Novel Radiomic Measurements of Tumor-Associated Vasculature Morphology on Clinical Imaging as a Biomarker of Treatment Response in Multiple Cancers

Abstract

Abstract 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.