{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:43:04Z","timestamp":1788846184230,"version":"build-2803163510"},"reference-count":43,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"8","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Early-onset biliary tract cancer (eoBTC) is among the fast-growing subset of early-onset cancers, yet little is known about its biology. We sought to identify novel molecular characteristics of eoBTC in relation to average-onset BTC (aoBTC) using a real-world multiomics data set.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>The study comprised patients with BTC whose tumors underwent molecular analyses at Caris Life Sciences and were categorized by age (&lt;50 years for eoBTC, \u226550 years for aoBTC). P values were adjusted for multiple testing and considered significant at Q &lt; 0.05 (molecular comparisons) or Q &lt; 0.25 (Gene Set Enrichment Analysis [GSEA]). Insurance claims data were used for survival analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The study included 5,587 patients with BTC (453 eoBTC, median age = 44 years and 5,134 aoBTC, median age = 68 years). FGFR2 fusion (15.7% in eoBTC v 5.9% in aoBTC) and NIPBL fusion (1.1% v 0%) were significantly more prevalent in eoBTC (both Q &lt; 0.001). The interferon gamma-IFG score (fold change [FC], 1.1; Q = 0.01) and T-cell inflammation score (FC, 17.3; Q = 0.03) were significantly higher in aoBTC. On GSEA, angiogenesis was enriched in eoBTC (normalized enrichment score [NES] = 1.51; Q = 0.16), whereas IFG (NES = \u20131.58; Q = 0.06) and inflammatory response (NES = \u20131.46; Q = 0.18) were enriched in aoBTC. The median overall survival (OS) was 16.5 (eoBTC) versus 13.3 months (aoBTC), hazard ratio = 0.86, P = .004. The median OS by FGFR2 fusion (with fusion v without) was 21.7 versus 15.0 months ( P = .47) for eoBTC and 18.6 versus 12.2 months ( P &lt; .001) for aoBTC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>We identified crucial differences including higher prevalence of FGFR2 fusions in eoBTC and variations in immunotherapy-related markers. Better outcomes in eoBTC were affected by the FGFR2 fusion status. Our findings underscore the need for ensuring access to next-generation sequencing testing, including prompt identification of actionable targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po.24.00138","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T16:07:40Z","timestamp":1722874060000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Molecular Differences With Therapeutic Implications in Early-Onset Compared With Average-Onset Biliary Tract Cancers"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3636-0353","authenticated-orcid":true,"given":"Thejus","family":"Jayakrishnan","sequence":"first","affiliation":[{"name":"Department of Hematology-Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH"},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, 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