Brain Metastases in Stage IV Esophageal Cancer: Incidence, Risk Factors and Radiation Utilization

Abstract

<h3>Purpose/Objective(s)</h3> Limited studies indicate that brain metastases from esophageal cancer are uncommon and associated with poor prognosis. This National Cancer Database (NCDB) study investigated the incidence and risk factors associated with brain metastases at diagnosis for Stage IV esophageal cancer patients, as well as radiation utilization and outcomes. <h3>Materials/Methods</h3> The NCDB was used to identify newly diagnosed Stage IV esophageal cancer patients with brain metastases between 2010-2017. A multivariate logistic regression model was used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) for brain metastases at diagnosis. Survival analysis was performed using the Kaplan-Meier method and Cox regression modeling. The multivariate model included age, gender, race, insurance status, income, facility type, Charlson-Deyo comorbidity score, histology, and tumor location. <h3>Results</h3> Of 23,930 patients diagnosed with Stage IV esophageal cancer, 1,532 (6.4%) patients had brain metastases. There was no significant change in the incidence of brain metastases over time with 6.1% in 2010 to 6.6% in 2017 (range: 5.7-7.4%; p=0.27). Patients who were older (aOR 0.98 [95% CI 0.98-0.99]; p<0.0001), female (aOR 0.81 [0.69-0.96]; p=0.015), or Black (aOR 0.77 [0.60-0.99]; p=0.045) were less likely to present with brain metastases. Mid esophageal tumors had higher probability of brain metastases vs. lower esophageal location (aOR 1.55 [1.27-1.89]; p<0.0001). Adenocarcinoma histology was strongly associated with increased risk of brain metastases vs. squamous cell carcinoma (aOR 2.41 [1.97-2.95]; p<0.0001). Of 679 patients with brain metastases who received brain radiotherapy as part of their primary treatment, 504 (74.2%) received whole-brain radiotherapy (WBRT) and 175 (25.8%) received stereotactic radiosurgery (SRS). The use of WBRT decreased over time from 86.4% in 2010 to 72.7% in 2017, while the use of SRS increased from 13.6% in 2010 to 27.3% in 2017 (p=0.035). For patients who received brain radiotherapy, median follow-up was 5.1 months and median survival was 5.2 months. Median survival for patients who received WBRT was 4.5 months vs. 7.8 months for SRS patients (p=0.0001). On multivariate analysis, SRS was associated with improved survival vs. WBRT (hazard ratio [HR] 0.72 [0.59-0.89]; p=0.002). <h3>Conclusion</h3> Approximately 6% of patients with Stage IV esophageal cancer present with brain metastases, with no change in incidence from 2010 to 2017. Older, female, or Black patients were less likely to present with brain metastases, while adenocarcinoma histology and mid esophagus location were significant risk factors for synchronous brain metastases. While survival rates remain dismal, SRS is associated with improved survival vs. WBRT, and its utilization in this population is increasing over time.