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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.
Zheng et al. (Mon,) studied this question.