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Combined with traditional radiomic texture features, StODeO showed superior performance in distinguishing pathologic response groups of rectal cancer patients post-chemoradiation (hold-out validation AUC 0.77) as well as segregating composite response groups in a clinical trial of immune checkpoint inhibitors (external validation accuracy 0.71; NCT02688712). The integrated StODeO-texture signature demonstrated robustness across annotation sources and imaging variations, intuitive modeling of therapy-associated structural changes, and statistical associations with tumor-immune biology, including macrophages and CD8+ T-cells from multiplexed biopsy analysis. 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