Liver Cancer
Hepatocellular carcinoma usually arises in a liver already affected by chronic disease, so liver function and underlying aetiology sit alongside tumour biology in every discussion of it.
Disease categories
Major disease categories
- Hepatocellular carcinoma
- Fibrolamellar carcinoma
- Hepatoblastoma
- Secondary liver tumours
Molecular
Molecular considerations
TERT promoter, CTNNB1 and TP53 alterations are frequently described. The underlying liver disease and its degree of impairment are integral to interpretation.
Markers commonly discussed in liver cancer
- AFP
- CTNNB1
- TERT promoter
- TP53
- PD-L1
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
Molecular profiling is discussed in advanced disease; targetable alterations are less common than in some other solid tumours.
Germline
Germline considerations
Germline assessment is considered where presentation or family history suggests a predisposition.
Molecular monitoring
ctDNA and liquid biopsy considerations
ctDNA in hepatocellular carcinoma is an area of active research.
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:
- Is underlying liver function documented alongside tumour staging?
- Has the aetiology of the underlying liver disease been established?
Resistance
Resistance and recurrence questions
- Has disease behaviour changed in a way that molecular reassessment might explain?
Trials
Clinical trial considerations
Liver function frequently affects trial eligibility as much as tumour characteristics do.
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.