{
  "abstract": "Background: Biliary Tract Cancers (BTCs) are difficult‐to‐treat malignancies with limited therapeutic options and dismal prognosis. Upfront comprehensive genomic profiling (CGP) is recommended for advanced BTC to identify actionable alterations, but its real‐world implementation remains underexplored.\n\nMethods: In 2019, we implemented upfront CGP for advanced BTC at our institution. Molecular profiling results were reviewed within our institutional molecular tumor board when clinically applicable. Patients were followed throughout their disease course.\n\nResults: A total of 80 patients with locally unresectable (n = 14) or metastatic (n = 66) BTC underwent CGP. Testing was performed on cytology material (6/80), tumor biopsies (38/80), or surgical specimens (36/80). In 59/80 cases (73.8%) testing was carried out prior to the beginning of palliative first‐line treatment. In 42/80 (52.5%) cases, at least one clinically actionable genomic alteration was identified. The most frequent actionable alterations involved IDH1 (13.8%), FGFR2 (8.8%), ERBB2 (HER2) (5.0%), KRAS G12C (2.5%), and BRAF (1.3%). Alterations in DNA damage response genes were detected in 11/80 tumors, and 3/80 were dMMR/MSI‐H. FGFR2 and IDH1 mutations were detected in ICC only, while HER2 alterations were more commonly detected in ECC and GBC. 11/42 patients with a clinically actionable alteration received targeted treatment during the disease course (1 first‐line, 10 later lines). Among patients with an evaluable preceding systemic treatment line, treatment duration was longer with molecularly matched treatment than with the immediately preceding treatment line (p = 0.0391). 2/14 patients with initially unresectable BTC achieved secondary resectability during molecularly matched treatment.\n\nConclusion: Upfront CGP is feasible in routine clinical practice and identifies clinically actionable alterations in a substantial proportion of patients with advanced BTC. However, only a subset received molecularly matched treatment, highlighting a gap between molecular actionability and treatment implementation. Timely access to matched therapies remains critical to the clinical utility of precision oncology in BTC.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Oncology and Hematology University Hospital Zurich Zurich Switzerland",
    "University of Zurich Zurich Switzerland",
    "Department of Medical Oncology Inselspital, University Hospital of Bern Bern Switzerland",
    "Department for BioMedical Research University of Bern Bern Switzerland",
    "Department of Pathology and Molecular Pathology University Hospital Zurich Zurich Switzerland",
    "Institute of Molecular Cancer Research (IMCR) University of Zurich Zurich Switzerland"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Saskia Hussung",
      "orcid": "0000-0001-7987-0065"
    },
    {
      "affs": [
        0
      ],
      "name": "Mia Roth"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Dilara Akhoundova"
    },
    {
      "affs": [
        0
      ],
      "name": "Clelia Pistoni",
      "orcid": "0000-0002-2644-8837"
    },
    {
      "affs": [
        0
      ],
      "name": "Judith Konrat",
      "orcid": "0000-0001-8996-6618"
    },
    {
      "affs": [
        0
      ],
      "name": "Franca Lisy"
    },
    {
      "affs": [
        0
      ],
      "name": "Tabea Ibach"
    },
    {
      "affs": [
        0
      ],
      "name": "Tomas Brezina"
    },
    {
      "affs": [
        4
      ],
      "name": "Markus Rechsteiner"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Daniela Lenggenhager",
      "orcid": "0000-0002-5382-9854"
    },
    {
      "affs": [
        4
      ],
      "name": "Martin Zoche"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Holger Moch",
      "orcid": "0000-0002-7986-2839"
    },
    {
      "affs": [
        1,
        4,
        5
      ],
      "name": "Achim Weber",
      "orcid": "0000-0003-0073-3637"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ralph Fritsch"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fgayec1dwv396.bib",
  "cited_by": 0,
  "doi": "10.1002/cam4.72461",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732104/",
  "id": "fgayec1dwv396",
  "issns": [
    "2045-7634"
  ],
  "landing_url": "https://doi.org/10.1002/cam4.72461",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2746|Cholangiocarcinoma and Gallbladder Cancer Studies"
    ]
  ],
  "openalex": "W7225251170",
  "pdf_url": null,
  "pmcid": "PMC13732104",
  "pmid": "42978272",
  "published": "2026-11-03",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/fgayec1dwv396.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:09Z",
      "native_id": "PMC13732104",
      "source": "pmc",
      "url": "https://doi.org/10.1002/cam4.72461"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Cholangiocarcinoma and Gallbladder Cancer Studies",
      "subfield": "surgery"
    }
  ],
  "title": "Upfront Comprehensive Genomic Profiling in Advanced Biliary Tract Cancer: Real‐World Implementation and Clinical Outcomes",
  "title_text": "Upfront Comprehensive Genomic Profiling in Advanced Biliary Tract Cancer: Real‐World Implementation and Clinical Outcomes",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:09Z",
  "url": "https://research.draconitic.com/paper/fgayec1dwv396",
  "venue": "Cancer Medicine",
  "versions": []
}