Authors: Grazia Lazzari, Tartarone A, Laurenzana I, Lamorte D, Valvano L, Statuto T, De Luca L, D’Auria F, Caivano A, Calice G, Bianculli A, Tucciariello R6, Lerose R, Benevento I, Montagna A, D’Andrea B, Castaldo G, Angela Solazzo.
Background: Pacific trial has revolutioned the outcome and the approach in locally advanced (LA) unresectable Non Small Cell Lung Cancer (NSCLC). In 2018 the European Medicine Agency (EMA) approved the use of Durvalumab only in adults whose tumours on biopsy specimen expresses PD-L1 on ≥ 1% of tumour cells despite this cut-off was not provided by the original randomised study. In vitro and in vivo studies have recorded the up regulation of PD-L1 expression in the tumor microenviroment (TME) after chemoradiation regrdless the expression on biopsy. Liquid biopsy could be helpful in detection of circulating PD-L1 in this set. Aim of this observational multicentre prospective study is to assess on liquid biopsy the up-regulation of PD-L1on serum and tumoral circulating extracellular vescicles (cEVS) from patients with LA NSCLC not expressing the PD-L1 on biopsy and treated with concurrent chemoradiation (CCRT).
Methods: Locally advanced NSCLC PD-L1 < 1 % biopsy proven will be enrolled in this study. A blood sample will be taken the day before (T0), 14 days after CCRT (T1) and 1 months later (T2). Patients will be treated with CCRT with platinum-based doublet and 60-66 Gy total radiation dose. Soluble PD-L1 will be analysed by ELISA. PD-L1on cEVs will be isolated from serum and phenotyped by nanoparticle tracking analysis, microscopy and flow cytometry. The statistical significant improvement in PD-L1 expression in serum and cEVs at T0 -T1-T2 will be assessed by t-test for p= 0.05 ; for multiple test p-value will be corrected with FDR.
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