Demographic and molecular landscape of biliary tract cancers in and near Bronx, NY.

Abstract

e16161 Background: Biliary tract cancers (BTCs), including gallbladder cancer (GBC) and intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) cholangiocarcinoma, are a rare diverese group of malignancies that have been linked to different demographic and environmental factors. Moreover, they are driven by both distinct and shared molecular mechanisms. We noticed an unfortunately high incidence of BTCs in our patient population – a population that is enriched in minority groups, immigrants, and socioeconomic barriers. Here we describe the landscape of our BTC cases to elucidate anthropologic and molecular drivers of BTC in our community. Methods: We reviewed the charts of BTC patients who were diagnosed between 2021-2022 who had a touchpoint with our healthcare system. We collected demographic information such as gender, date of birth, and self-reported race and ethnicity, and recorded diagnosis-specific details, such as BTC subtype, pathological date of diagnosis, and stage at diagnosis (n = 138). Molecular tumor characteristics obtained through tissue immunohistochemistry or NextGen Sequencing (NGS) at presentation were aggregated when available (n = 86). Results: GBC patients were more likely to be female than male (63% vs 37%) with median age of diagnosis of 63.5 (vs 70.5 in males). Among female BTC patients, there was near equal prevalence of GBC and iCCA (~40%). All CCA subtypes had male predominance and earlier median age of diagnosis with a notably early median age of diagnosis of 57 in the pCCA group. Among different race and ethnicity groups, iCCA and dCCA patients were primarily White non-Hispanic (WNH) (39% and 32%) with most remaining cases being Hispanic (29% and 26%) or Black non-Hispanic (BNH) (22% and 21%). Conversely, Hispanic and BNH patients each made up 27% of pCCA cases and WNH only 18%. Both Hispanic and BNH patients each had a 30-40% prevalence of GBC and iCCA per cancer, while iCCA was the most common BTC among WNH (61%). NGS studies show enrichment of TP53 mutations, especially in GBC and iCCA (75% vs 52%), which also showed frequent RAS-RAF-MAPK and RB1 pathways alterations and TERT promoter mutations. All but one IDH1 mutations were in iCCA. KRAS mutations, especially G12V, were frequent in pCCA and dCCA (18% and 30%). Uniquely, pCCA mutations were mainly related to DNA repair (MLH1, BRCA2), chromatin regulation (ARID1A, PBRM1), and RNA splicing (SF3B1, RBM10). Three cases each of GBC and iCCA were PDL1-positive; fewer had high TMB. Conclusions: The unique BTC patient population in our community recapitulates known trends in gender and race-ethnicity prevalence. Molecular alterations we detected also align with known BTC alterations in cell cycle, survival, epigenetic and metabolic signaling. Importantly, differences in the distribution of molecular signatures are emerging. We aim for our expanding database to serve as a hypothesis-generating tool to ultimately improve the care of all BTC patients.