Up-front mutation detection in circulating tumor DNA by droplet digital PCR has added diagnostic value in lung cancer
Identification of actionable mutations in advanced stage non-squamous non-small-cell lung cancer (NSCLC) patients is recommended by guidelines as it enables treatment with targeted therapies. In current practice, mutations are identified by next-generation sequencing of tumor DNA (tDNA-NGS), which r...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523322002480 |
| _version_ | 1811178135106879488 |
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| author | Esther Visser Remco de Kock Sylvia Genet Ben van den Borne Maggy Youssef-El Soud Huub Belderbos Gerben Stege Marleen de Saegher Susan van ’t Westeinde Maarten Broeren Federica Eduati Birgit Deiman Volkher Scharnhorst |
| author_facet | Esther Visser Remco de Kock Sylvia Genet Ben van den Borne Maggy Youssef-El Soud Huub Belderbos Gerben Stege Marleen de Saegher Susan van ’t Westeinde Maarten Broeren Federica Eduati Birgit Deiman Volkher Scharnhorst |
| author_sort | Esther Visser |
| collection | DOAJ |
| description | Identification of actionable mutations in advanced stage non-squamous non-small-cell lung cancer (NSCLC) patients is recommended by guidelines as it enables treatment with targeted therapies. In current practice, mutations are identified by next-generation sequencing of tumor DNA (tDNA-NGS), which requires tissue biopsies of sufficient quality. Alternatively, circulating tumor DNA (ctDNA) could be used for mutation analysis. This prospective, multicenter study establishes the diagnostic value of ctDNA analysis by droplet digital PCR (ctDNA-ddPCR) in patients with primary lung cancer.CtDNA from 458 primary lung cancer patients was analyzed using a panel of multiplex ddPCRs for EGFR (Ex19Del, G719S, L858R, L861Q and S768I), KRAS G12/G13 and BRAF V600 mutations. For 142 of 175 advanced stage non-squamous NSCLC patients tDNA-NGS results were available to compare to ctDNA-ddPCR. tDNA-NGS identified 98 mutations, of which ctDNA-ddPCR found 53 mutations (54%), including 32 of 45 (71%) targetable driver mutations. In 2 of these 142 patients, a mutation was found by ctDNA-ddPCR only. In 33 advanced stage patients lacking tDNA-NGS results, ctDNA-ddPCR detected 15 additional mutations, of which 7 targetable.Overall, ctDNA-ddPCR detected 70 mutations and tDNA-NGS 98 mutations in 175 advanced NSCLC patients. Using an up-front ctDNA-ddPCR strategy, followed by tDNA-NGS only if ctDNA-ddPCR analysis is negative, increases the number of mutations found from 98 to 115 (17%). At the same time, up-front ctDNA-ddPCR reduces tDNA-NGS analyses by 40%, decreasing the need to perform (additional) biopsies. |
| first_indexed | 2024-04-11T06:14:12Z |
| format | Article |
| id | doaj.art-79ac771ec13d4069bc3b639652b73652 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-04-11T06:14:12Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-79ac771ec13d4069bc3b639652b736522022-12-22T04:41:08ZengElsevierTranslational Oncology1936-52332023-01-0127101589Up-front mutation detection in circulating tumor DNA by droplet digital PCR has added diagnostic value in lung cancerEsther Visser0Remco de Kock1Sylvia Genet2Ben van den Borne3Maggy Youssef-El Soud4Huub Belderbos5Gerben Stege6Marleen de Saegher7Susan van ’t Westeinde8Maarten Broeren9Federica Eduati10Birgit Deiman11Volkher Scharnhorst12Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Catharina Hospital Eindhoven, Eindhoven, the Netherlands; Máxima Medical Center, Eindhoven, Veldhoven, the Netherlands; Expert Center Clinical Chemistry Eindhoven, Eindhoven, the Netherlands; Corresponding author at: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Catharina Hospital Eindhoven, Eindhoven, the Netherlands; Máxima Medical Center, Eindhoven, Veldhoven, the Netherlands; Expert Center Clinical Chemistry Eindhoven, Eindhoven, the NetherlandsDepartment of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Catharina Hospital Eindhoven, Eindhoven, the Netherlands; Expert Center Clinical Chemistry Eindhoven, Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the NetherlandsCatharina Hospital Eindhoven, Eindhoven, the NetherlandsMáxima Medical Center, Eindhoven, Veldhoven, the NetherlandsAmphia Hospital, Breda, the NetherlandsAnna Hospital, Geldrop, the NetherlandsSint Jans Gasthuis, Weert, the NetherlandsMaasstad Hospital, Rotterdam, the NetherlandsDepartment of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Máxima Medical Center, Eindhoven, Veldhoven, the Netherlands; Expert Center Clinical Chemistry Eindhoven, Eindhoven, the NetherlandsDepartment of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Expert Center Clinical Chemistry Eindhoven, Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands; Eindhoven Artificial Intelligence Systems Institute, Eindhoven University of Technology, Eindhoven, the NetherlandsCatharina Hospital Eindhoven, Eindhoven, the Netherlands; Expert Center Clinical Chemistry Eindhoven, Eindhoven, the NetherlandsDepartment of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands; Catharina Hospital Eindhoven, Eindhoven, the Netherlands; Expert Center Clinical Chemistry Eindhoven, Eindhoven, the Netherlands; Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands; Eindhoven Artificial Intelligence Systems Institute, Eindhoven University of Technology, Eindhoven, the NetherlandsIdentification of actionable mutations in advanced stage non-squamous non-small-cell lung cancer (NSCLC) patients is recommended by guidelines as it enables treatment with targeted therapies. In current practice, mutations are identified by next-generation sequencing of tumor DNA (tDNA-NGS), which requires tissue biopsies of sufficient quality. Alternatively, circulating tumor DNA (ctDNA) could be used for mutation analysis. This prospective, multicenter study establishes the diagnostic value of ctDNA analysis by droplet digital PCR (ctDNA-ddPCR) in patients with primary lung cancer.CtDNA from 458 primary lung cancer patients was analyzed using a panel of multiplex ddPCRs for EGFR (Ex19Del, G719S, L858R, L861Q and S768I), KRAS G12/G13 and BRAF V600 mutations. For 142 of 175 advanced stage non-squamous NSCLC patients tDNA-NGS results were available to compare to ctDNA-ddPCR. tDNA-NGS identified 98 mutations, of which ctDNA-ddPCR found 53 mutations (54%), including 32 of 45 (71%) targetable driver mutations. In 2 of these 142 patients, a mutation was found by ctDNA-ddPCR only. In 33 advanced stage patients lacking tDNA-NGS results, ctDNA-ddPCR detected 15 additional mutations, of which 7 targetable.Overall, ctDNA-ddPCR detected 70 mutations and tDNA-NGS 98 mutations in 175 advanced NSCLC patients. Using an up-front ctDNA-ddPCR strategy, followed by tDNA-NGS only if ctDNA-ddPCR analysis is negative, increases the number of mutations found from 98 to 115 (17%). At the same time, up-front ctDNA-ddPCR reduces tDNA-NGS analyses by 40%, decreasing the need to perform (additional) biopsies.http://www.sciencedirect.com/science/article/pii/S1936523322002480Liquid biopsyDroplet-digital PCRNSCLCMutation analysisCirculating tumor DNA |
| spellingShingle | Esther Visser Remco de Kock Sylvia Genet Ben van den Borne Maggy Youssef-El Soud Huub Belderbos Gerben Stege Marleen de Saegher Susan van ’t Westeinde Maarten Broeren Federica Eduati Birgit Deiman Volkher Scharnhorst Up-front mutation detection in circulating tumor DNA by droplet digital PCR has added diagnostic value in lung cancer Translational Oncology Liquid biopsy Droplet-digital PCR NSCLC Mutation analysis Circulating tumor DNA |
| title | Up-front mutation detection in circulating tumor DNA by droplet digital PCR has added diagnostic value in lung cancer |
| title_full | Up-front mutation detection in circulating tumor DNA by droplet digital PCR has added diagnostic value in lung cancer |
| title_fullStr | Up-front mutation detection in circulating tumor DNA by droplet digital PCR has added diagnostic value in lung cancer |
| title_full_unstemmed | Up-front mutation detection in circulating tumor DNA by droplet digital PCR has added diagnostic value in lung cancer |
| title_short | Up-front mutation detection in circulating tumor DNA by droplet digital PCR has added diagnostic value in lung cancer |
| title_sort | up front mutation detection in circulating tumor dna by droplet digital pcr has added diagnostic value in lung cancer |
| topic | Liquid biopsy Droplet-digital PCR NSCLC Mutation analysis Circulating tumor DNA |
| url | http://www.sciencedirect.com/science/article/pii/S1936523322002480 |
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