Impact of Emphysema on Therapeutic Efficacy and Immune-Related Pneumonitis Risk in NSCLC Patients Receiving ICIs: A Meta-Analysis of Improved Survival but Increased Toxicity

Wenjuan Li, Shilan Liu, Xiaodan Yu, Wenyi Lan, Xiao Liu Department of Pulmonary and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, 611130, People’s Republic of ChinaCorrespondence: Xiao Liu, Department of Pulmonary and Critical Care Medicine, Chengdu Fifth People’s Hospital, Chengdu, 611130, People’s Republic of China, Email lxzl111@126.comPurpose: To identify the impact of CT-defined emphysema on efficacy and immune checkpoint inhibitor-related pneumonitis (ICIP) risk among non-small cell lung cancer (NSCLC) patients who receive ICIs.Methods: PubMed, EMBASE, Web of Science and CNKI databases were searched up to January 8, 2025. Primary outcome was the therapeutic efficacy including the progression-free survival (PFS), overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR) and disease control rate (DCR). Second outcome was the ICIP. The hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) were combined.Results: Nine studies with 1076 cases were included. Pooled results demonstrated that the presence of emphysema was significantly associated with improved PFS (HR = 0.43, 95% CI: 0.28– 0.67, P < 0.001), OS (HR = 0.43, 95% CI: 0.25– 0.75, P = 0.003), PR (OR = 2.10, 95% CI: 1.18– 3.75, P = 0.012), PD (OR = 0.60, 95% CI: 0.43– 0.83, P = 0.002) and DCR (OR = 1.48, 95% CI: 1.14– 1.94, P = 0.004). However, emphysema was associated with increased incidence of ICIP (OR = 1.32, 95% CI: 1.15– 1.53, P < 0.001).Conclusion: Based on available evidence, CT-defined emphysema indicates better therapeutic efficacy with longer PFS and OS, but increased risk of ICIP among NSCLC patients receiving ICIs. These findings suggest emphysema may guide personalized immunotherapy decisions in NSCLC.Keywords: non-small cell lung cancer, emphysema, therapeutic efficacy, immune-related pneumonitis, immune checkpoint inhibitors