Monte Carlo simulation-based patient-specific QA using machine log files for line-scanning proton radiation therapy.

BACKGROUND: Quality assurance (QA) is a prerequisite for safe and accurate pencil-beam proton therapy. Conventional measurement-based patient-specific QA (pQA) can only verify limited aspects of patient treatment and is labor-intensive. Thus, a better method is needed to ensure the integrity of the treatment plan. PURPOSE: Line scanning, which involves continuous and rapid delivery of pencil beams, is a state-of-the-art proton therapy technique. Machine performance in delivering scanning protons is dependent on the complexity of the beam modulations. Moreover, it contributes to patient treatment accuracy. A Monte Carlo (MC) simulation-based QA method that reflects the uncertainty related to the machine during scanning beam delivery was developed and verified for clinical applications to pQA. METHODS: Herein, a tool for particle simulation (TOPAS) for nozzle modeling was used, and the code was commissioned against the measurements. To acquire the beam delivery uncertainty for each plan, patient plans were delivered. Furthermore, log files recorded every 60 µs by the monitors downstream of the nozzle were exported from the treatment control system. The spot positions and monitor unit (MU) counts in the log files were converted to dipole magnet strengths and number of particles, respectively, and entered into the TOPAS. For the 68 clinical cases, MC simulations were performed in a solid water phantom, and two-dimensional (2D) absolute dose distributions at 20-mm depth were measured using an ionization chamber array (Octavius 1500, PTW, Freiburg, Germany). Consequently, the MC-simulated 2D dose distributions were compared with the measured data, and the dose distributions in the pre-treatment QA plan created with RayStation (RaySearch Laboratories, Stockholm, Sweden). Absolute dose comparisons were made using gamma analysis with 3%/3 mm and 2%/2 mm criteria for 47 clinical cases without considering daily machine output variation in the MC simulation and 21 cases with daily output variation, respectively. All cases were analyzed with 90% or 95% of passing rate thresholds. RESULTS: For 47 clinical cases not considering daily output variations, the absolute gamma passing rates compared with the pre-treatment QA plan were 99.71% and 96.97%, and the standard deviations (SD) were 0.70% and 3.78% with the 3%/3 mm or 2%/2 mm criteria, respectively. Compared with the measurements, the passing rate of 2%/2 mm gamma criterion was 96.76% with 3.99% of SD. For the 21 clinical cases compared with pre-treatment QA plan data and measurements considering daily output variations, the 2%/2 mm absolute gamma analysis result was 98.52% with 1.43% of SD and 97.67% with 2.72% of SD, respectively. With a 95% passing rate threshold of 2%/2 mm criterion, the false-positive and false-negative were 21.8% and 8.3% for without and with considering output variation, respectively. With a 90% threshold, the false-positive and false-negative reduced to 11.4% and 0% for without and with considering output variation, respectively. CONCLUSIONS: A log-file-based MC simulation method for patient QA of line-scanning proton therapy was successfully developed. The proposed method exhibited clinically acceptable accuracy, thereby exhibiting a potential to replace the measurement-based dosimetry QA method with a 90% gamma passing rate threshold when applying the 2%/2 mm criterion.

FLASH dose rate calculation based on log files in proton pencil beam scanning therapy.

BACKGROUND: In radiation therapy, irradiating healthy normal tissues in the beam trajectories is inevitable. This unnecessary dose means that patients undergoing treatment risk developing side effects. Recently, FLASH radiotherapy delivering ultra-high-dose-rate beams has been re-examined because of its normal-tissue-sparing effect. To confirm the mean and instantaneous dose rates of the FLASH beam, stable and accurate dosimetry is required. PURPOSE: Detailed verification of the FLASH effect requires dosimeters and a method to measure the average and instantaneous dose rate stably for 2- or 3-dimensional dose distributions. To verify the delivered FLASH beam, we utilized machine log files from the built-in monitor chamber to develop a dosimetry method to calculate the dose and average/instantaneous dose rate distributions in two or three dimensions in a phantom. METHODS: To create a spread-out Bragg peak (SOBP) and deliver a uniform dose in a target, a mini-ridge filter was created with a 3D printer. Proton pencil beam line scanning plans of 2 × 2 cm2 , 3 × 3 cm2 , 4 × 4 cm2 , and round shapes with 2.3 cm diameter patterns delivering 230 MeV energy protons were created. The absorbed dose in the solid water phantom of each plan was measured using a PPC05 ionization chamber (IBA Dosimetry, Virginia, USA) in the SOBP region, and the log files for each plan were exported from the treatment control system console. Using these log files, the delivered dose and average dose rate were calculated using two methods: a direct method and a Monte Carlo (MC) simulation method that uses log file information. The computed and average dose rates were compared with the ionization chamber measurements. Additionally, instantaneous dose rates in user-defined volumes were calculated using the MC simulation method with a temporal resolution of 5 ms. RESULTS: Compared to ionization chamber dosimetry, 10 of 12 cases using the direct calculation method and 9 of 11 cases using the MC method had a dose difference below ±3%. Nine of 12 cases using the direct calculation method and 8 of 11 cases using the MC method had dose rate differences below ±3%. The average and maximum dose differences for the direct calculation and MC method were-0.17, +0.72%, and -3.15, +3.32%, respectively. For the dose rate difference, the average and maximum for the direct calculation and MC method were +1.26, +1.12%, and +3.75, +3.15%, respectively. In the instantaneous dose rate calculation with the MC simulation, a large fluctuation with a maximum of 163 Gy/s and a minimum of 4.29 Gy/s instantaneous dose rate was observed in a specific position, whereas the mean dose rate was 62 Gy/s. CONCLUSIONS: We successfully developed methods in which machine log files are used to calculate the dose and the average and instantaneous dose rates for FLASH radiotherapy and demonstrated the feasibility of verifying the delivered FLASH beams.

Feasibility of a GATE Monte Carlo platform in a clinical pretreatment QA system for VMAT treatment plans using TrueBeam with an HD120 multileaf collimator.

PURPOSE: To evaluate the quality of patient-specific complicated treatment plans, including commercialized treatment planning systems (TPS) and commissioned beam data, we developed a process of quality assurance (QA) using a Monte Carlo (MC) platform. Specifically, we constructed an interface system that automatically converts treatment plan and dose matrix data in digital imaging and communications in medicine to an MC dose-calculation engine. The clinical feasibility of the system was evaluated. MATERIALS AND METHODS: A dose-calculation engine based on GATE v8.1 was embedded in our QA system and in a parallel computing system to significantly reduce the computation time. The QA system automatically converts parameters in volumetric-modulated arc therapy (VMAT) plans to files for dose calculation using GATE. The system then calculates dose maps. Energies of 6 MV, 10 MV, 6 MV flattening filter free (FFF), and 10 MV FFF from a TrueBeam with HD120 were modeled and commissioned. To evaluate the beam models, percentage depth dose (PDD) values, MC calculation profiles, and measured beam data were compared at various depths (Dmax , 5 cm, 10 cm, and 20 cm), field sizes, and energies. To evaluate the feasibility of the QA system for clinical use, doses measured for clinical VMAT plans using films were compared to dose maps calculated using our MC-based QA system. RESULTS: A LINAC QA system was analyzed by PDD and profile according to the secondary collimator and multileaf collimator (MLC). Values for MC calculations and TPS beam data obtained using CC13 ion chamber (IBA Dosimetry, Germany) were consistent within 1.0%. Clinical validation using a gamma index was performed for VMAT treatment plans using a solid water phantom and arbitrary patient data. The gamma evaluation results (with criteria of 3%/3 mm) were 98.1%, 99.1%, 99.2%, and 97.1% for energies of 6 MV, 10 MV, 6 MV FFF, and 10 MV FFF, respectively. CONCLUSIONS: We constructed an MC-based QA system for evaluating patient treatment plans and evaluated its feasibility in clinical practice. We observed robust agreement between dose calculations from our QA system and measurements for VMAT plans. Our QA system could be useful in other clinical settings, such as small-field SRS procedures or analyses of secondary cancer risk, for which dose calculations using TPS are difficult to verify.

Investigations of line scanning proton therapy with dynamic multi-leaf collimator.

PURPOSE: Scanning proton therapy has dosimetric advantage over passive treatment, but has a large penumbra in low-energy region. This study investigates the penumbra reduction when multi-leaf collimators (MLCs) are used for line scanning proton beams and secondary neutron production from MLCs. METHODS: Scanning beam plans with and without MLC shaping were devised. Line scanning proton plan of 36 energy layers between 71.2 and 155.2 MeV was generated. The MLCs were shaped according to the cross-sectional target shape for each energy layer. The two-dimensional doses were measured through an ion-chamber array, depending on the presence of MLC field, and Monte Carlo (MC) simulations were performed. The plan, measurement, and MC data, with and without MLC, were compared at each depth. The secondary neutron dose was simulated with MC. Ambient neutron dose equivalents were computed for the line scanning with 10 × 10 × 5 cm3 volume and maximum proton energy of 150 MeV, with and without MLCs, at lateral distances of 25-200 cm from the isocenter. The neutron dose for a wobbling plan with 10 × 10 × 5 cm3 volume was also evaluated. RESULTS: The lateral penumbra width using MLC was reduced by 23.2% on average, up to a maximum of 32.2%, over the four depths evaluated. The ambient neutron dose equivalent was 18.52% of that of the wobbling beam but was 353.1% larger than the scanning open field. CONCLUSIONS: MLC field shaping with line scanning reduced the lateral penumbra and should be effective in sparing normal tissue. However, it is important to investigate the increase in neutron dose.

Proton range verification in inhomogeneous tissue: Treatment planning system vs. measurement vs. Monte Carlo simulation.

In particle radiotherapy, range uncertainty is an important issue that needs to be overcome. Because high-dose conformality can be achieved using a particle beam, a small uncertainty can affect tumor control or cause normal-tissue complications. From this perspective, the treatment planning system (TPS) must be accurate. However, there is a well-known inaccuracy regarding dose computation in heterogeneous media. This means that verifying the uncertainty level is one of the prerequisites for TPS commissioning. We evaluated the range accuracy of the dose computation algorithm implemented in a commercial TPS, and Monte Carlo (MC) simulation against measurement using a CT calibration phantom. A treatment plan was produced for eight different materials plugged into a phantom, and two-dimensional doses were measured using a chamber array. The measurement setup and beam delivery were simulated by MC code. For an infinite solid water phantom, the gamma passing rate between the measurement and TPS was 97.7%, and that between the measurement and MC was 96.5%. However, gamma passing rates between the measurement and TPS were 49.4% for the lung and 67.8% for bone, and between the measurement and MC were 85.6% for the lung and 100.0% for bone tissue. For adipose, breast, brain, liver, and bone mineral, the gamma passing rates computed by TPS were 91.7%, 90.6%, 81.7%, 85.6%, and 85.6%, respectively. The gamma passing rates for MC for adipose, breast, brain, liver, and bone mineral were 100.0%, 97.2%, 95.0%, 98.9%, and 97.8%, respectively. In conclusion, the described procedure successfully evaluated the allowable range uncertainty for TPS commissioning. The TPS dose calculation is inefficient in heterogeneous media with large differences in density, such as lung or bone tissue. Therefore, the limitations of TPS in heterogeneous media should be understood and applied in clinical practice.

Monte Carlo simulation of secondary neutron dose for scanning proton therapy using FLUKA.

Proton therapy is a rapidly progressing field for cancer treatment. Globally, many proton therapy facilities are being commissioned or under construction. Secondary neutrons are an important issue during the commissioning process of a proton therapy facility. The purpose of this study is to model and validate scanning nozzles of proton therapy at Samsung Medical Center (SMC) by Monte Carlo simulation for beam commissioning. After the commissioning, a secondary neutron ambient dose from proton scanning nozzle (Gantry 1) was simulated and measured. This simulation was performed to evaluate beam properties such as percent depth dose curve, Bragg peak, and distal fall-off, so that they could be verified with measured data. Using the validated beam nozzle, the secondary neutron ambient dose was simulated and then compared with the measured ambient dose from Gantry 1. We calculated secondary neutron dose at several different points. We demonstrated the validity modeling a proton scanning nozzle system to evaluate various parameters using FLUKA. The measured secondary neutron ambient dose showed a similar tendency with the simulation result. This work will increase the knowledge necessary for the development of radiation safety technology in medical particle accelerators.

Study on dependence of dose enhancement on cluster morphology of gold nanoparticles in radiation therapy using a body-centred cubic model.

Gold nanoparticles (GNPs) injected in a body for dose enhancement in radiation therapy are known to form clusters. We investigated the dependence of dose enhancement on the GNP morphology using Monte-Carlo simulations and compared the model predictions with experimental data. The cluster morphology was approximated as a body-centred cubic (BCC) structure by placing GNPs at the 8 corners and the centre of a cube with an edge length of 0.22-1.03 µm in a 4 × 4 × 4 µm3 water-filled phantom. We computed the dose enhancement ratio (DER) for 50 and 260 kVp photons as a function of the distance from the cube centre for 12 different cube sizes. A 10 nm-wide concentric shell shaped detector was placed up to 100 nm away from a GNP at the cube centre. For model validation, simulations based on BCC and nanoparticle random distribution (NRD) models were performed using parameters that corresponded to the experimental conditions, which measured increases in the relative biological effect due to GNPs. We employed the linear quadratic model to compute cell surviving fraction (SF) and sensitizer enhancement ratio (SER). The DER is inversely proportional to the distance to the GNPs. The largest DERs were 1.97 and 1.80 for 50 kVp and 260 kVp photons, respectively. The SF predicted by the BCC model agreed with the experimental value within 10%, up to a 5 Gy dose, while the NRD model showed a deviation larger than 10%. The SERs were 1.21 ± 0.13, 1.16 ± 0.11, and 1.08 ± 0.11 according to the experiment, BCC, and NRD models, respectively. We most accurately predicted the GNP radiosensitization effect using the BCC approximation and suggest that the BCC model is effective for use in nanoparticle dosimetry.

Secondary cancer-incidence risk estimates for external radiotherapy and high-dose-rate brachytherapy in cervical cancer: phantom study.

This study was designed to estimate radiation-induced secondary cancer risks from high-dose-rate (HDR) brachytherapy and external radiotherapy for patients with cervical cancer based on measurements of doses absorbed by various organs. Organ doses from HDR brachytherapy and external radiotherapy were measured using glass rod dosimeters. Doses to out-of-field organs were measured at various loca-tions inside an anthropomorphic phantom. Brachytherapy-associated organ doses were measured using a specialized phantom that enabled applicator insertion, with the pelvis portion of the existing anthropomorphic phantom replaced by this new phantom. Measured organ doses were used to calculate secondary cancer risk based on Biological Effects of Ionizing Radiation (BEIR) VII models. In both treatment modalities, organ doses per prescribed dose (PD) mostly depended on the distance between organs. The locations showing the highest and lowest doses were the right kidney (external radiotherapy: 215.2 mGy; brachytherapy: 655.17 mGy) and the brain (external radiotherapy: 15.82 mGy; brachytherapy: 2.49 mGy), respectively. Organ doses to nearby regions were higher for brachytherapy than for external beam therapy, whereas organ doses to distant regions were higher for external beam therapy. Organ doses to distant treatment regions in external radiotherapy were due primarily to out-of-field radiation resulting from scattering and leakage in the gantry head. For brachytherapy, the highest estimated lifetime attributable risk per 100,000 population was to the stomach (88.6), whereas the lowest risks were to the brain (0.4) and eye (0.4); for external radiotherapy, the highest and lowest risks were to the thyroid (305.1) and brain (2.4). These results may help provide a database on the impact of radiotherapy-induced secondary cancer incidence dur-ing cervical cancer treatment, as well as suggest further research on strategies to counteract the risks of radiotherapy-associated secondary malignancies.

Preclinical investigation for developing injectable fiducial markers using a mixture of BaSO4 and biodegradable polymer for proton therapy.

PURPOSE: The aim of this study is to investigate the use of mixture of BaSO4 and biodegradable polymer as an injectable nonmetallic fiducial marker to reduce artifacts in x-ray images, decrease the absorbed dose distortion in proton therapy, and replace permanent metal markers. METHODS: Two samples were made with 90 wt. % polymer phosphate buffer saline (PBS) and 10 wt. % BaSO4 (B1) or 20 wt. % BaSO4 (B2). Two animal models (mice and rats) were used. To test the injectability and in vivo gelation, a volume of 200 µl at a pH 5.8 were injected into the Sprague-Dawley rats. After sacrificing the rats over time, the authors checked the gel morphology. Detectability of the markers in the x-ray images was tested for two sizes (diameters of 1 and 2 mm) for B1 and B2. Four samples were injected into BALB/C mice. The polymer mixed with BaSO4 transform from SOL at 20 °C with a pH of 6.0 to GEL in the living body at 37 °C with a pH of 7.4, so the size of the fiducial marker could be controlled by adjusting the injected volume. The detectability of the BaSO4 marker was measured in x-ray images of cone beam CT (CBCT), on-board imager [anterior-posterior (AP), lateral], and fluoroscopy (AP, lateral) using a Novalis-TX (Varian Medical Systems, Palo Alto, CA) repeatedly over 4 months. The volume, HU, and artifacts for the markers were measured in the CBCT images. Artifacts were compared to those of gold marker by analyzing the HU distribution. The dose distortion in proton therapy was computed by using a Monte Carlo (MC) code. A cylindrical shaped marker (diameter: 1 or 2 mm, length: 3 mm) made of gold, stainless-steel [304], titanium, and 20 wt. % BaSO4 was positioned at the center of the spread-out Bragg peak (SOBP) in parallel or perpendicular to the beam entrance. The dose distortion was measured on the depth dose profile across the markers. RESULTS: Transformation to GEL and the biodegradation were verified. All BaSO4 markers could be detected in the CBCT. In the OBI and fluoroscopy images, all markers visible in the AP, but only B2(2 mm) could be identified in the lateral images. Changes of BaSO4 position were not detected in vivo (mice). The volume of the markers decreased by up to 65% and the HU increased by 22%, on average. The mean HU values around the B1, B2, and gold markers were 121.30 [standard deviation (SD): 54.86], 126.31 (SD: 62.13), and 1070.7 (SD: 235.16), respectively. The MC-simulated dose distortion for the BaSO4 markers was less than that of the commercially used markers. The dose reduction due to the gold marker was largest (15.05%) followed by stainless steel (7.92%) and titanium (6.92%). Dose reduction by B2 (2 mm) was 4.75% and 0.53% in parallel and perpendicular orientations, respectively. CONCLUSIONS: BaSO4 mixed with PBS is a good contrast agent in biodegradable polymer marker because of minimal artifacts in x-ray images and minimal dose reduction in proton therapy. The flexibility of the size is considered to be an advantage of this material over solid type fiducials.

Evaluation of radiation dose to organs during kilovoltage cone-beam computed tomography using Monte Carlo simulation.

Image-guided techniques for radiation therapy have improved the precision of radiation delivery by sparing normal tissues. Cone-beam computed tomography (CBCT) has emerged as a key technique for patient positioning and target localization in radiotherapy. Here, we investigated the imaging radiation dose delivered to radiosensitive organs of a patient during CBCT scan. The 4D extended cardiac-torso (XCAT) phantom and Geant4 Application for Tomographic Emission (GATE) Monte Carlo (MC) simulation tool were used for the study. A computed tomography dose index (CTDI) standard polymethyl methacrylate (PMMA) phantom was used to validate the MC-based dosimetric evaluation. We implemented an MC model of a clinical on-board imager integrated with the Trilogy accelerator. The MC model's accuracy was validated by comparing its weighted CTDI (CTDIw) values with those of previous studies, which revealed good agreement. We calculated the absorbed doses of various human organs at different treatment sites such as the head-and-neck, chest, abdomen, and pelvis regions, in both standard CBCT scan mode (125 kVp, 80 mA, and 25 ms) and low-dose scan mode (125 kVp, 40 mA, and 10 ms). In the former mode, the average absorbed doses of the organs in the head and neck and chest regions ranged 4.09-8.28 cGy, whereas those of the organs in the abdomen and pelvis regions were 4.30-7.48 cGy. In the latter mode, the absorbed doses of the organs in the head and neck and chest regions ranged 1.61-1.89 cGy, whereas those of the organs in the abdomen and pelvis region ranged between 0.79-1.85 cGy. The reduction in the radiation dose in the low-dose mode compared to the standard mode was about 20%, which is in good agreement with previous reports. We opine that the findings of this study would significantly facilitate decisions regarding the administration of extra imaging doses to radiosensitive organs.

Dosimetry in an IMRT phantom designed for a remote monitoring program.

An accurate delivery of prescribed dose is essential to ensure the most successful outcome from advanced radiation treatments such as intensity modulated radiation therapy (IMRT). An anthropomorphic phantom was designed and constructed to conduct a remote-audit program for IMRT treatments. The accuracy of the dosimetry in the phantom was assessed by comparing the results obtained from different detectors with those from Monte Carlo calculations. The developed phantom has a shape of a cylinder with one target and three organs at risk (OARs) inside the unit. The target and OARs were shaped similar to those of nasopharyngeal cancer patients, and manufactured for their identification during computed tomography imaging. The phantom was designed with thermoluminescent dosimeter (TLD) holders that were inserted inside the target and the OARs for the measurements of absolute dose. In addition, the phantom allowed measurements with ionization chambers placed at the TLD locations. As a result, an inter-comparison between the two types of dosimeters was possible. For the measurement of the relative dose distribution across the target and OARs, two film slots were orthogonally placed near the center of the phantom, which also enabled the insertion of inhomogeneities near the target. Measurements with TLDs, provided by Korea Food and Drug Administration and Radiological Physics Center, and measurements with an ionization chamber (IC) were performed in four cases. The first case was one anterior field of 6 MV x rays delivered to the phantom; the second case used the same anterior field, but with inhomogeneities inserted into the phantom. The third case was three fields of 6 MV beams at an equi-gantry angle for the homogeneous phantom, and the fourth case was IMRT delivery to the phantom without inhomogeneities. For each case, measurements with both TLDs and IC were performed. For cases 1-3, theoretical predictions were obtained by using the Monte Carlo (MC) codes (BEAMnrc and DOSXYZnrc6.0). The TLD measurements were larger than the IC readings by 2.2% (1.3-2.5%), 2.2% (1.2-2.9%), and 2.1% (0-3.3%) on average for case 1, case 2 and case 3, respectively. The average deviation between TLDs and MC results was 0.97% (-0.13-2.07%) for the first case, 1.27% (0.34-2.18%) for the second case, and 1.13% (0.31-1.94%) for the third case. The IC reading was less than the MC results; the average deviations were -1.2% (-2.44--0.43%), -0.96% (-1.74 - -0.54%) and -0.94% (-1.53-0.27%) for the first, second, and third cases, respectively. For the IMRT case, the average deviation between IC readings and TLD measurements was 0.5% (-7.0-3.9%). In conclusion, the TLD measurements in the developed phantom agreed with IC and MC results with less than 3% of an average difference. The developed phantom with TLD dosimeters should be useful for remote monitoring of IMRT.