Τίτλος:
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
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Kerr, K.M.
Thunnissen, E.
Dafni, U.
Finn, S.P.
Bubendorf, L.
Soltermann, A.
Verbeken, E.
Biernat, W.
Warth, A.
Marchetti, A.
Speel, E.-J.M.
Pokharel, S.
Quinn, A.M.
Monkhorst, K.
Navarro, A.
Madsen, L.B.
Radonic, T.
Wilson, J.
De Luca, G.
Gray, S.G.
Cheney, R.
Savic, S.
Martorell, M.
Muley, T.
Baas, P.
Meldgaard, P.
Blackhall, F.
Dingemans, A.-M.
Dziadziuszko, R.
Vansteenkiste, J.
Weder, W.
Polydoropoulou, V.
Geiger, T.
Kammler, R.
Peters, S.
Stahel, R.
for the Lungscape Consortium
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.lungcan.2019.03.012
