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Article Dans Une Revue Respiratory Medicine and Research Année : 2023

Clinical and molecular analysis of lung cancers associated with fibrosing interstitial lung disease

Valentin Héluain
  • Fonction : Auteur
Grégoire Prévot
  • Fonction : Auteur
Bastien Cabarrou
  • Fonction : Auteur
Estelle Taranchon- Clermont
  • Fonction : Auteur
Alain Didier
Sandrine Tabourier-Gouin
  • Fonction : Auteur
Julie Milia
  • Fonction : Auteur
Julien Mazières
  • Fonction : Auteur

Résumé

Background: Interstitial lung disease is a heterogeneous group of diseases, some of which are known to present an independent risk factor for lung cancer. Its pathophysiological mechanism has not been fully elucidated and therapeutic management is also complex. We aim to both describe a cohort of patients with lung cancer associated with pre-existing fibrosing interstitial lung disease and to characterize their molecular profile. Methods: We conducted a retrospective, single centre cohort study, at Toulouse University Hospital. Immunohistochemical (PD-L1, CD8) and molecular analysis was performed on archived tumour sample. Molecular signalling pathways involved were analysed with the Reactome Pathway Database. Results: Forty-nine patients were analysed. Most common histology was adenocarcinoma (65.3%), followed by squamous cell carcinoma (30.6%). Idiopathic pulmonary fibrosis (30.6%) and interstitial lung disease associated with connective tissue disease (22.4%) were mostly diagnosed. Usual interstitial pneumonia dominated the scans patterns. A high proportion of early tumour stages was observed and overall survival was 34.5 months. In metastatic stages response rate to first line chemotherapy was 38% and overall survival was 11.2 months. Main cause of death was complex cancer progression. PD-L1 expression (n=23) was low (0%) to intermediate (1-49%). Tumour mutational burden was low in 69.2% of analysed cases (n=12) and microsatellite status was stable in all cases (n=13). Sample genotyping (n=14) showed frequent involvement of the TP53 gene and the implication of signalling pathways common to fibrotic processes such as TGFb and PI3K/AKT. Conclusions: We suggest a particular phenotype of lung cancer associated with fibrosing interstitial lung disease that could provide the basis for specific therapeutic strategies.

Mots clés

IPF Idiopathic Pulmonary Fibrosis CTD-ILD ILD associated with Connective Tissue Disease SSC Systemic Sclerosis UIP Usual Interstitial Pneumonia NSIP Non-Specific Interstitial Pneumonia CI Confidence Interval NR Not Reached TMB Tumour Mutational Burden TGF-b Transforming Growth Factor beta PDGFR Platelet Derived Growth Factor Receptor FGFR Fibroblast Growth Factor Receptor EGFR Epidermal Growth Factor Receptor MAPK Mitogen Activated Protein Kinases ERBB2 Erythroblastic Oncogene B2 PI3K/AKT Phosphoinositide 3 Kinase/Protein Kinase B NOTCH1 lung cancer interstitial lung disease pulmonary fibrosis next generation sequencing Abbreviations: LC Lung Cancer ILD Interstitial Lung Disease AEILD acute exacerbation of ILD WHO World Health Organization CT Computer Tomography TNM Tumors Nodes Metastases PFS Progression Free Survival OS Overall Survival DLCO diffusing capacity for carbon monoxide IPF Idiopathic Pulmonary Fibrosis CTD-ILD ILD associated with Connective Tissue Disease SSC Systemic Sclerosis UIP Usual Interstitial Pneumonia NSIP Non-Specific Interstitial Pneumonia CI Confidence Interval NR Not Reached TMB Tumour Mutational Burden TGF-b Transforming Growth Factor beta PDGFR Platelet Derived Growth Factor Receptor FGFR Fibroblast Growth Factor Receptor EGFR Epidermal Growth Factor Receptor MAPK Mitogen Activated Protein Kinases ERBB2 Erythroblastic Oncogene B2 PI3K/AKT Phosphoinositide 3 Kinase/Protein Kinase B NOTCH1 Notch Homologue 1 Lung Cancer ILD Interstitial Lung Disease AEILD acute exacerbation of ILD WHO World Health Organization CT Computer Tomography TNM Tumors Nodes Metastases PFS Progression Free Survival OS Overall Survival DLCO diffusing capacity for carbon monoxide
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Dates et versions

hal-04308863 , version 1 (27-11-2023)

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Valentin Héluain, Grégoire Prévot, Bastien Cabarrou, Olivier Calvayrac, Estelle Taranchon- Clermont, et al.. Clinical and molecular analysis of lung cancers associated with fibrosing interstitial lung disease. Respiratory Medicine and Research, 2023, 83, pp.100946. ⟨10.1016/j.resmer.2022.100946⟩. ⟨hal-04308863⟩
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