Extra-hepatic (ehCCA) and intra-hepatic cholangiocarcinomas (iCCA): A genomic landscape comparison of peri-hilar (phCCA), common bile duct (cbdCCA) and gallbladder (gbCCA) with iCCA.

• DOI: 10.1200/jco.2025.43.4_suppl.630
• Publication Date: 2025-01-27T14:34:47Z
• Authors: Parth J. Sampat; Dean Pavlick; Jeffrey S. Ross; Alina Basnet
• Keywords: Peri

630 Background: Metastatic CCAs have poor prognosis. Comprehensive genomic profiling (CGP) was used to compare alterations (GA) in phCCA, with cbdCCA, gbCCA and iCCA. Frequencies of GA therapy targets such as FGFR2, IDH, ERBB2 & BRAF, Immuno-oncology (IO) drug response predictors (MSI status, TMB PDL1) were examined. Methods: DNA extracted from 110 cases 743 2983 9178 ihCCA underwent hybrid capture based CGP evaluate classes (GA), MSI levels, ancestry, signature, HRD score germline status. phCCA confirmed at surgery pathology originating either left, right or common hepatic ducts. cbdCCA by cbd biopsies Whipple procedures. PD-L1 expression determined IHC using the Dako 22C3 assay tumor proportional (TPS) system. Results: The pt age distributions similar; female gender more frequent gbCCA. featured higher GA/tumor (P=.0001). frequencies FGFR2 IDH1 targetable uncommon especially when compared iCCA (P<.0001). CDKN2A, MTAP PIK3CA like cbdCCA. At 16.5%, frequency highest all ehCCA KRAS including G12C greater both (P=.0015) (P.0001). TP53 (P=.0007). IO biomarker similar all. positive (gLOH) status MMR signature Conclusions: subtypes feature characteristic profiles that potential influence selection lower In contrast, are than iCCA, peri-hilarCCA P-value (phCCA vs cbdCCA) gbCCA) iCCA) BRAF 3.6% 4.7% NS 2.4% 5.1% 14.5% 10.6% 16.5% 0.002 0.9% 2.0% 1.5% 11.7% 0.001 0.8% 0.6% 13.9% 0.006 29.1% 46.2% 0.015 14.2% 0.0015 19.8% 0.071 45.5% 63.8% 0.011 65.7% 0.0007 33.9% 0.061 MSI-high 1.8% 1.3% 1.2% TMB≥10 mut/mb 4.2% 5.2% low 21.1% 31.3% 23.5% 23.7%