Molecular differences with therapeutic implications in early-onset compared to average-onset cholangiocarcinoma


Thejus Jayakrishnan, Yasmine Baca, Joanne Xiu, Mehrie Patel, Benjamin Adam Weinberg, Emil Lou, Jashodeep Datta, Moh’d M. Khushman, Pat Gulhati, Sanjay Goel, Tiago Biachi de Castria, Vaia Florou, Kanika G. Nair, Suneel Deepak Kamath, Alok A. Khorana

Key Findings:

  • Analysis of comprehensive molecular profiling data from 5,587 cholangiocarcinoma (CCA) patients identified distinct molecular signatures for early-onset (< 50 years of age, eoCCA) versus average-onset (aoCCA) tumors.
  • FGFR2 fusion, a targetable mutation, was significantly more prevalent in eoCCA, and the two tumor types had significant differences in immunotherapy-related markers, angiogenesis enrichment, and inflammatory response.
  • Patients with eoCCA experienced better outcomes with immunotherapy even though immune-oncology-relevant markers like MSI and TMB favored aoCCA.
  • These findings, especially higher FGFR2 fusion prevalence in eoCCA, underscore the need for NGS testing and the potential for age-tailored therapeutic strategies.
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