TY - JOUR
TI - 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
AU - Kerr, K.M.
AU - Thunnissen, E.
AU - Dafni, U.
AU - Finn, S.P.
AU - Bubendorf, L.
AU - Soltermann, A.
AU - Verbeken, E.
AU - Biernat, W.
AU - Warth, A.
AU - Marchetti, A.
AU - Speel, E.-J.M.
AU - Pokharel, S.
AU - Quinn, A.M.
AU - Monkhorst, K.
AU - Navarro, A.
AU - Madsen, L.B.
AU - Radonic, T.
AU - Wilson, J.
AU - De Luca, G.
AU - Gray, S.G.
AU - Cheney, R.
AU - Savic, S.
AU - Martorell, M.
AU - Muley, T.
AU - Baas, P.
AU - Meldgaard, P.
AU - Blackhall, F.
AU - Dingemans, A.-M.
AU - Dziadziuszko, R.
AU - Vansteenkiste, J.
AU - Weder, W.
AU - Polydoropoulou, V.
AU - Geiger, T.
AU - Kammler, R.
AU - Peters, S.
AU - Stahel, R.
AU - for the Lungscape Consortium
JO - Lung Cancer
PY - 2019
VL - 131
TODO - null
SP - 95-103
PB - Elsevier Ireland Ltd
SN - 0169-5002
TODO - 10.1016/j.lungcan.2019.03.012
TODO - epidermal growth factor receptor;  K ras protein;  phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase;  programmed death 1 ligand 1;  scatter factor receptor;  MET protein, human;  programmed death 1 ligand 1;  scatter factor receptor;  tumor marker, aged;  Article;  cancer prognosis;  cancer staging;  cancer survival;  cohort analysis;  controlled study;  female;  human;  immunohistochemistry;  major clinical study;  male;  non small cell lung cancer;  overall survival;  predictive value;  prevalence;  priority journal;  protein expression;  protein function;  recurrence free survival;  retrospective study;  smoking;  survival;  time to relapse survival;  tissue microarray;  adult;  clinical trial;  Europe;  follow up;  immunotherapy;  lung adenocarcinoma;  lung tumor;  metabolism;  middle aged;  mortality;  multicenter study;  non small cell lung cancer;  procedures;  prognosis;  survival analysis;  treatment outcome;  very elderly;  young adult, Adenocarcinoma of Lung;  Adult;  Aged;  Aged, 80 and over;  B7-H1 Antigen;  Biomarkers, Tumor;  Carcinoma, Non-Small-Cell Lung;  Cohort Studies;  Europe;  Follow-Up Studies;  Humans;  Immunotherapy;  Lung Neoplasms;  Male;  Middle Aged;  Neoplasm Staging;  Prognosis;  Proto-Oncogene Proteins c-met;  Retrospective Studies;  Survival Analysis;  Treatment Outcome;  Young Adult
TODO - 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. © 2019 Elsevier B.V.
ER -