EGFR突变的非小细胞肺癌脑转移的治疗策略

doi:10.3760/cma.j.issn.1673-422X.2017.04.014

摘要/Abstract

摘要： 约10%的非小细胞肺癌（NSCLC）患者初诊时出现脑转移，而脑转移为肺癌死亡的主要原因之一。目前全脑放疗（WBRT）仍为脑转移的标准治疗方案，但其疗效已达平台期。酪氨酸激酶抑制剂(TKI)在NSCLC脑转移治疗中取得了可观的疗效。TKI联合WBRT可能成为表皮生长因子受体(EGFR)突变的肺癌脑转移的主要治疗手段。

关键词: 癌, 非小细胞肺, 治疗, 转移, 表皮生长因子受体

Abstract: As the leading cause of death among lung cancer patients, brain metastasis occurs in approximately 10 percent of non-small cell lung cancer (NSCLC) patients at first diagnosis. Wholebrain radiation therapy (WBRT) is still the standard treatment for patients with brain metastasis, however, the efficacy of WBRT reaches a plateau. It has been proved that tyrosine kinase inhibitors (TKIs) make considerable therapeutic effect for NSCLC patients with brain metastasis. The combination therapy of TKIs with WBRT may provide new major treatment for epidermal growth factor receptor (EGFR) mutant NSCLC with brain metastasis.

Key words: Carcinoma, non-small-cell lung, Therapy, Metastasis, Epidermal growth factor receptor

张惠博,李祥攀,宋启斌. EGFR突变的非小细胞肺癌脑转移的治疗策略[J]. 国际肿瘤学杂志, 2017, 44(4): 294-296.

Zhang Huibo, Li Xiangpan, Song Qibin. Treatment strategies of EGFR-mutated non-small cell lung cancer with brain metastases[J]. Journal of International Oncology, 2017, 44(4): 294-296.

参考文献

［1］ Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016［J］. CA Cancer J Clin, 2016, 66(1): 7-30. DOI: 10.3322/caac.21332. ［2］ Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016［J］. CA Cancer J Clin, 2016, 66(4): 271-289. DOI: 10.3322/caac.21349. ［3］ Khuntia D, Brown P, Li J, et al. Wholebrain radiotherapy in the management of brain metastasis［J］. J Clin Oncol, 2006, 24(8): 1295-1304. DOI: 10.1200/JCO.2005.04.6185. ［4］ Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase Ⅲ, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS)［J］. J Clin Oncol, 2011, 29(21): 2866-2874. DOI: 10.1200/JCO.2010.33.4235. ［5］ Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial［J］. Lancet Oncol, 2012, 13(3): 239-246. DOI: 10.1016/S1470-2045(11)70393X. ［6］ Mak RH, Doran E, Muzikansky A, et al. Outcomes after combined modality therapy for EGFR-mutant and wild-type locally advanced NSCLC［J］. Oncologist, 2011, 16(6): 886-895. DOI: 10.1634/theoncologist.2011-0040. ［7］ 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. ［8］ Luo YH, Wu CH, Huang CY, et al. Brain metastasis features and association with tumor epidermal growth factor receptor mutation in patients with adenocarcinoma of the lung［J］. Asia Pac J Clin Oncol, 2016, In press. DOI: 10.1111/ajco.12576. ［9］ Han G, Bi J, Tan W, et al. A retrospective analysis in patients with EGFR-mutant lung adenocarcinoma: is EGFR mutation associated with a higher incidence of brain metastasis?［J］. Oncotarget, 2016, 7(35): 56998-57010. DOI: 10.18632/oncotarget.10933. ［10］ Zhuang H, Yuan Z, Wang J, et al. Phase Ⅱ study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma［J］. Drug Des Devel Ther, 2013, 7: 1179-1186. DOI: 10.2147/DDDT.S53011. ［11］ El Gantery MM, Abd El Baky HM, El Hossieny HA, et al. Management of brain metastases with stereotactic radiosurgery alone versus whole brain irradiation alone versus both［J］. Radiat Oncol, 2014, 9: 116. DOI: 10.1186/1748-717X-9-116. ［12］ Aoyama H, Tago M, Shirato H. Stereotactic radiosurgery with or without wholebrain radiotherapy for brain metastases: secondary analysis of the JROSG 99-1 randomized clinical trial［J］. JAMA Oncol, 2015, 1(4): 457-464. DOI: 10.1001/jamaoncol.2015.1145. ［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］ Hsiao S, Lin H, Chou Y, 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. ［15］ 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. ［16］ Porta R, Sanchez-Torres JM, Paz-Ares L, et al. Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation［J］. Eur Respir J, 2011, 37(3): 624-631. DOI: 10.1183/09031936.00195609. ［17］ Heon S, Yeap BY, Lindeman NI, et al. The impact of initial gefitinib or erlotinib versus chemotherapy on central nervous system progression in advanced non-small cell lung cancer with EGFR mutations［J］. Clin Cancer Res, 2012, 18(16): 4406-4414. DOI: 10.1158/1078-0432.CCR-12-0357. ［18］ Zeng YD, Liao H, Qin T, et al. Blood-brain barrier permeability of gefitinib in patients with brain metastases from non-small-cell lung cancer before and during whole brain radiation therapy［J］. Oncotarget, 2015, 6(10): 8366-8376. DOI: 10.18632/oncotarget.3187. ［19］ Provencio M, Sánchez A, Garrido P, et al. New molecular targeted therapies integrated with radiation therapy in lung cancer［J］. Clin Lung Cancer, 2010, 11(2): 91-97. DOI: 10.3816/CLC.2010.n.012. ［20］ 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. ［21］ Chen Y, Yang J, Li X, et al. Firstline epidermal growth factor receptor (EGFR)tyrosine kinase inhibitor alone or with whole-brain radiotherapy for brain metastases in patients with EGFR-mutated lung adenocarcinoma［J］. Cancer Sci, 2016, 107(12): 1800-1805. DOI: 10.1111/cas.13079. ［22］ Magnuson WJ, Yeung JT, Guillod PD, et al. Impact of deferring radiation therapy in patients with epidermal growth factor receptor-mutant non-small cell lung cancer who develop brain metastases［J］. Int J Radiat Oncol Biol Phy, 2016, 95(2): 673-679. DOI: 10.1016/j.ijrobp.2016.01.037. ［23］ Zhou L, He J, Xiong W, et al. Impact of whole brain radiation therapy on CSF penetration ability of Icotinib in EGFR-mutated non-small cell lung cancer patients with brain metastases: results of phase Ⅰ doseescalation study［J］. Lung Cancer, 2016, 96: 93-100. DOI: 10.1016/j.lungcan.2016.04.003.

[1]	钱晓涛, 石子宜, 胡格, 吴晓维. Ⅲ~ⅣA期食管鳞状细胞癌放化疗后行巩固化疗的疗效：一项真实世界临床研究[J]. 国际肿瘤学杂志, 2024, 51(6): 326-331.
[2]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊. 局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[3]	郭泽浩, 张俊旺. PFDN及其亚基在肿瘤发生发展中的作用[J]. 国际肿瘤学杂志, 2024, 51(6): 350-353.
[4]	张百红, 岳红云. 新作用机制的抗肿瘤药物进展[J]. 国际肿瘤学杂志, 2024, 51(6): 354-358.
[5]	许凤琳, 吴刚. EBV在鼻咽癌肿瘤免疫微环境和免疫治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 359-363.
[6]	王盈, 刘楠, 郭兵. 抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[7]	王丽, 刘志华, 杨伟洪, 蒋凤莲, 李全泳, 宋浩杰, 鞠文东. ROS1突变肺腺鳞癌合并脑梗死为主要表现的Trousseau综合征1例[J]. 国际肿瘤学杂志, 2024, 51(6): 382-384.
[8]	范志鹏, 余静, 胡静, 廖正凯, 徐禹, 欧阳雯, 谢丛华. 炎症标志物的变化趋势对一线接受免疫联合化疗的晚期非小细胞肺癌患者预后的预测价值[J]. 国际肿瘤学杂志, 2024, 51(5): 257-266.
[9]	王俊毅, 洪楷彬, 纪荣佳, 陈大朝. 癌结节对结直肠癌根治性切除术后肝转移的影响[J]. 国际肿瘤学杂志, 2024, 51(5): 280-285.
[10]	顾芳萌, 徐晨阳, 雷大鹏. 人工智能辅助电子喉镜检查在喉癌及喉癌前病变诊治中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(5): 303-307.
[11]	王培鑫, 赵军, 徐世红, 姜朝阳, 王小强, 杨红娟. 铁死亡相关机制在骨肉瘤中的应用进展[J]. 国际肿瘤学杂志, 2024, 51(5): 308-311.
[12]	张文馨, 夏泠, 彭晋, 周福祥. 甲胎蛋白升高型胃肝样腺癌1例并文献复习[J]. 国际肿瘤学杂志, 2024, 51(5): 312-315.
[13]	王昆, 周中新, 臧其威. 血清TGF-β1、VEGF水平对非小细胞肺癌患者单孔胸腔镜根治术后复发的预测价值[J]. 国际肿瘤学杂志, 2024, 51(4): 198-203.
[14]	杨毫, 施贵冬, 张程城, 张跃, 张力文, 付茂勇. 信迪利单抗与替雷利珠单抗在进展期食管鳞状细胞癌新辅助治疗中的疗效及安全性对比[J]. 国际肿瘤学杂志, 2024, 51(4): 210-216.
[15]	姚益新, 沈煜霖. 血清SOCS3、TXNIP水平对肝细胞癌TACE治疗预后的预测价值[J]. 国际肿瘤学杂志, 2024, 51(4): 217-222.