Patient-derived organoids support radiotherapy response and recurrence risk prediction in esophageal squamous cancer

Predicting individual responses to radiotherapy remains a major challenge in esophageal cancer. This study evaluated an cancer organoid-based diagnosis and reactivity prediction (CODRP) approach to estimate pathological response and recurrence risk after neoadjuvant chemoradiotherapy (NCRT) in esophageal squamous cell carcinoma. Organoids were established from endoscopic biopsy specimens and irradiated with doses of 2, 4, or 8 Gy. Growth inhibition-based area under the curve (GI-AUC) and cell growth rates were quantified and integrated with the clinical cancer stage to generate the CODRP index. Compared with single-parameter models, the CODRP showed improved apparent predictive performance for pathological response prediction in this feasibility cohort (sensitivity, 87.5%; specificity, 100%). Recurrence-free survival was significantly higher in the CODRP-classified radiation-sensitive group (71.43%) than in the radiation-resistant group (10%) (p = 0.0103). These findings support the feasibility of applying CODRP to radiotherapy response and recurrence risk prediction in esophageal squamous cell carcinoma.