Neurocognitive sparing of desktop microbeam irradiation

Bazyar, Soha; Inscoe, Christina R.; Benefield, Thad; Zhang, Lei; Lu, Jianping; Zhou, Otto; Lee, Yueh Z.

doi:10.1186/s13014-017-0864-2

Cited by 8 publications

(5 citation statements)

References 58 publications

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“…The EUD concept was used as an approach to translate the dose distribution of microbeam arc therapy into conventional radiotherapy dose. As the EUD followed the trend of the valley dose, it confirms the observation that normal tissue toxicity depends primarily on the valley dose [2] , [5] , [6] .…”

Section: Discussionsupporting

confidence: 80%

“…The biological effects of MRT are not fully understood yet [5] , and it is still unclear if a spatially fractionated target dose is more efficient than a homogeneous target dose [2] . Nevertheless, authors agree that a low valley dose, a high peak-to-valley dose ratio (PVDR), and steep lateral penumbras from the peaks to the valleys are crucial for sparing healthy tissue [5] , [6] , [7] .…”

Section: Introductionmentioning

confidence: 99%

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Clinical microbeam radiation therapy with a compact source: specifications of the line-focus X-ray tube

Winter

Galek

Matejcek

et al. 2020

Physics and Imaging in Radiation Oncology

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Background and purpose: Microbeam radiotherapy (MRT) is a preclinical concept in radiation oncology with arrays of alternating micrometer-wide high-dose peaks and low-dose valleys. Experiments demonstrated a superior normal tissue sparing at similar tumor control rates with MRT compared to conventional radiotherapy. Possible clinical applications are currently limited to large third-generation synchrotrons. Here, we investigated the line-focus X-ray tube as an alternative microbeam source. Materials and methods: We developed a concept for a high-voltage supply and an electron source. In Monte Carlo simulations, we assessed the influence of X-ray spectrum, focal spot size, electron incidence angle, and photon emission angle on the microbeam dose distribution. We further assessed the dose distribution of microbeam arc therapy and suggested to interpret this complex dose distribution by equivalent uniform dose. Results: An adapted modular multi-level converter can supply high-voltage powers in the megawatt range for a few seconds. The electron source with a thermionic cathode and a quadrupole can generate an eccentric, highpower electron beam of several 100 keV energy. Highest dose rates and peak-to-valley dose ratios (PVDRs) were achieved for an electron beam impinging perpendicular onto the target surface and a focal spot smaller than the microbeam cross-section. The line-focus X-ray tube simulations demonstrated PVDRs above 20. Conclusion: The line-focus X-ray tube is a suitable compact source for clinical MRT. We demonstrated its technical feasibility based on state-of-the-art high-voltage and electron-beam technology. Microbeam arc therapy is an effective concept to increase the target-to-entrance dose ratio of orthovoltage microbeams.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Clinical microbeam radiation therapy with a compact source: specifications of the line-focus X-ray tube

Winter

Galek

Matejcek

et al. 2020

Physics and Imaging in Radiation Oncology

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“…No acute skin toxicity was observed in mice that were irradiated with doses up to 150 Gy and 15 Gy in MBRT and CRT, respectively (figure 9). In a previous study, we demonstrated the sparing effect of MBRT on normal mice brain tissue post-irradiation, up to 8 months (Bazyar et al 2017). Currently, we are investigating the full extent of normal tissue toxicity, ED50 and TD50 of our technique on different tissues.…”

Section: Discussionmentioning

confidence: 81%

Minibeam radiotherapy with small animal irradiators; in vitro and in vivo feasibility studies

et al. 2017

Self Cite

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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.

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“…Indeed, numerous previous studies highlighted the different biological responses observed after MBRT or conventional broad beam irradiation, both in terms of normal tissue tolerance and tumour control [9,12,20,26]. Some relevant results from selected in vivo experiments are compiled in Table 6.…”

Section: Discussionmentioning

confidence: 99%

Orthovoltage X-ray Minibeam Radiation Therapy for the Treatment of Ocular Tumours—An In Silico Evaluation

Schneider

Denis

Pouzoulet

et al. 2023

Cancers

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(1) Background: Radiotherapeutic treatments of ocular tumors are often challenging because of nearby radiosensitive structures and the high doses required to treat radioresistant cancers such as uveal melanomas. Although increased local control rates can be obtained with advanced techniques such as proton therapy and stereotactic radiosurgery, these modalities are not always accessible to patients (due to high costs or low availability) and side effects in structures such as the lens, eyelids or anterior chamber remain an issue. Minibeam radiation therapy (MBRT) could represent a promising alternative in this regard. MBRT is an innovative new treatment approach where the irradiation field is composed of multiple sub-millimetric beamlets, spaced apart by a few millimetres. This creates a so-called spatial fractionation of the dose which, in small animal experiments, has been shown to increase normal tissue sparing while simultaneously providing high tumour control rates. Moreover, MBRT with orthovoltage X-rays could be easily implemented in widely available and comparably inexpensive irradiation platforms. (2) Methods: Monte Carlo simulations were performed using the TOPAS toolkit to evaluate orthovoltage X-ray MBRT as a potential alternative for treating ocular tumours. Dose distributions were simulated in CT images of a human head, considering six different irradiation configurations. (3) Results: The mean, peak and valley doses were assessed in a generic target region and in different organs at risk. The obtained doses were comparable to those reported in previous X-ray MBRT animal studies where good normal tissue sparing and tumour control (rat glioma models) were found. (4) Conclusions: A proof-of-concept study for the application of orthovoltage X-ray MBRT to ocular tumours was performed. The simulation results encourage the realisation of dedicated animal studies considering minibeam irradiations of the eye to specifically assess ocular and orbital toxicities as well as tumour response. If proven successful, orthovoltage X-ray minibeams could become a cost-effective treatment alternative, in particular for developing countries.

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Neurocognitive sparing of desktop microbeam irradiation

Cited by 8 publications

References 58 publications

Clinical microbeam radiation therapy with a compact source: specifications of the line-focus X-ray tube

Clinical microbeam radiation therapy with a compact source: specifications of the line-focus X-ray tube

Minibeam radiotherapy with small animal irradiators; in vitro and in vivo feasibility studies

Orthovoltage X-ray Minibeam Radiation Therapy for the Treatment of Ocular Tumours—An In Silico Evaluation

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