Haoxiang Zhang, Ze-Ning Huang, Qiu-Xian Chen, Lei Wang, Feng Chen, Cai-Ming Weng, Yifan Li, Yi Li, Zhi-Wei Liu, Jin-Quan Chen, Qi-Yue Chen, Jia-Bin Wang, Ping- Li, Chao-Hui Zheng, Chang‐Ming Huang, Bin Wang, Li-Sheng Cai, Jian‐Xian Lin, Jian-Wei Xie
Background The clinical efficacy of neoadjuvant immunotherapy combined with chemotherapy (NICT) in patients with locally advanced gastric cancer (LAGC) exhibits considerable variability. In this study, we developed and validated a radiomics-based scoring system to inform personalized neoadjuvant therapy strategies. Methods A retrospective analysis was conducted on a multicenter cohort comprising 633 LAGC patients who underwent neoadjuvant therapy between 2019 and 2023. The primary endpoint was major pathological response (MPR). Radiomic features were extracted and selected from contrast-enhanced CT images obtained before neoadjuvant therapy to construct a radiomics scoring system, which stratified patients into high-, intermediate-, and low-score groups. The therapeutic outcomes across different groups were compared to discern patients who are likely to benefit from NICT as opposed to those who would derive more benefit from neoadjuvant chemotherapy alone (NACT). Additionally, analysis of tumor microenvironment immune infiltration and functional enrichment were performed to explore the potential biological mechanisms underlying the radiomic signatures. Results In the intermediate-score group, the MPR rates were significantly higher among patients receiving NICT compared to those receiving NACT (training set: 49.2% vs. 26.0%, p = 0.005; validation set: 51.6% vs. 19.2%, p = 0.002). In contrast, no significant differences were observed in the high- or low-score groups. The analysis of immune infiltration indicated that the intermediate-score group exhibited significantly higher baseline levels of mast cells and dendritic cells compared to the combined high- and low-score groups ( p < 0.05). Post-treatment evaluation following NICT revealed a significant increase in CD8+ T-cell infiltration relative to baseline levels within the intermediate-score group ( p = 0.033). The gene KRT5 was identified as differentially expressed and correlated with dendritic cell abundance. Conclusion The radiomics scoring system exhibits potential for stratifying patients who may be appropriate candidates for NICT or for whom the de-escalation of immunotherapy might be considered in future prospective studies, thereby contributing to the optimization of neoadjuvant treatment strategies.