Comprehensive molecular profiling in patients with advanced biliary tract cancers (BTC) in a Latinx-rich cohort.

Abstract

605 Background: BTC are genetically diverse and heterogeneous. Despite knowledge of molecular subtypes of BTC, the distribution of molecular aberrations in the Latinx population has been understudied. These may have prognostic and/or predictive implications. Therefore, we analyzed our cohort of Latinx-rich patients with advanced BTC. Methods: We analyzed patients with advanced BTC, who were seen at the Mays Cancer Center from Jan 2018-Dec 2021. Tumor samples profiled by Next Generation Sequencing (NGS) were identified retrospectively. Associations between demographics, clinical characteristics, and genetic alterations were identified. Results: 88 patients with locally advanced/metastatic BTC were identified. 50 (56.2%) were Latinx. 42 (47.7%) had intrahepatic CA (IHCA), 14 (15.9%) had extrahepatic CA (EHCA), 16 (18.2%) had Gall Bladder Carcinoma (GBC) and 16 (18.2%) had Ampullary/Periampullary Carcinoma (APC). 49 (56%) had NGS on their tumors out of which 30 (61.2%) were Latinx and 19 (38.8%) were non-Latinx. The most commonly altered genes were TP53 (34.7%), KRAS (24.5%), ARID1A (16.3%), BRCA-2 (12.2%), PDL-1 (12.2%), FGFR (12.2%), MET (10.2%), PTEN (10.2%) and HER-2 (8.2%). 14.3% patients had no identifiable mutations. There was no significant difference observed in the rates of different molecular mutations between Latinx and non-Latinx (p=1) and among different histologies of IHCA, EHCA, GBC and APC (p=1). The Median Overall Survival (OS) for Latinx population was 16.1 months (95% CI 12.3-28.2) which was similar to the median OS for non-Latinx population of 15.5 months (95% CI 11.6-28.6) (p=0.69). The median OS was not different due to the presence or absence of any one mutation (p values ranged from 0.04 to 0.9). Conclusions: BTCs are genetically diverse. Somatic alterations were identified in 85% patients who were tested. Only 56 % had molecular testing, when it should be 100% in advanced BTC, per NCCN guidelines. This may be due to inadequate tissue, lack of funding, use of alternate ctDNA, or the patient may have died before getting to testing/repeat biopsy. The likelihood of having a genetic alteration was similar between Latinx and non-Latinx patients and among different sites of disease. Latinx and Non Latinx with advanced BTC had similar survival rates. Survival rate was not different due to the presence or absence of any one mutation. Future studies should prospectively investigate implementation programs for NGS in tumor and blood in all patients with BTCs.