Beltran, Chris J

Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing integral dose and reducing acute and late toxicities, such as dysgeusia, feeding tube dependence, xerostomia, secondary malignancies, and neurocognitive dysfunction. Despite its benefits in dose distribution and biological effectiveness, the application of proton therapy is challenged by uncertainties in its relative biological effectiveness (RBE). Overcoming the challenges related to RBE is key to fully realizing proton therapy’s potential, which extends beyond its physical dosimetric properties when compared with photon-based therapies. In this paper, we discuss the clinical significance of RBE within treatment volumes and adjacent serial organs at risk in the management of head and neck and skull-base tumors. We review proton RBE uncertainties and its modeling and explore clinical outcomes. Additionally, we highlight technological advancements and innovations in plan optimization and treatment delivery, including linear energy transfer/RBE optimizations and the development of spot-scanning proton arc therapy. These advancements show promise in harnessing the full capabilities of proton therapy from an academic standpoint, further technological innovations and clinical outcome studies, however, are needed for their integration into routine clinical practice.

AbstractPurposeSkin collimation is a useful tool in electron beam therapy (EBT) to decrease the penumbra at the field edge and minimize dose to nearby superficial organs at risk (OARs), but manually fabricating these collimation devices in the clinic to conform to the patient's anatomy can be a difficult and time intensive process. This work compares two types of patient‐specific skin collimation (in‐house 3D printed and vendor‐provided machined brass) using clinically relevant metrics.MethodsAttenuation measurements were performed to determine the thickness of each material needed to adequately shield both 6 and 9 MeV electron beams. Relative and absolute dose planes at various depths were measured using radiochromic film to compare the surface dose, flatness, and penumbra of the different skin collimation materials.ResultsClinically acceptable thicknesses of each material were determined for both 6 and 9 MeV electron beams. Field width, flatness, and penumbra results between the two systems were very similar and significantly improved compared to measurements performed with no surface collimation.ConclusionBoth skin collimation methods investigated in this work generate sharp penumbras at the field edge and can minimize dose to superficial OARs compared to treatment fields with no surface collimation. The benefits of skin collimation are greatest for lower energy electron beams, and the benefits decrease as the measurement depth increases. Using bolus with skin collimation is recommended to avoid surface dose enhancement seen with collimators placed on the skin surface. Ultimately, the appropriate choice of material will depend on the desire to create these devices in‐house or outsource the fabrication to a vendor.

Abstract Background Rescanning is a common technique used in proton pencil beam scanning to mitigate the interplay effect. Advances in machine operating parameters across different generations of particle therapy systems have led to improvements in beam delivery time (BDT). However, the potential impact of these improvements on the effectiveness of rescanning remains an underexplored area in the existing research. Methods We systematically investigated the impact of proton machine operating parameters on the effectiveness of layer rescanning in mitigating interplay effect during lung SBRT treatment, using the CIRS phantom. Focused on the Hitachi synchrotron particle therapy system, we explored machine operating parameters from our institution's current (2015) and upcoming systems (2025A and 2025B). Accumulated dynamic 4D dose were reconstructed to assess the interplay effect and layer rescanning effectiveness. Results Achieving target coverage and dose homogeneity within 2% deviation required 6, 6, and 20 times layer rescanning for the 2015, 2025A, and 2025B machine parameters, respectively. Beyond this point, further increasing the number of layer rescanning did not further improve the dose distribution. BDTs without rescanning were 50.4, 24.4, and 11.4 s for 2015, 2025A, and 2025B, respectively. However, after incorporating proper number of layer rescanning (six for 2015 and 2025A, 20 for 2025B), BDTs increased to 67.0, 39.6, and 42.3 s for 2015, 2025A, and 2025B machine parameters. Our data also demonstrated the potential problem of false negative and false positive if the randomness of the respiratory phase at which the beam is initiated is not considered in the evaluation of interplay effect. Conclusion The effectiveness of layer rescanning for mitigating interplay effect is affected by machine operating parameters. Therefore, past clinical experiences may not be applicable to modern machines.

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.