Incidence of brain metastasis in lung adenocarcinoma at initial diagnosis onthe basis of stage and genetic alterations

Abstract

Objective: Patients with lung adenocarcinoma (ADC) are at higher risk of the development of brain metastasis (BM), and genetic alterations are associated with BM. Patients and methods: A total of 598 patients with lung ADC in our institution between January 2014 and December 2014 were reviewed retrospectively. We evaluated the incidence of BM by stage and genetic al-terations. Results: Of the 598 patients, 97 (16.2%) had BM, which occurred across all stages. The incidence of BM showed a tendency to increase as the stage increased (p ˂ 0.001, trend test). Although patients with EGFR mutations had BM across all stages, those with ALK or K- mutations had BM only in stage III and IV diseases. Regardless of types of mutations, the incidence of BM showed a tendency to increase as the T or N staging increased (p ˂ 0.001 for each of EGFR, ALK, and K-RAS mutations, trend test). Whereas BM incidence showed a tendency to increase as the M staging increased in patients with EGFR-mutant lung ADC (p ˂ 0.001, trend test), there was no linear trend between M staging and ALK (p = 0.469, trend test) or K-RAS mutations (p = 0.066, trend test). After adjusting covariables, EGFR mutations were associated with BM in never-smokers (adjusted OR = 2.07, 95% CI = 1.02 – 4.34) and K-RAS mutations were risk factors for BM in males (adjusted OR = 3.86, 95% CI = 1.01–14.43). Conclusions: BM occurred in approximately 16% of lung ADC patients, including 3% with stage I diseases. Whereas EGFR-mutant lung ADC had BM across all stages, ALK- or K-RAS-mutant lung ADC had BM only in advanced stages. EGFR mutations were risk factors for BM among never-smokers and K-RAS mutations were risk factors among males.