Yun Fan, Zhiyu Huang, Luo Fang, Lulu Miu, Nengming Lin, Lei Gong, Haifeng Yu, Haiyan Yang, Weimin Mao Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology (Esophagus, Lung), Zhejiang Cancer Hospital, Zhejiang, People's Republic of China Background: Chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are controversial in the treatment of patients with brain metastases from non-small-cell lung cancer (NSCLC). Methods: We retrospectively studied the effects of solely localized treatment or localized treatment in combination with chemotherapy and/or EGFR tyrosine kinase inhibitors on outcomes in 210 NSCLC patients with brain metastases. The effects of treatment modality, Karnofsky performance status, age, primary tumor histology, number of brain metastases, and other factors on survival time were analyzed, and the robustness of two prognostic indices, ie, recursive partitioning analysis and graded prognostic assessment, was evaluated. Results: The median survival time in patients with systemic medication and localized treatments was higher than in those with localized treatments alone (11 versus 3 months, P=0.000). Within the systemic medication group, median survival time was significantly longer for EGFR tyrosine kinase inhibitors than for other types of chemotherapy (12 versus 9 months, P=0.002). In the EGFR tyrosine kinase inhibitor group, median survival time for patients with EGFR gene mutation was 20 months versus 8 months for those with the wild-type EGFR gene. The median survival time with pemetrexed was significantly higher than with other chemotherapies (13 versus 7 months, P=0.006). In multivariate analysis, the prognosis was significantly correlated with treatment modality (P=0.000), Karnofsky performance status (P=0.000), number of brain metastases (P=0.001), and histologic tumor type (P=0.007). In the graded prognostic assessment model, survival curves for the subgroups showed clear separations. Conclusion: NSCLC patients with brain metastasis benefited from pemetrexed and/or tyrosine kinase inhibitors along with localized treatments, and the graded prognostic assessment index is a robust model for prognostic evaluation. Keywords: epidermal growth factor receptor, tyrosine kinase inhibitors, brain metastases, non-small-cell lung cancer, pemetrexed, chemotherapy