Radiotherapy is used to treat 60% of the cancer patients and 40% of curative cases. However, normal tissue toxicities still prevent radiotherapy from achieving more effective tumor control in many patients despite decades of technological development in intensity-modulated radiation therapy and image-guided radiation therapy. Ultra- high dose rate, a.k.a., FLASH radiotherapy has recently re-emerged as a potential method to significantly improve the radiation biological dose conformality on top of the physical dose conformality. Although existing X- ray linac and proton systems can be modified to deliver the FLASH dose rate, they are limited in either field size, depth penetration, or dose conformality to be useful for treating most human tumors. Conceptual systems such as very high energy electron and PHASER will need to overcome significant and risky technological barriers to be clinically practical. In this Academic-Industrial Partnerships project, we propose to develop a high dose rate X-ray radiotherapy system that is a scale-up of existing technologies for clinical FLASH radiotherapy. There are three major technical challenges in achieving the FLASH dose rate with X-rays. The first is the linear accelerator that is capable to produce such a high dose rate. For this challenge, we hypothesize that a 12 MV X-ray beam >300 Gy/s uncollimated dose rate can be achieved using a combination of already-demonstrated accelerator technologies. The second challenge is the well-separated beam angles for good X-ray dosimetry. The third challenge is intensity modulation for conformal dose distribution. The tightly correlated second and third challenges are due to the slow mechanical movement of the common C-arm gantry and the MLC leaf speed. To overcome these two challenges, we propose to develop a rotational ring-gantry FLASH IMRT platform with many quasi-static MLCs. The fast-spinning ring-gantry system would deliver the entire treatment in an arc within a very short time. The intensity modulation is achieved by using a decoupled MLC ring with a large number of MLC banks each pre-shaping the aperture for rotational IMRT. The system would then be able to achieve highly conformal dose distribution comparable to state of the art VMAT, and at the same time take advantage of the FLASH radiobiology. We propose the following aims:
Aim 1. High dose rate linac development;
Aim 2. Development of ROtational direct Aperture optimization with a Decoupled (ROAD) MLC ring;
Aim 3. Demonstration of rotational FLASH using a benchtop system.

Public Health Relevance

Ultra-high dose rate radiotherapy a.k.a. FLASH radiotherapy has shown the potential to drastically reduce the normal tissue toxicity without compromising tumor cell killing. However, the delivery of FLASH is hampered by the limitations inherent to existing radiotherapy platforms. We propose to develop a groundbreaking new X-ray system ROAD to achieve the needed FLASH dose rate for significantly improved cancer radiotherapy efficacy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Obcemea, Ceferino H
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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