BackgroundNon-small cell lung cancer (NSCLC) is characterized by a high incidence of brain metastasis (BM) and the prognosis of NSCLC patients with BM is poor. Previous study demonstrated four prognostic factors, which were age, poor PS, presence of extracranial metastases (ECM), and number of BM, in NSCLC patients with BM. This study aimed to identify prognostic factors and clarify the survival in NSCLC patients with BM at the time of a diagnosis. MethodsA total of 566 NSCLC patients with BM from 15 institutions between January 2008 and December 2014. Among them, 176 patients had driver mutation, such as EGFR mutation and ALK-rearrangement, and 390 patients did not. This retrospective study focused on the 390 NSCLC patients without driver mutation, and identified clinical prognostic factors using Cox proportional hazards model. Moreover, we validated the disease specific Graded prognostic assessment (DS-GPA) in this cohort. ResultsMedian OS was 7.6 months, respectively (95% confidence interval [CI]; 6.5-8.7, data cut-off; December 2018). Multivariate analyses demonstrated the following independent prognostic factors; gender male (P=0.001), age > 64 years (P=0.009), poor PS (P<0.001), T factor (P=0.001), N factor (P=0.028), histological type of non-adenocarcinoma (P<0.001), presence of ECM (P<0.001), and number of BM (P=0.023). The median survival of four patient groups according to DS-GPA demonstrated 4.1 (GPA 0-1.0, n=146, 95% CI, 3.2-5.1), 8.3 (GPA 1.5-2.0, n=136, 95% CI, 6.5-10.1), 12.5 (GPA 2.5-3.0, n=96, 95% CI, 9.3-15.7), 21.4 (GPA 3.5-4.0, n=12, 95% CI, 0-43.2) months, respectively. ConclusionsPrognosis of NSCLC patients with EGFR, ALK negative and BM is poor. In addition to the known prognostic factors such as DS-GPA, this study shown that male, T factor, N factor, and histological type of non-adenocarcinoma, had a prognostic role in NSCLC patients with driver mutation negative and BM. Clinical trial identificationUMIN000030313, 08/12/2017. Legal entity responsible for the studyHokkaido Lung Cancer Clinical Study Group Trial: HOT. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.