# NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer

Source: https://onco.cc/key-papers/paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019/  
OnCo record `paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Clinical Cancer Research
- Year: 2019
- DOI: 10.1158/1078-0432.CCR-19-0624
- Authors: Leighl NB, Page RD, Raymond VM, et al.
- 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.
- What it means: 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.

## Sources

- Leighl et al., Clin Cancer Res 2019: NILE, cell-free DNA against tissue genotyping in 282 newly diagnosed metastatic lung cancers: https://doi.org/10.1158/1078-0432.CCR-19-0624
- PubMed: https://pubmed.ncbi.nlm.nih.gov/30988079/

## Connected records

- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- targets: [ALK](https://onco.cc/targets/alk/), [BRAF](https://onco.cc/targets/braf/), [EGFR](https://onco.cc/targets/egfr/), [HER2](https://onco.cc/targets/her2/), [KRAS](https://onco.cc/targets/kras/), [MET](https://onco.cc/targets/met/), [RET](https://onco.cc/targets/ret/), [ROS1](https://onco.cc/targets/ros1/)
- drugs: [Guardant360 CDx](https://onco.cc/drugs/guardant360-cdx/)
- pathways: [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/)
- terms: [Biopsy](https://onco.cc/terms/biopsy/), [Cell-free DNA (cfDNA)](https://onco.cc/terms/cfdna/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/)
- journals: [Clinical Cancer Research](https://onco.cc/journals/clinical-cancer-research/)

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