Prospective clinical evaluation of cell-free DNA next generation sequencing in patients with suspected metastatic lung cancer.

Molecular analysis of tumor material is standard in metastatic non-squamous non-small cell lung cancer (NSCLC), but it is not always feasible, limiting targeted treatment options. We investigated the clinical value of cell-free DNA (cfDNA) next-generation sequencing (NGS) in patients with clinically and radiologically suspected metastatic NSCLC. Within the comprehensive cancer network Southwest (The Netherlands), Erasmus MC launched the Lung Cancer Diagnosis (LCD) – cfDNA project. For patients with suspected metastatic lung cancer where tissue analysis was not feasible, thoracic oncologists submitted plasma samples for cfDNA NGS. Results were discussed by the Thoracic Oncology Molecular Tumor board. Between January 1st, 2019, and January 1st, 2023, 108 plasma samples were submitted and analyzed. In 6 patients (5.6%), an activating EGFR mutation was identified as a potential target for treatment. Additional actionable genomic alterations (AGA) include a BRAF p.V600E mutation (n = 1) and KRAS p.G12C mutations (n = 6). In 42 patients, other non-AGA (KRAS other than p.G12C, NRAS, BRAF p.G466V, PIK3CA, TP53) were detected that did not affect the choice of systemic therapy. In a real-world clinical practice setting, our study showed that NGS can detect AGAs in plasma when tumor tissue analysis is not feasible in suspected metastatic NSCLC. However, plasma diagnostics cannot replace histological diagnosis.