Diagnostic Utility of Next-Generation Sequencing vs. Conventional Liquid Biopsy for Early Detection of Epidermal Growth Factor Receptor T790M Mutations in Non-Small Cell Lung Cancer

International Journal of Medicine and Medical Sciences | Vol. 16, No. 8, August 2026 | pp. 81–88

DOI: 10.46882/2026/IJMMS/160081

Original Research Article

Diagnostic Utility of Next-Generation Sequencing vs. Conventional Liquid Biopsy for Early Detection of Epidermal Growth Factor Receptor T790M Mutations in Non-Small Cell Lung Cancer

David A. Kensington¹, Alistair M. Vance², Charles E. Sterling³*

¹Department of Oncology, Royal Marsden Hospital, Imperial College London, London, UK.

²Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

³Department of Laboratory Medicine and Pathobiology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.

Abstract:

The emergence of the epidermal growth factor receptor (EGFR) T790M gatekeeper mutation drives secondary resistance to first- and second-generation tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC), demanding ultra-sensitive diagnostic detection tools. This prospective diagnostic accuracy study evaluated the sensitivity and clinical precision of droplet digital polymerase chain reaction (ddPCR) next-generation sequencing (NGS) platform versus conventional plasma-derived cell-free DNA (cfDNA) cobas assays for tracking emerging T790M variants. We evaluated 110 adult patients with advanced EGFR-mutant NSCLC showing clinical or radiological disease progression on erlotinib or gefitinib. Paired blood and tumor tissue biopsy specimens were processed. Sieve analysis of tumor tissue served as the reference standard baseline, which confirmed T790M mutations in 58.2% (64/110) of the participants. The NGS assay demonstrated a sensitivity of 92.2%, a specificity of 95.7%, a positive predictive value (PPV) of 96.7%, and a negative predictive value (NPV) of 89.8% for identifying the resistance mutation. In comparison, the conventional cobas liquid biopsy assay achieved a sensitivity of only 73.4% and an NPV of 72.1% (p < 0.01). The Area Under the Curve (AUC) was significantly larger for liquid NGS (AUC = 0.94, 95% CI = 0.88–0.98) than for standard assays (AUC = 0.78, p < 0.01). Next-generation sequencing of plasma cfDNA offers superior diagnostic precision and avoids invasive repeat tissue sampling, permitting early therapeutic switching to third-generation inhibitors.

Keywords: Non-Small Cell Lung Cancer, Next-Generation Sequencing, Liquid Biopsy, EGFR T790M Mutation, Droplet Digital PCR, Therapeutic Resistance

Manuscript Timeline: Received: May 14, 2026; Revised: June 22, 2026; Accepted: July 10, 2026; Published: August 14, 2026.

Citation: Kensington DA, Vance AM, Sterling CE. Diagnostic Utility of Next-Generation Sequencing vs. Conventional Liquid Biopsy for Early Detection of Epidermal Growth Factor Receptor T790M Mutations in Non-Small Cell Lung Cancer. International Journal of Medicine and Medical Sciences, 2026, 16(8): 81–88. DOI: 10.46882/2026/IJMMS/160081

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