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The Importance of Brain Metastasis in EGFR Mutation Positive NSCLC Patients

DOI: 10.1155/2014/856156

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Abstract:

Introduction. Brain metastasis is a poor prognostic marker in lung cancer. However it is not known whether amongst patients with EGFR mutation those with brain metastases have a worse outcome. Methods. We compared the survival outcomes between EGFR mutation positive patients with and without brain metastases. In this retrospective analysis of prospective database of all metastatic lung cancer patients at our centre between July 2009 and December 2012, patients were treated with either combination chemotherapy or oral TKI. All patients with brain metastases received whole brain radiation. Kaplan Meier method was used for survival analysis and compared using log rank test. Results. 101 patients with EGFR mutated, metastatic lung cancer were studied. Fourteen had brain metastases and 87 did not. The common EGFR mutations were exon 19 deletion (61.3%) and exon 21 L858R mutation (28.7%). Overall response was 64% in extracranial metastasis group as compared to 50% in brain metastasis group. There was a significant worsening of median OS in the patients with brain metastases (11.6 months) compared with only extracranial metastases (18.7 months), . Conclusion. Amongst patients with EGFR mutant NSCLC, the presence of brain metastases leads to a worse outcome as compared to patients with extracranial metastases alone. 1. Introduction Metastatic lung cancer is one of the leading causes of cancer mortality worldwide. The presence of brain metastasis confers an even worse prognosis [1]. The median survival amongst patients with adenocarcinoma of the lung with brain metastasis in one of the early reports was around 73 days [1]. Whole brain radiotherapy (WBRT) improves median survival to 4–6 months [2, 3]. Non-small cell lung cancer (NSCLC) patients with brain metastases who have activating mutations of epidermal growth factor receptor (EGFR) tend to do significantly better as compared to those with wild type EGFR (median survival of 12.9 months as compared to 3.1 months) [4], when treated with oral tyrosine kinase inhibitors (TKIs) and cranial irradiation. EGFR mutation positivity is a good prognostic marker and patients with EGFR mutant lung cancer tend to have a longer survival. However, patients with EGFR mutated NSCLC have a predilection to develop brain metastases. The incidence of EGFR mutation positivity among patients with brain metastases is higher, ranging from 44 to 63%, as compared to the usually described 10% incidence of EGFR mutation in all patients diagnosed with NSCLC [5]. Although the development of brain metastases in general predicts for a poor

References

[1]  J. B. Sorensen, H. H. Hansen, M. Hansen, and P. Dombernowsky, “Brain metastases in adenocarcinoma of the lung: frequency, risk groups, and prognosis,” Journal of Clinical Oncology, vol. 6, no. 9, pp. 1474–1480, 1988.
[2]  M. A. Chidel, J. H. Suh, J. F. Greskovich, P. A. Kupelian, and G. H. Barnett, “Treatment outcome for patients with primary nonsmall-cell lung cancer and synchronous brain metastasis,” Radiation Oncology Investigations, vol. 7, no. 5, pp. 313–319, 1999.
[3]  E. C. A. Kaal, C. G. J. H. Ni?l, and C. J. Vecht, “Therapeutic management of brain metastasis,” The Lancet Neurology, vol. 4, no. 5, pp. 289–298, 2005.
[4]  R. Porta, J. M. Sánchez-Torres, L. Paz-Ares, et al., “Brain metastases from lung cancer responding to erlotinib: the importance of EGFR mutation,” European Respiratory Journal, vol. 37, no. 3, pp. 624–631, 2011.
[5]  V. R. Bhatt, S. Kedia, A. Kessinger, and A. K. Ganti, “Brain metastasis in patients with non-small-cell lung cancer and epidermal growth factor receptor mutations,” Journal of Clinical Oncology, vol. 31, no. 25, pp. 3162–3164, 2013.
[6]  A. Chougule, K. Prabhash, V. Noronha et al., “Frequency of EGFR mutations in 907 lung adenocarcioma patients of Indian ethnicity,” PLoS ONE, vol. 8, no. 10, Article ID e76164, 2013.
[7]  C. H. Gow, C. R. Chien, Y. L. Chang et al., “Radiotherapy in lung adenocarcinoma with brain metastases: effects of activating epidermal growth factor receptor mutations on clinical response,” Clinical Cancer Research, vol. 14, no. 1, pp. 162–168, 2008.
[8]  F. Cappuzzo, A. Ardizzoni, H. Soto-Parra et al., “Epidermal growth factor receptor targeted therapy by ZD 1839 (Iressa) in patients with brain metastases from non-small cell lung cancer (NSCLC),” Lung Cancer, vol. 41, no. 2, pp. 227–231, 2003.
[9]  F. A. Shepherd, J. R. Pereira, T. Ciuleanu et al., “Erlotinib in previously treated non-small-cell lung cancer,” The New England Journal of Medicine, vol. 353, no. 2, pp. 123–132, 2005.
[10]  S. M. Lee, I. Khan, S. Upadhyay, et al., “First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial,” The Lancet Oncology, vol. 13, no. 11, pp. 1161–1170, 2012.
[11]  P. A. J?nne, X. Wang, M. A. Socinski et al., “Randomized phase II trial of erlotinib alone or with carboplatin and paclitaxel in patients who were never or light former smokers with advanced lung adenocarcinoma: CALGB 30406 trial,” Journal of Clinical Oncology, vol. 30, no. 17, pp. 2063–2069, 2012.
[12]  D.-Y. Kim, K.-W. Lee, T. Yun et al., “Efficacy of platinum-based chemotherapy after cranial radiation in patients with brain metastasis from non-small cell lung cancer,” Oncology Reports, vol. 14, no. 1, pp. 207–211, 2005.
[13]  A. F. Eichler, K. T. Kahle, D. L. Wang et al., “EGFR mutation status and survival after diagnosis of brain metastasis in nonsmall cell lung cancer,” Neuro-Oncology, vol. 12, no. 11, pp. 1193–1199, 2010.
[14]  K. Hotta, K. Kiura, H. Ueoka et al., “Effect of gefitinib (“Iressa”, ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer,” Lung Cancer, vol. 46, no. 2, pp. 255–261, 2004.
[15]  J.-E. Kim, D. H. Lee, Y. Choi, et al., “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, vol. 65, no. 3, pp. 351–354, 2009.
[16]  H. Asahina, K. Yamazaki, I. Kinoshita et al., “A phase II trial of gefitinib as first-line therapy for advanced non-small cell lung cancer with epidermal growth factor receptor mutations,” British Journal of Cancer, vol. 95, no. 8, pp. 998–1004, 2006.
[17]  Y. H. Jung, C. W. Han, Y. D. Jung, Y. Y. Cho, and D. J. Han, “Complete remission of brain metastases in non-small cell lung cancer patients harboring an EGFR mutation treated with tyrosine kinase inhibitor without radiotherapy: a report of 3 cases,” Case Reports in Oncology, vol. 7, no. 1, pp. 149–154, 2014.
[18]  M. Jamal-Hanjani and J. Spicer, “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,” Clinical Cancer Research, vol. 18, no. 4, pp. 938–944, 2012.
[19]  H. G. Yi, H. J. Kim, Y. J. Kim et al., “Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are effective for leptomeningeal metastasis from non-small cell lung cancer patients with sensitive EGFR mutation or other predictive factors of good response for EGFR TKI,” Lung Cancer, vol. 65, no. 1, pp. 80–84, 2009.

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