The MEVION proton gantry and the Monte Carlo model of the nozzle components, showing the range shifter plates, the adaptive aperture and (in yellow) a single CT slice of the mouse. (Courtesy: Isabel Almeida)Image-guided radiation delivery systems for pre-clinical animal research have been helping researchers throughout the world to make discoveries and advancements in cancer treatment. If state-of-the-art photon research platforms could be economically adapted for proton therapy, this could open up a completely new field in pre-clinical research.
Researchers at Maastricht University Medical Centre and MAASTRO Clinic have investigated the feasibility of using a compact clinical proton therapy system for pre-clinical research with millimetric beams. They determined that the MEVION S250i proton system with HYPERSCAN pencil-beam scanning technology and adaptive aperture-controlled collimation could be potentially be used for small-animal radiation research (Br. J. Radiol. 10.1259/bjr.20180446).
The MEVION S250i uses a gantry-mounted superconducting synchrocyclotron proton accelerator, which rotates in the treatment room around a patient. The pencil-beam delivery path is designed to reduce delivery times, and the automated adaptive aperture generates layer-by-layer beam collimation with a 5–6 mm collimated spot sizes for all energies (0–32 cm depth).
For the dosimetric study, principal investigator Frank Verhaegen and colleagues examined a sub-millimetric cone-beam CT (CBCT) image of a mouse with an orthotopic lung tumour of a few millimetres. First, the team used the SmART-ATP small-animal radiotherapy planning system to design an X-ray photon irradiation plan that delivered a prescribed dose of 2 Gy to the tumour.
To create the proton plans, the researchers modelled the nozzle of the proton beam line, including the energy modulation system (EMS) and the adaptive aperture. They performed Monte Carlo simulations of a single spot proton pencil beam aimed at the tiny tumour site. They simulated seven treatment scenarios, which combined two to three treatment fields, used five field sizes and different energies, including energies of less than 40 MeV, in which the Bragg peak stopped inside the tumour, and higher energies that extended beyond the tumour.
The researchers calculated the dose–volume histogram metrics D95 and D5 (dose to 95% and 5% of the tumour, respectively) for the large number of dose distributions simulated for each treatment scenario. From these, they selected the best plan for each scenario and evaluated the dose received by the tumour and the organs-at-risk. They determined that the proton plans achieved good tumour coverage, with potentially less damage to the organs-at-risk than the photon plans.
The team also calculated the delivery efficiency of the system, to quantify the number of protons generated, and whether the prescribed 2 Gy dose could be delivered by such a small beam in an acceptable irradiation time for a laboratory animal. They determined that for very small fields and low energies, the number of protons arriving to the target dropped to 1-3%, but that treatment times would be below 5 s.
The best-case tumour coverage, with the steepest slope between D5 and D95, was achieved for a three-field delivery with field sizes of 5×4, 5×3 and 5×3 mm. Although the “shoot through” technique would be expected to give better target coverage, the use of a single spot beam resulted in a non-uniformity of the dose distribution in the lateral direction.
The authors noted that the EMS could be a disadvantage for pre-clinical work because it prevents the easy production of sharper beams. “The EMS is a set of plastic plates that can be inserted in the proton beam. By doing this, protons lose energy in the plates, which decreases their range,” Verhaegen explains. “The protons emerging from the accelerator before the range shifter always have the same energy, a characteristic of a cyclotron. Therefore, the proton Bragg peak has approximately the same shape for all combinations of range shifters, so we cannot make it much narrower in the longitudinal direction; this could be a disadvantage when irradiating small targets of a few millimetres or less. For very small targets, we may prefer the shoot-through technique with multiple crossing beams to create high dose in the crossfire.”
The authors also point out that to perform the experiments that they simulated, a high-precision positioning platform with a coupled high-resolution CBCT imager would be necessary to assure sub-millimetric uncertainty of the mouse positioning while keeping the gantry at a fixed angle.
Verhaegen tells Physics World that a single platform with an X-ray irradiator onboard and an X-ray imager would be needed. Ideally, researchers would like to dock this type of photon system to an existing proton beam line.
“Proton beamlines will always be too expensive to develop one dedicated to small-animal research,” Verhaegen explains. “In our case at Maastricht, the photon irradiator is too heavy to move due to lead radiation shielding. We have applied for funding to develop a next-generation mobile research platform that can handle photon irradiation and can be docked to a proton beam. This is what we expect researchers to do in the future.”