PURPOSE:Adaptive proton therapy using cone beam CT (CBCT) requires accurate CT numbers for dose calculation and sufficient soft tissue visibility for reliable target and organ delineation. However, scatter in conventional CBCT causes substantial CT number inaccuracies and poor soft tissue contrast, limiting its use in adaptive workflows. To address this, a novel 2-dimensional antiscatter grid (2D ASG) prototype and raw data correction algorithms were developed for a proton gantry-mounted CBCT system. This prospective study evaluated their impact on CBCT image quality in human subjects. METHODS AND MATERIALS:Ten patients undergoing proton therapy for prostate cancer were enrolled in an institutional review board-approved imaging study. Each participant underwent 2 CBCT scans on a gantry-mounted proton therapy CBCT system: (1) standard CBCT with software-based scatter correction and (2) CBCT with the 2D ASG. Acquisition parameters and imaging dose were identical. Quantitative image quality metrics, including CT number error and artifact amplitude relative to planning CT, adipose-soft tissue contrast, contrast-to-noise ratio, peak signal-to-noise ratio, and structural similarity index measure, were calculated. Differences between configurations were assessed using the Wilcoxon signed-rank test. RESULTS:Compared with scatter-corrected clinical CBCT, the 2D ASG reduced median (min-max) soft tissue CT number errors from 169 (150-185) HU to 38 (26-54) HU (P = .002), indicating reduced scatter-induced artifacts. Median soft tissue contrast increased from 62 (42-74) HU to 125 (97-144) HU (P = .002), and contrast-to-noise ratio improved from 0.99 (0.37-1.38) to 1.57 (1.28-1.75) (P = .002). Structural similarity index measure relative to the planning CT increased from 0.53 (0.38-0.67) to 0.87 (0.85-0.93) (P = .002). Similar improvements were observed for peak signal-to-noise ratio and artifact amplitude. CONCLUSIONS:This first prospective evaluation of a prototype 2D ASG-equipped CBCT system for proton therapy demonstrated significant improvements in CT number accuracy and soft tissue visualization, supporting its potential role in adaptive proton therapy workflows.

Purpose:To create LET-optimized pencil beam scanning proton prostate cancer treatment plans with clinically acceptable range robustness and urethral sparing. Methods:Two-beam, four-beam, and arc LET-optimized treatment plans were created for a prostate cancer patient with varying levels of robustness to evaluate LETd and several performance metrics. Urethral sparing was incorporated by de-escalating the physical dose to the urethra while maintaining high LETd to prevent underdosing the periurethral prostate by merit of its lower α / β . Four-beam and arc plans were created with a targeted robustness level for 12 patients along with reference SFO plans, and statistical comparisons were performed on clinical target volume prostate and seminal vesicles minus urethra (CTV PSV-U) mean LETd, target volume and organs at risk (OAR) relative biological effectiveness (RBE)-doses, minimum average RBE-doses, target-to-OAR dose ratios (TODRs), and OAR volumes receiving at least 80% of the CTV PSV D95 dose (V80%). Results:A tradeoff between robustness and high LETd was demonstrated. Statistically significant differences in LETd were found, with 2.5 keV/µm in SFO plans, 3.3 keV/µm in arc plans, and 3.5 keV/µm in four-beam plans. Statistically significant increases in CTV PSV-U D95 RBE-dose resulted in 6.3%-8.1% increases in four-beam plans over SFO. High LETd in the periurethral prostate prevented underdosage with urethral sparing. V80%s were statistically decreased in four-beam and most arc comparisons relative to SFO. While increased TODRs were demonstrated in a test patient, lack of statistical significance (or superiority in SFO over arc in the case of the rectum) in the 12 patient cohort occurred due to some patients already having low OAR RBE-doses in SFO plans, which could be addressed with additional optimization objectives at lower doses. Conclusion:LET-optimized treatment plans were created with high LETd and clinically acceptable robustness with the potential to increase the therapeutic ratio and implemented urethral sparing without underdosing the periurethral prostate.

Proton beam therapy (PBT) offers a unique potential for dose conformity to tumors while sparing surrounding healthy tissues. Current PBT accuracy, however, is fundamentally limited by range uncertainties from tissue density variations and anatomical changes, yet no clinically viable methods exist for localizing the dose delivery pulse-by-pulse inside patients during pencil beam scanning (PBS). We developed and clinically demonstrated a first-of-its-kind radiation acoustic beam localization (iRABL) system for real-time tracking PBS trajectory and mapping dose deposition deep in patient's body during PBT. A clinical-grade compact iRABL system featuring high speed, super-resolution, and high sensitivity was specifically designed for PBT applications. Its clinical feasibility was validated through the first-in-human study on prostate cancer patients, demonstrating the capability for in vivo proton dose mapping without interfering with treatment delivery. System performance, including spatial resolution, imaging speed for tracking beam trajectory and temporal dose accumulation, and dosimetric accuracy, was quantitatively characterized using tissue-equivalent phantoms and clinical treatment plans. This iRABL system achieved displacement resolution of 0.1 mm laterally and 0.2 mm axially, exceeding the acoustic diffraction limit by an order of magnitude and surpassing typical proton beam spot sizes. This super-resolution capability, combined with GPU-accelerated image reconstruction and processing, enabled single-pulse detection at a frame rate of 1 kHz, matching the proton system's pulse repetition rate. Dosimetric validation using clinical M-shaped treatment plans met clinical criteria with gamma index passing rates exceeding 90% at 3 mm/3% tolerance, confirming high accuracy for mapping delivered dose distributions. For the first time, by leveraging the high sensitivity and the high speed of our newly developed iRABL system, we are able to localize proton beam and map the proton dose deposition during PBS with sub-diffraction-limit spatial resolution, pulse-by-pulse imaging speed, and clinical grade accuracy. This capability, which addresses fundamental limitations in current treatment monitoring, holds promise for advancing PBT toward image-guided "proton surgery".

BACKGROUND:The dose-averaged linear energy transfer (LETD) in proton therapy (PT) has in pre-clinical studies been linked to the relative biological effectiveness (RBE) of protons. Until recently, the most common PT delivery method in prostate cancer has been double-scattered PT, with LETD only available through dedicated Monte Carlo (MC) simulations. However, as most studies of the relationship between LETD and RBE in double scattered PT have been focused on the head and neck region, existing MC implementations have not been capable of calculating LETD for the longer field ranges used, for example, in the pelvic region. PURPOSE:The initial aim of this study was to implement a MC code allowing for LETD calculations in double-scattered PT of prostate cancer. Additionally, we explored LETD profiles and LETD as a function of field configuration, by performing MC calculations for a large prostate cancer cohort treated with double-scattered PT. METHODS:The components of a passive scattered clinical treatment nozzle used for delivery of extended field ranges, with two associated modulation wheels, were implemented into an existing FLUKA MC framework for LETD calculations. The code was validated to spread out Bragg peak (SOBP) measurements conducted using the treatment nozzle with 11 different range and modulation width configurations. After validation, LETD distributions were calculated on the planning computed tomographies of 582 prostate cancer patients treated with two-field double-scattered PT. All patients had symmetric field configurations with respect to the sagittal plane, with one pair of posterior oblique, lateral opposing, or anterior oblique fields. Dose and LETD volume parameters and the mean LETD ratio between the bladder and rectum were compared across the three groups. RESULTS:The range differences were below 1 mm for all SOBP scenarios used for calibration. For 9 of 11 SOBP scenarios, the modulation width differences were below 2 mm. For the patient simulations, the mean gamma pass rates (3 mm/3%) were at least 98% in the PTV, bladder, and rectum. Comparing anterior to posterior field configurations, the mean LETD in the bladder increased within both the 10 and 70 Gy iso-dose regions, and conversely, the mean LETD decreased for the rectum. There was a marked difference in the mean bladder-to-rectum LETD ratios between anterior oblique, lateral opposing and posterior oblique field configurations. CONCLUSION:A MC code allowing for accurate calculations of dose and LETD in double-scattered PT of prostate cancer was implemented and validated. The LETD distributions in the rectum and bladder showed a systematic dependence on the field configuration.

Pediatric patients are more susceptible to late effects given their early age of radiation exposure during development. Extra clinical attention is devoted to ensuring accurate treatment delivery. For advanced radiation technology, such as stereotactic body radiation or proton therapy, even slight setup irregularities and beam delivery quality and accuracy can have a dramatic impact on the treatment. Herein, we share a unique situation involving a child undergoing proton pencil-beam scanning (PBS) for an ependymoma of the lumbar spine. During the patient's alignment process, we detected an artificial disk-shaped opacity on kV radiographs. Upon reviewing the radiographs within a timeline, we observed that the object was spun and displaced by the bowel peristalsis up to 2.5 cm superiorly during the total patient's alignment time. To decide on whether to continue treatment on that day, we confirmed there was a safe margin of distance between the object and the closest PBS spot using cone-beam computed tomography (CT) images. Additionally, we conducted a comprehensive phantom study with presumed objects to better estimate the characteristics of the foreign body (FB), allowing us to alleviate any potential medical concerns. While spine treatments utilizing two posterior oblique beams are rarely affected by bowel changes, the local proton dose can be perturbed by bowel filling or ingested high-atomic number objects that come to rest in bowel adjacent to treatment targets. To explore the impact of dose perturbation on a pediatric proton treatment clinical scenario, we calculated hypothetical doses using a pediatric patient's CT images and structures with the inclusion of a gastrointestinal FB. The simulated FB's characteristics were based on the phantom test results. We also discussed considerations regarding reviewing images, local dosimetric effect, and proton beam delivery to ensure safe and precise pediatric PBS treatment when a FB is observed close to the treatment area.

Proton treatment using pencil-beam scanning (PBS) for patients with breast cancer offers advantages in achieving a conformal dose distribution while also reducing the cardiac dose. However, when employing 2 anterior fields to mitigate the effects of respiratory motion on dose delivery, managing the ipsilateral lung doses becomes critical due to the high linear-energy transfer (LET) at the distal end of the beams. Although the incidence of radiation pneumonitis (RP) after breast radiation therapy is relatively low, it is essential to address the cases that develop RP following proton treatment to minimize lung toxicity. We conducted a retrospective case study analyzing follow-up computed tomography images taken at 1 week, 1.5 months, and 4.5 months after the onset of the patient's pneumonitis symptoms to correlate them with proton doses. The patient's PBS treatment was prescribed at a dose of 50 Gy with an additional 10 Gy boost, using a relative biological effectiveness (RBE) of 1.1, delivered in 2 Gy daily fractions. Our histogram analysis revealed noticeable increases in Hounsfield units at a dose of 40 Gy (RBE = 1.1), underscoring a potential dose-volume parameter that could help minimize the occurrence of RP. Furthermore, the lung volume associated with the RP was encompassed with an iso-LET level greater than 5.0 keV/μm, with a proton dose exceeding 40 Gy (RBE = 1.1). In examining the LET-dependent RBE-weighted dose using the McNamara model in the original treatment plan, we found the volumes receiving more than 50 Gy (V50Gy) and 40 Gy (V40Gy) were 110 cc and 267 cc, respectively. By incorporating dose objectives of V50Gy and V40Gy to limit the ipsilateral lung volume into PBS plans, the volumes were successfully reduced to 0 cc and 3 cc, while maintaining target dose coverage and robustness. Optimizing a breast PBS plan (RBE = 1.1) using objectives that addressed both the V50Gy and V40Gy to minimize lung exposure was shown to be clinically feasible and should be considered as a strategy to reduce lung toxicity when treating breast cancer with PBS proton therapy.

Background and purpose:Robust scatter mitigation by 2D anti-scatter grids (2D-ASG) in proton therapy cone beam computed tomography (CBCT) may improve target visualization and computed tomography (CT) number fidelity, allowing online dose verifications and plan adaptations. However, grid artifact-free implementation of 2D-ASG depends on the CBCT system characteristics. Thus, we investigated the feasibility of 2D-ASG implementation in a proton therapy gantry-mounted CBCT system and evaluated its impact on image quality. Materials and methods:A prototype 2D-ASG and a grid support platform were developed for a proton therapy CBCT system with a 340 cm source to imager distance. The effect of gantry flex on 2D-ASG's wall shadows and scan-to-scan reproducibility of 2D-ASG's wall shadows were evaluated. Experiments were conducted to assess 2D-ASG's wall shadow suppression and the effect of 2D-ASG on image quality. Results:While maximum displacement in 2D-ASG wall shadows was 103 µm during gantry rotation, the drift from baseline over 3 months was 8 µm and 1 µm in the transverse and axial directions. 2D-ASG shadows were successfully suppressed in CBCT images. With 2D-ASG, maximum Hounsfield Unit (HU) nonuniformity decreased from 134 to 45 HU, contrast-to-noise ratio (CNR) increased by a factor of 2.5, and HU errors were reduced from 34 % to 5 %. Conclusions:Proton therapy gantry flex was highly reproducible and did not noticeably affect 2D-ASG wall shadow suppression in CBCT images, supporting its feasibility in proton therapy CBCT system. Improved CT accuracy and artifact reduction with 2D-ASG could enhance CBCT-based proton therapy dose calculations.

Purpose:Most automatic error detection studies in radiation therapy focus on photon therapy, with limited attention to proton therapy. This study developed and validated an automated framework for initial proton therapy plan review to enhance error detection capabilities and workflow efficiency in pencil-beam scanning treatments. Materials and Methods:Auto-IniCheck, an automated plan review script, was designed following AAPM TG-275 guidelines to systematically verify initial physics plan integrity for proton therapy. Treatment site-specific and modality-specific checklists were integrated into a comprehensive process map indicating manual, automated, or hybrid review requirements with color-coded risk levels. Risk levels for each step were determined using failure modes and effects analysis, guiding a more effective plan review. The efficiency and effectiveness of Auto-IniCheck were assessed by comparing risk priority numbers and quantifying risk reduction between manual and automated plan reviews. Results:Auto-IniCheck enabled 60% to 65% of checklist items to be reviewed automatically, reducing plan review time to <10 s. It achieved an average 65% risk priority number reduction across all process categories by improving error detectability, with 15 high-risk items reclassified as low risk. The greatest improvements were observed in robustness optimization, couch confirmation, and target validation for optimization, each with a 75% risk reduction. Conclusion:Auto-Ini Check streamlines proton therapy plan reviews by delivering measurable gains in efficiency and safety. This automated system proactively addresses proton-specific failure modes and facilitates practical application during initial plan review. As proton therapy programs grow, this approach offers a scalable solution to maintain rigorous quality assurance.

This case study explores the strategic decision-making and safety considerations in managing a unique scenario where a pacemaker dependent patient, requiring adjuvant radiotherapy for bilateral breast cancer. The conventional pacemaker was located entirely within the treatment target, without the option for transposition because of the bilateral chest treatment, resulting in significant risk of malfunction caused by exposing it to the full prescribed dose. Consequently, the decision was made to replace the conventional pacemaker with a leadless device Micra implanted directly into the heart to mitigate direct device radiation and potential adverse effects of proton therapy on the cardiac device. Following Micra implantation, the patient underwent the proton treatment without complications or serious device malfunctions. This study explores solutions to address the challenges posed by within-the-field cardiac devices and highlights the use of pencil beam proton therapy for individuals with leadless cardiac devices while acknowledging the potential for neutron production and the associated risk of single-event upsets (SEU) in cardiac implantable electronic devices (CIEDs). The findings underscore the significance of strategic decision-making, risk assessment, and continuous monitoring for successful outcomes, particularly in the context of proton therapy for patients with advanced cardiac considerations.

Background and purpose: Compared to intensity modulated proton therapy (IMPT), proton arc therapy (PAT) is expected to improve dose conformality, delivery efficiency, and provide a more favorable LET distribution. Alternatively, the low-dose bath is potentially spread over larger volumes, which could impact the likelihood of developing a radiation-induced, secondary cancer (SC). The goal of this study was to evaluate this risk in several anatomical sites using newly developed commercial tools. Materials and methods: Treatment plans encompassing six anatomical sites, five patients per site, and three techniques per patient were created using RayStation. Techniques included PAT and IMPT for protons, and either volumetrically modulated radiotherapy (VMAT) or intensity modulated radiotherapy (IMRT) for photons. Risk estimates were based on the organ-equivalent dose (OED) concept using both Schneider's mechanistic dose-response model for carcinoma induction and a linear dose-response model. Results: With few exceptions, mean and integral dose were lowest with PAT. For protons, the factor OEDIMPT/ OEDPAT ranged from 0.7 to 1.8 with both the mechanistic and linear model, while for photons OEDphoton/OEDPAT ranged from 1.5 to 10 using the mechanistic model and 1.3 to using the linear model. A strong correlation was found between mean dose and OED for organs with significant repopulation/repair (high R value) and less cell death from single hit interactions (low alpha value). Conclusion: Based on results from both mechanistic and linear risk models, the transition from IMPT to PAT should not substantially affect SC risk in patients treated with proton therapy. Additionally, when using Schneider's model, the shapes of the dose-response curves can be used as a good predictor of how SC risk will respond to shifts from intermediate dose to low dose as anticipated when moving from IMPT to PAT.

Purpose: To demonstrate the feasibility of improving prostate cancer patient outcomes with PBS proton LETd optimization. Methods: SFO, IPT-SIB, and LET-optimized plans were created for 12 patients, and generalized-tissue and disease-specific LET-dependent RBE models were applied. The mean LETd in several structures was determined and used to calculate mean RBEs. LETd- and dose–volume histograms (LVHs/DVHs) are shown. TODRs were defined based on clinical dose goals and compared between plans. The impact of robust perturbations on LETd, TODRs, and DVH spread was evaluated. Results: LETd optimization achieved statistically significant increased target volume LETd of ~4 keV/µm compared to SFO and IPT-SIB LETd of ~2 keV/µm while mitigating OAR LETd increases. A disease-specific RBE model predicted target volume RBEs > 1.5 for LET-optimized plans, up to 18% higher than for SFO plans. LET-optimized target LVHs/DVHs showed a large increase not present in OARs. All RBE models showed a statistically significant increase in TODRs from SFO to IPT-SIB to LET-optimized plans. RBE = 1.1 does not accurately represent TODRs when using LETd optimization. Robust evaluations demonstrated a trade-off between increased mean target LETd and decreased DVH spread. Conclusion: The demonstration of improved TODRs provided via LETd optimization shows potential for improved patient outcomes.

Purpose This study aims to elucidate the dependence of the flat-panel detector’s response on the linear energy transfer (LET) and evaluate the practical viability of employing flat-panel detectors in proton dosimetry applications through LET-dependent correction factors. Methods The study assessed the flat-panel detector’s response across varying depths using solid water and distinct 100, 150, and 200 MeV proton beams by comparing the flat-panel readings against reference doses measured with an ionization chamber. A Monte Carlo code was used to derive LET values, and an LET-dependent response correction factor was determined based on the ratio of the uncorrected flat-panel dose to the ionization chamber dose. The implications of this under-response correction were validated by applying it to a measurement involving a spread-out Bragg peak (SOBP), followed by a comparative analysis against doses calculated using the Monte Carlo code and MatriXX ONE measurement. Results The association between LET and the flat-panel detector’s under-response displayed a positive correlation that intensified with increasing LET values. Notably, with a 10 keV/µm LET value, the detector’s under-response reached 50 %, while the measurement points in the SOBP demonstrated under-response greater than 20 %. However, post-correction, the adjusted flat-panel profile closely aligned with the Monte Carlo profile, yielding a 2-dimensional 3 %/3mm gamma passing rate of 100 % at various verification depths. Conclusion This study successfully defined the link between LET and the responsiveness of flat-panel detectors for proton dosimetric measurements and established a foundational framework for integrating flat-panel detectors in clinical proton dosimetry applications.

Abstract Background The purpose of this study is to assess the feasibility of mixed-reality (MixR) visualization for patient setup in breast and chest wall radiotherapy (RT) by performing a first-in-human clinical trial comparing MixR with a 3-point alignment. Methods IRB approval was granted for a study incorporating MixR during the setup process for patients undergoing proton (n = 10) or photon (n = 8) RT to the breast or chest wall. For each patient, MixR was utilized for five fractions and compared against another five fractions using 3-point alignment. During fractions with MixR, the patient was aligned by at least one therapist wearing a HoloLens 2 device who was able to guide the process by simultaneously and directly viewing the patient and a hologram of the patient’s surface derived from their simulation CT scan. Alignment accuracy was quantified with cone-beam CT (CBCT) for photon treatments and CBCT plus kV/kV imaging for proton treatments. Registration time was tracked throughout the setup process as well as the amount of image guidance (IGRT) utilized for final alignment. Results In the proton cohort, the mean 3D shift was 0.96 cm using 3-point alignment and 1.18 cm using MixR. An equivalence test indicated that the difference in registration accuracy between the two techniques was less than 0.5 cm. In the photon cohort, the mean 3D shift was 1.18 cm using 3-point alignment and 1.00 cm using MixR. An equivalence test indicated that the difference in registration accuracy was less than 0.3 cm. Minor differences were seen in registration time and the amount of IGRT utilization. Conclusions MixR for patient setup for breast cancer RT is possible at the level of accuracy and efficiency provided by a 3-point alignment. Further developments in marker tracking, feedback, and a better understanding of the perceptual challenges of MixR are needed to achieve a similar level of accuracy as provided by modern surface-guided radiotherapy (SGRT) systems. Trial registration ClinicalTrials.gov, UFHPTI 2015-BR05: Improving Breast Radiotherapy Setup and Delivery Using Mixed-Reality Visualization, NCT05178927.

BackgroundSimulated error training is a method to practice error detection in situations where the occurrence of error is low. Such is the case for the physics plan and chart review where a physicist may check several plans before encountering a significant problem. By simulating potentially hazardous errors, physicists can become familiar with how they manifest and learn from mistakes made during a simulated plan review.PurposeThe purpose of this project was to develop a series of training datasets that allows medical physicists and trainees to practice plan and chart reviews in a way that is familiar and accessible, and to provide exposure to the various failure modes (FMs) encountered in clinical scenarios.MethodsA series of training datasets have been developed that include a variety of embedded errors based on the risk-assessment performed by American Association of Physicists in Medicine (AAPM) Task Group 275 for the physics plan and chart review. The training datasets comprise documentation, screen shots, and digital content derived from common treatment planning and radiation oncology information systems and are available via the Cloud-based platform ProKnow.ResultsOverall, 20 datasets have been created incorporating various software systems (Mosaiq, ARIA, Eclipse, RayStation, Pinnacle) and delivery techniques. A total of 110 errors representing 50 different FMs were embedded with the 20 datasets. The project was piloted at the 2021 AAPM Annual Meeting in a workshop where participants had the opportunity to review cases and answer survey questions related to errors they detected and their perception of the project's efficacy. In general, attendees detected higher-priority FMs at a higher rate, though no correlation was found between detection rate and the detectability of the FMs. Familiarity with a given system appeared to play a role in detecting errors, specifically when related to missing information at different locations within a given software system. Overall, 96% of respondents either agreed or strongly agreed that the ProKnow portal and training datasets were effective as a training tool, and 75% of respondents agreed or strongly agreed that they planned to use the tool at their local institution.ConclusionsThe datasets and digital platform provide a standardized and accessible tool for training, performance assessment, and continuing education regarding the physics plan and chart review. Work is ongoing to expand the project to include more modalities, radiation oncology treatment planning and information systems, and FMs based on emerging techniques such as auto-contouring and auto-planning.