Systemic Immune–Inflammation Index, Thrombotic Status, and Mortality in Patients with Cancer: A Matched Cohort Study

Background: Cancer-associated thrombosis is a clinically important complication of malignancy. The systemic immune–inflammation index (SII), calculated from platelet, neutrophil, and lymphocyte counts, may reflect the inflammatory background of cancer, but its value in matched heterogeneous cancer cohorts remains unclear. Objective: To evaluate whether SII is associated with thrombotic status and recorded all-cause mortality in patients with solid cancers. Methods: This retrospective matched cohort study was derived from 2020 consecutive adult patients hospitalized with solid malignancies between September 2023 and December 2025 at the Oncology Clinic of University Hospital “Tsaritsa Yoanna—ISUL”, Sofia, Bulgaria. Patients with documented thrombosis were matched 1:2 to non-thrombotic controls using a nearest propensity-score approach, with preference for exact matching on sex and cancer type. The final cohort included 110 thrombotic patients and 220 matched controls. SII was analyzed in relation to thrombotic status and recorded all-cause mortality using logistic regression. Results: Thrombotic patients and controls were well balanced for matching variables. Mortality was similar between groups: 29.1% versus 28.2%. SII did not differ significantly between thrombotic patients and controls: 772 (516–1471) versus 783 (501–1292), p = 0.655, and showed poor discrimination for thrombotic status, with an AUC of 0.515. In the overall matched cohort, higher SII was associated with recorded all-cause mortality after adjustment for thrombotic status, age, sex, cancer type, stage, and metastatic disease: OR 1.31 per 1000-unit increase, 95% CI 1.05–1.64, p = 0.016. The association was numerically stronger among thrombotic patients, but interaction testing was not statistically significant. Conclusions: SII was not associated with thrombotic status in this matched cancer cohort. Higher SII was associated with recorded all-cause mortality, suggesting that SII may better reflect systemic inflammatory burden than cancer-associated thrombosis itself.