The main scope of radiotherapy is to exploit the specific energy deposition by different types of ionizing radiation in an optimal way, maximizing the damage to the tumor cells while minimizing that one to the normal tissues, in particular to organs at risk. The recent discovery, based on hypotheses argued already in the 60s, but evidenced in vivo only in the last 8 years, that irradiations delivered at ultra-high dose rate (UHDR) may have a relevant effect in differentially sparing healthy tissue while keeping the same killing effect on the tumor, thus, lead the potential to revolutionate the complete paradigm of radiotherapy and a new intense field of research called FLASH radiotherapy raised exponentially in the last few years. This mysterious differential biological effectiveness of UHDR irradiations, the so-called FLASH effect, steadily accumulating evidence in preclinical experiments, triggered in the last 3-4 years an exponentially growing number of biophysical modeling works attempting to investigate and explain it from the mechanistic point of view. Since it was appearing that such a phenomenon should imply several physical, chemical and biological stages of the radiation action, different spatio-temporal scales were considered and analyzed in these modeling approaches.
An overview of these investigations will be concisely reported, with a focus on the ongoing joint efforts of GSI and TIFPA in this context, especially in the attempt of combining different scales. In particular, radiation chemical based approaches, employing TRAXCHEM, the GSI radiation chemical track structure code and its specific extensions, allowing to go from the physical stage to the homogeneous chemical stage will be mentioned and a novel dedicated extension of the Generalized Stochastic Microdosimetric model (GSM2) for UHDR regime, aiming at combining the DNA damage and repair kinetics with the chemical stages on several levels. Impact of linear energy transfer (LET) and dose delivery features will be discussed as well.
Hybrid access via ZOOM:
Meeting ID: 984 5733 2925
Peter Thirolf (LMU) / Norbert Kaiser (TUM)