;compared with the TKI group, the WBRT+TKI group had significantly higher RR and 6-month CR as well as significantly longer IPFS (100% vs. 35%, P=0.000;100% vs. 55%, P=0.008;23.7 vs. 8.4 months, P=0.003). In 20 patients without exon 19 deletion, however, there were no significant differences in RR or 6-month CR between the WBRT+TKI group (n=12) and the TKI group (n=8)(64% vs. 50%, P=1.000;58% vs. 75%, P=0.642).The median IPFS was 14.4 and 8.4 months (P=0.864). Conclusions WBRT combined with TKI is superior to TKI alone in the treatment of NSCLC with brain metastasis. Patients with exon 19 deletion have substantially better treatment outcomes.
Su Pengcheng,Cao Jianzhong,Li Hongwei. The necessity of EGFR-targeted therapy combined with synchronized whole brain radiotherapy for non-small-cell lung cancer with mutated EGFR and brain metastasis[J]. Chinese Journal of Radiation Oncology, 2016, 25(8): 823-828.
[1] Maione P,Rossi A,Airoma G,et al. The role of targeted therapy in non-small cell lungcancer[J].Crit Rev Oncol Hematol,2004,51(1):29-44.DOI:10.1016/j.critrevonc.2004.02.002 [2] Eichler AF,Kahle KT,Wang DL,et al. EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer of brain metastasis in nonsmall cell lung cancer[J].Neuro Oncol,2010,12(11):1193-1199.DOI:10.1093/neuonc/noq076 [3] 傅华,张雪淋,肖瑜,等.吉非替尼联合放射治疗在NSCLC脑转移患者治疗中的作用[J].中华医学杂志,2012,92(8):524-527.DOI:10.3760/cma.j.issn.0376-2491.2012.08.007 Fu H,Zhang XL,Xiao Y,et al. Evaluation of gefitinib plus radiotherapy in non-small-cell lung cancer patients with brain metastases[J].Nat Med J China,2012,92(8):524-527.DOI:10.3760/cma.j.issn.0376-2491.2012.08.007 [4] Fan Y,Xu X,Xie C.EGFR-TKI therapy for patients with brain metastases from non-small-cell lung cancer:a pooled analysis of published data[J].OncoTargets Ther,2014,7:2075-2084.DOI:10.2147/OTT.S67586 [5] 蒋涛,周彩存.NSCLC脑转移靶向治疗研究进展[J].中国肺癌杂志,2014,17(11):824-828.DOI:10.3779/j.issn.1009-3419.2014.11.09 Jiang T,Zhou CC.Research progress of targeted therapy in non-small cell lung cancer brain metastases[J].Chin J Lung Cancer,2014,17(11):824-828.DOI:10.3779/j.issn.1009-3419.2014.11.09 [6] 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 [7] Won YW,Han JY,Lee GK,et al. Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations[J].J Clin Pathol,2011,64(11):947-952.DOI:10.1136/jclinpath-2011-200169 [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] 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.DOI:10.1200/JCO.2011.40.1174 [10] Li H,Zhang X,Cao J,et al. Exon 19 deletion of epidermal growth factor receptor is associated with prolonged survival in brain metastases from non-small-cell lung cancer[J].TumorBiol,2015,36(12):9251-9258.DOI:10.1007/s13277-015-3653-2 [11] Zhang YX,Sheng J,Kang SY,et al. Patients with exon 19 Deletion were associated with longer progression-free survival compared to those with L858R mutation after first-line EGFR-TKIs for advanced non-small cell lung cancer:a meta-analysis[J].PLoS One,2014,9(9):e107161.DOI:10.1371/journal.pone.0107161 [12] Iuchi T,Shingyoji M,Itakura M,et al. Frequency of brain metastases in non-small-cell lung cancer,and their association with epidermal growth factor receptor mutations[J].Int J Clin Oncol,2015,20(4):674-679.DOI:10.1007/s10147-014-0760-9 [13] 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 [14] 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 [15] Lee HL,Chung TS,Ting LL,et al. EGFR mutations are associated with favorable intracranial response and progression-free survival following brain irradiation in non-small cell lung cancer patients with brain metastases[J].Radiat Oncol,2012,7(1):181.DOI:10.1186/1748-717X-7-181 [16] Bianco C,Tortora G,Bianco R,et al. Enhancement of antitumor activity of ionizing radiation by combined treatment with the selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839(Iressa)[J].Clin Cancer Res,2002,8(10):3250-3258 [17] Chinnaiyan P,Huang S,Vallabhaneni G,et al. Mechanisms of enhanced radiation response following epidermal growth factor receptor signaling inhibition by erlotinib (Tarceva)[J].Cancer Res,2005,65(8):3328-3335.DOI:10.1158/0008-5472.CAN-04-3547
2016, Vol. 25 
