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Purpose: The tumor-associated vasculature (TAV) differs from healthy blood vessels by its convolutedness, leakiness, and chaotic architecture, and these attributes facilitate the creation of a treatment-resistant tumor microenvironment. Measurable differences in these attributes might also help stratify patients by likely benefit of systemic therapy (e.g., chemotherapy). In this work, we present a new category of computational image-based biomarkers called quantitative tumor-associated vasculature (QuanTAV) features, and demonstrate their ability to predict response and survival across multiple cancer types, imaging modalities, and treatment regimens involving chemotherapy.
Experimental Design: We isolated tumor vasculature and extracted mathematical measurements of twistedness and organization from routine pretreatment radiology (CT or contrast-enhanced MRI) of a total of 558 patients, who received one of four first-line chemotherapy-based therapeutic intervention strategies for breast (n = 371) or non-small cell lung cancer (NSCLC, n = 187).
Results: Across four chemotherapy-based treatment strategies, classifiers of QuanTAV measurements significantly (P < 0.05) predicted response in held out testing cohorts alone (AUC = 0.63-0.71) and increased AUC by 0.06-0.12 when added to models of significant clinical variables alone. Similarly, we derived QuanTAV risk scores that were prognostic of recurrence-free survival in treatment cohorts who received surgery following chemotherapy for breast cancer [P = 0.0022; HR = 1.25; 95% confidence interval (CI), 1.08-1.44; concordance index (C-index) = 0.66] and chemoradiation for NSCLC (P = 0.039; HR = 1.28; 95% CI, 1.01-1.62; C-index = 0.66). From vessel-based risk scores, we further derived categorical QuanTAV high/low risk groups that were independently prognostic among all treatment groups, including patients with NSCLC who received chemotherapy only (P = 0.034; HR = 2.29; 95% CI, 1.07-4.94; C-index = 0.62). QuanTAV response and risk scores were independent of clinicopathologic risk factors and matched or exceeded models of clinical variables including posttreatment response.
Conclusions: Across these domains, we observed an association of vascular morphology on CT and MRI-as captured by metrics of vessel curvature, torsion, and organizational heterogeneity-and treatment outcome. Our findings suggest the potential of shape and structure of the TAV in developing prognostic and predictive biomarkers for multiple cancers and different treatment strategies.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9588630 | PMC |
http://dx.doi.org/10.1158/1078-0432.CCR-21-4148 | DOI Listing |
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