Rare Tumours
Rare cancers are not under-studied versions of common cancers. Collectively they account for a substantial share of all cancer, yet individually each has a thin evidence base, dispersed expertise and a trial landscape that is difficult to search.
Disease categories
Major disease categories
- Rare solid tumours
- Rare haematological malignancies
- Rare paediatric tumours
- Tumours with rare molecular alterations
- Ultra-rare entities
Molecular
Molecular considerations
Because randomised evidence is frequently unavailable, molecular characterisation carries proportionally more weight. Tissue-agnostic alterations — NTRK fusions, mismatch repair deficiency, high tumour mutational burden, RET and BRAF alterations — are of particular interest.
Markers commonly discussed in rare tumours
- NTRK fusions
- MMR / MSI
- TMB
- RET
- BRAF V600E
- ALK
- Entity-defining 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, fusion-capable profiling is frequently discussed, because the defining or actionable alteration may be one a narrow panel would not cover.
Germline
Germline considerations
Germline assessment is often relevant, as rare tumours are enriched for predisposition syndromes.
Molecular monitoring
ctDNA and liquid biopsy considerations
Variable by entity and generally investigational.
Single-cell & computation
Single-cell and algorithmic approaches
In rare disease the computational burden shifts from analysis to synthesis. The analytical methods are the same; what differs is that no adequately powered cohort exists, so the work involves reasoning across small series, cross-disease molecular comparison, and registry data. Single-cell analysis is used where the entity is poorly characterised and its cellular composition is itself an open question. Algorithmic work centres on methylation-based classification for entities where histology is unreliable, and on retrieval methods built for literatures small enough to read exhaustively but scattered enough that nobody has.
In practice
What a review of this disease typically surfaces
The pattern is consistent across rare disease: a secure diagnosis is harder to obtain than expected, the literature is small enough to read in full but scattered enough that nobody has, and the trial search has been done by disease name when the relevant trial recruits by molecular alteration. Reviews here spend proportionally more effort on establishing what is actually known, and on saying clearly where the evidence runs out.
Patterns observed across precision oncology case reviews. Every case differs; these are the questions worth checking, not conclusions about any individual patient.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has the diagnosis been confirmed by a pathologist with experience of this entity?
- Has comprehensive profiling been performed, covering fusions?
- Have tissue-agnostic options been considered?
- Has international expertise been sought?
Resistance
Resistance and recurrence questions
- Has the diagnosis been reviewed if behaviour is atypical?
Trials
Clinical trial considerations
Trial identification in rare disease frequently requires international search and basket-trial consideration.
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.