A Monte Carlo study on the secondary neutron generation by oxygen ion beams for radiotherapy and its comparison to lighter ions.

Objective.To study the secondary neutrons generated by primary oxygen beams for cancer treatment and compare the results to those from primary protons, helium, and carbon ions. This information can provide useful insight into the positioning of neutron detectors in phantom for future experimental dose assessments.Approach.Mono-energetic oxygen beams and spread-out Bragg peaks were simulated using the Monte Carlo particle transport codesFLUktuierende KAskade, tool for particle simulation, and Monte Carlo N-Particle, with energies within the therapeutic range. The energy and angular distribution of the secondary neutrons were quantified.Main results.The secondary neutron spectra generated by primary oxygen beams present the same qualitative trend as for other primary ions. The energy distributions resemble continuous spectra with one peak in the thermal/epithermal region, and one other peak in the fast/relativistic region, with the most probable energy ranging from 94 up to 277 MeV and maximum energies exceeding 500 MeV. The angular distribution of the secondary neutrons is mainly downstream-directed for the fast/relativistic energies, whereas the thermal/epithermal neutrons present a more isotropic propagation. When comparing the four different primary ions, there is a significant increase in the most probable energy as well as the number of secondary neutrons per primary particle when increasing the mass of the primaries.Significance.Most previous studies have only presented results of secondary neutrons generated by primary proton beams. In this work, secondary neutrons generated by primary oxygen beams are presented, and the obtained energy and angular spectra are added as supplementary material. Furthermore, a comparison of the secondary neutron generation by the different primary ions is given, which can be used as the starting point for future studies on treatment plan comparison and secondary neutron dose optimisation. The distal penumbra after the maximum dose deposition appears to be a suitable location for in-phantom dose assessments.

Dosimetric study for breathing-induced motion effects in an abdominal pancreas phantom for carbon ion mini-beam radiotherapy.

BACKGROUND: Particle mini-beam therapy exhibits promise in sparing healthy tissue through spatial fractionation, particularly notable for heavy ions, further enhancing the already favorable differential biological effectiveness at both target and entrance regions. However, breathing-induced organ motion affects particle mini-beam irradiation schemes since the organ displacements exceed the mini-beam structure dimensions, decreasing the advantages of spatial fractionation. PURPOSE: In this study, the impact of breathing-induced organ motion on the dose distribution was examined at the target and organs at risk(OARs) during carbon ion mini-beam irradiation for pancreatic cancer. METHODS: As a first step, the carbon ion mini-beam pattern was characterized with Monte Carlo simulations. To analyze the impact of breathing-induced organ motion on the dose distribution of a virtual pancreas tumor as target and related OARs, the anthropomorphic Pancreas Phantom for Ion beam Therapy (PPIeT) was irradiated with carbon ions. A mini-beam collimator was used to deliver a spatially fractionated dose distribution. During irradiation, varying breathing motion amplitudes were induced, ranging from 5 to 15 mm. Post-irradiation, the 2D dose pattern was analyzed, focusing on the full width at half maximum (FWHM), center-to-center distance (ctc), and the peak-to-valley dose ratio (PVDR). RESULTS: The mini-beam pattern was visible within OARs, while in the virtual pancreas tumor a more homogeneous dose distribution was achieved. Applied motion affected the mini-beam pattern within the kidney, one of the OARs, reducing the PVDR from 3.78  ± $\pm$  0.12 to 1.478  ± $\pm$  0.070 for the 15 mm motion amplitude. In the immobile OARs including the spine and the skin at the back, the PVDR did not change within 3.4% comparing reference and motion conditions. CONCLUSIONS: This study provides an initial understanding of how breathing-induced organ motion affects spatial fractionation during carbon ion irradiation, using an anthropomorphic phantom. A decrease in the PVDR was observed in the right kidney when breathing-induced motion was applied, potentially increasing the risk of damage to OARs. Therefore, further studies are needed to explore the clinical viability of mini-beam radiotherapy with carbon ions when irradiating abdominal regions.

Linear Energy Transfer Measurements and Estimation of Relative Biological Effectiveness in Proton and Helium Ion Beams Using Fluorescent Nuclear Track Detectors.

PURPOSE: Our objective was to develop a methodology for assessing the linear energy transfer (LET) and relative biological effectiveness (RBE) in clinical proton and helium ion beams using fluorescent nuclear track detectors (FNTDs). METHODS AND MATERIALS: FNTDs were exposed behind solid water to proton and helium (4He) ion spread-out Bragg peaks. Detectors were imaged with a confocal microscope, and the LET spectra were derived from the fluorescence intensity. The track- and dose-averaged LET (LETF and LETD, respectively) were calculated from the LET spectra. LET measurements were used as input on RBE models to estimate the RBE. Human alveolar adenocarcinoma cells (A549) were exposed at the same positions as the FNTDs. The RBE was calculated from the resulting survival curves. All measurements were compared with Monte Carlo simulations. RESULTS: For protons, average relative differences between measurements and simulations were 6% and 19% for LETF and LETD, respectively. For helium ions, the same differences were 11% for both quantities. The position of the experimental LET spectra primary peaks agreed with the simulations within 9% and 14% for protons and helium ions, respectively. For the RBE models using LETD as input, FNTD-based RBE values ranged from 1.02 ± 0.01 to 1.25 ± 0.04 and from 1.08 ± 0.09 to 2.68 ± 1.26 for protons and helium ions, respectively. The average relative differences between these values and simulations were 2% and 4%. For A549 cells, the RBE ranged from 1.05 ± 0.07 to 1.47 ± 0.09 and from 0.89 ± 0.06 to 3.28 ± 0.20 for protons and helium ions, respectively. Regarding the RBE-weighted dose (2.0 Gy at the spread-out Bragg peak), the differences between simulations and measurements were below 0.10 Gy. CONCLUSIONS: This study demonstrates for the first time that FNTDs can be used to perform direct LET measurements and to estimate the RBE in clinical proton and helium ion beams.

Sensitivity correction of fluorescent nuclear track detectors using alpha particles: Determining LET spectra of light ions with enhanced accuracy.

BACKGROUND: Radiation fields encountered in proton therapy (PT) and ion-beam therapy (IBT) are characterized by a variable linear energy transfer (LET), which lead to a variation of relative biological effectiveness and also affect the response of certain dosimeters. Therefore, reliable tools to measure LET are advantageous to predict and correct LET effects. Fluorescent nuclear track detectors (FNTDs) are suitable to measure LET spectra within the range of interest for PT and IBT, but so far the accuracy and precision have been challenged by sensitivity variations between individual crystals. PURPOSE: To develop a novel methodology to correct changes in the fluorescent intensity due to sensitivity variations among FNTDs. This methodology is based on exposing FNTDs to alpha particles in order to derive a detector-specific correction factor. This will allow us to improve the accuracy and precision of LET spectra measurements with FNTDs. METHODS: FNTDs were exposed to alpha particles. Afterward, the detectors were irradiated to monoenergetic protons, 4 He-, 12 C-, and 16 O-ions. At each step, the detectors were imaged with a confocal laser scanning microscope. The tracks were reconstructed and analyzed using in-house developed tools. Alpha-particle tracks were used to derive a detector-specific sensitivity correction factor ( k s , i ${k_{s,i}}$ ). Proton, 4 He-, 12 C-, and 16 O-ion tracks were used to establish a traceable calibration curve that relates the fluorescence intensity with the LET in water ( L E T H 2 O $LE{T_{{{\rm{H}}_2}{\rm{O}}}}$ ). FNTDs from a second batch were exposed and analyzed following the same procedures, to test if k s , i ${k_{s,i}}$ can be used to extend the applicability of the calibration curve to detectors from different batches. Finally, a set of blind tests was performed to assess the accuracy of the proposed methodology without user bias. Throughout all stages, the main sources of uncertainty were evaluated. RESULTS: Based on a sample of 100 FNTDs, our findings show a high sensitivity heterogeneity between FNTDs, with k s , i ${k_{s,i}}$ having values between 0.57 and 2.55. The fitting quality of the calibration curve, characterized by the mean absolute percentage residuals and correlation coefficient, was improved when k s , i ${k_{s,i}}$ was considered. Results for detectors from the second batch show that, if the fluorescence signal is corrected by k s , i ${k_{s,i}}$ , the differences in the predicted L E T H 2 O $LE{T_{{{\rm{H}}_2}{\rm{O}}}}$ with respect to the reference set are reduced from 55%, 141%, 41%, and 186% to 4.2%, 6.5%, 5.0%, and 11.0%, for protons, 4 He-, 12 C-, and 16 O-ions, respectively. The blind tests showed that it is possible to measure the track- and dose-average L E T H 2 O $LE{T_{{{\rm{H}}_2}{\rm{O}}}}$ with an accuracy of 0.3%, 16%, and 9.6% and 1.7%, 28%, and 30% for protons, 12 C-ions and mixed beams, respectively. On average, the combined uncertainty of the measured L E T H 2 O $LE{T_{{{\rm{H}}_2}{\rm{O}}}}$ was 11%, 13%, 21%, and 26% for protons, 4 He-, 12 C-, and 16 O-ions, respectively. These values were increased by a mean factor of 2.0 when k s , i ${k_{s,i}}$ was not applied. CONCLUSIONS: We have demonstrated for the first time that alpha particles can be used to derive a detector-specific sensitivity correction factor. The proposed methodology allows us to measure LET spectra using FNTD-technology, with a degree of accuracy and precision unreachable before with sole experimental approaches.

A phantom to simulate organ motion and its effect on dose distribution in carbon ion therapy for pancreatic cancer.

Objective. Carbon ion radiotherapy is a promising radiation technique for malignancies like pancreatic cancer. However, organs' motion imposes challenges for achieving homogeneous dose delivery. In this study, an anthropomorphicPancreasPhantom forIon-beamTherapy (PPIeT) was developed to simulate breathing and gastrointestinal motion during radiotherapy.Approach. The developed phantom contains a pancreas, two kidneys, a duodenum, a spine and a spinal cord. The shell of the organs was 3D printed and filled with agarose-based mixtures. Hounsfield Units (HU) of PPIeTs' organs were measured by CT. The pancreas motion amplitude in cranial-caudal (CC) direction was evaluated from patients' 4D CT data. Motions within the obtained range were simulated and analyzed in PPIeT using MRI. Additionally, GI motion was mimicked by changing the volume of the duodenum and quantified by MRI. A patient-like treatment plan was calculated for carbon ions, and the phantom was irradiated in a static and moving condition. Dose measurements in the organs were performed using an ionization chamber and dosimetric films.Main results. PPIeT presented tissue equivalent HU and reproducible breathing-induced CC displacements of the pancreas between (3.98 ± 0.36) mm and a maximum of (18.19 ± 0.44) mm. The observed maximum change in distance of (14.28 ± 0.12) mm between pancreas and duodenum was consistent with findings in patients. Carbon ion irradiation revealed homogenous coverage of the virtual tumor at the pancreas in static condition with a 1% deviation from the treatment plan. Instead, the dose delivery during motion with the maximum amplitude yielded an underdosage of 21% at the target and an increased uncertainty by two orders of magnitude.Significance. A dedicated phantom was designed and developed for breathing motion assessment of dose deposition during carbon ion radiotherapy. PPIeT is a unique tool for dose verification in the pancreas and its organs at risk during end-to-end tests.

Assessment of secondary neutrons in particle therapy by Monte Carlo simulations.

Objective. The purpose of this study is to estimate the energy and angular distribution of secondary neutrons inside a phantom in hadron therapy, which will support decisions on detector choice and experimental setup design for in-phantom secondary neutron measurements.Approach. Dedicated Monte Carlo simulations were implemented, considering clinically relevant energies of protons, helium and carbon ions. Since scored quantities can vary from different radiation transport models, the codes FLUKA, TOPAS and MCNP were used. The geometry of an active scanning beam delivery system for heavy ion treatment was implemented, and simulations of pristine and spread-out Bragg peaks were carried out. Previous studies, focused on specific ion types or single energies, are qualitatively in agreement with the obtained results.Main results. The secondary neutrons energy distributions present a continuous spectrum with two peaks, one centred on the thermal/epithermal region, and one on the high-energy region, with the most probable energy ranging from 19 up to 240 MeV, depending on the ion type and its initial energy. The simulations show that the secondary neutron energies may exceed 400 MeV and, therefore, suitable neutron detectors for this energy range shall be needed. Additionally, the angular distribution of the low energy neutrons is quite isotropic, whereas the fast/relativistic neutrons are mainly scattered in the down-stream direction.Significance. It would be possible to minimize the influence of the heavy ions when measuring the neutron-generated recoil protons by selecting appropriate measurement positions within the phantom. Although there are discrepancies among the three Monte Carlo codes, the results agree qualitatively and in order of magnitude, being sufficient to support further investigations with the ultimate goal of mapping the secondary neutron doses both in- and out-of-field in hadrontherapy. The obtained secondary neutron spectra are available as supplementary material.