Brain metastasis in gastroesophageal adenocarcinoma: Outcomes and molecular features.

Abstract

347 Background: Brain metastases (BrM) rarely occur in patients with metastatic gastroesophageal adenocarcinoma (GEA) and represent a unique therapeutic challenge. We describe the unique clinical, molecular, and genomic factors associated with mGEA cancer and BrM development in order to help guide future clinical management. Methods: Patients (pts) with GEA seen at Memorial Sloan Kettering Cancer Center (MSKCC) from 2008-2019 and who had consented for genomic tumor profiling with MSK-IMPACT, a capture-based next-generation sequencing platform that detects mutations, copy-number variations, and select fusions, were retrospectively identified. Clinical and pathologic characteristics were reviewed. BrM were identified via International Classification of Diseases (ICD) billing codes and electronic medical record problem lists, and then manually validated. Survival was calculated from the time of BrM diagnosis until date of death or last follow up and estimated using the Kaplan-Meier method. Results: Fifty pts with GEA metastatic to the brain were identified. Most pts were male (86%) and white (80%), with primary tumor of the esophagus/gastroesophageal junction (82%) and intestinal-type Lauren histology (90%). Twenty-three pts (46%) were HER2 positive (defined as IHC 2+/FISH+ or IHC 3+). Frequencies of PTEN (16%) and EGFR (22%) alterations in primary or metastatic sites were enriched in pts with BM compared to that seen across the MSKCC retrospective cohort and the GEA Cancer Genome Atlas (TCGA) cohort. The majority (68%) of pts had stage IV disease at initial diagnosis, and 4 pts were found to have BrM within 1 month (mo) of stage IV diagnosis, while 27 pts developed BrM during therapy. Median time to BrM diagnosis was 18.3 mos (IQR 11.5-28.9) and 15.1 mos from stage IV diagnosis (IQR 4.8-25.5). Median survival was 7.6 mos from BrM diagnosis and 15.6 (95% CI 10.0-NR, n = 19), 7.6 (95% CI 2.5-NR, n = 13), and 4.3 (95% CI 3.5-12.3, n = 18) mos for pts with 1, 2-3, or 4+ BrM, respectively. Conclusions: GEA pts with BrM had increased frequency of HER2 positivity, as well as PTEN and EGFR alterations, compared to GEA pts overall historically. Further correlation between BrM development, molecular characteristics, and survival in a larger cohort will be presented.