Consuelo Guardiola

Optimization of the mechanical collimation for minibeam generation in proton minibeam radiation therapy

Purpose The dose tolerances of normal tissues continue to be the main barrier in radiation therapy. To lower it, a novel concept based on a combination of proton therapy and the use of arrays of parallel and thin beams has been recently proposed: proton minibeam radiation therapy (pMBRT). It allies the inherent advantages of protons with the remarkable normal tissue preservation observed when irradiated with submillimetric spatially fractionated beams. Due to multiple Coulomb scattering, the tumor receives a homogeneous dose distribution, while normal tissues in the beam path benefit from the spatial fractionation of the dose. This promising technique has already been implemented at a clinical center (Proton therapy Center of Orsay) by means of a first prototype of a multislit collimator. The main goal of this work was to optimize the minibeam generation by means of a mechanical collimation. Methods Monte Carlo simulations (GATE V7.1) were used to evaluate the influence of the collimator material (brass, nickel, iron, tungsten), thickness, phantom‐to‐collimator distance (PCD), among other parameters, on the dose distributions. Maximization of the peak‐to‐valley dose ratios (PVDR) in normal tissues along with minimization of full width at half maximum, penumbras and neutron contamination were used as figures of merit. As a starting point for the optimization, the collimator employed in our previous works was used. It consisted in 400 μm × 2 cm slits with a center‐to‐center distance (c‐t‐c) of 3200 μm. As the main targets of pMBRT will be neurological cases, 100 MeV energy proton minibeams were considered. This energy range would allow treating tumors located at the center of the brain (the worst scenario). Results Tungsten and brass are the most advantageous materials among those considered. A tungsten collimator provides the highest PVDR and lowest penumbra. Although the neutron yield generated in the tungsten collimator is 3 times higher than that of the other materials, the biologic neutron doses at the patient position amount to less than 0.05% and 0.7% of the peak and valley doses, respectively. In addition, shorter PCD than the one currently used (7 cm) leads to thinner beams (enhancing the dose‐volume effects), accompanied, however, by an increase of neutron dose at the phantom surface. Finally, no gain in dose distributions is obtained by using nonparallel slits. Conclusions The collimator design and irradiation configuration have been optimized to minimize the angular spread, deliver the highest PVDR and the lowest valley possible in the normal tissues in pMBRT. We have also confirmed that even though the neutron yield generated in the multislit collimator is higher with respect to the one produced by the collimators used in conventional proton therapy, the increase of biological neutron dose in the patient will remain low (less than 1%).

Measurement of carbon ion microdosimetric distributions with ultrathin 3D silicon diodes

The commissioning of an ion beam for hadrontherapy requires the evaluation of the biologically weighted effective dose that results from the microdosimetric properties of the therapy beam. The spectra of the energy imparted at cellular and sub-cellular scales are fundamental to the determination of the biological effect of the beam. These magnitudes are related to the microdosimetric distributions of the ion beam at different points along the beam path. This work is dedicated to the measurement of microdosimetric spectra at several depths in the central axis of a (12)C beam with an energy of 94.98 AMeV using a novel 3D ultrathin silicon diode detector. Data is compared with Monte Carlo calculations providing an excellent agreement (deviations are less than 2% for the most probable lineal energy value) up to the Bragg peak. The results show the feasibility to determine with high precision the lineal energy transfer spectrum of a hadrontherapy beam with these silicon devices.

Effect of X-ray minibeam radiation therapy on clonogenic survival of glioma cells

Highlights • First in vitro study performed in an X-ray SARRP for minibeam irradiations.• At equal mean dose, the same tumor control can be obtained with standard and minibeam irradiations.• This contradicts the established paradigms of the standard radiation therapy.

Transfer of Minibeam Radiation Therapy into a cost-effective equipment for radiobiological studies: a proof of concept

Minibeam radiation therapy (MBRT) is an innovative synchrotron radiotherapy technique able to shift the normal tissue complication probability curves to significantly higher doses. However, its exploration was hindered due to the limited and expensive beamtime at synchrotrons. The aim of this work was to develop a cost-effective equipment to perform systematic radiobiological studies in view of MBRT. Tumor control for various tumor entities will be addressable as well as studies to unravel the distinct biological mechanisms involved in normal and tumor tissues responses when applying MBRT. With that aim, a series of modifications of a small animal irradiator were performed to make it suitable for MBRT experiments. In addition, the brains of two groups of rats were irradiated. Half of the animals received a standard irradiation, the other half, MBRT. The animals were followed-up for 6.5 months. Substantial brain damage was observed in the group receiving standard RT, in contrast to the MBRT group, where no significant lesions were observed. This work proves the feasibility of the transfer of MBRT outside synchrotron sources towards a small animal irradiator.

Microdosimetry with micro-pattern silicon devices

Current techniques of cancer treatment using protons and heavy ions (hadrons) are an expanding branch of the external radiation therapy. Characterization of radiobiological efficiency of the hadron beams depends on the knowledge of the energy deposition distributions associated to their track structure. Novel manufacturing techniques led to the fabrication of micrometer-scale instruments for the measurement of such quantities. A 3D diode microdosimeter was tested under radiation sources, proton and carbon beams. The results are consistent with Monte Carlo simulations showing great agreement between them.