{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:23:01Z","timestamp":1790875381272,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: GBC is an aggressive biliary tract malignancy with limited survival. Although actionable genomic alterations (AGAs) are increasingly recognized in GBC, their prognostic association in real-world practice remains incompletely defined because genomic status is often confounded by stage at presentation and treatment selection. We evaluated the association between documented AGA status and overall survival (OS) using a tiered matching strategy to account for major clinical confounders. Methods: Using the TriNetX Global Collaborative Network, we identified adults with GBC and stratified them into patients with at least one documented AGA in KRAS, TP53, ERBB2, IDH1, FGFR1, PIK3CA, or ARID1A, and a comparison cohort with no documented AGA (representing a real-world population of untested and wild-type patients). Two 1:1 propensity score-matched models were constructed: Model 1 matched for age, sex, and race\/ethnicity; Model 2 additionally matched for metastatic disease, surgical resection, and chemotherapy history. Outcomes were evaluated using risk analysis and Kaplan\u2013Meier survival methods. Results: A marked disparity in genomic documentation was observed before matching, with unknown race recorded in 51.0% of the comparison cohort versus 3.7% of the documented AGA cohort. In the demographic-matched analysis (Model 1), the documented AGA cohort had higher mortality (52.8% vs. 42.5%, p &lt; 0.001) and shorter median OS (684 vs. 948 days; HR 1.23, p = 0.006). In the primary stage- and treatment-matched analysis (Model 2), mortality remained higher in the documented AGA cohort (56.2% vs. 43.0%), corresponding to an absolute risk difference of 13.2% (p &lt; 0.001). Median OS was numerically shorter in the documented AGA cohort (750 vs. 784 days), although the proportional hazards assumption was violated, supporting interpretation based primarily on absolute risk measures. In exploratory subgroup analyses, KRAS alterations were associated with worse survival, whereas the TP53 subgroup was limited by small sample size. Conclusions: In this real-world matched analysis, the presence of documented AGAs in GBC were associated with higher mortality even after matching for major demographic, stage-related, and treatment-related variables. These findings support the prognostic relevance of genomic status in GBC and underscore the need to address disparities in access to genomic documentation and testing.<\/jats:p>","DOI":"10.3390\/cancers18091452","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T09:33:17Z","timestamp":1777627997000},"page":"1452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Actionable Genomic Alterations and Survival in Gallbladder Cancer: A Documented Stage- and Treatment-Matched Real-World Global Analysis"],"prefix":"10.3390","volume":"18","author":[{"given":"Zeeshan","family":"Solangi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Boston Medical Center South, Brockton, MA 02301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherin","family":"Zambrano-Vera","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Berkshire Medical Center, Pittsfield, MA 01201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Surgery, Boston Medical Center Brighton, Boston, MA 02135, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8370-3996","authenticated-orcid":false,"given":"Antonio J.","family":"Arciniegas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3828-1705","authenticated-orcid":false,"given":"Zina","family":"Agha","sequence":"additional","affiliation":[{"name":"College of Medicine, Hawler Medical University, Erbil 44001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghulam","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Medicine, NYU Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Abbasi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Berkshire Medical Center, Pittsfield, MA 01201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5878-072X","authenticated-orcid":false,"given":"Werner","family":"Kristjanpoller","sequence":"additional","affiliation":[{"name":"Department of Industries, Universidad Tecnica Federico Santa Maria, Valparaiso 2390123, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-7972","authenticated-orcid":false,"given":"Olga","family":"Kozyreva","sequence":"additional","affiliation":[{"name":"Department of Oncology, Dana Farber at Boston Medical Center Brighton, Boston, MA 02135, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6557-0712","authenticated-orcid":false,"given":"Fernando","family":"Rotellar","sequence":"additional","affiliation":[{"name":"Department of Surgery, Clinica Universidad de Navarra, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4643-0634","authenticated-orcid":false,"given":"Eduardo A.","family":"Vega","sequence":"additional","affiliation":[{"name":"Department of Surgery, Boston Medical Center Brighton, Boston, MA 02135, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41572-022-00398-y","article-title":"Gallbladder Cancer","volume":"8","author":"Roa","year":"2022","journal-title":"Nat. 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