{"entity":{"id":"idea-bio1-outlier-lesion-biopsy","kind":"idea","name":"Biopsy the one lesion that is growing while the others shrink","aka":[],"tldr":"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.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Tumour heterogeneity and clonal evolution): Gerlinger et al., Intratumor heterogeneity and branched evolution (NEJM 2012)","url":"https://doi.org/10.1056/NEJMoa1113205"}],"tags":[],"related":[],"cancers":["nsclc","melanoma"],"sections":[],"technologies":["sbrt","cgp","ct"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["recist","oligometastatic"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity","b-resistance"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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.","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","cost":"small","horizonYears":2},"route":"/ideas/idea-bio1-outlier-lesion-biopsy/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"ct","kind":"technology","name":"CT (computed tomography)","route":"/technologies/ct/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"}],"term":[{"id":"oligometastatic","kind":"term","name":"Oligometastatic disease","route":"/terms/oligometastatic/"},{"id":"recist","kind":"term","name":"RECIST","route":"/terms/recist/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}]}}