Evaluation of specific RBE in different cells of hippocampus under high-dose proton irradiation in rats.

The study aimed to determine the specific relative biological effectiveness (RBE) of various cells in the hippocampus following proton irradiation. Sixty Sprague-Dawley rats were randomly allocated to 5 groups receiving 20 or 30 Gy of proton or photon irradiation. Pathomorphological neuronal damage in the hippocampus was assessed using Hematoxylin-eosin (HE) staining. The expression level of NeuN, Nestin, Caspase-3, Olig2, CD68 and CD45 were determined by immunohistochemistry (IHC). The RBE range established by comparing the effects of proton and photon irradiation at equivalent biological outcomes. Proton20Gy induced more severe damage to neurons than photon20Gy, but showed no difference compared to photon30Gy. The RBE of neuron was determined to be 1.65. Similarly, both proton20Gy and proton30Gy resulted in more inhibition of oligodendrocytes and activation of microglia in the hippocampal regions than photon20Gy and photon30Gy. However, the expression of Olig2 was higher and CD68 was lower in the proton20Gy group than in the photon30Gy group. The RBE of oligodendrocyte and microglia was estimated to be between 1.1 to 1.65. For neural stem cells (NSCs) and immune cells, there were no significant difference in the expression of Nestin and CD45 between proton and photon irradiation (both 20 and 30 Gy). Therefore, the RBE for NSCs and immune cell was determined to be 1.1. These findings highlight the varying RBE values of different cells in the hippocampus in vivo. Moreover, the actual RBE of the hippocampus may be higher than 1.1, suggesting that using as RBE value of 1.1 in clinical practice may underestimate the toxicities induced by proton radiation.

Dosimetric feasibility study ("proof of concept") of refractory ventricular tachycardia radioablation using proton minibeams.

PURPOSE: Preclinical data demonstrated that the use of proton minibeam radiotherapy reduces the risk of toxicity in healthy tissue. Ventricular tachycardia radioablation is an area under clinical investigation in proton beam therapy. We sought to simulate a ventricular tachycardia radioablation with proton minibeams and to demonstrate that it was possible to obtain a homogeneous coverage of an arrhythmogenic cardiac zone with this technique. MATERIAL AND METHODS: An arrhythmogenic target volume was defined on the simulation CT scan of a patient, localized in the lateral wall of the left ventricle. A dose of 25Gy was planned to be delivered by proton minibeam radiotherapy, simulated using a Monte Carlo code (TOPAS v.3.7) with a collimator of 19 0.4 mm-wide slits spaced 3mm apart. The main objective of the study was to obtain a plan ensuring at least 93% of the prescription dose in 93% of the planning target volume without exceeding 110% of the prescribed dose in the planning target volume. RESULTS: The average dose in the planning treatment volume in proton minibeam radiotherapy was 25.12Gy. The percentage of the planning target volume receiving 93% (V93%), 110% (V110%), and 95% (V95%) of the prescribed dose was 94.25%, 0%, and 92.6% respectively. The lateral penumbra was 6.6mm. The mean value of the peak-to-valley-dose ratio in the planning target volume was 1.06. The mean heart dose was 2.54Gy versus 5.95Gy with stereotactic photon beam irradiation. CONCLUSION: This proof-of-concept study shows that proton minibeam radiotherapy can achieve a homogeneous coverage of an arrhythmogenic cardiac zone, reducing the dose at the normal tissues. This technique, ensuring could theoretically reduce the risk of late pulmonary and breast fibrosis, as well as cardiac toxicity as seen in previous biological studies in proton minibeam radiotherapy.

An artificial neural network based approach for predicting the proton beam spot dosimetric characteristics of a pencil beam scanning technique.

Utilising Machine Learning (ML) models to predict dosimetric parameters in pencil beam scanning proton therapy presents a promising and practical approach. The study developed Artificial Neural Network (ANN) models to predict proton beam spot size and relative positional errors using 9000 proton spot data. The irradiation log files as input variables and corresponding scintillation detector measurements as the label values. The ANN models were developed to predict six variables: spot size in thex-axis,y-axis, major axis, minor axis, and relative positional errors in thex-axis andy-axis. All ANN models used a Multi-layer perception (MLP) network using one input layer, three hidden layers, and one output layer. Model performance was validated using various statistical tools. The log file recorded spot size and relative positional errors, which were compared with scintillator-measured data. The Root Mean Squared Error (RMSE) values for the x-spot and y-spot sizes were 0.356 mm and 0.362 mm, respectively. Additionally, the maximum variation for the x-spot relative positional error was 0.910 mm, while for the y-spot, it was 1.610 mm. The ANN models exhibit lower prediction errors. Specifically, the RMSE values for spot size prediction in the x, y, major, and minor axes are 0.053 mm, 0.049 mm, 0.053 mm, and 0.052 mm, respectively. Additionally, the relative spot positional error prediction model for the x and y axes yielded maximum errors of 0.160 mm and 0.170 mm, respectively. The normality of models was validated using the residual histogram and Q-Q plot. The data over fit, and bias were tested using K (k = 5) fold cross-validation, and the maximum RMSE value of the K fold cross-validation among all the six ML models was less than 0.150 mm (R-Square 0.960). All the models showed excellent prediction accuracy. Accurately predicting beam spot size and positional errors enhances efficiency in routine dosimetric checks.

Tuning spatially fractionated radiotherapy dose profiles using the moiré effect.

Spatially Fractionated Radiotherapy (SFRT) has demonstrated promising potential in cancer treatment, combining the advantages of reduced post-radiation effects and enhanced local control rates. Within this paradigm, proton minibeam radiotherapy (pMBRT) was suggested as a new treatment modality, possibly producing superior normal tissue sparing to conventional proton therapy, leading to improvements in patient outcomes. However, an effective and convenient beam generation method for pMBRT, capable of implementing various optimum dose profiles, is essential for its real-world application. Our study investigates the potential of utilizing the moiré effect in a dual collimator system (DCS) to generate pMBRT dose profiles with the flexibility to modify the center-to-center distance (CTC) of the dose distribution in a technically simple way.We employ the Geant4 Monte Carlo simulations tool to demonstrate that the angle between the two collimators of a DCS can significantly impact the dose profile. Varying the DCS angle from 10 ∘ to 50 ∘ we could cover CTC ranging from 11.8 mm to 2.4 mm, respectively. Further investigations reveal the substantial influence of the multi-slit collimator's (MSC) physical parameters on the spatially fractionated dose profile, such as period (CTC), throughput, and spacing between MSCs. These findings highlight opportunities for precision dose profile adjustments tailored to specific clinical scenarios.The DCS capacity for rapid angle adjustments during the energy transition stages of a spot scanning system can facilitate dynamic alterations in the irradiation profile, enhancing dose contrast in normal tissues. Furthermore, its unique attribute of spatially fractionated doses in both lateral directions could potentially improve normal tissue sparing by minimizing irradiated volume. Beyond the realm of pMBRT, the dual MSC system exhibits remarkable versatility, showing compatibility with different types of beams (X-rays and electrons) and applicability across various SFRT modalities.Our study illuminates the dual MSC system's potential as an efficient and adaptable tool in the refinement of pMBRT techniques. By enabling meticulous control over irradiation profiles, this system may expedite advancements in clinical and experimental applications, thereby contributing to the evolution of SFRT strategies.

Influence of Post-radiation Ocular Surface Disorder on Ocular Surgery: A Case Report and Review of the Literature.

BACKGROUND: Ocular surface disorder after ocular radiation therapy, even though commonly reported, is often overlooked. Any delay in diagnosis may lead to complications that threaten vision. The presented case highlights the clinical outcome of a severe post-radiation disorder of the ocular surface, the importance of intensive therapy, and the limitations of further surgical interventions. CASE PRESENTATION: A 34-year-old woman was referred for a second opinion due to a years-long history of pain and redness in her right eye (OD) after proton beam therapy for recurrent iris melanoma. The patient then developed post-radiation retinopathy with macula edema, secondary glaucoma, cataract, as well as a severe ocular surface disorder with corneal decompensation and band keratopathy. Several surgical treatments have been attempted, including phacoemulsification with IOL implantation and trabeculectomy with mitomycin C. Due to refractory glaucoma, Baerveldt glaucoma drainage was then necessary. Given the worsening clinical presentation of post-radiation ocular surface disorder with progressing band keratopathy, the possibility of penetrating keratoplasty (PKP) was discussed. CONCLUSION: The continuous worsening of clinical symptoms of the disorder of the ocular surface after proton beam radiotherapy can be the result of a post-radiation syndrome. Gradual expansion of ischemia, vasculitis, and inflammatory mediators compresses the retinal tissue, leading to recurrent macular edema as well as to secondary glaucoma and corneal decompensation. Band keratopathy is occasionally noted and seems to result from severe post-radiation disorder of the ocular surface. However, PKP would typically be indicated in cases of corneal perforation, uncontrolled infectious keratitis, or for improving vision in the presence of corneal opacification, none of which applied to our patient. Furthermore, post-radiation keratopathy implies compromised corneal stromal lymphogenesis and angiogenesis, both of which are now considered essential conditions for allograft rejection. Moreover, a previously performed Baerveldt glaucoma drainage surgery can affect the survival rate of the endothelial cells of the recipient cornea. Therefore, a penetrating or endothelial keratoplasty should be viewed as a high-risk procedure. In this instance, the rigorous treatment of the severe ocular surface disorder was crucial. We managed our patient's complex situation by following the latest guidelines set by the Tear Film & Ocular Surface Society and aimed to alleviate the symptoms as effectively as possible. In conclusion, careful decision-making regarding surgical treatment options should be considered, taking into account the complexities and potential risks involved.

First experimental time-of-flight-based proton radiography using low gain avalanche diodes.

Objective.Ion computed tomography (iCT) is an imaging modality for the direct determination of the relative stopping power (RSP) distribution within a patient's body. Usually, this is done by estimating the path and energy loss of ions traversing the scanned volume utilising a tracking system and a separate residual energy detector. This study, on the other hand, introduces the first experimental study of a novel iCT approach based on time-of-flight (TOF) measurements, the so-called Sandwich TOF-iCT concept, which in contrast to any other iCT systems, does not require a residual energy detector for the RSP determination.Approach.A small Sandwich TOF-iCT demonstrator was built based on low gain avalanche diodes (LGADs), which are 4D-tracking detectors that allow to simultaneously measure the particle position and time-of-arrival with a precision better than 100µm and 100 ps, respectively. Using this demonstrator, the material and energy-dependent TOF was measured for several homogeneous PMMA slabs in order to calibrate the acquired TOF against the corresponding water equivalent thickness (WET). With this calibration, two proton radiographs (pRads) of a small aluminium stair phantom were recorded at MedAustron using 83 MeV and 100.4 MeV protons.Main results.Due to the simplified WET calibration models used in this very first experimental study of this novel approach, the difference between the measured and theoretical WET ranged between 37.09% and 51.12%. Nevertheless, the first TOF-based pRad was successfully recorded showing that LGADs are suitable detector candidates for Sandwich TOF-iCT.Significance.While the system parameters and WET estimation algorithms require further optimization, this work was an important first step to realize Sandwich TOF-iCT. Due to its compact and cost-efficient design, Sandwich TOF-iCT has the potential to make iCT more feasible and attractive for clinical application, which, eventually, could enhance the treatment planning quality.

Study of a plastic scintillating plate-based quality assurance system for pencil beam scanning proton beams.

INTRODUCTION: The purpose of this study was to evaluate a plastic scintillating plate-based beam monitoring system to perform quality assurance (QA) measurements in pencil beam scanning proton beam. METHODS: Single spots and scanned fields were measured with the high-resolution dosimetry system, consisting of a plastic scintillation plate coupled to a camera in a dark box at the isocenter. The measurements were taken at 110-190 MeV beam energies with 30° gantry angle intervals at each energy. Spot positions were determined using the plastic scintillating plate-based dosimetry system at the isocenter for 70-230 MeV beam energies with 30° gantry angle intervals. The effect of gantry angle on dose distribution was also assessed by determining the scanning pattern for daily QA and 25 fields treated with intensity-modulated proton therapy. RESULTS: Spot size, field flatness, and field symmetry of plastic scintillating plate-based dosimetry system were consistent with EBT3 at all investigated energies and angles. In all investigated energies and angles, the spot size measured was ±10% of the average size of each energy, the spot position measured was within ±2 mm, field flatness was within ±2%, and field symmetry was within ±1%. The mean gamma passing rates with the 3%/3 mm gamma criterion of the scanning pattern and 25 fields were 99.2% and 99.8%, respectively. CONCLUSIONS: This system can be effective for QA determinations of spot size, spot position, field flatness, and field symmetry over 360° of gantry rotation in a time- and cost-effective manner, with spatial resolution comparable to that of EBT3 film.

Benchmarking proton RBE models.

Objective.To biologically optimise proton therapy, models which can accurately predict variations in proton relative biological effectiveness (RBE) are essential. Current phenomenological models show large disagreements in RBE predictions, due to different model assumptions and differences in the data to which they were fit. In this work, thirteen RBE models were benchmarked against a comprehensive proton RBE dataset to evaluate predictions when all models are fit using the same data and fitting techniques, and to assess the statistical robustness of the models.Approach.Model performance was initially evaluated by fitting to the full dataset, and then a cross-validation approach was applied to assess model generalisability and robustness. The impact of weighting the fit and the choice of biological endpoint (either single or multiple survival levels) was also evaluated.Main results.Fitting the models to a common dataset reduced differences between their predictions, however significant disagreements remained due to different underlying assumptions. All models performed poorly under cross-validation in the weighted fits, suggesting that some uncertainties on the experimental data were significantly underestimated, resulting in over-fitting and poor performance on unseen data. The simplest model, which depends linearly on the LET but has no tissue or dose dependence, performed best for a single survival level. However, when fitting to multiple survival levels simultaneously, more complex models with tissue dependence performed better. All models had significant residual uncertainty in their predictions compared to experimental data.Significance.This analysis highlights that poor quality of error estimation on the dose response parameters introduces substantial uncertainty in model fitting. The significant residual error present in all approaches illustrates the challenges inherent in fitting to large, heterogeneous datasets and the importance of robust statistical validation of RBE models.

The impact of motion on onboard MRI-guided pencil beam scanned proton therapy treatments.

Objective.Online magnetic resonance imaging (MRI) guidance could be especially beneficial for pencil beam scanned (PBS) proton therapy of tumours affected by respiratory motion. For the first time to our knowledge, we investigate the dosimetric impact of respiratory motion on MRI-guided proton therapy compared to the scenario without magnetic field.Approach.A previously developed analytical proton dose calculation algorithm accounting for perpendicular magnetic fields was extended to enable 4D dose calculations. For two geometrical phantoms and three liver and two lung patient cases, static treatment plans were optimised with and without magnetic field (0, 0.5 and 1.5 T). Furthermore, plans were optimised using gantry angle corrections (0.5 T +5° and 1.5 T +15°) to reproduce similar beam trajectories compared to the 0 T reference plans. The effect of motion was then considered using 4D dose calculations without any motion mitigation and simulating 8-times volumetric rescanning, with motion for the patient cases provided by 4DCT(MRI) data sets. Each 4D dose calculation was performed for different starting phases and the CTV dose coverageV95%and homogeneityD5%-D95%were analysed.Main results.For the geometrical phantoms with rigid motion perpendicular to the beam and parallel to the magnetic field, a comparable dosimetric effect was observed independent of the magnetic field. Also for the five 4DCT(MRI) cases, the influence of motion was comparable for all magnetic field strengths with and without gantry angle correction. On average, the motion-induced decrease in CTVV95%from the static plan was 17.0% and 18.9% for 1.5 T and 0.5 T, respectively, and 19.9% without magnetic field.Significance.For the first time, this study investigates the combined impact of magnetic fields and respiratory motion on MR-guided proton therapy. The comparable dosimetric effects irrespective of magnetic field strength indicate that the effects of motion for future MR-guided proton therapy may not be worse than for conventional PBS proton therapy.

Study on induced radioactivity and individual dose evaluation in Gantry room for Varian ProBeam Proton Therapy System.

Proton therapy has emerged as an advantageous modality for tumor radiotherapy due to its favorable physical and biological properties. However, this therapy generates induced radioactivity through nuclear reactions between the primary beam, secondary particles, and surrounding materials. This study focuses on systematically investigating the induced radioactivity in the gantry room during pencil beam scanning, utilizing both experimental measurements and Monte Carlo simulations. Results indicate that patients are the primary source of induced radioactivity, predominantly producing radionuclides such as 11C, 13N, and 15O. Long-term irradiation primarily generates radionuclides like 22Na, 24Na, and 54Mn etc. Additionally, this study estimates the individual doses received by medical workers in the gantry room, the irradiation dose for patient escorts, and the additional dose to patients from residual radiation. Finally, the study offers recommendations to minimize unnecessary irradiation doses to medical workers, patient escorts, and patients.

Comparing interplay effects in scanned proton therapy of lung cancer: Free breathing with various layer and volume rescanning versus respiratory gating with different gate widths.

PURPOSE: We investigated interplay effects and treatment time (TT) in scanned proton therapy for lung cancer patients. We compared free-breathing (FB) approaches with multiple rescanning strategies and respiratory-gating (RG) methods with various gating widths to identify the superior irradiation technique. METHODS: Plans were created with 4/1, 2/2, and 1/4 layered/volume rescans of FB (L4V1, L2V2, and L1V4), and 50%, 30%, and 10% gating widths of the total respiratory curves (G50, G30, and G10) of the RG plans with L4V1. We calculated 4-dimensional dynamic doses assuming a constant sinusoidal curve for six irradiation methods. The reconstructed doses per fraction were compared with planned doses in terms of dose differences in 99% clinical-target-volume (CTV) (ΔD99%), near-maximum dose differences (ΔD2%) at organs-at-risk (OARs), and TT. RESULTS: The mean/minimum CTV ΔD99% values for FB were -1.0%/-4.9%, -0.8%/-4.3%, and -0.1%/-1.0% for L4V1, L2V2, and L1V4, respectively. Those for RG were -0.3%/-1.7%, -0.1%/-1.0%, and 0.0%/-0.5% for G50, G30, and G10, respectively. The CTV ΔD99% of the RGs with less than 50% gate width and the FBs of L1V4 were within the desired tolerance (±3.0%), and the OARs ΔD2% for RG were lower than those for FB. The mean TTs were 90, 326, 824, 158, 203, and 422 s for L4V1, L2V2, L1V4, G50, G30, and G10, respectively. CONCLUSIONS: FB (L4V1) is the most efficient treatment, but not necessarily the optimal choice due to interplay effects. To satisfy both TT extensions and interplay, RG with a gate width as large as possible within safety limits is desirable.

Using the gamma-index analysis for inter-fractional comparison of in-beam PET images for head-and-neck treatment monitoring in proton therapy: A Monte Carlo simulation study.

GOAL: In-beam Positron Emission Tomography (PET) is a technique for in-vivo non-invasive treatment monitoring for proton therapy. To detect anatomical changes in patients with PET, various analysis methods exist, but their clinical interpretation is problematic. The goal of this work is to investigate whether the gamma-index analysis, widely used for dose comparisons, is an appropriate tool for comparing in-beam PET distributions. Focusing on a head-and-neck patient, we investigate whether the gamma-index map and the passing rate are sensitive to progressive anatomical changes. METHODS/MATERIALS: We simulated a treatment course of a proton therapy patient using FLUKA Monte Carlo simulations. Gradual emptying of the sinonasal cavity was modeled through a series of artificially modified CT scans. The in-beam PET activity distributions from three fields were evaluated, simulating a planar dual head geometry. We applied the 3D-gamma evaluation method to compare the PET images with a reference image without changes. Various tolerance criteria and parameters were tested, and results were compared to the CT-scans. RESULTS: Based on 210 MC simulations we identified appropriate parameters for the gamma-index analysis. Tolerance values of 3 mm/3% and 2 mm/2% were suited for comparison of simulated in-beam PET distributions. The gamma passing rate decreased with increasing volume change for all fields. CONCLUSION: The gamma-index analysis was found to be a useful tool for comparing simulated in-beam PET images, sensitive to sinonasal cavity emptying. Monitoring the gamma passing rate behavior over the treatment course is useful to detect anatomical changes occurring during the treatment course.

Development of porous structure for broadening Bragg-peak in scanning carbon-ion radiotherapy: Monte Carlo simulation and experimental validation.

PURPOSE: The present study aimed to develop a porous structure with plug-ins (PSP) to broaden the Bragg peak width (BPW, defined as the distance in water between the proximal and distal 80% dose) of the carbon ion beam while maintaining a sharp distal falloff width (DFW, defined as the distance along the beam axis where the dose in water reduces from 80% to 20%). METHODS: The binary voxel models of porous structure (PS) and PSP were established in the Monte Carlo code FLUKA and the corresponding physical models were manufactured by 3D printing. Both experiment and simulation were performed for evaluating the modulation capacity of PS and PSP. BPWs and DFWs derived from each integral depth dose curves were compared. Fluence homogeneity of 430 MeV/u carbon-ion beam passing through the PSP was recorded by analyzing radiochromic films at six different locations downstream the PSP in the experiment. Additionally, by changing the beam spot size and incident position on the PSP, totally 48 different carbon-ion beams were simulated and corresponding deviations of beam metrics were evaluated to test the modulating stability of PSP. RESULTS: According to the measurement data, the use of PSP resulted in an average increase of 0.63 mm in BPW and a decrease of 0.74 mm in DFW compared to PS. The 2D radiation field inhomogeneities were lower than 3 % when the beam passing through a ≥ 10 cm PMMA medium. Furthermore, employing a spot size of ≥ 6 mm ensures that beam metric deviations, including BPW, DFW, and range, remain within a deviation of 0.1 mm across various incident positions. CONCLUSION: The developed PSP demonstrated its capability to effectively broaden the BPW of carbon ion beams while maintaining a sharp DFW comparing to PS. The superior performance of PSP, indicates its potential for clinical use in the future.

Fano cavity test and investigation of the response of the Roos chamber irradiated by proton beams in perpendicular magnetic fields up to 1 T.

Objective. The aim of this work is to investigate the response of the Roos chamber (type 34001) irradiated by clinical proton beams in magnetic fields.Approach. At first, a Fano test was implemented in Monte Carlo software package GATE version 9.2 (based on Geant4 version 11.0.2) using a cylindrical slab geometry in a magnetic field up to 1 T. In accordance to an experimental setup (Fuchset al2021), the magnetic field correction factorskQB⃗of the Roos chamber were determined at different energies up to 252 MeV and magnetic field strengths up to 1 T, by separately simulating the ratios of chamber signalsMQ/MQB⃗,without and with magnetic field, and the dose-conversion factorsDw,QB⃗/Dw,Qin a small cylinder of water, with and without magnetic field. Additionally, detailed simulations were carried out to understand the observed magnetic field dependence.Main results. The Fano test was passed with deviations smaller than 0.25% between 0 and 1 T. The ratios of the chamber signals show both energy and magnetic field dependence. The maximum deviation of the dose-conversion factors from unity of 0.22% was observed at the lowest investigated proton energy of 97.4 MeV andB⃗= 1 T. The resultingkQB⃗factors increase initially with the applied magnetic field and decrease again after reaching a maximum at around 0.5 T; except for the lowest 97.4 MeV beam that show no observable magnetic field dependence. The deviation from unity of the factors is also larger for higher proton energies, where the maximum lies at 1.0035(5), 1.0054(7) and 1.0069(7) for initial energies ofE0= 152, 223.4 and 252 MeV, respectively.Significance. Detailed Monte Carlo studies showed that the observed effect can be mainly attributed to the differences in the transport of electrons produced both outside and inside of the air cavity in the presence of a magnetic field.

Hybrid-supervised deep learning for domain transfer 3D protoacoustic image reconstruction.

Objective. Protoacoustic imaging showed great promise in providing real-time 3D dose verification of proton therapy. However, the limited acquisition angle in protoacoustic imaging induces severe artifacts, which impairs its accuracy for dose verification. In this study, we developed a hybrid-supervised deep learning method for protoacoustic imaging to address the limited view issue.Approach. We proposed a Recon-Enhance two-stage deep learning method. In the Recon-stage, a transformer-based network was developed to reconstruct initial pressure maps from raw acoustic signals. The network is trained in a hybrid-supervised approach, where it is first trained using supervision by the iteratively reconstructed pressure map and then fine-tuned using transfer learning and self-supervision based on the data fidelity constraint. In the enhance-stage, a 3D U-net is applied to further enhance the image quality with supervision from the ground truth pressure map. The final protoacoustic images are then converted to dose for proton verification.Main results. The results evaluated on a dataset of 126 prostate cancer patients achieved an average root mean squared errors (RMSE) of 0.0292, and an average structural similarity index measure (SSIM) of 0.9618, out-performing related start-of-the-art methods. Qualitative results also demonstrated that our approach addressed the limit-view issue with more details reconstructed. Dose verification achieved an average RMSE of 0.018, and an average SSIM of 0.9891. Gamma index evaluation demonstrated a high agreement (94.7% and 95.7% for 1%/3 mm and 1%/5 mm) between the predicted and the ground truth dose maps. Notably, the processing time was reduced to 6 s, demonstrating its feasibility for online 3D dose verification for prostate proton therapy.Significance. Our study achieved start-of-the-art performance in the challenging task of direct reconstruction from radiofrequency signals, demonstrating the great promise of PA imaging as a highly efficient and accurate tool forinvivo3D proton dose verification to minimize the range uncertainties of proton therapy to improve its precision and outcomes.

Proton therapy induces a local microglial neuroimmune response.

BACKGROUND AND PURPOSE: Although proton therapy is increasingly being used in the treatment of paediatric and adult brain tumours, there are still uncertainties surrounding the biological effect of protons on the normal brain. Microglia, the brain-resident macrophages, have been shown to play a role in the development of radiation-induced neurotoxicity. However, their molecular and hence functional response to proton irradiation remains unknown. This study investigates the effect of protons on microglia by comparing the effect of photons and protons as well as the influence of age and different irradiated volumes. MATERIALS AND METHODS: Rats were irradiated with 14 Gy to the whole brain with photons (X-rays), plateau protons, spread-out Bragg peak (SOBP) protons or to 50 % anterior, or 50 % posterior brain sub-volumes with plateau protons. RNA sequencing, validation of microglial priming gene expression using qPCR and high-content imaging analysis of microglial morphology were performed in the cortex at 12 weeks post irradiation. RESULTS: Photons and plateau protons induced a shared transcriptomic response associated with neuroinflammation. This response was associated with a similar microglial priming gene expression signature and distribution of microglial morphologies. Expression of the priming gene signature was less pronounced in juvenile rats compared to adults and slightly increased in rats irradiated with SOBP protons. High-precision partial brain irradiation with protons induced a local microglial priming response and morphological changes. CONCLUSION: Overall, our data indicate that the brain responds in a similar manner to photons and plateau protons with a shared local upregulation of microglial priming-associated genes, potentially enhancing the immune response to subsequent inflammatory challenges.

A multicenter high-quality data registry for advanced proton therapy approaches: the POWER registry.

BACKGROUND: Paucity and low evidence-level data on proton therapy (PT) represent one of the main issues for the establishment of solid indications in the PT setting. Aim of the present registry, the POWER registry, is to provide a tool for systematic, prospective, harmonized, and multidimensional high-quality data collection to promote knowledge in the field of PT with a particular focus on the use of hypofractionation. METHODS: All patients with any type of oncologic disease (benign and malignant disease) eligible for PT at the European Institute of Oncology (IEO), Milan, Italy, will be included in the present registry. Three levels of data collection will be implemented: Level (1) clinical research (patients outcome and toxicity, quality of life, and cost/effectiveness analysis); Level (2) radiological and radiobiological research (radiomic and dosiomic analysis, as well as biological modeling); Level (3) biological and translational research (biological biomarkers and genomic data analysis). Endpoints and outcome measures of hypofractionation schedules will be evaluated in terms of either Treatment Efficacy (tumor response rate, time to progression/percentages of survivors/median survival, clinical, biological, and radiological biomarkers changes, identified as surrogate endpoints of cancer survival/response to treatment) and Toxicity. The study protocol has been approved by the IEO Ethical Committee (IEO 1885). Other than patients treated at IEO, additional PT facilities (equipped with Proteus®ONE or Proteus®PLUS technologies by IBA, Ion Beam Applications, Louvain-la-Neuve, Belgium) are planned to join the registry data collection. Moreover, the registry will be also fully integrated into international PT data collection networks.

Quality of life in patients with nasopharyngeal carcinoma receiving IMRT vs IMPT: a multicenter prospective longitudinal study.

PURPOSE: Nasopharyngeal carcinoma (NPC) patients may experience symptom distress and depression during and after radiation therapy, which negatively impacts quality of life (QOL). We sought to identify trajectories of symptom distress, depression, social support, and QOL in patients with NPC receiving intensity-modulated radiation therapy (IMRT) vs intensity-modulated proton therapy (IMPT). METHODS: A multicenter prospective longitudinal study recruited NPC patients from two leading medical centers in Taiwan. The 121 NPC patients were followed from before RT (T0), at 4 weeks after beginning RT (T1), at 6 weeks of RT or the end of treatment (T2), and at 4 weeks post-RT (T3). Generalized estimating equation analysis was used to identify the factors related to QOL. RESULTS: Patients' symptom distress and depression increased from T0, peaked at T2, and decreased at T3. Physical-QOL and psychosocial-QOL decreased from T0 to T2, then increased by T3. Patients who had early-stage cancer, received a lower RT dose, had less symptom distress, and had less depression were more likely to have better QOL. Greater physical-QOL was associated with IMPT receipt, higher education level, early cancer stage, lower radiation dose, less symptom distress, and less depression. Patients who had good physical performance, received a lower radiation dose, had less symptom distress, and had less depression were more likely to have better psychosocial-QOL. CONCLUSION: Radiation dose, symptom distress, and depression were the most important factors affecting QOL in patients with NPC. Understanding the factors associated with the trajectory of QOL can guide care during radiation treatment.