Biological and dosimetric characterisation of spatially fractionated proton minibeams

Abstract

The biological effectiveness of proton beams varies with depth, spot size and lateral distance from the beam central axis. The aim of this work is to incorporate proton relative biological effectiveness (RBE) and equivalent uniform dose (EUD) considerations into comparisons of broad beam and highly modulated proton minibeams. A Monte Carlo model of a small animal proton beamline is presented. Dose and variable RBE is calculated on a per-voxel basis for a range of energies (30-109 MeV). For an open beam, the RBE values at the beam entrance ranged from 1.02-1.04, at the Bragg peak (BP) from 1.3 to 1.6, and at the distal end of the BP from 1.4 to 2.0. For a 50 MeV proton beam, a minibeam collimator designed to produce uniform dose at the depth of the BP peak, had minimal impact on the open beam RBE values at depth. RBE changes were observed near the surface when the collimator was placed flush with the irradiated object, due to a higher neutron contribution derived from proton interactions with the collimator. For proton minibeams, the relative mean RBE weighted entrance dose (RWD) was ~25% lower than the physical mean dose. A strong dependency of the EUD with fraction size was observed. For 20 Gy fractions, the EUD varied widely depending on the radiosensitivity of the cells. For radiosensitive cells, the difference was up to ~50% in mean dose and ~40% in mean RWD and the EUD trended towards the valley dose rather than the mean dose. For comparative studies of uniform dose with spatially fractionated proton minibeams, EUD derived from a per-voxel RWD distribution is recommended for biological assessments of reproductive cell survival and related endpoints.

Implementation of planar proton minibeam radiation therapy using a pencil beam scanning system: A proof of concept study

“…An accurate quantification of these physical quantities should be the subject of a future study, especially since the measurement of lineal energy distributions with new solid‐state (silicon or diamond) microdosimeters now appears to be accessible . Lastly, EUD corrections could also be recommended when evaluating and comparing uniform with spatially fractionated irradiation geometries …”

“…52 Lastly, EUD corrections could also be recommended when evaluating and comparing uniform with spatially fractionated irradiation geometries. 53 A particularly interesting potential clinical application of pMBRT irradiations with pencil beam scanning would be management of intra-fraction motion during treatment delivery, as hypofractionation is typically a key objective of pMBRT (a few tens of grays per fraction, 5,6 ). In this work, mean dose-rates of 6 Gy/min were obtained for multislit conditions, allowing a dose of 60 Gy to be delivered within a reasonable treatment time of 10 min.…”

Clinical microbeam radiation therapy with a compact source: specifications of the line-focus X-ray tube

“…To interpret spatially fractionated dose distributions, the calculation of the equivalent uniform dose (EUD) has been suggested [26]. With the EUD concept, inhomogeneous dose distributions are assigned to a homogeneous dose that leads to the same clonogenic cell survival [27].…”

Dosimetry and characterization of a 25‐MeV proton beam line for preclinical radiobiology research

“…15 Currently, proton preclinical platforms (E ≤ 50 MeV) are burgeoning, offering the technical precision required to deliver precise millimeter-sized beams to localized regions within rodents. [16][17][18] Small-animal radiotherapy research platforms mimicking accurately human radiotherapy conditions are needed to reproduce pathologies observed in patients (improvement of animal models) and better understand the therapeutic possibilities and toxicities of PT. Several studies already improved the beam delivery and dose calculation for focal irradiation in the rat brain with gamma rays 19 and image-guided x rays.…”