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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-13667-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849226316389285888 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Tessa J. J. de Bitter |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-eb0e16c56473494f99d1cde2a6880892 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-eb0e16c56473494f99d1cde2a68808922025-08-24T11:30:30ZengNature PortfolioScientific Reports2045-23222025-08-0115111210.1038/s41598-025-13667-zClinical utility of liquid biopsy next-generation sequencing for advanced non-small cell lung cancer in the NetherlandsTessa J. J. de Bitter0Maartje J. Geerlings1Leonie I. Kroeze2Daniel von Rhein3Milou M. F. Schuurbiers4Janne M. Bibbe5Joyce A. M. G. Smeijers6Hicham Ouchene7Christian Gilissen8Tom G. J. Hofste9Marjan M. Weiss10LongkankernetLisenka E. L. M. Vissers11Michel M. van den Heuvel12Marjolijn J. L. Ligtenberg13Department of Human Genetics, Radboudumc Research Institute for Medical Innovation, Radboud university medical centerDepartment of Human Genetics, Radboudumc Research Institute for Medical Innovation, Radboud university medical centerDepartment of Pathology, Radboudumc Research Institute for Medical Innovation, Radboud university medical centerDepartment of Human Genetics, Radboudumc Research Institute for Medical Innovation, Radboud university medical centerDepartment of Respiratory Medicine, Radboud university medical centerDepartment of Pathology, Radboudumc Research Institute for Medical Innovation, Radboud university medical centerDepartment of Pathology, Radboudumc Research Institute for Medical Innovation, Radboud university medical centerDepartment of Human Genetics, Radboudumc Research Institute for Medical Innovation, Radboud university medical centerDepartment of Human Genetics, Radboudumc Research Institute for Medical Innovation, Radboud university medical centerDepartment of Human Genetics, Radboudumc Research Institute for Medical Innovation, Radboud university medical centerDepartment of Human Genetics, Radboudumc Research Institute for Medical Innovation, Radboud university medical centerDepartment of Human Genetics, Radboudumc Research Institute for Medical Innovation, Radboud university medical centerDepartment of Respiratory Medicine, Radboud university medical centerDepartment of Human Genetics, Radboudumc Research Institute for Medical Innovation, Radboud university medical centerAbstract 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.https://doi.org/10.1038/s41598-025-13667-zLiquid biopsyCirculating tumor DNAClinical utilityNon-small cell lung cancerActionable driverDiagnostic yield |
| spellingShingle | 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 Clinical utility of liquid biopsy next-generation sequencing for advanced non-small cell lung cancer in the Netherlands Scientific Reports Liquid biopsy Circulating tumor DNA Clinical utility Non-small cell lung cancer Actionable driver Diagnostic yield |
| title | Clinical utility of liquid biopsy next-generation sequencing for advanced non-small cell lung cancer in the Netherlands |
| title_full | Clinical utility of liquid biopsy next-generation sequencing for advanced non-small cell lung cancer in the Netherlands |
| title_fullStr | Clinical utility of liquid biopsy next-generation sequencing for advanced non-small cell lung cancer in the Netherlands |
| title_full_unstemmed | Clinical utility of liquid biopsy next-generation sequencing for advanced non-small cell lung cancer in the Netherlands |
| title_short | Clinical utility of liquid biopsy next-generation sequencing for advanced non-small cell lung cancer in the Netherlands |
| title_sort | clinical utility of liquid biopsy next generation sequencing for advanced non small cell lung cancer in the netherlands |
| topic | Liquid biopsy Circulating tumor DNA Clinical utility Non-small cell lung cancer Actionable driver Diagnostic yield |
| url | https://doi.org/10.1038/s41598-025-13667-z |
| work_keys_str_mv | AT tessajjdebitter clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT maartjejgeerlings clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT leonieikroeze clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT danielvonrhein clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT miloumfschuurbiers clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT jannembibbe clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT joyceamgsmeijers clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT hichamouchene clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT christiangilissen clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT tomgjhofste clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT marjanmweiss clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT longkankernet clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT lisenkaelmvissers clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT michelmvandenheuvel clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands AT marjolijnjlligtenberg clinicalutilityofliquidbiopsynextgenerationsequencingforadvancednonsmallcelllungcancerinthenetherlands |