Abstract
BACKGROUND: This study aimed to evaluate the survival predictability of preoperative systemic inflammation response index (SIRI), calculated as the absolute neutrophil count multiplied by the absolute monocyte count and divided by the absolute lymphocyte count, in patients with metachronous secondary primary head and neck squamous cell carcinoma (mspHNSCC) who had undergone prior radiotherapy for first primary HNSCC (fpHNSCC). METHODS: A total of 101 consecutive patients who underwent upfront surgery for mspHNSCC at a single institute between 2007 and 2016 were retrospectively reviewed between December 2023 and November 2024 and included in the analysis. The baseline leukocyte counts for the fpHNSCC and mspHNSCC were collected. Cox proportional hazards models were constructed using age and variables significant in univariate analysis to assess the impact of SIRI on overall survival (OS) and cancer-specific survival (CSS). Additionally, a SIRI-based nomogram was developed and validated. RESULTS: Statistically significant declines in baseline leukocyte counts were observed in mspHNSCC compared to fpHNSCC (p < 0.001). Among the inflammatory markers, the preoperative SIRI was the most predictive of survival outcomes for mspHNSCC. Higher SIRI values were significantly associated with poorer outcomes in both OS and CSS. The optimal SIRI cutoff for survival prediction was 1.383, as determined by receiver operating characteristic curve analysis with Youden's index; patients with SIRI ≥ 1.383 had significantly lower 5-year OS (32.9% vs 60.1%, p = 0.001) and CSS (64.7% vs 83.9%, p = 0.003). Multivariate analysis revealed lymphovascular invasion, extranodal extension, and high SIRI as independent adverse risk factors for CSS. The SIRI-based nomogram accurately predicted CSS, with a concordance index of 0.773. CONCLUSION: Data from preoperative SIRI assessment, coupled with the presence of pathological adverse features, serve as valuable references for risk stratification in patients with previously irradiated mspHNSCC.