Technical note: Vendor-agnostic water phantom for 3D dosimetry of complex fields in particle therapy.

PURPOSE: Three-dimensional (3D) dosimetry is a necessity to validate patient-specific treatment plans in particle therapy as well as to facilitate the development of novel treatment modalities. Therefore, a vendor-agnostic water phantom was developed and verified to measure high resolution 3D dose distributions. METHODS: The system was experimentally validated at the Marburger Ionenstrahl-Therapiezentrum using two ionization chamber array detectors (PTW Octavius 1500XDR and 1000P) with 150.68 MeV proton and 285.35 MeV/u 12 C beams. The dose distribution of several monoenergetic and complex scanned fields were measured with different step sizes to assess the reproducibility, absolute positioning accuracy, and general performance of the system. RESULTS: The developed system was successfully validated and used to automatically measure high resolution 3D dose distributions. The reproducibility in depth was better than ±25 micron. The roll and tilt uncertainty of the detector was estimated to be smaller than ±3 mrad. CONCLUSIONS: The presented system performed fully automated, high resolution 3D dosimetry, suitable for the validation of complex radiation fields in particle therapy. The measurement quality is comparable to commercially available systems.

Spread-out Bragg peak FLASH: quantifying normal tissue toxicity in a murine model.

Objective: A favorable effect of ultra-high dose rate (FLASH) radiation on normal tissue-sparing has been indicated in several preclinical studies. In these studies, the adverse effects of radiation damage were reduced without compromising tumor control. Most studies of proton FLASH investigate these effects within the entrance of a proton beam. However, the real advantage of proton therapy lies in the Spread-out Bragg Peak (SOBP), which allows for giving a high dose to a target with a limited dose to healthy tissue at the entrance of the beam. Therefore, a clinically relevant investigation of the FLASH effect would be of healthy tissues within a SOBP. Our study quantified the tissue-sparing effect of FLASH radiation on acute and late toxicity within an SOBP in a murine model. Material/Methods: Radiation-induced damage was assessed for acute and late toxicity in the same mice following irradiation with FLASH (Field dose rate of 60 Gy/s) or conventional (CONV, 0.34 Gy/s) dose rates. The right hindleg of unanesthetized female CDF1 mice was irradiated with single-fraction doses between 19.9-49.7 Gy for CONV and 30.4-65.9 Gy for FLASH with 5-8 mice per dose. The leg was placed in the middle of a 5 cm SOBP generated from a mono-energetic beam using a 2D range modulator. Acute skin toxicity quantified by hair loss, moist desquamation and toe separation was monitored daily within 29 days post-treatment. Late toxicity of fibrotic development measured by leg extendibility was monitored biweekly until 30 weeks post-treatment. Results: Comparison of acute skin toxicity following radiation indicated a tissue-sparing effect of FLASH compared to conventional single-fraction radiation with a mean protection ratio of 1.40 (1.35-1.46). Fibrotic development similarly indicated normal tissue sparing with a 1.18 (1.17-1.18) protection ratio. The acute skin toxicity tissue sparing was similar to data from entrance-beam irradiations of Sørensen et al. (4). Conclusion: Full dose-response curves for acute and late toxicity after CONV and FLASH radiation were obtained. Radiation within the SOBP retains the normal-tissue-sparing effect of FLASH with a dose-modifying factor of 40% for acute skin damage and 18% for fibrotic development.

Development, Monte Carlo simulations and experimental evaluation of a 3D range-modulator for a complex target in scanned proton therapy.

The purpose of this work was to develop and manufacture a 3D range-modulator (3D RM) for a complex target contour for scanned proton therapy. The 3D RM is considered to be a viable technique for the very fast dose application in patient-specific tumors with only one fixed energy. The RM was developed based on a tumor from a patient CT and manufactured with high-quality 3D printing techniques with both polymer resin and aluminum. Monte Carlo simulations were utilized to investigate its modulating properties and the resulting dose distribution. Additionally, the simulation results were validated with measurements at the Marburg Ion-Beam Therapy Centre. For this purpose, a previously developed water phantom was used to conduct fast, automated high-resolution dose measurements. The results show a very good agreement between simulations and measurements and indicate that highly homogeneous dose distributions are possible. The delivered dose is conformed to the distal as well as to the proximal edge of the target. The 3D range-modulator concept combines a high degree of dose homogeneity and conformity, comparable to standard IMPT with very short irradiation times, promising clinically applicable dose distributions for lung and/or FLASH treatment, comparable and competitive to those from conventional irradiation techniques.

Monte Carlo simulations and dose measurements of 2D range-modulators for scanned particle therapy.

This paper introduces the concept of a 2D range-modulator as a static device for generating spread-out Bragg peaks at very small distances to the target. The 2D range-modulator has some distinct advantages that can be highly useful for different research projects in particle therapy facilities. Most importantly, it creates an instantaneous, quasi-static irradiation field with only one energy, thus decreasing irradiation time tremendously. In addition, it can be manufactured fast and cost efficiently and its SOBP width and shape can be adjusted easily for the specific purpose/experiment. As the modulator is a static element, there is no need for rotation (e.g. like in a modulation wheel) or lateral oscillation and due to the small base structure period it can be positioned close to the target. Two different rapid prototyping manufacturing techniques were utilized. The modulation properties of one polymer and one steel modulator were investigated with both simulations and measurements. For this purpose, a sophisticated water phantom system (WERNER), that can perform fast, completely automated and high resolution dose measurements, was developed. Using WERNER, the dose distribution of a modulator can be verified quickly and reliably, both during experiments, as well as in a time constrained clinical environment. The maximum deviation between the Monte Carlo simulations and dose measurements in the spread-out Bragg peak region was 1.4% and 4% for the polymer and steel modulator respectively. They were able to create spread-out Bragg peaks with a high degree of dose homogeneity, thus validating the whole process chain, from the mathematical optimization and modulator development, to manufacturing, MC simulations and dose measurements. Combining the convenience, flexibility and cost-effectiveness of rapid prototyping with the advantages of highly customizable modulators, that can be adapted for different experiments, the 2D range-modulator is considered a very useful tool for a variety of research objectives. Moreover, we have successfully shown that the manufacturing of 2D modulators with high quality and high degree of homogeneity is possible, paving the way for the further development of the more complex 3D range-modulators, which are considered a viable option for the very fast treatment of moving targets and/or FLASH irradiation.

2D range modulator for high-precision water calorimetry in scanned carbon-ion beams.

Ionization chamber-based dosimetry for carbon-ion beams still shows a significantly higher standard uncertainty than high-energy photon dosimetry. This is mainly caused by the high standard uncertainty of the correction factor for beam quality [Formula: see text]. Due to a lack of experimental data, the given values for [Formula: see text] are based on theoretical calculations. To reduce this standard uncertainty, [Formula: see text] factors for different irradiation conditions and ionization chambers (ICs) can be determined experimentally by means of water calorimetry. To perform such measurements in a spread-out Bragg peak (SOBP) for a scanned carbon-ion beam, we describe the process of creating an almost cubic dose distribution of about 6 × 6 × 6 cm3 using a 2D range modulator. The aim is to achieve a field homogeneity with a standard deviation of measured dose values in the middle of the SOBP (over a lateral range and a depth of about 4 cm) below 2% within a scanning time of under 100 s, applying a dose larger than 1 Gy. This paper describes the optimization and characterization of the dose distribution in detail.

A new facility for proton radiobiology at the Trento proton therapy centre: Design and implementation.

We present a new facility dedicated to radiobiology research, which has been implemented at the Trento Proton Therapy Centre (Italy). A dual-ring double scattering system was designed to produce irradiation fields of two sizes (i.e. 6 and 16 cm diameter) starting from a fix pencil beam at 148 MeV. The modulation in depth was obtained with a custom-made range modulator, optimized to generate a 2.5 cm spread-out Bragg peak (SOBP). The resulting irradiation field was characterized in terms of lateral and depth-dose profiles. The beam characteristics and the geometry of the setup were implemented in the Geant4 Monte Carlo (MC) code. After benchmark against experimental data, the MC was used to characterize the distribution of dose-average linear energy transfer (LET) associated to the irradiation field. The results indicate that dose uniformity above 92.9% is obtained at the entrance channel as well as in the middle SOBP in the target regions for both irradiation fields. Dose rate in the range from 0.38 to 0.78 Gy/min was measured, which can be adjusted by proper selection of cyclotron output current, and eventually increased by about a factor 7. MC simulations were able to reproduce experimental data with good agreement. The characteristics of the facility are in line with the requirements of most radiobiology experiments. Importantly, the facility is also open to external users, after successful evaluation of beam proposals by the Program Advisory Committee.

Modulation power of porous materials and usage as ripple filter in particle therapy.

Porous materials with microscopic structures like foam, sponges, lung tissues and lung substitute materials have particular characteristics, which differ from those of solid materials. Ion beams passing through porous materials show much stronger energy straggling than expected for non-porous solid materials of the same thickness. This effect depends on the microscopic fine structure, the density and the thickness of the porous material. The beam-modulating effect from a porous plate enlarges the Bragg peak, yielding similar benefits in irradiation time reduction as a ripple filter. A porous plate can additionally function as a range shifter, which since a higher energy can be selected for the same penetration depth in the body reduces the scattering at the beam line and therefore improves the lateral fall-off. Bragg curve measurements of ion beams passing through different porous materials have been performed in order to determine the beam modulation effect of each. A mathematical model describing the correlation between the mean material density, the porous pore structure size and the strength of the modulation has been developed and a new material parameter called 'modulation power' is defined as the square of the Gaussian sigma divided by the mean water-equivalent thickness of the porous absorber. Monte Carlo simulations have been performed in order to validate the model and to investigate the Bragg peak enlargement, the scattering effects of porosity and the lateral beam width at the end of the beam range. The porosity is found to only influence the lateral scattering in a negligible way. As an example of a practical application, it is found that a 20 mm and 50 mm plate of Gammex LN300 performs similar to a 3 mm and 6 mm ripple filter, respectively, and at the same time can improve the sharpness of the lateral beam due to its multifunctionality as a ripple filter and a range shifter.

3D range-modulator for scanned particle therapy: development, Monte Carlo simulations and experimental evaluation.

The purpose of this work was to design and manufacture a 3D range-modulator for scanned particle therapy. The modulator is intended to create a highly conformal dose distribution with only one fixed energy, simultaneously reducing considerably the treatment time. As a proof of concept, a 3D range-modulator was developed for a spherical target volume with a diameter of 5 cm, placed at a depth of 25 cm in a water phantom. It consists of a large number of thin pins with a well-defined shape and different lengths to modulate the necessary shift of the Bragg peak. The 3D range-modulator was manufactured with a rapid prototyping technique. The FLUKA Monte Carlo package was used to simulate the modulating effect of the 3D range-modulator and the resulting dose distribution. For that purpose, a special user routine was implemented to handle its complex geometrical contour. Additionally, FLUKA was extended with the capability of intensity modulated scanning. To validate the simulation results, dose measurements were carried out at the Heidelberg Ion Beam Therapy Center with a 400.41 MeV/u 12C beam. The high resolution dosimetric measurements show a good agreement between simulated and measured dose distributions. Irradiation of the monoenergetic raster plan took 3 s, which is approximately 20 times shorter than a comparable plan with 16 different energies. The combination of only one energy and a 3D range-modulator leads to a tremendous decrease in irradiation time. 'Interplay effects', typical for moving targets and pencil beam scanning, can be immensely reduced or disappear completely, making the delivery of a homogeneous dose to moving targets more reliable. Combining high dose conformity, very good homogeneity and extremely short irradiation times, the 3D range-modulator is considered to become a clinically applicable method for very fast treatment of lung tumours.

Dosimetric comparisons of carbon ion treatment plans for 1D and 2D ripple filters with variable thicknesses.

A ripple filter (RiFi)-also called mini-ridge filter-is a passive energy modulator used in particle beam treatments that broadens the Bragg peak (BP) as a function of its maximum thickness. The number of different energies requested from the accelerator can thus be reduced, which significantly reduces the treatment time. A new second generation RiFi with 2D groove shapes was developed using rapid prototyping, which optimizes the beam-modulating material and enables RiFi thicknesses of up to 6 mm. Carbon ion treatment plans were calculated using the standard 1D 3 mm thick RiFi and the new 4 and 6 mm 2D RiFis for spherical planning target volumes (PTVs) in water, eight stage I non-small cell lung cancer cases, four skull base chordoma cases and three prostate cancer cases. TRiP98 was used for treatment planning with facility-specific base data calculated with the Monte Carlo code SHIELD-HIT12A. Dose-volume-histograms, spatial dose distributions and dosimetric indexes were used for plan evaluation. Plan homogeneity and conformity of thinner RiFis were slightly superior to thicker RiFis but satisfactory results were obtained for all RiFis investigated. For the 6 mm RiFi, fine structures in the dose distribution caused by the larger energy steps were observed at the PTV edges, in particular for superficial and/or very small PTVs but performances for all RiFis increased with penetration depth due to straggling and scattering effects. Plans with the new RiFi design yielded for the studied cases comparable dosimetric results to the standard RiFi while the 4 and 6 mm RiFis lowered the irradiation time by 25-30% and 45-49%, respectively.