In some cases, e.g. small brain tumor metastases, responses to single or multiple fraction high-dose radiation therapy (HD-RT) have been remarkable, suggesting that HD-RT tumor control is at least as effective as biologically equivalent doses of conventional fractionated radiation therapy (CF-RT), even in radioresistant tumors. Although the mechanism for its effectiveness is not well understood, HD-RT is becoming accepted practice for a variety of tumors, including brain tumors. Our recent preclinical study using MRI measures of short-term changes in tumor physiology after HD-RT in a small-animal model of cerebral tumor suggests a physiological response that includes vascular effects, but is multifactorial and temporally variable. Hypothesizing that these short-term changes may both explain the increased effectiveness of HD-RT, and serve as a predictor of long-term response, we propose to investigate the relationship between short-term physiological changes after HD-RT and long-term outcome as a result of that therapy. In counterpoint, we will also study physiological changes during and after CF-RT. Detailed poroelastic modeling is proposed to generate a map of local solid and fluid parameters (stress, flow) that will help explain short-term changes in physiology.
Aim 1 studies short-term changes in measures of tumor physiology as predictors of response.
Aim 2 describes the behavior of these same measures over the course of CF-RT. Our long-range goals are to develop noninvasive biomarkers of response that predict tumor control after HD-RT and CF-RT, and to describe physiological changes and related biomarkers that might be used to optimize the order and timing of RT and adjuvant chemotherapies.
Radiotherapy (RT) is an essential component in the treatment of brain tumors. This proposal uses dynamic magnetic resonance imaging (MRI) to explore why high-dose radiotherapy (HD-RT) is sometimes more effective in brain tumor treatment than conventional fractionated radiotherapy (CF-RT). By creating a comprehensive picture of tumor physiology during response to the differing radiotherapy strategies, early physiologic changes detected by MRI will be used to predict long-term treatment response, generating new tactics for the more effective use of RT in cancer treatment.
|Kim, Jae Ho; Jenrow, Kenneth A; Brown, Stephen L (2018) Novel biological strategies to enhance the radiation therapeutic ratio. Radiat Oncol J 36:172-181|