Commissioning of an ultra-high dose rate pulsed electron beam medical LINAC for FLASH RT preclinical animal experiments and future clinical human protocols

Treatment Use

FLASH-RT

Cancer Indication

Electron-beam FLASH

Number of Patients

0

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.

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Treatment of a first patient with FLASH-radiotherapy

Treatment Use

FLASH-RT

Cancer Indication

Electron-beam FLASH

Number of Patients

1

Summary/Conclusion

When compared to conventional radiotherapy (RT) in pre-clinical studies, FLASH-RT was shown to reproducibly spare normal tissues, while preserving the anti-tumor activity. This marked increase of the differential effect between normal tissues and tumors prompted its clinical translation. In this context, we present here the treatment of a first patient with FLASH-RT.

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Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species

Treatment Use

FLASH-RT

Cancer Indication

Electron-beam FLASH

Number of Patients

0

Summary/Conclusion

We highlight the potential translational benefits of delivering FLASH radiotherapy using ultra-high dose rates (>100 Gy·s−1). Compared with conventional dose-rate (CONV; 0.07–0.1 Gy·s−1) modalities, we showed that FLASH did not cause radiation-induced deficits in learning and memory in mice. Moreover, 6 months after exposure, CONV caused permanent alterations in neurocognitive end points, whereas FLASH did not induce behaviors characteristic of anxiety and depression and did not impair extinction memory.

Mechanistic investigations showed that increasing the oxygen tension in the brain through carbogen breathing reversed the neuroprotective effects of FLASH, while radiochemical studies confirmed that FLASH produced lower levels of the toxic reactive oxygen species hydrogen peroxide. In addition, FLASH did not induce neuroinflammation, a process described as oxidative stress-dependent, and was also associated with a marked preservation of neuronal morphology and dendritic spine density. The remarkable normal tissue sparing afforded by FLASH may someday provide heretofore unrealized opportunities for dose escalation to the tumor bed, capabilities that promise to hasten the translation of this groundbreaking irradiation modality into clinical practice.

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Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s

Treatment Use

FLASH-RT

Cancer Indication

Electron-beam FLASH

Number of Patients

0

Summary/Conclusion

This study shows for the first time that normal brain tissue toxicities after WBI can be reduced with increased dose rate. Spatial memory is preserved after WBI with mean dose rates above 100 Gy/s, whereas 10 Gy WBI at a conventional radiotherapy dose rate (0.1 Gy/s) totally impairs spatial memory.

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Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice

Treatment Use

FLASH-RT

Cancer Indication

Electron-beam FLASH

Number of Patients

0

Summary/Conclusion

Pulsed irradiation (FLASH) was performed using the 4.5 MeV linear electron accelerator (LINAC) described in (34). The system allows exposure of cells or animals to a single submicrosecond pulse, to any sequence of pulses, or to split-dose irradiation with an interval between fractions ranging from fractions of seconds to a few minutes.

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