Complementing Tissue Testing With Plasma Mutation Profiling Improves Therapeutic Decision-Making for Patients With...

Area of Science:

• Oncology
• Molecular Diagnostics
• Genomics

Background:

• Tissue biopsy is standard for lung cancer diagnosis but is invasive and can be limited by sample heterogeneity.
• Liquid biopsies offer a less invasive alternative, potentially providing crucial molecular insights, especially when tissue acquisition is challenging.

Purpose of the Study:

• To evaluate the concordance and clinical utility of plasma next-generation sequencing (NGS) compared to tissue biopsy for detecting actionable mutations in lung cancer patients.
• To assess the impact of plasma NGS on diagnostic yield and turnaround time in the first-line setting.

Main Methods:

• Prospective recruitment of 71 patients with suspected lung cancer, collecting paired blood and tissue samples.
• Plasma cfDNA was analyzed using an ultrasensitive amplicon-based NGS panel.
• Tissue biopsy was used for targeted epidermal growth factor receptor (EGFR) mutation testing where available.

Main Results:

• Plasma NGS provided results for 98.1% of cases, compared to 70.3% for tissue testing due to sample inadequacy.
• Plasma NGS identified actionable mutations in 37.7% of cases, including EGFR, KRAS, BRAF, and MET.
• Adding plasma NGS to tissue testing increased actionable mutation detection by 1.9-fold (42.6% vs. 22.2%) with a significantly shorter turnaround time (10 vs. 29.9 days).

Conclusions:

• Plasma NGS is highly concordant with tissue EGFR testing in the first-line lung cancer setting.
• Plasma NGS enhances the detection of actionable findings and reduces time to results, demonstrating significant clinical utility.
• Complementary plasma mutation profiling should be considered in the routine management of lung cancer patients.