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Peer-reviewedCC BY 4.0Cancer Medicine

Upfront Comprehensive Genomic Profiling in Advanced Biliary Tract Cancer: Real‐World Implementation and Clinical Outcomes

  • Saskia Hussung1,2
  • Mia Roth1
  • Dilara Akhoundova3,4
  • Clelia Pistoni1
  • Judith Konrat1
  • Franca Lisy1
  • Tabea Ibach1
  • Tomas Brezina1
  • Markus Rechsteiner5
  • Daniela Lenggenhager2,5
  • Martin Zoche5
  • Holger Moch2,5
2 more authors
  • Achim Weber2,5,6
  • Ralph Fritsch1,2
6 affiliations
  1. 1Department of Medical Oncology and Hematology University Hospital Zurich Zurich Switzerland
  2. 2University of Zurich Zurich Switzerland
  3. 3Department of Medical Oncology Inselspital, University Hospital of Bern Bern Switzerland
  4. 4Department for BioMedical Research University of Bern Bern Switzerland
  5. 5Department of Pathology and Molecular Pathology University Hospital Zurich Zurich Switzerland
  6. 6Institute of Molecular Cancer Research (IMCR) University of Zurich Zurich Switzerland
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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.

Methods: 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.

Results: 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.

Conclusion: 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.

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Cite

BibTeXRIS
BibTeX
@article{hussung2026upfront,
  title = {{Upfront Comprehensive Genomic Profiling in Advanced Biliary Tract Cancer: Real‐World Implementation and Clinical Outcomes}},
  author = {Saskia Hussung and Mia Roth and Dilara Akhoundova and Clelia Pistoni and Judith Konrat and Franca Lisy and Tabea Ibach and Tomas Brezina and Markus Rechsteiner and Daniela Lenggenhager and Martin Zoche and Holger Moch and Achim Weber and Ralph Fritsch},
  journal = {Cancer Medicine},
  year = {2026},
  month = nov,
  doi = {10.1002/cam4.72461},
  url = {https://doi.org/10.1002/cam4.72461},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Upfront Comprehensive Genomic Profiling in Advanced Biliary Tract Cancer: Real‐World Implementation and Clinical Outcomes
AU  - Saskia Hussung
AU  - Mia Roth
AU  - Dilara Akhoundova
AU  - Clelia Pistoni
AU  - Judith Konrat
AU  - Franca Lisy
AU  - Tabea Ibach
AU  - Tomas Brezina
AU  - Markus Rechsteiner
AU  - Daniela Lenggenhager
AU  - Martin Zoche
AU  - Holger Moch
AU  - Achim Weber
AU  - Ralph Fritsch
PY  - 2026
DA  - 2026/11/03
JO  - Cancer Medicine
DO  - 10.1002/cam4.72461
UR  - https://doi.org/10.1002/cam4.72461
AB  - 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.  Methods: 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.  Results: 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.  Conclusion: 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.
SN  - 2045-7634
ER  -