Minibeam therapy shows great potential to improve the process further. By turning uniform beams of protons and light ions into arrays of parallel pencil-shaped or planar minibeams with 0.3 mm incident size – which gradually broaden and merge to produce a solid beam – proximal tissues can be spared.

Prior research has shown that this tissue sparing is due to the dose-volume effect and the rapid repair of capillary blood vessels via regeneration of angiogenic cells surviving between the beams. What this means for future treatment of children with brain tumours is less risk of developing neurocognitive and neurological defects.

To investigate this approach further, F Avraham Dilmanian, professor of research in the departments of radiation oncology, neurology and radiology at Stony Brook University Medical Center, and co-authors Sunil Krishnan and John Eley from the University of Texas MD Anderson Cancer Center, conducted studies using pristine proton beams from a synchrotron (Int. J. Radiat. Oncol. Biol. Phys. 92 469).

The researchers produced 100 and 109 MeV protons (corresponding to a range of 8–10 cm) with a 0.3 mm pinhole collimator. A stack of radiochromatic films interspersed with 2 mm plastic sheets was positioned downstream of the collimator and irradiated to 10 Gy peak dose to measure the minibeam's broadening. They also exposed film to an array of planar proton minibeams, produced using a 5 cm thick tungsten multislit collimator of 0.3 mm beam width and 1 mm on-centre beam spacing.

They reported that "the minibeams' ideal on-centre spacing to allow merging of 0.3 mm incident minibeams when they are 0.7 mm in size is 0.7 mm. However, for a deeper proximal side of the target, either larger spacing or a heavier ion species such as helium or lithium can be used." The research suggests that, due to a larger production yield and ease of collimator custom fabrication, planar beams may be preferable over pencil beams for clinical translation.

The method's tissue sparing depth (where the beam full-width at half-maximum reached 0.7 mm) was approximately 25 mm for protons and much larger for light ions – sufficient to cover the skull and much of the cortex. This method could improve the performance of proton therapy in treating paediatric brain tumours by sparing the cortex. The authors suggested that other applications could include head-and-neck tumours where parotid glands are to be spared, tumours near the eye socket and paediatric spine tumours. Hyperfractionization may be another application, particularly for lung and liver tumours where the chest and abdomen wall could be exposed to much higher doses.

The authors advised that ongoing studies are currently being performed at the University of Texas MD Anderson Cancer Center to demonstrate the tissue-sparing effect of proton minibeams in the mouse brain compared to solid proton beams. If funding can be obtained, they hope to next measure the proton minibeams' tissue sparing in the normal rat brain and to treat rats with intracranial brain tumours. Because the method is not so different to conventional proton therapy, they hope that after that, they can proceed to limited Phase I human studies.

"We think that some of the future hurdles to implementation may be to optimize the spacing between the minibeams (assuming a fixed 0.3-mm incident minibeam thickness) so that they merge with each other at the proximal side of the target," the authors told medicalphysicsweb. "To avoid smearing of the minibeams' dose into a solid beam in the first few centimetres of the tissue, a frame positioned in front of the multislit collimator will need to be pressed against the subject. The frame's function will be also to introduce a gap between the collimator and the subject to reduce the subject's exposure to an already small dose of neutrons being knocked out from the collimator by the incident solid proton beam."

The authors state that proton minibeams can be implemented quite easily at existing particle therapy centres using passively scattered proton beams or pencil-beam spot scanning techniques. This will require positioning of a multi-slit collimator downstream from the gantry head beyond the aperture, calculating the new dose distribution in the subject and performing dosimetric quality assurance before treatment.

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