Interpretable dynamic quantitative vascular morphometry features using SHAP for anti-angiogenic therapy response prediction

Anti-angiogenic therapy benefits vary, with response rates of 40 to 70%, highlighting the need for early biomarkers to identify responders. We developed an automated machine learning framework that uses delta quantitative vascular morphometry features from standard contrast-enhanced CT to evaluate treatment response. This workflow combines automated tumor and vessel segmentation with feature extraction from routine scans for clinical use. Shapley additive explanations (SHAP)-based attributions identify key vascular and clinical features, providing meaningful, imaging-visible evidence aligned with therapy targets beyond traditional radiomics. Using baseline and follow-up CTs from 163 patients with lung cancer, we built three models using fivefold cross-validation, with the delta-merge model achieving high accuracy (area under the receiver operating characteristic curve = 0.842 internally, 0.806 externally). SHAP analysis uncovered an "arterial-dominant, venous-adaptive" pattern, where arterial involvement and venous recovery distinguish responders. This automated workflow and visualization support early, imaging-based response assessment and personalized treatment.