Efficacy and Safety of Thoracic Radiotherapy in Locally Advanced Non-Small Cell Lung Cancer Patients With Pre-Existing Interstitial Lung Diseases: A Single Center Experience of 85 Cases

Background: Whether thoracic radiotherapy (TRT) could be applied to interstitial lung diseases and lung cancer(ILD-LC) patients safely remains unclear. This retrospective study aims to evaluate the efficacy and safety of definitive TRT in locally advanced non-small cell lung cancer (LA-NSCLC) patients with pre-existing ILD, and to analyze the associated risk factors for radiation induced lung toxicities (RILTs) in the clinical setting. Methods: Patients with histologically confirmed LA-NSCLC and pre-existing ILD treated definitive TRT between 2010 and 2019 were retrospectively reviewed. Patient, tumor, and treatment characteristics were evaluated to determine the risk factors for RILTs. Pre-radiation CT of all patients were reviewed by two radiologists and one pulmonologist and are scored according to Muller’s thin-section CT scoring system for IPF: 0-no discrete honeycombing, with interlobular septal thickening; 1-honeycombing involving 0-5% of the lobe; 2-honeycombing 6-24%; 3-honeycombing 25-49%; 4-honeycombing 50-74%;5-honeycombing >75%. Univariate and multivariate analyses with logistic regression models and cox proportional hazards approach were performed to identify the risk factor(s) of RILTs and overall survival(OS) respectively. Findings: Among 1261 LA-NSCLC patients, 85 were found with pre-existing ILD and enrolled in the analysis. 36·5% of them were scored more than 1 point on CT. 20% patients developed G3+ RILTs within 1 year after the last irradiation, with remarkably 11·8% dying from lung toxicities. And the incidence of symptomatic (G3+) RILTs abruptly dropped to 11·1%(6/54),3·8%(1/26),and 0%(0/19)for patients with CT score≤1, V20 1 and V20≥20% were independently associated with higher risk of G3+ RILTs. The median OS and PFS were 14·0 months and 7·4 month respectively. In the univariate analysis for OS, clinical stage and G3+RILT were evaluated as risk factors while patients in low-risk group, defined as honeycombing score<1 and V20<20%, had shown a protective tendency(HR=0·52,95%CI:0·27-1·04,P=0·063). In multivariate analysis, G3+RILT was the only independent risk factor associated with OS(HR=2·40,95%CI:1·32-4·36,P=0·004). However, the median OS of low-risk group was quite longer than the whole group (26·5 months versus 14·5 months), indicating that patients at low risk might benefit from thoracic radiation therapy. Interpretation: Honeycombing score >1 and V20≥20% were significantly associated with high incidence of severe lung toxicities, leading to poor survival. However, patients at low risk might benefit from TRT with a considerable overall survival. Funding: None to declare Declaration of Interest: None to declare. Ethical Approval: The study was approved by the institutional review board of National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College (IRB No·NCC2612).