BackgroundSensitivity to neoadjuvant chemotherapy in locally advanced gastric cancer patients varies; however, an effective predictive marker is currently lacking. We aimed to propose and validate a practical treatment efficacy prediction method based on contrast-enhanced computed tomography (CECT) radiomics. MethodData of l24 locally advanced gastric carcinoma patients who underwent neoadjuvant chemotherapy were acquired retrospectively between December 2012 and August 2020 from three different cancer centers. In total, 1216 radiomics features were initially extracted from each lesion's pretreatment portal venous phase computed tomography image. Subsequently, a radiomics predictive model was constructed using machine learning software. Clinicopathological data and radiological parameters of the enrolled patients were collected and analyzed retrospectively. Univariate and multivariate logistic regression analyses were performed to screen for independent predictive indices. Finally, we developed an integrated model combining clinicopathological predictive parameters and radiomics features. ResultIn the training set, 10 (14.9%) patients achieved a good response (GR) after preoperative neoadjuvant chemotherapy (n = 77), whereas in the testing set, seven (17.5%) patients achieved a GR (n = 47). The radiomics predictive model showed competitive prediction efficacy in both the training and independent external validation sets. The areas under the curve (AUC) values were 0.827 (95% confidence interval [CI]: 0.609-1.000) and 0.854 (95% CI: 0.610-1.000), respectively. Similarly, when only the single hospital data were included as an independent external validation set (testing set 2), AUC values of the models were 0.827 (95% CI: 0.650-0.952) and 0.889 (95% CI: 0.663-1.000) in the training set and testing set 2, respectively. ConclusionOur study is the first to discover that CECT radiomics could provide powerful and consistent predictions of therapeutic sensitivity to neoadjuvant chemotherapy among gastric cancer patients across different hospitals.