Abstract
BACKGROUND: Graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA) for brain metastases is a powerful prognostic tool. However, it has not been validated for non-small-cell lung cancer (NSCLC) patients with synchronous or metachronous brain metastases. METHODS: A total of 1184 NSCLC patients with synchronous or metachronous brain metastases were reviewed in this study. Comparative clinicopathological variables and survival analysis for these two groups (synchronous vs metachronous), as well as complimentary analysis of prognostic factors for the entire patient cohort, were performed. Afterward, patients were stratified using Lung-molGPA to evaluate the accuracy of the survival estimates. RESULTS: A total of 763 patients (64.4%) had synchronous metastases while 35.6% (421 patients) had metachronous metastasis. Patients with synchronous metastases were more likely to have a smoking history, limited metastatic lesions, and absence of cerebral symptoms (P<0.05). Patients with metachronous metastatic NSCLC had an overall survival (OS) period of 16.5 (95% CI 14.5-18.6) months and were longer compared to patients with synchronous metastases (16.5 vs 13.5 [12.5-14.6] months, P=0.004). In Cox regression multivariable analysis, age (HR=1.25, P=0.008), Karnofsky performance status (HR=1.30, P=0.005), extracranial metastases (HR=1.57, P<0.001), number of brain metastases (HR=1.22, P=0.043), gene mutation (HR=1.40 [wild type vs mutation], P=0.050; HR=1.42 [unknown vs mutation], P=0.007), and treatment (including TKI, chemotherapy, and local brain treatment, P<0.05) were independent prognostic predictors of OS. Additionally, metachronous metastatic patients were at lower risk for disease-related death compared to synchronous metastatic patients (HR=0.69, P<0.001). Importantly, median OS stratified by Lung-molGPA of 0-1, 1.5-2, 2.5-3 and 3.5-4 scores were 11.0, 14.0, 24.9, and 26.3 months for synchronous brain metastases, and 13.1, 17.0, 37.2, and 66.5 months for metachronous metastases, respectively (P<0.001). CONCLUSION: Lung-molGPA could estimate the prognosis of NSCLC patients with synchronous or metachronous brain metastases. Hence, patients should be carefully stratified for consideration of aggressive therapy.