Decline of Tumor Vascular Function as Assessed by Dynamic Contrast-Enhanced Magnetic Resonance Imaging Is Associated With Poor Responses to Radiation Therapy and Chemotherapy

Abstract

Purpose To investigate whether changes in the volume transfer coefficient (Ktrans) in a growing tumor could be used as a surrogate marker for predicting tumor responses to radiation therapy (RT) and chemotherapy (CT). Methods and Materials Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was consecutively performed on tumor-bearing mice, and temporal and spatial changes of Ktrans values were measured along with tumor growth. Tumor responses to RT and CT were studied before and after observed changes in Ktrans values with time. Results Dynamic changes with an initial increase and subsequent decline in Ktrans values were found to be associated with tumor growth. When each tumor was divided into core and peripheral regions, the Ktrans decline was greater in core, although neither vascular structure or necrosis could be linked to this spatial difference. Tumor responses to RT were worse if applied after the decline of Ktrans, and there was less drug distribution and cell death in the tumor core after CT. Conclusion The Ktrans value in growing tumors, reflecting the changes of tumor microenvironment and vascular function, is strongly associated with tumor responses to RT and CT and could be a potential surrogate marker for predicting the tumor response to these treatments.