{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T02:28:08Z","timestamp":1786328888108,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Victor Babes University of Medicine and Pharmacy Timisoara"},{"id":[{"id":"https:\/\/ror.org\/00afdp487","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Early identification of breast cancer patients unlikely to benefit from neoadjuvant chemotherapy (NAC) remains a pressing clinical problem because ineffective therapy delays definitive surgery and exposes patients to unnecessary toxicity. Quantitative ultrasound (QUS) and shear wave elastography (SWE) probe complementary tissue properties\u2014scatterer microstructure and mechanical stiffness\u2014that may change before macroscopic tumor shrinkage. This study aimed to evaluate whether multi-parametric ultrasound (mpUS) radiomic kinetics, analyzed with a machine learning ensemble and interpreted with SHAP, could predict pathologic response to NAC. Methods: A prospective observational cohort enrolled 135 women with biopsy-proven stage II\u2013III breast cancer treated with NAC within the multidisciplinary breast pathway shared between Vasile Goldis Western University of Arad and Victor Babes University of Medicine and Pharmacy Timisoara (Pius Brinzeu County Emergency Hospital). All patients underwent standardized QUS and SWE acquisitions at baseline, week 1, and week 3. Response was defined pathologically at surgery as residual cancer burden (RCB) class 0\/I versus II\/III. Group comparisons used Welch\u2019s t-test, Mann\u2013Whitney U, chi-square, and Fisher\u2019s exact tests; correlations used Spearman\u2019s rho. A stacked machine learning ensemble (four base learners\u2014XGBoost, random forest, support vector machine, and L2-penalized logistic regression\u2014combined by a separate second-stage logistic meta-learner) was trained with nested 10-fold cross-validation, bootstrap stability assessment, SHAP-based interpretability, and decision curve analysis. Results: Sixty patients (44.4%) were responders and 75 (55.6%) were non-responders. Responders showed greater week 3 increases in mid-band fit (3.4 \u00b1 0.9 vs. 1.2 \u00b1 0.8 dB, p &lt; 0.001), entropy (0.7 \u00b1 0.2 vs. 0.2 \u00b1 0.2, p &lt; 0.001), and more pronounced SWE mean stiffness reduction (\u221244.1 \u00b1 9.7 vs. \u221212.1 \u00b1 8.6 kPa, p &lt; 0.001). The stacked ensemble integrating clinical, QUS, and SWE kinetic features reached an AUC of 0.93 (95% CI 0.88\u20130.97) versus 0.71 for the clinical-only model (all reported performance figures represent internal cross-validation only). SHAP analysis identified \u0394 MBF and \u0394 entropy at week 3 as the dominant features, with high bootstrap stability. Conclusions: Multi-parametric ultrasound radiomic kinetics integrated through a machine learning ensemble may provide an interpretable early-response biomarker for NAC in breast cancer, pending external validation.<\/jats:p>","DOI":"10.3390\/diagnostics16162504","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:20:03Z","timestamp":1786324803000},"page":"2504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Parametric Ultrasound Radiomic Kinetics with Machine Learning Ensemble for Early Prediction of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer"],"prefix":"10.3390","volume":"16","author":[{"given":"Ramona","family":"Putin","sequence":"first","affiliation":[{"name":"Doctoral School, Faculty of Medicine, Vasile Goldis Western University of Arad, 310414 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Stanga","sequence":"additional","affiliation":[{"name":"Discipline of Microbiology, Faculty of Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8619-0479","authenticated-orcid":false,"given":"Ciprian Ilie","family":"Ro\u0219ca","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I\u2014Medical Semiotics II, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7896-1253","authenticated-orcid":false,"given":"Horia Silviu","family":"Branea","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I\u2014Medical Semiotics II, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian Cosmin","family":"Ilie","sequence":"additional","affiliation":[{"name":"Department of Functional Sciences, Discipline of Public Health, Center for Translational Research and Systems Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Tanase","sequence":"additional","affiliation":[{"name":"Department of Professional Legislation in Dental Medicine, Faculty of Dental Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"},{"name":"Research Centre in Dental Medicine Using Conventional and Alternative Technologies, Faculty of Dental Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coralia","family":"Cotoraci","sequence":"additional","affiliation":[{"name":"Doctoral School, Faculty of Medicine, Vasile Goldis Western University of Arad, 310414 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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