Systemic inflammation response index (SIRI) predicts outcomes and chemotherapy benefit in metastatic pancreatic cancer: A study by the PANTHEIA- SEOM group.

BACKGROUND: Systemic inflammation is a key driver of progression in pancreatic ductal adenocarcinoma (PDAC). We aimed to externally validate the Systemic Inflammation Response Index (SIRI) and define its non-linear prognostic value in a large multicenter cohort. METHODS: We analyzed 672 patients with metastatic PDAC receiving first-line chemotherapy across 30 centers. SIRI was assessed using a validated cut-off (>2.3) and as a log-transformed continuous variable in multivariable Weibull accelerated failure-time models with restricted cubic splines. RESULTS: Patients with low SIRI (≤2.3) had longer median OS (14.0 vs 9.2 months; p < 0.001) and PFS (5.9 vs 3.9 months; p < 0.001) than those with high SIRI. High SIRI was associated with a lower objective response rate (25% vs 37%; p < 0.001). In multivariable analyses, higher SIRI independently predicted inferior OS and PFS (75th vs 25th percentile: HR 1.14 [95% CI 1.05-1.25], HR 1.11 [95% CI 1.03-1.21]) and poorer tumor response (OR 0.78; 95% CI 0.62-1.00). Higher SIRI correlated with greater hepatic tumor burden and cachexia. CONCLUSIONS: SIRI is a robust, independent prognostic marker in metastatic PDAC. Higher values identify a phenotype with inferior survival and poorer tumor response. An open-access web calculator is provided to illustrate and explore the nonlinear, continuous prognostic gradient of SIRI and its impact on outcome.