| |  Online-Ressource |
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| Verfasst von: | Finn, Stephen P. [VerfasserIn]  |
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| | Addeo, Alfredo [VerfasserIn] |
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| | Dafni, Urania [VerfasserIn] |
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| | Thunnissen, Erik [VerfasserIn] |
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| | Bubendorf, Lukas [VerfasserIn] |
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| | Madsen, Line Bille [VerfasserIn] |
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| | Biernat, Wojciech [VerfasserIn] |
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| | Verbeken, Eric [VerfasserIn] |
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| | Hernandez-Losa, Javier [VerfasserIn] |
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| | Marchetti, Antonio [VerfasserIn] |
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| | Cheney, Richard [VerfasserIn] |
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| | Warth, Arne [VerfasserIn] |
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| | Speel, Ernst-Jan M. [VerfasserIn] |
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| | Quinn, Anne Marie [VerfasserIn] |
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| | Monkhorst, Kim [VerfasserIn] |
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| | Jantus-Lewintre, Eloisa [VerfasserIn] |
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| | Tischler, Verena [VerfasserIn] |
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| | Marti, Nesa [VerfasserIn] |
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| | Dimopoulou, Georgia [VerfasserIn] |
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| | Molina-Vila, Miguel A. [VerfasserIn] |
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| | Kammler, Roswitha [VerfasserIn] |
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| | Kerr, Keith M. [VerfasserIn] |
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| | Peters, Solange [VerfasserIn] |
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| | Stahel, Rolf A. [VerfasserIn] |
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| Titel: | Prognostic impact of KRAS G12C mutation in patients with NSCLC |
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| Titelzusatz: | results from the European Thoracic Oncology Platform Lungscape project |
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| Verf.angabe: | Stephen P. Finn, Alfredo Addeo, Urania Dafni, Erik Thunnissen, Lukas Bubendorf, Line Bille Madsen, Wojciech Biernat, Eric Verbeken, Javier Hernandez-Losa, Antonio Marchetti, Richard Cheney, Arne Warth, Ernst-Jan M. Speel, Anne Marie Quinn, Kim Monkhorst, Eloisa Jantus-Lewintre, Verena Tischler, Nesa Marti, Georgia Dimopoulou, Miguel A. Molina-Vila, Roswitha Kammler, Keith M. Kerr, Solange Peters, Rolf A. Stahel on behalf of the European Thoracic Oncology Platform Lungscape Investigators |
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| E-Jahr: | 2021 |
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| Jahr: | 26 February 2021 |
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| Umfang: | 13 S. |
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| Fussnoten: | Gesehen am 18.02.2022 |
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| Titel Quelle: | Enthalten in: Journal of thoracic oncology |
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| Ort Quelle: | Amsterdam : Elsevier, 2006 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 16(2021), 6 vom: Juni, Seite 990-1002 |
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| ISSN Quelle: | 1556-1380 |
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| Abstract: | Introduction - KRAS mutations, the most frequent gain-of-function alterations in NSCLC, are currently emerging as potential predictive therapeutic targets. The role of KRAS-G12C (Kr_G12C) is of special interest after the recent discovery and preclinical analyses of two different Kr_G12C covalent inhibitors (AMG-510, MRTX849). - Methods - KRAS mutations were evaluated in formalin-fixed, paraffin-embedded tissue sections by a microfluidic-based multiplex polymerase chain reaction platform as a component of the previously published European Thoracic Oncology Platform Lungscape 003 Multiplex Mutation study, of clinically annotated, resected, stage I to III NSCLC. In this study, -Kr_G12C mutation prevalence and its association with clinicopathologic characteristics, molecular profiles, and postoperative patient outcome (overall survival, relapse-free survival, time-to-relapse) were explored. - Results - KRAS gene was tested in 2055 Lungscape cases (adenocarcinomas: 1014 [49%]) with I or II or III stage respective distribution of 53% or 24% or 22% and median follow-up of 57 months. KRAS mutation prevalence in the adenocarcinoma cohort was 38.0% (95% confidence interval (CI): 35.0% to 41.0%), with Kr_G12C mutation representing 17.0% (95% CI: 14.7% to 19.4%). In the "histologic-subtype" cohort, Kr_G12C prevalence was 10.5% (95% CI: 9.2% to 11.9%). When adjusting for clinicopathologic characteristics, a significant negative prognostic effect of Kr_G12C presence versus other KRAS mutations or nonexistence of KRAS mutation was identified in the adenocarcinoma cohort alone and in the "histologic-subtype" cohort. For overall survival in adenocarcinomas, hazard ratio (HR)G12C versus other KRAS is equal to 1.39 (95% CI: 1.03 to 1.89, p = 0.031) and HRG12C versus no KRAS is equal to 1.32 (95% CI: 1.03 to 1.69, p = 0.028) (both also significant in the "histologic-subtype" cohort). For time-to-relapse, HRG12C versus other KRAS is equal to 1.41 (95% CI: 1.03 to 1.92, p = 0.030). In addition, among all patients, for relapse-free survival, HRG12C versus no KRAS is equal to 1.27 (95% CI: 1.04 to 1.54, p = 0.017). - Conclusions - In this large, clinically annotated stage I to III NSCLC cohort, the specific Kr_G12C mutation is significantly associated with poorer prognosis (adjusting for clinicopathologic characteristics) among adenocarcinomas and in unselected NSCLCs. |
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| DOI: | doi:10.1016/j.jtho.2021.02.016 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1016/j.jtho.2021.02.016 |
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| | Volltext: https://www.sciencedirect.com/science/article/pii/S1556086421017342 |
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| | DOI: https://doi.org/10.1016/j.jtho.2021.02.016 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Kr_G12C |
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| | KRAS |
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| | Multiplex PCR platform |
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| | NSCLC |
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| K10plus-PPN: | 1790041945 |
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| Verknüpfungen: | → Zeitschrift |
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Prognostic impact of KRAS G12C mutation in patients with NSCLC / Finn, Stephen P. [VerfasserIn]; 26 February 2021 (Online-Ressource)
