Predicting Stereotactic Body Radiation Therapy Response Using an AI-Based Tumor Vessel Biomarker

Introduction Abnormal tumor vasculature impairs oxygen delivery and induces hypoxia, contributing to treatment resistance and poor prognosis in non-small cell lung cancer (NSCLC). Although radiation therapy can modulate tumor vessels, its effects vary widely due to vascular heterogeneity. Therefore, a reliable and noninvasive method to quantify vascular abnormality is needed to better predict treatment outcomes. Methods We developed a deep learning–based imaging biomarker, the Vessel Risk Score (VRS), to quantify tumor vascular abnormality from contrast-enhanced CT scans. Trained on multi-institutional data from 126 NSCLC patients treated with hypofractionated radiotherapy, the model learned vascular morphology patterns from tumor–vessel images. Using these learned patterns, vascular heterogeneity was quantified as the distributional difference from normal vessel morphology. The generalizability of VRS was then evaluated in an external cohort of 128 early-stage NSCLC patients who underwent stereotactic body radiotherapy (SBRT). Results VRS showed significantly better prediction of SBRT radiation therapy response compared to vessel density. The VRS of the responder group was 0.494 (95% CI: 0.47-0.52), significantly lower than the non-responder group's 0.578 (95% CI: 0.54-0.62). Additionally, patients with high VRS showed significantly shorter PFS compared to those with low VRS (p