A Retrospective Study on Predicting Ki-67 Expression in Esophageal Cancer Patients Based on Delta Radiomics

Ki-67 is a pivotal biomarker of tumor proliferative activity in esophageal cancer, yet its clinical application is hindered by reliance on invasive biopsy. Radiomics offers a non-invasive alternative, but conventional methods may be confounded by inter-individual baseline variations. This exploratory study aims to develop a radiomics-based biomarker for predicting Ki-67 expression.

This single-center retrospective study included 59 patients with esophageal cancer. Delta-radiomics features were derived from preoperative CT images by calculating the difference between radiomic features from the tumor and paired normal esophageal tissue. Feature selection (mRMR, k = 3) was nested within leave-one-out cross-validation (LOOCV) to prevent data leakage. A Random Forest model was compared with Logistic Regression and Support Vector Machine across three feature types, five Ki-67 thresholds, and clinical variables. SHAP analysis was used for interpretability.

The Random Forest model achieved an AUC of 0.643 (95% CI: 0.483-0.792). Delta radiomics outperformed esotarget (AUC = 0.546) and eso (AUC = 0.514) models. The combined model (AUC = 0.619) did not outperform delta radiomics alone. SHAP analysis identified GrayLevelVariance and SmallAreaEmphasis as the most influential features.

This exploratory study demonstrates that delta radiomics provides moderate discriminatory performance for predicting Ki-67 expression. External validation in independent multi-center cohorts is required before clinical application.