Systemic inflammation is associated with inferior disease control and survival in stage III non-small cell lung cancer

BACKGROUND: The systemic immune-inflammation index (SII) correlates with patient survival in various types of solid malignancies, including non-small cell lung cancer (NSCLC). However, limited information is available on the prognostic implication and disease-specific survival of SII in patients undergoing definitive chemoradiation therapy (CRT) for stage III NSCLC. METHODS: We retrospectively reviewed 125 patients who underwent curative intent CRT for stage III NSCLC with sufficient laboratory assessment from 2010–2019. SII was calculated at the time of diagnosis as platelet count × neutrophil count/lymphocyte count. Chi-squared analysis was used to compare categorical variables. A Kaplan-Meier analysis was performed to estimate progression-free survival (PFS), disease specific survival (DSS), and overall survival (OS) rates, with Cox regression used to determine absolute hazards. RESULTS: At a median follow-up of 19.7 months, 5-year OS, DSS, and PFS rates were 22.6%, 30.9%, and 13.4%, respectively. A low SII (<1,266) at diagnosis was independently associated with an improved OS (HR: 0.399, 95%, CI: 0.247–0.644, P<0.001), DSS (HR: 0.383, 95%, CI: 0.228–0.645, P<0.001), and PFS (HR: 0.616, 95%, CI: 0.407–0.932, P=0.022). We did not detect an association between SII and freedom from recurrence (FFR), freedom from locoregional recurrence (FFLRR), or freedom from distant recurrence (FFDR). NSAID (1,483.4 vs. 2,302.9, P=0.038) and statin usage (1,443.9 vs. 2,201.7, P=0.046) were associated with a lower SII while COPD exacerbations (2,699.7 vs. 1,573.7, P=0.032) and antibiotic prescriptions (2,384.6 vs. 1,347.9, P=0.009) were associated with an elevated SII. These factors were not independently associated with improved survival outcomes. CONCLUSIONS: Low SII scores were independently associated with improved OS, DSS, and PFS rates in patients with stage III NSCLC undergoing definitive CRT. NSAIDs and statin usage may be associated with lower SII at diagnosis of NSCLC. This study suggests that SII may be an effective prognostic indicator of patient mortality. Further investigation of the therapeutic potential of these agents in patients with an elevated SII in this setting may be warranted.