Racial and Sex Differences in Genomic Profiling of Intrahepatic Cholangiocarcinoma.

Abstract

Racial and sex disparities in the incidence and outcomes of patients with intrahepatic cholangiocarcinoma (iCCA) exist, yet potentialgenomic variations of iCCA based on race and sex that might be contributing to disparate outcomeshave not been well studied. Data from the American Association for Cancer ResearchProject GENIE registry (version 15.0) were analyzed to assess genetic variations in iCCA. Adult patients (age >18 years) with histologically confirmed iCCA who underwent next-generation sequencing were included in the analytic cohort. Racial and sex variations in genomic profiling of iCCA were examined. The study enrolled 1068 patients from 19 centers (White, 71.9%; Black, 5.1%; Asian, 8.4%, other, 14.6%). The male-to-female ratio was 1:1. The majority of the patients had primary tumors (73.7%), whereas 23.0% had metastatic disease sequenced. While IDH1 mutations occurred more frequently in White versus Black patients (20.8% vs. 5.6%; p = 0.021), FGFR2 mutations tended to be more common among Black versus White populations (27.8% vs. 16.1%; p = 0.08). Males were more likely to have TP53 mutations than females (24.3% vs. 18.2%, p = 0.016), whereas females more frequently had IDH1 (23.3% vs 16.0 %), FGFR2 (21.0% vs. 11.3%), and BAP1 (23.4% vs. 14.5%) mutations than males (all p < 0.05). Marked variations in the prevalence of other common genomic alterations in iCCA were noted across different races and sexes. Distinct genomic variations exist in iCCA across race and sex. Differences in mutational profiles of iCCA patients highlight the importance of including a diverse patient population in iCCA clinical trials as well as the importance ofrecognizing different genetic drivers that may be targetable to treatdistinct patient cohorts.