Bo Li¹, Suozhu Sun², Zhengming Wang³, Kaijin Wang¹, Jianling Shi², Bing Liu¹, Zhenzhen Li¹, Lei Sun¹, Min Zuo¹, Huoming Chen¹

¹Department of Oncology, The Second Artillery General Hospital PLA, ²Department of Pathology, The Second Artillery General Hospital PLA, ³Department of Imaging, The Second Artillery General Hospital PLA

Objective:To explore the risk factors of brain metastasis (BM) and the role of tyrosine kinase inhibitors in patients with adenocarcinima of the lung. Method: Clinical data of 263 adenocarcinoma patients of the lung who were diagnosed between September 1997 and January 2013 were analyzed retrospectively. Factors including gender (male vs female), age (<60ys vs ≥60ys), stage (I/II vs III/IV), pathology subtype (adenocarcinoma vs Bronchioloalveolar carcinoma), EGFR status (wild type vs mutation), smoking status (never vs current) were analyzed. Result: Younger patients (P=0.03), those with advanced disease at diagnosis (P<0.001), and adenocarcinoma (P=0.005) had significantly higher incidence of BM. While the incidence between gender (P=0.2), smoking status (P=0.5) and EGFR mutation status (P=0.3) were similar. In terms of brain-metastasis-free survival (BMFS), those younger than 60 (P=0.008) and with advanced disease (P=0.002) at diagnosis had significantly shorter BMFS. While the BMFS between gender (P=0.5), smoking status (P=0.6) and pathological subtype were comparable (P=0.08). In 100 patients with known EGFR status, patients with EGFR sensitive mutations (mutation at exon 19/21/ and dualmutation) had significantly shorter BMFS compared with patients with wild-type EGFR (P=0.01). In patients with sensitive EGFR mutation treated with TKIs before BM had longer BMFS compared with patients treated conventional chemotherapy only, but the difference was not significant (P=0.4). In patients with BM and EGFR sensitive mutations, those treated with tyrosine kinase inhibitors (TKIs) had significantly longer overall survival compared with those treated with chemotherapy only (P=0.008). Conclusion: In patients with adenocarcinoma of the lung, those younger than 60 and with advanced disease at diagnosis had significantly higher incidence of BM and shorter BMFS. Patientswith EGFR sensitive mutation had significantly shorter BMFS compared with those with wild-type EGFR. Compared with conventional chemotherapy, TKIs could significantly improve survival of BM patients who harbored EGFR sensitive mutation.

Key Words: Non-small cell lung cancer  adenocarcinoma  brain metastasis