Prognostic value of the pre-treatment systemic inflammation response index (SIRI) for progression-free survival in EGFR-mutant advanced lung adenocarcinoma.

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Background: Although EGFR-tyrosine kinase inhibitors (TKIs) serve as the cornerstone of treatment for advanced lung adenocarcinoma with sensitizing mutations, predicting long-term therapeutic durability remains challenging. Given the established role of host systemic inflammation in driving malignancy progression and drug resistance, we investigated the baseline Systemic Inflammation Response Index (SIRI) as a potential tool for outcome prediction and risk stratification in these patients. Methods: This retrospective study analyzed 101 patients with EGFR-mutant advanced lung adenocarcinoma receiving first- through third-generation TKIs (January 2022 – December 2025). SIRI was determined using baseline absolute blood counts: (Neutrophils x Monocytes) / Lymphocytes. An optimal threshold was identified via ROC curve analysis. Progression-free survival (PFS) distributions were assessed using Kaplan-Meier estimates. A multivariate Cox proportional hazards model was employed to determine independent prognostic significance, adjusting for performance status, intracranial involvement, TKI type, and mutation patterns. Results: The optimal SIRI cutoff was 2.53 (AUC: 0.651). The cohort’s median PFS was 10.0 months. Patients in the low-SIRI group (≤ 2.53) achieved a significantly superior median PFS compared to those in the high-SIRI group (13.0 vs. 7.0 months; log-rank p = 0.002). Multivariate analysis confirmed that an elevated pre-treatment SIRI independently predicted shorter PFS (Hazard Ratio [HR]: 2.020; 95% CI: 1.251–3.260; p = 0.004). Notably, other clinical parameters, including ECOG status (p = 0.208) and TKI generation (p = 0.206), did not retain independent prognostic weight. Conclusions: Baseline SIRI is a robust, non-invasive, and easily accessible biomarker that independently predicts PFS in patients with advanced lung adenocarcinoma on EGFR-TKI therapy. Incorporating this index into routine clinical evaluation facilitates improved risk stratification and supports more personalized management strategies in the targeted therapy era.

Survival outcomes and multivariate Cox regression analysis (n=101).