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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)\u2013based 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\u00a0=\u00a00.842 internally, 0.806 externally). SHAP analysis uncovered an \u201carterial-dominant, venous-adaptive\u201d pattern, where arterial involvement and venous recovery distinguish responders. This automated workflow and visualization support early, imaging-based response assessment and personalized treatment.<\/jats:p>","DOI":"10.1126\/sciadv.aeb3543","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:58:33Z","timestamp":1784915913000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Interpretable dynamic quantitative vascular morphometry features using SHAP for anti-angiogenic therapy response prediction"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0918-6310","authenticated-orcid":true,"given":"Kui","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis &amp; Treatment, Wuhan 430074, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5702-7585","authenticated-orcid":true,"given":"Qian","family":"Cai","sequence":"additional","affiliation":[{"name":"Thoracic Inner Department I, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0545-3493","authenticated-orcid":true,"given":"Jia","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Biomedical Engineering, South-Central Minzu University, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7334-0581","authenticated-orcid":true,"given":"Shuangquan","family":"Ai","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1958-7062","authenticated-orcid":true,"given":"Wuling","family":"Ou","sequence":"additional","affiliation":[{"name":"Thoracic Inner Department I, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1887-3769","authenticated-orcid":true,"given":"Yulin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China."},{"name":"Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis &amp; Treatment, Wuhan 430074, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01891"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1366-x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.07.009"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3390\/medsci13030143","article-title":"Combining immune checkpoint inhibitors and anti-angiogenesis approaches: Treatment of advanced non-small cell lung cancer","volume":"13","author":"Barney T.","year":"2025","unstructured":"T. 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