367. SPATIAL ORGANIZATION OF TUMOR-INFILTRATING LYMPHOCYTES PREDICTS PROGNOSIS OF PATIENTS WITH ESOPHAGEAL CANCER RECEIVING IMMUNOTHERAPY—A DEEP-LEARNING APPROACH

Abstract

Abstract Background Neoadjuvant immunotherapy plus chemotherapy has shown satisfying efficacy and manageable safety in locally advanced esophageal squamous cell carcinoma (ESCC) patients. Tumor-infiltrating lymphocytes (TILs) have been shown to be associated with the prognosis of various cancer types. It is unknown whether these TILs-associated characteristics can be adopted as a reliable prognostic biomarker for immunotherapy-based regimen. The current study aimed to assess the prognostic power of spatial organization of TILs in patients with advanced ESCC treated with immunochemotherapy. Methods In this retrospective, multicenter cohort study, pathologically confirmed locally advanced ESCC that was potentially resectable after neoadjuvant immunochemotherapy were included. Image segmentation was performed using UNet++ algorithm and H&E-stained nuclei were segmented using the StarDist deep-learning image segmentation. For the nuclei classification task, we choose to train and validate the classic convolutional neural network (CNN) Resnet50. We calculated tumor density and TiLs density in the tumor region (T_TiLs), TILs in the peritumoral region (P_TiLs) as well as TiLs density in the stromal region (S_TiLs). Based on the relative position relationship of tumor cells and lymphocytes, we subclassified the TILs spatial patterns into TILs-dominant, TILs-infiltrating, and TILs-circulating. Results Among the enrolled 86 patients, the male to female ratio approached 4:1. In this study, the mean IoU (mIoU) for nuclei segmentation is 0.9369 and the mean Dice coefficient is 0.9209. The areas under curve (AUC) for lymphocyte, tumor cell, and stromal cells classification are 0.92, 0.90 and 0.86, respectively. Through univariate analysis, TILs in tumor region (HR = 1.285, 95% CI: 1.042–1.586, p = 0.019), and TILs spatial organization (HR = 3.652, 95% CI: 1.216–10.967, p = 0.021) were identified as significant prognostic factors for OS. Multivariate analysis further revealed TILs in tumor region as the independent prognostic factor (HR = 1.248, 95% CI: 1.006–1.547, p = 0.044). Discussion The present study indicates that spatial organization and T_TILs are significant prognostic factors for ESCC patients receiving neoadjuvant immunochemotherapy. Future prospective studies with large sample size are needed to further validate the prognostic role of interaction between TILs spatial characteristic and distribution density in predicting overall survival.