# Biopsy the one lesion that is growing while the others shrink

Source: https://onco.cc/ideas/idea-bio1-outlier-lesion-biopsy/  
OnCo record `idea-bio1-outlier-lesion-biopsy` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Idea
- Last checked: 2026-09-08
- 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.
- Proposed test: 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
- Actor: clinic

## Sources

- Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012): https://doi.org/10.1056/NEJMoa1113205

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [CT (computed tomography)](https://onco.cc/technologies/ct/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/)
- terms: [Oligometastatic disease](https://onco.cc/terms/oligometastatic/), [RECIST](https://onco.cc/terms/recist/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)

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