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Assessment of early tumor response to cytotoxic chemotherapy with dynamic contrast-enhanced ultrasound in human breast cancer xenografts.

Wang JW, Zheng W, Liu JB, Chen Y, Cao LH, Luo RZ, Li AH, Zhou JH - PLoS ONE (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Department of Ultrasound, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.

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.

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Related in: MedlinePlus

US image of a subcutaneous MCF7 breast cancer tumor.A, US scan showed gray-scale ultrasound image of tumor (T) adjacent to the right lobe of the liver (L). B, CEUS shows enhancement of normal liver parenchyma and tumor. Measurements obtained from one ROI drawn on the tumor (green ROI) and one drawn at matched depth in liver parenchyma (yellow ROI).
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pone-0058274-g001: US image of a subcutaneous MCF7 breast cancer tumor.A, US scan showed gray-scale ultrasound image of tumor (T) adjacent to the right lobe of the liver (L). B, CEUS shows enhancement of normal liver parenchyma and tumor. Measurements obtained from one ROI drawn on the tumor (green ROI) and one drawn at matched depth in liver parenchyma (yellow ROI).

Mentions: All datasets were transferred to a commercially available computer workstation (SonoTumor software, Bracco Research SA, Geneva, Switzerland). A region of interest (ROI) that drawn along the margin of the tumor and a ROI at matched depth in the region of the right lobe of the liver parenchyma were selected by one investigator (J.W.W., with 3 years experience in contrast-enhanced ultrasound) who was blind to the treatment information (Figure 1). The selected ROI was automatically positioned by the software on subsequent images, with minor adjustments to correct for respiratory motion when necessary. The analysis applies first linearization at the pixel level to revert the effects of “log” compression in the ultrasound system. Results obtained from the selected ROI represented an approximately linear depiction of the backscattered intensity. The average of the linearized intensities of all the pixels in the ROI was calculated to produce a time-signal intensity curve, where the intensity is theoretically linked to microbubble concentration [13].


Assessment of early tumor response to cytotoxic chemotherapy with dynamic contrast-enhanced ultrasound in human breast cancer xenografts.

Wang JW, Zheng W, Liu JB, Chen Y, Cao LH, Luo RZ, Li AH, Zhou JH - PLoS ONE (2013)

US image of a subcutaneous MCF7 breast cancer tumor.A, US scan showed gray-scale ultrasound image of tumor (T) adjacent to the right lobe of the liver (L). B, CEUS shows enhancement of normal liver parenchyma and tumor. Measurements obtained from one ROI drawn on the tumor (green ROI) and one drawn at matched depth in liver parenchyma (yellow ROI).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585723&req=5

pone-0058274-g001: US image of a subcutaneous MCF7 breast cancer tumor.A, US scan showed gray-scale ultrasound image of tumor (T) adjacent to the right lobe of the liver (L). B, CEUS shows enhancement of normal liver parenchyma and tumor. Measurements obtained from one ROI drawn on the tumor (green ROI) and one drawn at matched depth in liver parenchyma (yellow ROI).
Mentions: All datasets were transferred to a commercially available computer workstation (SonoTumor software, Bracco Research SA, Geneva, Switzerland). A region of interest (ROI) that drawn along the margin of the tumor and a ROI at matched depth in the region of the right lobe of the liver parenchyma were selected by one investigator (J.W.W., with 3 years experience in contrast-enhanced ultrasound) who was blind to the treatment information (Figure 1). The selected ROI was automatically positioned by the software on subsequent images, with minor adjustments to correct for respiratory motion when necessary. The analysis applies first linearization at the pixel level to revert the effects of “log” compression in the ultrasound system. Results obtained from the selected ROI represented an approximately linear depiction of the backscattered intensity. The average of the linearized intensities of all the pixels in the ROI was calculated to produce a time-signal intensity curve, where the intensity is theoretically linked to microbubble concentration [13].

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Oncology in South China, Department of Ultrasound, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.

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.

Show MeSH
Related in: MedlinePlus