Radiation toxicity and survival in patients with interstitial lung disease and non-small cell lung cancer: A case control study

Abstract

Purpose: Lung cancers associated with interstitial lung disease are challenging to diagnose and manage. We investigated the prevalence of interstitial lung disease among consecutively irradiated cancer patients, and the tolerance and prognosis of patients with or without interstitial lung disease after thoracic radiotherapy. Material and methods: This bicentric study was designed as a case-control study of patients with interstitial lung disease prior to radiotherapy (cases) and controls without interstitial lung disease. Patients were irradiated with curative intent for localized, locally advanced or oligometastatic non-small cell lung cancer. Consecutive lung cancer patients undergoing curative radiotherapy between January 2018 and December 2020 had centralized review of their baseline and 6-month CT scans by a multidisciplinary board. Functional evaluation, radiological scores, clinical toxicities, best objective response, progression-free survival and overall survival were assessed. Results: Twelve cases were detected out of 166 patients (7.2 %), including six diagnosed a posteriori by central review (50 %). Initial patient, tumour and lung cancer treatment characteristics were similar between cases and controls except for performance status (P = 0.004), Kazerooni scores of fibrosis and ground glass patterns (P < 0.001). Cases and controls underwent three-dimensional radiotherapy in 0 and 37 (24.2 %), intensity-modulated radiotherapy in eight (66.7 %) and 60 (39.2 %), stereotactic body radiotherapy in four (33.3 %) and 56 (36.6 %), respectively (P = 0.079). Grade ≥ 2 pneumonitis occurred in 41.7 % of cases versus 11 %, of controls (P = 0.01). Hospitalization rates were 16 % in cases versus 2 % in controls and one case died of lung toxicity. Best objective response was worse for cases (P = 0.046). Median progression-free survival was 9.35 months for cases and 18.56 months for controls. Median overall survival was 17 months for cases and not reached for controls (P = 0.002). Sex, tumour stage, histology, and interstitial pulmonary fibrosis were prognostic factors for overall survival on univariate analysis. Conclusion: Interstitial lung disease was present in 7 % of the patients with lung cancer. Patients with interstitial lung disease had higher risks of toxicity events and poorer prognosis, suggesting the lungs should be assessed carefully and that specific management strategies are warranted.