Clinical Evidence

Summary/Conclusion

Recent preclinical evidence has shown that ionizing radiation given at an ultra-high dose rate (UHDR), also known as FLASH radiation therapy (FLASH-RT), can selectively reduce radiation injury to normal tissue while remaining isoeffective to conventional radiation therapy (CONV-RT) with respect to tumor killing. Unresectable pancreatic cancer is challenging to control without ablative doses of radiation, but this is difficult to achieve without significant gastrointestinal toxicity. In this review article, we explore the propsed mechanisms of FLASH-RT and its tissue-sparing effect, as well as its relevance and suitability for the treatment of pancreatic cancer. We also briefly discuss the challenges with regard to dosimetry, dose rate, and fractionation for using FLASH-RT to treat this disease.

Summary/Conclusion

This is the first study to demonstrate the physical and biological effects of FLASH RT achieved with a FLASH Mobetron unit. Two independent institutions were able to demonstrate similar biological sparing effects resulting from high-dose, single-fraction abdominal irradiation delivered with FLASH RT versus CONV RT. The FLASH Mobetron was available to both institutions, and the beam parameters used were nearly identical. The most striking finding was that, despite differences in selected endpoints and in euthanasia criteria, both institutions found that FLASH RT produced significantly different responses than CONV RT. When comparing to and including previously published literature using similar endpoints and with similar irradiation beam parameters but on different irradiation units, we can show that the FLASH effect is robust and reproducible regardless of the unit used, as long as the same set of beam parameters are used.

Summary/Conclusion

The BCTs were implemented and validated on a pulsed electron beam medical LINAC, thus improving current dosimetric procedures and allowing for a more complete analysis of beam characteristics. BCTs were shown to be a valid method for beam monitoring for UHDR (and therefore FLASH) experiments.

Summary/Conclusion

The dual BCT system integrated within the FLASH Mobetron was shown to be a reliable monitoring system able to quantify accelerator performance and capture all essential physical beam parameters on a pulse-by-pulse basis, and the ratio between the two BCTs was strongly correlated with beam energy. The fast signal readout and processing enables the BCTs to provide real-time information on beam output and energy and is proposed as a system suitable for accurate beam monitoring and control of eFLASH beams.

Summary/Conclusion

The Mobetron device was evaluated with electron beams of 9 MeV in conventional (CONV) mode and of 6 and 9 MeV in UHDR mode (nominal energy). The acceptance was performed according to the acceptance protocol of the company. The commissioning consisted of determining the short- and long-term stability of the device, the measurement of percent depth dose curves (PDDs) and profiles at two different positions (with two different dose per pulse regimen) and for different collimator sizes, and the evaluation of the variability of these parameters when changing the pulse width and pulse repetition frequency. Measurements were performed using a redundant and validated dosimetric strategy with alanine and radiochromic films, as well as Advanced Markus ionization chamber for some measurements.