Cholangiocarcinoma With Genetic Aberrations: A Unique Clinical Phenotype.

PURPOSE

genetic aberrations (GAs) occur in an estimated 10% to 16% of intrahepatic cholangiocarcinomas (CCAs). The natural history of CCA with GAs, the prognostic role of coexisting GAs, and the outcome with FGFR-targeted inhibitors are unknown.

PATIENTS AND METHODS

Patients with CCA with GAs were identified using next-generation sequencing or fluorescence in situ hybridization from four tertiary cancer centers and compared with wild-type counterparts. Data reviewed included demographic, treatment, overall survival (OS), and GA data. Fisher's exact test, Kaplan-Meier plots, and log-rank tests were used for statistical analysis.

RESULTS

Three hundred seventy-seven patients with CCA were identified, and 95 had GAs. GA was most common (n = 74, with 63 fusions) and seen in intrahepatic CCA. In patients with CCA, GAs occurred more frequently in younger patients (≤ 40 years; 20%) compared with older patients (> 40 years; 6.7%; < .001), presented at an earlier stage (TNM stage I/II III/IV: 35.8% 22%, respectively; = .001), and were associated with a longer OS compared with patients without GAs (37 20 months, respectively; < .001). This difference remained significant after excluding 36 patients treated with FGFR inhibitors. There was no OS difference ( = .60) between CCA with fusions (n = 63) versus other GAs (n = 29). Patients with GAs had a better OS with FGFR-targeted therapy compared with standard treatment ( = .01). mutation was the most common coexisting mutation without prognostic impact, whereas ( = .04) and ( = .04) were correlated with a shorter OS.

CONCLUSION

CCA with GAs represents a unique subtype occurring in younger patients with an indolent disease course. FGFR-targeted therapy may have a positive impact on OS in this subgroup.