Research Dirk Verellen

Abstract

Ultra-short pulsed high dose rate radiation therapy, known as FLASH, has recently created a serious ripple effect in the radiation oncology community. Pre-clinical data has shown single-pulse doses above certain thresholds to decrease normal tissue radiotoxicity with a factor of nearly two, and as such increasing the differential response between healthy and tumour tissue. The effect had already been described by Hornsey et al. in 1966, but a recent series of publications by the Franco-Swiss team from the Institut Curie (France) and Centre Hospitalier Universitaire Vaudois (CHUV, Switzerland) has revived the interest prompting various reviews and a special edition of the Radiotherapy and Oncology Journal dedicated to the topic [Vol 139, 2019]. Radiation oncology has been improved over the last century in a series of distinct evolutions from increasing photon energy from kV to MV, introducing proton therapy, the implementation of CT and 3D conformal radiation therapy including increasingly more accurate dose calculation algorithms, intensity-modulated radiation therapy, biological conformal radiation therapy, stereotactic (body) radiation therapy, and image-guided radiation therapy; all of which caused stepwise improvements in treatment outcome and toxicity. FLASH, once confirmed by independent pre-clinical research & clinical trials, has on the contrary the potential to cause a genuine revolution in the field. In all of this, precise dose-measurement is of tremendous importance to monitor and evaluate radiation delivery, which is essential for performing quality assurance in radiation oncology by monitoring, benchmarking and comparing treatment outcomes. This, up to now, is not yet available for FLASH-delivered radiation therapy. At this moment, there are still many questions to be addressed before we will be able to apply the FLASH effect in clinical practice. The radiobiological mechanism underlying the FLASH effect is still unknown and requires substantial pre-clinical research, which is not the primary focus of this project proposal. In addition, the dosimetry of FLASH beams poses considerable challenges due to the ultra-high dose rates (UHDR) per pulse. Modern radiation therapy operates at typical dose rates of 1 to 25 Gy per minute, whereas FLASH operates between 40 and 1000 Gy per second. Moreover, preliminary results indicate that the dose per pulse is more relevant than the average dose per (mili)second to induce this FLASH effect. Secondary standard ionization chambers, typically used for absolute dosimetry in a clinical setting, suffer from significant limitations and require large correction factors for charge collection inefficiencies in FLASH regimes. It comes to no surprise that dosimetric characteristics of these previous reports on the FLASH effect were based on alanine EPR and radiochromic dose assessments, both off-line solutions and presenting considerable uncertainties. The current project aims roexplore and identify the dosimetric challenges related to FLASH and contribute to standardized codes of practice in absolute dosimetry and dose reporting. With none of the available dosimetry techniques being developed to be operational within the extreme exposure conditions as faced with UHDR radiotherapy, it is the goal of this PhD project to - Challenge the existing dosimetry systems and further develop/improve them to have accurate and reliable dosimetry techniques for FLASH radiotherapy - Establish a UHDR-dedicated dosimetry protocol for both reference and online dosimetry

Researcher(s)

• Promoter: Verellen Dirk

Research team(s)

• Center for Oncological Research (CORE)

Project type(s)

• Research Project