Wilfredo González

Theoretical dosimetric evaluation of carbon and oxygen minibeam radiation therapy

Purpose Charged particles have several advantages over x‐ray radiations, both in terms of physics and radiobiology. The combination of these advantages with those of minibeam radiation therapy (MBRT) could help enhancing the therapeutic index for some cancers with poor prognosis. Among the different ions explored for therapy, carbon ions are considered to provide the optimum physical and biological characteristics. Oxygen could be advantageous due to a reduced oxygen enhancement ratio along with a still moderate biological entrance dose. The aforementioned reasons justified an in‐depth evaluation of the dosimetric features of carbon and oxygen minibeam radiation therapy to establish the interest of further explorations of this avenue. Materials and methods The GATE/Geant4 6.2 Monte Carlo simulation platform was employed to simulate arrays of rectangular carbon and oxygen minibeams (600 μm × 2 cm) at a water phantom entrance. They were assumed to be generated by means of a magnetic focusing. The irradiations were performed with a 2‐cm‐long spread‐out Bragg peak (SOBP) centered at 7‐cm‐depth. Several center‐to‐center (c‐t‐c) distances were considered. Peak and valley doses, as well as peak‐to‐valley dose ratio (PVDR) and the relative contribution of nuclear fragments and electromagnetic processes were assessed. In addition, the type and proportion of the secondary nuclear fragments were evaluated in both peak and valley regions. Results Carbon and oxygen MBRT lead to very similar dose distributions. No significant advantage of oxygen over carbon ions was observed from physical point of view. Favorable dosimetric features were observed for both ions. Thanks to the reduced lateral scattering, the standard shape of the depth dose curves (in the peaks) is maintained even for submillimetric beam sizes. When a narrow c‐t‐c is considered (910‐980 μm), a (quasi) homogenization of the dose can be obtained at the target, while a spatial fractionation of the dose is maintained in the proximal normal tissues with low PVDR. In contrast when a larger c‐t‐c is used (3500 μm) extremely high PVDR (≥ 50) are obtained in normal tissues, corresponding to very low valley doses. This suggests that carbon and oxygen MBRT might lead to a significant reduction of normal tissue complication probability. The main participant to the valley doses are secondary nuclear products at all depths. Among them the highest yield in normal tissues corresponds to the lightest fragments, neutrons and protons. Heavier fragments are dominant in the valleys only at the target position, which might favor tumor control. Conclusions The computed dose distributions suggest that a spatial fractionation of the dose combined to the use of submillimetric field sizes might allow profiting from the high efficiency of carbon and oxygen ions for the treatment of radioresistant tumors, while preserving normal tissues. Only biological experiments could confirm the shifting of the normal tissue complication probability curves. The authors’ results support the further exploration of this avenue.

Carbon and oxygen minibeam radiation therapy: an experimental dosimetric evaluation

Purpose: To perform dosimetric characterization of a minibeam collimator in both carbon and oxygen ion beams to guide optimal setup geometry and irradiation for future radiobiological studies. Methods: Carbon and oxygen minibeams were generated using a prototype tungsten multislit collimator presenting line apertures 700 μm wide, which are spaced 3500 μm centre‐to‐centre distance apart. Several radiation beam spots generated the desired field size of 15 × 15 mm2 and production of a 50 mm long spread out Bragg peak (SOBP) centered at 80 mm depth in water. Dose evaluations were performed with two different detectors: a PTW microDiamondSymbol single crystal diamond detector and radiochromic films (EBT3). Peak‐to‐valley dose ratio (PVDR) values, output factors (OF), penumbras, and full width at half maximum (FWHM) were measured. Symbol. No Caption available. Results: Measured lateral dose profiles exhibited spatial fractionation of dose at depth in a water phantom in the expected form of peaks and valleys for both carbon and oxygen radiation fields. The diamond detector and radiochromic film provided measurements of PVDR in good agreement. PVDR values at shallow depth were about 60 and decreased to about 10 at 80 mm depth in water. OF in the center of the SOBP was about 0.4; this value is larger than the corresponding one in proton minibeam radiation therapy measured using a comparable collimator due to a reduced lateral scattering for carbon and oxygen minibeams. Conclusions: Carbon and oxygen minibeams may be produced by a mechanical collimator. PVDR values and output factors measured in this first study of these minibeam radiation types indicate there is potential for their therapeutic use. Optimization of minibeam collimator design and the number and size of focal spots for irradiation are advocated to improve PDVR values and dose distributions for each specific applied use.

Spatial fractionation of the dose in heavy ions therapy: An optimization study

PURPOSE The alliance of charged particle therapy and the spatial fractionation of the dose, as in minibeam or Grid therapy, is an innovative strategy to improve the therapeutic index in the treatment of radioresistant tumors. The aim of this work was to assess the optimum irradiation configuration in heavy ion spatially fractionated radiotherapy (SFRT) in terms of ion species, beam width, center-to-center distances, and linear energy transfer (LET), information that could be used to guide the design of the future biological experiments. The nuclear fragmentation leading to peak and valley regions composed of different secondary particles, creates the need for a more complete dosimetric description that the classical one in SFRT. METHODS Monte Carlo simulations (GATE 6.2) were performed to evaluate the dose distributions for different ions, beam widths, and spacings. We have also assessed the 3D-maps of dose-averaged LET and proposed a new parameter, the peak-to-valley-LET ratio, to offer a more thorough physical evaluation of the technique. RESULTS Our results show that beam widths larger than 400 μm are needed in order to keep a ratio between the dose in the entrance and the dose in the target of the same order as in conventional irradiations. A large ctc distance (3500 μm) would favor tissue sparing since it provides higher PVDR, it leads to a reduced contribution of the heavier nuclear fragments and a LET value in the valleys a factor 2 lower than the LET in the ctc leading to homogeneous distributions in the target. CONCLUSIONS Heavy ions MBRT provide advantageous dose distributions. Thanks to the reduced lateral scattering, the use of submillimetric beams still allows to keep a ratio between the dose in the entrance and the dose in the target of the same order as in conventional irradiations. Large ctc distances (3500 μm) should be preferred since they lead to valley doses composed of lighter nuclear fragments resulting in a much reduced dose-averaged LET values in normal tissue, favoring its preservation. Among the different ions species evaluated, Ne stands out as the one leading to the best balance between high PVDR and PVLR in normal tissues and high LET values (close to 100 keV/μm) and a favorable oxygen enhancement ratio in the target region.

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.