Risk Factors of Brain Metastases in IIIA-N2 Non-Small Cell Lung Cancer After Complete Resection

Abstract

Purpose/Objective(s)Brain metastasis (BM) is one of the most common failure pattern of locally advanced non-small cell lung cancer (NSCLC) after multidisciplinary therapy. Prophylactic Cranial Irradiation (PCI) can improve intracranial control but not overall survival. Thus, it is particularly important to identify risk factors associated with BM and subsequently provide instructions for selecting patients who will optimally benefit from PCI.Materials/MethodsBetween 2003 and 2015, patients with pIIIA-N2 NSCLC who underwent complete resection in our single institution were reviewed and enrolled into the study. Clinical characteristics, pathological parameters, treatment mode, BM time and overall survival (OS) were analyzed. The cumulative incidence of BM was estimated by the Kaplan-Meier method, and the log-rank test was used to analyze differences between the groups. Multivariate Cox regression analysis was used to assess risk factors of BM. Statistically significant difference was set as P < 0.05.ResultsTotally 1400 patients were enrolled, including 900 (64.3%) males and 500 (35.7%) females. The median age was 58.0 (25.0-84.0) years old. 1003 (71.6%) patients were non-squamous cell carcinoma, and 397 (28.4%) were squamous cell carcinoma. The number of patients with pT1, pT2, and pT3 were 174 (12.4%), 995 (71.1%), and 231 (16.5%), respectively. 899 patients (64.2%) received adjuvant chemotherapy, and 334 patients (23.9%) underwent postoperative radiotherapy. The median follow-up time was 38.7 months. The 1, 3 and 5-year OS rates were 92.9%, 66.4% and 52.1%, respectively. The 1, 3 and 5-year cumulative incidence of BM were 6%, 13.9% and 22.2%, respectively. In univariate analysis, patients ≤ 60 years old, non-smokers, non-squamous cell carcinoma, lymph node metastases number≥ 4, lymph node metastases rate > 30%, and adjuvant chemotherapy were more likely to develop BM. In multivariate analysis, non-squamous cell carcinoma (HR:2.789, 95༅CI:1.779-4.372;P < 0.001), lymph node metastasis number≥4 (HR:1.448, 95༅CI:1.042-2.011;P = 0.027) and adjuvant chemotherapy (HR:2.168, 95༅CI:1.507-3.120;P < 0.001) were independent risk factors of BM.ConclusionNon-squamous cell carcinoma, lymph node metastasis number ≥ 4 and adjuvant chemotherapy are the high-risk factors of BM in patients with pIIIA-N2 NSCLC after complete resection. These groups of patients may benefit from PCI and can be enrolled in the further study. Brain metastasis (BM) is one of the most common failure pattern of locally advanced non-small cell lung cancer (NSCLC) after multidisciplinary therapy. Prophylactic Cranial Irradiation (PCI) can improve intracranial control but not overall survival. Thus, it is particularly important to identify risk factors associated with BM and subsequently provide instructions for selecting patients who will optimally benefit from PCI. Between 2003 and 2015, patients with pIIIA-N2 NSCLC who underwent complete resection in our single institution were reviewed and enrolled into the study. Clinical characteristics, pathological parameters, treatment mode, BM time and overall survival (OS) were analyzed. The cumulative incidence of BM was estimated by the Kaplan-Meier method, and the log-rank test was used to analyze differences between the groups. Multivariate Cox regression analysis was used to assess risk factors of BM. Statistically significant difference was set as P < 0.05. Totally 1400 patients were enrolled, including 900 (64.3%) males and 500 (35.7%) females. The median age was 58.0 (25.0-84.0) years old. 1003 (71.6%) patients were non-squamous cell carcinoma, and 397 (28.4%) were squamous cell carcinoma. The number of patients with pT1, pT2, and pT3 were 174 (12.4%), 995 (71.1%), and 231 (16.5%), respectively. 899 patients (64.2%) received adjuvant chemotherapy, and 334 patients (23.9%) underwent postoperative radiotherapy. The median follow-up time was 38.7 months. The 1, 3 and 5-year OS rates were 92.9%, 66.4% and 52.1%, respectively. The 1, 3 and 5-year cumulative incidence of BM were 6%, 13.9% and 22.2%, respectively. In univariate analysis, patients ≤ 60 years old, non-smokers, non-squamous cell carcinoma, lymph node metastases number≥ 4, lymph node metastases rate > 30%, and adjuvant chemotherapy were more likely to develop BM. In multivariate analysis, non-squamous cell carcinoma (HR:2.789, 95༅CI:1.779-4.372;P < 0.001), lymph node metastasis number≥4 (HR:1.448, 95༅CI:1.042-2.011;P = 0.027) and adjuvant chemotherapy (HR:2.168, 95༅CI:1.507-3.120;P < 0.001) were independent risk factors of BM. Non-squamous cell carcinoma, lymph node metastasis number ≥ 4 and adjuvant chemotherapy are the high-risk factors of BM in patients with pIIIA-N2 NSCLC after complete resection. These groups of patients may benefit from PCI and can be enrolled in the further study.