Biliary Tract Cancer
Biliary tract cancers are uncommon and molecularly notable: a meaningful proportion carry alterations that are the subject of active targeted-therapy research, which makes comprehensive profiling a common part of the discussion.
Disease categories
Major disease categories
- Intrahepatic cholangiocarcinoma
- Extrahepatic cholangiocarcinoma
- Gallbladder cancer
- Ampullary carcinoma
Molecular
Molecular considerations
FGFR2 fusions and IDH1 alterations are described particularly in intrahepatic cholangiocarcinoma. HER2 alterations, BRAF V600E, mismatch repair deficiency and NTRK fusions are also assessed.
Markers commonly discussed in biliary tract cancer
- FGFR2 fusions
- IDH1
- HER2
- BRAF V600E
- MMR / MSI
- NTRK fusions
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
Comprehensive somatic profiling is frequently discussed given the proportion of cases with alterations of active research interest.
Germline
Germline considerations
Germline assessment is considered where the clinical picture suggests it.
Molecular monitoring
ctDNA and liquid biopsy considerations
ctDNA is studied both for profiling where tissue is limited and for monitoring.
Single-cell & computation
Single-cell and algorithmic approaches
In gastrointestinal and hepatobiliary disease, single-cell sequencing is used chiefly to characterise the tumour microenvironment and to resolve clonal structure in tumours that are heterogeneous between regions. Single-cell DNA analysis helps establish whether a RAS or driver alteration is clonal or subclonal, which bears directly on how much weight it should carry. Algorithm work here includes molecular residual disease detection from serial samples, mismatch repair classification from sequencing data, and pipelines that reconcile findings across multiple biopsy sites.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has comprehensive profiling been performed, including fusion detection?
- Does the assay used actually detect fusions, or only sequence variants?
Resistance
Resistance and recurrence questions
- Have resistance alterations emerged on targeted therapy?
Trials
Clinical trial considerations
Alteration-specific trials are a significant part of the biliary tract cancer landscape.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.