Speaker
Description
Ultra-high dose rate, FLASH radiotherapy has now emerged as one of the most promising innovations over the last decade in the field of radiation oncology, with the potential to eradicate radiation resistant primary tumors and improve the therapeutic index of radiotherapy. A biological effect called the FLASH effect for which rapid delivery of radiation doses is necessary but not always sufficient. FLASH may position modern radiation therapy over the next few years to become the center of safe, affordable and efficient anti-cancer care. While work is in progress, FLASH-dedicated research is challenging and exciting as it involves muti-disciplinary expertise at the interface of physics, chemistry, biology and clinics.
Interestingly, while the FLASH effect has been demonstrated in preclinical in vivo models with electron, photon, proton and heavier ion beams, the optimal beam parameters required for safe clinical translation in terms of dosimetry, radioprotection and treatment planning systems are still under investigations. and will be. It has been reported to occur when using single and hypo-fractionated dose regimens in several experimental animal models (mice, rat, zebrafish, pig, cats) and in multiple organs (lung, skin, gut, brain) by numerous groups worldwide and emerging evidence suggests that FLASH could also be delivered with standard fractionation regimen. The current knowledge, limitations and challenges for safe clinical translation will be presented in this lecture.
Similarly, while pre-clinical in vivo data seem to show that the majority anti-tumor efficacy of cytotoxic doses is not dependent on dose rate, while normal tissues seem generally dose rate sensitive, some tumors show enhanced sensitivity to FLASH while others are resistant. Some normal tissue (such as the liver) might be insensitive to FLASH due to intrinsic biochemical characteristics. Mechanistic investigations have also been performed at the physico-chemical and biological levels. Current results tend to suggest that the FLASH effect is biochemical and depends upon the biological milieu. Mechanisms involving the preservation of redox and metabolic homeostasis as well as reduction of the peroxidation of biomolecules have been demonstrated and more recently FLASH-specific induction of dedicated transcription factors involved in the activation of intrinsic regenerative and radio-resistance signals in normal tissue vs death program in tumors have been shown using omics methodologies. The perspectives of these new findings will also be presented along with their relevance for safe clinical translation.