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

// Heling Zhou 1 , Zhang Zhang 2 , Rebecca Denney 1 , Jessica S. Williams 3 , Jeni Gerberich 1 , Strahinja Stojadinovic 2 , Debabrata Saha 2 , John M. Shelton 3 and Ralph P. Mason 1 1 Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States 2 Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States 3 Department 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, T 2 * and DCE. At baseline, most tumors showed a positive BOLD signal response (%ΔSI) and increased T 2 * 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 T 2 * (-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.