Single proton LET characterization with the Timepix detector and artificial intelligence for advanced proton therapy treatment planning.

Objective.Protons have advantageous dose distributions and are increasingly used in cancer therapy. At the depth of the Bragg peak range, protons produce a mixed radiation field consisting of low- and high-linear energy transfer (LET) components, the latter of which is characterized by an increased ionization density on the microscopic scale associated with increased biological effectiveness. Prediction of the yield and LET of primary and secondary charged particles at a certain depth in the patient is performed by Monte Carlo simulations but is difficult to verify experimentally.Approach.Here, the results of measurements performed with Timepix detector in the mixed radiation field produced by a therapeutic proton beam in water are presented and compared to Monte Carlo simulations. The unique capability of the detector to perform high-resolution single particle tracking and identification enhanced by artificial intelligence allowed to resolve the particle type and measure the deposited energy of each particle comprising the mixed radiation field. Based on the collected data, biologically important physics parameters, the LET of single protons and dose-averaged LET, were computed.Main results.An accuracy over 95% was achieved for proton recognition with a developed neural network model. For recognized protons, the measured LET spectra generally agree with the results of Monte Carlo simulations. The mean difference between dose-averaged LET values obtained from measurements and simulations is 17%. We observed a broad spectrum of LET values ranging from a fraction of keVµm-1to about 10 keVµm-1for most of the measurements performed in the mixed radiation fields.Significance.It has been demonstrated that the introduced measurement method provides experimental data for validation of LETDor LET spectra in any treatment planning system. The simplicity and accessibility of the presented methodology make it easy to be translated into a clinical routine in any proton therapy facility.

Quantification of biological range uncertainties in patients treated at the Krakow proton therapy centre.

BACKGROUND: Variable relative biological effectiveness (vRBE) in proton therapy might significantly modify the prediction of RBE-weighted dose delivered to a patient during proton therapy. In this study we will present a method to quantify the biological range extension of the proton beam, which results from the application of vRBE approach in RBE-weighted dose calculation. METHODS AND MATERIALS: The treatment plans of 95 patients (brain and skull base patients) were used for RBE-weighted dose calculation with constant and the McNamara RBE model. For this purpose the Monte Carlo tool FRED was used. The RBE-weighted dose distributions were analysed using indices from dose-volume histograms. We used the volumes receiving at least 95% of the prescribed dose (V95) to estimate the biological range extension resulting from vRBE approach. RESULTS: The vRBE model shows higher median value of relative deposited dose and D95 in the planning target volume by around 1% for brain patients and 4% for skull base patients. The maximum doses in organs at risk calculated with vRBE was up to 14 Gy above dose limit. The mean biological range extension was greater than 0.4 cm. DISCUSSION: Our method of estimation of biological range extension is insensitive for dose inhomogeneities and can be easily used for different proton plans with intensity-modulated proton therapy (IMPT) optimization. Using volumes instead of dose profiles, which is the common method, is more universal. However it was tested only for IMPT plans on fields arranged around the tumor area. CONCLUSIONS: Adopting a vRBE model results in an increase in dose and an extension of the beam range, which is especially disadvantageous in cancers close to organs at risk. Our results support the need to re-optimization of proton treatment plans when considering vRBE.

Study of relationship between dose, LET and the risk of brain necrosis after proton therapy for skull base tumors.

PURPOSE: We investigated the relationship between RBE-weighted dose (DRBE) calculated with constant (cRBE) and variable RBE (vRBE), dose-averaged linear energy transfer (LETd) and the risk of radiographic changes in skull base patients treated with protons. METHODS: Clinical treatment plans of 45 patients were recalculated with Monte Carlo tool FRED. Radiographic changes (i.e. edema and/or necrosis) were identified by MRI. Dosimetric parameters for cRBE and vRBE were computed. Biological margin extension and voxel-based analysis were employed looking for association of DRBE(vRBE) and LETd with brain edema and/or necrosis. RESULTS: When using vRBE, Dmax in the brain was above the highest dose limits for 38% of patients, while such limit was never exceeded assuming cRBE. Similar values of Dmax were observed in necrotic regions, brain and temporal lobes. Most of the brain necrosis was in proximity to the PTV. The voxel-based analysis did not show evidence of an association with high LETd values. CONCLUSIONS: When looking at standard dosimetric parameters, the higher dose associated with vRBE seems to be responsible for an enhanced risk of radiographic changes. However, as revealed by a voxel-based analysis, the large inter-patient variability hinders the identification of a clear effect for high LETd.

RADIOTHERAPY PROTON BEAM PROFILOMETRY WITH scCVD DIAMOND DETECTOR IN SINGLE PARTICLE MODE.

Proton radiotherapy requires precise knowledge of the volumetric dose distribution. In proton beam delivery systems, based on narrow pencil beams, a contribution from small doses in low-intensity regions, consisting mainly of scattered protons, may have not negligible influence on total dose delivered to patient. Insufficient information about dose profile can cause underestimation of dose and potential delivery of inflated dose during hadrontherapy treatment. Presented work aims to verify applicability of diamond detectors, produced by Chemical Vapor Deposition method, for therapeutic proton beam profilometry at large fields. This requires the capability of measuring the core of the beam intensity profile (wide dynamic range) as well as its lateral spread (very high sensitivity) with a single device.

Chemically tuned linear energy transfer dependent quenching in a deformable, radiochromic 3D dosimeter.

Most solid-state detectors, including 3D dosimeters, show lower signal in the Bragg peak than expected, a process termed quenching. The purpose of this study was to investigate how variation in chemical composition of a recently developed radiochromic, silicone-based 3D dosimeter influences the observed quenching in proton beams. The dependency of dose response on linear energy transfer, as calculated through Monte Carlo simulations of the dosimeter, was investigated in 60 MeV proton beams. We found that the amount of quenching varied with the chemical composition: peak-to-plateau ratios (1 cm into the plateau) ranged from 2.2 to 3.4, compared to 4.3 using an ionization chamber. The dose response, and thereby the quenching, was predominantly influenced by the curing agent concentration, which determined the dosimeter's deformation properties. The dose response was found to be linear at all depths. All chemical compositions of the dosimeter showed dose-rate dependency; however this was not dependent on the linear energy transfer. Track-structure theory was used to explain the observed quenching effects. In conclusion, this study shows that the silicone-based dosimeter has potential for use in measuring 3D-dose-distributions from proton beams.

Technical Note: Improving proton stopping power ratio determination for a deformable silicone-based 3D dosimeter using dual energy CT.

PURPOSE: The aim of this study was to investigate whether the stopping power ratio (SPR) of a deformable, silicone-based 3D dosimeter could be determined more accurately using dual energy (DE) CT compared to using conventional methods based on single energy (SE) CT. The use of SECT combined with the stoichiometric calibration method was therefore compared to DECT-based determination. METHODS: The SPR of the dosimeter was estimated based on its Hounsfield units (HUs) in both a SECT image and a DECT image set. The stoichiometric calibration method was used for converting the HU in the SECT image to a SPR value for the dosimeter while two published SPR calibration methods for dual energy were applied on the DECT images. Finally, the SPR of the dosimeter was measured in a 60 MeV proton by quantifying the range difference with and without the dosimeter in the beam path. RESULTS: The SPR determined from SECT and the stoichiometric method was 1.10, compared to 1.01 with both DECT calibration methods. The measured SPR for the dosimeter material was 0.97. CONCLUSIONS: The SPR of the dosimeter was overestimated by 13% using the stoichiometric method and by 3% when using DECT. If the stoichiometric method should be applied for the dosimeter, the HU of the dosimeter must be manually changed in the treatment planning system in order to give a correct SPR estimate. Using a wrong SPR value will cause differences between the calculated and the delivered treatment plans.

Response of human lymphocytes to proton radiation of 60 MeV compared to 250 kV X-rays by the cytokinesis-block micronucleus assay.

Particle radiotherapy such as protons provides a new promising treatment modality to cancer. However, studies on its efficacy and risks are relatively sparse. Using the cytokinesis-blocked micronucleus assay, we characterized response of human peripheral blood lymphocytes, obtained from health donors irradiated in vitro in the dose range: 0-4. 0 Gy, to therapeutic proton radiation of 60 MeV from AIC-144 isochronous cyclotron, by studying nuclear division index and DNA damage and compared them with X-rays. Peripheral blood lymphocytes show decreased ability to proliferate with increasing radiation doses for both radiation types, however, in contrast to X-rays, irradiation with protons resulted in a higher proliferation index at lower doses of 0.75 and 1.0 Gy. Protons are more effective in producing MN at doses above 1.75 Gy compared to X-rays. Dose-response curves for micronucleus incidence can be best described by a cubic model for protons, while for X-rays the response was linear. The differences in the energy spectrum and intracellular distribution of energy between radiation types are also apparent at the intracellular distribution of cytogenetic damage as seen by the distribution of various numbers of micronuclei in binucleated cells. Our studies, although preliminary, further contribute to the understanding of the mechanistic differences in the response of HPBL in terms of cellular proliferation and cytogenetic damage induced by protons and X-rays as well as intra-cellular distribution of energy and thus radiobiological effectiveness.