Risk factors for brain metastases in patients with non-small cell lung cancer: a meta-analysis of 43 studies.

Background: Lung cancer is a leading cause of cancer-related mortality worldwide. The purpose of our meta-analysis was to assess the risk factors for brain metastases (BM) in patients with non-small cell lung cancer (NSCLC).
Methods: Multiple databases, including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang, were systematically searched to recruit relevant studies investigating the risk factors for BM in NSCLC patients. The Newcastle-Ottawa Scale was used to evaluate literature quality, and the meta-analysis was performed using the Review Manager 5.3. Evidence quality evaluation was carried out according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) standard. The estimated odds ratio (OR) and 95% confidence intervals (CIs) were set as effect measures. Funnel plots and sensitivity analyses were used to assess publication bias and the robustness and reliability of the combined results, respectively.
Results: A total of 43 studies with 11,415 participants were included in this meta-analysis. The results indicated that the following factors were significantly associated with an increased risk of BM in NSCLC patients (P<0.05): (I) gender (female) (OR =1.32, 95% CI: 1.17-1.49, P<0.00001); (II) adenocarcinoma (OR =2.34, 95% CI: 1.76-3.11, P<0.00001) or non-squamous cell carcinoma (OR =0.63, 95% CI: 0.42-0.94, P=0.02); (III) advanced tumor stage (OR =1.48, 95% CI: 1.01-2.17, P=0.04); (IV) node stage (OR =2.19, 95% CI: 1.39-3.45, P=0.0007); (V) lymphatic metastasis (OR =2.43, 95% CI: 1.76-3.36, P<0.00001); (VI) epidermal growth factor receptor (EGFR) gene mutation (OR =1.88, 95% CI: 1.26-2.80, P=0.002); (VII) kirsten rat sarcoma viral oncogene (KRAS) gene mutation (OR =2.99, 95% CI: 1.82-4.91, P<0.00001); (VIII) higher levels of carcinoembryonic antigen (P<0.00001), carbohydrate antigen 199 (P<0.0001), cytokeratin-19 fragment (P=0.04), neuron-specific enolase (P<0.00001), and carbohydrate antigen 125 (P=0.0005).
Conclusions: This meta-analysis demonstrated that NSCLC patients with BM have more aggressive clinical features.