The mediating role of inflammation in the association between platinum-based chemotherapy and cardiovascular adverse events in older non-small cell lung cancer patients.

Abstract

e20026 Background: Chemotherapy increases the risk of cardiovascular toxicity, leading to cardiovascular adverse events (CVAE) in cancer patients. However, the underlying mechanisms and the role of mediators in this association remain poorly understood. This study aims to investigate the mediating role of inflammation in the association between platinum-based chemotherapy (PBC) and the increased risk of CVAE in older patients with non-small cell lung cancer (NSCLC). Methods: We retrospectively analyzed data from NSCLC patients aged ≥50 years, initially diagnosed between 2018 and 2020 at our institution. All patients were free from prior cardiovascular events and received at least one documented treatment within a year of diagnosis. The treatment group included patients who received PBC, while the control group consisted of those who did not receive PBC. The mediator was defined as the maximum Neutrophil-to-Lymphocyte ratio (NLR) measured between the initial chemotherapy and one year after diagnosis. The outcome was the occurrence of CVAE during follow-up. Causal mediation analysis was employed to explore the mediation effect of inflammation in the PBC-CVAE relationship. Results: A total of 1,472 patients (55% male, 45% female) were included, with a median age at diagnosis of 61.6 years (IQR [56.2, 66.6]). Of these, 245 (16.6%) developed CVAE during follow-up. After adjusting for covariates (e.g., demographics, baseline NLR, and medical history), causal mediation analysis revealed significant mediation effects in both the treatment and control groups. The average direct effect (ADE) was similar across both groups (control: 0.048, p = 0.016; treatment: 0.050, p = 0.016), indicating a consistent direct impact of PBC on CVAE occurrence. However, the proportion of the total effect mediated by inflammation was higher in the treatment group (12.67%, p = 0.008) than in the control group (9.88%, p = 0.008). Additionally, the average causal mediation effect (ACME) was stronger in the treatment group (0.007, p < 0.001) compared to the control group (0.005, p < 0.001). Conclusions: Inflammation plays a crucial role in mediating the association between PBC and the increased risk of CVAE in older NSCLC patients. The mediating effect is more prominent in patients receiving PBC, emphasizing the need for monitoring and managing inflammation to mitigate cardiovascular risks in NSCLC patients undergoing PBC. Estimate 95% CI Lower 95% CI Upper pvalue ACME (Ctrl) 0.00543 0.00162 0.01 <2e-16 ACME (Tx) 0.00696 0.00213 0.01 <2e-16 ADE (Ctrl) 0.04797 0.00721 0.09 0.016 ADE (Tx) 0.04950 0.00757 0.09 0.016 Total Effect 0.05492 0.01558 0.09 0.008 Prop. Mediated (Ctrl) 0.09878 0.02176 0.51 0.008 Prop. Mediated (Tx) 0.12668 0.03092 0.54 0.008 ACME (Avg.) 0.00619 0.00188 0.01 <2e-16 ADE (Avg.) 0.04873 0.00741 0.09 0.016 Prop. Mediated (Avg.) 0.11273 0.02628 0.52 0.008