Development and Implementation of a Novel Composite Immune Score to Predict 5-Year Mortality in Soft Tissue Sarcoma Patients: A Multi-Center, Retrospective Analysis

Abstract Background: Systemic inflammation has been implicated in soft tissue sarcoma (STS) progression and prognosis. This study evaluated whether a composite Immune Score (IS), derived from complete blood count (CBC) biomarkers, could more accurately predict 5-year survival in STS patients compared to individual biomarkers. Methods: We retrospectively reviewed 275 patients with STS treated between 2012 and 2023 at two institutions. CBCs were collected pre-treatment (Period 1) and >4 weeks post-treatment (Period 2). Patients were stratified by disease stage: primary (Instance 1) or advanced (Instance 2+). IS was calculated by assigning quartile-based scores (1–4) to eight inflammatory biomarkers, including white blood cell (WBC) count, red blood cell distribution width (RDW), absolute neutrophil, lymphocyte, and monocyte counts, as well as neutrophil-, monocyte-, and platelet-to-lymphocyte ratios. Following IS stratification, survival and the predictive utility of the IS were analyzed using Kaplan-Meier and receiver operating characteristic (ROC) curves, respectively. Results: Mean IS values were significantly higher in deceased patients than survivors at all examined time points, except during post-treatment surveillance in advanced disease (Instance 2+, Period 2) (p < 0.05). Survival declined stepwise with increasing IS. The IS showed its strongest prognostic value for 5-year survival (AUC = 0.75; cutoff = 2.68) during post-treatment surveillance of primary disease (Instance 1, Period 2), outperforming individual biomarkers. Conclusion: A higher IS, reflecting greater systemic inflammation, was associated with worse long-term survival. The IS demonstrated the strongest predictive value during post-treatment surveillance, supporting its potential utility for risk stratification and guiding follow-up care in STS patients. Level of Evidence: III