Clinical and molecular analysis of lung cancer associated with fibrosing and diffuse interstitial lung disease

Abstract

<b>Introduction:</b> Interstitial lung disease (ILD) can be characterized by progressive fibrosis and are an independent risk factor for lung cancer (LC). In this study, we aimed to describe clinical characteristics, therapeutic management and molecular features of LC associated with fibrosing ILD. <b>Methods:</b> Patients presenting LC and pre-existing fibrosing ILD were included in this ambispective, monocentric study. Immunohistochemistry (PD-L1, CD8) and next generation sequencing (FoundationOne®CDx) were performed on tumor samples. Reactome Pathway Database was used. <b>Results:</b> 49 patients were analyzed. The most represented histology was adenocarcinoma (65.3%), followed by squamous cell carcinoma (30.6%). Usual interstitial pneumonia pattern was dominant. There was a majority of idiopathic pulmonary fibrosis (30.6%) and systemic sclerosis (18.3%). In early stages, overall survival (OS) was 34.5 months. In advanced stages, response to first line chemotherapy was 38.1%, immunotherapy was never proposed and OS was 11.2 months. Cancer was the main cause of death. Immunohistochemical analyses conducted in 28 patients showed low (0%) to intermediate (1-49%) PD-L1 expression. Tumor mutational burden was low (0-5 Mut/Mb for 70% of the patients) and microsatellite status was stable in 14 tumor samples eligible. Next generation sequencing showed alteration in 197 genes. Pathways preferentially involved were TGFβ, PDGFR, FGFR, Wnt, MAPK, NOTCH1 and PI3K/AKT signaling pathways. No targetable oncogenic addiction was found. <b>Conclusion:</b> These observations suggest a particular phenotype of LC associated with fibrosing ILD and does not support targeted therapies or immune checkpoint inhibitor use.