Shoot-through proton FLASH irradiation lowers linear energy transfer in organs at risk for neurological tumors and is robust against density variations

The goal of the study was to test the hypothesis that shoot-through FLASH proton beams would lead to lower dose-averaged LET (LET ) values in critical organs, while providing at least equal normal tissue sparing as clinical proton therapy plans. 

 For five neurological tumor patients, Pencil Beam Scanning (PBS) shoot-through plans were made, using the maximum energy of 227 MeV and assuming a hypothetical FLASH protective factor (FPF) of 1.5. The effect of different FPF ranging from 1.2-1.8 on the clinical goals were also considered. LET was calculated for the clinical plan and the shoot-through plan, applying a 2 Gy total dose threshold (RayStation 8A/9B and 9A-IonRPG). Robust evaluation was performed considering density uncertainty (±3% throughout entire volume).

 
Clinical plans showed large LET variations compared to shoot-through plans and the maximum LET in OAR is 1.2 - 8 times lower for the latter. Although less conformal, shoot-through plans met the same clinical goals as the clinical plans, for FLASH protection factors above 1.4. The FLASH shoot-through plans were more robust to density uncertainties with a maximum OAR D increase of 0.6 Gy versus 5.7 Gy in the clinical plans.

 
Shoot-through proton FLASH beams avoid uncertainties in LET distributions and proton range, provide adequate target coverage, meet planning constraints and are robust to density variations.&#xD.