Facilitation ultRahigh dOse-rate aNd spaTIally-fractionatEd Radiotherapy (FRONTIER)

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Each year about 80,000 Canadians succumb to cancer, the leading cause of death in our country corresponding to 30% of deaths. Radiation therapy, along with surgery and chemotherapy, is one of the three most common treatment options, but unfortunately its efficacy is limited by radiation side effects. Two novel RT techniques - ultrahigh dose-rate (FLASH) and spatially-fractionated radiotherapy (SFRT) have recently shown great promise in improving outcomes of radiotherapy in a laboratory setting. FLASH radiotherapy consists of treatment dose delivery in sub-second intervals that are much shorter than the typical minute-long treatments. SFRT, on the other hand, is delivered with a set of small beams rather than with a uniform beam used in conventional radiotherapy. By means of FLASH and SFRT small animal studies performed on specialized equipment, reductions in radiotherapy side effects have been demonstrated for both treatment modalities. For example, mouse brains irradiated with FLASH experienced almost no cognitive function deterioration unlike mouse brains irradiated conventionally. SFRT performed on a rat model of glioblastoma multiforme, an aggressive form of brain cancer, resulted in a significantly increased mean survival from 34 days after conventional radiotherapy to 170 days. These two novel radiotherapy techniques, especially FLASH, are undoubtedly on the forefront of all current radiotherapy research and their translation to clinical use is tantalizing. Unfortunately, many obstacles must be overcome before these two radiotherapy modalities can be translated to the clinic for cancer patients' benefit. The overarching goal of this proposal is to accelerate the clinical translation of FLASH and SFRT by means of 1) building three FLASH and/or SFRT systems to enable widespread preclinical testing of these two treatment modalities, 2) providing accurate dose calculation methods for an objective interinstitutional comparison of FLASH and SFRT treatment outcomes and 3) developing equipment for real-time FLASH and SFRT dosimetry. Upon a successful completion of the proposed research, we will have provided the radiation oncology community with a number of necessary tools for widespread preclinical testing and clinical translation of FLASH and SFRT.