Pencil Beam Scanning Research Articles

Spatially Fractionated Radiotherapy with Very High Energy Electron Pencil Beam Scanning.


To evaluate spatially fractionated radiation therapy (SFRT) for very-high-energy electrons (VHEEs) delivered with pencil beam scanning. Radiochromic film was irradiated at the CERN Linear Electron Accelerator for Research (CLEAR) using 194 MeV electrons with a step-and-shoot technique, moving films within a water tank. Peak-to-valley dose ratios (PVDRs), depths of convergence (PVDR≤1.1), peak doses, and valley doses assessed SFRT dose distribution quality. A Monte Carlo (MI) model of the pencil beams was developed using TOPAS and applied to a five-beam VHEE SFRT treatment for a canine glioma patient, compared to a clinical 6 MV VMAT plan. The plans were evaluated based on dose-volume histograms, mean dose, and maximum dose to the planning target volume (PTV) and organs at risk (OARs).
Main Results:
Experimental PVDR values were maximized at 15.5 ± 0.1 at 12 mm depth for 5 mm spot spacing. A depth of convergence of 76.5 mm, 70.7 mm, and 56.6 mm was found for 5 mm, 4 mm, and 3 mm beamlet spacings, respectively. MC simulations and experiments showed good agreement, with maximum relative dose differences of 2% in percentage depth dose curves and less than 3% in beam profiles. Simulated PVDR values reached 180 ± 4, potentially achievable with reduced leakage dose. VHEE SFRT plans for the canine glioma patient showed a decrease in mean dose (>16%) to OARs while increasing the PTV mean dose by up to 15%. Lowering beam energy enhanced PTV dose homogeneity and reduced OAR maximum doses. The presented work demonstrates that pencil beam scanning SFRT with VHEEs could treat deep-seated tumors such as head and neck cancer or lung lesions, though small beam size and leakage dose may limit the achievable PVDR.&#xD.

Effects of spot size errors in DynamicARC pencil beam scanning proton therapy planning.

Spot size stability is crucial in pencil beam scanning (PBS) proton therapy, and variations in spot size can disrupt dose distributions. Recently, a novel proton beam delivery method known as DynamicARC PBS scanning has been introduced. The current study investigates the dosimetric impact of spot size errors in DynamicARC proton therapy for head and neck (HNC), prostate, and lung cancers.
Approach: Robustly optimized DynamicARC proton therapy plans were created for HNC (n=4), prostate (n=4), and lung (n=4) cancer patients. Spot size errors of ±10%, ±15%, and ±20% were introduced, and their effects on target coverage (D95% and D99%), homogeneity index (HI), and organ-at-risk (OAR) doses were analyzed across different cancer sites.
Main Results: HNC and lung cancer plans showed greater vulnerability to spot size errors, with reductions in target coverage of up to 4.8% under -20% spot size errors. Dose homogeneity was also more affected in these cases, with HI degrading by 0.12 in lung cancer. Prostate cancer demonstrated greater resilience to spot size variations, even under errors of ±20%. For spot size errors ±10%, the oral cavity, parotid glands, and constrictor muscles experienced Dmean deviations within ±1.2%, while deviations were limited to ±0.5% for D10% of the bladder and rectum and ±0.3% for V20Gy(RBE) of the lungs. The robustness analysis indicated that lung cancer plans were most susceptible to robustness reductions caused by spot size errors, while HNC plans demonstrated moderate sensitivity. Conversely, prostate cancer plans demonstrated high robustness, experiencing only minimal reductions in target coverage.
Significance: While the ±10% spot size tolerance is appropriate in the majority of the cases, lung cancer plans may require more stringent criteria. As DynamicARC becomes clinically available, measuring spot size errors in practice will be essential to validate these findings and refine tolerance thresholds for clinical use.

Assessment of pencil beam scanning proton therapy beam delivery accuracy through machine learning and log file analysis

PurposeComprehensive Quality Assurance (QA) protocols are necessary for complex beam delivery systems like Pencil Beam Scanning (PBS) proton therapy. This study focuses on automating the evaluation of beam delivery accuracy using irradiation log files and machine learning (ML) models. MethodsIrradiation log files of 935 clinical treatment fields and routine QA beams were analysed to evaluate spot parameters and Monitor Unit (MU) accuracy. ML models predicted spot size along the X, Y, major, and minor axes. In-house scripts automated log file analysis and spot size predictions. Predicted spot sizes were compared with expected baselines, and the accuracy of spot position, symmetry, and MU for each spot in the beam was evaluated. ResultsMore than 99.5 % of spot positions were accurate within a 1 mm. The mean and Standard Deviation (SD) of X positional error were −0.021 mm (SD: 0.181 mm), and for Y positional error, they were −0.002 mm (SD: 0.132 mm). ML models accurately predicted spot sizes, with over 95 % of spots demonstrating size variations within 10 % of the baseline. The Root Mean Squared Error (RMSE) of X and Y spot size differences were 0.15 mm and 0.16 mm, respectively. Spot symmetry was within 10 %, and MU accuracy showed 95 % of spots with MU per spot variation less than 2 %. ConclusionThis method can validate the vendor’s beam delivery safety interlock system and serve as a quick alternative to patient-specific QA in adaptive treatment, where time is limited, as well as for routine QA spot parameter evaluations.

Implementation and validation of a very-high-energy electron model in the matRad treatment planning system.

While electron beams of up to 20 MeV are commonly used in radiotherapy, the use of very-high-energy electrons (VHEEs) in the range of 100-200 MeV is now becoming a realistic option thanks to the recent advancements in accelerator technology. Indeed, VHEE offers several clinically attractive features and can be delivered using various conformation methods (including scanning, collimation, and focussing) at ultra-high dose rates. To date, there is a lack of research tools for fast simulation of treatment plans using VHEE beams. This work aims to implement and validate a simple and fast dose calculation algorithm based on the Fermi-Eyges theory of multiple Coulomb scattering for VHEE radiation therapy, with energies up to 200 MeV. A treatment planning system (TPS) toolkit with VHEE modality would indeed allow for further preclinical investigations, including treatment plan optimization and evaluation, and thus contribute to the gradual introduction of VHEE radiotherapy in clinical practice. A VHEE pencil beam scanning double Gaussian model was introduced into the open-source TPS matRad environment along with new functions and options dedicated to VHEE dose calculations. Various geometries and field configurations were then calculated in matRad (up to 200 MeV and 15×15 cm2, with complex bone or lung heterogeneities) and the results were compared to Monte Carlo simulations in the TOPAS/Geant4 toolkit. Two types of beam model (divergent or focused) were also tested. Examples of clinical treatment plans were computed, and the results were compared between the two codes. VHEE modality was fully implemented in matRad with GUI capabilities while preserving all original TPS features. New relevant options such as the importation of specific spot-lists or adjustment of the lateral dose calculation cutoff to optimize the calculation speed were validated. Single spot and square field dose distributions were validated in water alone as well as in clinically relevant inhomogeneities. Dose maps from the VHEE model in matRad were in good agreement with TOPAS (2D gamma index [2%/1mm] with passing rates superior to 90%, <6% mean dose differences), except for large interface heterogeneities. This work describes the implementation of a simple but efficient VHEE simulation model in matRad. A few configurations were studied in order to validate the model against accurate Monte Carlo simulations, demonstrating its usefulness for carrying out preliminary studies involving VHEE radiotherapy.

Evaluation of a prototype array for daily quality assurance in spot scanning proton therapy.

Quality assurance (QA) on a daily basis is an essential task in radiotherapy. In pencil beam scanning proton therapy (PBS), there is a lack of available practical QA devices for routine daily QA in comparison to conventional radiotherapy. The aim was to characterize and evaluate a prototype for the task of daily QA routine for PBS with parameters recommended by the AAPM TG 224, that is, the dose output constancy, the spot position and the distal range verification. Furthermore, a time efficient calibration method for fast and reliable daily QA routine was established for theprototype. First, a calibration routine was designed and evaluated, which characterizes the array response and allows for a conversion of the measured signal to clinically needed QA parameters. Finally, a time and resource efficient daily QA routine was developed andtested. The prototype array can distinguish spot position deviations with sub-millimeter accuracy, as well as changes in the spot size in terms of FWHM with a 2 sensitivity. The range and thus the energy can be evaluated at different depths also with sub-millimeter precision. After some training, the setup of the prototype device took roughly two minutes and the total beamtime was about one minuteon cyclotron site and five minutesfor synchrotrons. A prototype for daily QA in spot scanning proton therapy was evaluated, which features a fast and easy setup and allows for measuring relevant beam parameters, typically within less than a minute of beam time. All QA parameters as recommended by the AAPM TG 224 report can be analyzed with sufficientaccuracy.

Dosimetric and On-treatment Clinical Results of a Volumetric-based Skin-sparing Planning Technique for Patients Treated to the Breast and Chest Wall With Pencil-Beam Scanning Proton Therapy

PurposeThis study evaluates the hypothesis that a volumetric skin-sparing planning technique (SSPT) will reduce acute dermatitis in patients treated to the breast or chest wall (CW) with proton pencil beam scanning (PBS). MethodsIn January 2022, our center incorporated volumetric-based skin-sparing objectives in addition to skin hot-spot evaluation as a SSPT. The SSPT incorporated an objective to limit the volume of a skin evaluation structure (skin-eval) receiving 95% of the prescription dose or more (V95%Rx) to ideally <50%. We compared target coverage, robustness, skin-eval dosimetry, and acute on-treatment skin toxicity in patients treated with and without incorporation of this SSPT. Patients with skin/dermal lymphatic invasion or inflammatory breast cancer were excluded. Results84 patients who received breast/CW PBS were included (43 planned without and 41 with the SSPT). There was no difference in percentages of patients treated to the intact breast/CW/immediate CW reconstruction between groups. Mean skin-evalV95%Rx was 72% vs. 30%, p<0.0001, for those treated without versus with a SSPT. Maximum %Rx to the skin-eval volume of 0.03 cc, 0.3cc, and 1cc was higher in patients treated without versus with a SSPT (103.1% vs. 101.5%; 101.3% vs. 100.4%; and 101.8% vs. 99.7% (all p=<0.0001)), respectively. There was a small difference in the mean CTV V97.5%Rx in patients treated without versus with the SSPT (97.8% vs. 96.5%, p=0.0003). Patients planned utilizing the SSPT demonstrated reduced rates of Grade 1 breast pain at Week 2 (12% vs. 33%, p=0.0424) and Grade 2 and 3 dermatitis at Weeks 4 and 5 (Week 4 dermatitis ≥ grade 2, 18% vs. 43%, p=0.0224; Week 5 dermatitis ≥ grade 2, 45% vs. 69%, p=0.0006). There were numerically more patients requiring a treatment break or not completing the full intended prescription (4 vs. 1) in the pre-SSPT cohort. ConclusionsUse of a SSPT may reduce acute skin toxicity in breast cancer patients treated with PBS.

Stochastic model for predicting the temporal structure of the plan delivery in a synchrotron-based pencil beam scanning proton therapy system

Accurately predicting dose delivery is crucial for achieving fully personalized treatments in external beam radiation therapy. However, this task remains challenging in some current technologies. In the case of Proton Therapy, for example, current systems employ complex strategies where a pencil beam is scanned in the tumor for treatment delivery. Some parameters in these treatments fluctuate and cannot be fully controlled. Therefore, a stochastic model that accounts for temporal uncertainties can be the best approach to describe these behaviors, particularly when the time-dependent beam interacts with other processes such as moving tumors or organs at risk.This paper aims to provide medical physicists with a tool for accurately predicting the temporal structure of beam delivery. To achieve this, we followed a two-step process. First, we characterized the probability distributions for all relevant times in dose delivery. Second, we developed a model based on the measured data. This model serves as a starting point to improve treatment planning performance by providing a range of expected times for dose delivery. While the process was carried out using a compact synchrotron at our university, it can be easily adapted to other technologies.

Cardiac Conduction System as an OAR in Radiation Therapy: Doses to SA/AV Nodes and Their Reduction

PurposeDespite advancements in radiation techniques, concerns persist regarding the adverse effects of radiation therapy, particularly cardiotoxicity or radiation-induced heart disease. Recently, arrhythmogenic toxicity has come to the forefront—the impact of radiation therapy on the cardiac conduction system. Our objective was to conduct a dosimetric study and subsequently investigate the feasibility of optimizing the sinoatrial (SA) and atrioventricular (AV) nodes as organs at risk (OARs) in proton radiation therapy for non–small cell lung cancer with N3 disease. Patients and MethodsThirty-two non–small cell lung cancer patients with N3 disease undergoing proton radiation therapy were included. Sinoatrial and AV nodes, along with standard OARs, were delineated. Dosimetric analysis and optimization were performed using intensity-modulated proton therapy. ResultsPatients surpassing a predefined SA node dose threshold underwent dose optimization. Proton radiation therapy with pencil beam scanning demonstrated a significant reduction in SA and AV node doses without compromising target volume coverage or significant shift in the dose to other monitored OARs. ConclusionDose reduction to the SA and AV nodes for pencil beam scanning is a relatively simple task, and the reduction can be very substantial. Larger cohort studies and diverse radiotherapeutic modalities are needed for further validation and refinement of dose constraints.

Real-time tracking of the Bragg peak during proton therapy via 3D protoacoustic Imaging in a clinical scenario

Proton radiotherapy favored over X-ray photon therapy due to its reduced radiation exposure to surrounding healthy tissues, is highly dependent on the accurate positioning of the Bragg peak. Existing methods like PET and prompt gamma imaging to localize Bragg peak face challenges of low precision and high complexity. Here we introduce a 3D protoacoustic imaging with a 2D matrix array of 256 ultrasound transducers compatible with 256 parallel data acquisition channels provides real-time imaging capability (up to 75 frames per second with 10 averages), achieving high precision (5 mm/5% Gamma index shows accuracy better than 95.73%) at depths of tens of centimeters. We have successfully implemented this method in liver treatment with 5 pencil beam scanning and in prostate cancer treatment on a human torso phantom using a clinical proton machine. This demonstrates its capability to accurately identify the Bragg peak in practical clinical scenarios. It paves the way for adaptive radiotherapy with real-time feedback, potentially revolutionizing radiotherapy by enabling closed-loop treatment for improved patient outcomes.

Long-term stability of a PTW 34070 large-area parallel ionization chamber in clinical proton scanning beams.

In the modeling of beam data for proton therapy planning systems, absolute dose measurements are performed utilizing a Bragg peak chamber (BPC), which is a parallel-plate ionization chamber. The long-term stability of the BPC is crucial for ensuring accurate absolute dose measurement. The study aims to assess the long-term stability of the BPC in clinical proton pencil beam scanning delivery. The long-term stability evaluation focused on the BPC-Type 34070 (PTW Freiburg, Germany), utilizing clinical proton scanning beams from December 2022 to November 2023. Monthly investigations were conducted to evaluate the response and cross-calibration factor of the BPC and a reference chamber, employing the spread-out Bragg peak (SOBP) field. Additionally, assessments were made regarding the BPC's response to monoenergetic beams, along with an examination of the impact of polarity and ion recombination on the BPC. The response and cross-calibration factor of the BPC varied up to 1.9% and 1.8%, respectively, while the response of the reference chamber remained within a 0.5% range. The BPC's response to the mono-energetic beams varied up to 2.0% across all energies, demonstrating similar variation trends in both the SOBP field and mono-energetic beams. Furthermore, the variations in polarity and ion recombination effect remained stable within a 0.4% range throughout the year. Notably, the reproducibility of the BPC remained high for each measurement conducted, whether for the SOBP field or mono-energetic beams, with a maximum deviation observed at 0.1%. The response and cross-calibration factor of the BPC demonstrated significant variations, with maximum changes of 1.9% and 1.8%, respectively. However, the reproducibility of the BPC remained consistently high for each measurement. It is recommended that when conducting absolute dose measurements using a BPC, its response should be compared and corrected against the reference chamber for each measurement.

Development of a three-dimensional scintillation detector for pencil beam verification in proton therapy patient-specific quality assurance.

Pencil Beam Scanning proton therapy has many advantages from a therapeutic point of view, but raises technical constraints in terms of treatment verification. The treatment relies on a large number of planned pencil beams (PB) (up to thousands), whose delivery is divided in several low-intensity pulses delivered a high frequency (1kHz in this study). The purpose of this study was to develop a three-dimensional quality assurance system allowing to verify all the PBs' characteristics (position, energy, intensity in terms of delivered monitor unit-MU) of patient treatment plans on a pulse-by-pulse or a PB-by-PB basis. A system named SCICOPRO has been developed. It is based on a 10×10×10cm3 scintillator cube and a fast camera, synchronized with beam delivery, recording two views (direct and using a mirror) of the scintillation distribution generated by the pulses. A specific calibration and analysis process allowed to extract the characteristics of all the pulses delivered during the treatment, and consequently of all the PBs. The system uncertainties, defined here as average value + standard deviation, were characterized with a customized irradiation plan at different PB intensities (0.02, 0.1, and 1 MU) and with two patient's treatment plans of three beams each. The system's ability to detect potential treatment delivery problems, such as positioning errors of the treatment table in this work (1° rotations and a 2mm translation), was assessed by calculating the confidence intervals (CI) for the different characteristics and evaluating the proportion of PBs within these intervals. The performances of SCICOPRO were evaluated on a pulse-by-pulse basis. They showed a very good signal-to-noise ratio for all the pulse intensities (between 2×10-3MU and 150×10-3MU) allowing uncertainties smaller than 580µm for the position, 180keV for the energy and 3% for the intensity on patients treatment plans. The position and energy uncertainties were found to be little dependent from the pulse intensities whereas the intensity uncertainty depends on the pulses number and intensity distribution. Finally, treatment plans evaluations showed that 98% of the PBs were within the CIs with a nominal positioning against 83% or less with the table positioning errors, thus proving the ability of SCICOPRO to detect this kind of errors. The high acquisition rate and the very high sensitivity of the system developed in this work allowed to record pulses of intensities as low as 2×10-3MU. SCICOPRO was thus able to measure all the characteristics of the spots of a treatment (position, energy, intensity) in a single measurement, making it possible to verify their compliance with the treatment plan. SCICOPRO thus proved to be a fast and accurate tool that would be useful for patient-specific quality assurance (PSQA) on a pulse-by-pulse or PB-by-PB verification basis.

Whole Abdominal Pencil Beam Scanned Proton FLASH Increases Acute Lethality

PurposeUltra-high dose-rate FLASH radiotherapy (RT) has emerged as a modality which promises to reduce normal tissue toxicity while maintaining tumor control. Previous studies of gastrointestinal toxicity using passively scattered FLASH proton therapy (PRT) have, however, yielded mixed results, suggesting that the requirements for gastrointestinal sparing by FLASH are an open question. Furthermore, the more clinically relevant pencil beam scanned (PBS) FLASH PRT has not yet been assessed in this context, despite differences in the spatiotemporal dose-rate distributions compared to passively scattered PRT. Here, we provide the first report on the effects of PBS FLASH PRT on acute gastrointestinal injury in mice after whole abdominal irradiation. Methods and MaterialsWhole abdominal irradiation was performed on C57BL/6J mice using the entrance channel of the Bragg curve of a 250 MeV PBS proton beam at field-averaged dose-rates of 0.6 Gy/s for conventional (CONV) and 80-100 Gy/s for FLASH PRT. A 2D strip ionization chamber array was used to measure the dose and dose rate for each mouse. Survival was assessed at 14 Gy. Intestines were harvested and processed as Swiss rolls for analysis using a novel artificial intelligence (AI)-based crypt assay to quantify crypt regeneration 4 days post-irradiation. ResultsSurvival was significantly reduced following 14 Gy FLASH PRT compared to CONV (P<0.001). Our AI-based crypt assays demonstrated no significant difference in intestinal crypts/cm or crypt depth between groups 4 days post-irradiation. Furthermore, we found no significant difference in EdU+ cells/crypt or Olfactomedin4+ intestinal stem cells with FLASH relative to CONV PRT. ConclusionsOverall, our data demonstrate significantly impaired survival following abdominal PBS FLASH PRT without apparent differences in intestinal histology 4 days post-irradiation.

Setting the Stage: Feasibility and Baseline Characteristics in the PARTIQoL Trial Comparing Proton Therapy Versus Intensity Modulated Radiation Therapy for Localized Prostate Cancer

Men with localized prostate cancer may receive either photon-based intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT). The PARTIQoL trial (NCT01617161) demonstrates the feasibility of performing a large, multicenter phase 3 randomized trial comparing IMRT with PBT for localized prostate cancer. Here, we report baseline features of patients enrolled on this trial and present strategies to improve feasibility of other similar trials. Patients with low- or intermediate-risk prostate cancer were randomly assigned to either PBT or IMRT with stratification by institution, age, use of rectal spacer, and fractionation schedule (conventional fractionation: 79.2 Gy in 44 fractions vs moderate hypofractionation: 70.0 Gy in 28 fractions). The primary endpoint is a change from baseline bowel health using the Expanded Prostate Index Composite score 24 months after radiation therapy. Secondary objectives include treatment-related differences in urinary and erectile functions, adverse events, and efficacy endpoints. Between July 2012 and November 2021, 450 patients were successfully accrued. Patients were randomly assigned to either PBT (N = 226) or to IMRT (N = 224); 13 were ineligible or withdrew before treatment. The median age of 437 analyzed patients was 68 years (range, 46-89 years). A total of 41% of patients had low-risk and 59% had intermediate-risk disease. In total, 49% of patients were treated with conventional fractionation and 51% with moderately hypofractionation. 48% of patients used a rectal spacer. For patients receiving PBT, pencil beam scanning was used in 48%. PBT and IMRT arms were balanced for baseline variables. Despite significant challenges, the PARTIQoL trial demonstrated that, with targeted recruitment approaches, multicenter collaboration, payer engagement, and protocol updates to incorporate contemporary techniques, it is feasible to perform a large phase 3 randomized clinical trial to assess whether PBT improves outcomes. We will separately report primary results and continue to monitor participants for longer follow-up and secondary endpoints.

Online Adaptive Proton Therapy Facilitated by Artificial Intelligence–Based Autosegmentation in Pencil Beam Scanning Proton Therapy

PurposeOnline adaptive proton therapy (oAPT) is essential to address interfractional anatomical changes in patients receiving pencil beam scanning proton therapy (PBSPT). Artificial intelligence (AI)-based auto-segmentation can increase the efficiency and accuracy. Linear energy transfer (LET)-based biological effect evaluation can potentially mitigate possible adverse events caused by high LET. New spot arrangement based on the verification CT (vCT) can further improve the re-plan quality. We propose an oAPT workflow that incorporates all these functionalities and validate its clinical implementation feasibility with prostate patients. Methods and MaterialsAI-based auto-segmentation tool AccuContourTM (Manteia, Xiamen, China) was seamlessly integrated into oAPT. Initial spot arrangement tool on the vCT for re-optimization was implemented using raytracing. An LET-based biological effect evaluation tool was developed to assess the overlap region of high dose and high LET in selected OARs. Eleven prostate cancer patients were retrospectively selected to verify the efficacy and efficiency of the proposed oAPT workflow. The time cost of each component in the workflow was recorded for analysis. ResultsThe verification plan showed significant degradation of the CTV coverage and rectum and bladder sparing due to the interfractional anatomical changes. Re-optimization on the vCT resulted in great improvement of the plan quality. No overlap regions of high dose and high LET distributions were observed in bladder or rectum in re-plans. 3D Gamma analyses in PSQA confirmed the accuracy of the re-plan doses before delivery (Gamma passing rate = 99.57 ± 0.46%), and after delivery (98.59 ± 1.29%). The robustness of the re-plans passed all clinical requirements. The average time for the complete execution of the workflow was 9.12 ± 0.85 minutes, excluding manual intervention time. ConclusionThe AI-facilitated oAPT workflow was demonstrated to be both efficient and effective by generating a re-plan that significantly improved the plan quality in prostate cancer treated with PBSPT.

1085: Pencil-beam scanning proton therapy for low-grade glioma patients

1085: Pencil-beam scanning proton therapy for low-grade glioma patients

Reducing Radiation Dermatitis for PBS Proton Therapy Breast Cancer Patients Using SpotDelete

PurposeThe purpose of this work was to reduce the severity of radiation dermatitis for breast cancer patients receiving pencil beam scanning proton therapy. The hypothesis was that eliminating proton spots (SpotDelete) in the 0.5 cm skin rind would reduce the potentially higher relative biological effectiveness (RBE) known to occur at the Bragg Peak. Patients and MethodsOur center has been using an in-house developed Python script in RayStation since 2021 to remove spots from the skin rind of breast patients. In this work, we retrospectively reviewed the on-treatment visit data from a cohort of breast patients treated with hypofractionation (16 fractions) before this technique (MinDepth) and after (SpotDelete) to acquire the physician-reported radiation dermatitis scores. We evaluated the delivered treatment plans, calculating the linear energy transfer (LET) and applying 3 variable RBE models, Carabe-Fernandez, Wedenberg, and McNamara. An α/β of 10 was assumed for the skin. ResultsIn the MinDepth cohort (n = 28), grade 1, 2, and 3 dermatitis accounted for 57%, 36%, and 7% of the cases, respectively. For SpotDelete (n = 27), the incidence rate of grade 1 and 2 acute radiation dermatitis was 67% and 37%, respectively. There were 0 instances of grade 3 dermatitis observed in the SpotDelete cohort. The onset of radiation dermatitis in the SpotDelete cohort was delayed compared to MinDepth, occurring 1 week later in the course of treatment. There was no significant difference in LET or in any of the variable RBE models when analyzing the 0.5 cm skin rind between the cohorts. ConclusionDespite the lack of correlation in LET or RBE, SpotDelete has been shown to reduce the severity and onset of radiation dermatitis. Possibly, more research into the α/β for skin and RBE models based on skin cell lines could provide insight into the efficacy of the SpotDelete technique.

Proton pencil beam scanning radiotherapy in the postoperative treatment of p16 positive squamous cell tonsillar cancer – evaluation of toxicity and effectivity

PurposePatients with p16 positive tonsillar cancer (p16 + TC) have an excellent prognosis and long-life expectancy. Deintensification of therapy is a prevalent topic of discussion. Proton radiotherapy is one way to reduce radiation exposure and thus reduce acute and late toxicity. The aim is to evaluate treatment outcomes and toxicity of postoperative treatment with intensity-modulated proton therapy (IMPT).MethodsBetween September 2013 and November 2021, 47 patients with p16 + TC were treated postoperatively with IMPT. Median age was 54.9 (38.2–74.9) years, 31 were males and 16 were females. All patients had squamous cell carcinoma and underwent surgery as a primary treatment. Median dose of radiotherapy was 66 GyE in 33 fractions. Bilateral neck irradiation was used in 39 patients and unilateral in 8. Concomitant chemotherapy was applied in 24 patients.ResultsMedian follow-up time was 4.2 (0.15–9.64) years. Five-year overall survival, relapse free survival and local control were 95.7%, 97.8% and 100%. The most common acute toxicities were dermatitis and mucositis, with grade 2 + in 61.7% and 70.2% of patients. No acute percutaneous gastrostomy insertion was necessary and intravenous rehydration was used in 12.8% of patients. The most common late toxicity was grade 1 xerostomia in 70.2% of patients and grade 2 in 10.6% of patients. Subcutaneous fibrosis of grades 2 and 3 occurred in 17.0% and 2.1% of patients, respectively. One patient developed late severe dysphagia and became PEG-dependent.ConclusionIMPT for the postoperative treatment of p16 + TC is feasible with excellent efficiency and acceptable acute and late toxicity.

PTCOG international survey of practice patterns and trends in utilization of proton therapy for breast cancer

Purpose/objectivesThe indications, techniques, and extent to which proton beam therapy (PBT) is employed for breast cancer are unknown. We seek to determine PBT utilization for breast cancer. Materials/methodsThe Particle Therapy Co-Operative Group (PTCOG) Breast Subcommittee developed an IRB-approved 29-question survey and sent it to breast cancer radiation oncologists at all active PBT centers worldwide in June 2023. Descriptive statistics were used to summarize responses, and comparisons by continent were performed using Fisher’s exact tests. ResultsOf 79 surveys distributed, 28 recipients submitted responses (35 % response rate) representing fifteen U.S., 8 European, and 5 Asian centers (continent response rate 50 %, 38 %, and 18 %, respectively). Overall, 93 % reported treating breast cancer patients with PBT; 13 (50 %) have treated ≥100 breast cancer patients at their center since opening. Most (89 %) have pencil beam scanning technology. Nearly half (46 %) use moderate hypofractionation (15–20 fractions) for regional nodal irradiation and 42 % conventional fractionation (25–30 fractions). More European centers prefer hypofractionation (88 %) vs. Asian (50 %) and U.S. (21 %) centers (p = 0.003). Common patient selection methods were practitioner determination/patient preference (n = 16) and comparative plan evaluation (n = 15). U.S. centers reported the most experience with breast PBT, with 71 % having treated ≥100 breast cancer patients vs. 38 % in Europe and none in Asia (p = 0.001). Of respondent centers, 39 % enrolled ≥75 % of breast PBT patients on a research study. ConclusionUtilization, patient selection methods, and dose-fractionation approaches for breast cancer PBT vary worldwide. These survey data serve as a benchmark from which successor surveys can provide insight on practice pattern evolution.

Investigation of linear energy transfer (LET)-dependence behavior and dosimetric response of a flat-panel detector in pencil beam scanning proton therapy

PurposeThis 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. MethodsThe 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. ResultsThe 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. ConclusionThis 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.

Time structures of proton pencil beam scanning delivery on a microsecond scale measured with a pixelated semiconductor detector Timepix3.

The time structures of proton spot delivery in proton pencil beam scanning (PBS) radiation therapy are essential in many clinical applications. This study aims to characterize the time structures of proton PBS delivered by both synchrotron and synchrocyclotron accelerators using a non-invasive technique based on scattered particle tracking. A pixelated semiconductor detector, AdvaPIX-Timepix3, with a temporal resolution of 1.56ns, was employed to measure time of arrival of secondary particles generated by a proton beam. The detector was placed laterally to the high-flux area of the beam in order to allow for single particle detection and not interfere with the treatment. The detector recorded counts of radiation events, their deposited energy and the timestamp associated with the single events. Individual recorded events and their temporal characteristics were used to analyze beam time structures, including energy layer switch time, magnet switch time, spot switch time, and the scanning speeds in the x and y directions. All the measurements were repeated 30 times on three dates, reducing statistical uncertainty. The uncertainty of the measured energy layer switch times, magnet switch time, and the spot switch time were all within 1% of average values. The scanning speeds uncertainties were within 1.5% and are more precise than previously reported results. The measurements also revealed continuous sub-milliseconds proton spills at a low dose rate for the synchrotron accelerator and radiofrequency pulses at 7µs and 1ms repetition time for the synchrocyclotron accelerator. The AdvaPIX-Timepix3 detector can be used to directly measure and monitor time structures on microseconds scale of the PBS proton beam delivery. This method yielded results with high precision and is completely independent of the machine log files.