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Clinical Development of FLASH-RT with Protons
Abstract
Abstract Body
With the use of radiation in the therapeutic armamentarium against cancer, the delivery of radiotherapy techniques has allowed gradual dose conformity improvement, by sophisticated beam delivery techniques. One disadvantage al of modern photon beam techniques however is the exposure of organs at risk with ‘parasitic’ radiation, which is associated to the emergence of potentially severe acute and late radiation-induced adverse events. In order to reduce the risk of aforementioned toxicity, the delivery of charged particles radiotherapy for selected cancer patients have been advocated. Particle therapy, be it with protons, carbons or other ions, have a remarkable dose deposition in patients, i.e. delivering radiation dose in a small area called the Bragg peak, with no dose delivery distal to the target volume. The French and Swiss teams have recently described Flash effect with conventional RT that shows normal tissue protection in various animal models thanks to dose delivery by beam pulses of high dose rate (ca. >40 Gy/sec) with a certain fractional dose (most in vivo FLASH studies to date have used doses of around 10Gy or higher). The idea of utilizing protons (or carbons) for FLASH delivery is to exploit the ultra-high dose OARs sparing effect whilst combining the dose radiation conformality of particles, providing that there are not delivered with a transmission paradigm.
For instance, proton radiation delivery to the brain can reduce the integral dose to this OAR (and thus neuro toxicity such as neuro-cognition) but until recently it was unknown if the neuro-cognitive effect with FLASH observed with electrons would also be observed with Protons. At PSI/CHUV we have showed that proton irradiation in FLASH mode does not elicit neurocognitive deficits in mice. The presentation will detail the clinical results of the FAST-01 which was activated in November 2020. This single site prospective trial enrolled 10 bone M+ (1-3) patients who received 8 Gy with (on average) a dose rate of 56Gy/sec, utilizing a maximum field size of 7.5x20cm. This seminal study showed that the clinical delivery of FLASH proton therapy was both feasible and safe. The new FAST-02 study proposal will also be detailed in this talk.