Longitudinal Trajectories of Hematologic Inflammatory Markers and Their Prognostic and Mediating Roles in Nasopharyngeal Carcinoma: A Multi-institutional Cohort Study

Objective.: To examine the longitudinal trajectories of hematologic inflammatory markers and their prognostic and mediating roles in nasopharyngeal carcinoma (NPC). Methods.: This retrospective cohort study used group-based trajectory modeling (GBTM) on 1,867 NPC patients in Taiwan across three time points during radiotherapy. Results.: A high-inflammation systemic immune-inflammation index (SII), calculated from platelet, neutrophil, and lymphocyte counts on routine blood tests (platelet × neutrophil / lymphocyte), trajectory (3.4% of patients) independently predicted poorer overall survival (adjusted HR, 1.89) and greater odds of disease persistence (adjusted OR, 2.09). Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) trajectories were not significantly associated with outcomes. Disease persistence mediated 14.7% of the total survival effect of SII. Conclusion.: In this exploratory analysis, high-inflammation SII trajectories were associated with inferior survival and increased residual disease risk in NPC. However, as SII was not associated with recurrence and disease persistence explained only a small proportion of the survival association, the pathway linking SII to survival remains unclear and warrants prospective investigation.