ideasIdea
Biopsy the one lesion that is growing while the others shrink
When a scan shows most tumours shrinking but one growing, that odd lesion holds the escape mechanism. Sampling it, and treating it locally, should be routine.
Mixed responses are common on targeted therapy and immunotherapy, yet the discordant lesion is rarely biopsied and the systemic drug is often abandoned. The proposal is a protocolised pathway: automated lesion-level response tracking on CT, biopsy of the outlier, targeted sequencing, and continuation of systemic therapy with local ablation or SBRT to the outlier lesion.
Hypothesis
Outlier-lesion biopsy identifies a distinct resistance mechanism in over half of mixed responders, and continuing systemic therapy plus local treatment yields longer time to next systemic line than switching drugs.
Rationale
Oligoprogression management with local therapy is already practised in EGFR and ALK lung cancer; adding the biopsy converts each case into a resistance mechanism datum and prevents premature drug switches.
What would test it
Single-arm study of 100 mixed responders across tumour types with paired outlier and responding-lesion sequencing; endpoints are mechanism discordance rate and time to next systemic therapy versus matched historical controls.
Maturity
early clinical
Who has to act
clinic
Cost to try
Small (under $1M)
Years to first evidence
2
Bottlenecks it attacks
- Tumour heterogeneity and clonal evolution · A tumour is many tumours. Treatments that kill most cells leave the rest to grow back, changed.
- Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.