Progression of central nervous system metastases in advanced non-small cell lung
PUBLISHED: 2015-11-26  558 total views, 1 today

Yongmei Liu1, Qian Zhao2, Xiaojuan Zhou3, Yong Xu4Youling Gong4,Meijuan Huang4, Feng Peng4, Lin Zhou4, Jiang Zhu4Jin Wang4, Li Ren4, Mei Hou4, You Lu4, Yongmei Liu3

1Department of ThoracicOncology, Cancer Center, West China Hospital, Sichuan University, 2School of Medicine, WestChina Sichuan University, 3Sichuan University,Department of Thorac West China Hospital, 4Department of ThoracicOncology,

West China Sichuan University


Objective:Central nervous system (CNS) progressionis frequently detected in patients with favorable initial responses toEpidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs), butdata are incomplete with respect to clinical features and prognostic factors ofCNS failure in this population. Method: We retrospectively evaluated 308advanced Non-Small Cell Lung Cancer (NSCLC) patients treated with first orsecond-line gefitinib for over 6 months. We studied CNS progression of thosepatients, defining this as newly developed CNS metastases or progression ofpreexisting brain lesions after gefitinib treatment. Result: Of the 308patients, 89 with CNS progression after gefitinib initiation were identified.The median time to CNS progression was 12 months (95% CI 10.5-13.5). Forpatients with previous brain metastases, the median time to CNS progression ofpatients with gefitinib and local CNS therapy was significantly longer thanthose treated with gefitinib alone (23.6 months vs. 15.5 months; P=0.014).Patients with L858R mutations were more likely to experience CNS failure thanthose with exon 19 deletions (P=0.05). The median survival time afterCNS progression was 10.4 months (95%CI 7.5-13.3). Localized CNS therapy was theonly independent predictor of overall survival (OS) for these patientsaccording to both univariate and multivariate analysis. In subset analysiswithin patients harboring EGFR common activating mutations, the median OS afterCNS progression of patients harboring L858R mutation are significantly shorterthan those with exon 19 deletions (9.5vs.33.2, P=0.037). Conclusion: Foradvanced NSCLC patients treated successfully with gefitinib, careful monitoringfor CNS failure and localized CNS therapy should be considered for CNSprogression. L858R mutations might be associated with higher risk of CNSprogression and represent a negative prognostic factor, compared with exon 19deletions.


Key Words: Non-small cell lung cancer  gefitinb central nervous

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