First systematic in vivo tumor irradiation in mice with laser-accelerated and dose-homogenized proton beams from the Draco PW laser

After the rediscovery of the normal tissue sparing effect of high dose rate radiation, i.e. the so-called FLASH effect, by Favaudon et al. in 2014, research activities on this topic have been revived and are flourishing ever since. Yet, the exact biological mechanism as well as the required boundary conditions and radiation qualities to reach said sparing remain mostly unclear. We present a laser-based irradiation platform at the Draco PW facility that enables systematic studies into the FLASH regime using proton peak dose rates of up to 10^9 Gy/s. Besides the PW class laser acceleration source, a key component is a pulsed high-field beamline to transport and shape the laser driven proton bunches spectrally and spatially in order to generate homogeneous dose distributions tailored to match the irradiation sample. Making use of the diverse capabilities of the laser driven irradiation platform a pilot experiment of highest complexity has been conducted – a systematic in-vivo tumor irradiation in a specifically developed mouse model. A plethora of online particle diagnostics, including Time-of-Flight, bulk scintillators and screens as well as ionization chambers, in conjunction with diagnostics for retrospective absolute dosimetry (radiochromic films) allowed for an unprecedented level of precision in mean dose delivery (±10 %) and dose homogeneity (±5 %) for the challenging beam qualities of a laser accelerator. The tailored detector suite is complemented by predictive simulations. The talk addresses how our interdisciplinary team overcame all hurdles from animal model development, over enhancing the laser and laser acceleration stability, to dose delivery and online dose monitoring. Results on radiation induced tumor growth delay by laser driven as well as conventionally accelerated proton beams are critically discussed.