Deformable vector fields warping for modelling of irregular breathing.

Purpose 4D computed tomography (4DCT) is the clinical standard to image organ motion in radiotherapy, although it is limited in imaging breathing variability. We propose a method to transfer breathing motion across longitudinal imaging datasets to include intra-patient variability and verify its performance in lung cancer patients. Methods Five repeated control 4DCTs for 6 non-small cell lung cancer patients were combined into multi-breath datasets (m4DCT) by merging stages of deformable image registration to isolate respiratory motion. The displacement of the centre of mass of the primary tumour and its volume changes were evaluated to quantify intra-patient differences. Internal target volumes defined on the m4DCT were compared with those conventionally drawn on the 4DCT. Results Motion analysis suggests no discontinuity at the junction between successive breaths, confirming the method's ability to merge repeated imaging into a continuum. Motion (variability) is primarily in superior-inferior direction and goes from 14.4 mm (8.7 mm) down to 0.1 mm (0.6 mm), respectively for tumours located in the lower lobes or most apical ones. On average, up to 65% and 74% of the tumour volume was subject to expansion or contraction in the inhalation and exhalation phases. These variations lead to an enlargement of the ITV up to 8% of its volume in our dataset. Conclusion 4DCT can be extended to model variable breathing motion by adding synthetic phases from multiple time-resolved images. The inclusion of this improved knowledge of patients' breathing allows better definition of treatment volumes and their margins for radiation therapy. .

Quantification of deformable image registration uncertainties for dose accumulation on head and neck cancer proton treatments.

PURPOSE: Head and neck cancer (HNC) patients in radiotherapy require adaptive treatment plans due to anatomical changes. Deformable image registration (DIR) is used in adaptive radiotherapy, e.g. for deformable dose accumulation (DDA). However, DIR's ill-posedness necessitates addressing uncertainties, often overlooked in clinical implementations. DIR's further clinical implementation is hindered by missing quantitative commissioning and quality assurance tools. This study evaluates one pathway for more quantitative DDA uncertainties. METHODS: For five HNC patients, each with multiple repeated CTs acquired during treatment, a simultaneous-integrated boost (SIB) plan was optimized. Recalculated doses were warped individually using multiple DIRs from repeated to reference CTs, and voxel-by-voxel dose ranges determined an error-bar for DDA. Followed by evaluating, a previously proposed early-stage DDA uncertainty estimation method tested for lung cancer, which combines geometric DIR uncertainties, dose gradients and their directional dependence, in the context of HNC. RESULTS: Applying multiple DIRs show dose differences, pronounced in high dose gradient regions. The patient with largest anatomical changes (-13.1 % in ROI body volume), exhibited 33 % maximum uncertainty in contralateral parotid, with 54 % of voxels presenting an uncertainty >5 %. Accumulation over multiple CTs partially mitigated uncertainties. The estimation approach predicted 92.6 % of voxels within ±5 % to the reference dose uncertainty across all patients. CONCLUSIONS: DIR variations impact accumulated doses, emphasizing DDA uncertainty quantification's importance for HNC patients. Multiple DIR dose warping aids in quantifying DDA uncertainties. An estimation approach previously described for lung cancer was successfully validated for HNC, for SIB plans, presenting different dose gradients, and for accumulated treatments.

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.

Technical note: development of a simulation framework, enabling the investigation of locally tuned single energy proton radiography.

Range uncertainties remain a limitation for the confined dose distribution that proton therapy can offer. The uncertainty stems from the ambiguity when translating CT Hounsfield Units (HU) into proton stopping powers. Proton Radiography (PR) can be used to verify the proton range. Specifically, PR can be used as a quality-control tool for CBCT-based synthetic CTs. An essential part of the work illustrating the potential of PR has been conducted using multi-layer ionization chamber (MLIC) detectors and mono-energetic PR. Due to the dimensions of commercially available MLICs, clinical adoption is cumbersome. Here, we present a simulation framework exploring locally-tuned single energy (LTSE) proton radiography and corresponding potential compact PR detector designs. Based on a planning CT data set, the presented framework models the water equivalent thickness. Subsequently, it analyses the proton energies required to pass through the geometry within a defined ROI. In the final step, an LTSE PR is simulated using the MCsquare Monte Carlo code. In an anatomical head phantom, we illustrate that LTSE PR allows for a significantly shorter longitudinal dimension of MLICs. We compared PR simulations for two exemplary 30 × 30 mm2proton fields passing the phantom at a 90° angle at an anterior and a posterior location in an iso-centric setup. The longitudinal distance over which all spots per field range out is significantly reduced for LTSE PR compared to mono-energetic PR. In addition, we illustrate the difference in shape of integral depth dose (IDD) when using constrained PR energies. Finally, we demonstrate the accordance of simulated and experimentally acquired IDDs for an LTSE PR acquisition. As the next steps, the framework will be used to investigate the sensitivity of LTSE PR to various sources of errors. Furthermore, we will use the framework to systematically explore the dimensions of an optimized MLIC design for daily clinical use.

Feasibility of the J-PET to monitor the range of therapeutic proton beams.

PURPOSE: The aim of this work is to investigate the feasibility of the Jagiellonian Positron Emission Tomography (J-PET) scanner for intra-treatment proton beam range monitoring. METHODS: The Monte Carlo simulation studies with GATE and PET image reconstruction with CASToR were performed in order to compare six J-PET scanner geometries. We simulated proton irradiation of a PMMA phantom with a Single Pencil Beam (SPB) and Spread-Out Bragg Peak (SOBP) of various ranges. The sensitivity and precision of each scanner were calculated, and considering the setup's cost-effectiveness, we indicated potentially optimal geometries for the J-PET scanner prototype dedicated to the proton beam range assessment. RESULTS: The investigations indicate that the double-layer cylindrical and triple-layer double-head configurations are the most promising for clinical application. We found that the scanner sensitivity is of the order of 10-5 coincidences per primary proton, while the precision of the range assessment for both SPB and SOBP irradiation plans was found below 1 mm. Among the scanners with the same number of detector modules, the best results are found for the triple-layer dual-head geometry. The results indicate that the double-layer cylindrical and triple-layer double-head configurations are the most promising for the clinical application, CONCLUSIONS:: We performed simulation studies demonstrating that the feasibility of the J-PET detector for PET-based proton beam therapy range monitoring is possible with reasonable sensitivity and precision enabling its pre-clinical tests in the clinical proton therapy environment. Considering the sensitivity, precision and cost-effectiveness, the double-layer cylindrical and triple-layer dual-head J-PET geometry configurations seem promising for future clinical application.

Automatic lung segmentation of magnetic resonance images: A new approach applied to healthy volunteers undergoing enhanced Deep-Inspiration-Breath-Hold for motion-mitigated 4D proton therapy of lung tumors.

Background and purpose: Respiratory suppression techniques represent an effective motion mitigation strategy for 4D-irradiation of lung tumors with protons. A magnetic resonance imaging (MRI)-based study applied and analyzed methods for this purpose, including enhanced Deep-Inspiration-Breath-Hold (eDIBH). Twenty-one healthy volunteers (41-58 years) underwent thoracic MR scans in four imaging sessions containing two eDIBH-guided MRIs per session to simulate motion-dependent irradiation conditions. The automated MRI segmentation algorithm presented here was critical in determining the lung volumes (LVs) achieved during eDIBH. Materials and methods: The study included 168 MRIs acquired under eDIBH conditions. The lung segmentation algorithm consisted of four analysis steps: (i) image preprocessing, (ii) MRI histogram analysis with thresholding, (iii) automatic segmentation, (iv) 3D-clustering. To validate the algorithm, 46 eDIBH-MRIs were manually contoured. Sørensen-Dice similarity coefficients (DSCs) and relative deviations of LVs were determined as similarity measures. Assessment of intrasessional and intersessional LV variations and their differences provided estimates of statistical and systematic errors. Results: Lung segmentation time for 100 2D-MRI planes was âˆ¼ 10 s. Compared to manual lung contouring, the median DSC was 0.94 with a lower 95 % confidence level (CL) of 0.92. The relative volume deviations yielded a median value of 0.059 and 95 % CLs of -0.013 and 0.13. Artifact-based volume errors, mainly of the trachea, were estimated. Estimated statistical and systematic errors ranged between 6 and 8 %. Conclusions: The presented analytical algorithm is fast, precise, and readily available. The results are comparable to time-consuming, manual segmentations and other automatic segmentation approaches. Post-processing to remove image artifacts is under development.

Retrospective reconstruction of four-dimensional magnetic resonance from interleaved cine imaging - A comparative study with four-dimensional computed tomography in the lung.

Background and purpose: Imaging of respiration-induced anatomical changes is essential to ensure high accuracy in radiotherapy of lung cancer. We expanded here on methods for retrospective reconstruction of time-resolved volumetric magnetic resonance (4DMR) of the thoracic region and benchmarked the results against 4D computed tomography (4DCT). Materials and method: MR data of six lung cancer patients were collected by interleaving cine-navigator images with 2D data frame images, acquired across the thorax. The data frame images have been stacked in volumes based on a similarity metric that considers the anatomical deformation of lungs, while addressing ambiguities in respiratory phase detection and interpolation of missing data. The resulting images were validated against cine-navigator images and compared to paired 4DCTs in terms of amplitude and period of motion, assessing differences in internal target volume (ITV) margin definition. Results: 4DMR-based motion amplitude was on average within 1.8 mm of that measured in the corresponding 2D cine-navigator images. In our dataset, the 4DCT motion and the 4DMR median amplitude were always within 3.8 mm. The median period was generally close to CT references, although deviations up to 24 % have been observed. These changes were reflected in the ITV, which was generally larger for MRI than for 4DCT (up to 39.7 %). Conclusions: The proposed algorithm for retrospective reconstruction of time-resolved volumetric MR provided quality anatomical images with high temporal resolution for motion modelling and treatment planning. The potential for imaging organ motion variability makes 4DMR a valuable complement to standard 4DCT imaging.

Technical note: Towards more realistic 4DCT(MRI) numerical lung phantoms.

BACKGROUND: Numerical 4D phantoms, together with associated ground truth motion, offer a flexible and comprehensive data set for realistic simulations in radiotherapy and radiology in target sites affected by respiratory motion. PURPOSE: We present an openly available upgrade to previously reported methods for generating realistic 4DCT lung numerical phantoms, which now incorporate respiratory ribcage motion and improved lung density representation throughout the breathing cycle. METHODS: Density information of reference CTs, toget her with motion from multiple breathing cycle 4DMRIs have been combined to generate synthetic 4DCTs (4DCT(MRI)s). Inter-subject correspondence between the CT and MRI anatomy was first established via deformable image registration (DIR) of binary masks of the lungs and ribcage. Ribcage and lung motions were extracted independently from the 4DMRIs using DIR and applied to the corresponding locations in the CT after post-processing to preserve sliding organ motion. In addition, based on the Jacobian determinant of the resulting deformation vector fields, lung densities were scaled on a voxel-wise basis to more accurately represent changes in local lung density. For validating this process, synthetic 4DCTs, referred to as 4DCT(CT)s, were compared to the originating 4DCTs using motion extracted from the latter, and the dosimetric impact of the new features of ribcage motion and density correction were analyzed using pencil beam scanned proton 4D dose calculations. RESULTS: Lung density scaling led to a reduction of maximum mean lung Hounsfield units (HU) differences from 45 to 12 HU when comparing simulated 4DCT(CT)s to their originating 4DCTs. Comparing 4D dose distributions calculated on the enhanced 4DCT(CT)s to those on the original 4DCTs yielded 2%/2 mm gamma pass rates above 97% with an average improvement of 1.4% compared to previously reported phantoms. CONCLUSIONS: A previously reported 4DCT(MRI) workflow has been successfully improved and the resulting numerical phantoms exhibit more accurate lung density representations and realistic ribcage motion.

Treatment planning comparison for head and neck cancer between photon, proton, and combined proton-photon therapy - From a fixed beam line to an arc.

BACKGROUND AND PURPOSE: This study investigates whether combined proton-photon therapy (CPPT) improves treatment plan quality compared to single-modality intensity-modulated radiation therapy (IMRT) or intensity-modulated proton therapy (IMPT) for head and neck cancer (HNC) patients. Different proton beam arrangements for CPPT and IMPT are compared, which could be of specific interest concerning potential future upright-positioned treatments. Furthermore, it is evaluated if CPPT benefits remain under inter-fractional anatomical changes for HNC treatments. MATERIAL AND METHODS: Five HNC patients with a planning CT and multiple (4-7) repeated CTs were studied. CPPT with simultaneously optimized photon and proton fluence, single-modality IMPT, and IMRT treatment plans were optimized on the planning CT and then recalculated and reoptimized on each repeated CT. For CPPT and IMPT, plans with different degrees of freedom for the proton beams were optimized. Fixed horizontal proton beam line (FHB), gantry-like, and arc-like plans were compared. RESULTS: The target coverage for CPPT without adaptation is insufficient (average V95%=88.4 %), while adapted plans can recover the initial treatment plan quality for target (average V95%=95.5 %) and organs-at-risk. CPPT with increased proton beam flexibility increases plan quality and reduces normal tissue complication probability of Xerostomia and Dysphagia. On average, Xerostomia NTCP reductions compared to IMRT are -2.7 %/-3.4 %/-5.0 % for CPPT FHB/CPPT Gantry/CPPT Arc. The differences for IMPT FHB/IMPT Gantry/IMPT Arc are + 0.8 %/-0.9 %/-4.3 %. CONCLUSION: CPPT for HNC needs adaptive treatments. Increasing proton beam flexibility in CPPT, either by using a gantry or an upright-positioned patient, improves treatment plan quality. However, the photon component is substantially reduced, therefore, the balance between improved plan quality and costs must be further determined.

Uncertainty-aware MR-based CT synthesis for robust proton therapy planning of brain tumour.

BACKGROUND AND PURPOSE: Deep learning techniques excel in MR-based CT synthesis, but missing uncertainty prediction limits its clinical use in proton therapy. We developed an uncertainty-aware framework and evaluated its efficiency in robust proton planning. MATERIALS AND METHODS: A conditional generative-adversarial network was trained on 64 brain tumour patients with paired MR-CT images to generate synthetic CTs (sCT) from combined T1-T2 MRs of three orthogonal planes. A Bayesian neural network predicts Laplacian distributions for all voxels with parameters (µ, b). A robust proton plan was optimized using three sCTs of µ and µ±b. The dosimetric differences between the plan from sCT (sPlan) and the recalculated plan (rPlan) on planning CT (pCT) were quantified for each patient. The uncertainty-aware robust plan was compared to conventional robust (global ± 3 %) and non-robust plans. RESULTS: In 8-fold cross-validation, sCT-pCT image differences (Mean-Absolute-Error) were 80.84 ± 9.84HU (body), 35.78 ± 6.07HU (soft tissues) and 221.88 ± 31.69HU (bones), with Dice scores of 90.33 ± 2.43 %, 95.13 ± 0.80 %, and 85.53 ± 4.16 %, respectively. The uncertainty distribution positively correlated with absolute prediction error (Correlation Coefficient: 0.62 ± 0.01). The uncertainty-conditioned robust optimisation improved the rPlan-sPlan agreement, e.g., D95 absolute difference (CTV) was 1.10 ± 1.24 % compared to conventional (1.64 ± 2.71 %) and non-robust (2.08 ± 2.96 %) optimisation. This trend was consistent across all target and organs-at-risk indexes. CONCLUSION: The enhanced framework incorporates 3D uncertainty prediction and generates high-quality sCTs from MR images. The framework also facilitates conditioned robust optimisation, bolstering proton plan robustness against network prediction errors. The innovative feature of uncertainty visualisation and robust analyses contribute to evaluating sCT clinical utility for individual patients.

Multi-camera optical tracking and fringe pattern analysis for eye surface profilometry in ocular proton therapy.

Background and purpose: An optical tracking system for high-precision measurement of eye position and orientation during proton irradiation of intraocular tumors was designed. The system performed three-dimensional (3D) topography of the anterior eye segment using fringe pattern analysis based on Fourier Transform Method (FTM). Materials and methods: The system consisted of four optical cameras and two projectors. The design and modifications to the FTM pipeline were optimized for the realization of a reliable measurement system. Of note, phase-to-physical coordinate mapping was achieved through the combination of stereo triangulation and fringe pattern analysis. A comprehensive pre-clinical validation was carried out. Then, the system was set to acquire the eye surface of patients undergoing proton therapy. Topographies of the eye were compared to manual contouring on MRI. Results: Pre-clinical results demonstrated that 3D topography could achieve sub-millimetric accuracy (median:0.58 mm) and precision (RMSE:0.61 mm) in the clinical setup. The absolute median discrepancy between MRI and FTM-based anterior eye segment surface reconstruction was 0.43 mm (IQR:0.65 mm). Conclusions: The system complied with the requirement of precision and accuracy for image guidance in ocular proton therapy radiation and is expected to be clinically tested soon to evaluate its performance against the current standard.

A fast analytical dose calculation approach for MRI-guided proton therapy.

Objective.Magnetic resonance (MR) is an innovative technology for online image guidance in conventional radiotherapy and is also starting to be considered for proton therapy as well. For MR-guided therapy, particularly for online plan adaptations, fast dose calculation is essential. Monte Carlo (MC) simulations, however, which are considered the gold standard for proton dose calculations, are very time-consuming. To address the need for an efficient dose calculation approach for MRI-guided proton therapy, we have developed a fast GPU-based modification of an analytical dose calculation algorithm incorporating beam deflections caused by magnetic fields.Approach.Proton beams (70-229 MeV) in orthogonal magnetic fields (0.5/1.5 T) were simulated using TOPAS-MC and central beam trajectories were extracted to generate look-up tables (LUTs) of incremental rotation angles as a function of water-equivalent depth. Beam trajectories are then reconstructed using these LUTs for the modified ray casting dose calculation. The algorithm was validated against MC in water, different materials and for four example patient cases, whereby it has also been fully incorporated into a treatment plan optimisation regime.Main results.Excellent agreement between analytical and MC dose distributions could be observed with sub-millimetre range deviations and differences in lateral shifts <2 mm even for high densities (1000 HU). 2%/2 mm gamma pass rates were comparable to the 0 T scenario and above 94.5% apart for the lung case. Further, comparable treatment plan quality could be achieved regardless of magnetic field strength.Significance.A new method for accurate and fast proton dose calculation in magnetic fields has been developed and successfully implemented for treatment plan optimisation.

Exploring beamline momentum acceptance for tracking respiratory variability in lung cancer proton therapy: a simulation study.

Objective. Investigating the aspects of proton beam delivery to track organ motion with pencil beam scanning therapy. Considering current systems as a reference, specify requirements for next-generation units aiming at real-time image-guided treatments.Approach. Proton treatments for six non-small cell lung cancer (NSCLC) patients were simulated using repeated 4DCTs to model respiratory motion variability. Energy corrections required for this treatment site were evaluated for different approaches to tumour tracking, focusing on the potential for energy adjustment within beamline momentum acceptance (dp/p). A respiration-synchronised tracking, taking into account realistic machine delivery limits, was compared to ideal tracking scenarios, in which unconstrained energy corrections are possible. Rescanning and the use of multiple fields to mitigate residual interplay effects and dose degradation have also been investigated.Main results. Energy correction requirements increased with motion amplitudes, for all patients and tracking scenarios. Higher dose degradation was found for larger motion amplitudes, rescanning has beneficial effects and helped to improve dosimetry metrics for the investigated limited dp/pof 1.2% (realistic) and 2.4%. The median differences between ideal and respiratory-synchronised tracking show minimal discrepancies, 1% and 5% respectively for dose coverage (CTV V95) and homogeneity (D5-D95). Multiple-field planning improves D5-D95 up to 50% in the most extreme cases while it does not show a significant effect on V95.Significance. This work shows the potential of implementing tumour tracking in current proton therapy units and outlines design requirements for future developments. Energy regulation within momentum acceptance was investigated to tracking tumour motion with respiratory-synchronisation, achieving results in line with the performance of ideal tracking scenarios. ±5% Δp/p would allow to compensate for all range offsets in our NSCLC patient cohort, including breathing variability. However, the realistic momentum of 1.2% dp/prepresentative of existing medical units limitations, has been shown to preserve plan quality.

A bi-directional beam-line energy ramping for efficient patient treatment with scanned proton therapy.

Objective.The treatment of mobile tumours using Pencil Beam Scanning (PBS) has become more prevalent in the last decade. However, to achieve the same beam delivery quality as for static tumours, treatments have to be combined with motion mitigation techniques, not limited but including, breath hold, gating and re-scanning, which typically prolong treatment time. In this article we present a novel method of bi-directional energy modulation and demonstrate our initial experience in improvement of treatment efficiency. Approach.At Paul Scherrer Institute Gantry 2 mobile tumours are treated by combining PBS with gating and volumetric re-scanning (VR), where the target volume is irradiated multiple times. Initial implementation of VR used only descending beam energies, creating a substantial dead time due to the beam-line initialization (ramping) before each re-scan. In 2019 we commissioned an energy meandering strategy that allows us to avoid beam line ramping in-between energy series while maintaining beam delivery quality.Main results.The measured beam parameters difference for both energy sequence are in the order of the typical daily variations: 0.2 mm in beam position and 0.2 mm in range. Using machine log files, we performed point-to-point dose difference calculations between original and new applications where we observed dose differences of less than 2%. After three years of operation employing bi-directional energy modulation, we have analysed the individual beam delivery time for 181 patients and have compared this to simulations of the timing behaviour assuming uni-directional energy sequence application. Depending on treatment complexity, we obtained plan delivery time reductions of up to 55%, with a median time gain of 17% for all types of treatments.Significance. Bi-directional energy modulation can help improving patient treatment efficiency by reducing delivery times especially for complex and specialised irradiations. It could be implemented in many existing facilities without significant additional hardware upgrades.

Detection of range shifts in proton beam therapy using the J-PET scanner: a patient simulation study.

OBJECTIVE: The Jagiellonian PET (J-PET) technology, based on plastic scintillators, has been proposed as a cost effective tool for detecting range deviations during proton therapy. This study investigates the feasibility of using J-PET for range monitoring by means of a detailed Monte Carlo simulation study of 95 patients who underwent proton therapy at the Cyclotron Centre Bronowice (CCB) in Krakow, Poland. Approach: Discrepancies between prescribed and delivered treatments were artificially introduced in the simulations by means of shifts in patient positioning and in the Hounsfield unit to the relative proton stopping power calibration curve. A dual-layer, cylindrical J-PET geometry was simulated in an in-room monitoring scenario and a triple-layer, dual-head geometry in an in-beam protocol. The distribution of range shifts in reconstructed PET activity was visualised in the beam's eye view. Linear prediction models were constructed from all patients in the cohort, using the mean shift in reconstructed PET activity as a predictor of the mean proton range deviation. Main results: Maps of deviations in the range of reconstructed PET distributions showed agreement with those of deviations in dose range in most patients. The linear prediction model showed a good fit, with coefficient of determination r^2 = 0.84 (in-room) and 0.75 (in-beam). Residual standard error was below 1 mm: 0.33 mm (in-room) and 0.23 mm (in-beam). Significance: The precision of the proposed prediction models shows the sensitivity of the proposed J-PET scanners to shifts in proton range for a wide range of clinical treatment plans. Furthermore, it motivates the use of such models as a tool for predicting proton range deviations and opens up new prospects for investigations into the use of intra-treatment PET images for predicting clinical metrics that aid in the assessment of the quality of delivered treatment. .

Patient-specific quality assurance for deformable IMRT/IMPT dose accumulation: Proposition and validation of energy conservation based validation criterion.

BACKGROUND: Deformable image registration (DIR)-based dose accumulation (DDA) is regularly used in adaptive radiotherapy research. However, the applicability and reliability of DDA for direct clinical usage are still being debated. One primary concern is the validity of DDA, particularly for scenarios with substantial anatomical changes, for which energy-conservation problems were observed in conceptual studies. PURPOSE: We present and validate an energy-conservation (EC)-based DDA validation workflow and further investigate its usefulness for actual patient data, specifically for lung cancer cases. METHODS: For five non-small cell lung cancer (NSCLC) patients, DDA based on five selective DIR methods were calculated for five different treatment plans, which include one intensity-modulated photon therapy (IMRT), two intensity-modulated proton therapy (IMPT), and two combined proton-photon therapy (CPPT) plans. All plans were optimized on the planning CT (planCT) acquired in deep inspiration breath-hold (DIBH) and were re-optimized on the repeated DIBH CTs of three later fractions. The resulting fractional doses were warped back to the planCT using each DIR. An EC-based validation of the accumulation process was implemented and applied to all DDA results. Correlations between relative organ mass/volume variations and the extent of EC violation were then studied using Bayesian linear regression (BLR). RESULTS: For most OARs, EC violation within 10% is observed. However, for the PTVs and GTVs with substantial regression, severe overestimation of the fractional energy was found regardless of treatment type and applied DIR method. BLR results show that EC violation is linearly correlated to the relative mass variation (R^2 > 0.95) and volume variation (R^2 > 0.60). CONCLUSION: DDA results should be used with caution in regions with high mass/volume variation for intensity-based DIRs. EC-based validation is a useful approach to provide patient-specific quality assurance of the validity of DDA in radiotherapy.

Detailed Monte-Carlo characterization of a Faraday cup for proton therapy.

BACKGROUND: Experiments with ultra-high dose rates in proton therapy are of increasing interest for potential treatment benefits. The Faraday Cup (FC) is an important detector for the dosimetry of such ultra-high dose rate beams. So far, there is no consensus on the optimal design of a FC, or on the influence of beam properties and magnetic fields on shielding of the FC from secondary charged particles. PURPOSE: To perform detailed Monte Carlo simulations of a Faraday cup to identify and quantify all the charge contributions from primary protons and secondary particles that modify the efficiency of the FC response as a function of a magnetic field employed to improve the detector's reading. METHODS: In this paper, a Monte Carlo (MC) approach was used to investigate the Paul Scherrer Institute (PSI) FC and quantify contributions of charged particles to its signal for beam energies of 70, 150, and 228 MeV and magnetic fields between 0 and 25 mT. Finally, we compared our MC simulations to measurements of the response of the PSI FC. RESULTS: For maximum magnetic fields, the efficiency (signal of the FC normalized to charged delivered by protons) of the PSI FC varied between 99.97% and 100.22% for the lowest and highest beam energy. We have shown that this beam energy-dependence is mainly caused by contributions of secondary charged particles, which cannot be fully suppressed by the magnetic field. Additionally, it has been demonstrated that these contributions persist, making the FC efficiency beam energy dependent for fields up to 250 mT, posing inevitable limits on the accuracy of FC measurements if not corrected. In particular, we have identified a so far unreported loss of electrons via the outer surfaces of the absorber block and show the energy distributions of secondary electrons ejected from the vacuum window (VW) (up to several hundred keV), together with electrons ejected from the absorber block (up to several MeV). Even though, in general, simulations and measurements were well in agreement, the limitation of the current MC calculations to produce secondary electrons below 990 eV posed a limit in the efficiency simulations in the absence of a magnetic field as compared to the experimental data. CONCLUSION: TOPAS-based MC simulations allowed to identify various and previously unreported contributions to the FC signal, which are likely to be present in other FC designs. Estimating the beam energy dependence of the PSI FC for additional beam energies could allow for the implementation of an energy-dependent correction factor to the signal. Dose estimates, based on accurate measurements of the number of delivered protons, provided a valid instrument to challenge the dose determined by reference ionization chambers, not only at ultra-high dose rates but also at conventional dose rates.

Clinical outcome after pencil beam scanning proton therapy and dysphagia/xerostomia NTCP calculations of proton and photon radiotherapy delivered to patients with cancer of the major salivary glands.

OBJECTIVES: The purpose of this study is to report the oncological outcome, observed toxicities and normal tissue complication probability (NTCP) calculation for pencil beam scanning (PBS) PT delivered to salivary gland tumour (SGT) patients. METHODS: We retrospectively reviewed 26 SGT patients treated with PBSPT (median dose, 67.5 Gy(RBE)) between 2005 and 2020 at our institute. Toxicities were recorded according to CTCAEv.4.1. Overall survival (OS), local control (LC), locoregional control (LRC) and distant control (DC) were estimated. For all patients, a photon plan was re-calculated in order to assess the photon/proton NTCP. RESULTS: With a median follow-up time of 46 months (range, 3-118), 5 (19%), 2 (8%), 3 (12%) and 2 (8%) patients presented after PT with distant, local, locoregional failures and death, respectively. The estimated 4 year OS, LC, LCR and DC were 90%, 90%, 87 and 77%, respectively. Grade 3 late toxicity was observed in 2 (8%) patients. The estimated 4 year late high-grade (≥3) toxicity-free survival was 78.4%. The calculated mean difference of NTCP-values after PBSPT and VMAT plans for developing Grade 2 or 3 xerostomia were 3.8 and 2.9%, respectively. For Grade 2-3 dysphagia, the grade corresponding percentages were 8.6 and 1.9%. Not using an up-front model-based approach to select patients for PT, only 40% of our patients met the Dutch eligibility criteria. CONCLUSION: Our data suggest excellent oncological outcome and low late toxicity rates for patients with SGT treated with PBSPT. NTCP calculation showed a substantial risk reduction for Grade 2 or 3 xerostomia and dysphagia in some SGT patients, while for others, no clear benefit was seen with protons, suggesting that comparative planning should be performed routinely for these patients. ADVANCES IN KNOWLEDGE: We have reported that the clinical outcome of SGT patients treated with PT and compared IMPT to VMAT for the treatment of salivary gland tumour and have observed that protons delivered significantly less dose to organs at risks and were associated with less NTCP for xerostomia and dysphagia. Noteworthy, not using an up-front model-based approach, only 40% of our patients met the Dutch eligibility criteria.

Large anatomical changes in head-and-neck cancers - A dosimetric comparison of online and offline adaptive proton therapy.

Purpose: This work evaluates an online adaptive (OA) workflow for head-and-neck (H&N) intensity-modulated proton therapy (IMPT) and compares it with full offline replanning (FOR) in patients with large anatomical changes. Methods: IMPT treatment plans are created retrospectively for a cohort of eight H&N cancer patients that previously required replanning during the course of treatment due to large anatomical changes. Daily cone-beam CTs (CBCT) are acquired and corrected for scatter, resulting in 253 analyzed fractions. To simulate the FOR workflow, nominal plans are created on the planning-CT and delivered until a repeated-CT is acquired; at this point, a new plan is created on the repeated-CT. To simulate the OA workflow, nominal plans are created on the planning-CT and adapted at each fraction using a simple beamlet weight-tuning technique. Dose distributions are calculated on the CBCTs with Monte Carlo for both delivery methods. The total treatment dose is accumulated on the planning-CT. Results: Daily OA improved target coverage compared to FOR despite using smaller target margins. In the high-risk CTV, the median D98 degradation was 1.1 % and 2.1 % for OA and FOR, respectively. In the low-risk CTV, the same metrics yield 1.3 % and 5.2 % for OA and FOR, respectively. Smaller setup margins of OA reduced the dose to all OARs, which was most relevant for the parotid glands. Conclusion: Daily OA can maintain prescription doses and constraints over the course of fractionated treatment, even in cases of large anatomical changes, reducing the necessity for manual replanning in H&N IMPT.