Treatment Toxicity and Outcomes Following Definitive Radiation Therapy for Patients With Early-Stage Non-Small Cell Lung Cancers and Pre-Existing Interstitial Lung Disease—A Systematic Review and Dosimetric Analysis

Background: Patients with interstitial lung disease (ILD) who develop lung cancer represent a unique challenge, as they are at higher risk for serious toxicity from local and systemic therapies. The aim of this study is to provide an up-to-date analysis on toxicities and outcomes associated with definitive radiation therapy (RT) in patients with ILD and early-stage non-small cell lung cancer (ES-NSCLC). Methods and Materials: We performed a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed (MEDLINE), EMBASE, and Cochrane Library databases were searched from inception until June 2024, for studies including patients with ILD who underwent definitive RT alone for ES-NSCLC. Data including treatment-related mortality, toxicity, local control, and overall survival were collected and analyzed. Results: Of 3545 records reviewed, 24 studies were identified for full data abstraction, contributing a total of 705 patients. A specific ILD subtype was not reported for 71% (n = 502) of patients. ILD severity was not reported for 62% (n = 440) of patients. Risk of treatment-related mortality was 7.9%, with severe treatment-related respiratory toxicity 15.7%. A higher volume of lung receiving ≥5 Gy (V5) was significantly correlated with mortality. The estimated local control at 3 year was 76% and median overall survival was 2.5 years. Conclusions: The relative merits of RT for the treatment of ES-NSCLC in patients with ILD should be considered in the context of the rates of treatment-related mortality and toxicity. Future studies would benefit from consistent reporting of ILD characteristics, which may help in risk stratification in this challenging clinical scenario.