Clinical utility of liquid biopsy next-generation sequencing for advanced non-small cell lung cancer in the Netherlands

Clinical utility of liquid biopsy next-generation sequencing for advanced non-small cell lung cancer in the Netherlands

Abstract Tumor molecular profiling is essential for therapeutic management of advanced non-small cell lung cancer (NSCLC). However, a biopsy is not for every patient possible and can have complications, which plasma derived circulating tumor DNA (ctDNA) analysis could overcome. We assessed the clini...

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Main Authors: Tessa J. J. de Bitter, Maartje J. Geerlings, Leonie I. Kroeze, Daniel von Rhein, Milou M. F. Schuurbiers, Janne M. Bibbe, Joyce A. M. G. Smeijers, Hicham Ouchene, Christian Gilissen, Tom G. J. Hofste, Marjan M. Weiss, Longkankernet, Lisenka E. L. M. Vissers, Michel M. van den Heuvel, Marjolijn J. L. Ligtenberg
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
Subjects:
Liquid biopsy
Circulating tumor DNA
Clinical utility
Non-small cell lung cancer
Actionable driver
Diagnostic yield
Online Access:https://doi.org/10.1038/s41598-025-13667-z
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Summary:Abstract Tumor molecular profiling is essential for therapeutic management of advanced non-small cell lung cancer (NSCLC). However, a biopsy is not for every patient possible and can have complications, which plasma derived circulating tumor DNA (ctDNA) analysis could overcome. We assessed the clinical utility of ctDNA next-generation sequencing (ctDNA-NGS) in 72 NSCLC patients, including 59 who underwent both standard of care (SoC) tissue- or cytology-based genotyping and ctDNA-NGS and 13 who underwent only ctDNA-NGS. Hypothetical shifts in diagnostic yield of a ctDNA-first strategy were modelled using real-world NSCLC molecular testing data from The Netherlands. Concordance between SoC and ctDNA-NGS was 71.2%. In fifteen patients (25.4%) results were discordant, but without direct therapeutic impact. In two patients (3.4%), ctDNA-NGS missed an actionable driver, which would directly impact therapy. Hypothetical shifts in diagnostic yield of a ctDNA-first strategy were determined. This predicted a 7.0% decrease in diagnostic yield for (non-) actionable drivers if all patients underwent ctDNA-NGS, including those currently tested in SoC and those not. Offering ctDNA-NGS only to patients not tested in SoC would increase the diagnostic yield by 6.7%. In conclusion, ctDNA-NGS shows promise for predictive diagnostics in advanced NSCLC, offering added value alongside SoC, but comes with assay-specific and biological challenges.
ISSN:2045-2322

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