DD MMMM YYYY \acceptedDD MMMM YYYY BackgroundThe prognostic role of systemic inflammation markers in pediatric soft tissue sarcomas (STS) remains unclear. ProcedureThis multicenter study investigated the prognostic significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), C-reactive protein (CRP), and lactate dehydrogenase (LDH) in 213 pediatric patients diagnosed with STS in years 2002-2023. Patients were categorized into groups: rhabdomyosarcoma (RMS, n=126), RMS-like (n=57), and non-RMS (n=30). Clinicopathological data, including complete blood counts (CBCs), CRP, and LDH levels, were collected and age-adjusted. Optimal cutoffs for predicting outcomes were determined, and the prognostic value of the inflammatory markers was assessed using Kaplan-Meier survival analysis, log-rank tests, and Cox regression models. ResultsNo significant differences in NLR, PLR, LMR, and CRP levels were observed between RMS, RMS-like, and non-RMS groups. However, LDH levels were significantly elevated in the RMS group compared to the RMS-like group. A consistent trend toward higher NLR, PLR, and CRP values was noted in patients with more advanced disease stages. Multivariate Cox regression analysis across the entire cohort identified CRP (HR 3.39, 95% CI 1.55-7.4, p=0.002), NLR (HR 2.06, 95% CI 1.07-3.99, p=0.03), and disease stage (HR=0.49, 95% CI 0.26-0.95, p=0.035) as independent prognostic factors for survival. Subgroup analyses revealed that the prognostic impact of these markers varied across histopathological subtypes, with limited utility in the RMS-like group. Conclusions These findings highlight the prognostic value of systemic inflammatory markers in pediatric STS, emphasizing their potential to refine risk assessment and guide treatment.