Assessment of Early Tumor Response to Cytotoxic Chemotherapy with Dynamic Contrast-Enhanced Ultrasound in Human Breast Cancer Xenografts

Abstract

There is a strong need to assess early tumor response to chemotherapy in order to avoid adverse effects from unnecessary chemotherapy and allow early transition to second-line therapy. This study was to quantify tumor perfusion changes with dynamic contrast-enhanced ultrasound (CEUS) in the evaluation of early tumor response to cytotoxic chemotherapy. Sixty nude mice bearing with MCF-7 breast cancer were administrated with either adriamycin or sterile saline. CEUS was performed on days 0, 2, 4 and 6 of the treatment, in which time-signal intensity (SI) curves were obtained from the intratumoral and depth-matched liver parenchyma. Four perfusion parameters including peak enhancement (PE), area under the curve of wash-in (WiAUC), wash-in rate (WiR) and wash-in perfusion index (WiPI) were calculated from perfusion curves and normalized with respect to perfusion of adjacent liver parenchyma. Histopathological analysis was conducted to evaluate tumor perfusion, tumor cell density, microvascular density (MVD) and proliferating cell density. Significant decreases of tumor normalized perfusion parameters (i.e., nPE, nWiAUC, nWiR and nWiPI) were noticed between adriamycin-treated and control groups (P<0.01) 2 days after therapy. There were significant differences of tumor volumes between control and treated groups on day 6 (P<0.001) while there were no significant differences in tumor volume on days 0, 2 and 4 (P>0.05). Significant decreases of tumor perfusion, tumor cell density, MVD and proliferating cell density were seen in adrianycin-treated group 2 days after therapy when compared to control group (P<0.001). Dynamic CEUS for quantification of tumor perfusion could be used for early detection of cancer response to cytotoxic chemotherapy prior to notable tumor shrinkage.

Early prediction of tumor response to bevacizumab treatment in murine colon cancer models using three-dimensional dynamic contrast-enhanced ultrasound imaging

“…Over the past decade, DCE-US has been increasingly investigated in preclinical [24,26,27] and clinical [28,29] studies to depict therapy induced changes in tumor perfusion. However, a major drawback of conventional DCE-US to date is its limitation to 2D, which results in limited perfusion assessments to a single 2D plane, and results in longitudinal sampling errors.…”

“…[19,22]. The following perfusion parameters were calculated as previously described [9,23,24] from the fitted TIC [22]: peak enhancement (PE, arbitrary units, a.u. ), area under the curve (AUC, a.u.…”

New clinical research strategies in thoracic oncology: clinical trial design, adaptive, basket and umbrella trials, new end-points and new evaluations of response

“…Dynamic contrast enhancing ultrasound provides both morphological and functional perfusion data [57]. It helps evaluate lymph node vascularity and perfusion, and might help in assessing early tumour response [58,59].…”

Contrast-Enhanced Ultrasound for Early Prediction of Response of Breast Cancer to Neoadjuvant Chemotherapy

“…The reason for performing the second CEUS examination after the first cycle was that prediction of the response at an early time point is important for treatment modification in non-responders [3,4]. Several studies have evaluated the ability of CEUS to predict early response to NAC [20][21][22][23][24][25]. CEUS is superior to conventional imaging methods when measuring angiogenic changes as an indicator of response.…”