cad a22 4500 569307384 CHVBK 20200229061546.0 cr unu---uuuuu 190726e201905 xx s 000 0 eng 10.1016/j.lungcan.2019.03.012 doi 10.5167/uzh-171739 doi (ZORA)oai:www.zora.uzh.ch:171739 (SERVAL)BIB_C471070F0828 610 ddc 31027705 pmid 000468721500014 isiid A retrospective cohort study of PD-L1 prevalence, molecular associations and clinical outcomes in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape Project [Elektronische Daten] [Keith M Kerr, Erik Thunnissen, Urania Dafni, Stephen P Finn, Lukas Bubendorf, Alex Soltermann, Eric Verbeken, Wojciech Biernat, Arne Warth, Antonio Marchetti, Ernst-Jan M Speel, Sarawati Pokharel, Anne Marie Quinn, Kim Monkhorst, Atilio Navarro, Line Bille Madsen, Teodora Radonic, Joan Wilson, Graziano De Luca, Steven G Gray, Richard Cheney, Spasenija Savic, Miguel Martorell, Thomas Muley, Paul Baas, Peter Meldgaard, Fiona Blackhall, Anne-Marie Dingemans, Rafal Dziadziuszko, Johan Vansteenkiste, Walter Weder, Rrolf Stahel, et al] closedAccess eu-repo INTRODUCTION The PD-L1 biomarker is an important factor in selecting patients with non-small cell lung cancer for immunotherapy. While several reports suggest that PD-L1 positivity is linked to a poor prognosis, others suggest that PD-L1 positive status portends a good prognosis. METHODS PD-L1 positivity prevalence, assessed via immunohistochemistry (IHC) on tissue microarrays (TMAs), and its association with clinicopathological characteristics, molecular profiles and patient outcome- Relapse-free Survival (RFS), Time-to-Relapse (TTR) and Overall Survival (OS)- is explored in the ETOP Lungscape cohort of stage I-III non-small cell lung cancer (NSCLC). Tumors are considered positive if they have ≥1/5/25/50% neoplastic cell membrane staining. RESULTS PD-L1 expression was assessed in 2182 NSCLC cases (2008 evaluable, median follow-up 4.8 years, 54.6% still alive), from 15 ETOP centers. Adenocarcinomas represent 50.9% of the cohort (squamous cell: 42.4%). Former smokers are 53.7% (current: 31.6%, never: 10.5%). PD-L1 positivity prevalence is present in more than one third of the Lungscape cohort (1%/5% cut-offs). It doesn't differ between adenocarcinomas and squamous cell histologies, but is more frequently detected in higher stages, never smokers, larger tumors (1/5/25% cut-offs). With ≥1% cut-off it is significantly associated with IHC MET overexpression, expression of PTEN, EGFR and KRAS mutation (only for adenocarcinoma). Results for 5%, 25% and 50% cut-offs were similar, with MET being significantly associated with PD-L1 positivity both for AC (p < 0.001, 5%/25%/50% cut-offs) and SCC (p < 0.001, 5% & 50% cut-offs and p = 0.0017 for 25%). When adjusting for clinicopathological characteristics, a significant prognostic effect was identified in adenocarcinomas (adjusted p-values: 0.024/0.064/0.063 for RFS/TTR/OS 1% cut-off, analogous for 5%/25%, but not for 50%). Similar results obtained for the model including all histologies, but no effect was found for the squamous cell carcinomas. CONCLUSION PD-L1 positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients. Clinic for Oncology and Hematology zora Institute of Pathology and Molecular Pathology zora Clinic for Thoracic Surgery zora Kerr Keith M. joint author Thunnissen Erik joint author Dafni Urania joint author Finn Stephen P. joint author Bubendorf Lukas joint author Soltermann Alex joint author Verbeken Eric joint author Biernat Wojciech joint author Warth Arne joint author Marchetti Antonio joint author Speel Ernst-Jan M. joint author Pokharel Sarawati joint author Quinn Anne Marie joint author Monkhorst Kim joint author Navarro Atilio joint author Madsen Line Bille joint author Radonic Teodora joint author Wilson Joan joint author De Luca Graziano joint author Gray Steven G. joint author Cheney Richard joint author Savic Spasenija joint author Martorell Miguel joint author Muley Thomas joint author Baas Paul joint author Meldgaard Peter joint author Blackhall Fiona joint author Dingemans Anne-Marie joint author Dziadziuszko Rafal joint author Vansteenkiste Johan joint author Weder Walter joint author Stahel Rrolf joint author et al joint author Lung Cancer 131:95-103 https://www.zora.uzh.ch/id/eprint/171739/1/Kerr_Lung_Cancer_2019.pdf text/html WWW-Backlink auf das Repository 1 Journal Article PeerReviewed zora ZORA 856 40 https://www.zora.uzh.ch/id/eprint/171739/1/Kerr_Lung_Cancer_2019.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- Kerr Keith M. joint author ZORA 700 1- Thunnissen Erik joint author ZORA 700 1- Dafni Urania joint author ZORA 700 1- Finn Stephen P. joint author ZORA 700 1- Bubendorf Lukas joint author ZORA 700 1- Soltermann Alex joint author ZORA 700 1- Verbeken Eric joint author ZORA 700 1- Biernat Wojciech joint author ZORA 700 1- Warth Arne joint author ZORA 700 1- Marchetti Antonio joint author ZORA 700 1- Speel Ernst-Jan M. joint author ZORA 700 1- Pokharel Sarawati joint author ZORA 700 1- Quinn Anne Marie joint author ZORA 700 1- Monkhorst Kim joint author ZORA 700 1- Navarro Atilio joint author ZORA 700 1- Madsen Line Bille joint author ZORA 700 1- Radonic Teodora joint author ZORA 700 1- Wilson Joan joint author ZORA 700 1- De Luca Graziano joint author ZORA 700 1- Gray Steven G. joint author ZORA 700 1- Cheney Richard joint author ZORA 700 1- Savic Spasenija joint author ZORA 700 1- Martorell Miguel joint author ZORA 700 1- Muley Thomas joint author ZORA 700 1- Baas Paul joint author ZORA 700 1- Meldgaard Peter joint author ZORA 700 1- Blackhall Fiona joint author ZORA 700 1- Dingemans Anne-Marie joint author ZORA 700 1- Dziadziuszko Rafal joint author ZORA 700 1- Vansteenkiste Johan joint author ZORA 700 1- Weder Walter joint author ZORA 700 1- Stahel Rrolf joint author ZORA 700 -- et al joint author ZORA 773 0- Lung Cancer 131:95-103 SERVAL 700 1- Kerr K.M. aut SERVAL 700 1- Thunnissen E. aut SERVAL 700 1- Dafni U. aut SERVAL 700 1- Finn S.P. aut SERVAL 700 1- Bubendorf L. aut SERVAL 700 1- Soltermann A. aut SERVAL 700 1- Verbeken E. aut SERVAL 700 1- Biernat W. aut SERVAL 700 1- Warth A. aut SERVAL 700 1- Marchetti A. aut SERVAL 700 1- Speel E.M. aut SERVAL 700 1- Pokharel S. aut SERVAL 700 1- Quinn A.M. aut SERVAL 700 1- Monkhorst K. aut SERVAL 700 1- Navarro A. aut SERVAL 700 1- Madsen L.B. aut SERVAL 700 1- Radonic T. aut SERVAL 700 1- Wilson J. aut SERVAL 700 1- De Luca G. aut SERVAL 700 1- Gray S.G. aut SERVAL 700 1- Cheney R. aut SERVAL 700 1- Savic S. aut SERVAL 700 1- Martorell M. aut SERVAL 700 1- Muley T. aut SERVAL 700 1- Baas P. aut SERVAL 700 1- Meldgaard P. aut SERVAL 700 1- Blackhall F. aut SERVAL 700 1- Dingemans A.M. aut SERVAL 700 1- Dziadziuszko R. aut SERVAL 700 1- Vansteenkiste J. aut SERVAL 700 1- Weder W. aut SERVAL 700 1- Polydoropoulou V. aut SERVAL 700 1- Geiger T. aut SERVAL 700 1- Kammler R. aut SERVAL 700 1- Peters S. aut SERVAL 700 1- Stahel R. aut SERVAL 773 0- Lung cancer 131(2019-05), 95-103 131<95-103 2019 131 BK010053 XK010053 XK010000 ZORA ZORA ZORA Journal Article closedAccess SERVAL SERVAL SERVAL article