Flash beyond doubt, and beyond

Principal Investigators: dr. Steven Habraken (Erasmus MC), dr. ir. Dennis Schaart (TU Delft), prof dr. Coen Rasch (LUMC), prof. dr. Mischa Hoogeman (HollandPTC)

PhD students: Manon van Zon (Erasmus MC), Simone Visser (LUMC), Anne Zur Horst (HollandPTC)

Funding: HollandPTC-Varian 2020

Description

Despite the superior physical properties of proton beams and image guidance, fractionated proton therapy still has a limited therapeutic bandwidth and may come with severe side effects. In animal experiments and a first patient treatment, it has been demonstrated that with FLASH irradiation – high dose (≥ 8 Gy) at ultrahigh dose rate (≥ 40 Gy/s) – the radiosensitivity of healthy tissue may be reduced by an enhancement factor up to 1.8 (typically 1.3 – 1.4), without affecting tumor cell kill. This amounts to a significant potential increase of the therapeutic bandwidth of radiotherapy. In its current form, however, FLASH radiotherapy is limited to superficial targets up to a centimeter, while most critical clinical applications of radiotherapy deal with larger, deeper-seated tumors. With dose rates of hundreds of Gy/s readily available in therapeutic proton beams and in view of their ability to reach deep-seated targets, the first clinical testing and further development of FLASH proton therapy (FLASH-PT) is highly timely.

In this project, FLASH beyond doubt, and beyond, we will clinically prepare FLASH-PT, develop Bragg-peak FLASH-PT and make significant technological progress to unlock its full potential. The key objectives are (i) to clinically develop and implement  gated proton therapy, thereby enabling fast and optimal targeting in future FLASH-PT patient treatments; (ii) to develop and implement clinically realistic forward treatment planning and robustness evaluation strategies with FLASH-PT with Bragg-peak beams; (iii) to develop methods for independent monitoring of the temporal distribution of dose deposition at all time scales of interest in FLASH-PT; and (iv) to develop Pareto optimization of FLASH-PT, biological modeling and novel clinical applications of FLASH-PT with transmission and Bragg-peak beams.