Single-center retrospective cohort study of lung cancer associated with interstitial lung disease: Prognostic factors and molecular profile

A Goga; G Soussi; A Mogenet; P Habert; A Fourdrain; R Naud; J Milesi; B Coiffard; J Bermudez; E Pollien; E Gouton; M Barboni; M Reynaud-Gaubert; P Tomasini; L Greillier; J Pluvy

doi:10.1016/j.lungcan.2026.109379

Single-center retrospective cohort study of lung cancer associated with interstitial lung disease: Prognostic factors and molecular profile

Lung Cancer. 2026 Mar 21:215:109379. doi: 10.1016/j.lungcan.2026.109379. Online ahead of print.

Authors

A Goga¹, G Soussi², A Mogenet¹, P Habert³, A Fourdrain⁴, R Naud¹, J Milesi¹, B Coiffard⁵, J Bermudez¹, E Pollien¹, E Gouton⁵, M Barboni⁵, M Reynaud-Gaubert¹, P Tomasini⁶, L Greillier⁶, J Pluvy⁷

Affiliations

¹ Département de Pneumologie, Hôpital Nord, AP-HM, Marseille, France; Aix Marseille Université, Marseille, France.
² Département de Pneumologie, Hôpital Forcilles - Fondation Cognacq-Jay, Férolles-Attily, France.
³ Aix Marseille Université, Marseille, France; Service de Radiologie Hôpital Nord, AP-HM, Marseille, France; LIIE/UR 4264, Aix Marseille Université, Marseille, France; CERIMED, Aix Marseille Univ, Marseille, France.
⁴ Aix Marseille Université, Marseille, France; Service de Chirurgie Thoracique Hopital Nord, AP-HM, Marseille France.
⁵ Département de Pneumologie, Hôpital Nord, AP-HM, Marseille, France.
⁶ Département de Pneumologie, Hôpital Nord, AP-HM, Marseille, France; Aix Marseille Université, Marseille, France; Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille France; INSERM, France; CNRS, France.
⁷ Département de Pneumologie, Hôpital Nord, AP-HM, Marseille, France. Electronic address: Johan.pluvy@ap-hm.fr.

PMID: 41887129
DOI: 10.1016/j.lungcan.2026.109379

Abstract

Background: Lung cancer associated with interstitial lung disease (LC-ILD) represents a highly vulnerable population with limited therapeutic options and increased risk of treatment-related complications. Data from Western cohorts remain scarce, especially regarding molecular characteristics and prognostic determinants.

Methods: We conducted a retrospective single-center cohort study of all consecutive LC-ILD patients discussed in a thoracic oncology multidisciplinary team (MDT) at Marseille University Hospital between June 2010 and July 2025.

Results: A total of 102 patients were included. Mean age was 68.8 years and 83% were men. UIP was the most frequent ILD pattern (61%). Molecular profiling (available for 57%) showed a landscape dominated by TP53 (38%), KRAS (24% including 9% G12C) and PI3KCA (16%), with no EGFR alterations detected. ARE occurred in 42% of patients and were fatal in 67%. Median OS was 17.7 months. In multivariable analysis, higher KCO (HR 0.97 per 1% increase), good performance status, and curative-intent strategy were independently associated with improved survival.

Conclusion: KCO and performance status are the strongest independent predictors of survival in LC-ILD. AREs are frequent and highly lethal. Dedicated therapeutic guidelines and an adapted ILD-GAP-cancer prognostic tool are urgently needed. Beyond clinical parameters our findings suggest a distinct molecular landscape dominated by TP53, KRAS and PI3K pathway alteration.

Keywords: Idiopathic pulmonary fibrosis NGS; Interstitial lung disease; KCO; Lung cancer; Surgery.