Associations of baseline [18F]FDG PET/CT metabolic parameters with the efficacy of neoadjuvant immunotherapy plus concurrent chemoradiotherapy in patients with locally advanced gastric adenocarcinoma: a post hoc analysis of the Neo-PLANET phase II tr

Although perioperative immunotherapy has shown promising results in locally advanced gastric adenocarcinoma (LAGA), the predictive biomarkers remain unclear. Our study aimed to investigate the predictive value of [18F]FDG PET/CT characteristics at baseline for the efficacy of neoadjuvant immunotherapy plus concurrent chemoradiotherapy in the post hoc analysis of the Neo-PLANET phase II trial. A total of 29 patients with LAGA receiving neoadjuvant immunotherapy plus concurrent chemoradiotherapy from the Neo-PLANET phase II trial (Zhongshan Hospital Fudan University, NCT03631615, 2018-08-13) were included in our study. Semiautomated techniques were used to analyze pre-operative [18F]FDG PET/CT images to determine primary tumor, nodal metabolic and spleen parameter scores [including max and mean adjusted for lean body mass standardized uptake values (SUV), metabolic tumour volume (MTV) and total lesional glycolysis (TLG)]. Kaplan–Meier method and log-rank test to evaluate the associations between PET/CT parameters and disease-free survival (DFS) and overall survival (OS). Pathological complete response (pCR) and major pathological response (mPR) were not related to DFS and OS in patients receiving neoadjuvant immunotherapy plus concurrent chemoradiotherapy. Interestingly, a higher SUVmean of the spleen (S-SUVmean) is positively associated with longer DFS (HR = 0.19, 95%CI: 0.037–0.94, p = 0.042) and OS (HR = 0.12, 95%CI: 0.016–0.83, p = 0.032). This association is linked to an increased combined positive score of PD-L1. Tumor size assessed by length (HR = 9.03, 95%CI: 1.77–46.14, p = 0.0082), width (HR = 9.65, 95%CI: 1.75–53.39, p = 0.0094), radius vector (HR = 9.65, 95%CI: 1.75–53.4, p = 0.0094) and MTV (HR = 4.53, 95CI: 1.09–70.33, p = 0.042) were significantly associated with shorter DFS, but not OS. When S-SUVmean and mPR were combined, GC patients with higher S-SUVmean or mPR showed both significant survival benefit in DFS (HR = 0.09, 95%CI 0.014-0.60, p = 0.013) and OS (HR = 0.08, 95%CI: 0.0087-0.74, p = 0.026). Our study suggests that S-SUVmean may be a valuable indicator for the DFS and OS of neoadjuvant immunotherapy in LAGA, highlighting the importance of “Tumor-Spleen Immunity Cycle”. These findings need to be validated in a large population. Studies have shown that [18F]FDG PET metabolic parameters may serve as predictive biomarkers for early pathological responses and survival benefit of ICI therapy, but no evidence was reported in gastric cancer. S-SUVmean was significantly associated with both disease-free survival and overall survival. Our study specifically focuses on the role of spleen-related parameters in the context of neoadjuvant immunotherapy for LAGA. This adds a new dimension to our understanding of the“Tumor-Spleen Immunity Cycle”in the predictive value for immunotherapy.