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High probability and frequency of EGFR mutations in non-small cell lung cancer with brain metastases

Journal of Neuro-Oncology volume 135, pages 413–418 (2017)Cite this article

Abstract

Lung cancer is the leading cause of cancer death in men and women worldwide. Brain metastasis (BMs) of non-small cell lung cancer (NSCLC) is the most important cause of death. This study aimed to explore the association of epidermal growth factor receptor (EGFR) mutations and BMs in NSCLC. We analyzed 50 NSCLC patients with BMs and 50 match-paired NSCLC patients with no brain metastases (NBMs). The EGFR mutation status of primary lesions was detected using the amplification refractory mutation system polymerase chain reaction. The BMs patients had a higher frequency of EGFR mutations than the NBMs patients (52.0 vs. 22.0% respectively, P < 0.001), in both adenocarcinoma (60.5 vs. 30.6%, P = 0.003) and squamous carcinoma (37.5 vs. 0%, P = 0.04). The incidence of BMs in patients with EGFR mutations was higher than in patients with wild-type EGFR (70.3 vs. 38.1%, P = 002). NSCLC patients with BMs had a higher incidence of EGFR mutations and those with mutant EGFR had a higher frequency of BMs. EGFR mutations may promote brain metastasis growth of NSCLC.

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References

  1. Gril B, Evans L, Palmieri D, Steeg PS (2010) Translational research in brain metastasis is identifying molecular pathways that may lead to the development of new therapeutic strategies. Eur J Cancer 46(7):1204–1210. doi:10.1016/j.ejca.2010.02.033

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Zimm S, Wampler GL, Stablein D, Hazra T, Young HF (1981) Intracerebral metastases in solid-tumor patients: natural history and results of treatment. Cancer 48(2):384–394

    CAS  Article  PubMed  Google Scholar 

  3. Taillibert S, Le Rhun E (2015) [Epidemiology of brain metastases]. Cancer Radiother 19(1):3–9. doi:10.1016/j.canrad.2014.11.001

    CAS  Article  PubMed  Google Scholar 

  4. Peacock KH, Lesser GJ (2006) Current therapeutic approaches in patients with brain metastases. Curr Treat Options Oncol 7(6):479–489

    Article  PubMed  Google Scholar 

  5. Won YK, Lee JY, Kang YN, Jang JS, Kang JH, Jung SL, Sung SY, Jo IY, Park HH, Lee DS, Chang JH, Lee YH, Kim YS (2015) Stereotactic radiosurgery for brain metastasis in non-small cell lung cancer. Radiat Oncol J 33(3):207–216. doi:10.3857/roj.2015.33.3.207

    Article  PubMed  PubMed Central  Google Scholar 

  6. Parlak C, Mertsoylu H, Guler OC, Onal C, Topkan E (2014) Definitive chemoradiation therapy following surgical resection or radiosurgery plus whole-brain radiation therapy in non-small cell lung cancer patients with synchronous solitary brain metastasis: a curative approach. Int J Radiat Oncol Biol Phys 88(4):885–891. doi:10.1016/j.ijrobp.2013.12.017

    Article  PubMed  Google Scholar 

  7. Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C (2011) Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 12(8):735–742. doi:10.1016/S1470-2045(11)70184-X

    CAS  Article  PubMed  Google Scholar 

  8. Huang Y, Zhang L, Shi Y, Ma S, Liao M, Bai C, Zhang Q, Wang C, Luo F, Yu S, Qin S, Zhi X, Zhou C (2015) Efficacy of erlotinib in previously treated patients with advanced non-small cell lung cancer: analysis of the Chinese subpopulation in the TRUST study. Jpn J Clin Oncol 45(6):569–575. doi:10.1093/jjco/hyv036

    Article  PubMed  Google Scholar 

  9. Wu YL, Fukuoka M, Mok TS, Saijo N, Thongprasert S, Yang JC, Chu DT, Yang JJ, Rukazenkov Y (2013) Tumor response and health-related quality of life in clinically selected patients from Asia with advanced non-small-cell lung cancer treated with first-line gefitinib: post hoc analyses from the IPASS study. Lung Cancer 81(2):280–287. doi:10.1016/j.lungcan.2013.03.004

    Article  PubMed  Google Scholar 

  10. Luo D, Ye X, Hu Z, Peng K, Song Y, Yin X, Zhu G, Ji Q, Peng Y (2014) EGFR mutation status and its impact on survival of Chinese non-small cell lung cancer patients with brain metastases. Tumour Biol 35(3):2437–2444. doi:10.1007/s13277-013-1323-9

    CAS  Article  PubMed  Google Scholar 

  11. Tomasini P, Serdjebi C, Khobta N, Metellus P, Ouafik L, Nanni I, Greillier L, Loundou A, Fina F, Mascaux C, Barlesi F (2016) EGFR and KRAS mutations predict the incidence and outcome of brain metastases in non-small cell lung cancer. Int J Mol Sci 17(12):2132. doi:10.3390/ijms17122132

    Article  PubMed Central  Google Scholar 

  12. Baek MY, Ahn HK, Park KR, Park HS, Kang SM, Park I, Kim YS, Hong J, Sym SJ, Park J, Lee JH, Shin DB, Cho EK (2016) Epidermal growth factor receptor mutation and pattern of brain metastasis in patients with non-small cell lung cancer. Korean J Intern Med. doi:10.3904/kjim.2015.158

    Google Scholar 

  13. Jin J, Zhou X, Liang X, Huang R, Chu Z, Jiang J, Zhan Q (2013) Brain metastases as the first symptom of lung cancer: a clinical study from an Asian medical center. J Cancer Res Clin Oncol 139(3):403–408. doi:10.1007/s00432-012-1344-6

    Article  PubMed  Google Scholar 

  14. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386. doi:10.1002/ijc.29210

    CAS  Article  PubMed  Google Scholar 

  15. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66(2):115–132. doi:10.3322/caac.21338

    Article  PubMed  Google Scholar 

  16. Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW (2003) Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res 284(1):31–53

    CAS  Article  PubMed  Google Scholar 

  17. Rosell R, Moran T, Queralt C, Porta R, Cardenal F, Camps C, Majem M, Lopez-Vivanco G, Isla D, Provencio M, Insa A, Massuti B, Gonzalez-Larriba JL, Paz-Ares L, Bover I, Garcia-Campelo R, Moreno MA, Catot S, Rolfo C, Reguart N, Palmero R, Sanchez JM, Bastus R, Mayo C, Bertran-Alamillo J, Molina MA, Sanchez JJ, Taron M (2009) Screening for epidermal growth factor receptor mutations in lung cancer. N Engl J Med 361(10):958–967. doi:10.1056/NEJMoa0904554

    CAS  Article  PubMed  Google Scholar 

  18. Tanaka T, Matsuoka M, Sutani A, Gemma A, Maemondo M, Inoue A, Okinaga S, Nagashima M, Oizumi S, Uematsu K, Nagai Y, Moriyama G, Miyazawa H, Ikebuchi K, Morita S, Kobayashi K, Hagiwara K (2010) Frequency of and variables associated with the EGFR mutation and its subtypes. Int J Cancer 126(3):651–655. doi:10.1002/ijc.24746

    CAS  Article  PubMed  Google Scholar 

  19. Shin DY, Na II, Kim CH, Park S, Baek H, Yang SH (2014) EGFR mutation and brain metastasis in pulmonary adenocarcinomas. J Thorac Oncol 9(2):195–199. doi:10.1097/JTO.0000000000000069

    CAS  Article  PubMed  Google Scholar 

  20. Gomez-Roca C, Raynaud CM, Penault-Llorca F, Mercier O, Commo F, Morat L, Sabatier L, Dartevelle P, Taranchon E, Besse B, Validire P, Italiano A, Soria JC (2009) Differential expression of biomarkers in primary non-small cell lung cancer and metastatic sites. J Thorac Oncol 4(10):1212–1220. doi:10.1097/JTO.0b013e3181b44321

    Article  PubMed  Google Scholar 

  21. Zhang Q, Zhang X, Yan H, Jiang B, Xu C, Yang J, Chen Z, Su J, Wu YL, Zhou Q (2016) Effects of epidermal growth factor receptor-tyrosine kinase inhibitors alone on EGFR-mutant non-small cell lung cancer with brain metastasis. Thorac Cancer 7(6):648–654. doi:10.1111/1759-7714.12379

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Jamal-Hanjani M, Spicer J (2012) Epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of epidermal growth factor receptor-mutant non-small cell lung cancer metastatic to the brain. Clin Cancer Res 18(4):938–944. doi:10.1158/1078-0432.CCR-11-2529

    CAS  Article  PubMed  Google Scholar 

  23. Kim JE, Lee DH, Choi Y, Yoon DH, Kim SW, Suh C, Lee JS (2009) Epidermal growth factor receptor tyrosine kinase inhibitors as a first-line therapy for never-smokers with adenocarcinoma of the lung having asymptomatic synchronous brain metastasis. Lung Cancer 65(3):351–354. doi:10.1016/j.lungcan.2008.12.011

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was granted partly by Natural Science Foundation of Shanghai, China (No. 16ZR1404300), Municipal Commission of Health and Family Planning of Shanghai, China (No. 201440584) and Science and Technology Development Foundation of Baoshan, Shanghai, China (No. 14-E-27).

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Affiliations

  1. Department of Oncology, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China

    Mengxi Ge, Xinli Zhou, Ruofan Huang, Xiaohua Liang & Qiong Zhan

  2. Company 4, Battalion 1, Cadet Brigade 1, Fourth Military Medical University, Xi’an, 710032, China

    Yingjie Zhuang

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  1. Mengxi Ge
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  2. Yingjie Zhuang
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  3. Xinli Zhou
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  5. Xiaohua Liang
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Correspondence to Xiaohua Liang.

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Ge, M., Zhuang, Y., Zhou, X. et al. High probability and frequency of EGFR mutations in non-small cell lung cancer with brain metastases. J Neurooncol 135, 413–418 (2017). https://doi.org/10.1007/s11060-017-2590-x

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  • DOI: https://doi.org/10.1007/s11060-017-2590-x

Keywords

  • Brain metastases
  • Non-small cell lung cancer
  • Epidermal growth factor receptor
  • Tyrosine kinase inhibitor