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Reflex testing in non-small cell lung carcinoma using DNA- and RNA-based next-generation sequencing—a single-center experience
BACKGROUND: Targeted treatment modalities for non-small cell lung carcinoma (NSCLC) patients are expanding rapidly and demand a constant adaptation of molecular testing strategies. In this regard, broad reflex testing via next-generation sequencing (NGS) might have several advantages. However, real-...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674594/ https://www.ncbi.nlm.nih.gov/pubmed/35004252 http://dx.doi.org/10.21037/tlcr-21-570 |
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author | Zacharias, Martin Absenger, Gudrun Kashofer, Karl Wurm, Robert Lindenmann, Jörg Terbuch, Angelika Konjic, Selma Sauer, Stefan Gollowitsch, Franz Gorkiewicz, Gregor Brcic, Luka |
author_facet | Zacharias, Martin Absenger, Gudrun Kashofer, Karl Wurm, Robert Lindenmann, Jörg Terbuch, Angelika Konjic, Selma Sauer, Stefan Gollowitsch, Franz Gorkiewicz, Gregor Brcic, Luka |
author_sort | Zacharias, Martin |
collection | PubMed |
description | BACKGROUND: Targeted treatment modalities for non-small cell lung carcinoma (NSCLC) patients are expanding rapidly and demand a constant adaptation of molecular testing strategies. In this regard, broad reflex testing via next-generation sequencing (NGS) might have several advantages. However, real-world data regarding practical feasibility and clinical relevance are scarce, especially for RNA-based NGS. METHODS: We performed a retrospective study comparing NGS use in two consecutive years (2019 and 2020). In 2019, reflex testing mainly consisted of DNA-based NGS for mutations and immunohistochemistry (IHC) for ALK, ROS1, and NTRK fusion products. At the beginning of 2020, our approach has changed, with DNA- and RNA-based NGS panels now being simultaneously performed. This change in protocol allowed us to retrospectively evaluate if broad molecular reflex testing brings additional value to lung cancer patients. RESULTS: Within the whole cohort (n=432), both DNA- and RNA-based NGS yielded almost always evaluable results. Only in 6 cases, the RNA content was too little for an appropriate analysis. After integrating RNA-based NGS in the reflex testing approach, the number of detected fusions increased significantly (2.6% vs. 8.2%; P=0.0021), but also more patients received targeted therapies. Furthermore, exceedingly rare alterations were more likely to be detected, including the so far undescribed EGFR-NUP160 fusion. CONCLUSIONS: Our study demonstrates that a comprehensive approach to reflex NGS testing is practically feasible and clinically relevant. Including RNA-based panels in the reflex testing approach results in more detected fusions and more patients receiving targeted therapies. Additionally, this broad molecular profiling strategy identifies patients with emerging biomarkers, underscoring its usefulness in the rapidly evolving landscape of targeted therapies. |
format | Online Article Text |
id | pubmed-8674594 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-86745942022-01-06 Reflex testing in non-small cell lung carcinoma using DNA- and RNA-based next-generation sequencing—a single-center experience Zacharias, Martin Absenger, Gudrun Kashofer, Karl Wurm, Robert Lindenmann, Jörg Terbuch, Angelika Konjic, Selma Sauer, Stefan Gollowitsch, Franz Gorkiewicz, Gregor Brcic, Luka Transl Lung Cancer Res Original Article BACKGROUND: Targeted treatment modalities for non-small cell lung carcinoma (NSCLC) patients are expanding rapidly and demand a constant adaptation of molecular testing strategies. In this regard, broad reflex testing via next-generation sequencing (NGS) might have several advantages. However, real-world data regarding practical feasibility and clinical relevance are scarce, especially for RNA-based NGS. METHODS: We performed a retrospective study comparing NGS use in two consecutive years (2019 and 2020). In 2019, reflex testing mainly consisted of DNA-based NGS for mutations and immunohistochemistry (IHC) for ALK, ROS1, and NTRK fusion products. At the beginning of 2020, our approach has changed, with DNA- and RNA-based NGS panels now being simultaneously performed. This change in protocol allowed us to retrospectively evaluate if broad molecular reflex testing brings additional value to lung cancer patients. RESULTS: Within the whole cohort (n=432), both DNA- and RNA-based NGS yielded almost always evaluable results. Only in 6 cases, the RNA content was too little for an appropriate analysis. After integrating RNA-based NGS in the reflex testing approach, the number of detected fusions increased significantly (2.6% vs. 8.2%; P=0.0021), but also more patients received targeted therapies. Furthermore, exceedingly rare alterations were more likely to be detected, including the so far undescribed EGFR-NUP160 fusion. CONCLUSIONS: Our study demonstrates that a comprehensive approach to reflex NGS testing is practically feasible and clinically relevant. Including RNA-based panels in the reflex testing approach results in more detected fusions and more patients receiving targeted therapies. Additionally, this broad molecular profiling strategy identifies patients with emerging biomarkers, underscoring its usefulness in the rapidly evolving landscape of targeted therapies. AME Publishing Company 2021-11 /pmc/articles/PMC8674594/ /pubmed/35004252 http://dx.doi.org/10.21037/tlcr-21-570 Text en 2021 Translational Lung Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Zacharias, Martin Absenger, Gudrun Kashofer, Karl Wurm, Robert Lindenmann, Jörg Terbuch, Angelika Konjic, Selma Sauer, Stefan Gollowitsch, Franz Gorkiewicz, Gregor Brcic, Luka Reflex testing in non-small cell lung carcinoma using DNA- and RNA-based next-generation sequencing—a single-center experience |
title | Reflex testing in non-small cell lung carcinoma using DNA- and RNA-based next-generation sequencing—a single-center experience |
title_full | Reflex testing in non-small cell lung carcinoma using DNA- and RNA-based next-generation sequencing—a single-center experience |
title_fullStr | Reflex testing in non-small cell lung carcinoma using DNA- and RNA-based next-generation sequencing—a single-center experience |
title_full_unstemmed | Reflex testing in non-small cell lung carcinoma using DNA- and RNA-based next-generation sequencing—a single-center experience |
title_short | Reflex testing in non-small cell lung carcinoma using DNA- and RNA-based next-generation sequencing—a single-center experience |
title_sort | reflex testing in non-small cell lung carcinoma using dna- and rna-based next-generation sequencing—a single-center experience |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674594/ https://www.ncbi.nlm.nih.gov/pubmed/35004252 http://dx.doi.org/10.21037/tlcr-21-570 |
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