A novel prognostic signature combining serum inflammatory cytokines and cell-free telomere length in small cell lung cancer

Background: Small Cell Lung Cancer (SCLC) is a deadly cancer with few reliable prognostic biomarkers. Although systemic inflammation contributes to SCLC progression, no studies have combined cellular senescence biomarkers with inflammatory markers. We proposed that measuring both serum inflammatory cytokines and cell-free telomere length together could improve prognostic accuracy. Methods: We enrolled 187 patients with extensive-stage SCLC before they started first-line chemo-immunotherapy. At baseline, we measured serum levels of IL-6, IL8, TNF-a, CRP, and cell-free telomere length (cfTL). We used Cox regression to create an Inflamm-Ageing Index (IAI). The main outcome was overall survival (OS). Results: High IL-6 (HR 2.14, 95% CI 1.45-3.16, p<0.001) and short cfTL (HR 2.87, 95% CI 1.92-4.29, p<0.001) were each linked to worse overall survival. The IAI grouped patients into low-, intermediate-, and high-risk groups, with median OS of 14.2, 9.1, and 5.3 months, respectively (p<0.001). The IAI stayed an independent predictor after adjusting for other factors (HR 3.42, 95% CI 2.18-5.37, p<0.001) and outperformed individual biomarkers (C-index 0.78). Conclusion: After a median follow-up of 16.8 months and 148 events (79.1%), the Inflamm-Aging Index, which combines inflammatory cytokines and cellular senescence biomarkers, showed promise for risk stratification in extensive-stage SCLC. However, since the biomarker thresholds were set using this cohort, external validation with pre-set cutoffs is needed before clinical use.