{"entity":{"id":"paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019","kind":"paper","name":"NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer","aka":[],"tldr":"Testing a blood sample found at least as many treatable mutations as testing the tumour did, found them six days sooner, and when both were done together found half as many again.","summary":"Prospectively enrolled patients with previously untreated metastatic non-small-cell lung cancer undergoing physician-discretion standard-of-care tissue genotyping also submitted a pretreatment blood sample for comprehensive cell-free DNA analysis. Among 282 patients, tissue genotyping identified a guideline-recommended biomarker in 60 patients against 77 identified by cell-free DNA, 21.3% against 27.3%, meeting non-inferiority. In tissue-positive patients the biomarker was identified by tissue alone in 12 of 60 and concordantly in 48 of 60, an 80% clinical sensitivity for cell-free DNA. For the alterations with approved drugs, EGFR, ALK, ROS1 and BRAF, concordance exceeded 98% with 100% positive predictive value for cell-free DNA against tissue in 34 positive patients. Using cell-free DNA in addition to tissue increased detection by 48%, from 60 to 89 patients. Median turnaround was 9 days against 15 days for tissue, and guideline-complete genotyping was far more likely.","asOf":"2026-09-25","links":[{"label":"Leighl et al., Clin Cancer Res 2019: NILE, cell-free DNA against tissue genotyping in 282 newly diagnosed metastatic lung cancers","url":"https://doi.org/10.1158/1078-0432.CCR-19-0624"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30988079/"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":["liquid-biopsy","cgp"],"targets":["egfr","alk","ros1","braf","ret","met","her2","kras"],"drugs":["guardant360-cdx"],"companies":[],"institutions":[],"pathways":["rtk-activation"],"terms":["ctdna","cfdna","ngs","biopsy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2019,"doi":"10.1158/1078-0432.CCR-19-0624","pmid":"30988079","authors":"Leighl NB, Page RD, Raymond VM, et al.","paperType":"observational","findings":["Cell-free DNA found a guideline biomarker in 27.3% of patients against 21.3% by tissue, meeting non-inferiority.","Clinical sensitivity of plasma against tissue was 80% for any guideline biomarker.","Positive predictive value was 100% for EGFR, ALK and BRAF positives.","Adding plasma to tissue raised detection by 48% and cut turnaround from 15 to 9 days."],"whatItMeans":"It is the evidence behind running plasma and tissue together at diagnosis rather than in sequence, and the 80% sensitivity figure is the reason a negative plasma result never ends the work-up.","caveats":["Tissue genotyping was at physician discretion, so the comparator is real-world practice rather than complete sequencing.","Cell-free DNA detection depends on tumour shedding, which varies with disease site and burden.","One commercial assay was tested."],"changedPractice":true,"participants":282},"route":"/key-papers/paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019/","neighbours":{"cancer":[{"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":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"},{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"},{"id":"ret","kind":"target","name":"RET","route":"/targets/ret/"},{"id":"ros1","kind":"target","name":"ROS1","route":"/targets/ros1/"}],"drug":[{"id":"guardant360-cdx","kind":"drug","name":"Guardant360 CDx","route":"/drugs/guardant360-cdx/"}],"pathway":[{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"}],"term":[{"id":"biopsy","kind":"term","name":"Biopsy","route":"/terms/biopsy/"},{"id":"cfdna","kind":"term","name":"Cell-free DNA (cfDNA)","route":"/terms/cfdna/"},{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"}],"journal":[{"id":"clinical-cancer-research","kind":"journal","name":"Clinical Cancer Research","route":"/journals/clinical-cancer-research/"}]}}