Extracellular volume fraction derived from routine chest dual-energy CT for the characterization of breast tumor: Comparison with apparent diffusion coefficient and validation against histopathological findings

Abstract Background: Tumor aggressiveness and therapeutic response are influenced not only by cancer cells but also by the extracellular matrix in tumor microenvironment, which can be quantified by extracellular volume (ECV) fraction derived from dual-energy CT (DECT). We aimed to investigate the feasibility of using routine chest DECT-derived ECV fraction for the characterization of breast tumor, compared to apparent diffusion coefficient (ADC) and validated against histopathological findings.Methods: The ECV fraction and ADC value were retrospectively assessed in patients with breast tumor using routine chest DECT and breast MRI, respectively. The diagnostic performance in predicting the histopathological characteristics [benign vs. malignant, invasive carcinoma vs. ductal carcinoma in situ (DCIS)], immunohistochemical biomarker status and pathological complete response (pCR) status. Histopathological sections (H&E staining) were analyzed to assess histopathological ECV by digital image analysis. Pearson’s correlation analysis was used to correlate between DECT-derived ECV and histopathological ECV fractions.Results: This study included 271 patients, with 314 breast lesions (61 benign and 253 malignant). The ECV fraction and ADC value showed comparable area under the curve (AUC) for distinguishing benign from malignant lesions (0.777 and 0.822, p = 0.123) and invasive carcinoma from DCIS (0.640 and 0.727, p = 0.115). There were significant differences in ECV fraction between different hormone receptor and Ki67 states (p = 0.001 ~ 0.014), while ADC values only differed among various Ki67 states (p < 0.001). The ECV fraction was lower (p = 0.007), while the ADC value was higher (p = 0.013) in the pCR than in the non-pCR group, with an AUC value of 0.748 and 0.730 (p = 0.887), respectively. There was a positive correlation between DECT-derived ECV and histopathological ECV fractions (r = 0.615, p < 0.01).Conclusions: Routine chest DECT-derived ECV fraction is a viable quantitative imaging biomarker for the characterization of breast tumor.