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.
Highlights
Cancer treatment is a great challenge for medical research and clinical practice
It was noticed that contrast-enhanced ultrasound (CEUS) demonstrated a reduction of tumor perfusion 2 days after treatment which was 4 days earlier before the difference of tumor sizes became measurable by conventional imaging
At day 6, changes in the four normalized perfusion parameters measured by CEUS well correlated with the tumor volume change
Summary
Chemotherapy is still one of the most important methods for cancer treatment, in which more than half of all patients with malignant tumors receive chemotherapy. The criteria most commonly used to assess the effectiveness of chemotherapy is the Response Evaluation Criteria in Solid Tumor(RECIST)which have become widely applicable in clinical oncological trials since it was published in 2000 [2]. It is useful protocol for estimating tumor response to chemotherapy based on morphologic changes, the RECIST has some disadvantages and limitations by using morphologic imaging methods. It is critical to develop functional imaging techniques to better monitor tumor response to cytotoxic chemotherapy, which overcome the limitation of current criteria based on measurement of tumor size [1]
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