Systemic inflammation and aggressive clinical behavior in small cell lung cancer

Abstract

Aims: Small cell lung cancer (SCLC) is characterized by rapid progression, early metastasis, and poor survival outcomes. While its aggressive behavior has traditionally been attributed to near universal genetic alterations, emerging evidence suggests that systemic inflammation and tumor host immune interactions may play a critical role in shaping disease aggressiveness. However, the prognostic significance of multiple inflammation-based biomarkers beyond established clinical factors remains incompletely defined. Methods: In this retrospective cohort study, 104 patients with histologically confirmed SCLC treated between January 2016 and December 2024 were analyzed. Baseline systemic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), Systemic Immune-inflammation Index (SII), Systemic Inflammation Response Index (SIRI), and hemoglobin to red cell distribution width ratio (HGB/RDW), were calculated from peripheral blood samples obtained at diagnosis. Overall survival (OS) and disease-specific survival (DSS) were evaluated using Kaplan Meier analysis and Cox proportional hazards regression models. Multivariable analyses were performed using a clinical base model incorporating age, disease stage, ECOG performance status, and chemotherapy exposure, with inflammatory markers added individually. Results: During follow-up, 67 patients (64.4%) died. In univariate analyses, older age, lack of chemotherapy, and all inflammation based biomarkers were significantly associated with worse OS and DSS. In multivariable analyses, age and chemotherapy status remained independent predictors of OS. When added individually to the clinical base model, higher SII, SIRI, NLR, PLR, and MLR were independently associated with increased risks of both overall and disease-specific mortality, whereas higher HGB/RDW ratios were associated with improved survival. Kaplan Meier analyses demonstrated significantly poorer OS and DSS in patients with high NLR values compared with those with low NLR (log-rank p<0.001 for both). Conclusions: Multiple inflammation-based biomarkers were significantly associated with both OS and DSS in patients with SCLC. These associations remained evident after adjustment for established clinical prognostic factors, suggesting that systemic inflammation may provide additional prognostic information beyond conventional clinical variables. The consistent associations observed across several inflammatory indices support their potential utility in risk stratification. Further prospective studies are warranted to validate these findings and clarify the biological mechanisms underlying these associations.