Assessment of bias in scoring of AI-based radiotherapy segmentation and planning studies using modified TRIPOD and PROBAST guidelines as an example.

BACKGROUND AND PURPOSE: Studies investigating the application of Artificial Intelligence (AI) in the field of radiotherapy exhibit substantial variations in terms of quality. The goal of this study was to assess the amount of transparency and bias in scoring articles with a specific focus on AI based segmentation and treatment planning, using modified PROBAST and TRIPOD checklists, in order to provide recommendations for future guideline developers and reviewers. MATERIALS AND METHODS: The TRIPOD and PROBAST checklist items were discussed and modified using a Delphi process. After consensus was reached, 2 groups of 3 co-authors scored 2 articles to evaluate usability and further optimize the adapted checklists. Finally, 10 articles were scored by all co-authors. Fleiss' kappa was calculated to assess the reliability of agreement between observers. RESULTS: Three of the 37 TRIPOD items and 5 of the 32 PROBAST items were deemed irrelevant. General terminology in the items (e.g., multivariable prediction model, predictors) was modified to align with AI-specific terms. After the first scoring round, further improvements of the items were formulated, e.g., by preventing the use of sub-questions or subjective words and adding clarifications on how to score an item. Using the final consensus list to score the 10 articles, only 2 out of the 61 items resulted in a statistically significant kappa of 0.4 or more demonstrating substantial agreement. For 41 items no statistically significant kappa was obtained indicating that the level of agreement among multiple observers is due to chance alone. CONCLUSION: Our study showed low reliability scores with the adapted TRIPOD and PROBAST checklists. Although such checklists have shown great value during development and reporting, this raises concerns about the applicability of such checklists to objectively score scientific articles for AI applications. When developing or revising guidelines, it is essential to consider their applicability to score articles without introducing bias.

Systematic Implementation of Effective Quality Assurance Processes for the Assessment of Radiation Target Volumes in Head and Neck Cancer.

PURPOSE: Significant heterogeneity exists in clinical quality assurance (QA) practices within radiation oncology departments, with most chart rounds lacking prospective peer-reviewed contour evaluation. This has the potential to significantly affect patient outcomes, particularly for head and neck cancers (HNC) given the large variance in target volume delineation. With this understanding, we incorporated a prospective systematic peer contour-review process into our workflow for all patients with HNC. This study aims to assess the effectiveness of implementing prospective peer review into practice for our National Cancer Institute Designated Cancer Center and to report factors associated with contour modifications. METHODS AND MATERIALS: Starting in November 2020, our department adopted a systematic QA process with real-time metrics, in which contours for all patients with HNC treated with radiation therapy were prospectively peer reviewed and graded. Contours were graded with green (unnecessary), yellow (minor), or red (major) colors based on the degree of peer-recommended modifications. Contours from November 2020 through September 2021 were included for analysis. RESULTS: Three hundred sixty contours were included. Contour grades were made up of 89.7% green, 8.9% yellow, and 1.4% red grades. Physicians with >12 months of clinical experience were less likely to have contour changes requested than those with <12 months (8.3% vs 40.9%; P < .001). Contour grades were significantly associated with physician case load, with physicians presenting more than the median number of 50 cases having significantly less modifications requested than those presenting <50 (6.7% vs 13.3%; P = .013). Physicians working with a resident or fellow were less likely to have contour changes requested than those without a trainee (5.2% vs 12.6%; P = .039). Frequency of major modification requests significantly decreased over time after adoption of prospective peer contour review, with no red grades occurring >6 months after adoption. CONCLUSIONS: This study highlights the importance of prospective peer contour-review implementation into systematic clinical QA processes for HNC. Physician experience proved to be the highest predictor of approved contours. A growth curve was demonstrated, with major modifications declining after prospective contour review implementation. Even within a high-volume academic practice with subspecialist attendings, >10% of patients had contour changes made as a direct result of prospective peer review.

FIELDRT: an open-source platform for the assessment of target volume delineation in radiation therapy.

OBJECTIVES: Target volume delineation (TVD) has been identified as a weakness in the accuracy of radiotherapy, both within and outside of clinical trials due to the intra/interobserver variations affecting the TVD quality. Sources of variations such as poor compliance or protocol violation may have adverse effect on treatment outcomes. In this paper, we present and describe the FIELDRT software developed for the ARENA project to improve the quality of TVD through qualitative and quantitative feedbacks and individual and personalized summary of trainee"s performance. METHODS: For each site-specific clinical case included in the FIELDRT software, reference volumes, minimum and maximum "acceptable" volumes and organ at risk were derived by outlines of consultants and senior trainees. The software components currently developed include: (a) user-friendly importing interface (b) analysis toolbox to compute quantitative and qualitative (c) visualiser and (d) structured report generator for personalised feedback. The FIELDRT software was validated by comparing the performance of 63 trainees and by measuring performance over time. In addition, a trainee evaluation day was held in 2019 to collect feedback on FIELDRT. RESULTS: Results show the trainees' improvement when reoutlining a case after reviewing the feedback generated from the FIELDRT software. Comments and feedback received after evaluation day were positive and confirmed that FIELDRT can be a useful application for training purposes. CONCLUSION: We presented a new open-source software to support education in TVD and ongoing continuous professional development for clinical oncology trainees and consultants. ARENA in combination with FIELDRT implements site-specific modules with reference target and organs at risk volumes and automatically evaluates individual performance using several quantitative and qualitative feedbacks. Pilot results suggests this software could be used as an education tool to reduce variation in TVD so to guarantee high quality in radiotherapy. ADVANCES IN KNOWLEDGE: FIELDRT is a new easy and free to use software aiming at supporting education in TVD and ongoing continuous professional development. The software provides quantitative/qualitative feedback and an exportable report with an individual and personalised summary of trainee's performance.

TriB-RT: Simultaneous optimization of photon, electron and proton beams.

PURPOSE: To develop a novel treatment planning process (TPP) with simultaneous optimization of modulated photon, electron and proton beams for improved treatment plan quality in radiotherapy. METHODS: A framework for fluence map optimization of Monte Carlo (MC) calculated beamlet dose distributions is developed to generate treatment plans consisting of photon, electron and spot scanning proton fields. Initially, in-house intensity modulated proton therapy (IMPT) plans are compared to proton plans created by a commercial treatment planning system (TPS). A triple beam radiotherapy (TriB-RT) plan is generated for an exemplary academic case and the dose contributions of the three particle types are investigated. To investigate the dosimetric potential, a TriB-RT plan is compared to an in-house IMPT plan for two clinically motivated cases. Benefits of TriB-RT for a fixed proton beam line with a single proton field are investigated. RESULTS: In-house optimized IMPT are of at least equal or better quality than TPS-generated proton plans, and MC-based optimization shows dosimetric advantages for inhomogeneous situations. Concerning TriB-RT, for the academic case, the resulting plan shows substantial contribution of all particle types. For the clinically motivated case, improved sparing of organs at risk close to the target volume is achieved compared to IMPT (e.g. myelon and brainstem [Formula: see text] -37%) at cost of an increased low dose bath (healthy tissue V 10% +22%). In the scenario of a fixed proton beam line, TriB-RT plans are able to compensate the loss in degrees of freedom to substantially improve plan quality compared to a single field proton plan. CONCLUSION: A novel TPP which simultaneously optimizes photon, electron and proton beams was successfully developed. TriB-RT shows the potential for improved treatment plan quality and is especially promising for cost-effective single-room proton solutions with a fixed beamline in combination with a conventional linac delivering photon and electron fields.

OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized open label trial.

BACKGROUND: Conservative surgery followed by breast and nodal irradiation is the standard loco-regional early breast cancer (BC) treatment for patients with four or more involved lymph nodes. However, the treatment strategy when fewer nodes are involved remains unclear, especially when lymphadenectomy has not been performed. Sensitive nodal status assessment molecular techniques as the One-Step Nucleic Acid Amplification (OSNA) assay can contribute to the definition and standardization of the treatment strategy. Therefore, the OPTIMAL study aims to demonstrate the feasibility of incidental irradiation of axillary nodes in patients with early-stage BC and limited involvement of the SLN. METHODS: BC patients who underwent conservative surgery and whose SLN total tumour load assessed with OSNA ranged between 250-15,000 copies/µL will be eligible. Patients will be randomized to receive irradiation on the breast, tumour bed, axillary and supraclavicular lymph node areas (intentional arm) or only on the breast and tumour bed (incidental arm). All areas, including the internal mammary chain, will be contoured. The mean, median, D5% and D95% doses received in all volumes will be calculated. The primary endpoint is the non-inferiority of the incidental irradiation of axillary nodes compared to the intentional irradiation in terms of 5-year disease free survival. Secondary endpoints comprise the comparison of acute and chronic toxicity and loco-regional and distant disease recurrence rates. DISCUSSION: Standardizing the treatment and diagnosis of BC patients with few nodes affected is crucial due to the lack of consensus. Hence, the quantitative score for the metastatic burden of SLN provided by OSNA can contribute by improving the discrimination of which BC patients with limited nodal involvement can benefit from incidental radiation as an adjuvant treatment strategy. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02335957; https://clinicaltrials.gov/ct2/show/NCT02335957.

A robust optimization method for weighted-layer-stacking proton beam therapy.

The layer-stacking method can provide three-dimensional conformal dose distributions to the target based on a passive scattering method using mini-spread-out Bragg peak (SOBP). The purpose of this work is to demonstrate the effectiveness of a new weight optimization algorithm that can enhance the robustness of dose distributions against layer depth variation in layer-stacking proton beam therapy. In the robustness algorithm, the upper limit of the layer's weight was adapted to the conventional algorithm and varied for 620 weight set evaluations. The optimal weight set was selected by using an analytical objective function based on Gaussian function with σ = 3 mm for WED variation. Then, we evaluated the stabilities of the one-dimensional depth dose distribution against WED variation generated by Gaussian samples. Three-dimensional dose distributions in the water phantom were also evaluated using the Monte-Carlo dose calculation. The variation of dose as well as dose volume histograms for the spherical target and the organ at risk (OAR) were evaluated. The robustness algorithm reduced the change of the dose distribution due to the WED variation by a factor of almost 3/4 compared to those with the conventional procedure. The rate of 91.8% in total samples was maintained within 5% change of the maximum dose, compared with the rate of 64.9% in the conventional algorithm. In the MC calculation, the high dose-volume in the OAR was reduced around the lateral penumbra and distal falloff region by the robustness algorithm. The stability of depth dose distributions was enhanced under the WED variation, compared to the conventional algorithm. This robust algorithm in layer-stacking proton therapy may be useful for treatment in which the sharpness of the distal falloff along the depth distribution needs to be maintained to spare the organ at risk and keep the dose coverage for the target tumor.

Update on yesterday's dose-Use of delivery log-files for daily adaptive proton therapy (DAPT).

In daily adaptive proton therapy (DAPT), the treatment plan is re-optimized on a daily basis. It is a straightforward idea to incorporate information from the previous deliveries during the optimization to refine this daily proton delivery. A feedback signal was used to correct for delivery errors and errors from an inaccurate dose calculation used for plan optimization. This feedback signal consisted of a dose distribution calculated with a Monte Carlo algorithm and was based on the spot delivery information from the previous deliveries in the form of log-files. We therefore called the method Update On Yesterday's Dose (UYD). The UYD method was first tested with a simulated DAPT treatment and second with dose measurements using an anthropomorphic phantom. For both, the simulations and the measurements, a better agreement between the delivered and the intended dose distribution could be observed using UYD. Gamma pass rates (1%/1 mm) increased from around 75% to above 90%, when applying the closed-loop correction for the simulations, as well as the measurements. For a DAPT treatment, positioning errors or anatomical changes are incorporated during the optimization and therefore are less dominant in the overall dose uncertainty. Hence, the relevance of algorithm or delivery machine errors even increases compared to standard therapy. The closed-loop process described here is a method to correct for these errors, and potentially further improve DAPT.

The impact of the field width on VMAT plan quality and the assessment of half field method.

PURPOSE: The goal of this work is to investigate the field width dependence of the volumetric modulated arc therapy (VMAT) plan quality and to propose a half field method to irradiate large volumes effectively with VMAT. MATERIALS AND METHODS: We compared four different VMAT methods; namely three full field (3ff), four full field (4ff), three half field (3hf), four half field (4hf). To evaluate the impact of the field width on VMAT plan quality, 12 different size PTVs were created in the virtual phantom and treatment plans generated for each PTV were compared. The effectiveness of our half field method was tested using computed tomography (CT) data of 10 nasopharyngeal carcinoma patients. RESULTS: In the virtual phantom study, organs at risk (OAR) mean dose, the maximum point dose, and Homogeneity Index (HI) were found to be field width dependent. Conformation Number (CN) was not significantly affected. In the clinical study, 4hf plans obtained statistically significant dose reduction at brainstem (P < 0.001), right parotid (P = 0.034), oral cavity (P < 0.001), larynx (P = 0.003), cochlea (P = 0.017), lips (P = 0.024), and Body-PTV (P = 0.04) compared to 4ff plans. CONCLUSION: Our results indicate that VMAT plan quality is dependent on the field width. Half field VMAT method, with the help of reduced field width, shows a clear advantage for the irradiation of large size targets compared to traditionally used full field VMAT plans.

A standardized commissioning framework of Monte Carlo dose calculation algorithms for proton pencil beam scanning treatment planning systems.

PURPOSE: Treatment planning systems (TPSs) from different vendors can involve different implementations of Monte Carlo dose calculation (MCDC) algorithms for pencil beam scanning (PBS) proton therapy. There are currently no guidelines for validating non-water materials in TPSs. Furthermore, PBS-specific parameters can vary by 1-2 orders of magnitude among different treatment delivery systems (TDSs). This paper proposes a standardized framework on the use of commissioning data and steps to validate TDS-specific parameters and TPS-specific heterogeneity modeling to potentially reduce these uncertainties. METHODS: A standardized commissioning framework was developed to commission the MCDC algorithms of RayStation 8A and Eclipse AcurosPT v13.7.20 using water and non-water materials. Measurements included Bragg peak depth-dose and lateral spot profiles and scanning field outputs for Varian ProBeam. The phase-space parameters were obtained from in-air measurements and the number of protons per MU from output measurements of 10 × 10 cm2 square fields at a 2 cm depth. Spot profiles and various PBS field measurements at additional depths were used to validate TPS. Human tissues in TPS, Gammex phantom materials, and artificial materials were used for the TPS benchmark and validation. RESULTS: The maximum differences of phase parameters, spot sigma, and divergence between MCDC algorithms are below 4.5 µm and 0.26 mrad in air, respectively. Comparing TPS to measurements at depths, both MC algorithms predict the spot sigma within 0.5 mm uncertainty intervals, the resolution of the measurement device. Beam Configuration in AcurosPT is found to underestimate number of protons per MU by ~2.5% and requires user adjustment to match measured data, while RayStation is within 1% of measurements using Auto model. A solid water phantom was used to validate the range accuracy of non-water materials within 1% in AcurosPT. CONCLUSIONS: The proposed standardized commissioning framework can detect potential issues during PBS TPS MCDC commissioning processes, and potentially can shorten commissioning time and improve dosimetric accuracies. Secondary MCDC can be used to identify the root sources of disagreement between primary MCDC and measurement.

Transitioning from measurement-based to combined patient-specific quality assurance for intensity-modulated proton therapy.

OBJECTIVE: This study is part of ongoing efforts aiming to transit from measurement-based to combined patient-specific quality assurance (PSQA) in intensity-modulated proton therapy (IMPT). A Monte Carlo (MC) dose-calculation algorithm is used to improve the independent dose calculation and to reveal the beam modeling deficiency of the analytical pencil beam (PB) algorithm. METHODS: A set of representative clinical IMPT plans with suboptimal PSQA results were reviewed. Verification plans were recalculated using an MC algorithm developed in-house. Agreements of PB and MC calculations with measurements that quantified by the γ passing rate were compared. RESULTS: The percentage of dose planes that met the clinical criteria for PSQA (>90% γ passing rate using 3%/3 mm criteria) increased from 71.40% in the original PB calculation to 95.14% in the MC recalculation. For fields without beam modifiers, nearly 100% of the dose planes exceeded the 95% γ passing rate threshold using the MC algorithm. The model deficiencies of the PB algorithm were found in the proximal and distal regions of the SOBP, where MC recalculation improved the γ passing rate by 11.27% (p < 0.001) and 16.80% (p < 0.001), respectively. CONCLUSIONS: The MC algorithm substantially improved the γ passing rate for IMPT PSQA. Improved modeling of beam modifiers would enable the use of the MC algorithm for independent dose calculation, completely replacing additional depth measurements in IMPT PSQA program. For current users of the PB algorithm, further improving the long-tail modeling or using MC simulation to generate the dose correction factor is necessary. ADVANCES IN KNOWLEDGE: We justified a change in clinical practice to achieve efficient combined PSQA in IMPT by using the MC algorithm that was experimentally validated in almost all the clinical scenarios in our center. Deficiencies in beam modeling of the current PB algorithm were identified and solutions to improve its dose-calculation accuracy were provided.

Off-axis dose distribution with stand-in and stand-off configurations for superficial radiotherapy treatments.

Current practice when delivering dose for superficial skin radiotherapy is to adjust the monitor units so that the prescribed dose is delivered to the central axis of the superficial unit applicator. Variations of source-to-surface distance due to patient's anatomy protruding into the applicator or extending away from the applicator require adjustments to the monitor units using the inverse square law. Off-axis dose distribution varies significantly from the central axis dose and is not currently being quantified. The dose falloff at the periphery of the field is not symmetrical in the anode-cathode axis due to the heel effect. This study was conducted to quantify the variation of dose across the surface being treated and model a simple geometric shape to estimate a patient's surface with stand-in and stand-off. Isodose plots and color-coded dose distribution maps were produced from scans of GAFChromic EBT-3 film irradiated by a Gulmay D3300 orthovoltage x-ray therapy system. It was clear that larger applicators show a greater dose falloff toward the periphery than smaller applicators. Larger applicators were found to have a lower percentage of points above 90% of central axis dose (SA90). Current clinical practice does not take this field variation into account. Stand-in can result in significant dose falloff off-axis depending on the depth and width of the protrusion, while stand-off can result in a flatter field due to the high-dose region near the central axis being further from the source than the peripheral regions. The central axis also received a 7% increased or decreased dose for stand-in or stand-off, respectively.

Feasibility of a GATE Monte Carlo platform in a clinical pretreatment QA system for VMAT treatment plans using TrueBeam with an HD120 multileaf collimator.

PURPOSE: To evaluate the quality of patient-specific complicated treatment plans, including commercialized treatment planning systems (TPS) and commissioned beam data, we developed a process of quality assurance (QA) using a Monte Carlo (MC) platform. Specifically, we constructed an interface system that automatically converts treatment plan and dose matrix data in digital imaging and communications in medicine to an MC dose-calculation engine. The clinical feasibility of the system was evaluated. MATERIALS AND METHODS: A dose-calculation engine based on GATE v8.1 was embedded in our QA system and in a parallel computing system to significantly reduce the computation time. The QA system automatically converts parameters in volumetric-modulated arc therapy (VMAT) plans to files for dose calculation using GATE. The system then calculates dose maps. Energies of 6 MV, 10 MV, 6 MV flattening filter free (FFF), and 10 MV FFF from a TrueBeam with HD120 were modeled and commissioned. To evaluate the beam models, percentage depth dose (PDD) values, MC calculation profiles, and measured beam data were compared at various depths (Dmax , 5 cm, 10 cm, and 20 cm), field sizes, and energies. To evaluate the feasibility of the QA system for clinical use, doses measured for clinical VMAT plans using films were compared to dose maps calculated using our MC-based QA system. RESULTS: A LINAC QA system was analyzed by PDD and profile according to the secondary collimator and multileaf collimator (MLC). Values for MC calculations and TPS beam data obtained using CC13 ion chamber (IBA Dosimetry, Germany) were consistent within 1.0%. Clinical validation using a gamma index was performed for VMAT treatment plans using a solid water phantom and arbitrary patient data. The gamma evaluation results (with criteria of 3%/3 mm) were 98.1%, 99.1%, 99.2%, and 97.1% for energies of 6 MV, 10 MV, 6 MV FFF, and 10 MV FFF, respectively. CONCLUSIONS: We constructed an MC-based QA system for evaluating patient treatment plans and evaluated its feasibility in clinical practice. We observed robust agreement between dose calculations from our QA system and measurements for VMAT plans. Our QA system could be useful in other clinical settings, such as small-field SRS procedures or analyses of secondary cancer risk, for which dose calculations using TPS are difficult to verify.

Benchmarking of Monte Carlo model of Siemens Oncor® linear accelerator for 18MV photon beam: Determination of initial electron beam parameters.

OBJECTIVE: This study aims to benchmark a Monte Carlo (MC) model of the 18 MV photon beam produced by the Siemens Oncor® linac using the BEAMnrc and DOSXYZnrc codes. METHODS: By matching the percentage depth doses and beam profiles calculated by MC simulations with measurements, the initial electron beam parameters including electron energy, full width at half maximum (spatial FWHM), and mean angular spread were derived for the 10×10 cm2 and 20×20 cm2 field sizes. The MC model of the 18 MV photon beam was then validated against the measurements for different field sizes (5×5, 30×30 and 40×40 cm2) by gamma index analysis. RESULTS: The optimum values for electron energy, spatial FWHM and mean angular spread were 14.2 MeV, 0.08 cm and 0.8 degree, respectively. The MC simulations yielded the comparable measurement results of these optimum parameters. The gamma passing rates (with acceptance criteria of 1% /1 mm) for percentage depth doses were found to be 100% for all field sizes. For cross-line profiles, the gamma passing rates were 100%, 97%, 95%, 96% and 95% for 5×5, 10×10, 20×20, 30×30 and 40×40 cm2 field sizes, respectively. CONCLUSIONS: By validation of the MC model of Siemens Oncor® linac using various field sizes, it was found that both dose profiles of small and large field sizes were very sensitive to the changes in spatial FWHM and mean angular spread of the primary electron beam from the bending magnet. Hence, it is recommended that both small and large field sizes of the 18 MV photon beams should be considered in the Monte Carlo linac modeling.

Monte Carlo calculation of beam quality correction factors in proton beams using PENH.

This work calculates beam quality correction factors ([Formula: see text]) in both modulated and unmodulated proton beams using the Monte Carlo (MC) code [Formula: see text]. The latest ICRU 90 recommendations on key data for ionizing-radiation dosimetry were adopted to calculate the electronic stopping powers and to select the mean energy to create an ion pair in dry air ([Formula: see text]). For modulated proton beams, [Formula: see text] factors were calculated in the middle of a spread-out Bragg peak, while for monoenergetic proton beams they were calculated at the entrance region. Fifteen ionization chambers were simulated. The [Formula: see text] factors calculated in this work were found to agree within 0.8% or better with the experimental data reported in the literature. For some ionization chambers, the simulation of proton nuclear interactions were found to have an effect on the [Formula: see text] factors of up to 1%; while for some others, perturbation factors were found to differ from unity by more than 1%. In addition, the combined standard uncertainty in the MC calculated [Formula: see text] factors in proton beams was estimated to be of the order of 1%. Thus, the results of this work seem to indicate that: (i) the simulation of proton nuclear interactions should be included in the MC calculation of [Formula: see text] factors in proton beams, (ii) perturbation factors in proton beams should not be neglected, and (iii) the detailed MC simulation of ionization chambers allows for an accurate and precise calculation of [Formula: see text] factors in clinical proton beams.

Plan Quality and Secondary Cancer Risk Assessment in Patients with Benign Intracranial Lesions after Radiosurgery using the CyberKnife M6 Robotic Radiosurgery System.

This study was performed to examine the quality of planning and treatment modality using a CyberKnife (CK) robotic radiosurgery system with multileaf collimator (MLC)-based plans and IRIS (variable aperture collimator system)-based plans in relation to the dose-response of secondary cancer risk (SCR) in patients with benign intracranial tumors. The study population consisted of 15 patients with benign intracranial lesions after curative treatment using a CyberKnife M6 robotic radiosurgery system. Each patient had a single tumor with a median volume of 6.43 cm3 (range, 0.33-29.72 cm3). The IRIS-based plan quality and MLC-based plan quality were evaluated by comparing the dosimetric indices, taking into account the planning target volume (PTV) coverage, the conformity index (CI), and the dose gradient (R10% and R50%). The dose-response SCR with sarcoma/carcinoma induction was calculated using the concept of the organ equivalent dose (OED). Analyses of sarcoma/carcinoma induction were performed using excess absolute risk (EAR) and various OED models of dose-response type/lifetime attributable risk (LAR). Moreover, analyses were performed using the BEIR VII model. PTV coverage using both IRIS-based plans and MLC-based plans was identical, although the CI values obtained using the MLC-based plans showed greater statistical significance. In comparison with the IRIS-based plans, the MLC-based plans showed better dose falloff for R10% and R50% evaluation. The estimated difference between Schneider's model and BEIR VII in linear-no-threshold (Lnt) cumulative EAR was about twofold. The average values of LAR/EAR for carcinoma, for the IRIS-based plans, were 25% higher than those for the MLC-based plans using four SCR models; for sarcoma, they were 15% better in Schneider's SCR models. MLC-based plans showed slightly better conformity, dose gradients, and SCR reduction. There was a slight increase in SCR with IRIS-based plans in comparison with MLC-based plans. EAR analyses did not show any significant difference between PTV and brainstem analyses, regardless of the tumor volume. Nevertheless, an increase in target volume led to an increase in the probability of SCR. EAR showed statistically significant differences in the soft tissue according to tumor volume (1-10 cc and ≥10 cc).

Comparative study of alternative Geant4 hadronic ion inelastic physics models for prediction of positron-emitting radionuclide production in carbon and oxygen ion therapy.

The distribution of fragmentation products predicted by Monte Carlo simulations of heavy ion therapy depend on the hadronic physics model chosen in the simulation. This work aims to evaluate three alternative hadronic inelastic fragmentation physics options available in the Geant4 Monte Carlo radiation physics simulation framework to determine which model most accurately predicts the production of positron-emitting fragmentation products observable using in-beam PET imaging. Fragment distributions obtained with the BIC, QMD, and INCL + + physics models in Geant4 version 10.2.p03 are compared to experimental data obtained at the HIMAC heavy-ion treatment facility at NIRS in Chiba, Japan. For both simulations and experiments, monoenergetic beams are applied to three different block phantoms composed of gelatin, poly(methyl methacrylate) and polyethylene. The yields of the positron-emitting nuclei 11C, 10C and 15O obtained from simulations conducted with each model are compared to the experimental yields estimated by fitting a multi-exponential radioactive decay model to dynamic PET images using the normalised mean square error metric in the entrance, build up/Bragg peak and tail regions. Significant differences in positron-emitting fragment yield are observed among the three physics models with the best overall fit to experimental 12C and 16O beam measurements obtained with the BIC physics model.

Assessment of Image Quality and Dosimetric Performance of CT Simulators.

BACKGROUND: CT simulator for radiation therapy aims to produce high-quality images for dose calculation and delineation of target and organs at risk in the process of treatment planning. Selection of CT imaging protocols that achieve a desired image quality while minimizing patient dose depends on technical CT parameters and their relationship with image quality and radiation dose. For similar imaging protocols using comparable technical CT parameters, there are also variations in image quality metrics between different CT simulator models. Understanding the relationship and variation is important for selecting appropriate imaging protocol and standardizing QC process. Here, we proposed an automated method to determine the relationship between image quality and radiation dose for various CT technical parameters. MATERIAL AND METHOD: The impact of scan parameters on various aspects of image quality and volumetric CT dose index for a Philips Brilliance Big Bore and a Toshiba Aquilion One CT scanners were determined by using commercial phantom and automated image quality analysis software and cylindrical radiation dose phantom. RESULTS AND DISCUSSION: Both scanners had very similar and satisfactory performance based on the diagnostic acceptance criteria recommended by ACR, International Atomic Energy Agency, and American Association of Physicists in Medicine. However, our results showed a compromise between different image quality components such as low-contrast and spatial resolution with the change of scanning parameters and revealed variations between the two scanners on their image quality performance. Measurement using a generic phantom and analysis by automated software was unbiased and efficient. CONCLUSION: This method provides information that can be used as a baseline for CT scanner image quality and dosimetric QC for different CT scanner models in a given institution or across sites.

Dosimetric accuracy and radiobiological implications of ion computed tomography for proton therapy treatment planning.

Ion computed tomography (iCT) represents a potential replacement for x-ray CT (xCT) in ion therapy treatment planning to reduce range uncertainties, inherent in the semi-empirical conversion of xCT information into relative stopping power (RSP). In this work, we aim to quantify the increase in dosimetric accuracy associated with using proton-, helium- and carbon-CT compared to conventional xCT for clinical scenarios in proton therapy. Three cases imaged with active beam-delivery using an ideal single-particle-tracking detector were investigated using FLUKA Monte-Carlo (MC) simulations. The RSP accuracy of the iCTs was evaluated against the ground truth at similar physical dose. Next, the resulting dosimetric accuracy was investigated by using the RSP images as a patient model in proton therapy treatment planning, in comparison to common uncertainties associated with xCT. Finally, changes in relative biological effectiveness (RBE) with iCT particle type/spectrum were investigated by incorporating the repair-misrepair-fixation (RMF) model into FLUKA, to enable first insights on the associated biological imaging dose. Helium-CT provided the lowest overall RSP error, whereas carbon-CT offered the highest accuracy for bone and proton-CT for soft tissue. For a single field, the average relative proton beam-range variation was -1.00%, +0.09%, -0.08% and -0.35% for xCT, proton-, helium- and carbon-CT, respectively. Using a 0.5%/0.5mm gamma-evaluation, all iCTs offered comparable accuracy with a better than 99% passing rate, compared to 83% for xCT. The RMF model predictions for RBE for cell death relative to a diagnostic xCT spectrum were 0.82-0.85, 0.85-0.89 and 0.97-1.03 for proton-, helium-, and carbon-CT, respectively. The corresponding RBE for DNA double-strand break induction was generally below one. iCT offers great clinical potential for proton therapy treatment planning by providing superior dose calculation accuracy as well as lower physical and potentially biological dose exposure compared to xCT. For the investigated dose level and ideal detector, proton-CT and helium-CT yielded the best performance.

Impact of machine log-files uncertainties on the quality assurance of proton pencil beam scanning treatment delivery.

Irradiation log-files store useful information about the plan delivery, and together with independent Monte Carlo dose engine calculations can be used to reduce the time needed for patient-specific quality assurance (PSQA). Nonetheless, machine log-files carry an uncertainty associated to the measurement of the spot position and intensity that can influence the correct evaluation of the quality of the treatment delivery. This work addresses the problem of the inclusion of these uncertainties for the final verification of the treatment delivery. Dedicated measurements performed in an IBA Proteus Plus gantry with a pencil beam scanning (PBS) dedicated nozzle have been carried out to build a 'room-dependent' model of the spot position uncertainties. The model has been obtained through interpolation of the look-up tables describing the systematic and random uncertainties, and it has been tested for a clinical case of a brain cancer patient irradiated in a dry-run. The delivered dose has been compared with the planned dose with the inclusion of the errors obtained applying the model. Our results suggest that the accuracy of the treatment delivery is higher than the spot position uncertainties obtained from the log-file records. The comparison in terms of DVHs shows that the log-reconstructed dose is compatible with the planned dose within the 95% confidence interval obtained applying our model. The initial mean dose difference between the calculated dose to the patient based on the plan and recorded data is around 1%. The difference is essentially due to the log-file uncertainties and it can be removed with a correct treatment of these errors. In conclusion our new PSQA protocol allows for a fast verification of the dose delivered after every treatment fraction through the use of machine log-files and an independent Monte Carlo dose engine. Moreover, the inclusion of log-file uncertainties in the dose calculation allows for a correct evaluation of the quality of the treatment plan delivery.

Design and commissioning of the non-dedicated scanning proton beamline for ocular treatment at the synchrotron-based CNAO facility.

PURPOSE: Only few centers worldwide treat intraocular tumors with proton therapy, all of them with a dedicated beamline, except in one case in the USA. The Italian National Center for Oncological Hadrontherapy (CNAO) is a synchrotron-based hadrontherapy facility equipped with fixed beamlines and pencil beam scanning modality. Recently, a general-purpose horizontal proton beamline was adapted to treat also ocular diseases. In this work, the conceptual design and main dosimetric properties of this new proton eyeline are presented. METHODS: A 28 mm thick water-equivalent range shifter (RS) was placed along the proton beamline to shift the minimum beam penetration at shallower depths. FLUKA Monte Carlo (MC) simulations were performed to optimize the position of the RS and patient-specific collimator, in order to achieve sharp lateral dose gradients. Lateral dose profiles were then measured with radiochromic EBT3 films to evaluate the dose uniformity and lateral penumbra width at several depths. Different beam scanning patterns were tested. Discrete energy levels with 1 mm water-equivalent step within the whole ocular energy range (62.7-89.8 MeV) were used, while fine adjustment of beam range was achieved using thin polymethylmethacrylate additional sheets. Depth-dose distributions (DDDs) were measured with the Peakfinder system. Monoenergetic beam weights to achieve flat spread-out Bragg Peaks (SOBPs) were numerically determined. Absorbed dose to water under reference conditions was measured with an Advanced Markus chamber, following International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice. Neutron dose at the contralateral eye was evaluated with passive bubble dosimeters. RESULTS: Monte Carlo simulations and experimental results confirmed that maximizing the air gap between RS and aperture reduces the lateral dose penumbra width of the collimated beam and increases the field transversal dose homogeneity. Therefore, RS and brass collimator were placed at about 98 cm (upstream of the beam monitors) and 7 cm from the isocenter, respectively. The lateral 80%-20% penumbra at middle-SOBP ranged between 1.4 and 1.7 mm depending on field size, while 90%-10% distal fall-off of the DDDs ranged between 1.0 and 1.5 mm, as a function of range. Such values are comparable to those reported for most existing eye-dedicated facilities. Measured SOBP doses were in very good agreement with MC simulations. Mean neutron dose at the contralateral eye was 68 µSv/Gy. Beam delivery time, for 60 Gy relative biological effectiveness (RBE) prescription dose in four fractions, was around 3 min per session. CONCLUSIONS: Our adapted scanning proton beamline satisfied the requirements for intraocular tumor treatment. The first ocular treatment was delivered in August 2016 and more than 100 patients successfully completed their treatment in these 2 yr.