Inflammation Mediates Platinum-Based Chemotherapy-Induced Risk of Adverse Cardiac Events in Older NSCLC Patients: A Pilot Study

Background Chemotherapy increases the risk of cardiovascular toxicity, leading to adverse cardiac events (ACEs) in cancer patients. However, the underlying mechanisms and roles of mediators in this association remain poorly understood. Objectives This study aimed to investigate the mediating role of inflammation in the association between platinum-based chemotherapy (PBC) and increased risk of ACEs 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. The treatment group included patients who received PBC, whereas the control group consisted of patients who did not. The mediator was the maximum neutrophil-to-lymphocyte ratio (NLR) measured between initial chemotherapy and one year after diagnosis. The outcome was the occurrence of ACEs during follow-up period. Causal mediation analysis was conducted to assess the mediating effect of inflammation on the PBC–ACE association. Results Among the 1,450 patients included (55% male, 45% female; median age: 61.6 years), 242 (16.7%) developed ACEs during the follow-up. The average direct effect was similar across both groups (control: 0.050, p  = 0.018; treatment: 0.052, p  = 0.018), indicating the consistent direct impact of PBC on the occurrence of ACE. However, the proportion of the total effect mediated by inflammation was higher in the treatment group (11.83%, p  = 0.01) than that in the control group (9.12%, p  = 0.01). Additionally, the average causal mediation effect was greater in the treatment group (0.0067, p  < 0.01) than in the control group (0.0052, p  < 0.001). Conclusions Inflammation plays a crucial role in mediating the association between PBC and increased risk of ACEs in older patients with NSCLC. The mediating effect was more prominent in patients receiving PBC, emphasizing the need to monitor and manage inflammation to mitigate cardiovascular risks in patients with NSCLC undergoing PBC.