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This study introduces a novel iterative Bragg peak removal with automatic intensity correction (IBR-AIC) methodology for X-ray absorption spectroscopy (XAS), specifically addressing the challenge of Bragg peak interference in the analysis of crystalline materials. The approach integrates experimental adjustments and sophisticated post-processing, including an iterative algorithm for robust calculation of the scaling factor of the absorption coefficients and efficient elimination of the Bragg peaks, a common obstacle in accurately interpreting XAS data, particularly in crystalline samples. The method was thoroughly evaluated on dilute catalysts and thin films, with fluorescence mode and large-angle rotation. The results underscore the technique's effectiveness, adaptability and substantial potential in improving the precision of XAS data analysis. While demonstrating significant promise, the method does have limitations related to signal-to-noise ratio sensitivity and the necessity for meticulous angle selection during experimentation. Overall, IBR-AIC represents a significant advancement in XAS, offering a pragmatic solution to Bragg peak contamination challenges, thereby expanding the applications of XAS in understanding complex materials under diverse experimental conditions.

Introduction: FLASH proton therapy (FLASH-PT) requires ultra-high dose rate (= 40 Gy/s) protons to be delivered in a short timescale whilst conforming to a patient-specific target. This study investigates the feasibility and constraints of Bragg peak FLASH-PT treatment planning, and compares the in silico results produced to plans for intensity modulated proton therapy (IMPT). Materials and method: Bragg peak FLASH-PT and IMPT treatment plans were generated for bone (n=3), brain (n=3), and lung (n=4) targets using the MIROpt research treatment planning system and the Conformal FLASH library developed by Applications SA from the open-source version of UCLouvain. FLASH-PT beams were simulated using monoenergetic spot-scanned protons traversing through a conformal energy modulator, a range shifter, and an aperture. A dose rate constraint of = 40 Gy/s was included in each FLASH-PT plan optimisation. Results: Space limitations in the FLASH-PT adapted beam nozzle imposed a maximum target width constraint, excluding 4 cases from the study. FLASH-PT plans did not satisfy the imposed target dose constraints (D95% = 95% and D2%= 105%) but achieved clinically acceptable doses to organs at risk (OARs). IMPT plans adhered to all target and OAR dose constraints. FLASH-PT plans showed a reduction in both target homogeneity (p < 0.001) and dose conformity (nonsignificant) compared to IMPT. Conclusion: Without accounting for a sparing effect, IMPT plans were superior in target coverage, dose conformity, target homogeneity, and OAR sparing compared to FLASH-PT. Further research is warranted in treatment planning optimisation and beam delivery for clinical implementation of Bragg peak FLASH-PT. [ABSTRACT FROM AUTHOR]

The mean ionization potential (I-value) is a primary determinant of the position of the heavy ion Bragg peak. To minimize their impact on beam range errors and quantify their uncertainties, the currently used I-values in Geant4 material database are revisited. The study aims at comparing set of I-values in different Geant4 versions and cross validation with PHITS Monte Carlo (MC) code. The Bragg curves of mono-energetic 290 MeV/u carbon ion beams in a Polymethyl Methacrylate (PMMA) phantom were simulated using Geant4 versions 10.6.2 and 11.2.1. Similar beam energies were replicated using the PHITS code. The Bragg curves showed good agreement between the two versions of Geant4 MC code for an I-value of 74 eV, corresponding to G4_PLEXIGLASS in the material database. When the I-value was lowered to 65 eV and 48 eV, the Bragg curves from Geant4 version 11.2.1 shifted to shallower depths. This research provides insights for evaluating the Geant4 physics model.

IntroductionFLASH proton therapy (FLASH-PT) requires ultra-high dose rate (≥ 40 Gy/s) protons to be delivered in a short timescale whilst conforming to a patient-specific target. This study investigates the feasibility and constraints of Bragg peak FLASH-PT treatment planning, and compares the in silico results produced to plans for intensity modulated proton therapy (IMPT).Materials and methodBragg peak FLASH-PT and IMPT treatment plans were generated for bone (n=3), brain (n=3), and lung (n=4) targets using the MIROpt research treatment planning system and the Conformal FLASH library developed by Applications SA from the open-source version of UCLouvain. FLASH-PT beams were simulated using monoenergetic spot-scanned protons traversing through a conformal energy modulator, a range shifter, and an aperture. A dose rate constraint of ≥ 40 Gy/s was included in each FLASH-PT plan optimisation.ResultsSpace limitations in the FLASH-PT adapted beam nozzle imposed a maximum target width constraint, excluding 4 cases from the study. FLASH-PT plans did not satisfy the imposed target dose constraints (D95% ≥ 95% and D2%≤ 105%) but achieved clinically acceptable doses to organs at risk (OARs). IMPT plans adhered to all target and OAR dose constraints. FLASH-PT plans showed a reduction in both target homogeneity (p < 0.001) and dose conformity (non-significant) compared to IMPT.ConclusionWithout accounting for a sparing effect, IMPT plans were superior in target coverage, dose conformity, target homogeneity, and OAR sparing compared to FLASH-PT. Further research is warranted in treatment planning optimisation and beam delivery for clinical implementation of Bragg peak FLASH-PT.

Following carbon ion beam irradiation in mammalian cells, such as used in carbon ion radiotherapy (CIRT), it has been suggested that the balance between whether nonhomologous end joining (NHEJ) or homologous recombination (HR) is utilized depends on the DNA double‐strand break (DSB) complexity. Here, we quantified DSB distribution and identified the importance of each DSB repair pathway at increasing depths within the carbon ion spread‐out Bragg peak (SOBP) beam range. Chinese hamster ovary (CHO) cell lines were irradiated in a single biological system capable of incorporating the full carbon ion SOBP beam range. Cytotoxicity and DSB distribution/repair kinetics were examined at increasing beam depths using cell survival as an endpoint and γ‐H2AX as a surrogate marker for DSBs. We observed that proximal SOBP had the highest number of total foci/cell and lowest survival, while distal SOBP had the most dense tracks. Both NHEJ‐ and HR‐deficient CHO cells portrayed an increase in radiosensitivity throughout the full carbon beam range, although NHEJ‐deficient cells were the most radiosensitive cell line from beam entrance up to proximal SOBP and demonstrated a dose‐dependent decrease in ability to repair DSBs. In contrast, HR‐deficient cells had the greatest ratio of survival fraction at entrance depth to the lowest survival fraction within the SOBP and demonstrated a linear energy transfer (LET)‐dependent decrease in ability to repair DSBs. Collectively, our results provide insight into treatment planning and potential targets to inhibit, as HR was a more beneficial pathway to inhibit than NHEJ to enhance the cell killing effect of CIRT in targeted tumor cells within the SOBP while maintaining limited unwanted damage to surrounding healthy cells. [ABSTRACT FROM AUTHOR]

The number of patients treated with charged-particle radiotherapy as well as the number of treatment centers is increasing worldwide, particularly regarding protons. However, high-linear energy transfer (LET) particles, mainly carbon ions, are of special interest for application in radiotherapy, as their special physical features result in high precision and hence lower toxicity, and at the same time in increased efficiency in cell inactivation in the target region, i.e., the tumor. The radiobiology of high-LET particles differs with respect to DNA damage repair, cytogenetic damage, and cell death type, and their increased LET can tackle cells' resistance to hypoxia. Recent developments and perspectives, e.g., the return of high-LET particle therapy to the US with a center planned at Mayo clinics, the application of carbon ion radiotherapy using cost-reducing cyclotrons and the application of helium is foreseen to increase the interest in this type of radiotherapy. However, further preclinical research is needed to better understand the differential radiobiological mechanisms as opposed to photon radiotherapy, which will help to guide future clinical studies for optimal exploitation of high-LET particle therapy, in particular related to new concepts and innovative approaches. Herein, we summarize the basics and recent progress in high-LET particle radiobiology with a focus on carbon ions and discuss the implications of current knowledge for charged-particle radiotherapy. We emphasize the potential of high-LET particles with respect to immunogenicity and especially their combination with immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Many studies have utilized optical camera systems with volumetric scintillators for quality assurances (QA) to estimate the proton beam range. However, previous analytically driven range estimation methods have the difficulty to derive the dose distributions from the scintillation images with quenching and optical effects. Purpose: In this study, a deep learning method utilized to QA was used to predict the beam range and spread‐out Bragg peak (SOBP) for two‐dimensional (2D) map conversion from the scintillation light distribution (LD) into the dose distribution in a water phantom. Methods: The 2D residual U‐net modeling for deep learning was used to predict the 2D water dose map from a 2D scintillation LD map. Monte Carlo simulations for dataset preparation were performed with varying monoenergetic proton beam energies, field sizes, and beam axis shifts. The LD was reconstructed using photons backpropagated from the aperture as a virtual lens. The SOBP samples were constructed based on monoenergetic dose distributions. The training set, including the validation set, consisted of 8659 image pairs of LD and water dose maps. After training, dose map prediction was performed using a 300 image pair test set generated under random conditions. The pairs of simulated and predicted dose maps were analyzed by Bragg peak fitting and gamma index maps to evaluate the model prediction. Result: The estimated beam range and SOBP width resolutions were 0.02 and 0.19 mm respectively for varying beam conditions, and the beam range and SOBP width deviations from the reference simulation result were less than 0.1 and 0.8 mm respectively. The simulated and predicted distributions showed good agreement in the gamma analysis, except for rare cases with failed gamma indices in the proximal and field‐marginal regions. Conclusion: The deep learning conversion method using scintillation LDs in an optical camera system with a scintillator is feasible for estimating proton beam range and SOBP width with high accuracy. [ABSTRACT FROM AUTHOR]

Proton beam therapy (PBT) can achieve the effect of precision radiotherapy due to its unique Bragg peak. In the process of proton therapy, the peak can be accurately located to the tumor area, which can give the tumor a larger dose of irradiation, reduce the damage to normal tissues and organs, and reduce the occurrence of side effects. Therefore, it is very important to locate the Bragg peak of proton beam in real time in proton therapy. In this paper, a cyclotron is used to generate proton beam, and a diamond detector is used to test the radiation characteristics of proton beam, and the Bragg peak and the beam spot center are measured (0, 35 mm). Thus, accurate Bragg peak value of proton beam was obtained, which guaranteed the accuracy of proton therapy.

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Lithium fluoride (LiF) crystals and thin films are utilized as radiation detectors for energy diagnostics of proton beams. This is achieved by analyzing the Bragg curves in LiF obtained by imaging the radiophotoluminescence of color centers created by protons. In LiF crystals, the Bragg peak depth increases superlinearly with the particle energy. A previous study has shown that, when 35 MeV protons impinge at grazing incidence onto LiF films deposited on Si(100) substrates, the Bragg peak in the films is located at the depth where it would be found in Si rather than in LiF due to multiple Coulomb scattering. In this paper, Monte Carlo simulations of proton irradiations in the 1–8 MeV energy range are performed and compared to experimental Bragg curves in optically transparent LiF films on Si(100) substrates. Our study focuses on this energy range because, as energy increases, the Bragg peak gradually shifts from the depth in LiF to that in Si. The impact of grazing incidence angle, LiF packing density, and film thickness on shaping the Bragg curve in the film is examined. At energies higher than 8 MeV, all these quantities must be considered, although the effect of packing density plays a minor role. [ABSTRACT FROM AUTHOR]

In order to increase the absorbed dose around the Bragg peak region, it is proposed to use the p+11B → 3α reaction for proton therapy. This reaction is not implemented in the Geant4 software package. A simplified model of this reaction is proposed which will allow its full-scale simulation. The model is fully compatible with the Geant4 software package and can be integrated with it. The model predictions and background events from other processes are discussed. [ABSTRACT FROM AUTHOR]

Experimental results have shown that dadding boron to tumor tissue during proton therapy increases the mortality of cancer cells. This work has investigated how to form a spread-out Bragg peak in the proton therapy of a liver-located tumor by simulating the MIRD phantom and designing a range modulator. The simulations were carried out using a GEANT4 Monte Carlo toolkit. Also, the absorbed dose of the different organs near the liver was determined via simulations. To study the effect of boron on liver proton therapy, a tumor impregnated with different percentages of boron was simulated and the effect of energy released in the tumor as a result of alpha particles, protons and their combinations was investigated. The absorbed dose in the tumor at different proton energies and with varying percentages of boron was investigated. It was found that the absorbed dose in the tumor increases by adding boron, however; it decreases by increasing the energy from a certain limit (~80 MeV) of more than 60% boron.

In particle therapy, bioabsorbable polyglycolic acid (PGA) spacer was developed to reduce the healthy organ irradiation dose, especially in the gastrointestinal tract. The PGA spacer is safe and effective; however, there are no reports that have confirmed whether the PGA spacer which inserted in the body actually stops the carbon-ion (C-ion) beams. Here, we visualized and confirmed that the PGA spacer stops the C-ion beams in the body based on the dose distribution using auto-activation positron emission tomography (AAPET). A 59-year-old dedifferentiated retroperitoneal liposarcoma patient underwent C-ion radiotherapy (C-ion RT) on referral. A month before C-ion RT initiation, the patient underwent PGA spacer placement. Postoperatively, the patient received 4.4 Gy (RBE) per fraction of C-ion RT, followed by AAPET. AAPET revealed lower positron emitter concentrations at the distal tissue ventral to the PGA spacer than in the planning target volume. In observing the efficacy of the PGA spacer, the AAPET images and the average count per second of the positron emitter suggested that the PGA spacer stopped the C-ion beams in the body in accordance with the dose distribution. Therefore, AAPET was useful in confirming the PGA spacer’s effectiveness in this study, and the PGA spacer stopped the C-ion beams.

Purpose: Proton therapy is an emerging therapy for several malignancies owing to its favorable therapeutic ratio. There are very limited data on the use of proton therapy in the management of thyroid carcinoma. Our objective was to review the safety, feasibility, and outcomes of proton therapy for patients with thyroid cancer treated to the head and neck. Methods: From our institution's proton database from 2012 to 2021, we identified 22 patients with thyroid cancer treated with proton beam therapy. We evaluated outcomes and toxicities. Results: Median follow-up was 26 months. Of the 22 patients, 50% were female. The mean age was 65 years. Three patients had anaplastic cancer; 13, papillary carcinoma; 2, follicular carcinoma; and 2, poorly differentiated carcinoma. Forty-six percent had T4 disease. Primary targets were the central neck compartment, level VI, and upper mediastinum. Radiation dose was 60 GyRBE adjuvantly, and 70 GyRBE for gross disease (range, 6000-7600 GyRBE). Eight patients underwent upfront adjuvant radiation, and 3 received definitive radiation for unresectable disease upfront. Eleven patients received either salvage or palliative radiation. Fifty-nine percent of patients had extrathyroidal extension, and 64% of patients had gross disease in the neck before treatment. Fifty percent of patients had metastatic disease before treatment. Sixteen patients received concurrent chemotherapy, 63% of these patients received doxorubicin. For all patients, 1-year local regional recurrence (LRR) was 0%, and overall survival (OS) was 90%. Acute grade 3+ toxicities occurred in 27% of patients, the most frequent being dermatitis (27%). Three patients required a percutaneous endoscopic gastrostomy tube after radiation therapy (RT), 2 owing to progression. There were no grade 4+ toxicities. Conclusions: Proton therapy for thyroid cancer appears feasible and effective with minimal toxicities. Prospective studies comparing proton therapy with intensity-modulated RT, to evaluate the clinical efficacy of using proton therapy to reduce toxicities in patients undergoing radiation for thyroid cancer, are warranted.

The present study aimed to evaluate the morphological, cytogenetic and biochemical changes in wheat seedlings as affected by seed exposure to a proton beam at the Bragg peak. The average energy of the proton beam was of 171 MeV at the entrance into the irradiator room while at the point of sample irradiation the beam energy was of 150 MeV, with the average value of the Linear Energy Transfer of 0.539 keV/μm and the dose rate of 0.55 Gy/min, the radiation doses being of the order of tens of Gy. Cytogenetic investigation has revealed the remarkable diminution of the mitotic index as linear dose-response curve as well as the spectacular linear increase of the aberration index. Analyzing some biometric parameters, it was found that neither dry matter nor water content of wheat seedlings was influenced by proton beam exposure. Studying the biochemical parameters related to the antioxidant defense system, we found that the irradiation caused the slight increasing tendency of peroxidase activity as well as the decreasing trend in the activity of superoxidedismutase in the seedlings grown from the irradiated seeds. The level of malonedialdehyde (MDA) and total polyphenols showed an increasing tendency in all seedling variants corresponding to irradiated seeds, compared to the control. We conclude that the irradiation clearly induced dose-response curves at the level of cytogenetic parameters together with relatively slight variation tendency of some biochemical parameters related to the antioxidant defense system while imperceptible changes could be noticed in the biometric parameters. [ABSTRACT FROM AUTHOR]

Background: This study aimed to compare the results of irradiation with protons versus irradiation with carbon ions in a raster scan technique in patients with skull base chordomas and to identify risk factors that may compromise treatment results. Methods: A total of 147 patients (85 men, 62 women) were irradiated with carbon ions (111 patients) or protons (36 patients) with a median dose of 66 Gy (RBE (Relative biological effectiveness); carbon ions) in 4 weeks or 74 Gy (RBE; protons) in 7 weeks at the Heidelberg Ion Beam Therapy Center (HIT) in Heidelberg, Germany. The median follow-up time was 49.3 months. All patients had gross residual disease at the beginning of RT. Compression of the brainstem was present in 38%, contact without compression in 18%, and no contact but less than 3 mm distance in 16%. Local control and overall survival were evaluated using the Kaplan–Meier Method based on scheduled treatment (protons vs. carbon ions) and compared via the log rank test. Subgroup analyses were performed to identify possible prognostic factors. Results: During the follow-up, 41 patients (27.9%) developed a local recurrence. The median follow-up time was 49.3 months (95% CI: 40.8–53.8; reverse Kaplan–Meier median follow-up time 56.3 months, 95% CI: 51.9–60.7). No significant differences between protons and carbon ions were observed regarding LC, OS, or overall toxicity. The 1‑year, 3‑year, and 5‑year LC rates were 97%, 80%, and 61% (protons) and 96%, 80%, and 65% (carbon ions), respectively. The corresponding OS rates were 100%, 92%, and 92% (protons) and 99%, 91%, and 83% (carbon ions). No significant prognostic factors for LC or OS could be determined regarding the whole cohort; however, a significantly improved LC could be observed if the tumor was > 3 mm distant from the brainstem in patients presenting in a primary situation. Conclusion: Outcomes of proton and carbon ion treatment of skull base chordomas seem similar regarding tumor control, survival, and toxicity. Close proximity to the brainstem might be a negative prognostic factor, at least in patients presenting in a primary situation. [ABSTRACT FROM AUTHOR]

In recent years, proton therapy has gained importance as a cancer treatment modality due to its conformality with the tumor and the sparing of healthy tissue. However, in the interaction of the protons with the beam line elements and patient tissues, potentially harmful secondary neutrons are always generated. To ensure that this neutron dose is as low as possible, treatment plans could be created to also account for and minimize the neutron dose. To monitor such a treatment plan, a compact, easy to use, and inexpensive dosimeter must be developed that not only measures the physical dose, but which can also distinguish between proton and neutron contributions. To that end, plastic optical fibers with scintillation materials (Gd2O2S:Tb, Gd2O2S:Eu, and YVO4:Eu) were irradiated with protons and neutrons. It was confirmed that sensors with different scintillation materials have different sensitivities to protons and neutrons. A combination of these three scintillators can be used to build a detector array to create a biological dosimeter. [ABSTRACT FROM AUTHOR]

Background: The purpose of this research was to show how the Bragg peak (BP) characteristics were affected by changing the voxel size in longitudinal and transverse directions in Monte Carlo (MC) simulations by using Geant4 and to calculate BP characteristics accurately by considering the voxel size effect for 68 MeV and 235.81 MeV. Materials and methods: Different interpolation techniques were applied to simulation data to find the closest results to the experimental data. Results: When the x-size of the voxel was increased 2 times at low energy, the maximum dose increase in the entrance and plateau regions were 17.8% and 17%, respectively, while BP curve shifted to the shallower region, resulting in a 0.5 mm reduction in the curable tumor width (W80pd). At high energy, the maximum dose increase at the entrance and plateau regions were 0.4% and 0.6%, respectively, while it was observed that W80pd did not change. When the y-z sizes of the voxel were increased 2 times at low energy, the maximum dose reduction at the entrance and plateau regions was 3.4%, but no change was observed in W80pd. At high energy, when the y-z sizes of the voxel were increased 2.2 times, the maximum dose reduction at the entrance and plateau regions were 8.9% and 9.1%, respectively, while W80pd increased by 0.5 mm. When linear, cubic spline, and Akima interpolations were applied to the simulation data, it was found that the results closest to the experimental data were obtained for Akima interpolations for both energies. Conclusion: it has been shown that the voxel size effect for the longitudinal direction was more effective at low energy than at high energy. However, the voxel size effect for the transverse direction was more effective for high energy. [ABSTRACT FROM AUTHOR]

BackgroundIn particle radiotherapy, the Bragg peak (BP) width of carbon ion beam is required to be broadened whilst Ripple filter (RiFi) is often used as a clinical broadening device. However, it may cause extra lateral scattering. Porous material expressed as the porous structure 1.0 (PS 1.0) can be used to reduce such scattering but bring an oversized distal falloff width (DFW).PurposeThis study aims to develop a novel porous structure, described as a porous structure 2.0 (PS 2.0), to broaden the BP width.MethodsFirst of all, the Monte Carlo code, FLUKA was selected as the tool for this simulation. Two geometry models of broadening structure (1D-RiFi and PS 1.0) were built. Then, the PS 2.0 was simulated by inserting numerous of Polymethyl Methacrylate (PMMA) sticks in the PS 1.0 with a certain proportion. The performance of PS 2.0 was evaluated by analyzing the DFW and isocenter spot size of the modulated carbon ion beams. Finally, a plane homogeneous radiation field was simulated and fluence homogeneities were compared by using a 2D (X-Z) dose distribution and quantized by calculating the 1D-lateral flatness.ResultsCompared to the PS 1.0, the DFW is reduced by at most 1.11 mm by using PS 2.0 with a similar BP width broadening ability at the same beam range. Fluence homogeneity of PS 2.0 is excellent in all the downstream locations, and the isocenter spot size is reduced by at most 1.72 mm at the same beam range.ConclusionsThis study provides a new method for simulating the PS 2.0 as a BP broadening device with smaller DFW, better homogeneous and reduced isocenter spot size in comparison to PS 1.0.

Radiation therapy for cancer using the Bragg peak of an ion beam has been making steady progress after being proposed by Robert Wilson in 1946. At the end of 2020, 12 dedicated treatment devices existed in operation worldwide, and approximately 40,000 patients have been treated with ion beams (mostly carbon ions). To date, ion beam therapy is superior to other treatments for rare cancers in the head and neck as well as bone and soft tissues; however, most recently, evidence submitted in Japan for the 2022 revision of public health insurance shows that ion beam therapy outperforms photon therapy for intractable common cancers such as pancreatic cancer and liver cancer. This may greatly expand its indications. Lawrence Berkeley Laboratory in the United States started research of ion beam therapy, National Institute of Radiological Sciences in Japan built the first dedicated device Heavy Ion Accelerator in Chiba and started systematic clinical research, and GSI in Germany developed the scanning irradiation method and rotating gantry for the first time. This paper presents the history and future challenges of ion beam therapy in three fields: accelerator and beam delivery system, physical/biological model and treatment planning system, and clinical research. This study is divided into three parts describing the achievements and roles of the three laboratories. In Part 1, accelerator and beam delivery system are described. [ABSTRACT FROM AUTHOR]

In particle therapy, bioabsorbable polyglycolic acid (PGA) spacer was developed to reduce the healthy organ irradiation dose, especially in the gastrointestinal tract. The PGA spacer is safe and effective; however, there are no reports that have confirmed whether the PGA spacer which inserted in the body actually stops the carbon-ion (C-ion) beams. Here, we visualized and confirmed that the PGA spacer stops the C-ion beams in the body based on the dose distribution using auto-activation positron emission tomography (AAPET). A 59-year-old dedifferentiated retroperitoneal liposarcoma patient underwent C-ion radiotherapy (C-ion RT) on referral. A month before C-ion RT initiation, the patient underwent PGA spacer placement. Postoperatively, the patient received 4.4 Gy (RBE) per fraction of C-ion RT, followed by AAPET. AAPET revealed lower positron emitter concentrations at the distal tissue ventral to the PGA spacer than in the planning target volume. In observing the efficacy of the PGA spacer, the AAPET images and the average count per second of the positron emitter suggested that the PGA spacer stopped the C-ion beams in the body in accordance with the dose distribution. Therefore, AAPET was useful in confirming the PGA spacer's effectiveness in this study, and the PGA spacer stopped the C-ion beams. [ABSTRACT FROM AUTHOR]

Due to the unique properties of carbons in depth-dose deposition, this study investigated the carbon therapy of brain tumors using the Geant4 toolkit. To see the effect of phantom material on the dose calculations, three phantoms consisting of realistic brain tissue, soft tissue, and water were considered. The spherical tumor was considered at the center of the brain and the Bragg peak was calculated at the center of the tumor. The dose deposition in depth was different for all three phantoms, so that this difference is about 3 mm for the Bragg peak in the brain phantom and soft tissue phantom, and about 4 mm for the Bragg peak in the soft tissue and water. The depth dose distribution of the secondary particles indicates that the photons deposit most of their dose close to the surface, while for alpha and protons it depends on the Bragg peak depth. Also, the deposited dose in the tumor is more than one hundred times larger than the deposited dose in the brain healthy tissue, and ten thousand times higher than the organs such as the thymus gland and thyroid. The results of this investigation confirmed that more effort should be made to use more realistic phantoms in treatment design.

Purpose: To investigate DNA double strand breaks (DSBs) induced by therapeutic proton beams in plateau and Bragg peak to demonstrate DSB induction due to the higher LET in the Bragg peak. Materials and Methods: pUC19 plasmid DNA samples were irradiated to doses of 1000 and 3000 Gy on a Mevion S250i proton system with a monoenergetic, 110 MeV, proton beam at depths of 2 and 9.4 cm, corresponding to a position on the plateau and distal Bragg peak of the beam, respectively. The irradiated DNA samples were imaged by atomic force microscopy for visualization of individual DNA molecules, either broken or intact, and quantification of the DNA fragment length distributions for each of the irradiated samples. Percentage of the broken DNA and average number of DSBs per DNA molecule were obtained. Results: Compared to irradiation effects in the plateau region, DNA irradiated at the Bragg peak sustained more breakage at the same dose, yielding more short DNA fragments and higher numbers of DSB per DNA molecule. Conclusion: The higher LET of proton beams at the Bragg peak results in more densely distributed DNA DSBs, which supports an underlying mechanism for the increased cell killing by protons at the Bragg peak. [ABSTRACT FROM AUTHOR]

Objective: The energy deposition of photons and protons differs. It depends on the position in the proton Bragg peak (BP) and the linear energy transfer (LET) leading to a variable relative biological effectiveness (RBE). Here, we investigate LET dependent alterations on metabolic viability and proliferation of sarcoma and endothelium cell lines following proton irradiation in comparison to photon exposure.&#xD;Approach: Using a multi-step range shifter (MSRS), each column of a 96-well plate was positioned in a different depth along four BP curves with increasing intensities. The high-throughput experimental setup covers dose, LET, and RBE changes seen in a treatment field. Photon irradiation was performed to calculate the RBE along the BP curve. Two biological information out of one experiment were extracted allowing a correlation between metabolic viability and proliferation of the cells.&#xD;Main results: The metabolic viability and cellular proliferation were column-wise altered showing a depth-dose profile. Endothelium cell viability recovers within 96 h post BP irradiation while sarcoma cell viability remains reduced. Highest RBE values were observed at the BP distal fall-off regarding proliferation of the sarcoma and endothelial cells.&#xD;Significance: The high-throughput experimental setup introduced here I) covers dose, LET, and RBE changes seen in a treatment field, II) measures short-term effects within 48 h to 96 h post irradiation, and III) can additionally be transferred to various cell types without time consuming experimental adaptations. Traditionally, RBE values are calculated from clonogenic cell survival. Measured RBE profiles strongly depend on physical characteristics such as dose and LET and biological characteristics for example cell type and time point. Metabolic viability and proliferation proofed to be in a similar effect range compared to clonogenic survival results. Based on limited data of combined irradiation with doxorubicin, future experiments will test combined treatment with systemic therapies applied in clinics e.g. cyclin-dependent inhibitors.&#xD;&#xD., (Creative Commons Attribution license.)

PurposeTo investigate DNA double strand breaks (DSBs) induced by therapeutic proton beams in plateau and Bragg peak to demonstrate DSB induction due to the higher LET in the Bragg peak.Materials and MethodspUC19 plasmid DNA samples were irradiated to doses of 1000 and 3000 Gy on a Mevion S250i proton system with a monoenergetic, 110 MeV, proton beam at depths of 2 and 9.4 cm, corresponding to a position on the plateau and distal Bragg peak of the beam, respectively. The irradiated DNA samples were imaged by atomic force microscopy for visualization of individual DNA molecules, either broken or intact, and quantification of the DNA fragment length distributions for each of the irradiated samples. Percentage of the broken DNA and average number of DSBs per DNA molecule were obtained.ResultsCompared to irradiation effects in the plateau region, DNA irradiated at the Bragg peak sustained more breakage at the same dose, yielding more short DNA fragments and higher numbers of DSB per DNA molecule.ConclusionThe higher LET of proton beams at the Bragg peak results in more densely distributed DNA DSBs, which supports an underlying mechanism for the increased cell killing by protons at the Bragg peak.

Lithium fluoride (LiF) crystals and thin films are utilized as radiation detectors for energy diagnostics of proton beams. This is achieved by analyzing the Bragg curves in LiF obtained by imaging the radiophotoluminescence of color centers created by protons. In LiF crystals, the Bragg peak depth increases superlinearly with the particle energy. A previous study has shown that, when 35 MeV protons impinge at grazing incidence onto LiF films deposited on Si(100) substrates, the Bragg peak in the films is located at the depth where it would be found in Si rather than in LiF due to multiple Coulomb scattering. In this paper, Monte Carlo simulations of proton irradiations in the 1–8 MeV energy range are performed and compared to experimental Bragg curves in optically transparent LiF films on Si(100) substrates. Our study focuses on this energy range because, as energy increases, the Bragg peak gradually shifts from the depth in LiF to that in Si. The impact of grazing incidence angle, LiF packing density, and film thickness on shaping the Bragg curve in the film is examined. At energies higher than 8 MeV, all these quantities must be considered, although the effect of packing density plays a minor role.

The Nebulizer spray pyrolysis technique is used to make tin disulphide thin films at various substrate temperatures. SnS2 thin films structural, electrical and optical properties are investigated. The polycrystalline nature was confirmed by Xray diffraction (XRD) analysis, which revealed a hexagonal structure with a preferred orientation along the (0 0 2) plane. The full width half maximum value of the Bragg peak is used to calculate the size of SnS2 crystallization. Scanning Electron Microscope (SEM) is used to examine the composition and surface morphology of SnS2 thin films. The wavelength range of 400-1110 nm is used to determine the transmittance and absorption spectra of these films. With increasing substrate temperature, the optical band gap of tin disulphide thin films decreases from 3.17 eV to 2.61 eV. With regard to substrate temperature, the absorption coefficient and activation energy were reduced with SnS2 deposition. [ABSTRACT FROM AUTHOR]

The first paper of a series of three publications briefly presents the characteristics a proton beam, as well as the information of companies producing noncommercial techniques for photon and proton therapies. The following second and third parts will briefly consider the clinical and economic efficiency of proton versus photon radiotherapy in the treatment of cancer patients and prospects for its development in oncological practice.

The exploitation of visible radiophotoluminescence in lithium fluoride (LiF) crystals, due to local aggregate point defects produced by ionizing radiation in the crystal lattice, is demonstrated for fluorescent imaging of single tracks of protons at low energies. LiF crystals were irradiated perpendicularly with respect to nearly monochromatic, collimated proton beams at the energies of about 1 MeV in a fluence range from ∼5.8 × 105 p/cm2 up to ∼3.4 × 107 p/cm2 and of about 2.6 MeV in a fluence range from ∼9.6 × 105 p/cm2 up to ∼4.7 × 106 p/cm2. The fluence values were estimated by detecting and automatically counting the tracks on the images acquired with a fluorescence microscope at high magnification; they were found to be in agreement with those obtained using CR39 plastic detectors irradiated under the same experimental conditions. Despite the very short range in matter of these charged particles, by focusing the excitation blue light at discrete depths in the irradiated LiF crystals, an estimate of the proton energies was also obtained. These first results are encouraging for the utilization of LiF crystals as fluorescent nuclear track detectors under typical conditions employed in ion radiobiology. • Imaging of fluorescent tracks of 1 and 2.6 MeV protons in LiF crystals. • Proton beam energy estimated by fluorescent track image analysis at different depth. • Automatic counting of the tracks in the fluorescence images at high magnification. • Beam fluence of 1.4 × 106 p/cm2 in LiF in good agreement with that in CR39 detector. • Fluence in LiF crystals estimated up to 2.2 × 107 p/cm2 without track superposition. [ABSTRACT FROM AUTHOR]

The present study aimed to evaluate the morphological, cytogenetic and biochemical changes in wheat seedlings as affected by seed exposure to a proton beam at the Bragg peak. The average energy of the proton beam was of 171 MeV at the entrance into the irradiator room while at the point of sample irradiation the beam energy was of 150 MeV, with the average value of the Linear Energy Transfer of 0.539 keV/μm and the dose rate of 0.55 Gy/min, the radiation doses being of the order of tens of Gy. Cytogenetic investigation has revealed the remarkable diminution of the mitotic index as linear dose-response curve as well as the spectacular linear increase of the aberration index. Analyzing some biometric parameters, it was found that neither dry matter nor water content of wheat seedlings was influenced by proton beam exposure. Studying the biochemical parameters related to the antioxidant defense system, we found that the irradiation caused the slight increasing tendency of peroxidase activity as well as the decreasing trend in the activity of superoxidedismutase in the seedlings grown from the irradiated seeds. The level of malonedialdehyde (MDA) and total polyphenols showed an increasing tendency in all seedling variants corresponding to irradiated seeds, compared to the control. We conclude that the irradiation clearly induced dose-response curves at the level of cytogenetic parameters together with relatively slight variation tendency of some biochemical parameters related to the antioxidant defense system while imperceptible changes could be noticed in the biometric parameters.

Objective To establish a computerized-tomography water equivalent penetration length (C T-WEPL） calibration curve for the carbon ion treatment planning (ci Panl) system. Methods Several tissue-equivalent materials were adopted for measuring the WEPL coefficients. The CT-WEPL was acquired by fitting the corresponding curve according to the experiment data. Results CT-WEPL = 1.075 × 10-3 CT + 1.068（CT<-85）;CT-WEPL = 4.247×10-4 CT + 1.014（CT ≥-85）.Conclusion On the experimental basis, there is no fixed general calibration curve between CT number and WEPL coefficient in carbon ion beams. For a specific CT machine, a dedicated CT-WEPL calibration curve should be established. [ABSTRACT FROM AUTHOR]

DNA double-strand breaks (DSBs) are the main factor behind carbon-ion radiation therapy (CIRT)-induced cell death. Nuclear interactions along the beam path between the primary carbon ions and targets result in nuclear fragmentation of carbon ions and recoiled particles. These secondary particles travel further distances past the Bragg peak to the tail region, leading to unwanted biological effects that may result in cytotoxicity in critical organs and secondary induced tumors following CIRT. Here, we confirmed that the density of the DSB distributions increases as the cell survival decreases at the Bragg peak and demonstrated that by visualizing DSBs, the various LET fragmentation ions and recoiled particles produced differences in their biological effects in the post-Bragg peak tail regions. This suggests that the density of the DSBs within the high-LET track structures, rather than only their presence, is important for inducing cell death. These results are essential for CIRT treatment planning to limit the amount of healthy cell damage and reducing both the late effect and the secondary tumor-associated risk. [ABSTRACT FROM AUTHOR]

Heavy ions have a high potential for destroying deep tumors that carry the highest dose at the peak of Bragg. The peak caused by a single-energy carbon beam is too narrow, which requires special measures for improvement. Here, carbon-12 (12C) ion with different energies has been used as a source for calculating the dose distribution in the water phantom, soft tissue and bone by the code of Monte Carlo-based FLUKA code. By increasing the energy of the initial beam, the amount of absorbed dose at Bragg peak in all three targets decreased, but the trend for this reduction was less severe in bone. While the maximum absorbed dose per bone-mass unit in energy of 200 MeV/u was about 30% less than the maximum absorbed dose per unit mass of water or soft tissue, it was merely 2.4% less than soft tissue in 400 MeV/u. The simulation result showed a good agreement with experimental data at GSI Darmstadt facility of biophysics group by 0.15 cm average accuracy in Bragg peak positioning. From 200 to 400 MeV/u incident energy, the Bragg peak location increased about 18 cm in soft tissue. Correspondingly, the bone and soft tissue revealed a reduction dose ratio by 2.9 and 1.9. Induced neutrons did not contribute more than 1.8% to the total energy deposited in the water phantom. Also during 12C ion bombardment, secondary fragments showed 76% and 24% of primary 200 and 400 MeV/u, respectively, were present at the Bragg-peak position. The combined treatment of carbon ions with neutron or electron beams may be more effective in local dose delivery and also treating malignant tumors.

DNA double-strand breaks (DSBs) are the main factor behind carbon-ion radiation therapy (CIRT)-induced cell death. Nuclear interactions along the beam path between the primary carbon ions and targets result in nuclear fragmentation of carbon ions and recoiled particles. These secondary particles travel further distances past the Bragg peak to the tail region, leading to unwanted biological effects that may result in cytotoxicity in critical organs and secondary induced tumors following CIRT. Here, we confirmed that the density of the DSB distributions increases as the cell survival decreases at the Bragg peak and demonstrated that by visualizing DSBs, the various LET fragmentation ions and recoiled particles produced differences in their biological effects in the post-Bragg peak tail regions. This suggests that the density of the DSBs within the high-LET track structures, rather than only their presence, is important for inducing cell death. These results are essential for CIRT treatment planning to limit the amount of healthy cell damage and reducing both the late effect and the secondary tumor-associated risk.

The use of the digital imaging detector (DID) for calibrating the Prometeus proton accelerator before a beam therapy session is considered. The results of the DID detector operation in the mode of recording spots (low-intensity pulses), obtained during a Prometeus accelerator beam session, are presented for the first time. The DID detector makes it possible to obtain on-line the distribution of the energy release of each spot over the irradiated target region per several accelerator pulses. [ABSTRACT FROM AUTHOR]

Purpose: Reirradiation in the scalp area can be challenging given the proximity to organs at risk (OARs), such as the eye and brain. Our aim is to evaluate the dosimetric differences of volumetric modulated arc therapy (VMAT) and electron beam therapy (EBT) compared with 3-dimensional proton beam therapy (PBT). Patients and Methods: We evaluated a patient with recurrent angiosarcoma of the left temporal scalp after prior surgical resections and radiation therapy to 60 Gy in 30 fractions who needed reirradiation. We generated VMAT, EBT, and PBT plans using the Pinnacle Treatment Planning System (TPS). Both VMAT and EBT plans used a skin bolus, whereas no bolus was used for the proton plan. Doses to the OARs, including cochlea, eyes, lens, lacrimal glands, optic nerves, optic chiasm, pituitary gland, and underlying brain, were compared. Results: The reirradiation treatment dose was 60 Gy(RBE). Target volume coverage was comparable in all plans. Compared with VMAT and EBT, the PBT plan showed reductions in mean and maximum doses to all OARs. Without the use of protons, several OARs would have exceeded dose tolerance utilizing VMAT or electrons. Dose reduction of up to 100% was achieved for central and contralateral OARs. Conclusion: Compared with VMAT and EBT, PBT resulted in dose reductions to all OARs, while maintaining excellent target coverage. PBT showed a significant advantage in treating superficially located skin cancers, such as angiosarcoma, without the need for a bolus. PBT can be considered in the upfront treatment and certainly in the reirradiation setting.

This study introduces a novel iterative Bragg peak removal with automatic intensity correction (IBR-AIC) methodology for X-ray absorption spectroscopy (XAS), specifically addressing the challenge of Bragg peak interference in the analysis of crystalline materials. The approach integrates experimental adjustments and sophisticated post-processing, including an iterative algorithm for robust calculation of the scaling factor of the absorption coefficients and efficient elimination of the Bragg peaks, a common obstacle in accurately interpreting XAS data, particularly in crystalline samples. The method was thoroughly evaluated on dilute catalysts and thin films, with fluorescence mode and large-angle rotation. The results underscore the technique's effectiveness, adaptability and substantial potential in improving the precision of XAS data analysis. While demonstrating significant promise, the method does have limitations related to signal-to-noise ratio sensitivity and the necessity for meticulous angle selection during experimentation. Overall, IBR-AIC represents a significant advancement in XAS, offering a pragmatic solution to Bragg peak contamination challenges, thereby expanding the applications of XAS in understanding complex materials under diverse experimental conditions., (open access.)