Citations

Abstract Objectives . (1) To examine to what extent the cell- and exposure- specific information neglected in the phenomenological proton relative biological effectiveness (RBE) models could influence the computed RBE in proton therapy. (2) To explore similarities and differences in the formalism and the results between the linear energy transfer (LET)-based phenomenological proton RBE models and the microdosimetry-based Mayo Clinic Florida microdosimetric kinetic model (MCF MKM). (3) To investigate how the relationship between the RBE and the dose-mean proton LET is affected by the proton energy spectrum and the secondary fragments. Approach . We systematically compared six selected phenomenological proton RBE models with the MCF MKM in track-segment simulations, monoenergetic proton beams in a water phantom, and two spread-out Bragg peaks. A representative comparison with in vitro data for human glioblastoma cells (U87 cell line) is also included. Main results . Marked differences were observed between the results of the phenomenological proton RBE models, as reported in previous studies. The dispersion of these models’ results was found to be comparable to the spread in the MCF MKM results obtained by varying the cell-specific parameters neglected in the phenomenological models. Furthermore, while single cell-specific correlation between RBE and the dose-mean proton LET seems reasonable above 2 keV μ m −1 , caution is necessary at lower LET values due to the relevant contribution of secondary fragments. The comparison with in vitro data demonstrates comparable agreement between the MCF MKM predictions and the results of the phenomenological models. Significance . The study highlights the importance of considering cell-specific characteristics and detailed radiation quality information for accurate RBE calculations in proton therapy. Furthermore, these results provide confidence in the use of the MCF MKM for clonogenic survival RBE calculations in proton therapy, offering a more mechanistic approach compared to phenomenological models.

AbstractBackgroundUsing the pencil beam raster scanning method employed at most carbon beam treatment facilities, spots can be moved without interrupting the beam, allowing for the delivery of a dose between spots (move dose). This technique is also known as Dose‐Driven‐Continuous‐Scanning (DDCS). To minimize its impact on HIMAK patient dosimetry, there's an upper limit to the move dose. Spots within a layer are grouped into sets, or “break points,” allowing continuous irradiation. The beam is turned off when transitioning between sets or at the end of a treatment layer or spill. The control system beam‐off is accomplished by turning off the RF Knockout (RFKO) extraction and after a brief delay the High Speed Steering Magnet (HSST) redirects the beam transport away from isocenter to a beam dump.PurposeThe influence of the move dose and beam on/off control on the dose distribution and irradiation time was evaluated by measurements never before reported and modelled for Hitachi Carbon DDCS.MethodWe conducted fixed‐point and scanning irradiation experiments at three different energies, both with and without breakpoints. For fixed‐point irradiation, we utilized a 2D array detector and an oscilloscope to measure beam intensity over time. The oscilloscope data enabled us to confirm beam‐off and beam‐on timing due to breakpoints, as well as the relative timing of the RFKO signal, HSST signal, and dose monitor (DM) signals. From these measurements, we analyzed and modelled the temporal characteristics of the beam intensity. We also developed a model for the spot shape and amplitude at isocenter occurring after the beam‐off signal which we called flap dose and its dependence on beam intensity. In the case of scanning irradiation, we measured move doses using the 2D array detector and compared these measurements with our model.ResultWe observed that the most dominant time variation of the beam intensity was at 1 kHz and its harmonic frequencies. Our findings revealed that the derived beam intensity cannot reach the preset beam intensity when each spot belongs to different breakpoints. The beam‐off time due to breakpoints was approximately 100 ms, while the beam rise time and fall time (tdecay) were remarkably fast, about 10 ms and 0.2 ms, respectively. Moreover, we measured the time lag (tdelay) of approximately 0.2 ms between the RFKO and HSST signals. Since tdelay ≈ tdecay at HIMAK then the HSST is activated after the residual beam intensity, resulting in essentially zero flap dose at isocenter from the HSST. Our measurements of the move dose demonstrated excellent agreement with the modelled move dose.ConclusionWe conducted the first move dose measurement for a Hitachi Carbon synchrotron, and our findings, considering beam on/off control details, indicate that Hitachi's carbon synchrotron provides a stable beam at HIMAK. Our work suggests that measuring both move dose and flap dose should be part of the commissioning process and possibly using our model in the Treatment Planning System (TPS) for new facilities with treatment delivery control systems with higher beam intensities and faster beam‐off control.

Abstract Introduction . Dispersion in an accelerator quantifies the deviation of the proton trajectory when there is a momentum deviation. We present for the first time a safe method of measuring dispersion in the clinic, using a scintillator detector and the momentum deviations within a spill. This is an important accelerator quantity as we found that this is the reason behind the large dose fluctuation in our absolute dosimetry measurement. Methods . Dispersions are measured for nine energies in a Hitachi ProBeat system at three locations (isocenter and at two profile monitors) and at two gantry angles (0 and 90 degrees) by first measuring the spot position and momentum drift within a spill. The spot position drift is measured by the XRV-4000 at the isocenter, and by the two profile monitors located at 0.57 and 2.27 m from the isocenter. The momentum drift is calculated from the intra-spill range drift which is measured using the Ranger accessory. The dispersion at isocenter and its gradient are calculated using the weighted least square regression on the measured dispersions at the three locations. A constraint is formulated on the dispersion and its gradient to ensure minimal intra-spill spot position deviation around the isocenter. Results . The measured intra-spill range and spot positional drift at isocenter are less than 0.25 mm and 0.7 mm respectively. The momentum spread calculated from the range drift are less than 0.08%. The dispersion at the isocenter ranged from 0.50 to 4.30 m and the zero-crossing happens upstream of isocenter for all energies. 2 of the 9 energies (168.0 and 187.5 MeV) violated the constraint and has an intra-spill spot positional deviation greater than 1.0 within 5 cm from the isocenter. Conclusion . This measurement is recommended as part of commissioning and annual quality assurance for accelerator monitoring and to ensure intra-spill spot deviations remain low.

Abstract The Mayo Clinic Florida microdosimetric kinetic model (MCF MKM) is a recently developed clonogenic survival model. Since the MCF MKM relies on novel strategies to a priori determine the cell-specific model parameters, the only experiment-specific input values are the α and ß terms of the linear–quadratic model (LQM) of clonogenic survival for the reference photon exposure. Because the two LQM terms are anti-correlated, the fitting process of the reference photon survival curve was found to significantly influence the MCF MKM calculations. This article reports this effect for two clinically relevant cell lines (human brain glioblastoma A-172, human healthy foreskin fibroblasts AG01522) and ions (1H and 12C ions).

Abstract Objective . To investigate the impact of scan path optimization on the dose accuracy and beam delivery time (BDT) of proton pencil beam scanning in the dose-driven continuous scanning (DDCS). Approach . A diverse set of six clinical plans, representing various spot patterns and treatment sites, was used to evaluate the effectiveness of scan time optimization and scan length optimization. The DDCS dose discrepancy and BDT with optimized scan paths was compared to the default serpentine scan path. Main results . Both scan time optimization and scan path optimization were able to reduce the DDCS dose discrepancy compared to the default serpentine scan path. All plans, except for the layer repainting lung plan, achieved a 2%/2 mm gamma pass rate of over 99% and less than 1% PTV DVH root mean square error (RMSE) through scan path optimization. In the case of the layer repainting lung plan, when compared to the default serpentine scan path, the 2%/2 mm gamma pass rate showed improvements from 91.3% to 93.1% and 95.8%, while the PTV DVH RMSE decreased from 2.1% to 1.7% and 1.1% for scan time optimization and scan length optimization, respectively. Although scan time optimization resulted in shorter total scan times for all plans compared to the default scan path and scan length optimization tended to have longer total scan times. However, due to the short total scan times and their minimal contribution to the total BDT, the impact of scan path optimization on the total BDT was practically negligible. Significance . Both scan time optimization and scan length optimization proved to be effective in minimizing DDCS dose discrepancy. No definitive winner can be determined between these two optimization approaches. Both scan time and scan length optimization had minimal effect on the total BDT.

AbstractBackgroundKilo‐voltage cone‐beam computed tomography (CBCT) is a prevalent modality used for adaptive radiotherapy (ART) due to its compatibility with linear accelerators and ability to provide online imaging. However, the widely‐used Feldkamp‐Davis‐Kress (FDK) reconstruction algorithm has several limitations, including potential streak aliasing artifacts and elevated noise levels. Iterative reconstruction (IR) techniques, such as total variation (TV) minimization, dictionary‐based methods, and prior information‐based methods, have emerged as viable solutions to address these limitations and improve the quality and applicability of CBCT in ART.PurposeOne of the primary challenges in IR‐based techniques is finding the right balance between minimizing image noise and preserving image resolution. To overcome this challenge, we have developed a new reconstruction technique called high‐resolution CBCT (HRCBCT) that specifically focuses on improving image resolution while reducing noise levels.MethodsThe HRCBCT reconstruction technique builds upon the conventional IR approach, incorporating three components: the data fidelity term, the resolution preservation term, and the regularization term. The data fidelity term ensures alignment between reconstructed values and measured projection data, while the resolution preservation term exploits the high resolution of the initial Feldkamp‐Davis‐Kress (FDK) algorithm. The regularization term mitigates noise during the IR process. To enhance convergence and resolution at each iterative stage, we applied Iterative Filtered Backprojection (IFBP) to the data fidelity minimization process.ResultsWe evaluated the performance of the proposed HRCBCT algorithm using data from two physical phantoms and one head and neck patient. The HRCBCT algorithm outperformed all four different algorithms; FDK, Iterative Filtered Back Projection (IFBP), Compressed Sensing based Iterative Reconstruction (CSIR), and Prior Image Constrained Compressed Sensing (PICCS) methods in terms of resolution and noise reduction for all data sets. Line profiles across three line pairs of resolution revealed that the HRCBCT algorithm delivered the highest distinguishable line pairs compared to the other algorithms. Similarly, the Modulation Transfer Function (MTF) measurements, obtained from the tungsten wire insert on the CatPhan 600 physical phantom, showed a significant improvement with HRCBCT over traditional algorithms.ConclusionThe proposed HRCBCT algorithm offers a promising solution for enhancing CBCT image quality in adaptive radiotherapy settings. By addressing the challenges inherent in traditional IR methods, the algorithm delivers high‐definition CBCT images with improved resolution and reduced noise throughout each iterative step. Implementing the HR CBCT algorithm could significantly impact the accuracy of treatment planning during online adaptive therapy.

Pencil beam scanning delivered with continuous scanning has several advantages over conventional discrete spot scanning. Such advantages include improved beam delivery efficiency and reduced beam delivery time. However, a move dose is delivered between consecutive spots with continuous scanning, and current treatment planning systems do not take this into account. Therefore, continuous scanning and discrete spot plans have an inherent dose discrepancy. Using the operating parameters of the state-of-the-art particle therapy system, we conducted a proof-of-concept study in which we systematically generated 28 plans for cubic targets with different combinations of plan parameters and simulated the dose discrepancies between continuous scanning and a planned one. A nomograph to guide the selection of plan parameters was developed to reduce the dose discrepancy. The effectiveness of the nomograph was evaluated with two clinical cases (one prostate and one liver). Plans with parameters guided by the nomograph decreased dose discrepancy than those used standard plan parameters. Specifically, the 2%/2 mm gamma passing rate increased from 96.3% to 100% for the prostate case and from 97.8% to 99.7% for the liver case. The CTV DVH root mean square error decreased from 2.2% to 0.2% for the prostate case and from 1.8% to 0.9% for the liver case. The decreased dose discrepancy may allow the relaxing of the delivery constraint for some cases, leading to greater benefits in continuous scanning. Further investigation is warranted.

Abstract Objective . UNet-based deep-learning (DL) architectures are promising dose engines for traditional linear accelerator (Linac) models. Current UNet-based engines, however, were designed differently with various strategies, making it challenging to fairly compare the results from different studies. The objective of this study is to thoroughly evaluate the performance of UNet-based models on magnetic-resonance (MR)-Linac-based intensity-modulated radiation therapy (IMRT) dose calculations. Approach . The UNet-based models, including the standard-UNet, cascaded-UNet, dense-dilated-UNet, residual-UNet, HD-UNet, and attention-aware-UNet, were implemented. The model input is patient CT and IMRT field dose in water, and the output is patient dose calculated by DL model. The reference dose was calculated by the Monaco Monte Carlo module. Twenty training and ten test cases of prostate patients were included. The accuracy of the DL-calculated doses was measured using gamma analysis, and the calculation efficiency was evaluated by inference time. Results . All the studied models effectively corrected low-accuracy doses in water to high-accuracy patient doses in a magnetic field. The gamma passing rates between reference and DL-calculated doses were over 86% (1%/1 mm), 98% (2%/2 mm), and 99% (3%/3 mm) for all the models. The inference times ranged from 0.03 (graphics processing unit) to 7.5 (central processing unit) seconds. Each model demonstrated different strengths in calculation accuracy and efficiency; Res-UNet achieved the highest accuracy, HD-UNet offered high accuracy with the fewest parameters but the longest inference, dense-dilated-UNet was consistently accurate regardless of model levels, standard-UNet had the shortest inference but relatively lower accuracy, and the others showed average performance. Therefore, the best-performing model would depend on the specific clinical needs and available computational resources. Significance . The feasibility of using common UNet-based models for MR-Linac-based dose calculations has been explored in this study. By using the same model input type, patient training data, and computing environment, a fair assessment of the models’ performance was present.

AbstractBackgroundAbsolute dosimetry measurement is an integral part of Treatment Planning System (TPS) commissioning and it involves measuring the integrated absorbed dose to water for all energies in a pencil beam scanning delivery system. During the commissioning of Singapore's first proton therapy center, a uniform scanned field with an Advanced Markus chamber method was employed for this measurement, and a large dose fluctuation of at least 5% was observed for 10% of the energy layers during repeated measurements.PurposeThis study aims to understand the root cause of this fluctuation by relating the actual delivered spot information in the log file with the charge measurement by the ion chambers.MethodsA dedicated pencil beam dose algorithm was developed, taking into account the log file parameters, to calculate the dose for a single energy layer in a homogeneous water phantom. Three energies, 70.2, 182.7, and 228.7 MeV were used in this study, with the 182.7 MeV energy exhibiting large dose fluctuation. The dose fluctuation was investigated as a function of detector's sizes (pinpoint 3D, Advanced Markus, PTW 34070, and PTW 34089) and water depth (2 , 6, and 20 cm). Twelve ion chambers measurements were performed for each chamber and depth. The comparison of the theoretically predicted integrated dose and the charge measurement served as a validation of the algorithm.ResultsAbout 5.9% and 9.6% dose fluctuation were observed in Advanced Markus and pinpoint 3D measurements at 2 cm depth for 182.7 MeV, while fluctuation of 1.6% and 1.1% were observed in Advanced Markus with 228.7 and 70.2 MeV at similar depth. Fluctuation of less than 0.1% was observed for PTW34070 and PTW 34089 for all energies. The fluctuation was found to diminish with larger spot size at 20 cm depth to 1.3% for 182.7 MeV. The theoretical and measured charge comparison showed a high linear correlation of for all datasets, indicating the fluctuation originated from the delivered spot characteristics. The cause of fluctuation was identified to be due to the spill change occurring close to the detector, and since the spot positional deviation profiles were different between two spills, this resulted in local hot spots between columns of spots. The actual position of spill change varies randomly during measurement, which led to a random occurrence of hot spot within the detector's sensitive volume and a fluctuating dose measurement.ConclusionThis is the first report of a dose fluctuation greater than 5% in absolute dosimetry measurement with a uniform scanned field and the cause of the fluctuation has been conclusively determined. It is important to choose the MU and scanning pattern carefully to avoid spill change happening when the spot delivery is near the detector.