Mechanistic modelling of relative biological effectiveness of carbon ion beams and comparison with experiments.

Objective.Relative biological effectiveness (RBE) plays a vital role in carbon ion radiotherapy, which is a promising treatment method for reducing toxic effects on normal tissues and improving treatment efficacy. It is important to have an effective and precise way of obtaining RBE values to support clinical decisions. A method of calculating RBE from a mechanistic perspective is reported.Approach.Ratio of dose to obtain the same number of double strand breaks (DSBs) between different radiation types was used to evaluate RBE. Package gMicroMC was used to simulate DSB yields. The DSB inductions were then analyzed to calculate RBE. The RBE values were compared with experimental results.Main results.Furusawa's experiment yielded RBE values of 1.27, 2.22, 3.00 and 3.37 for carbon ion beam with dose-averaged LET of 30.3 keVµm-1, 54.5 keVµm-1, 88 keVµm-1and 137 keVµm-1, respectively. RBE values computed from gMicroMC simulations were 1.75, 2.22, 2.87 and 2.97. When it came to a more sophisticated carbon ion beam with 6 cm spread-out Bragg peak, RBE values were 1.61, 1.63, 2.19 and 2.36 for proximal, middle, distal and distal end part, respectively. Values simulated by gMicroMC were 1.50, 1.87, 2.19 and 2.34. The simulated results were in reasonable agreement with the experimental data.Significance.As a mechanistic way for the evaluation of RBE for carbon ion radiotherapy by combining the macroscopic simulation of energy spectrum and microscopic simulation of DNA damages, this work provides a promising tool for RBE calculation supporting clinical applications such as treatment planning.

Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy-Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling.

High-Z gold nanoparticles (AuNPs) conjugated to a targeting antibody can help to improve tumor control in radiotherapy while simultaneously minimizing radiotoxicity to adjacent healthy tissue. This paper summarizes the main findings of a joint research program which applied AuNP-conjugates in preclinical modeling of radiotherapy at the Klinikum rechts der Isar, Technical University of Munich and Helmholtz Zentrum München. A pharmacokinetic model of superparamagnetic iron oxide nanoparticles was developed in preparation for a model simulating the uptake and distribution of AuNPs in mice. Multi-scale Monte Carlo simulations were performed on a single AuNP and multiple AuNPs in tumor cells at cellular and molecular levels to determine enhancements in the radiation dose and generation of chemical radicals in close proximity to AuNPs. A biologically based mathematical model was developed to predict the biological response of AuNPs in radiation enhancement. Although simulations of a single AuNP demonstrated a clear dose enhancement, simulations relating to the generation of chemical radicals and the induction of DNA strand breaks induced by multiple AuNPs showed only a minor dose enhancement. The differences in the simulated enhancements at molecular and cellular levels indicate that further investigations are necessary to better understand the impact of the physical, chemical, and biological parameters in preclinical experimental settings prior to a translation of these AuNPs models into targeted cancer radiotherapy.

Radiological tissue equivalence of deformable silicone-based chemical radiation dosimeters (FlexyDos3D).

FlexyDos3D, a silicone-based chemical radiation dosimeter, has great potential to serve as a three-dimensional (3D) deformable dosimetric tool to verify complex dose distributions delivered by modern radiotherapy techniques. To facilitate its clinical application, its radiological tissue needs to be clarified. In this study we investigated its tissue-equivalence in comparison with water and Solid Water (RMI457). We found that its effective and mean atomic numbers were 40% and 20% higher and the total interaction probabilities for kV x-ray photons were larger than those of water respectively. To assess the influence of its over-response to kV photons, its HU value was measured by kV computed tomography (CT) and was found higher than all the soft-tissue substitutes. When applied for dose calculation without correction, this effect led to an 8% overestimation in electron density via HU-value mapping and 0.65% underestimation in target dose. Furthermore, depth dose curves (PDDs) and off-axis ratios (profiles) at various beam conditions as well as the dose distribution of a full-arc VMAT plan in FlexyDos3D and reference materials were simulated by Monte Carlo, where the results showed great agreement. As indicated, FlexyDos3D exhibits excellent radiological water-equivalence for clinical MV x-ray dosimetry, while its nonwater-equivalent effect for low energy x-ray dosimetry requires necessary correction. The key findings of this study provide pertinent reference for further FlexyDos3D characterization research.

Imaging Dose, Cancer Risk and Cost Analysis in Image-guided Radiotherapy of Cancers.

The purpose of this retrospective study is to evaluate the cumulative imaging doses, the associated cancer risk and the cost related to the various radiological imaging procedures in image-guided radiotherapy of cancers. Correlations between patients' size and Monte Carlo simulated organ doses were established and validated for various imaging procedures, and then used for patient-specific organ dose estimation of 4,832 cancer patients. The associated cancer risk was estimated with published models and the cost was calculated based on the standard billing codes. The average (range) cumulative imaging doses to the brain, lungs and red bone marrow were 38.0 (0.5-177.3), 18.8 (0.4-246.5), and 49.1 (0.4-274.4) cGy, respectively. The associated average (range) lifetime attributable risk of cancer incidence per 100,000 persons was 78 (0-2798), 271 (1-8948), and 510 (0-4487) for brain cancer, lung cancer and leukemia, respectively. The median (range) imaging cost was $5256 (4268-15896) for the head scans, $5180 (4268-16274) for the thorax scans, and $7080 (4268-15288) for the pelvic scans, respectively. The image-guidance procedures and the accumulated imaging doses should be incorporated into clinical decision-making to personalize radiotherapy for individual patients.

Monte Carlo simulation of beam characteristics from small fields based on TrueBeam flattening-filter-free mode.

PURPOSE: Through the Monte Carlo (MC) simulation of 6 and 10 MV flattening-filter-free (FFF) beams from Varian TrueBeam accelerator, this study aims to find the best incident electron distribution for further studying the small field characteristics of these beams. METHODS: By incorporating the training materials of Varian on the geometry and material parameters of TrueBeam Linac head, the 6 and 10 MV FFF beams were modelled using the BEAMnrc and DOSXYZnrc codes, where the percentage depth doses (PDDs) and the off-axis ratios (OARs) curves of fields ranging from 4 × 4 to 40 × 40 cm(2) were simulated for both energies by adjusting the incident beam energy, radial intensity distribution and angular spread, respectively. The beam quality and relative output factor (ROF) were calculated. The simulations and measurements were compared using Gamma analysis method provided by Verisoft program (PTW, Freiburg, Germany), based on which the optimal MC model input parameters were selected and were further used to investigate the beam characteristics of small fields. RESULTS: The Full Width Half Maximum (FWHM), mono-energetic energy and angular spread of the resultant incident Gaussian radial intensity electron distribution were 0.75 mm, 6.1 MeV and 0.9° for the nominal 6 MV FFF beam, and 0.7 mm, 10.8 MeV and 0.3° for the nominal 10 MV FFF beam respectively. The simulation was mostly comparable to the measurement. Gamma criteria of 1 mm/1 % (local dose) can be met by all PDDs of fields larger than 1 × 1 cm(2), and by all OARs of no larger than 20 × 20 cm(2), otherwise criteria of 1 mm/2 % can be fulfilled. Our MC simulated ROFs agreed well with the measured ROFs of various field sizes (the discrepancies were less than 1 %), except for the 1 × 1 cm(2) field. CONCLUSIONS: The MC simulation agrees well with the measurement and the proposed model parameters can be clinically used for further dosimetric studies of 6 and 10 MV FFF beams.

Concomitant Imaging Dose and Cancer Risk in Image Guided Thoracic Radiation Therapy.

PURPOSE: Kilovoltage cone beam computed tomography (CT) (kVCBCT) imaging guidance improves the accuracy of radiation therapy but imposes an extra radiation dose to cancer patients. This study aimed to investigate concomitant imaging dose and associated cancer risk in image guided thoracic radiation therapy. METHODS AND MATERIALS: The planning CT images and structure sets of 72 patients were converted to CT phantoms whose chest circumferences (Cchest) were calculated retrospectively. A low-dose thorax protocol on a Varian kVCBCT scanner was simulated by a validated Monte Carlo code. Computed doses to organs and cardiac substructures (for 5 selected patients of various dimensions) were regressed as empirical functions of Cchest, and associated cancer risk was calculated using the published models. The exposures to nonthoracic organs in children were also investigated. RESULTS: The structural mean doses decreased monotonically with increasing Cchest. For all 72 patients, the median doses to the heart, spinal cord, breasts, lungs, and involved chest were 1.68, 1.33, 1.64, 1.62, and 1.58 cGy/scan, respectively. Nonthoracic organs in children received 0.6 to 2.8 cGy/scan if they were directly irradiated. The mean doses to the descending aorta (1.43 ± 0.68 cGy), left atrium (1.55 ± 0.75 cGy), left ventricle (1.68 ± 0.81 cGy), and right ventricle (1.85 ± 0.84 cGy) were significantly different (P<.05) from the heart mean dose (1.73 ± 0.82 cGy). The blade shielding alleviated the exposure to nonthoracic organs in children by an order of magnitude. CONCLUSIONS: As functions of patient size, a series of models for personalized estimation of kVCBCT doses to thoracic organs and cardiac substructures have been proposed. Pediatric patients received much higher doses than did the adults, and some nonthoracic organs could be irradiated unexpectedly by the default scanning protocol. Increased cancer risks and disease adverse events in the thorax were strongly related to higher imaging doses and smaller chest dimensions.

Personalized assessment of kV cone beam computed tomography doses in image-guided radiotherapy of pediatric cancer patients.

PURPOSE: To develop a quantitative method for the estimation of kV cone beam computed tomography (kVCBCT) doses in pediatric patients undergoing image-guided radiotherapy. METHODS AND MATERIALS: Forty-two children were retrospectively analyzed in subgroups of different scanned regions: one group in the head-and-neck and the other group in the pelvis. Critical structures in planning CT images were delineated on an Eclipse treatment planning system before being converted into CT phantoms for Monte Carlo simulations. A benchmarked EGS4 Monte Carlo code was used to calculate three-dimensional dose distributions of kVCBCT scans with full-fan high-quality head or half-fan pelvis protocols predefined by the manufacturer. Based on planning CT images and structures exported in DICOM RT format, occipital-frontal circumferences (OFC) were calculated for head-and-neck patients using DICOMan software. Similarly, hip circumferences (HIP) were acquired for the pelvic group. Correlations between mean organ doses and age, weight, OFC, and HIP values were analyzed with SigmaPlot software suite, where regression performances were analyzed with relative dose differences (RDD) and coefficients of determination (R(2)). RESULTS: kVCBCT-contributed mean doses to all critical structures decreased monotonically with studied parameters, with a steeper decrease in the pelvis than in the head. Empirical functions have been developed for a dose estimation of the major organs at risk in the head and pelvis, respectively. If evaluated with physical parameters other than age, a mean RDD of up to 7.9% was observed for all the structures in our population of 42 patients. CONCLUSIONS: kVCBCT doses are highly correlated with patient size. According to this study, weight can be used as a primary index for dose assessment in both head and pelvis scans, while OFC and HIP may serve as secondary indices for dose estimation in corresponding regions. With the proposed empirical functions, it is possible to perform an individualized quantitative dose assessment of kVCBCT scans.