| |  Online-Ressource |
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| Verfasst von: | Christopoulos, Petros [VerfasserIn]  |
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| | Kirchner, Martina [VerfasserIn] |
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| | Bozorgmehr, Farastuk [VerfasserIn] |
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| | Endris, Volker [VerfasserIn] |
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| | El Sayed, Mei [VerfasserIn] |
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| | Budczies, Jan [VerfasserIn] |
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| | Ristau, Jonas [VerfasserIn] |
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| | Penzel, Roland [VerfasserIn] |
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| | Herth, Felix [VerfasserIn] |
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| | Heußel, Claus Peter [VerfasserIn] |
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| | Eichhorn, Martin E. [VerfasserIn] |
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| | Muley, Thomas [VerfasserIn] |
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| | Meister, Michael [VerfasserIn] |
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| | Rieken, Stefan [VerfasserIn] |
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| | Lasitschka, Felix [VerfasserIn] |
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| | Bischoff, Helge [VerfasserIn] |
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| | Sotillo, Rocio [VerfasserIn] |
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| | Schirmacher, Peter [VerfasserIn] |
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| | Thomas, Michael [VerfasserIn] |
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| | Stenzinger, Albrecht [VerfasserIn] |
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| Titel: | Identification of a highly lethal V3+TP53+ subset in ALK+ lung adenocarcinoma |
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| Verf.angabe: | P. Christopoulos, M. Kirchner, F. Bozorgmehr, V. Endris, M. Elsayed, J. Budczies, J. Ristau, R. Penzel, F.J. Herth, C.P. Heussel, M. Eichhorn, T. Muley, M. Meister, J.R. Fischer, S. Rieken, F. Lasitschka, H. Bischoff, R. Sotillo, P. Schirmacher, M. Thomas, A. Stenzinger |
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| E-Jahr: | 2019 |
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| Jahr: | [1 January 2019] |
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| Umfang: | 10 S. |
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| Fussnoten: | Die Pluszeichen sind im Titel hochgestellt ; First published: 26 September 2018 ; Gesehen am07.05.2019 |
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| Titel Quelle: | Enthalten in: International journal of cancer |
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| Ort Quelle: | Bognor Regis : Wiley-Liss, 1966 |
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| Jahr Quelle: | 2019 |
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| Band/Heft Quelle: | 144(2019), 1, Seite 190-199 |
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| ISSN Quelle: | 1097-0215 |
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| Abstract: | Tyrosine kinase inhibitors (TKI) have improved prognosis in metastatic anaplastic lymphoma kinase (ALK)-driven lung adenocarcinoma, but patient outcomes vary widely. We retrospectively analyzed the clinical course of all cases with assessable baseline TP53 status and/or ALK fusion variant treated at our institutions (n = 102). TP53 mutations were present in 17/87 (20%) and the echinoderm microtubule-associated protein-like 4 (EML4)-ALK variant 3 (V3) in 41/92 (45%) patients. The number of metastatic sites at diagnosis was affected more by the presence of V3 than by TP53 mutations, and highest with both factors (mean 5.3, p < 0.001). Under treatment with ALK TKI, progression-free survival (PFS) was shorter with either TP53 mutations or V3, while double positive cases appeared to have an even higher risk (hazard ratio [HR] = 2.9, p = 0.015). The negative effect of V3 on PFS of TKI-treated patients was strong already in the first line (HR = 2.5, p = 0.037) and decreased subsequently, whereas a trend for PFS impairment under first-line TKI by TP53 mutations became stronger and statistically significant only when considering all treatment lines together. Overall survival was impaired more by TP53 mutations (HR = 4.9, p = 0.003) than by V3 (HR = 2.4, p = 0.018), while patients with TP53 mutated V3-driven tumors carried the highest risk of death (HR = 9.1, p = 0.02). Thus, TP53 mutations and V3 are independently associated with enhanced metastatic spread, shorter TKI responses and inferior overall survival in ALK+ lung adenocarcinoma. Both markers could assist selection of cases for more aggressive management and guide development of novel therapeutic strategies. In combination, they define a patient subset with very poor outcome. |
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| DOI: | doi:10.1002/ijc.31893 |
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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/10.1002/ijc.31893 |
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| | Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.31893 |
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| | DOI: https://doi.org/10.1002/ijc.31893 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | ALK+ NSCLC |
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| | EML4-ALK fusion variant |
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| | metastasis |
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| | overall survival |
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| | TP53 mutation |
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| | treatment failure |
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| K10plus-PPN: | 1664903720 |
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| Verknüpfungen: | → Zeitschrift |
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Identification of a highly lethal V3+TP53+ subset in ALK+ lung adenocarcinoma / Christopoulos, Petros [VerfasserIn]; [1 January 2019] (Online-Ressource)
