Development and Validation of Multiparametric MRI-based Radiomics Models for Preoperative Risk Stratification of Endometrial Cancer.

Background Stratifying high-risk histopathologic features in endometrial carcinoma is important for treatment planning. Radiomics analysis at preoperative MRI holds potential to identify high-risk phenotypes. Purpose To evaluate the performance of multiparametric MRI three-dimensional radiomics-based machine learning models for differentiating low- from high-risk histopathologic markers-deep myometrial invasion (MI), lymphovascular space invasion (LVSI), and high-grade status-and advanced-stage endometrial carcinoma. Materials and Methods This dual-center retrospective study included women with histologically proven endometrial carcinoma who underwent 1.5-T MRI before hysterectomy between January 2011 and July 2015. Exclusion criteria were tumor diameter less than 1 cm, missing MRI sequences or histopathology reports, neoadjuvant therapy, and malignant neoplasms other than endometrial carcinoma. Three-dimensional radiomics features were extracted after tumor segmentation at MRI (T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI). Predictive features were selected in the training set with use of random forest (RF) models for each end point, and trained RF models were applied to the external test set. Five board-certified radiologists conducted MRI-based staging and deep MI assessment in the training set. Areas under the receiver operating characteristic curve (AUCs) were reported with balanced accuracies, and radiologists' readings were compared with radiomics with use of McNemar tests. Results In total, 157 women were included: 94 at the first institution (training set; mean age, 66 years ± 11 [SD]) and 63 at the second institution (test set; 67 years ± 12). RF models dichotomizing deep MI, LVSI, high grade, and International Federation of Gynecology and Obstetrics (FIGO) stage led to AUCs of 0.81 (95% CI: 0.68, 0.88), 0.80 (95% CI: 0.67, 0.93), 0.74 (95% CI: 0.61, 0.86), and 0.84 (95% CI: 0.72, 0.92), respectively, in the test set. In the training set, radiomics provided increased performance compared with radiologists' readings for identifying deep MI (balanced accuracy, 86% vs 79%; P = .03), while no evidence of a difference was observed in performance for advanced FIGO stage (80% vs 78%; P = .27). Conclusion Three-dimensional radiomics can stratify patients by using preoperative MRI according to high-risk histopathologic end points in endometrial carcinoma and provide nonsignificantly different or higher performance than radiologists in identifying advanced stage and deep myometrial invasion, respectively. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kido and Nishio in this issue.

Head and neck squamous cell carcinoma: prediction of cervical lymph node metastasis by dual-energy CT texture analysis with machine learning.

OBJECTIVES: This study was conducted in order to evaluate a novel risk stratification model using dual-energy CT (DECT) texture analysis of head and neck squamous cell carcinoma (HNSCC) with machine learning to (1) predict associated cervical lymphadenopathy and (2) compare the accuracy of spectral versus single-energy (65 keV) texture evaluation for endpoint prediction. METHODS: Eighty-seven patients with HNSCC were evaluated. Texture feature extraction was performed on virtual monochromatic images (VMIs) at 65 keV alone or different sets of multi-energy VMIs ranging from 40 to 140 keV, in addition to iodine material decomposition maps and other clinical information. Random forests (RF) models were constructed for outcome prediction with internal cross-validation in addition to the use of separate randomly selected training (70%) and testing (30%) sets. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for predicting positive versus negative nodal status in the neck. RESULTS: Depending on the model used and subset of patients evaluated, an accuracy, sensitivity, specificity, PPV, and NPV of up to 88, 100, 67, 83, and 100%, respectively, could be achieved using multi-energy texture analysis. Texture evaluation of VMIs at 65 keV alone or in combination with only iodine maps had a much lower accuracy. CONCLUSIONS: Multi-energy DECT texture analysis of HNSCC is superior to texture analysis of 65 keV VMIs and iodine maps alone and can be used to predict cervical nodal metastases with relatively high accuracy, providing information not currently available by expert evaluation of the primary tumor alone. KEY POINTS: • Texture features of HNSCC tumor are predictive of nodal status. • Multi-energy texture analysis is superior to analysis of datasets at a single energy. • Dual-energy CT texture analysis with machine learning can enhance noninvasive diagnostic tumor evaluation.

Time-resolved diode dosimetry calibration through Monte Carlo modeling for in vivo passive scattered proton therapy range verification.

PURPOSE: Our group previously introduced an in vivo proton range verification methodology in which a silicon diode array system is used to correlate the dose rate profile per range modulation wheel cycle of the detector signal to the water-equivalent path length (WEPL) for passively scattered proton beam delivery. The implementation of this system requires a set of calibration data to establish a beam-specific response to WEPL fit for the selected 'scout' beam (a 1 cm overshoot of the predicted detector depth with a dose of 4 cGy) in water-equivalent plastic. This necessitates a separate set of measurements for every 'scout' beam that may be appropriate to the clinical case. The current study demonstrates the use of Monte Carlo simulations for calibration of the time-resolved diode dosimetry technique. METHODS: Measurements for three 'scout' beams were compared against simulated detector response with Monte Carlo methods using the Tool for Particle Simulation (TOPAS). The 'scout' beams were then applied in the simulation environment to simulated water-equivalent plastic, a CT of water-equivalent plastic, and a patient CT data set to assess uncertainty. RESULTS: Simulated detector response in water-equivalent plastic was validated against measurements for 'scout' spread out Bragg peaks of range 10 cm, 15 cm, and 21 cm (168 MeV, 177 MeV, and 210 MeV) to within 3.4 mm for all beams, and to within 1 mm in the region where the detector is expected to lie. CONCLUSION: Feasibility has been shown for performing the calibration of the detector response for three 'scout' beams through simulation for the time-resolved diode dosimetry technique in passive scattered proton delivery.

Implementation of an efficient Monte Carlo calculation for CBCT scatter correction: phantom study.

Cone-beam computed tomography (CBCT) images suffer from poor image quality, in a large part due to contamination from scattered X-rays. In this work, a Monte Carlo (MC)-based iterative scatter correction algorithm was implemented on measured phantom data acquired from a clinical on-board CBCT scanner. An efficient EGSnrc user code (egs_cbct) was used to transport photons through an uncorrected CBCT scan of a Catphan 600 phantom. From the simulation output, the contribution from primary and scattered photons was estimated in each projection image. From these estimates, an iterative scatter correction was performed on the raw CBCT projection data. The results of the scatter correction were compared with the default vendor reconstruction. The scatter correction was found to reduce the error in CT number for selected regions of interest, while improving contrast-to-noise ratio (CNR) by 18%. These results demonstrate the performance of the proposed scatter correction algorithm in improving image quality for clinical CBCT images.

Late radiation toxicity in Hodgkin lymphoma patients: proton therapy's potential.

In 2010, all young patients treated for intrathoracic Hodgkin lymphoma (HL) at one of 10 radiotherapy centers in the province of Quebec received 3D conformal photon therapy. These patients may now be at risk for late effects of their treatment, notably secondary malignancies and cardiac toxicity. We hypothesized that more complex radiotherapy, including intensity-modulated proton therapy (IMPT) and possibly IMRT (in the form of helical tomotherapy (HT)), could benefit these patients. With institutional review board approval at 10 institutions, all treatment plans for patients under the age of 30 treated for HL during a six-month consecutive period of 2010 were retrieved. Twenty-six patients were identified, and after excluding patients with extrathoracic radiation or treatment of recurrence, 20 patients were replanned for HT and IMPT. Neutron dose for IMPT plans was estimated from published measurements. The relative seriality model was used to predict excess risk of cardiac mortality. A modified linear quadratic model was used to predict the excess absolute risk for induction of lung cancer and, in female patients, breast cancer. Model parameters were derived from published data. Predicted risk for cardiac mortality was similar among the three treatment techniques (absolute excess risk of cardiac mortality was not reduced for HT or IMPT (p > 0.05, p > 0.05) as compared to 3D CRT). Predicted risks were increased for HT and reduced for IMPT for secondary lung cancer (p < 0.001, p < 0.001) and breast cancers (p< 0.001, p< 0.001) as compared to 3D CRT.

Monte Carlo investigation of collapsed versus rotated IMRT plan verification.

IMRT QA requires, among other tests, a time-consuming process of measuring the absorbed dose, at least to a point, in a high-dose, low-dose-gradient region. Some clinics use a technique of measuring this dose with all beams delivered at a single gantry angle (collapsed delivery), as opposed to the beams delivered at the planned gantry angle (rotated delivery). We examined, established, and optimized Monte Carlo simulations of the dosimetry for IMRT verification of treatment plans for these two different delivery modes (collapsed versus rotated). The results of the simulations were compared to the treatment planning system dose calculations for the two delivery modes, as well as to measurements taken. This was done in order to investigate the validity of the use of a collapsed delivery technique for IMRT QA. The BEAMnrc, DOSXYZnrc, and egs_chamber codes were utilized for the Monte Carlo simulations along with the MMCTP system. A number of different plan complexity metrics were also used in the analysis of the dose distributions in a bid to qualify why verification in a collapsed delivery may or may not be optimal for IMRT QA. Following the Alfonso et al. formalism, the kfclin,frefQclin,Q correction factor was calculated to correct the deviation of small fields from the reference conditions used for beam calibration. We report on the results obtained for a cohort of 20 patients. The plan complexity was investigated for each plan using the complexity metrics of homogeneity index, conformity index, modulation complexity score, and the fraction of beams from a particular plan that intersect the chamber when performing the QA. Rotated QA gives more consistent results than the collapsed QA technique. The kfclin,frefQclin,Qfactor deviates less from 1 for rotated QA than for collapsed QA. If the homogeneity index is less than 0.05 then the kfclin,frefQclin,Q factor does not deviate from unity by more than 1%. A value this low for the homogeneity index can only be obtained with the rotated QA technique.

Radiochromic film based dosimetry of image-guidance procedures on different radiotherapy modalities.

In this work we compare doses from imaging procedures performed on today's state-of-the-art integrated imaging systems using a reference radiochromic film dosimetry system. Skin dose and dose profile measurements from different imaging systems were performed using radiochromic films at different anatomical sites on a humanoid RANDO phantom. EBT3 film was used to measure imaging doses from a TomoTherapy MVCT system, while XRQA2 film was used for dose measurements from kilovoltage imaging systems (CBCT on 21eX and TrueBeam Varian linear accelerators and CyberKnife stereoscopic orthogonal imagers). Maximum measured imaging doses in cGy at head, thorax, and pelvis regions were respectively 0.50, 1.01, and 4.91 for CBCT on 21eX, 0.38, 0.84, and 3.15 for CBCT on TrueBeam, 4.33, 3.86, and 6.50 for CyberKnife imagers, and 3.84, 1.90, and 2.09 for TomoTherapy MVCT. In addition, we have shown how an improved calibration system of XRQA2 film can achieve dose uncertainty level of better than 2% for doses above 0.25 cGy. In addition to simulation-based studies in literature, this study provides the radiation oncology team with data necessary to aid in their decision about imaging frequency for image-guided radiation therapy protocols.

A semi-analytical procedure to determine the ion recombination correction factor in high dose-per-pulse beams.

BACKGROUND: The conventional theories and methods of determining the ion recombination correction factor, such as Boag theory and the related two voltage method and Jaffé plot extrapolation, do not seem to yield accurate results in FLASH /high dose per pulse (DPP) beams ( > $>$ 10 mGy DPP). This is due to the presence of a large free electron fraction that distorts the electric field inside the chamber sensitive volume. To understand the influence of these effects on the ion recombination correction factor and to develop new expressions for it, it is necessary to re-visit the underlying physics. PURPOSE: To present a mathematical procedure to develop an analytical expression for the ion recombination correction factor. The expression is the basis for an extrapolation method so the correction factor can be determined in a clinical setting. METHODS: A semi-analytical solution method, the homotopy perturbation method (HPM), is used to solve the partial differential equations (PDEs) describing the charge carrier physics, including space charge and free electrons. The electron velocity and attachment rate are modeled as functions of the electric field strength. An expression for the charge collection efficiency and ion recombination correction factor are developed. A fit procedure based on this expression is used to compare it to measured data from previously published articles. Another fit procedure using a general equation is also proposed and compared to the data. RESULTS: The series obtained for the charge collection efficiency and the ion recombination correction factor are determined to be asymptotic series and the optimal truncation established. The ion recombination correction factor exhibits a 1 / V 2 $1/V^2$ dependency due to the free electron presence. The fit using this expression agrees well with measured data as long as (1) the DPP is below 1 Gy for chambers with a 1 mm plate separation and (2) when the DPP is below 3 Gy for chambers with a 0.5 mm plate separation. In these DPP ranges, the deviation between measured and fit value did not exceed 6%. In both chamber cases the voltage range where the fit applies decreases as DPP increases. The general equation yielded comparable results. CONCLUSIONS: The HPM was shown to be applicable to a complex system of PDEs and generate meaningful and novel solutions, as they include both space charge and free electrons. The HPM also lends itself to other chamber geometries. The fit procedure was also shown to yield accurate results for the ion recombination correction up to the 1 Gy DPP level.

A joint ESTRO and AAPM guideline for development, clinical validation and reporting of artificial intelligence models in radiation therapy.

BACKGROUND AND PURPOSE: Artificial Intelligence (AI) models in radiation therapy are being developed with increasing pace. Despite this, the radiation therapy community has not widely adopted these models in clinical practice. A cohesive guideline on how to develop, report and clinically validate AI algorithms might help bridge this gap. METHODS AND MATERIALS: A Delphi process with all co-authors was followed to determine which topics should be addressed in this comprehensive guideline. Separate sections of the guideline, including Statements, were written by subgroups of the authors and discussed with the whole group at several meetings. Statements were formulated and scored as highly recommended or recommended. RESULTS: The following topics were found most relevant: Decision making, image analysis, volume segmentation, treatment planning, patient specific quality assurance of treatment delivery, adaptive treatment, outcome prediction, training, validation and testing of AI model parameters, model availability for others to verify, model quality assurance/updates and upgrades, ethics. Key references were given together with an outlook on current hurdles and possibilities to overcome these. 19 Statements were formulated. CONCLUSION: A cohesive guideline has been written which addresses main topics regarding AI in radiation therapy. It will help to guide development, as well as transparent and consistent reporting and validation of new AI tools and facilitate adoption.

An investigation into the use of MMCTP to tune accelerator source parameters and testing its clinical application.

This paper presents an alternative method to tune Monte Carlo electron beam parameters to match measured data using a minimal set of variables in order to reduce the model setup time prior to clinical implementation of the model. Monte Carlo calculations provide the possibility of a powerful treatment planning verification technique. The nonstandardized and nonautomated process of tuning the required accelerator model is one of the reasons for delays in the clinical implementation of Monte Carlo techniques. This work aims to establish and verify an alternative tuning method that can be carried out in a minimal amount of time, allowing it to be easily implemented in a clinical setting by personnel with minimal experience with Monte Carlo methods. This tuned model can then be incorporated into the MMCTP system to allow the system to be used as a second dose calculation check for IMRT plans. The technique proposed was used to establish the primary electron beam parameters for accelerator models for the Varian Clinac 2100 6 MV photon beam using the BEAMnrc Monte Carlo system. The method is intended to provide a clear, direct, and efficient process for tuning an accelerator model using readily available clinical quality assurance data. The tuning provides a refined model, which agrees with measured dose profile curves within 1.5% outside the penumbra or 3 mm in the penumbra, for square fields with sides of 3 cm up to 30 cm. These models can then be employed as the basis for Monte Carlo recalculations of dose distributions, using the MMCTP system, for clinical treatment plans, providing an invaluable assessment tool. This was tested on six IMRT plans and compared to the measurements performed for the pretreatment QA process. These Monte Carlo values for the average dose to the chamber volume agreed with measurements to within 0.6%.

Applying the column generation method to the intensity modulated high dose rate brachytherapy inverse planning problem.

Objective.Intensity modulated high dose rate brachytherapy (IMBT) is a rapidly developing application of brachytherapy where anisotropic dose distributions can be produced at each source dwell position. This technique is made possible by placing rotating metallic shields inside brachytherapy needles or catheters. By dynamically directing the radiation towards the tumours and away from the healthy tissues, a more conformal dose distribution can be obtained. The resulting treatment planning involves optimizing dwell position and shield angle (DPSA). The aim of this study was to investigate the column generation method for IMBT treatment plan optimization.Approach.A column generation optimization algorithm was developed to optimize the dwell times and shield angles. A retrospective study was performed on 10 prostate cases using RapidBrachyMCTPS. At every iteration, the plan was optimized with the chosen DPSA which would best improve the cost function that was added to the plan. The optimization process was stopped when the remaining DPSAs would not add value to the plan to limit the plan complexity.Main results.The average number of DPSAs and voxels were 2270 and 7997, respectively. The column generation approach yielded near-optimal treatment plans by using only 11% of available DPSAs on average in ten prostate cases. The coverage and organs at risk constraints passed in all ten cases.Significance.The column generation method produced high-quality deliverable prostate IMBT plans. The treatment plan quality reached a plateau, where adding more DPSAs had a minimal effect on dose volume histogram parameters. The iterative nature of the column generation method allows early termination of the treatment plan creation process as soon as the dosimetric indices from dose volume histogram satisfy the clinical requirements or if their values stabilize.

Robust mixed electron-photon radiation therapy planning for soft tissue sarcoma.

BACKGROUND: Mixed electron-photon beam radiation therapy (MBRT) is an emerging technique in which external electron and photon beams are simultaneously optimized into a single treatment plan. MBRT exploits the steep dose falloff and high surface dose of electrons while maintaining target conformity by leveraging the sharp penumbra of photons. PURPOSE: This study investigates the dosimetric benefits of MBRT for soft tissue sarcoma (STS) patients. MATERIAL AND METHODS: A retrospective cohort of 22 STS of the lower extremity treated with conventional photon-based Volumetric Modulated Arc Therapy (VMAT) were replanned with MBRT. Both VMAT and MBRT treatments were planned on the Varian TrueBeam linac using the Millenium multi-leaf collimator. No electron applicator, cutout or additional collimating devices were used for electron beams of MBRT plans. MBRT plans were optimized to use a combination of 6 MV photons and five electron energies (6, 9, 12, 16, 20 MeV) by a robust column generation algorithm. Electron beams in this study were planned at standard 100 cm source-axis distance (SAD). The dose to the clinical target volume (CTV), bone, normal tissue strip and other organs-at-risk (OARs) were compared using a Wilcoxon signed-rank test. RESULTS: As part of the original VMAT treatment, tissue-equivalent bolus was required in 10 of the 22 patients. MBRT plans did not require bolus by virtue of the higher electron entrance dose. CTV coverage by the prescription dose was found to be clinically equivalent between plans of either modality: V 50Gy $V_{\text{50Gy}}$ (MBRT) = 97.9 ± 0.2% versus V 50Gy $V_{\text{50Gy}}$ (VMAT) = 98.1 ± 0.6% (p=0.34). Evaluating the absolute paired difference between doses to OARs in MBRT and VMAT plans, we observed lower V 20Gy $V_{\text{20Gy}}$ to normal tissue in MBRT plans by 14.9 ± 3.2% ( p < 10 - 6 $p<10^{-6}$ ). Similarly, V 50Gy $V_{\text{50Gy}}$ to bone was found to be decreased by 8.2 ± 4.0% ( p < 10 - 3 $p<10^{-3}$ ) of the bone volume. CONCLUSION: For STS with subcutaneous involvement, MBRT offers statistically significant sparing of OARs without sacrificing target coverage when compared to VMAT. MBRT plans are deliverable on conventional linacs without the use of electron applicators, shortened source-to-surface distance (SSD) or bolus. This study shows that MBRT is a logistically feasible technique with clear dosimetric benefits.

Proton Therapy Equipment Installation, Upgrades, and Building Design.

PURPOSE: This work aims at reviewing challenges and pitfalls in proton facility design related to equipment upgrade or replacement. Proton therapy was initially developed at research institutions in the 1950s which ushered in the use of hospital-based machines in 1990s. We are approaching an era where older commercial machines are reaching the end of their life and require replacement. The future widespread application of proton therapy depends on cost reduction; customized building design and installation are significant expenses. METHODS AND MATERIALS: We take this opportunity to discuss how commercial proton machines have been installed and how buildings housing the equipment have been designed. RESULTS: Data on dimensions and weights of the larger components of proton systems (cyclotron main magnet and gantries) are presented and innovative, non-gantry-based, patient positioning systems are discussed. CONCLUSIONS: We argue that careful consideration of the building design to include larger elevators, hoistways from above, wide corridors and access slopes to below grade installations, generic vault and treatment room layouts to accommodate multiple vendor's equipment, and modular system design can provide specific benefits during planning, installation, maintenance, and replacement phases of the project. Room temperature magnet coils can be constructed in a more modular manner: a potential configuration is presented. There is scope for constructing gantries and magnet yokes from smaller modular sub-units. These considerations would allow a hospital to replace a commercial machine at its end of life in a manner similar to a linac.

Effects of incoming particle energy and cluster size on the G-value of hydrated electrons.

In hydrated electron (e-aq) dosimetry, absorbed radiation dose to water is measured by monitoring the concentration of radiation-induced e-aq. However, to obtain accurate dose, the radiation chemical yield of e-aq, G(e-aq), is needed for the radiation quality/setup under investigation. The aim of this study was to investigate the time-evolution of the G-values for the main generated reactive species during water radiolysis using GEANT4-DNA. The effects of cluster size and linear energy transfer (LET) on G(e-aq) were examined. Validity of GEANT4-DNA for calculation of G(e-aq) for clinically relevant energies was studied. Three scenarios were investigated with different phantom sizes and incoming electron energies (1 keV to 1 MeV). The time evolution of G(e-aq) was in good agreement with published data and did not change with decreasing phantom size. The time-evolution of the G-values increases with increasing LET for all radiolytic species. The particle tracks formed with high-energy electrons are separated and the resulting reactive species develop independently in time. With decreasing energy, the mean separation distance between reactive species decreases. The particle tracks might not initially overlap but will overlap shortly thereafter due to diffusion of reactive species, increasing the probability of e-aq recombination with other species. This also explains the decrease of G(e-aq) with cluster size and LET. Finally, if all factors are kept constant, as the incoming electron energy increases to clinically relevant energies, G(e-aq) remains similar to its value at 1 MeV, hence GEANT4-DNA can be used for clinically relevant energies.

Validation of an orthotopic non-small cell lung cancer mouse model, with left or right tumor growths, to use in conformal radiotherapy studies.

Orthotopic non-small cell lung cancer (NSCLC) mice models are important for establishing translatability of in vitro results. However, most orthotopic lung models do not produce localized tumors treatable by conformal radiotherapy (RT). Here we report on the performance of an orthotopic mice model featuring conformal RT treatable tumors following either left or right lung tumor cell implantation. Athymic Nude mice were surgically implanted with H1299 NSCLC cell line in either the left or right lung. Tumor development was tracked bi-weekly using computed tomography (CT) imaging. When lesions reached an appropriate size for treatment, animals were separated into non-treatment (control group) and RT treated groups. Both RT treated left and right lung tumors which were given a single dose of 20 Gy of 225 kV X-rays. Left lung tumors were treated with a two-field parallel opposed plan while right lung tumors were treated with a more conformal four-field plan to assess tumor control. Mice were monitored for 30 days after RT or after tumor reached treatment size for non-treatment animals. Treatment images from the left and right lung tumor were also used to assess the dose distribution for four distinct treatment plans: 1) Two sets of perpendicularly staggered parallel opposed fields, 2) two fields positioned in the anterior-posterior and posterior-anterior configuration, 3) an 180° arc field from 0° to 180° and 4) two parallel opposed fields which cross through the contralateral lung. Tumor volumes and changes throughout the follow-up period were tracked by three different types of quantitative tumor size approximation and tumor volumes derived from contours. Ultimately, our model generated delineable and conformal RT treatable tumor following both left and right lung implantation. Similarly consistent tumor development was noted between left and right models. We were also able to demonstrate that a single 20 Gy dose of 225 kV X-rays applied to either the right or left lung tumor models had similar levels of tumor control resulting in similar adverse outcomes and survival. And finally, three-dimensional tumor approximation featuring volume computed from the measured length across three perpendicular axes gave the best approximation of tumor volume, most closely resembled tumor volumes obtained with contours.

Quality assurance for mixed electron-photon beam radiation therapy using treatment log files and MapCHECK.

BACKGROUND: Mixed photon-electron beam radiotherapy (MBRT) is a technique that combines the use of both photons and electrons in one single treatment plan to exploit their advantageous and complimentary characteristics. Compared to other photon treatment modalities, it has been shown that the MBRT technique contributes to better target coverage and organ-at-risk (OAR) sparing. However, the use of combined photons and electrons in one delivery makes the technique more complex and a well-established quality assurance (QA) protocol for MBRT is essential. PURPOSE: To investigate the feasibility of using MapCHECK and log file-dose reconstruction for MBRT plan verification and to recommend a patient-specific quality assurance (PSQA) protocol for MBRT. METHODS: MBRT plans were robustly optimized for five soft-tissue sarcoma (STS) patients. Each plan comprised step-and-shoot deliveries of a six MV photon beam and a combination of five electron beam energies at an SAD of 100 cm. The plans were delivered to the MapCHECK device with collapsed gantry angle and the 2D dose distributions at the detector depth were measured. To simulate the expected dose distribution delivered to the MapCHECK, a MapCHECK computational phantom was modeled in EGSnrc based on vendor-supplied blueprint information. The dose to the detectors in the model was scored using the DOSXYZnrc user code. The agreement between the measured and the simulated dose distribution was evaluated using 2D gamma analysis with a gamma criterion of 3%/2 mm and a low dose threshold of 10%. One of the plans was selected and delivered with a rotating gantry angle for trajectory log file collection. To evaluate the potential interlinac and intralinac differences, the plan was delivered repeatedly on three linacs. From the collected log files, delivery parameters were retrieved to recalculate the 3D dose distributions in the patient's anatomy with DOSXYZnrc. The recalculated mean dose to the clinical target volume (CTV) and OARs from all deliveries were computed and compared with the planned dose in terms of percentage difference. To validate the accuracy of log file-based QA, the log file-recalculated dose was also compared with film measurement. RESULTS: The agreement of the total dose distribution between the MapCHECK measurement and simulation showed gamma passing rates of above 97% for all five MBRT plans. In the log file-dose recalculation, the difference between the recalculated and the planned dose to the CTV and OARs was below 1% for all deliveries. No significant inter- or intralinac differences were observed. The log file-dose had a gamma passing rate of 98.6% compared to film measurement. CONCLUSION: Both the MapCHECK measurements and log file-dose recalculations showed excellent agreement with the expected dose distribution. This study demonstrates the potential of using MapCHECK and log files as MBRT QA tools.

Evaluation of Dosimetry Formalisms in Intraoperative Radiation Therapy of Glioblastoma.

PURPOSE: The intraoperative radiotherapy in newly diagnosed glioblastoma multiforme (INTRAGO) clinical trial assesses survival in patients with glioblastoma treated with intraoperative radiation therapy (IORT) using the INTRABEAM. Treatment planning for INTRABEAM relies on vendor-provided in-water depth dose curves obtained according to the TARGeted Intraoperative radioTherapy (TARGIT) dosimetry protocol. However, recent studies have shown discrepancies between the estimated TARGIT and delivered doses. This work evaluates the effect of the choice of dosimetry formalism on organs at risk (OAR) doses. METHODS AND MATERIALS: A treatment planning framework for INTRABEAM was developed to retrospectively calculate the IORT dose in 8 INTRAGO patients. These patients received an IORT prescription dose of 20 to 30 Gy in addition to external beam radiation therapy. The IORT dose was obtained using (1) the TARGIT method; (2) the manufacturer's V4.0 method; (3) the CQ method, which uses an ionization chamber Monte Carlo (MC) calculated factor; (4) MC dose-to-water; and (5) MC dose-to-tissue. The IORT dose was converted to 2 Gy fractions equivalent dose. RESULTS: According to the TARGIT method, the OAR dose constraints were respected in all cases. However, the other formalisms estimated a higher mean dose to OARs and revealed 1 case where the constraint for the brain stem was exceeded. The addition of the external beam radiation therapy and TARGIT IORT doses resulted in 10 cases of OARs exceeding the dose constraints. The more accurate MC calculation of dose-to-tissue led to the highest dosimetric differences, with 3, 3, 2, and 2 cases (out of 8) exceeding the dose constraint to the brain stem, optic chiasm, optic nerves, and lenses, respectively. Moreover, the mean cumulative dose to brain stem exceeded its constraint of 66 Gy with the MC dose-to-tissue method, which was not evident with the current INTRAGO clinical practice. CONCLUSIONS: The current clinical approach of calculating the IORT dose with the TARGIT method may considerably underestimate doses to nearby OARs. In practice, OAR dose constraints may have been exceeded, as revealed by more accurate methods.

GEANT4-DNA simulation of temperature-dependent and pH-dependent yields of chemical radiolytic species.

Objective.GEANT4-DNA can simulate radiation chemical yield (G-value) for radiolytic species such as the hydrated electron (eaq-) with the independent reaction times (IRT) method, however, only at room temperature and neutral pH. This work aims to modify the GEANT4-DNA source code to enable the calculation ofG-values for radiolytic species at different temperatures and pH values.Approach.In the GEANT4-DNA source code, values of chemical parameters such as reaction rate constant, diffusion coefficient, Onsager radius, and water density were replaced by corresponding temperature-dependent polynomials. The initial concentration of hydrogen ion (H+)/hydronium ion (H3O+) was scaled for a desired pH using the relationship pH = -log10[H+]. To validate our modifications, two sets of simulations were performed. (A) A water cube with 1.0 km sides and a pH of 7 was irradiated with an isotropic electron source of 1 MeV. The end time was 1µs. The temperatures varied from 25 °C to 150 °C. (B) The same setup as (A) was used, however, the temperature was set to 25 °C while the pH varied from 5 to 9. The results were compared with published experimental and simulated work.Main results.The IRT method in GEANT4-DNA was successfully modified to simulateG-values for radiolytic species at different temperatures and pH values. Our temperature-dependent results agreed with experimental data within 0.64%-9.79%, and with simulated data within 3.52%-12.47%. The pH-dependent results agreed well with experimental data within 0.52% to 3.19% except at a pH of 5 (15.99%) and with simulated data within 4.40%-5.53%. The uncertainties were below ±0.20%. Overall our results agreed better with experimental than simulation data.Significance.Modifications in the GEANT4-DNA code enabled the calculation ofG-values for radiolytic species at different temperatures and pH values.

An international approach to estimating the indications and number of eligible patients for carbon ion radiation therapy (CIRT) in Australia.

BACKGROUND AND PURPOSE: To establish the treatment indications and potential patient numbers for carbon ion radiation therapy (CIRT) at the proposed national carbon ion (and proton) therapy facility in the Westmead precinct, New South Wales (NSW), Australia. METHODS: An expert panel was convened, including representatives of four operational and two proposed international carbon ion facilities, as well as NSW-based CIRT stakeholders. They met virtually to consider CIRT available evidence and experience. Information regarding Japanese CIRT was provided pre- and post- the virtual meeting. Published information for South Korea was included in discussions. RESULTS: There was jurisdictional variation in the tumours treated by CIRT due to differing incidences of some tumours, referral patterns, differences in decisions regarding which tumours to prioritise, CIRT resources available and funding arrangements. The greatest level of consensus was reached that CIRT in Australia can be justified currently for patients with adenoid cystic carcinomas and mucosal melanomas of the head and neck, hepatocellular cancer and liver metastases, base of skull meningiomas, chordomas and chondrosarcomas. Almost 1400 Australian patients annually meet the consensus-derived indications now. CONCLUSION: A conservative estimate is that 1% of cancer patients in Australia (or 2% of patients recommended for radiation therapy) may preferentially benefit from CIRT for initial therapy of radiation resistant tumours, or to boost persistently active disease after other therapies, or for re-irradiation of recurrent disease. On this basis, one national carbon ion facility with up to four treatment rooms is justified for Australian patients.