Risk stratification of EGFR+ lung cancer diagnosed with panel-based next-generation sequencing
Objective - Panel-based next-generation sequencing (NGS) is increasingly used for the diagnosis of EGFR-mutated non-small-cell lung cancer (NSCLC) and could improve risk assessment in combination with clinical parameters. - Materials and methods - To this end, we retrospectively analyzed the outcome...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
22 August 2020
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| In: |
Lung cancer
Year: 2020, Volume: 148, Pages: 105-112 |
| ISSN: | 1872-8332 |
| DOI: | 10.1016/j.lungcan.2020.08.007 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.lungcan.2020.08.007 Verlag, lizenzpflichtig, Volltext: https://www.lungcancerjournal.info/article/S0169-5002(20)30579-1/pdf Resolving-System, Informationsseite zum Volltext: https://doi.org/10.1016/j.lungcan.2020.08.007 
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| Author Notes: | P. Christopoulos, M. Kirchner, J. Roeper, F. Saalfeld, M. Janning, F. Bozorgmehr, N. Magios, D. Kazdal, A.L. Volckmar, L.M. Brückner, T. Bochtler, M. Kriegsmann, V. Endris, R. Penzel, K. Kriegsmann, M. Eichhorn, F.J.F. Herth, C.P. Heussel, R.A. El Shafie, M.A. Schneider, T. Muley, M. Meister, M. Faehling, J.R. Fischer, L. Heukamp, P. Schirmacher, H. Bischoff, M. Wermke, S. Loges, F. Griesinger, A. Stenzinger, M. Thomas |
| Summary: | Objective - Panel-based next-generation sequencing (NGS) is increasingly used for the diagnosis of EGFR-mutated non-small-cell lung cancer (NSCLC) and could improve risk assessment in combination with clinical parameters. - Materials and methods - To this end, we retrospectively analyzed the outcome of 400 tyrosine kinase inhibitor (TKI)-treated EGFR+ NSCLC patients with validation of results in an independent cohort (n = 130). - Results - EGFR alterations other than exon 19 deletions (non-del19), TP53 co-mutations, and brain metastases at baseline showed independent associations of similar strengths with progression-free (PFS hazard ratios [HR] 2.1-2.3) and overall survival (OS HR 1.7-2.2), in combination defining patient subgroups with distinct outcome (EGFR+ NSCLC risk Score, "ENS", p < 0.001). Co-mutations beyond TP53 were rarely detected by our multigene panel (<5%) and not associated with clinical endpoints. Smoking did not affect outcome independently, but was associated with non-del19 EGFR mutations (p < 0.05) and comorbidities (p < 0.001). Laboratory parameters, like the blood lymphocyte-to-neutrophil ratio and serum LDH, correlated with the metastatic pattern (p < 0.01), but had no independent prognostic value. Reduced ECOG performance status (PS) was associated with comorbidities (p < 0.05) and shorter OS (p < 0.05), but preserved TKI efficacy. Non-adenocarcinoma histology was also associated with shorter OS (p < 0.05), but rare (2-3 %). The ECOG PS and non-adenocarcinoma histology could not be validated in our independent cohort, and did not increase the range of prognostication alongside the ENS. - Conclusions - EGFR variant, TP53 status and brain metastases predict TKI efficacy and survival in EGFR+ NSCLC irrespective of other currently available parameters ("ENS"). Together, they constitute a practical and reproducible approach for risk stratification of newly diagnosed metastatic EGFR+ NSCLC. |
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| Item Description: | Gesehen am 19.01.2021 Im Titel ist das Pluszeichen hochgestellt |
| Physical Description: | Online Resource |
| ISSN: | 1872-8332 |
| DOI: | 10.1016/j.lungcan.2020.08.007 |