Abstract
PurposeDespite the success of fractionation in clinical practice to spare healthy tissue, it remains common for mouse models used to study the efficacy of radiation therapy to use minimal or no fractionation. The goal of our study was to create a fractionated mouse model of radiation necrosis that we could compare to our single fraction model.MethodsPrecision X-Ray’s X-Rad 320 cabinet irradiator was used to irradiate the cerebrum of mice with four different fractionation schemes, while a 7 T Bruker magnetic resonance imaging (MRI) scanner using T2 and post-contrast T1 imaging was used to track the development of radiation necrosis over the span of six weeks.ResultsAll four fractionation schemes with single fraction equivalent doses (SFED) less than 50 Gy for the commonly accepted alpha/beta ratio (α/β) value of 2–3 Gy produced radiation necrosis comparable to what would be achieved with single fraction doses of 80 and 90 Gy. This is surprising when previous work using single fractions of 50 Gy produced no visible radiation necrosis, with the results of this study showing fractionation not sparing brain tissue as much as expected.ConclusionFurther interpretation of these results must take into consideration other studies which have shown a lack of sparing when fractionation has been incorporated, as well as consider factors such as the use of large doses per fraction, the time between fractions, and the limitations of using a murine model to analyze the human condition.
Highlights
Radiation therapy is essential to cancer treatment, with approximately 50% of cancer patients receiving radiation therapy and radiation contributing toward 40% of the curative treatments of the disease [1]
The original purpose of our study was to create a fractionated mouse model of radiation necrosis that we could compare to our single fraction model
Mice were irradiated with four fractionation schemes and tracked up to 6 weeks with lesion volumes being measured
Summary
Radiation therapy is essential to cancer treatment, with approximately 50% of cancer patients receiving radiation therapy and radiation contributing toward 40% of the curative treatments of the disease [1]. Fractionation serves clinically to reduce the complications attributed to radiation therapy [4,5,6,7]. Though fractionation is the established approach clinically, it remains common in preclinical studies to perform experiments and generate animal models with high single fraction doses [8,9,10,11,12] This unfractionated approach has practical advantages such as a shorter time commitment and avoiding potential confounds due to the potentially limited reproducibility of positioning for focal treatments. Ideally animal models of radiation-induced injury should be performed with fractionated regimes to ensure that the radiation exposure is as human-like as possible
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