Abstract
Minibeam radiation therapy (MBRT) delivers an ultrahigh dose of x-ray (⩾100 Gy) in 200–1000 µm beams (peaks), separated by wider non-irradiated regions (valleys) usually as a single temporal fraction. Preclinical studies performed at synchrotron facilities revealed that MBRT is able to ablate tumors while maintaining normal tissue integrity. The main purpose of the present study was to develop an efficient and accessible method to perform MBRT using a conventional x-ray irradiator. We then tested this new method both in vitro and in vivo. Using commercially available lead ribbon and polyethylene sheets, we constructed a collimator that converted the cone beam of an industrial irradiator to 44 identical beams (collimator size ≈ 4 × 10 cm). The dosimetry characteristics of the generated beams were evaluated using two different radiochromic films (beam FWHM = 246 ± 32 µm; center-to-center = 926 ± 23 µm; peak-to-valley dose ratio = 24.35 ± 2.10; collimator relative output factor = 0.84 ± 0.04). Clonogenic assays demonstrated the ability of our method to induce radiobiological cell death in two radioresistant murine tumor cell lines (TRP = glioblastoma; B16-F10 = melanoma). A radiobiological equivalent dose (RBE) was calculated by evaluating the acute skin response to graded doses of MBRT and conventional radiotherapy (CRT). Normal mouse skin demonstrated resistance to doses up to 150 Gy on peak. MBRT significantly extended the survival of mice with flank melanoma tumors compared to CRT when RBE were applied (overall p < 0.001). Loss of spatial resolution deep in the tissue has been a major concern. The beams generated using our collimator maintained their resolution in vivo (mouse brain tissue) and up to 10 cm deep in the radiochromic film. In conclusion, the initial dosimetric, in vitro and in vivo evaluations confirmed the utility of this affordable and easy-to-replicate minibeam collimator for future preclinical studies.
Highlights
Normal tissue toxicity is the dominant dose-limiting side effect of radiotherapy (RT) (Hendry et al 2006)
This effect occurs after conventional RT (CRT), and following intensity-modulated radiotherapy (IMRT) and proton therapy (Armoogum and Thorp 2015)
The dosimetric characteristics of the collimator are shown in table 3
Summary
Normal tissue toxicity is the dominant dose-limiting side effect of radiotherapy (RT) (Hendry et al 2006). Applying therapeutic doses of ionizing radiation to radiosensitive tissues such as in the brain almost always produces a certain level of radiation side effect This effect occurs after conventional RT (CRT), and following intensity-modulated radiotherapy (IMRT) and proton therapy (Armoogum and Thorp 2015). Preclinical studies have consistently demonstrated the selective tumoricidal and normal tissue sparing effects of this method (Bouchet et al 2016, Smyth et al 2016). This suggests that a potential advantage of MRT is reduced radiation-related normal tissue toxicity, and improved tumor control rates. MRT has not yet been clinically applied, mainly due to a lack of sufficient preclinical data
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