Abstract
BACKGROUND: Opportunistic fungal infections represent a serious treatment-related complication in patients with advanced non-small cell lung carcinoma (NSCLC) undergoing chemotherapy, closely associated with treatment intensity-induced immunosuppression. OBJECTIVES: To investigate the influence of relative dose intensity (RDI) of first-line platinum-based doublet chemotherapy on the risk of invasive fungal infection (IFI) in patients with stage IIIB-IV NSCLC and its underlying mechanisms. METHODS: A total of 195 patients with stage IIIB-IV NSCLC who received first-line platinum-based doublet chemotherapy between January 2022 and December 2025 were enrolled. Based on the average RDI of chemotherapy, patients were categorized into high-intensity (RDI > 85%, n = 68), standard-intensity (RDI 70%-85%, n = 74), and low-intensity (RDI < 70%, n = 53) groups. Data on the incidence of IFI, febrile neutropenia (FN), infection-related progression-free survival (irPFS), nadir absolute neutrophil count (ANC nadir), duration of profound neutropenia, total infection-related hospitalization days, rate of empirical antifungal use, and overall survival (OS) were retrospectively collected and compared among the three groups. RESULTS: The incidence of IFI was higher in the high-intensity group than in the low-intensity group (χ(2) = 15.837, P < 0.001). Multivariate Cox regression analysis indicated that high-intensity chemotherapy was independently associated with an increased risk of IFI compared with low-intensity chemotherapy (HR = 8.241, P = 0.005). The incidence of FN was higher in the high-intensity group than in the low-intensity group (χ(2) = 7.892, P = 0.019). The duration of infection-related hospitalization was longer in the high-intensity group than in the low-intensity group (H = 19.037, P < 0.001). The rate of empirical antifungal use was higher in the high-intensity group than in the low-intensity group (χ(2) = 13.275, P = 0.001). A significant difference in irPFS was observed among the three groups (Log-rank χ(2) = 11.524, P = 0.003), while no significant difference was found in OS (Log-rank χ(2) = 2.137, P = 0.344). Mediation analysis suggested that ANC nadir partially mediated the effect of chemotherapy intensity on IFI risk. CONCLUSION: In patients with advanced NSCLC, high relative dose intensity of first-line chemotherapy is independently associated with an increased risk of invasive fungal infection. This association is partly mediated by treatment-induced myelosuppression and is accompanied by a significant increase in clinical burden.