Integrating Reinforcement Learning and Monte Carlo Tree Search for enhanced neoantigen vaccine design.

Recent advances in cancer immunotherapy have highlighted the potential of neoantigen-based vaccines. However, the design of such vaccines is hindered by the possibility of weak binding affinity between the peptides and the patient's specific human leukocyte antigen (HLA) alleles, which may not elicit a robust adaptive immune response. Triggering cross-immunity by utilizing peptide mutations that have enhanced binding affinity to target HLA molecules, while preserving their homology with the original one, can be a promising avenue for neoantigen vaccine design. In this study, we introduced UltraMutate, a novel algorithm that combines Reinforcement Learning and Monte Carlo Tree Search, which identifies peptide mutations that not only exhibit enhanced binding affinities to target HLA molecules but also retains a high degree of homology with the original neoantigen. UltraMutate outperformed existing state-of-the-art methods in identifying affinity-enhancing mutations in an independent test set consisting of 3660 peptide-HLA pairs. UltraMutate further showed its applicability in the design of peptide vaccines for Human Papillomavirus and Human Cytomegalovirus, demonstrating its potential as a promising tool in the advancement of personalized immunotherapy.

RadPhysBio: A Radiobiological Database for the Prediction of Cell Survival upon Exposure to Ionizing Radiation.

Based on the need for radiobiological databases, in this work, we mined experimental ionizing radiation data of human cells treated with X-rays, γ-rays, carbon ions, protons and α-particles, by manually searching the relevant literature in PubMed from 1980 until 2024. In order to calculate normal and tumor cell survival α and ß coefficients of the linear quadratic (LQ) established model, as well as the initial values of the double-strand breaks (DSBs) in DNA, we used WebPlotDigitizer and Python programming language. We also produced complex DNA damage results through the fast Monte Carlo code MCDS in order to complete any missing data. The calculated α/ß values are in good agreement with those valued reported in the literature, where α shows a relatively good association with linear energy transfer (LET), but not ß. In general, a positive correlation between DSBs and LET was observed as far as the experimental values are concerned. Furthermore, we developed a biophysical prediction model by using machine learning, which showed a good performance for α, while it underscored LET as the most important feature for its prediction. In this study, we designed and developed the novel radiobiological 'RadPhysBio' database for the prediction of irradiated cell survival (α and ß coefficients of the LQ model). The incorporation of machine learning and repair models increases the applicability of our results and the spectrum of potential users.

High-Spatial-Resolution Benchtop X-ray Fluorescence Imaging through Bragg-Diffraction-Based Focusing with Bent Mosaic Graphite Crystals: A Simulation Study.

X-ray fluorescence imaging (XFI) can localize diagnostic or theranostic entities utilizing nanoparticle (NP)-based probes at high resolution in vivo, in vitro, and ex vivo. However, small-animal benchtop XFI systems demonstrating high spatial resolution (variable from sub-millimeter to millimeter range) in vivo are still limited to lighter elements (i.e., atomic number Z≤45). This study investigates the feasibility of focusing hard X-rays from solid-target tubes using ellipsoidal lens systems composed of mosaic graphite crystals with the aim of enabling high-resolution in vivo XFI applications with mid-Z (42≤Z≤64) elements. Monte Carlo simulations are performed to characterize the proposed focusing-optics concept and provide quantitative predictions of the XFI sensitivity, in silico tumor-bearing mice models loaded with palladium (Pd) and barium (Ba) NPs. Based on simulation results, the minimum detectable total mass of PdNPs per scan position is expected to be on the order of a few hundred nanograms under in vivo conform conditions. PdNP masses as low as 150 ng to 50 ng could be detectable with a resolution of 600 µm when imaging abdominal tumor lesions across a range of low-dose (0.8 µGy) to high-dose (8 µGy) exposure scenarios. The proposed focusing-optics concept presents a potential step toward realizing XFI with conventional X-ray tubes for high-resolution applications involving interesting NP formulations.

A comparative study on the dose-effect of low-dose radiation based on microdosimetric analysis and single-cell sequencing technology.

The biological mechanisms triggered by low-dose exposure still need to be explored in depth. In this study, the potential mechanisms of low-dose radiation when irradiating the BEAS-2B cell lines with a Cs-137 gamma-ray source were investigated through simulations and experiments. Monolayer cell population models were constructed for simulating and analyzing distributions of nucleus-specific energy within cell populations combined with the Monte Carlo method and microdosimetric analysis. Furthermore, the 10 × Genomics single-cell sequencing technology was employed to capture the heterogeneity of individual cell responses to low-dose radiation in the same irradiated sample. The numerical uncertainties can be found both in the specific energy distribution in microdosimetry and in differential gene expressions in radiation cytogenetics. Subsequently, the distribution of nucleus-specific energy was compared with the distribution of differential gene expressions to guide the selection of differential genes bioinformatics analysis. Dose inhomogeneity is pronounced at low doses, where an increase in dose corresponds to a decrease in the dispersion of cellular-specific energy distribution. Multiple screening of differential genes by microdosimetric features and statistical analysis indicate a number of potential pathways induced by low-dose exposure. It also provides a novel perspective on the selection of sensitive biomarkers that respond to low-dose radiation.

CERN-based experiments and Monte-Carlo studies on focused dose delivery with very high energy electron (VHEE) beams for radiotherapy applications.

Very High Energy Electron (VHEE) beams are a promising alternative to conventional radiotherapy due to their highly penetrating nature and their applicability as a modality for FLASH (ultra-high dose-rate) radiotherapy. The dose distributions due to VHEE need to be optimised; one option is through the use of quadrupole magnets to focus the beam, reducing the dose to healthy tissue and allowing for targeted dose delivery at conventional or FLASH dose-rates. This paper presents an in depth exploration of the focusing achievable at the current CLEAR (CERN Linear Electron Accelerator for Research) facility, for beam energies >200 MeV. A shorter, more optimal quadrupole setup was also investigated using the TOPAS code in Monte Carlo simulations, with dimensions and beam parameters more appropriate to a clinical situation. This work provides insight into how a focused VHEE radiotherapy beam delivery system might be achieved.

Geographical distribution of nitrate pollution and its risk assessment using GIS and Monte Carlo simulation in drinking water in urban areas of Fars province-Iran during 2017-2021.

Pollution of water resources with nitrate is currently one of the major challenges at the global level. In order to make macro-policy decisions in water safety plans, it is necessary to carry out nitrate risk assessment in underground water, which has not been done in Fars province for all urban areas. In the current study, 9494 drinking water samples were collected in four seasons in 32 urban areas of Fars province in Iran, between 2017 and 2021 to investigate the non-carcinogenic health risk assessment. Geographical distribution maps of hazard quotient were drawn using geographical information system software. The results showed that the maximum amount of nitrate in water samples in 4% of the samples in 2021, 2.5% of the samples in 2020 and 3% of the samples in 2019 were more than the standard declared by World Health Organization guidelines (50 mg/L). In these cases, the maximum amount of nitrate was reported between 82 and 123 mg/L. The HQ values for infants did not exceed 1 in any year, but for children (44% ± 10.8), teenagers (10.8% ± 8.4), and adults (3.2% ± 1.7) exceeded 1 in cities, years, and seasons, indicating that three age groups in the studied area are at noticeably significant non-carcinogenic risk. The results of the Monte Carlo simulation showed that the average value of non-carcinogenic risk was less than 1 for all age groups. Moreover, the maximum HQ values (95%) were higher than 1 for both children and teenager, indicating a significant non-carcinogenic risk for the two age groups.

Hyperspectral dark-field microscopy of human breast lumpectomy samples for tumor margin detection in breast-conserving surgery.

Significance: Hyperspectral dark-field microscopy (HSDFM) and data cube analysis algorithms demonstrate successful detection and classification of various tissue types, including carcinoma regions in human post-lumpectomy breast tissues excised during breast-conserving surgeries. Aim: We expand the application of HSDFM to the classification of tissue types and tumor subtypes in pre-histopathology human breast lumpectomy samples. Approach: Breast tissues excised during breast-conserving surgeries were imaged by the HSDFM and analyzed. The performance of the HSDFM is evaluated by comparing the backscattering intensity spectra of polystyrene microbead solutions with the Monte Carlo simulation of the experimental data. For classification algorithms, two analysis approaches, a supervised technique based on the spectral angle mapper (SAM) algorithm and an unsupervised technique based on the K-means algorithm are applied to classify various tissue types including carcinoma subtypes. In the supervised technique, the SAM algorithm with manually extracted endmembers guided by H&E annotations is used as reference spectra, allowing for segmentation maps with classified tissue types including carcinoma subtypes. Results: The manually extracted endmembers of known tissue types and their corresponding threshold spectral correlation angles for classification make a good reference library that validates endmembers computed by the unsupervised K-means algorithm. The unsupervised K-means algorithm, with no a priori information, produces abundance maps with dominant endmembers of various tissue types, including carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma. The two carcinomas' unique endmembers produced by the two methods agree with each other within <2% residual error margin. Conclusions: Our report demonstrates a robust procedure for the validation of an unsupervised algorithm with the essential set of parameters based on the ground truth, histopathological information. We have demonstrated that a trained library of the histopathology-guided endmembers and associated threshold spectral correlation angles computed against well-defined reference data cubes serve such parameters. Two classification algorithms, supervised and unsupervised algorithms, are employed to identify regions with carcinoma subtypes of invasive ductal carcinoma and invasive mucinous carcinoma present in the tissues. The two carcinomas' unique endmembers used by the two methods agree to <2% residual error margin. This library of high quality and collected under an environment with no ambient background may be instrumental to develop or validate more advanced unsupervised data cube analysis algorithms, such as effective neural networks for efficient subtype classification.

Dose and DNA damage modelling of diffusing alpha-emitters radiation therapy using Geant4.

PURPOSE: Diffusing alpha-emitters radiation therapy (DaRT) is a brachytherapy technique using α-particles to treat solid tumours. The high linear energy transfer (LET) and short range of α-particles make them good candidates for the targeted treatment of cancer. Treatment planning of DaRT requires a good understanding of the dose from α-particles and the other particles released in the 224Ra decay chain. METHODS: The Geant4 Monte Carlo toolkit has been used to simulate a DaRT seed to better understand the dose contribution from all particles and simulate the DNA damage due to this treatment. RESULTS: Close to the seed α-particles deliver the majority of dose, however at radial distances greater than 4 mm, the contribution of ß-particles is greater. The RBE has been estimated as a function of number of double strand breaks (DSBs) and complex DSBs. A maximum seed spacing of 5.5 mm and 6.5 mm was found to deliver at least 20 Gy RBE weighted dose between the seeds for RBEDSB and RBEcDSB respectively. CONCLUSIONS: The DNA damage changes with radial distance from the seed and has been found to become less complex with distance, which is potentially easier for the cell to repair. Close to the seed α-particles contribute the majority of dose, however the contribution from other particles cannot be neglected and may influence the choice of seed spacing.

Enhancing tumor's skin photothermal therapy using Gold nanoparticles : a Monte Carlo simulation.

The aim of this study is to investigate how the introduction of Gold nanoparticles GNPs into a skin tumor affects the ability to absorb laser light during multicolor laser exposure. The Monte Carlo Geant4 technique was used to construct a cubic geometry simulating human skin, and a 5 mm tumor spheroid was implanted at an adjustable depth x. Our findings show that injecting a very low concentration of 0.01% GNPs into a tumor located 1 cm below the skin's surface causes significant laser absorption of up to 25%, particularly in the 900 nm to 1200 nm range, resulting in a temperature increase of approximately 20%. It is an effective way to raise a tumor's temperature and cause cell death while preserving healthy cells. The addition of GNPs to a tumor during polychromatic laser exposure with a wavelength ranging from 900 nm to 1200 nm increases laser absorption and thus temperature while preserving areas without GNPs.

[Research Photon Energy Spectrum of Medical Linear Accelerator by Monte Carlo Method].

Objective: The distribution of the photon energy spectrum in isocenter plane of the medical linear accelerator and the influence of secondary collimator on the photon energy spectrum are studied. Methods Use the BEAMnrc program to simulate the transmission of the 6 MeV electrons and photons in 5 cm×5 cm,10 cm×10 cm,15 cm×15 cm and 20 cm×20 cm fields in treatment head of the medical linear accelerator, where a phase space file was set up at the isocenter plane to record the particle information passing through this plane. The BEAMdp program is used to analyze the phase space file, in order to obtain the distribution of the photon energy spectrum in isocenter plane and the influence of secondary collimator on the photon energy spectrum. Results: By analyzing the photon energy spectrum of a medical linear accelerator with a nominal energy of 6 MV, it is found that the secondary collimator has little effect on the photon energy spectrum; different fields have different photon energy spectrum distributions; the photon energy spectrum in different central regions of the same field have the same normalized distribution. Conclusion: In the dose calculation of radiation therapy, the influence of photon energy spectrum should be carefully considered.

Tuning spatially fractionated radiotherapy dose profiles using the moiré effect.

Spatially Fractionated Radiotherapy (SFRT) has demonstrated promising potential in cancer treatment, combining the advantages of reduced post-radiation effects and enhanced local control rates. Within this paradigm, proton minibeam radiotherapy (pMBRT) was suggested as a new treatment modality, possibly producing superior normal tissue sparing to conventional proton therapy, leading to improvements in patient outcomes. However, an effective and convenient beam generation method for pMBRT, capable of implementing various optimum dose profiles, is essential for its real-world application. Our study investigates the potential of utilizing the moiré effect in a dual collimator system (DCS) to generate pMBRT dose profiles with the flexibility to modify the center-to-center distance (CTC) of the dose distribution in a technically simple way.We employ the Geant4 Monte Carlo simulations tool to demonstrate that the angle between the two collimators of a DCS can significantly impact the dose profile. Varying the DCS angle from 10 ∘ to 50 ∘ we could cover CTC ranging from 11.8 mm to 2.4 mm, respectively. Further investigations reveal the substantial influence of the multi-slit collimator's (MSC) physical parameters on the spatially fractionated dose profile, such as period (CTC), throughput, and spacing between MSCs. These findings highlight opportunities for precision dose profile adjustments tailored to specific clinical scenarios.The DCS capacity for rapid angle adjustments during the energy transition stages of a spot scanning system can facilitate dynamic alterations in the irradiation profile, enhancing dose contrast in normal tissues. Furthermore, its unique attribute of spatially fractionated doses in both lateral directions could potentially improve normal tissue sparing by minimizing irradiated volume. Beyond the realm of pMBRT, the dual MSC system exhibits remarkable versatility, showing compatibility with different types of beams (X-rays and electrons) and applicability across various SFRT modalities.Our study illuminates the dual MSC system's potential as an efficient and adaptable tool in the refinement of pMBRT techniques. By enabling meticulous control over irradiation profiles, this system may expedite advancements in clinical and experimental applications, thereby contributing to the evolution of SFRT strategies.

Dosimetric feasibility study ("proof of concept") of refractory ventricular tachycardia radioablation using proton minibeams.

PURPOSE: Preclinical data demonstrated that the use of proton minibeam radiotherapy reduces the risk of toxicity in healthy tissue. Ventricular tachycardia radioablation is an area under clinical investigation in proton beam therapy. We sought to simulate a ventricular tachycardia radioablation with proton minibeams and to demonstrate that it was possible to obtain a homogeneous coverage of an arrhythmogenic cardiac zone with this technique. MATERIAL AND METHODS: An arrhythmogenic target volume was defined on the simulation CT scan of a patient, localized in the lateral wall of the left ventricle. A dose of 25Gy was planned to be delivered by proton minibeam radiotherapy, simulated using a Monte Carlo code (TOPAS v.3.7) with a collimator of 19 0.4 mm-wide slits spaced 3mm apart. The main objective of the study was to obtain a plan ensuring at least 93% of the prescription dose in 93% of the planning target volume without exceeding 110% of the prescribed dose in the planning target volume. RESULTS: The average dose in the planning treatment volume in proton minibeam radiotherapy was 25.12Gy. The percentage of the planning target volume receiving 93% (V93%), 110% (V110%), and 95% (V95%) of the prescribed dose was 94.25%, 0%, and 92.6% respectively. The lateral penumbra was 6.6mm. The mean value of the peak-to-valley-dose ratio in the planning target volume was 1.06. The mean heart dose was 2.54Gy versus 5.95Gy with stereotactic photon beam irradiation. CONCLUSION: This proof-of-concept study shows that proton minibeam radiotherapy can achieve a homogeneous coverage of an arrhythmogenic cardiac zone, reducing the dose at the normal tissues. This technique, ensuring could theoretically reduce the risk of late pulmonary and breast fibrosis, as well as cardiac toxicity as seen in previous biological studies in proton minibeam radiotherapy.

Concentrations, compositional profiles, and health risks of benzophenones among the Taiwanese population based on analysis of 23 daily consumed foods.

In this study, we analyzed the occurrence and distribution of 11 benzophenone-type ultraviolet filters (BPs) in 893 food samples spanning 7 food categories in Taiwan. We conducted a Monte Carlo simulation to determine the carcinogenic and noncarcinogenic risks of BPs. The results indicated that cornflakes had the highest mean level of BPs (103 ng/g), followed by bread (101 ng/g) and pastries (59 ng/g). BP was the most prevalent category, followed by 4-methylbenzophenone (4-MBP), 2-hydroxybenzophenone, and benzophenone-3. Estimation of the lifetime cancer risk (LTCR) of BP (average life expectancy of 80 years) placed them in the 50th and 97.5th percentiles [P50 (P97.5)] LTCR of 1.9 × 10-7 (5.7 × 10-6), indicating that BP in food poses a low renal hazard to the Taiwanese population. The noncarcinogenic risk of BPs was evaluated using a hazard quotient and combined margin of exposure (MOET), revealing a P50 (P97.5) hazard index of < 1 for BP, 4-MBP, and methyl-2-benzoylbenzoate. Although the P50 MOET values for all age groups were within the moderate range of concern, with a more conservative extreme (P2.5), the MOET values for the 0-3, 3-6, and 6-12 age groups fell below 100, indicating a high concern for renal degeneration and hyperplasia.

Monitoring multistage healthcare processes using state space models and a machine learning based framework.

Monitoring healthcare processes, such as surgical outcomes, with a keen focus on detecting changes and unnatural conditions at an early stage is crucial for healthcare professionals and administrators. In line with this goal, control charts, which are the most popular tool in the field of Statistical Process Monitoring, are widely employed to monitor therapeutic processes. Healthcare processes are often characterized by a multistage structure in which several components, states or stages form the final products or outcomes. In such complex scenarios, Multistage Process Monitoring (MPM) techniques become invaluable for monitoring distinct states of the process over time. However, the healthcare sector has seen limited studies employing MPM. This study aims to fill this gap by developing an MPM control chart tailored for healthcare data to promote early detection, confirmation, and patient safety. As it is important to detect unnatural conditions in healthcare processes at an early stage, the statistical control charts are combined with machine learning techniques (i.e., we deal with Intelligent Control Charting, ICC) to enhance detection ability. Through Monte Carlo simulations, our method demonstrates better performance compared to its statistical counterparts. To underline the practical application of the proposed ICC framework, real data from a two-stage thyroid cancer surgery is utilized. This real-world case serves as a compelling illustration of the effectiveness of the developed MPM control chart in a healthcare setting.

A Monte Carlo simulation-based decision support system for radiation oncologists in the treatment of glioblastoma multiforme.

In the present research, we have developed a model-based crisp logic function statistical classifier decision support system supplemented with treatment planning systems for radiation oncologists in the treatment of glioblastoma multiforme (GBM). This system is based on Monte Carlo radiation transport simulation and it recreates visualization of treatment environments on mathematical anthropomorphic brain (MAB) phantoms. Energy deposition within tumour tissue and normal tissues are graded by quality audit factors which ensure planned dose delivery to tumour site thereby minimising damages to healthy tissues. The proposed novel methodology predicts tumour growth response to radiation therapy from a patient-specific medicine quality audit perspective. Validation of the study was achieved by recreating thirty-eight patient-specific mathematical anthropomorphic brain phantoms of treatment environments by taking into consideration density variation and composition of brain tissues. Dose computations accomplished through water phantom, tissue-equivalent head phantoms are neither cost-effective, nor patient-specific customized and is often less accurate. The above-highlighted drawbacks can be overcome by using open-source Electron Gamma Shower (EGSnrc) software and clinical case reports for MAB phantom synthesis which would result in accurate dosimetry with due consideration to the time factors. Considerable dose deviations occur at the tumour site for environments with intraventricular glioblastoma, haematoma, abscess, trapped air and cranial flaps leading to quality factors with a lower logic value of 0. Logic value of 1 depicts higher dose deposition within healthy tissues and also leptomeninges for majority of the environments which results in radiation-induced laceration.

Planar dose calculation of electron therapy.

Purpose.The aim of this study is to determine the planar dose distribution of irregularly-shaped electron beams at their maximum dose depth (zmax) using the modied lateral build-up ratio (LBR) and curve-fitting methods.Methods.Circular and irregular cutouts were created using Cerrobend alloy for a 14 × 14 cm2applicator. Percentage depth dose (PDD) at the standard source-surface-distance (SSD = 100 cm) and point dose at different SSD were measured for each cutout. Orthogonal profiles of the cutouts were measured atzmax. Data were collected for 6, 9, 12, and 15 MeV electron beam energies on a VERSA HDTMLINAC using the IBA Blue Phantom23D water phantom system. The planar dose distributions of the cutouts were also measured atzmaxin solid water using EDR2 films.Results.The measured PDD curves were normalized to a normalization depth (d0) of 1 mm. The lateral-buildup-ratio (LBR), lateral spread parameter (σR(z)), and effective SSD (SSDeff) for each cutout were calculated using the PDD of the open applicator as the reference field. The modified LBR method was then employed to calculate the planar dose distribution of the irregular cutouts within the field at least 5 mm from the edge. A simple curve-fitting model was developed based on the profile shapes of the circular cutouts around the field edge. This model was used to calculate the planar dose distribution of the irregular cutouts in the region from 3 mm outside to 5 mm inside the field edge. Finally, the calculated planar dose distribution was compared with the film measurement.Conclusions.The planar dose distribution of electron therapy for irregular cutouts atzmaxwas calculated using the improved LBR method and a simple curve-fitting model. The calculated profiles were within 3% of the measured values. The gamma passing rate with a 3%/3 mm and 10% dose threshold was more than 96%.

TOPAS simulation of photoneutrons in radiotherapy: accuracy and speed with variance reduction.

Objective. We provide optimal particle split numbers for speeding up TOPAS Monte Carlo simulations of linear accelerator (linac) treatment heads while maintaining accuracy. In addition, we provide a new TOPAS physics module for simulating photoneutron production and transport.Approach.TOPAS simulation of a Siemens Oncor linac was used to determine the optimal number of splits for directional bremsstrahlung splitting as a function of the field size for 6 MV and 18 MV x-ray beams. The linac simulation was validated against published data of lateral dose profiles and percentage depth-dose curves (PDD) for the largest square field (40 cm side). In separate simulations, neutron particle split and the custom TOPAS physics module was used to generate and transport photoneutrons, called 'TsPhotoNeutron'. Verification of accuracy was performed by comparing simulations with published measurements of: (1) neutron yields as a function of beam energy for thick targets of Al, Cu, Ta, W, Pb and concrete; and (2) photoneutron energy spectrum at 40 cm laterally from the isocenter of the Oncor linac from an 18 MV beam with closed jaws and MLC.Main results.The optimal number of splits obtained for directional bremsstrahlung splitting enhanced the computational efficiency by two orders of magnitude. The efficiency decreased with increasing beam energy and field size. Calculated lateral profiles in the central region agreed within 1 mm/2% from measured data, PDD curves within 1 mm/1%. For the TOPAS physics module, at a split number of 146, the efficiency of computing photoneutron yields was enhanced by a factor of 27.6, whereas it improved the accuracy over existing Geant4 physics modules.Significance.This work provides simulation parameters and a new TOPAS physics module to improve the efficiency and accuracy of TOPAS simulations that involve photonuclear processes occurring in high-Zmaterials found in linac components, patient devices, and treatment rooms, as well as to explore new therapeutic modalities such as very-high energy electron therapy.

IOeRT conventional and FLASH treatment planning system implementation exploiting fast GPU Monte Carlo: The case of breast cancer.

Partial breast irradiation for the treatment of early-stage breast cancer patients can be performed by means of Intra Operative electron Radiation Therapy (IOeRT). One of the main limitations of this technique is the absence of a treatment planning system (TPS) that could greatly help in ensuring a proper coverage of the target volume during irradiation. An IOeRT TPS has been developed using a fast Monte Carlo (MC) and an ultrasound imaging system to provide the best irradiation strategy (electron beam energy, applicator position and bevel angle) and to facilitate the optimisation of dose prescription and delivery to the target volume while maximising the organs at risk sparing. The study has been performed in silico, exploiting MC simulations of a breast cancer treatment. Ultrasound-based input has been used to compute the absorbed dose maps in different irradiation strategies and a quantitative comparison between the different options was carried out using Dose Volume Histograms. The system was capable of exploring different beam energies and applicator positions in few minutes, identifying the best strategy with an overall computation time that was found to be completely compatible with clinical implementation. The systematic uncertainty related to tissue deformation during treatment delivery with respect to imaging acquisition was taken into account. The potential and feasibility of a GPU based full MC TPS implementation of IOeRT breast cancer treatments has been demonstrated in-silico. This long awaited tool will greatly improve the treatment safety and efficacy, overcoming the limits identified within the clinical trials carried out so far.

Experimental comparison of cylindrical and plane parallel ionization chambers for reference dosimetry in continuous and pulsed scanned proton beams.

Objective. In this experimental work we compared the determination of absorbed dose to water using four ionization chambers (ICs), a PTW-34045 Advanced Markus, a PTW-34001 Roos, an IBA-PPC05 and a PTW-30012 Farmer, irradiated under the same conditions in one continuous- and in two pulsed-scanned proton beams.Approach. The ICs were positioned at 2 cm depth in a water phantom in four square-field single-energy scanned-proton beams with nominal energies between 80 and 220 MeV and in the middle of 10 × 10 × 10 cm3dose cubes centered at 10 cm or 12.5 cm depth in water. The water-equivalent thickness (WET) of the entrance window and the effective point of measurement was considered when positioning the plane parallel (PP) ICs and the cylindrical ICs, respectively. To reduce uncertainties, all ICs were calibrated at the same primary standards laboratory. We used the beam quality (kQ) correction factors for the ICs under investigation from IAEA TRS-398, the newly calculated Monte Carlo (MC) values and the anticipated IAEA TRS-398 updated recommendations.Main results. Dose differences among the four ICs ranged between 1.5% and 3.7% using both the TRS-398 and the newly recommendedkQvalues. The spread among the chambers is reduced with the newlykQvalues. The largest differences were observed between the rest of the ICs and the IBA-PPC05 IC, obtaining lower dose with the IBA-PPC05.Significance. We provide experimental data comparing different types of chambers in different proton beam qualities. The observed dose differences between the ICs appear to be related to inconsistencies in the determination of thekQvalues. For PP ICs, MC studies account for the physical thickness of the entrance window rather than the WET. The additional energy loss that the wall material invokes is not negligible for the IBA-PPC05 and might partially explain the lowkQvalues determined for this IC. To resolve this inconsistency and to benchmark MC values,kQvalues measured using calorimetry are needed.

Evaluation of radiation detectors for the determination of field output factors in Leksell Gamma Knife dosimetry using 3D printed phantom inserts.

The Leksell Gamma Knife® Perfexion™ and Icon™ have a unique geometry, containing 192 60Co sources with collimation for field sizes of 4 mm, 8 mm, and 16 mm. 4 mm and 8 mm collimated fields lack lateral charged particle equilibrium, so accurate field output factors are essential. This study performs field output factor measurements for the microDiamond, microSilicon, and RAZOR™ Nano detectors. 3D printed inserts for the spherical Solid Water® Phantom were fabricated for microDiamond detector, the microSilicon unshielded diode and the RAZOR™ Nano micro-ionisation chamber. Detectors were moved iteratively to identify the peak detector signal for each collimator, representing the effective point of measurement of the chamber. In addition, field output correction factors were calculated for each detector relative to vendor supplied Monte Carlo simulated field output factors and field output factors measured with a W2 scintillator. All field output factors where within 1.1 % for the 4 mm collimator and within 2.3 % for the 8 mm collimator. The 3D printed phantom inserts were suitable for routine measurements if the user identifies the effective point of measurement, and ensures a reproducible setup by marking the rotational alignment of the cylindrical print. Measurements with the microDiamond and microSilicon can be performed faster compared to the RAZOR™ Nano due to differences in the signal to noise ratio. All detectors are suitable for field output factor measurements for the Leksell Gamma Knife® Perfexion™ and Icon™.