Abstract
BACKGROUND: Current research presents conflicting evidence on whether pre-existing interstitial lung disease (ILD) serves as a risk factor for radiation pneumonitis (RP) and checkpoint inhibitor pneumonitis (CIP) in patients with lung cancer. OBJECTIVES: This study aims to systematically evaluate the impact of pre-existing ILD on the risk of developing RP and CIP in lung cancer patients. DESIGN: A systematic review and meta-analysis was conducted using a random-effects model. DATA SOURCES AND METHODS: PubMed, Embase, and Web of Science were searched to identify relevant studies. A random-effects model was applied to estimate the risk and incidence of RP and CIP in lung cancer patients with pre-existing ILD compared to those without ILD. Sensitivity analyses were performed to assess the robustness of the pooled findings, and potential publication bias was evaluated using Begg's and Egger's tests. RESULTS: A total of 12 studies involving 2576 patients were included in the RP risk assessment, while 29 studies with 8037 patients were analyzed for CIP risk. The pooled results indicated that pre-existing ILD significantly increased the risk of developing any-grade RP (odds ratio (OR): 3.63, 95% confidence interval (CI): 2.26-5.83) and severe RP (OR: 6.10, 95% CI: 2.68-13.86) in lung cancer patients. Subgroup analyses identified stereotactic body radiation therapy as the modality associated with the lowest risk of any-grade RP in these patients. Similarly, pre-existing ILD was associated with a significantly higher risk of any-grade CIP (OR: 3.86, 95% CI: 2.65-5.61) and severe CIP (OR: 3.24, 95% CI: 2.07-5.07), with anti-programmed cell death 1 therapies showing the highest CIP risk. CONCLUSION: Pre-existing ILD markedly increases the risk of both RP and CIP in lung cancer patients. These findings underscore the critical importance of thorough ILD evaluation and the development of personalized treatment strategies to mitigate these risks prior to initiating cancer therapy.