Abstract 1497: In vivo discrimination of tumor modifications during antiangiogenic and cytotoxic therapy using ultrasonography modalities: Shear Wave Elastography (SWE), Contrast Enhanced Ultrasound (CEUS) and Quantitative Ultrasound (QUS)
Authors: Dizeux Alexandre , Payen Thomas , Barrois Guillaume , Lamuraglia Michele , Baldini Capucine , Le Guillou Delphine , Comperat Eva , Gennisson Jean-Luc , Tanter Mickael , Oelze Michael , Bridal S. Lori 
Published: August 2015

Robust, novel image-based information on the tumor microenvironment would improve therapeutic follow-up in oncology. SWE evaluates tissue stiffness, CEUS assesses microvascular flow using intravascular microbubbles and QUS measures tissue microstructure. Our goal was to evaluate sensitivity and complementarity of these techniques during cytotoxic and antiangiogenic therapies in ectopic, murine tumors.

A multi-targeted receptor tyrosine kinase antiangiogenic drugs inhibiting vascularization (sunitinib, N = 24, 40mg/kg/day), an alkylating cytotoxic agent that adds an alkyl group to DNA to interfere with DNA replication (cyclophosphamide, N = 26, 150mg/kg for 3 days) and placebo (N = 26) were administered in murine Lewis Lung Carcinomas bearing C57BL6 mice. Six days after implantation, tumors were imaged (SWE, CEUS and QUS) prior to therapy (Day 0) and on Days 1, 3, 7, 9 and 13. Tumors were harvested at Day 9 (N = 2 per group) and Day 13 (N = 10 per group) and stained to evaluate% necrosis and fibrosis.

Table. 1 summarizes the% variation of each measured parameter from the start to the end of therapy. Imaging parameters for microvascular function and stiffness were most strongly modified for tumors treated with sunitinib compared to cytotoxic and placebo therapies. At Day 13, tumors treated with sunitinib presented a heterogeneous structure with more fibrosis and necrosis than for other treatment groups. This heterogeneous structure may explain why the standard deviation of stiffness was highest for the antiangiogenic group. The sensitivity of CEUS to microvascular modifications and SWE to biomarkers such as necrosis and fibrosis, in this model, underline potential for monitoring complementarity aspects of the tumor microenvironment during therapy.

CytotoxicAnti-angiogenicPlaceboVariation(%)P-valueVariation(%)P-valueVariation(%)P-valueSWEStiffness20*0.03680*&lt;0.000169*&lt;0.00001CEUSPeak Enhancement-8.70.892-68*&lt;0.00001-48*&lt;0.005Wash in rate-390.162-83*&lt;0.00001-78*&lt;0.00001Wash out rate-0.20.545-76*&lt;0.00001-46*&lt;0.001Mean transit time1.10.65015*&lt;0.00517*&lt;0.005

Table 1: Variation between Day 0 and Day 13 of mean values of each parameter for each group.

Citation Format: Alexandre Dizeux, Thomas Payen, Guillaume Barrois, Michele Lamuraglia, Capucine Baldini, Delphine Le Guillou, Eva Comperat, Jean-Luc Gennisson, Mickael Tanter, Michael Oelze, S. Lori Bridal. In vivo discrimination of tumor modifications during antiangiogenic and cytotoxic therapy using ultrasonography modalities: Shear Wave Elastography (SWE), Contrast Enhanced Ultrasound (CEUS) and Quantitative Ultrasound (QUS). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1497. doi:10.1158/1538-7445.AM2015-1497