Abstract
BACKGROUND: Cyclotron-based proton therapy systems utilize the highest proton energies to achieve an ultra-high dose rate (UHDR) for FLASH radiotherapy. The deep-penetrating range associated with this high energy can be modulated by inserting a uniform plate of proton-stopping material, known as a range shifter, in the beam path at the nozzle to bring the Bragg peak within the target while ensuring high proton transport efficiency for UHDR. Aluminum has been recently proposed as a range shifter material mainly due to its high compactness and its mechanical properties. A possible drawback lies in the fact that aluminum has a larger cross-section of producing secondary neutrons compared to conventional plastic range shifters. Accordingly, an increase in secondary neutron contamination was expected during the delivery of range-modulated FLASH proton therapy, potentially heightening neutron-induced carcinogenic risks to the patient. PURPOSE: We conducted neutron dosimetry using simulations and measurements to evaluate excess dose due to neutron exposure during UHDR proton irradiation with aluminum range shifters compared to plastic range shifters. METHODS: Monte Carlo simulations in TOPAS were performed to investigate the secondary neutron production characteristics with aluminum range shifter during 225 MeV single-spot proton irradiation. The computational results were validated against measurements with a pair of ionization chambers in an out-of-field region ( ≤ 30 cm) and with a Proton Recoil Scintillator-Los Alamos rem meter in a far-out-of-field region (0.5-2.5 m). The assessments were repeated with solid water slabs as a surrogate for the conventional range shifter material to evaluate the impact of aluminum on neutron yield. The results were compared with the International Electrotechnical Commission (IEC) standards to evaluate the clinical acceptance of the secondary neutron yield. RESULTS: For a range modulation up to 26 cm in water, the maximum simulated and measured values of out-of-field secondary neutron dose equivalent per therapeutic dose with aluminum range shifter were found to be (0.57 ± 0.02) mSv/Gy and (0.46 ± 0.04) mSv/Gy , respectively, overall higher than the solid water cases (simulation: (0.332 ± 0.003) mSv/Gy ; measurement: (0.33 ± 0.03) mSv/Gy ). The maximum far out-of-field secondary neutron dose equivalent was found to be ( 8.8 ± 0.5 ) μSv/Gy and ( 1.62 ± 0.02 ) μSv/Gy for the simulations and rem meter measurements, respectively, also higher than the solid water counterparts (simulation: ( 3.3 ± 0.3 ) μSv/Gy ; measurement: ( 0.63 ± 0.03 ) μSv/Gy ). CONCLUSIONS: We conducted simulations and measurements of secondary neutron production under proton irradiation at FLASH energy with range shifters. We found that the secondary neutron yield increased when using aluminum range shifters compared to conventional materials while remaining well below the non-primary radiation limit constrained by the IEC regulations.