Early-onset biliary tract cancers: clinical and molecular insights.

@article{odonnell2026earlyonset,
  title = {{Early-onset biliary tract cancers: clinical and molecular insights.}},
  author = {C D O'Donnell and J Nunnelee and A Ness and P Shah and O Mosalem and U Majeed and H Babiker and J Jones and J S Starr and M Borad and N Okano and A Pirozzi and T S Bekaii-Saab and C Wu and R R McWilliams and T R Halfdanarson and Z Jin and L Washburn and P Starlinger and J Heimbach and L R Roberts and G J Gores and F-S Ou and N H Tran},
  journal = {ESMO gastrointestinal oncology},
  year = {2026},
  month = jun,
  doi = {10.1016/j.esmogo.2026.100350},
  url = {https://europepmc.org/article/MED/42948669},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Early-onset biliary tract cancers: clinical and molecular insights.
AU  - C D O'Donnell
AU  - J Nunnelee
AU  - A Ness
AU  - P Shah
AU  - O Mosalem
AU  - U Majeed
AU  - H Babiker
AU  - J Jones
AU  - J S Starr
AU  - M Borad
AU  - N Okano
AU  - A Pirozzi
AU  - T S Bekaii-Saab
AU  - C Wu
AU  - R R McWilliams
AU  - T R Halfdanarson
AU  - Z Jin
AU  - L Washburn
AU  - P Starlinger
AU  - J Heimbach
AU  - L R Roberts
AU  - G J Gores
AU  - F-S Ou
AU  - N H Tran
PY  - 2026
DA  - 2026/06/24
JO  - ESMO gastrointestinal oncology
DO  - 10.1016/j.esmogo.2026.100350
UR  - https://europepmc.org/article/MED/42948669
AB  - Background  The incidence of early-onset biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder adenocarcinoma, is rising, but factors underlying this trend remain unclear.Materials and methods  We conducted a retrospective study of BTC patients across three Mayo Clinic sites (2008-2024). Patients were categorized as early-onset (aged <50 years) or older-onset (aged ≥50 years). Clinical characteristics, comorbidities, molecular alterations, treatment patterns, and survival outcomes were compared between groups.Results  A total of 549 patients were included; 170 were enriched for early-onset cases, compared with a cohort of older-onset patients (n = 379) identified through the TEMPUS registry. Compared with older-onset patients [median age 68.0 years, interquartile range (IQR) 60.4, 73.0], early-onset patients (median age 40.5 years, IQR 34.5, 45.1) had significantly fewer metabolic comorbidities, higher frequency of FGFR2 alteration (18.8% versus 6.3%, P < 0.001) and lower frequency of KRAS alteration (15.3% versus 23.0%, P = 0.040). Tumor mutational burden was modestly lower in early-onset disease (3.0 versus 3.7 mutations/megabase, P = 0.003). Early-onset patients were more likely to enroll in clinical trials (25.9% versus 14.0%, P < 0.001) and received more lines of therapy (P = 0.005). Overall survival did not differ significantly between age groups. Among patients receiving first-line gemcitabine-cisplatin with immune checkpoint inhibition, progression-free survival was similar between early-onset and older-onset disease (7.6 versus 6.6 months; hazard ratio, 1.12; P = 0.59).Conclusions  Early-onset BTC demonstrated distinct clinical and molecular profiles, but survival outcomes remained comparable to older-onset BTC. These findings highlight the need for further research into specific oncogenic drivers and tailored therapeutic strategies.
SN  - 2949-8198
ER  -