An integrated SII-PNI immune-nutritional scoring system predicts efficacy and immune-related adverse events in locally advanced gastric cancer patients undergoing neoadjuvant immunotherapy.

BACKGROUND

Immune checkpoint inhibitors (ICIs) have transformed treatment of locally advanced gastric cancer (LAGC), yet response heterogeneity and immune-related adverse events (irAEs) remain major challenges. Systemic inflammation and nutritional status critically modulate antitumor immunity. This study evaluated the dual predictive value of a combined Systemic Immune-Inflammation Index and Prognostic Nutritional Index (SII-PNI) score for therapeutic efficacy and safety in LAGC patients receiving neoadjuvant PD-1/PD-L1 inhibitor-based therapy.

METHODS

We retrospectively analyzed 276 LAGC patients who received PD-1/PD-L1 inhibitor-based neoadjuvant immunotherapy (January 2019-December 2021). Blood samples were collected within 7 days before treatment initiation. Optimal cut-off values for SII and PNI were determined via ROC analysis to construct the SII-PNI score (Score 0-2). Primary endpoints were disease-free survival (DFS), overall survival (OS), tumor response (RECIST 1.1), and irAE incidence.

RESULTS

The optimal cut-off values were 736.2 for SII and 48.5 for PNI. Patients with a high SII-PNI score (Score 2) exhibited significantly poorer objective response rates (ORR) compared to the low-risk Score 0 group (22.6% vs. 71.2%, P < 0.001). The SII-PNI score demonstrated superior predictive accuracy for immunotherapy response (AUC = 0.750) compared to PD-L1 CPS (AUC = 0.711) and Tumor Mutational Burden (TMB, AUC = 0.625). Multivariate Cox analysis identified the SII-PNI score as an independent prognostic factor; compared to Score 0, patients with Score 2 faced a more than threefold increased risk of disease recurrence (HR = 3.45, 95% CI: 2.40-4.95, P < 0.001) and mortality (HR = 3.15, 95% CI: 1.85-5.36, P < 0.001). Furthermore, the high-risk group (Score 2) had a significantly higher incidence of severe (Grade 3-4) irAEs compared to the low-risk group (28.6% vs. 3.6%, P < 0.001).

CONCLUSIONS

The SII-PNI score is a robust, non-invasive, and economically accessible biomarker that effectively stratifies outcomes in gastric cancer patients receiving neoadjuvant immunotherapy. It serves as a dual predictor for both poor therapeutic response and increased toxicity, outperforming traditional biomarkers like PD-L1 CPS. This scoring system holds promise for guiding personalized treatment strategies and optimizing patient selection.