Journal
NEOPLASIA
Volume 42, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neo.2023.100910
Keywords
Cholangiocarcinoma; Next-generation sequencing; Precision oncology
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In this study, integrative clinical sequencing was performed on advanced biliary tract cancer (BTC) tumors. The results revealed actionable and potentially actionable genomic alterations in a significant portion of the patients, and those who received matched targeted therapy showed improved overall survival. The study also identified recurrent mutations in FGFR2 and a novel association between KRAS and BRAF mutations with high expression of immune modulatory protein NT5E (CD73).
Background: Biliary tract cancers (BTCs) including intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder cancer, are rare but aggressive malignancies with few effective standard of care therapies. Methods: We implemented integrative clinical sequencing of advanced BTC tumors from 124 consecutive pa-tients who progressed on standard therapies (N = 92 with MI-ONCOSEQ and N = 32 with commercial gene panels) enrolled between 2011-2020. Results: Genomic profiling of paired tumor and normal DNA and tumor transcriptome (RNA) sequencing identified actionable somatic and germline genomic alterations in 54 patients (43.5%), and potentially actionable alterations in 79 (63.7%) of the cohort. Of these, patients who received matched targeted therapy (22; 40.7%) had a median overall survival of 28.1 months compared to 13.3 months in those who did not receive matched targeted therapy (32; P < 0.01), or 13.9 months in those without actionable mutations (70; P < 0.01). Additionally, we discovered recurrent activating mutations in FGFR2, and a novel association between KRAS and BRAF mutant tumors with high expression of immune modulatory protein NT5E (CD73) that may represent novel therapeutic avenues. Conclusions: Overall, the identification of actionable/ potentially actionable aberrations in a large proportion of cases, and improvement in survival with precision oncology supports molecular analysis and clinical sequencing for all patients with advanced BTC.
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