Risk Factors Associated with Interval Time between Initial Non-Small Cell Lung Cancer (NSCLC) Diagnosis and Development of Brain Metastases

Abstract

Lung cancer remains the leading cause of brain metastases (BM). Our goal is to identify potential NSCLC risk factors associated with decreased time to BM. We retrospectively reviewed all NSCLC patients with BM treated with radiotherapy at a single institution from 1997 to 2015. Interval time (IT) to BM development was defined as pathological diagnosis of NSCLC to radiographic diagnosis of BM. Patients were stratified by clinical stage of initial NSCLC diagnosis. Stage 4 patients with BM present on initial staging MRI were excluded from the study. Prognostic factors were analyzed through the Kaplan-Meier method and Cox proportional hazards model. Survival curves were calculated with the Kaplan-Meier method using development of BM as the primary endpoint. A cohort of 109 patients were included in this study for analysis. Median IT for the entire cohort was 23 months. On Kaplan-Meier analysis for IT clinical stage at primary diagnosis, tumor histology, and surgical history showed significant differences between groups Stage III patients had median IT of 22 months and stage IV patients had median IT of 16 months compared to stage I patients with a median IT of 62 months. Non-adenocarcinoma histology had a median IT of 9 months compared to adenocarcinoma histology with a median IT of 25 months. Patients with no surgical resection of primary lung cancer had a median IT of 16 months compared to patients who underwent surgical resection with a median IT of 46 months. On univariate analysis stage III, stage IV, nodal-status of N2 disease, nodal-status of N3 disease, no surgical resection of primary lung cancer, and non-adenocarcinoma tumor histology were associated with decreased IT. On multivariate analysis stage III, stage IV, no surgical resection of primary lung cancer, and non-adenocarcinoma tumor histology were associated with decreased IT. Clinical stage, tumor histology, and surgical history could be associated with timing to BM development in NSCLC patients and should be further investigated to better characterize patients at risk for developing brain metastases at a shorter time interval.