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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Predicting histopathology markers of endometrial carcinoma with a quantitative image analysis approach based on spherical harmonics in multiparametric MRI.

PURPOSE: Identifying optimal machine learning pipelines for computer-aided diagnosis is key for the development of robust, reproducible, and clinically relevant imaging biomarkers for endometrial carcinoma. The purpose of this study was to introduce the mathematical development of image descriptors computed from spherical harmonics (SPHARM) decompositions as well as the associated machine learning pipeline, and to evaluate their performance in predicting deep myometrial invasion (MI) and histopathological high-grade in preoperative multiparametric magnetic resonance imaging (MRI). PATIENTS AND METHODS: This retrospective study included 128 women with histopathology-confirmed endometrial carcinomas who underwent 1.5-T MRI before hysterectomy between January 2011 and July 2015. SPHARM descriptors of each tumor were computed on multiparametric MRI images (T2-weighted, diffusion-weighted, dynamic contrast-enhanced-MRI and apparent diffusion coefficient maps). Tensor-based logistic regression was used to classify two-dimensional SPHARM rotationally-invariant descriptors. Head-to-head comparisons with radiomics analyses were performed with DeLong tests with Bonferroni-Holm correction to compare diagnostic performances. RESULTS: With all MRI contrasts, SPHARM analysis resulted in area under the curve, sensitivity, specificity, and balanced accuracy values of 0.94 (95% confidence interval [CI]: 0.85, 1.00), 100% (95% CI: 100, 100), 74% (95% CI: 51, 92), 87% (95% CI: 78, 98), respectively, for predicting deep MI. For predicting high-grade tumor histology, the corresponding values for the same diagnostic metrics were 0.81 (95% CI: 0.64, 0.90), 93% (95% CI: 67, 100), 63% (95% CI: 45, 79) and 78% (95% CI: 64, 86). The corresponding values achieved via radiomics were 0.92 (95% CI: 0.82, 0.95), 82% (95% CI: 65, 93), 80% (95% CI: 51, 94), 81% (95% CI: 70, 91) for deep MI and 0.72 (95% CI: 0.58, 0.83), 93% (95% CI: 65, 100), 55% (95% CI: 41, 69), 74% (95% CI: 52, 88) for high-grade histology. The diagnostic performance of the SPHARM analysis was not significantly different (P = 0.62) from that of radiomics for predicting deep MI but was significantly higher (P = 0.044) for predicting high-grade histology. CONCLUSION: The proposed SPHARM analysis yields similar or higher diagnostic performance than radiomics in identifying deep MI and high-grade status in histology-proven endometrial carcinoma.

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.

Monte Carlo calculation of the TG-43 dosimetry parameters for the INTRABEAM source with spherical applicators.

OBJECTIVE: The relative TG-43 dosimetry parameters of the INTRABEAM (Carl Zeiss Meditec AG, Jena, Germany) bare probe were recently reported by Ayala Alvarezet al(2020Phys. Med. Biol.65245041). The current study focuses on the dosimetry characterization of the INTRABEAM source with the eight available spherical applicators according to the TG-43 formalism using Monte Carlo (MC) simulations. APPROACH: This report includes the calculated dose-rate conversion coefficients that determine the absolute dose rate to water at a reference point of 10 mm from the applicator surface, based on calibration air-kerma rate measurements at 50 cm from the source on its transverse plane. Since the air-kerma rate measurements are not yet provided from a standards laboratory for the INTRABEAM, the values in the present study were calculated with MC. This approach is aligned with other works in the search for standardization of the dosimetry of electronic brachytherapy sources. As a validation of the MC model, depth dose calculations along the source axis were compared with calibration data from the source manufacturer. MAIN RESULTS: The calculated dose-rate conversion coefficients were 434.0 for the bare probe, and 683.5, 548.3, 449.9, 376.5, 251.0, 225.6, 202.8, and 182.6 for the source with applicators of increasing diameter from 15 to 50 mm, respectively. The radial dose and the 2D anisotropy functions of the TG-43 formalism were also obtained and tabulated in this document. SIGNIFICANCE: This work presents the data required by a treatment planning system for the characterization of the INTRABEAM system in the context of intraoperative radiotherapy applications.

Feasibility of operating a millimeter-scale graphite calorimeter for absolute dosimetry of small-field photon beams in the clinic.

PURPOSE: To characterize and build a cylindrically layered graphite calorimeter the size of a thimble ionization chamber for absolute dosimetry of small fields. This detector has been designed in a familiar probe format to facilitate integration into the clinical workflow. The feasibility of operating this absorbed dose calorimeter in quasi-adiabatic mode is assessed for high-energy accelerator-based photon beams. METHODS: This detector, herein referred to as Aerrow MK7, is a miniaturized version of a previously validated aerogel-insulated graphite calorimeter known as Aerrow. The new model was designed and developed using numerical methods. Medium conversion factors from graphite to water, small-field output correction factors, and layer perturbation factors for this dosimeter were calculated using the EGSnrc Monte Carlo code system. A range of commercially available aerogel densities were studied for the insulating layers, and an optimal density was selected by minimizing the small-field output correction factors. Heat exchange within the detector was simulated using a five-body compartmental heat transfer model. In quasi-adiabatic mode, the sensitive volume (a 3 mm diameter cylindrical graphite core) experiences a temperature rise during irradiation on the order of 1.3 mK·Gy-1 . The absorbed dose is obtained by calculating the product of this temperature rise with the specific heat capacity of the graphite. The detector was irradiated with 6 MV ( % dd ( 10 ) x  = 63.5%) and 10 MV ( % dd ( 10 ) x  = 71.1%) flattening filter-free (FFF) photon beams for two field sizes, characterized by S clin dimensions of 2.16 and 11.0 cm. The dose readings were compared against a calibrated Exradin A1SL ionization chamber. All dose values are reported at d max in water. RESULTS: The field output correction factors for this dosimeter design were computed for field sizes ranging from S clin  = 0.54 to 11.0 cm. For all aerogel densities studied, these correction factors did not exceed 1.5%. The relative dose difference between the two dosimeters ranged between 0.3% and 0.7% for all beams and field sizes. The smallest field size experimentally investigated, S clin  = 2.16 cm, which was irradiated with the 10 MV FFF beam, produced readings of 84.4 cGy (±1.3%) in the calorimeter and 84.5 cGy (±1.3%) in the ionization chamber. CONCLUSION: The median relative difference in absorbed dose values between a calibrated A1SL ionization chamber and the proposed novel graphite calorimeter was 0.6%. This preliminary experimental validation demonstrates that Aerrow MK7 is capable of accurate and reproducible absorbed dose measurements in quasi-adiabatic mode.

Comparison of quantitative and qualitative scoring approaches for radiation-induced pulmonary fibrosis as applied to a preliminary investigation into the efficacy of mesenchymal stem cell delivery methods in a rat model.

OBJECTIVES: Compare a quantitative, algorithm-driven, and qualitative, pathologist-driven, scoring of radiation-induced pulmonary fibrosis (RIPF). And using these scoring models to derive preliminary comparisons on the effects of different mesenchymal stem cell (MSC) administration modalities in reducing RIPF. METHODS: 25 rats were randomized into 5 groups: non-irradiated control (CG), irradiated control (CR), intraperitoneally administered granulocyte-macrophage colony stimulating factor or GM-CSF (Drug), intravascularly administered MSC (IV), and intratracheally administered MSC (IT). All groups, except CG, received an 18 Gy conformal dose to the right lung. Drug, IV and IT groups were treated immediately after irradiation. After 24 weeks of observation, rats were euthanized, their lungs excised, fixed and stained with Masson's Trichrome. Samples were anonymized and RIPF was scored qualitatively by a certified pathologist and quantitatively using ImageScope. An analysis of association was conducted, and two binary classifiers trained to validate the integrity of both qualitative and quantitative scoring. Differences between the treatment groups, as assessed by the pathologist score, were then tested by variance component analysis and mixed models for differences in RIPF outcomes. RESULTS: There is agreement between qualitative and quantitative scoring for RIPF grades from 4 to 7. Both classifiers performed similarly on the testing set (AUC = 0.923) indicating accordance between the qualitative and quantitative scoring. For comparisons between MSC infusion modalities, the Drug group had better outcomes (mean pathologist scoring of 3.96), correlating with significantly better RIPF outcomes than IV [lower by 0.97, p = 0.047, 95% CI = (0.013, 1.918)] and resulting in an improvement over CR [lower by 0.93, p = 0.037, 95% CI = (0.062, 1.800]. CONCLUSION: Quantitative image analysis may help in the assessment of therapeutic interventions for RIPF and can serve as a scoring surrogate in differentiating between severe and mild cases of RIPF. Preliminary data demonstrate that the use of GM-CSF was best correlated with lower RIPF severity. ADVANCES IN KNOWLEDGE: Quantitative image analysis can be a viable supplemental system of quality control and triaging in situations where pathologist work hours or resources are limited. The use of different MSC administration methods can result in different degrees of MSC efficacy and study outcomes.

Ion chamber and film-based quality assurance of mixed electron-photon radiation therapy.

PURPOSE: In previous work, we demonstrated that mixed electron-photon radiation therapy (MBRT) produces treatment plans with improved normal tissue sparing and similar target coverage, when compared to photon-only plans. The purpose of this work was to validate the MBRT delivery process on a Varian TrueBeam accelerator and laying the groundwork for a patient-specific quality assurance (QA) protocol based on ion chamber point measurements and 2D film measurements. METHODS: MC beam models used to calculate the MBRT dose distributions of each modality (photons/electrons) were validated with a single-angle beam MBRT treatment plan delivered on a slab of Solid Water phantom with a film positioned at a depth of 2 cm. The measured film absorbed dose was compared to the calculated dose. To validate clinical deliveries, a polymethyl methacrylate (PMMA) cylinder was machined and holes were made to fit an ionization chamber. A complex MBRT plan involving a photon arc and three electron delivery angles was created with the aim of reproducing a clinically realistic dose distribution in typical soft tissue sarcoma tumours of the extremities. The treatment plan was delivered on the PMMA cylinder. Point measurements were taken with an Exradin A1SL chamber at two nominal depths: 1.4 cm and 2.1 cm. The plan was also delivered on a second identical phantom with an insert at 2 cm depth, where a film was placed. An existing EGSnrc user-code, SPRRZnrc, was modified to calculate the stopping power ratios between any materials in the same voxelized geometry used for dose calculation purposes. This modified code, called SPRXYZnrc, was used to calculate a correction factor, k MBRT , accounting for the differences in electron fluence spectrum at the measurement point compared to that at reference conditions. The uncertainty associated with neglecting potential ionization chamber fluence perturbation correction factors using this approach was estimated. RESULTS: The film measurement from the Solid Water phantom treatment plan was in good agreement with the simulated dose distribution, with a gamma pass rate of 96.1% for a 3%/2 mm criteria. For the PMMA phantom delivery, for the same gamma criteria, the pass rate was 97.3%. The ion chamber measurements of the total delivered dose agreed with the MC-simulated dose within 2.1%. The beam quality correction factors amounted to, at most, a 4% correction on the ion chamber measurement. However, individual contribution of low electron energies proved difficult to precisely measure due to their steep dose gradients, with disagreements of up to 28% ± 15% at 2.1 cm depth (6 MeV). Ion chamber measurement procedure of electron beams was achieved in less than 5 min, and the entire validation process including phantom setup was performed in less than 30 min. CONCLUSION: The agreement between measured and simulated MBRT doses indicates that the dose distributions obtained from the MBRT treatment planning algorithm are realistically achievable. The SPRXYZnrc MC code allowed for convenient calculations of k MBRT simultaneously with the dose distributions, laying the groundwork for patient-specific QA protocol practical for clinical use. Further investigation is needed to establish the accuracy of our ionization chamber correction factors k MBRT calculations at low electron energies.

Determination of field output correction factors of radiophotoluminescence glass dosimeter and CC01 ionization chamber and validation against IAEA-AAPM TRS-483 code of practice.

PURPOSE: To determine the field output correction factors of the radiophotoluminescence glass dosimeter (RPLGD) in parallel and perpendicular orientations with reference to CC01, the ionization chamber. METHODS: The dose to a small water volume and the sensitive volume of the RPLGD and the IBA-CC01 were determined for 6-MV, 100-cm SAD, 10-cm depth using egs_chamber user-code. The RPLGD in perpendicular and parallel orientations to the beam axis were studied. The field output correction factors of each detector for 0.5 × 0.5 to 10 × 10 cm2 field sizes were determined. These field output correction factors were validated by comparing field output factors against data determined from IAEA-AAPM TRS-483 code of practice. RESULTS: The field output correction factors of all detectors were within 5% for field sizes down to 0.8 × 0.8 cm2. For 0.5 × 0.5 cm2, the field output correction factors of CC01, RPLGD in perpendicular and parallel orientations differed from unity by 14%, 19%, and 5%, respectively. The percentage difference between field output factors determined using RPLGD and CC01 data, corrected using the field output correction factors determined in this work and measurements with CC01 data corrected using TRS-483, was less than 3% for all field sizes, except for the smallest field size of RPLGD in perpendicular orientation and the CC01. CONCLUSIONS: The field output correction factors of RPLGD and CC01 are reported. The validation proves that RPLGD in parallel orientation combined with the field output correction factors is the most suitable for determining the field output factors for the smallest field used in this study.

The Rapidly-Developing Area of Radiocardiology: Principles, Complications and Applications of Radiotherapy on the Heart.

Ventricular arrhythmias are the leading cause of sudden cardiac death. Current treatment strategies for ventricular tachycardia, including antiarrhythmic drugs and catheter ablation, have limited efficacy in patients with structural heart disease. Noninvasive ablation with the use of externally applied radiation (cardiac radioablation) has emerged as a promising and novel approach to treating recurrent ventricular tachycardias. However, the heart is generally an "organ at risk" for radiation treatments, such that very little is known on the effects of radiotherapy on cardiac ultrastructure and electrophysiologic properties. Furthermore, there has been limited interaction between the fields of cardiology and radiation oncology and physics. The advent of cardiac radioablation will undoubtedly increase interactions between cardiologists, cardiac electrophysiologists, radiation oncologists and physicists. There is an important knowledge gap separating these specialties, but scientific developments, technical optimisation, and improvements depend on intense multidisciplinary collaboration. This manuscript seeks to review the basic of radiation physics and biology for cardiovascular specialists in an effort to facilitate constructive scientific and clinical collaborations to improve patient outcomes.