Dose-Rate Variations for Patient Treatments in Flash and conventional radiation therapy

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Radiation therapy has been an important component in the treatment of cancer for many decades. While the parameters of tumor control have been relatively well understood, normal tissue complication proba- bilities (NTCPs) are often only thought of as constraining factors in the design of a treatment regimen. However, with continuously improving treatments of primary lesions, NTCP and their impact on the quality of life have moved into the focus of research. One of the most prominent methods reported to spare healthy tissue is FLASH radiation therapy, i.e. ul- trafast (>40 Gy/s) irradiations, which reportedly results in incredible tissue sparing effects without com- promising efficacy for tumor cure. Conversely, very low dose-rate irradiations have also been reported to offer protective features. Together, these experiments suggest that the current clinical routine, treating patients with a medium dose-rate of ~2 Gy/min, could in fact be the least favorable when considering healthy tissue side effects. In clinical practice, patients are treated with a variety of radiation treatment modalities. While the result- ing target doses are similar across modalities, the dose delivered to the normal tissue and the time struc- ture of the delivery can vary significantly. Despite the range of dose-rates across treatment plans, the biological effect is estimated only based on the total dose received. We hypothesize that dose-rate plays an important role in the outcome of radiation therapy that can be exploited for specific treatment scenarios. For extreme cases such as FLASH therapy, averaged dose- rates do not capture the relevant time structures adequately. We will apply Monte Carlo simulations to determine time structures from the clinical scale of minutes (spot scanning / gantry rotation time) to na- noseconds (intra-spot delivery time) and assess potential effects on healthy tissue sparing that would im- prove the quality of life for radiation therapy patients.