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Adjuvant osimertinib is the standard of care for patients with resected stage IB-IIIA EGFR-mutated non-squamous non-small cell lung cancer (NS-NSCLC).1 Consequently, preoperative EGFR status assessment is essential to identify candidates for adjuvant osimertinib (EGFR-mutated patients) versus neoadjuvant immunotherapy (EGFR wild-type (WT) patients).1 EGFR mutations are detected in DNA from tumour tissue biopsy via next-generation sequencing (NGS) or single-gene sequencing.1 However, obtaining adequate tumour tissue can be challenging due to tumour inaccessibility or patient condition. Alternatively, liquid biopsies (LB) allow detection of mutations in cell-free DNA (cfDNA) from blood, offering a rapid and minimally invasive method that may also better capture tumour heterogeneity.2 However, current data on preoperative LB use for EGFR status evaluation in early-stage NSCLC are limited. Multiplex droplet digital PCR (ddPCR) provides a rapid, cost-effective and sensitive option for detecting gene mutations in cf-DNA, but tumour fraction (TF) can be very low in early-stage NS-NSCLC.3 To address this, DNA methylation signatures have been developed to distinguish and quantify TF from non-tumour cf-DNA, reducing ‘false’ negative or non-informative results.4
Our study evaluated the value of preoperative LB for EGFR mutation screening at diagnosis in early-stage NS-NSCLC by performing cfDNA-ddPCR and cfDNA methylation-ddPCR analyses in preoperative blood and paired tissue samples from resected EGFR-mutated patients with NS-NSCLC.
Tissue DNA was extracted, sequenced and analysed as previously described (figure 1A).5
OPA tissue (A) and cfDNA ddPCR EGFR (B) workflows. cfDNA, cell-free DNA; ddPCR, droplet digital PCR;
Blood (18 mL) was collected in EDTA or Streck tubes (Madison Industries Holdings LLC, USA) and processed within 2 hours after sampling. Tubes were first centrifuged at 2000 g for 10 min at 4°C. Plasma was then collected into a new 15 mL tube and centrifuged at 5000 g for 10 min at 4°C. Plasma …
Footnotes
Handling editor Vikram Deshpande.
Contributors CB: validation, formal analysis, investigation, data curation, writing—original draft, visualisation. JB: resources, investigation, data curation, writing—review and editing. VTal: validation, investigation, methodology, formal analysis, data curation, writing—review and editing. AB: validation, investigation, methodology, formal analysis, data curation, writing—review and editing. MA: validation, investigation, data curation, writing—review and editing. CL: validation, investigation, data curation, writing—review and editing. VTan: validation, investigation, data curation, writing—review and editing. GR: investigation, writing—review and editing. J-PB: resources, writing—review and editing. C-HM: resources, writing—review and editing. VL-F: validation, investigation, data curation, writing—review and editing. OB: validation, investigation, data curation, writing—review and editing. SG: investigation, writing—review and editing. MI: investigation, writing—review and editing. VH: investigation, writing—review and editing. PH: conceptualisation, methodology, resources, supervision, project administration, writing—review and editing.
Funding This work was supported by a grant from the French government managed by ‘Agence Nationale de la Recherche’ under the France 2030 programme, reference ANR-23-IAHU-007.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.