Granzyme B PET/CT predicts chemo-immunotherapy outcomes in microsatellite stable gastric cancers.

Abstract

Prognostic stratification for microsatellite stable (MSS) gastric cancer (GC) remains challenging. This study evaluated the predictive and prognostic value of [⁶⁸Ga]Ga-NOTA-GSI PET/CT imaging in a large cohort of MSS GC patients receiving chemo-immunotherapy. In this retrospective study, 145 patients with MSS GC underwent [⁶⁸Ga]Ga-NOTA-GSI PET/CT after two or three cycles of chemo-immunotherapy. Measurements included SUVmax, SUVmean, GSI tumor volume (GSI-TV), total lesion uptake (TLU), tumor-liver ratio (TLR), and tumor-blood ratio (TBR). The study analyzed associations between short-term treatment response (RECIST 1.1 or tumor regression grade score) and progression-free survival (PFS) using receiver operating characteristic (ROC) curves, logistic regression, and Cox proportional hazards models. Responders exhibited significantly higher uptake of [⁶⁸Ga]Ga-NOTA-GSI than non-responders, including SUVmax, sumSUVmax, and TBR (all P < 0.05) across all patients and various subgroups, while volumetric parameters (GSI-TV, TLU) showed no notable difference. SUVmax was a reliable predictor of response (AUC = 0.755 for all patients; AUC = 0.882 for the neoadjuvant subgroup). In survival analysis, an SUVmax ≥ 2.6 independently predicted significantly longer PFS (median PFS of 14.0 vs. 9.0 months; hazard ratio, 0.673; P = 0.016). The study highlighted the significant value of [⁶⁸Ga]Ga-NOTA-GSI PET/CT in assessing the effectiveness of chemo-immunotherapy and predicting outcomes in MSS gastric cancer patients. Subgroup analysis confirmed its reliable predictive power across neoadjuvant, palliative, and adjuvant treatments, supporting the potential for its broad clinical application.