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Background: Deep learning has shown promising results to generate MRI‐based synthetic CTs and to enable accurate proton dose calculations on MRIs. For clinical implementation of synthetic CTs, quality assurance tools that verify their quality and reliability are required but still lacking. Purpose: This study aims to evaluate the predictive value of uncertainty maps generated with Monte Carlo dropout (MCD) for verifying proton dose calculations on deep‐learning‐based synthetic CTs (sCTs) derived from MRIs in online adaptive proton therapy. Methods: Two deep‐learning models (DCNN and cycleGAN) were trained for CT image synthesis using 101 paired CT‐MR images. sCT images were generated using MCD for each model by performing 10 inferences with activated dropout layers. The final sCT was obtained by averaging the inferred sCTs, while the uncertainty map was obtained from the HU variance corresponding to each voxel of 10 sCTs. The resulting uncertainty maps were compared to the observed HU‐, range‐, WET‐, and dose‐error maps between the sCT and planning CT. For range and WET errors, the generated uncertainty maps were projected along the 90‐degree angle. To evaluate the dose distribution, a mask based on the 5%‐isodose curve was applied to only include voxels along the beam paths. Pearson's correlation coefficients were calculated to determine the correlation between the uncertainty maps and HUs, range, WET, and dose errors. To evaluate the dosimetric accuracy of synthetic CTs, clinical proton treatment plans were recalculated and compared to the pCTs Results: Evaluation of the correlation showed an average of r = 0.92 ± 0.03 and r = 0.92 ± 0.03 for errors between uncertainty‐HU, r = 0.66 ± 0.09 and r = 0.62 ± 0.06 between uncertainty‐range, r = 0.64 ± 0.06 and r = 0.58 ± 0.07 between uncertainty‐WET, and r = 0.65 ± 0.09 and r = 0.67 ± 0.07 between uncertainty and dose difference for DCNN and cycleGAN model, respectively. Dosimetric comparison for target volumes showed an average 3%/3 mm gamma pass rate of 99.76 ± 0.43 (DCNN) and 99.10 ± 1.27 (cycleGAN). Conclusion: The observed correlations between uncertainty maps and the various metrics (HU, range, WET, and dose errors) demonstrated the potential of MCD‐based uncertainty maps as a reliable QA tool to evaluate the accuracy of deep learning‐based sCTs. [ABSTRACT FROM AUTHOR]

Background: Proton radiography (PR) uses highly energetic proton beams to create images where energy loss is the main contrast mechanism. Waterequivalent path length (WEPL) measurements using flat panel PR (FP-PR) have potential for in vivo range verification. However, an accurate WEPL measurement via FP-PR requires irradiation with multiple energy layers, imposing high imaging doses. Purpose: A FP-PR method is proposed for accurate WEPL determination based on a patient-specific imaging field with a reduced number of energies (n) to minimize imaging dose. Methods: Patient-specific FP-PRs were simulated and measured for a head and neck (HN) phantom.An energy selection algorithm estimated spot-wise the lowest energy required to cross the anatomy (Emin) using a water-equivalent thickness map.Starting from Emin, n was restricted to certain values (n = 26, 24, 22, …, 2 for simulations, n = 10 for measurements), resulting in patient-specific FP-PRs. A reference FP-PR with a complete set of energies was compared against patient-specific FP-PRs covering the whole anatomy via mean absolute WEPL differences (MAD), to evaluate the impact of the developed algorithm. WEPL accuracy of patient-specific FP-PRs was assessed using mean relative WEPL errors (MRE) with respect to measured multi-layer ionization chamber PRs (MLIC-PR) in the base of skull, brain, and neck regions. Results: MADs ranged from 2.1 mm (n = 26) to 21.0 mm (n = 2) for simulated FP-PRs, and 7.2 mm for measured FP-PRs (n = 10). WEPL differences below 1 mm were observed across the whole anatomy,except at the phantom surfaces. Measured patient-specific FP-PRs showed good agreement against MLIC-PRs, with MREs of 1.3 ± 2.0%, −0.1 ± 1.0%, and −0.1 ± 0.4% in the three regions of the phantom. Conclusion: A method to obtain accurate WEPL measurements using FP-PR with a reduced number of energies selected for the individual patient anatomy was established in silico and validated experimentally. Patient-specific FP-PRs could provide means of in vivo range verification. [ABSTRACT FROM AUTHOR]

The registration of multi-source radiation oncology data is a time-consuming and labour-intensive procedure. The standardisation of data collection offers the possibility for the acquisition of quality data for research and clinical purposes. With this study, we present an overview of the different tumour group data lists in the Dutch national proton therapy registry. Furthermore, as a representative example of the workings of these different tumour-specific knowledge graphs, we present the FAIR (Findable, Accessible, Interoperable, Reusable) data principles-compliant knowledge graph approach describing the head and neck tumour variables using radiotherapy domain ontologies and semantic web technologies. Our goal is to provide the radiotherapy community with a flexible and interoperable data model for data exchange between centres. We highlight data variables that are needed for models used in the model-based approach (MBA), which ensures a fair selection of patients that will benefit most from proton therapy. [ABSTRACT FROM AUTHOR]

Purpose: The number of pencil beam scanned proton therapy (PBS‐PT) facilities equipped with cone‐beam computed tomography (CBCT) imaging treating thoracic indications is constantly rising. To enable daily internal motion monitoring during PBS‐PT treatments of thoracic tumors, we assess the performance of Motion‐Aware RecOnstructiOn method using Spatial and Temporal Regularization (MA‐ROOSTER) four‐dimensional CBCT (4DCBCT) reconstruction for sparse‐view CBCT data and a realistic data set of patients treated with proton therapy. Methods: Daily CBCT projection data for nine non‐small cell lung cancer (NSCLC) patients and one SCLC patient were acquired at a proton gantry system (IBA Proteus® One). Four‐dimensional CBCT images were reconstructed applying the MA‐ROOSTER and the conventional phase‐correlated Feldkamp‐Davis‐Kress (PC‐FDK) method. Image quality was assessed by visual inspection, contrast‐to‐noise ratio (CNR), signal‐to‐noise ratio (SNR), and the structural similarity index measure (SSIM). Furthermore, gross tumor volume (GTV) centroid motion amplitudes were evaluated. Results: Image quality for the 4DCBCT reconstructions using MA‐ROOSTER was superior to the PC‐FDK reconstructions and close to FDK images (median CNR: 1.23 [PC‐FDK], 1.98 [MA‐ROOSTER], and 1.98 [FDK]; median SNR: 2.56 [PC‐FDK], 4.76 [MA‐ROOSTER], and 5.02 [FDK]; median SSIM: 0.18 [PC‐FDK vs FDK], 0.31 [MA‐ROOSTER vs FDK]). The improved image quality of MA‐ROOSTER facilitated GTV contour warping and realistic motion monitoring for most of the reconstructions. Conclusion: MA‐ROOSTER based 4DCBCTs performed well in terms of image quality and appear to be promising for daily internal motion monitoring in PBS‐PT treatments of (N)SCLC patients. [ABSTRACT FROM AUTHOR]

Purpose: Compared to photons, using particle radiation in radiotherapy reduces the dose and irradiated volume of normal tissues, potentially reducing side effects. The biological effect of dose deposited by particles such as carbon ions, however, differs from that of dose deposited by photons. The inaccuracy in models to estimate the biological effects of particle radiation remains the most important source of uncertainties in particle therapy. Improving this requires high-precision studies on biological effects of particle radiation. Therefore, the authors aimed to develop a facility for reproducible and high-precision carbon-ion irradiation of cells in culture. The combined dose nonuniformity in the lateral and longitudinal direction should not exceed ±1.5%. Dose to the cells from particles than other carbon ions should not exceed 5%. Methods: A uniform lateral dose distribution was realized using a single scatter foil and quadrupole magnets. A modulator wheel was used to create a uniform longitudinal dose distribution. The choice of beam energy and the optimal design of these components was determined using GEANT4 and SRIM Monte Carlo simulations. Verification of the uniformity of the dose distribution was performed using a scintillating screen (lateral) and a water phantom (longitudinal). The reproducibility of dose delivery between experiments was assessed by repeated measurements of the spatial dose distribution. Moreover, the reproducibility of dose-response measurements was tested by measuring the survival of irradiated HEK293 cells in three independent experiments. Results: The relative contribution of dose from nuclear reaction fragments to the sample was found to be <5% when using 90 MeV/u carbon ions. This energy still allows accurate dosimetry conforming to the IAEA Report TRS-398, facilitating comparison to dose-effect data obtained with other radiation qualities. A 1.3 mm long spread-out Bragg peak with a diameter of 30 mm was created, allowing the irradiation of cell samples with the specified accuracy. Measurements of the transverse and longitudinal dose distribution showed that the dose variation over the sample volume was ±0.8% and ±0.7% in the lateral and longitudinal directions, respectively. The track-averaged LET of 132±10 keV/μm and dose-averaged LET of 189±15 keV/μm at the position of the sample were obtained from a GEANT4 simulation, which was validated experimentally. Three separately measured cell-survival curves yielded nearly identical results. Conclusions: With the new facility, high-precision carbon-ion irradiations of biological samples can be performed with highly reproducible results. [ABSTRACT FROM AUTHOR]

Background: Proton arc technology has recently shown dosimetric gains for various treatment indications. The increased number of beams and energy layers (ELs) in proton arc plans, increases the degrees of freedom in plan optimization and thereby flexibility to spare dose in organs at risk (OARs). A relationship exists between dosimetric plan quality, delivery efficiency, the number of ELs -and beams in a proton arc plan., Purpose: This work aims to investigate the effect of the number of beams and ELs in a proton arc plan, on toxicity and delivery time for oropharyngeal cancer patients (OPC) selected for intensity modulated proton therapy (IMPT) based on the Dutch model-based approach., Methods: The EL reduction algorithm iteratively selects ELs from beams equidistantly spaced over a 360° arc. The beams in the final plan may contain multiple ELs, making them suited for static delivery on the studied treatment machine. The produced plans can therefore be called "step and shoot" proton arc plans. The number of beams and ELs were varied to determine the relationship with the planning cost function value, normal tissue complication probability (NTCP) and delivery time. Proton arc plans with robust target coverage and optimal energy layer reduction (ELR) settings to reduce NTCP, were generated for 10 OPC patients. Proton arc plans were compared to clinical volumetric modulated arc therapy (VMAT) and IMPT plans in terms of integral dose, OAR dose, NTCP for xerostomia and dysphagia and delivery time. Furthermore, dose-weighted average linear energy transfer (LET d ) distributions were compared between the IMPT and proton arc plans. A dry run delivery of a plan containing 20 beams and 360 ELs was performed to evaluate delivery time and accuracy., Results: We found 360 ELs distributed over 30 beams generated proton arc plans with near minimal expected plan toxicity. Relative to corresponding IMPT and VMAT plans, an average reduction of 21 ± 3% and 58 ± 10% in integral dose was observed. D mean was reduced most in the pharyngeal constrictor muscle (PCM) medius structure, with on average 9.0 ± 4.2 Gy(RBE) (p=0.0002) compared to the clinical IMPT plans. The average NTCP for grade⩾2 and grade⩾3 xerostomia at six months after treatment significantly decreased with 4.7 ± 1.8% (p = 0.002) and 1.7 ± 0.8% (p=0.002), respectively, while the average NTCP for grade⩾2 and grade⩾3 dysphagia decreased with 4.4 ± 2.9% (p=0.002) and 0.9 ± 0.4% (p=0.002), respectively, increasing the benefit of protons relative to VMAT. For a "step and shoot" proton arc delivery with auto beam sequencing the estimated delivery time is 11 min, similar to the delivery time of a 6-field IMPT treatment. Gamma analysis between the planned and delivered dose distribution resulted in a 99.99% pass rate using 1mm/1% dose difference/distance to agreement criteria., Conclusions: "Step and shoot" proton arc demonstrates potential to further reduce toxicity compared to IMPT and VMAT in OPC treatment. By employing 360 ELs and 30 beams in the proposed ELR method, delivery time can reach clinically acceptable levels without compromising plan toxicity when automatic beam sequencing is available. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)