Clinical practice and implications of biomarker testing in biliary tract cancer: An observational study
Bibliographic record
Abstract
Background & Aims Biliary tract cancers (BTC) comprise a group of aggressive malignancies with limited therapeutic options. Owing to the high frequency of actionable genomic alterations (GA) and the availability of targeted therapies, molecular testing has gained increasing importance; however, its implementation in clinical practice varies across centers. The aim of our analysis was to provide a comprehensive real-world assessment of molecular testing, annotate the molecular landscape in BTC patients, and understand the prognostic and predictive implications of selected GA. Methods We retrospectively analyzed genomic and clinical information of 1521 patients treated at 18 centers in Germany and Austria. A side-by-side comparison of clinical grade reports generated on two different sequencing platforms was performed for 90 patients. Results 24 different NGS panels were used across 18 centers. A comparative analysis highlighted the significant variability in reports used to inform therapeutic decisions in clinical practice. Although there were substantial differences in the number of GA covered, the broader panels identified a similar number of actionable GA, indicating that key therapeutic targets are sufficiently represented. Integration with clinical data suggested that certain GA, such as HER2 amplifications (3%) , BRAF V600E mutations (2%), and FGFR2 alterations (14%), may have prognostic significance beyond their predictive value. Patients with actionable alterations (610, 40%) that were treated accordingly (n=204, 13%) had prolonged overall survival (31.8 mo vs 22.8 mo, p<0.01). Conclusion Standardized biomarker testing is crucial for effective integration of targeted therapies in the management of BTC. Our findings reinforce the value of targeted treatments and underscore the predictive and prognostic significance of selected GA. Impact and Implications Genomic profiling is recommended in patients with biliary tract cancers (BTC) but lacks harmonization across platforms and centers. By retrospectively analyzing genomic and clinical information from 1521 BTC patients diagnosed and treated at 18 centers in Germany and Austria, we provide real-world insights into the implementation of molecular profiling in BTC, highlighting variability in NGS-based testing and its impact on the detection of genomic alterations. Standardized molecular testing strategies will be key to enable the integration of more consistent and comparable genomic datasets across studies. Further, by elucidating the prognostic relevance of individual genomic alterations, our insights carry significant implications for interpreting single-arm clinical trials within genomically stratified patient cohorts and underscore the importance of randomized studies to delineate the benefit of targeted therapies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".