Correlative Effects of Carbon Support Structures and Surface Properties on ORR Catalytic Activities of Loaded Catalysts.

As a complex three-phase heterogeneous catalyst, the oxygen reduction reaction (ORR) catalyst activity is determined by the interfacial and surface structures and chemical state of the catalyst support. As a typical biomass carbon-based support, rice husk-based porous carbon (RHPC) has natural unique hierarchical porous structures, which easily regulate the microstructure and surface properties. This study explored the correlative effects of RHPC structure and surface properties on ORR catalytic activity through the typical modification methods, namely, alkali etching, high temperature, oxidation, and ball milling. The various factors for the joint effects are defined as the specific surface area, oxygen-containing functional groups, graphite edge defects, resistivity, and contact angle. The analysis of such joint influences is difficult to quantitatively evaluate due to the large number of experimental factors and small sample sizes. Partial least-squares (PLS) can better deal with such problems. Therefore, a PLS regression model was established to evaluate the relative weight of each factor on the catalytic activity for the RHPC-based support catalysts. The results reveal that the regression coefficients of four factors yield similar magnitude for the effect of the half-wave potential (E1/2). However, graphite edge defects had a more significant impact on the limiting diffusion current density (J) and electron transfer number (n). Furthermore, an optimal support named BM-RHPC-3 was prepared with more defects and oxygen-containing functional groups, which prepared Fe-NS/BM-RHPC-3 presenting the best ORR catalytic activity (E1/2 = 0.880 V, J of 5.15 mA cm-2), superior to Pt/C (E1/2 = 0.844 V, J of 4.99 mA cm-2). The statistical regression model is validated with a relative error of less than 5% between predicted and true values for analyzing RHPC-based ORR catalysts' catalytic performance. It shows the feasibility of experiment-informed learning for data-driven material discovery and design.

Proton Therapy for Spinal Tumors: A Consensus Statement from the Particle Therapy Cooperative Group.

PURPOSE/OBJECTIVES: Proton beam therapy (PBT) plays an important role in the management of primary spine tumors. The purpose of this consensus statement is to summarize safe and optimal delivery of PBT for spinal tumors. MATERIALS/METHODS: The Particle Therapy Co-Operative Group (PTCOG) Skull Base/Central nervous system (CNS)/Sarcoma Subcommittee consisting of radiation oncologists and medical physicists with specific expertise in spinal irradiation developed expert recommendations discussing treatment planning considerations and current approaches in the treatment of primary spinal tumors. RESULTS: CT Simulation: Factors that require significant consideration include: 1) patient comfort, 2) setup reproducibility and stability, and 3) accessibility of appropriate beam angles. SPINE STABILIZATION HARDWARE: If present, hardware should be placed with cross-links well above/below the level of the primary tumor to reduce the metal burden at the level of the tumor bed. New materials that can reduce uncertainties include polyether-ether-ketone (PEEK) and composite PEEK-carbon fiber implants. FIELD ARRANGEMENT: Appropriate beam selection is required to ensure robust target coverage and OAR sparing. Commonly, 2-4 treatment fields, typically from posterior and/or posterior-oblique directions, are utilized. TREATMENT PLANNING METHODOLOGY: Robust optimization is recommended for all pencil beam scanning plans (the preferred treatment modality) and should consider setup uncertainty (between 3-7 mm) and range uncertainty (3-3.5%). In the presence of metal hardware, use of an increased range uncertainty up to 5% is recommended. CONCLUSIONS: The PTCOG Skull Base/CNS/Sarcoma Subcommittee has developed recommendations to enable centers to deliver PBT safely and effectively for the management of primary spinal tumors.

Investigation of diaphragmatic motion and projected lung area in diaphragm paralysis patients using dynamic chest radiography.

Background: Dynamic chest radiography (DCR) is a novel and supplementary examination in respiratory diseases. The investigation of other chest diseases using DCR has been explored, identifying a certain correlation of the pulmonary function test (PFT). However, there is a lack of research using DCR parameters to quantitatively evaluate chest disease. The purpose of this study was to investigate the diagnostic value of DCR for diaphragm paralysis (DP). Methods: This retrospective study recruited 118 participants, which include 18 patients with DP, 48 healthy volunteers, and 52 patients with respiratory disease. Comparison of DCR parameters relationships among 3 groups was performed using one-way analysis of variance (ANOVA) and Kruskal-Wallis test. The receiver operating characteristic (ROC) curve was used to compare the value of the DCR parameters to diagnose DP. Results: The differences of excursion of diaphragm (ED) in normal (nb) and forced breathing (fb), ED(fb)-ED(nb), and the parameters of projected lung area (PLA) in inspiratory (ins) and expiratory phase (exp), PLA.exp(fb), PLA.ins(fb)-PLA.ins(nb), and PLA.exp(fb)-PLA.exp(nb) among the 3 groups were statistically significant. The highest area under the curve (AUC) of right-side parameter was the ED(fb)-ED(nb), for which the AUC was 0.8950 [95% confidence interval (CI): 0.7618-1.000], whereas that of the left-side parameter was ED(fb), for which the AUC was 0.9176 [95% confidence interval (CI): 0.8524-0.9829]. Conclusions: The parameters of DCR have good diagnostic value for DP. The highest diagnostic efficiency for DP on the right side is the ED(fb)-ED(nb), with a sensitivity of 95% and a specificity of 78.6%, whereas on the left side is ED(fb), with a sensitivity of 80% and a specificity of 88.2%.

The Accuracy of Artificial Intelligence ChatGPT in Oncology Examination Questions.

The aim of this study is to assess the accuracy of Chat Generative Pretrained Transformer (ChatGPT) in response to oncology examination questions in the setting of one-shot learning. Consecutive national radiation oncology in-service multiple-choice examinations were collected and inputted into ChatGPT 4o and ChatGPT 3.5 to determine ChatGPT's answers. ChatGPT's answers were then compared with the answer keys to determine whether ChatGPT correctly or incorrectly answered each question and to determine if improvements in responses were seen with the newer ChatGPT version. A total of 600 consecutive questions were inputted into ChatGPT. ChatGPT 4o answered 72.2% questions correctly, whereas 3.5 answered 53.8% questions correctly. There was a significant difference in performance by question category (P < .01). ChatGPT performed poorer with respect to knowledge of landmark studies and treatment recommendations and planning. ChatGPT is a promising technology, with the latest version showing marked improvement. Although it still has limitations, with further evolution, it may be considered a reliable resource for medical training and decision making in the oncology space.

Clinical validation of commercial deep-learning based auto-segmentation models for organs at risk in the head and neck region: a single institution study.

Purpose: To evaluate organ at risk (OAR) auto-segmentation in the head and neck region of computed tomography images using two different commercially available deep-learning-based auto-segmentation (DLAS) tools in a single institutional clinical applications. Methods: Twenty-two OARs were manually contoured by clinicians according to published guidelines on planning computed tomography (pCT) images for 40 clinical head and neck cancer (HNC) cases. Automatic contours were generated for each patient using two deep-learning-based auto-segmentation models-Manteia AccuContour and MIM ProtégéAI. The accuracy and integrity of autocontours (ACs) were then compared to expert contours (ECs) using the Sørensen-Dice similarity coefficient (DSC) and Mean Distance (MD) metrics. Results: ACs were generated for 22 OARs using AccuContour and 17 OARs using ProtégéAI with average contour generation time of 1 min/patient and 5 min/patient respectively. EC and AC agreement was highest for the mandible (DSC 0.90 ± 0.16) and (DSC 0.91 ± 0.03), and lowest for the chiasm (DSC 0.28 ± 0.14) and (DSC 0.30 ± 0.14) for AccuContour and ProtégéAI respectively. Using AccuContour, the average MD was<1mm for 10 of the 22 OARs contoured, 1-2mm for 6 OARs, and 2-3mm for 6 OARs. For ProtégéAI, the average mean distance was<1mm for 8 out of 17 OARs, 1-2mm for 6 OARs, and 2-3mm for 3 OARs. Conclusions: Both DLAS programs were proven to be valuable tools to significantly reduce the time required to generate large amounts of OAR contours in the head and neck region, even though manual editing of ACs is likely needed prior to implementation into treatment planning. The DSCs and MDs achieved were similar to those reported in other studies that evaluated various other DLAS solutions. Still, small volume structures with nonideal contrast in CT images, such as nerves, are very challenging and will require additional solutions to achieve sufficient results.

Effectiveness and safety of Governor vessel acupuncture therapy for post-stroke cognitive impairment: A meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this study was to evaluate the effectiveness of Governor vessel acupuncture (GV Ac) in treating post-stroke cognitive impairment (PSCI). METHODS: There was a total of seven databases examined. Four English databases (Cochrane Library, PubMed, Embase, and Medline) and three Chinese databases (Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Databases (VIP), and Wan Fang Database) contain all randomized controlled trials (RCTs) comparing Governor vessel acupuncture to other treatments or none acupuncture for PSCI. The exact dates for the search period are from January 1, 2000, to January 1, 2023.Two researchers independently reviewed the literature, gathered RCT data, and performed statistical analysis. All data were analyzed using Review Manager software (Rev Man) 5.3. RESULTS: This meta-analysis includes a total of 39 trials with 2044 patients. There were 1022 participants in each of the test and control groups. Following 12-120 days of acupuncture treatment, a meta-analysis revealed that the treatment groups (GV Ac combined with conventional treatment groups) significantly increased their scores on the Curative ratio (OR = 3.00, 95 %CI = 2.37-3.79, P = 0.98, I² = 0 %), Montreal Cognitive Assessment (MoCA)(MD = 1.82, 95 %CI = 1.60-2.03, P = 0.11, I² = 25 %), Mini-Mental State Examination (MMSE)(MD = 2.18, 95 %CI = 1.64-2.72, P<0.005, I² = 92 %), and Activity of Daily Living (ADL)(MD = 5.99, 95 %CI = 5.33-6.64, P = 0.19, I² = 26 %). CONCLUSION: The results suggested that acupuncture on points of the Governor vessel enhanced cognitive function in stroke survivors.

A Novel Dose Rate Optimization Method to Maximize Ultrahigh-Dose-Rate Coverage of Critical Organs at Risk Without Compromising Dosimetry Metrics in Proton Pencil Beam Scanning FLASH Radiation Therapy.

PURPOSE: This study aimed to investigate a dose rate optimization framework based on the spot-scanning patterns to improve ultrahigh-dose-rate coverage of critical organs at risk (OARs) for proton pencil beam scanning (PBS) FLASH radiation therapy (ultrahigh dose-rate (often referred to as >40 Gy per second) delivery) and present implementation of a genetic algorithm (GA) method for spot sequence optimization to achieve PBS FLASH dose rate optimization under relatively low nozzle beam currents. METHODS AND MATERIALS: First, a multifield FLASH plan was developed to meet all the dosimetric goals and optimal FLASH dose rate coverage by considering the deliverable minimum monitor unit constraint. Then, a GA method was implemented into the in-house treatment platform to maximize the dose rate by exploring the best spot delivery sequence. A phantom study was performed to evaluate the effectiveness of the dose rate optimization. Then, 10 consecutive plans for patients with lung cancer previously treated using PBS intensity-modulated proton therapy were optimized using 45 GyRBE in 3 fractions for both transmission and Bragg peak FLASH radiation therapy for further validation. The spot delivery sequence of each treatment field was optimized using this GA. The ultrahigh-dose-rate-volume histogram and dose rate coverage V40GyRBE/s were investigated to assess the efficacy of dose rate optimization quantitatively. RESULTS: Using a relatively low monitor unit/spot of 150, corresponding to a nozzle beam current of 65 nA, the FLASH dose rate ratio V40GyRBE/s of the OAR contour of the core was increased from 0% to ∼60% in the phantom study. In the patients with lung cancer, the ultrahigh-dose-rate coverage V40GyRBE/s was improved from 15.2%, 15.5%, 17.6%, and 16.0% before the delivery sequence optimization to 31.8%, 43.5%, 47.6%, and 30.5% after delivery sequence optimization in the lungs-GTV (gross tumor volume), spinal cord, esophagus, and heart (for all, P < .001). When the beam current increased to 130 nA, V40GyRBE/s was improved from 45.1%, 47.1%, 51.2%, and 51.4% to 65.3%, 83.5%, 88.1%, and 69.4% (P < .05). The averaged V40GyRBE/s for the target and OARs increased from 12.9% to 41.6% and 46.3% to 77.5% for 65 and 130 nA, respectively, showing significant improvements based on a clinical proton system. After optimizing the dose rate for the Bragg peak FLASH technique with a beam current of 340 nA, the V40GyRBE/s values for the lung GTV, spinal cord, esophagus, and heart were increased by 8.9%, 15.8%, 22%, and 20.8%, respectively. CONCLUSIONS: An optimal plan quality can be maintained as the spot delivery sequence optimization is a separate independent process after the plan optimization. Both the phantom and patient results demonstrated that novel spot delivery sequence optimization can effectively improve the ultrahigh-dose-rate coverage for critical OARs, which can potentially be applied in clinical practice for better OARs-sparing efficacy.

A comprehensive pre-clinical treatment quality assurance program using unique spot patterns for proton pencil beam scanning FLASH radiotherapy.

BACKGROUND: Quality assurance (QA) for ultra-high dose rate (UHDR) irradiation is a crucial aspect in the emerging field of FLASH radiotherapy (FLASH-RT). This innovative treatment approach delivers radiation at UHDR, demanding careful adoption of QA protocols and procedures. A comprehensive understanding of beam properties and dosimetry consistency is vital to ensure the safe and effective delivery of FLASH-RT. PURPOSE: To develop a comprehensive pre-treatment QA program for cyclotron-based proton pencil beam scanning (PBS) FLASH-RT. Establish appropriate tolerances for QA items based on this study's outcomes and TG-224 recommendations. METHODS: A 250 MeV proton spot pattern was designed and implemented using UHDR with a 215nA nozzle beam current. The QA pattern that covers a central uniform field area, various spot spacings, spot delivery modes and scanning directions, and enabling the assessment of absolute, relative and temporal dosimetry QA parameters. A strip ionization chamber array (SICA) and an Advanced Markus chamber were utilized in conjunction with a 2 cm polyethylene slab and a range (R80) verification wedge. The data have been monitored for over 3 months. RESULTS: The relative dosimetries were compliant with TG-224. The variations of temporal dosimetry for scanning speed, spot dwell time, and spot transition time were within ± 1 mm/ms, ± 0.2 ms, and ± 0.2 ms, respectively. While the beam-to-beam absolute output on the same day reached up to 2.14%, the day-to-day variation was as high as 9.69%. High correlation between the absolute dose and dose rate fluctuations were identified. The dose rate of the central 5 × 5 cm2 field exhibited variations within 5% of the baseline value (155 Gy/s) during an experimental session. CONCLUSIONS: A comprehensive QA program for FLASH-RT was developed and effectively assesses the performance of a UHDR delivery system. Establishing tolerances to unify standards and offering direction for future advancements in the evolving FLASH-RT field.

Validation and reproducibility of in vivo dosimetry for pencil beam scanned FLASH proton treatment in mice.

PURPOSE: To investigate quality assurance (QA) techniques for in vivo dosimetry and establish its routine uses for proton FLASH small animal experiments with a saturated monitor chamber. METHODS AND MATERIALS: 227 mice were irradiated at FLASH or conventional (CONV) dose rates with a 250 MeV FLASH-capable proton beamline using pencil beam scanning to characterize the proton FLASH effect on abdominal irradiation and examining various endpoints. A 2D strip ionization chamber array (SICA) detector was positioned upstream of collimation and used for in vivo dose monitoring during irradiation. Before each irradiation series, SICA signal was correlated with the isocenter dose at each delivered dose rate. Dose, dose rate, and 2D dose distribution for each mouse were monitored with the SICA detector. RESULTS: Calibration curves between the upstream SICA detector signal and the delivered dose at isocenter had good linearity with minimal R2 values of 0.991 (FLASH) and 0.985 (CONV), and slopes were consistent for each modality. After reassigning mice, standard deviations were less than 1.85 % (FLASH) and 0.83 % (CONV) for all dose levels, with no individual subject dose falling outside a ± 3.6 % range of the designated dose. FLASH fields had a field-averaged dose rate of 79.0 ± 0.8 Gy/s and mean local average dose rate of 160.6 ± 3.0 Gy/s. In vivo dosimetry allowed for the accurate detection of variation between the delivered and the planned dose. CONCLUSION: In vivo dosimetry benefits FLASH experiments through enabling real-time dose and dose rate monitoring allowing mouse cohort regrouping when beam fluctuation causes delivered dose to vary from planned dose.

Acupuncture for cognitive impairment after stroke: A systematic review and meta-analysis.

Objective: Acupuncture as an alternative therapy for post-stroke cognitive impairment (PSCI) has emerged as a research focus. The inclusion of additional external treatments in many previous studies prevents a clear, direct assessment of acupuncture's impact on PSCI. In order to prevent patients from developing hypersensitivity to other treatments and misinterpreting acupuncture's true therapeutic value, this study establish stricter intervention criteria and exclude therapies beyond acupuncture. The review aimed to offering a clearer evaluation of acupuncture's efficacy and safety in PSCI treatment. Methods: This research involved a comprehensive search for randomized controlled trials (RCTs) across eight databases, adhering to the Cochrane Systematic Reviewer's Handbook 5.1.0 for risk-of-bias and quality assessments. A meta-analysis was conducted using RevMan 5.3 software. Results: The inclusion of 18 publications, totaling 1361 patients, was achieved. The meta-analysis demonstrated a significantly higher overall efficacy of acupuncture for PSCI compared to controls (OR = 4.06, 95 % CI 2.86-5.76, Z = 7.82). Notable statistical differences were observed in the Montreal Cognitive Assessment scores (MD = 2.32, 95 % CI 1.68-2.97, Z = 7.10) and the Mini-Mental State Examination scores (MD = 2.02, 95 % CI 1.06-2.98, Z = 4.13) between the groups. Improvements in the Barthel Index scores were noted for the experimental group (MD = 5.70, 95 % CI 4.68-6.72, Z = 10.92). Conclusion: Integrating acupuncture with Western medications offers significant benefits for treating PSCI over Western medications alone. However, the long-term efficacy of acupuncture in PSCI treatment and its potential in reducing recurrence rates remain undetermined. Further high-standard RCTs are essential to explore acupuncture's effectiveness in PSCI treatment more thoroughly.

Prospective evaluation of patient-reported outcomes of invisible ink tattoos for the delivery of external beam radiation therapy: the PREFER trial.

Introduction: Invisible ink tattoos (IITs) avoid cosmetic permanence of visible ink tattoos (VITs) while serving as more reliable landmarks for radiation setup than tattooless setups. This trial evaluated patient-reported preference and feasibility of IIT implementation. Methods and materials: In an IRB-approved, single institution, prospective trial, patients receiving proton therapy underwent IIT-based treatment setup. A survey tool assessed patient preference on tattoos using a Likert scale. Matched patients treated using our institutional standard tattooless setup were identified; treatment times and image guidance requirements were evaluated between tattooless and IIT-based alignment approaches. Distribution differences were estimated using Wilcoxon rank-sum tests or Chi-square tests. Results: Of 94 eligible patients enrolled, median age was 58 years, and 58.5% were female. Most common treatment sites were breast (18.1%), lung (17.0%) and pelvic (14.9%). Patients preferred to receive IITs versus VITs (79.8% pre-treatment and 75.5% post-treatment, respectively). Patients were willing to travel farther from home to avoid VITs versus IITs (p<0.01). Females were willing to travel (45.5% vs. 23.1%; p=0.04) and pay additional money to avoid VITs (34.5% vs. 5.1%; p<0.01). Per-fraction average +treatment time and time from on table/in room to first beam were shorter with IIT-based vs. tattooless setup (12.3min vs. 14.1min; p=0.04 and 24.1min vs. 26.2min; p=0.02, respectively). Discussion: In the largest prospective trial on IIT-based radiotherapy setup to date, we found that patients prefer IITs to VITs. Additionally, IIT-based alignment is an effective and efficient strategy in comparison with tattooless setup. Standard incorporation of IITs for patient setup should be strongly considered.

An Analysis of Positron Emission Tomography Maximum Standard Uptake Value Among Patients With Head and Neck Cancer Receiving Photon and Proton Radiation.

PURPOSE: One main advantage of proton therapy versus photon therapy is its precise radiation delivery to targets without exit dose, resulting in lower dose to surrounding healthy tissues. This is critical, given the proximity of head and neck tumors to normal structures. However, proton planning requires careful consideration of factors, including air-tissue interface, anatomic uncertainties, surgical artifacts, weight fluctuations, rapid tumor response, and daily variations in setup and anatomy, as these heterogeneities can lead to inaccuracies in targeting and creating unwarranted hotspots to a greater extent than photon radiation. In addition, the elevated relative biological effectiveness at the Bragg peak's distal end can also increase hot spots within and outside the target area. METHODS AND MATERIALS: The purpose of this study was to evaluate for a difference in positron emission tomography (PET) standard uptake value (SUV) after definitive treatment, between intensity modulated proton therapy (IMPT) and intensity modulated photon therapy (IMRT). In addition, we compared the biologic dose between PET areas of high and low uptake within the clinical target volume-primary of patients treated with IMPT. This work is assuming that the greater SUV may potentially result in greater toxicities. For the purposes of this short communication, we are strictly focusing on the SUV and do not have correlation with toxicity outcomes. To accomplish this, we compared the 3- and 6-month posttreatment fluorodeoxyglucose PET scans for 100 matched patients with oropharyngeal cancer treated definitively without surgery using either IMPT (n = 50) or IMRT (n = 50). RESULTS: Our study found a significant difference in biologic dose between the high- and low-uptake regions on 3-month posttreatment scans of IMPT. However, this difference did not translate to a significant difference in PET uptake in the clinical target volume-primary at 3 and 6 months' follow-up between patients who received IMPT versus IMRT. CONCLUSIONS: Studies have proposed that proton's greater relative biological effectiveness at the Bragg peak could lead to tissue inflammation. Our study did not corroborate these findings. This study's conclusion underscores the need for further investigations with ultimate correlation with clinical toxicity outcomes.

Serum proteomics identifies novel diagnostic biomarkers for asthma in preschool children.

Background: Asthma is characterized by airway hyperresponsiveness, reversible airway obstruction, and chronic airway inflammation. It is the most common chronic disease in childhood. However, the diagnosis of childhood asthma remains challenging, and there is an urgent need to develop new diagnostic methods. Methods: To identify biomarkers of asthma in children, we adopted the Orbitrap-based data-independent acquisition (DIA) mass spectrometry proteomics method to analyze the serum proteomic signatures of children with acute asthma and convalescent children. Results: We identified 747 proteins in 46 serum samples and 50 differentially expressed proteins (DEPs) that distinguished between asthmatic and healthy children. Next, functional enrichment analysis of the DEPs was conducted, it was indicated that the DEPs were significantly enriched in immune-related and function terms and pathways. Furthermore, we performed statistical analysis and identified MMP14, ABHD12B, PCYOX1, LTBP1, CFHR4, APOA1, IGHG4, ANG and IGFALS proteins as the diagnostic biomarker candidates. Ultimately, a promising asthma diagnostic model for preschool children based on IGFALS was built and evaluated. The area under the curve (AUC) of the IGFALS model was 0.959. Conclusions: In this study, the DIA proteome strategy was used and the largest number of proteins of asthmatic children serum proteomics was identified. The proteomics results showed that the DEPs play the central role of the inflammation-immune mechanism in asthma pathogenesis, suggesting that these proteins may be used in asthma diagnosis, prognosis, or therapy, and suggested biomarkers for asthma of preschool children. In conclusion, our results provide insight into the pathophysiology of asthma. We believe that the diagnostic model will facilitate clinical decision-making regarding asthma in preschool children.

Pencil Beam Scanning Proton Bragg Peak Conformal FLASH in Prostate Cancer Stereotactic Body Radiotherapy.

Bragg peak FLASH radiotherapy (RT) uses a distal tracking method to eliminate exit doses and can achieve superior OAR sparing. This study explores the application of this novel method in stereotactic body radiotherapy prostate FLASH-RT. An in-house platform was developed to enable intensity-modulated proton therapy (IMPT) planning using a single-energy Bragg peak distal tracking method. The patients involved in the study were previously treated with proton stereotactic body radiotherapy (SBRT) using the pencil beam scanning (PBS) technique to 40 Gy in five fractions. FLASH plans were optimized using a four-beam arrangement to generate a dose distribution similar to the conventional opposing beams. All of the beams had a small angle of two degrees from the lateral direction to increase the dosimetry quality. Dose metrics were compared between the conventional PBS and the Bragg peak FLASH plans. The dose rate histogram (DRVH) and FLASH metrics of 40 Gy/s coverage (V40Gy/s) were investigated for the Bragg peak plans. There was no significant difference between the clinical and Bragg peak plans in rectum, bladder, femur heads, large bowel, and penile bulb dose metrics, except for Dmax. For the CTV, the FLASH plans resulted in a higher Dmax than the clinical plans (116.9% vs. 103.3%). For the rectum, the V40Gy/s reached 94% and 93% for 1 Gy dose thresholds in composite and single-field evaluations, respectively. Additionally, the FLASH ratio reached close to 100% after the application of the 5 Gy threshold in composite dose rate assessment. In conclusion, the Bragg peak distal tracking method can yield comparable plan quality in most OARs while preserving sufficient FLASH dose rate coverage, demonstrating that the ultra-high dose technique can be applied in prostate FLASH SBRT.

A review of the clinical introduction of 4D particle therapy research concepts.

Background and purpose: Many 4D particle therapy research concepts have been recently translated into clinics, however, remaining substantial differences depend on the indication and institute-related aspects. This work aims to summarise current state-of-the-art 4D particle therapy technology and outline a roadmap for future research and developments. Material and methods: This review focused on the clinical implementation of 4D approaches for imaging, treatment planning, delivery and evaluation based on the 2021 and 2022 4D Treatment Workshops for Particle Therapy as well as a review of the most recent surveys, guidelines and scientific papers dedicated to this topic. Results: Available technological capabilities for motion surveillance and compensation determined the course of each 4D particle treatment. 4D motion management, delivery techniques and strategies including imaging were diverse and depended on many factors. These included aspects of motion amplitude, tumour location, as well as accelerator technology driving the necessity of centre-specific dosimetric validation. Novel methodologies for X-ray based image processing and MRI for real-time tumour tracking and motion management were shown to have a large potential for online and offline adaptation schemes compensating for potential anatomical changes over the treatment course. The latest research developments were dominated by particle imaging, artificial intelligence methods and FLASH adding another level of complexity but also opportunities in the context of 4D treatments. Conclusion: This review showed that the rapid technological advances in radiation oncology together with the available intrafractional motion management and adaptive strategies paved the way towards clinical implementation.

Enhancement of Stopping Power Ratio (SPR) Estimation Accuracy through Image-Domain Dual-Energy Computer Tomography for Pencil Beam Scanning System: A Simulation Study.

Our study aims to quantify the impact of spectral separation on achieved theoretical prediction accuracy of proton-stopping power when the volume discrepancy between calibration phantom and scanned object is observed. Such discrepancy can be commonly seen in our CSI pediatric patients. One of the representative image-domain DECT models is employed on a virtual phantom to derive electron density and effective atomic number for a total of 34 ICRU standard human tissues. The spectral pairs used in this study are 90 kVp/140 kVp, without and with 0.1 mm to 0.5 mm additional tin filter. The two DECT images are reconstructed via a conventional filtered back projection algorithm (FBP) on simulated noiseless projection data. The best-predicted accuracy occurs at a spectral pair of 90 kVp/140 kVp with a 0.3 mm tin filter, and the root-mean-squared average error is 0.12% for tissue substitutes. The results reveal that the selected image-domain model is sensitive to spectral pair deviation when there is a discrepancy between calibration and scanning conditions. This study suggests that an optimization process may be needed for clinically available DECT scanners to yield the best proton-stopping power estimation.

Advancing knowledge-based intensity modulated proton planning for adaptive treatment of high-risk prostate cancer.

To assess the performance of a knowledge-based planning (KBP) model for generating intensity-modulated proton therapy (IMPT) treatment plans as part of an adaptive radiotherapy (ART) strategy for patients with high-risk prostate cancer. A knowledge-based planning (KBP) model for proton adaptive treatment plan generation was developed based on thirty patient treatment plans utilizing RapidPlanTM PT (Varian Medical Systems, Palo Alto, CA). The model was subsequently validated using an additional eleven patient cases. All patients in the study were administered a prescribed dose of 70.2 Gy to the prostate and seminal vesicle (CTV70.2), along with 46.8 Gy to the pelvic lymph nodes (CTV46.8) through simultaneous integrated boost (SIB) technique. To assess the quality of the validation knowledge-based proton plans (KBPPs), target coverage and organ-at-risk (OAR) dose-volume constraints were compared against those of clinically used expert plans using paired t-tests. The KBP model training statistics (R2) (mean ± SD, 0.763 ± 0.167, range, 0.406 to 0.907) and χ² values (1.162 ± 0.0867, 1.039-1.253) indicate acceptable model training quality. Moreover, the average total treatment planning optimization and calculation time for adaptive plan generation is approximately 10 minutes. The CTV70.2 D98% for the KBPPs (mean ± SD, 69.1 ± 0.08 Gy) and expert plans (69.9 ± 0.04 Gy) shows a significant difference (p < 0.05) but are both within 1.1 Gy of the prescribed dose which is clinically acceptable. While the maximum dose for some organs-at-risk (OARs) such as the bladder and rectum is generally higher in the KBPPs, the doses still fall within clinical constraints. Among all the OARs, most of them received comparable results to the expert plan, except the cauda equina Dmax, which shows statistical significance and was lower in the KBPPs than in expert plans (48.5 ± 0.06 Gy vs 49.3 ± 0.05 Gy). The generated KBPPs were clinically comparable to manually crafted plans by expert treatment planners. The adaptive plan generation process was completed within an acceptable timeframe, offering a quick same-day adaptive treatment option. Our study supports the integration of KBP as a crucial component of an ART strategy, including maintaining plan consistency, improving quality, and enhancing efficiency. This advancement in speed and adaptability promises more precise treatment in proton ART.

Proton pencil beam scanning craniospinal irradiation (CSI) with a single posterior brain beam: Dosimetry and efficiency.

This study explores the feasibility and potential dosimetric and time efficiency benefit of proton Pencil Beam Scanning (PBS) craniospinal irradiation with a single posterior-anterior (SPA) brain field. The SPA approach was compared to our current clinical protocol using Bilateral Posterior Oblique brain fields (BPO). Ten consecutive patients were simulated in the head-first supine position on a long BOS frame and scanned using 3 mm CT slice thickness. A customized thermoplastic mask immobilized the patient's head, neck, and shoulders. A vac-lock was used to secure the legs. PBS proton plans were robustly optimized with 3mm setup errors and 3.5% range uncertainties in the Eclipse V15.6 treatment planning system (n = 12 scenarios). In order to achieve a smooth gradient dose match at the junction area, at least 5 cm overlap region was maintained between the segments and 5 mm uncertainty along the cranial-cauda direction was applied to each segment independently as additional robust optimization scenarios. The brain doses were planned by SPA or BPO fields. All spine segments were planned with a single PA field. Dosimetric differences between the BPO and SPA approaches were compared, and the treatment efficiency was analyzed according to timestamps of beam delivery. Results: The maximum brain dose increases to 111.1 ± 2.1% for SPA vs. 109.0 ± 1.7% for BPO (p < 0.01). The dose homogeneity index (D5/D95) in brain CTV was comparable between techniques (1.037 ± 0.010 for SPA and 1.033 ± 0.008 for BPO). Lens received lower maximum doses by 2.88 ± 1.58 Gy (RBE) (left) and 2.23 ± 1.37 Gy (RBE) (right) in the SPA plans (p < 0.01). No significant cochlea dose change was observed. SPA reduced the treatment time by more than 4 minutes on average and ranged from 2 to 10 minutes, depending on the beam waiting and allocation time. SPA is dosimetrically comparable to BPO, with reduced lens doses at the cost of slightly higher dose inhomogeneity and hot spots. Implementation of SPA is feasible and can help to improve the treatment efficiency of PBS CSI treatment.

Multi-institutional consensus on machine QA for isochronous cyclotron-based systems delivering ultra-high dose rate (FLASH) pencil beam scanning proton therapy in transmission mode.

BACKGROUND: The first clinical trials to assess the feasibility of FLASH radiotherapy in humans have started (FAST-01, FAST-02) and more trials are foreseen. To increase comparability between trials it is important to assure treatment quality and therefore establish a standard for machine quality assurance (QA). Currently, the AAPM TG-224 report is considered as the standard on machine QA for proton therapy, however, it was not intended to be used for ultra-high dose rate (UHDR) proton beams, which have gained interest due to the observation of the FLASH effect. PURPOSE: The aim of this study is to find consensus on practical guidelines on machine QA for UHDR proton beams in transmission mode in terms of which QA is required, how they should be done, which detectors are suitable for UHDR machine QA, and what tolerance limits should be applied. METHODS: A risk assessment to determine the gaps in the current standard for machine QA was performed by an international group of medical physicists. Based on that, practical guidelines on how to perform machine QA for UHDR proton beams were proposed. RESULTS: The risk assessment clearly identified the need for additional guidance on temporal dosimetry, addressing dose rate (constancy), dose spillage, and scanning speed. In addition, several minor changes from AAPM TG-224 were identified; define required dose rate levels, the use of clinically relevant dose levels, and the use of adapted beam settings to minimize activation of detector and phantom materials or to avoid saturation effects of specific detectors. The final report was created based on discussions and consensus. CONCLUSIONS: Consensus was reached on what QA is required for UHDR scanning proton beams in transmission mode for isochronous cyclotron-based systems and how they should be performed. However, the group discussions also showed that there is a lack of high temporal resolution detectors and sufficient QA data to set appropriate limits for some of the proposed QA procedures.