{"entity":{"id":"paper-abbosh-phylogenetic-ctdna-lung-cancer-nature-2017","kind":"paper","name":"Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution","aka":[],"tldr":"By building a family tree of each tumour's mutations first, the TRACERx team could find the cancer's DNA in blood after surgery and tell which patients would relapse, before any scan showed anything.","summary":"Abbosh, Birkbak, Wilson and colleagues, with Swanton as senior author, profiled circulating tumour DNA in the first 100 TRACERx participants using a tumour-specific phylogenetic approach, including one patient also recruited to the PEACE post-mortem study.\n\nThe method is the contribution. Rather than looking for a generic panel of mutations, the assay is built from the tumour's own phylogeny, which makes it sensitive enough to detect residual disease and specific enough to say which subclone is responsible for the relapse. It is the lung cancer arm of the minimal residual disease field that ctDNA-guided colorectal trials later industrialised.","asOf":"2026-09-25","links":[{"label":"Nature 2017","url":"https://doi.org/10.1038/nature22364"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28445469/"},{"label":"ClinicalTrials.gov NCT01888601","url":"https://clinicaltrials.gov/study/NCT01888601"}],"tags":["lung-evidence"],"related":["paper-jamal-hanjani-tracerx-evolution-nsclc-nejm-2017","ctdna-tests","paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008"],"cancers":["lung-cancer","nsclc","resectable-nsclc"],"sections":["diagnostics","early-detection"],"technologies":["liquid-biopsy","ngs","wes-wgs"],"targets":[],"drugs":[],"companies":[],"institutions":["francis-crick"],"pathways":[],"terms":["ctdna","mrd","clonal-evolution"],"trials":[],"people":["charles-swanton"],"bottlenecks":["b-dormancy-mrd","b-early-detection","b-tumor-heterogeneity"],"keyPapers":[],"journals":["nature"],"dependsOn":[],"notes":[],"journal":"Nature","year":2017,"doi":"10.1038/nature22364","pmid":"28445469","authors":"Abbosh C, Birkbak NJ, Wilson GA, et al.","paperType":"translational","findings":["Independent predictors of ctDNA release were identified and the tumour-volume detection limit analysed.","Blinded profiling of postoperative plasma showed evidence of adjuvant chemotherapy resistance and identified patients very likely to experience recurrence.","Phylogenetic ctDNA profiling tracked the subclonal nature of lung cancer relapse and metastasis."],"whatItMeans":"The foundation of minimal residual disease testing in lung cancer: a blood test that says a patient will relapse months before a scan does, and says which part of the tumour is doing it. Whether acting on that signal changes outcome is what the ctDNA-guided trials are for.","caveats":["100 patients, and ctDNA release depends on tumour volume and histology, so the test is least sensitive in the smallest tumours where it would be most useful.","A bespoke per-patient assay built from tissue sequencing, which is expensive and slow compared with a fixed panel.","Prognostic, not yet predictive: no randomised trial in lung cancer has shown that treating a ctDNA-positive patient earlier improves survival."],"changedPractice":false,"participants":100},"route":"/key-papers/paper-abbosh-phylogenetic-ctdna-lung-cancer-nature-2017/","neighbours":{"paper":[{"id":"paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008","kind":"paper","name":"Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group","route":"/key-papers/paper-lace-adjuvant-cisplatin-pooled-analysis-jco-2008/"},{"id":"paper-jamal-hanjani-tracerx-evolution-nsclc-nejm-2017","kind":"paper","name":"Tracking the evolution of non-small-cell lung cancer","route":"/key-papers/paper-jamal-hanjani-tracerx-evolution-nsclc-nejm-2017/"}],"roadmap":[{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"},{"id":"lung-cancer-evidence-roadmap","kind":"roadmap","name":"Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch","route":"/roadmaps/lung-cancer-evidence-roadmap/"}],"cancer":[{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"resectable-nsclc","kind":"cancer","name":"Resectable stage I to III non-small-cell lung cancer","route":"/cancers/resectable-nsclc/"}],"section":[{"id":"diagnostics","kind":"section","name":"Diagnostics & Biomarkers","route":"/fronts/diagnostics/"},{"id":"early-detection","kind":"section","name":"Early Detection & Screening","route":"/fronts/early-detection/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"wes-wgs","kind":"technology","name":"Whole-exome & whole-genome sequencing","route":"/technologies/wes-wgs/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}],"institution":[{"id":"francis-crick","kind":"institution","name":"The Francis Crick Institute","route":"/institutions/francis-crick/"}],"pathway":[{"id":"clonal-evolution","kind":"pathway","name":"Clonal evolution & minimal residual disease","route":"/pathways/clonal-evolution/"}],"person":[{"id":"charles-swanton","kind":"person","name":"Charles Swanton","route":"/people/charles-swanton/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-early-detection","kind":"bottleneck","name":"The hardest cancers are found late","route":"/bottlenecks/b-early-detection/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"journal":[{"id":"nature","kind":"journal","name":"Nature","route":"/journals/nature/"}]}}