دورية أكاديمية
Prognostic Impact of KRAS G12C Mutation in Patients With NSCLC:Results From the European Thoracic Oncology Platform Lungscape Project
| العنوان: | Prognostic Impact of KRAS G12C Mutation in Patients With NSCLC:Results From the European Thoracic Oncology Platform Lungscape Project |
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| المؤلفون: | Finn, Stephen P., Addeo, Alfredo, Dafni, Urania, Thunnissen, Erik, Bubendorf, Lukas, Madsen, Line Bille, Biernat, Wojciech, Verbeken, Eric, Hernandez-Losa, Javier, Marchetti, Antonio, Cheney, Richard, Warth, Arne, Speel, Ernst-Jan M., Quinn, Anne Marie, Monkhorst, Kim, Jantus-Lewintre, Eloisa, Tischler, Verena, Marti, Nesa, Dimopoulou, Georgia, Molina-Vila, Miguel A., Kammler, Roswitha, Kerr, Keith M., Peters, Solange, Stahel, Rolf A. |
| المصدر: | Finn , S P , Addeo , A , Dafni , U , Thunnissen , E , Bubendorf , L , Madsen , L B , Biernat , W , Verbeken , E , Hernandez-Losa , J , Marchetti , A , Cheney , R , Warth , A , Speel , E-J M , Quinn , A M , Monkhorst , K , Jantus-Lewintre , E , Tischler , V , Marti , N , Dimopoulou , G , Molina-Vila , M A , Kammler , R , Kerr , K M , Peters , S , Stahel .... |
| سنة النشر: | 2021 |
| المجموعة: | Maastricht University Research Publications |
| مصطلحات موضوعية: | NSCLC, KRAS, Kr_G12C, Multiplex PCR platform, CELL LUNG-CANCER, CLINICAL-ASSOCIATION, PREDICTIVE-VALUE, PD-1 BLOCKADE, PREVALENCE, LANDSCAPE, OUTCOMES |
| الوصف: | Introduction: KRAS mutations, the most frequent gain-of function alterations in NSCLC, are currently emerging as potential predictive therapeutic targets. The role of KRASG12C (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 "histologicsubtype" 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, ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1016/j.jtho.2021.02.016 |
| الإتاحة: | https://doi.org/10.1016/j.jtho.2021.02.016Test https://cris.maastrichtuniversity.nl/en/publications/29cd671b-031e-4fb4-83a2-71898860ca05Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.D5DA8D5E |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jtho.2021.02.016 |
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