Oncotarget

Research Papers:

Tumor physiological changes during hypofractionated stereotactic body radiation therapy assessed using multi-parametric magnetic resonance imaging

Heling Zhou, Zhang Zhang, Rebecca Denney, Jessica S. Williams, Jeni Gerberich, Strahinja Stojadinovic, Debabrata Saha, John M. Shelton and Ralph P. Mason _

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Oncotarget. 2017; 8:37464-37477. https://doi.org/10.18632/oncotarget.16395

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Abstract

Heling Zhou1, Zhang Zhang2, Rebecca Denney1, Jessica S. Williams3, Jeni Gerberich1, Strahinja Stojadinovic2, Debabrata Saha2, John M. Shelton3 and Ralph P. Mason1

1Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States

2Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States

3Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States

Correspondence to:

Ralph P. Mason, email: Ralph.Mason@UTSouthwestern.edu

Keywords: hypofractionated stereotactic body radiation therapy (SBRT), oxygen-sensitive MRI, blood oxygen level dependent (BOLD), dynamic contrast enhanced (DCE), treatment response

Received: June 30, 2016    Accepted: March 02, 2017    Published: March 21, 2017

ABSTRACT

Radiation therapy is a primary treatment for non-resectable lung cancer and hypoxia is thought to influence tumor response. Hypoxia is expected to be particularly relevant to the evolving new radiation treatment scheme of hypofractionated stereotactic body radiation therapy (SBRT). As such, we sought to develop non-invasive tools to assess tumor pathophysiology and response to irradiation. We applied blood oxygen level dependent (BOLD) and tissue oxygen level dependent (TOLD) MRI, together with dynamic contrast enhanced (DCE) MRI to explore the longitudinal effects of SBRT on tumor oxygenation and vascular perfusion using A549 human lung cancer xenografts in a subcutaneous rat model. Intra-tumor heterogeneity was seen on multi-parametric maps, especially in BOLD, T2* and DCE. At baseline, most tumors showed a positive BOLD signal response (%ΔSI) and increased T2* in response to oxygen breathing challenge, indicating increased vascular oxygenation. Control tumors showed similar response 24 hours and 1 week later. Twenty-four hours after a single dose of 12 Gy, the irradiated tumors showed a significantly decreased T2* (-2.9±4.2 ms) and further decrease was observed (-4.0±6.0 ms) after 1 week, suggesting impaired vascular oxygenation. DCE revealed tumor heterogeneity, but showed minimal changes following irradiation. Rats were cured of the primary tumors by 3x12 Gy, providing long term survival, though with ultimate metastatic recurrence.


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