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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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

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., Competing Interests: Disclosures Dr Maughan reports consulting activity with Proton Therapy Partners, Inc for a purpose unrelated to the submitted work. The authors have no other relationships to report that could be construed as a conflict of interest., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

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., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

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 C Q 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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 of G -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 (H 3 O + ) was scaled for a desired pH using the relationship pH = -log 10 [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 1 μ s. 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 simulate G -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 of G -values for radiolytic species at different temperatures and pH values., (Creative Commons Attribution license.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (Creative Commons Attribution license.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2022. Published by Elsevier Masson SAS.)

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.

Objective: The relative TG-43 dosimetry parameters of the INTRABEAM (Carl Zeiss Meditec AG, Jena, Germany) bare probe were recently reported by Ayala Alvarez et al (2020 Phys. Med. Biol. 65 245041). 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., (© 2021 Institute of Physics and Engineering in Medicine.)

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., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

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., (© 2021 American Association of Physicists in Medicine.)

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., (© 2021 American Association of Physicists in Medicine.)

Purpose: Radiomic texture calculation requires discretizing image intensities within the region-of-interest. FBN (fixed-bin-number), FBS (fixed-bin-size) and FBN and FBS with intensity equalization (FBNequal, FBSequal) are four discretization approaches. A crucial choice is the voxel intensity (Hounsfield units, or HU) binning range. We assessed the effect of this choice on radiomic features., Methods: The dataset comprised 95 patients with head-and-neck squamous-cell-carcinoma. Dual energy CT data was reconstructed at 21 electron energies (40, 45,… 140 keV). Each of 94 texture features were calculated with 64 extraction parameters. All features were calculated five times: original choice, left shift (-10/-20 HU), right shift (+10/+20 HU). For each feature, Spearman correlation between nominal and four variants were calculated to determine feature stability. This was done for six texture feature types (GLCM, GLRLM, GLSZM, GLDZM, NGTDM, and NGLDM) separately. This analysis was repeated for the four binning algorithms. Effect of feature instability on predictive ability was studied for lymphadenopathy as endpoint., Results: FBN and FBNequal algorithms showed good stability (correlation values consistently >0.9). For FBS and FBSequal algorithms, while median values exceeded 0.9, the 95% lower bound decreased as a function of energy, with poor performance over the entire spectrum. FBNequal was the most stable algorithm, and FBS the least., Conclusions: We believe this is the first multi-energy systematic study of the impact of CT HU range used during intensity discretization for radiomic feature extraction. Future analyses should account for this source of uncertainty when evaluating the robustness of their radiomic signature., (Copyright © 2021 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

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 cm 2 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 cm 2 . For 0.5 × 0.5 cm 2 , 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., (Copyright © 2021 Associazione Italiana di Fisica Medica. All rights reserved.)

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., (© 2021 The Authors. Published by the British Institute of Radiology.)

Despite widespread adoption of electronic health records (EHRs), most hospitals are not ready to implement data science research in the clinical pipelines. Here, we develop MEDomics, a continuously learning infrastructure through which multimodal health data are systematically organized and data quality is assessed with the goal of applying artificial intelligence for individual prognosis. Using this framework, currently composed of thousands of individuals with cancer and millions of data points over a decade of data recording, we demonstrate prognostic utility of this framework in oncology. As proof of concept, we report an analysis using this infrastructure, which identified the Framingham risk score to be robustly associated with mortality among individuals with early-stage and advanced-stage cancer, a potentially actionable finding from a real-world cohort of individuals with cancer. Finally, we show how natural language processing (NLP) of medical notes could be used to continuously update estimates of prognosis as a given individual's disease course unfolds., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: To evaluate the 15-year impact of a transdisciplinary research training program for graduate students, postdoctoral fellows, and clinical trainees focused on radiation science, entitled Strategic Training in Transdisciplinary Radiation Science for the 21st Century (STARS21) with a primary objective to build capacity in radiation research., Methods and Materials: Alumni (n = 128) and mentors (n = 41) who participated in STARS21 between 2003 and 2018 were sent an anonymized online survey designed to evaluate the program. Twelve alumni and 7 mentors also volunteered to participate in semistructured interviews. The transcribed interviews were coded and analyzed using NVivo12-Pro software. Alumni employment and publications were assessed from program records and by web-based search queries., Results: Alumni are located in 11 countries, and nearly 90% are employed in a research-oriented career and continue to publish in radiation medicine- or cancer-related fields. Of those invited, 46 alumni (36%) and 12 mentors (29%) completed the online survey. Approximately 87% of alumni valued interdisciplinary collaboration, and 80% indicated that STARS21 had encouraged them to pursue such collaborations. Alumni emphasized that STARS21 assisted their career development, and the majority of alumni and mentors would recommend STARS21 to other trainees (4.48 and 4.58, respectively; 5 = strongly agree). The time invested in the program was perceived by mentors as worthwhile for the knowledge and skills gained by trainees (4.67; 5 = strongly agree), and 64% of mentors indicated that these benefits were associated with improved trainee research productivity. From the alumni and mentor perspectives, the valuable skills acquired from STARS21 included scientific communication (85% and 83%, respectively) and networking (83% and 92%, respectively)., Conclusions: STARS21 is an innovative research training program that promotes interdisciplinary collaboration in radiation medicine research, which is valued by alumni and mentor respondents. Alumni can acquire important skill sets for career development, with a large proportion of alumni currently engaged in radiation research around the world., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The American Association of Physicists in Medicine (AAPM) formed Task Group 178 (TG-178) to perform the following tasks: review in-phantom and in-air calibration protocols for gamma stereotactic radiosurgery (GSR), suggest a dose rate calibration protocol that can be successfully utilized with all gamma stereotactic radiosurgery (GSR) devices, and update quality assurance (QA) protocols in TG-42 (AAPM Report 54, 1995) for static GSR devices. The TG-178 report recommends a GSR dose rate calibration formalism and provides tabulated data to implement it for ionization chambers commonly used in GSR dosimetry. The report also describes routine mechanical, dosimetric, and safety checks for GSR devices, and provides treatment process quality assurance recommendations. Sample worksheets, checklists, and practical suggestions regarding some QA procedures are given in appendices. The overall goal of the report is to make recommendations that help standardize GSR physics practices and promote the safe implementation of GSR technologies., (© 2021 American Association of Physicists in Medicine.)

Purpose: The purpose of this study is to provide data for the calibration of the recent RefleXion TM biology-guided radiotherapy (BgRT) machine (Hayward, CA, USA) following the International Atomic Energy Agency (IAEA) and the American Association of Physicists in Medicine (AAPM) TRS-483 code of practice (COP) (Palmans et al. International Atomic Energy Agency, Vienna, 2017) and (Mirzakhanian et al. Med Phys, 2020)., Methods: In RefleXion BgRT machine, reference dosimetry was performed using two methodologies described in TRS-483 and (Mirzakhanian et al. Med Phys, 2020) In the first approach (Approach 1), the generic beam quality correction factor k Q A , Q 0 f A , f ref was calculated using an accurate Monte Carlo (MC) model of the beam and of six ionization chamber types. The k Q A , Q 0 f A , f ref is a beam quality factor that corrects N D , w , Q 0 f ref (absorbed dose to water calibration coefficient in a calibration beam quality Q 0 ) for the differences between the response of the chamber in the conventional reference calibration field f ref with beam quality Q 0 at the standards laboratory and the response of the chamber in the user's A field f A with beam quality Q A . Field A represents the reference calibration field that does not fulfill msr conditions. In the second approach (Approach 2), a square equivalent field size was determined for field A of 10 × 2 cm 2 and 10 × 3 cm 2 . Knowing the equivalent field size, the beam quality specifier for the hypothetical 10 × 10 cm 2 field size was derived. This was used to calculate the beam quality correction factor analytically for the six chamber types using the TRS-398. (Andreo et al. Int Atom Energy Agency 420, 2001) Here, TRS-398 was used instead of TRS-483 since the beam quality correction values for the chambers used in this study are not tabulated in TRS-483. The accuracy of Approach 2 is studied in comparison to Approach 1., Results: Among the chambers, the PTW 31010 had the largest k Q A , Q 0 f A , f ref correction due to the volume averaging effect. The smallest-volume chamber (IBA CC01) had the smallest correction followed by the other microchambers Exradin-A14 and -A14SL. The equivalent square fields sizes were found to be 3.6 cm and 4.8 cm for the 10 × 2 cm 2 and 10 × 3 cm 2 field sizes, respectively. The beam quality correction factors calculated using the two approaches were within 0.27% for all chambers except IBA CC01. The latter chamber has an electrode made of steel and the differences between the correction calculated using the two approaches was the largest, that is, 0.5%., Conclusions: In this study, we provided the k Q A , Q 0 f A , f ref values as a function of the beam quality specifier at the RefleXion BgRT setup ( TPR 20 , 10 ( S ) and % d d ( 10 , S ) x ) for six chamber types. We suggest using the first approach for calibration of the RefleXion BgRT machine. However, if the MC correction is not available for a user's detector, the user can use the second approach for estimating the beam quality correction factor to sufficient accuracy (0.3%) provided the chamber electrode is not made of high Z material., (© 2020 American Association of Physicists in Medicine.)

Purpose: Intraoperative radiation therapy (IORT) using the INTRABEAM, a miniature x-ray source, has shown to be effective in treating breast cancer. However, recent investigations have suggested a significant deviation between the reported and delivered doses. In this work, the dose delivered by INTRABEAM in the TARGIT breast protocol was investigated, along with the dose from the Xoft Axxent, another source used in breast IORT., Methods and Materials: The absorbed dose from the INTRABEAM was determined from ionization chamber measurements using: (a) the manufacturer-recommended formula (Zeiss V4.0 method), (b) a Monte Carlo calculated chamber conversion factor (C Q method), and (c) the formula consistent with the TARGIT breast protocol (TARGIT method). The dose from the Xoft Axxent was determined from ionization chamber measurements using the Zeiss V4.0 method and calculated using the American Association of Physicists in Medicine TG-43 formalism., Results: For a nominal TARGIT prescription of 20 Gy, the dose at the INTRABEAM applicator surface ranged from 25.2 to 31.7 Gy according to the C Q method for the largest (5 cm) and smallest (1.5 cm) diameter applicator, respectively. The Zeiss V4.0 method results were 7% to 10% lower (23.2 to 28.6 Gy). At 1 cm depth, the C Q and Zeiss V4.0 absorbed doses were also larger than those predicted by the TARGIT method. The dose at 1 cm depth from the Xoft Axxent for a surface dose of 20 Gy was slightly less than INTRABEAM (3%-7% compared with C Q method). An exception was for the 3 cm applicator, where the Xoft dose was appreciably lower (31%)., Conclusions: The doses delivered in the TARGIT breast protocol with INTRABEAM were significantly greater than the prescribed 20 Gy and depended on the size of spherical applicator used. Breast IORT treatments with the Xoft Axxent received less dose compared with TARGIT INTRABEAM, which could have implications for studies comparing clinical outcomes between the 2 devices., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

The INTRABEAM system (Carl Zeiss Meditec AG, Jena, Germany) is an electronic brachytherapy (eBT) device designed for intraoperative radiotherapy applications. To date, the INTRABEAM x-ray source has not been characterized according to the AAPM TG-43 specifications for brachytherapy sources. This restricts its modelling in commercial treatment planning systems (TPSs), with the consequence that the doses to organs at risk are unknown. The aim of this work is to characterize the INTRABEAM source according to the TG-43 brachytherapy dosimetry protocol. The dose distribution in water around the source was determined with Monte Carlo (MC) calculations. For the validation of the MC model, depth dose calculations along the source longitudinal axis were compared with measurements using a soft x-ray ionization chamber (PTW 34013) and two synthetic diamond detectors (microDiamond PTW TN60019). In our results, the measurements in water agreed with the MC model calculations within uncertainties. The use of the microDiamond detector yielded better agreement with MC calculations, within estimated uncertainties, compared to the ionization chamber at points of steeper dose gradients. The radial dose function showed a steep fall-off close to the INTRABEAM source ([Formula: see text]10 mm) with a gradient higher than that of commonly used brachytherapy radionuclides ( 192 Ir, 125 I and 103 Pd), with values of 2.510, 1.645 and 1.232 at 4, 6 and 8 mm, respectively. The radial dose function partially flattens at larger distances with a fall-off comparable to that of the Xoft Axxent® (iCAD, Inc., Nashua, NH) eBT system. The simulated 2D polar anisotropy close to the bare probe walls showed deviations from unity of up to 55% at 10 mm and 155°. This work presents the MC calculated TG-43 parameters for the INTRABEAM, which constitute the necessary data for the characterization of the source as required by a TPS used in clinical dose calculations.

Purpose: To quantify and verify the dosimetric impact of high-dose rate (HDR) source positional uncertainty in brachytherapy, and to introduce a model for three-dimensional (3D) position tracking of the HDR source based on a two-dimensional (2D) measurement. This model has been utilized for the development of a comprehensive source quality assurance (QA) method using radiochromic film (RCF) dosimetry including assessment of different digitization uncertainties., Methods: An algorithm was developed and verified to generate 2D dose maps of the mHDR-V2 192 Ir source (Elekta, Veenendaal, Netherlands) based on the AAPM TG-43 formalism. The limits of the dosimetric error associated with source (0.9 mm diameter) positional uncertainty were evaluated and experimentally verified with EBT3 film measurements for 6F (2.0 mm diameter) and 4F (1.3 mm diameter) size catheters at the surface (4F, 6F) and 10 mm further (4F only). To quantify this uncertainty, a source tracking model was developed to incorporate the unique geometric features of all isodose lines (IDLs) within any given 2D dose map away from the source. The tracking model normalized the dose map to its maximum, then quantified the IDLs using blob analysis based on features such as area, perimeter, weighted centroid, elliptic orientation, and circularity. The Pearson correlation coefficients (PCCs) between these features and source coordinates (x, y, z, θ y , θ z ) were calculated. To experimentally verify the accuracy of the tracking model, EBT3 film pieces were positioned within a Solid Water® (SW) phantom above and below the source and they were exposed simultaneously., Results: The maximum measured dosimetric variations on the 6F and 4F catheter surfaces were 39.8% and 36.1%, respectively. At 10 mm further, the variation reduced to 2.6% for the 4F catheter which is in agreement with the calculations. The source center (x, y) was strongly correlated with the low IDL-weighted centroid (PCC = 0.99), while the distance to source (z) was correlated with the IDL areas (PCC = 0.96) and perimeters (PCC = 0.99). The source orientation θ y was correlated with the difference between high and low IDL-weighted centroids (PCC = 0.98), while θ z was correlated with the elliptic orientation of the 60-90% IDLs (PCC = 0.97) for a maximum distance of z = 5 mm. Beyond 5 mm, IDL circularity was significant, therefore limiting the determination of θ z (PCC ≤ 0.48). The measured positional errors from the film sets above and below the source indicated a source position at the bottom of the catheter (-0.24 ± 0.07 mm)., Conclusions: Isodose line features of a 2D dose map away from the HDR source can reveal its spatial coordinates. RCF was shown to be a suitable dosimeter for source tracking and dosimetry. This technique offers a novel source QA method and has the potential to be used for QA of commercial and customized applicators., (© 2020 American Association of Physicists in Medicine.)

Trivalent praseodymium exhibits a wide range of luminescent phenomena when doped into a variety of different materials. Herein, radioluminescent NaLuF4:20%Pr3+ nanoparticles are studied. Four different samples of this composition were prepared ranging from 400-70 nm in size. Kinetic studies of radioluminescence as a function of X-ray irradiation time revealed a decrease in the emissions originating from the 1S0 level, due to the formation or optical activation of defects during excitation, and a simultaneous increase in the visible emissions resulting from the lower optical levels. Thermoluminescence measurements elucidated that a local de-trapping mechanism was responsible for the increase in steady state emission and persistent luminescence originating from the lower optical levels. The results and mechanism described through this study serve to provide a novel nanoparticle composition with versatile luminescent properties and provides experimental evidence in favor of a local trapping model.

Purpose: The purpose of this study is to provide a calibration methodology for radiation therapy machines where the closest field to the conventional reference field may not meet the lateral charged particle equilibrium (LCPE) condition of the machine-specific reference (msr) field. We provided two methodologies by extending the International Atomic Energy Agency (IAEA) and the American Association of Physicists in Medicine (AAPM) TRS-483 code of practice (COP) (Palmans et al. TRS-483: Dosimetry of small static fields used in external beam radiotherapy: an international code of practice for reference and relative dose determination; 2017) methodology for the calibration of radiation therapy machines with 6 MV flattening filter free (FFF) beam and with field sizes down to 10 ×  2 cm 2 ., Methods: Two methods of calibration were provided following the TRS-483. In calibration Method I, the generic correction factors k Q A , Q 0 f A , f ref were calculated using Monte Carlo (MC) for seven detectors and rectangular physical field sizes ranging from 10 × 2 cm 2 to 10 × 10 cm 2 . In calibration Method II, we extended the methodology in TRS-483 for deriving the equivalent square msr field sizes for rectangular field sizes down to 10 × 2 cm 2 . The beam quality specifier for a hypothetical 10 × 10 cm 2 field was derived by extending the methodology provided in the TRS-483. Since the beam quality correction values for the conventional reference field ( k Q , Q 0 f ref ) tabulated in TRS-483 are provided only for large reference chambers, we calculated the k Q , Q 0 f ref values analytically for our beam quality specifier and chambers used, using interaction data in TRS-398 (Andreo, et al. TRS-398: Absorbed dose determination in external beam radiotherapy: an international code of practice for dosimetry based on standards of absorbed dose to water; 2001)., Results: The k Q A , Q 0 f A , f ref correction values calculated using the first method for chambers with an electrode made of C552 almost did not vary across the different field sizes studied (within 0.1%) while it varied by 1.6% for IBA CC01 with electrode made of steel. Extending the equivalent field and beam quality specifier determination methodology of TRS-483 resulted in a maximum error of 1.3% on the beam quality specifier for the 2 × 2 cm 2 field size. However, this had a negligible impact on the k Q A , Q 0 f A , f ref values (less than 0.1%). For chambers with C552 and Al electrode material, the correction factors determined using the two methods of calibration were in agreement to within 0.5%. However, for the chambers with electrode made of higher atomic number (Z), the difference between the two methodologies could be as large as 1.5%. It was shown that this difference can be reduced to less than 0.5% if central electrode perturbation effects and k Q A FFF , Q FFF f A , f ref values introduced in TRS-483 were taken into account., Conclusions: In this study, applying the k Q A , Q 0 f A , f ref correction values calculated using the calibration Method I to the chamber reading improved the consistency on an absorbed dose determination from 0.5% to 0.1% standard deviation (except for the Exradin A16). For this reason we recommend using calibration Method I. If the k Q A , Q 0 f A , f ref values are not available for the user's detector, calibration Method II can be used to predict the correction factors. However, the second methodology should not be used for chambers with electrode made of high-Z material unless the electrode perturbation effects and k Q A FFF , Q FFF f A , f ref values are taken into account., (© 2020 American Association of Physicists in Medicine.)

Purpose: Previous work presented and validated in-water Cherenkov emission (CE)-based radiotherapy dosimetry. Condensed history Monte Carlo (MC)-calculated electron beam CE-to-dose conversion with <4π CE detection, however, could exhibit step-size dependence. This work presents a physics update and numerical study of this step-size dependence in photon and electron beams, elucidates the CE generation physics, and guides further research., Methods: The CE-to-dose conversion, k C θ±δθ , is calculated for photons (6X, 15X) and electrons (6E, 20E) on-axis in-water with: θ±δθ∈{90°±90°(4π),90°±5°,45°±45°,90°±45°}, 10 cm equivalent square, 100 cm SSD, 1cm voxel radius and beam-dependent length. Relative deviation from single-scattering (SS) simulation is evaluated on maximum fractional electron step energy loss ESTEPE∈0.01-0.25. Standard uncertainties (k=1, 10 8 histories) are reported. A simplified method considering only the straight step direction is also implemented., Results: No significant step-size effect (>0.1%) was observed for dose and all k C θ±δθ , except for surface dosimetry at 90°±5° (-1.6%±0.5%, 20E), which is not recommended. Electron SS deviation uncertainties (k=1), otherwise, varied from <0.2% overall to <0.1% with large apertures. Photon uncertainties varied from <1.1% overall to <0.2% non-superficially with large apertures. The simplified straight-step method exhibited overall greater deviation from SS, most notably -2.8%±0.1% (6E) and -2.5%±0.4% (20E) superficially with 90°±45°, and -1.4%±0.3% (6X) and -0.6%±0.2% (15X) non-superficially with 90°±5° for ESTEPE∈[0.10,0.25]., Conclusions: We demonstrate step-size independence of newly-implemented correction in EGSnrc directional Cherenkov calculations. This advances clinical CE-based dosimetry and is useful for the general Monte Carlo community., (Copyright © 2020 Associazione Italiana di Fisica Medica. All rights reserved.)

Owing to its short computation time and simplicity, the Ray-Tracing algorithm (RAT) has long been used to calculate dose distributions for the CyberKnife system. However, it is known that RAT fails to fully account for tissue heterogeneity and is therefore inaccurate in the lung. The aim of this study is to make a dosimetric assessment of 219 non-small cell lung cancer CyberKnife plans by recalculating their dose distributions using an independent Monte Carlo (MC) method. For plans initially calculated by RAT without heterogeneity corrections, target coverage was found to be significantly compromised when considering MC doses. Only 35.4% of plans were found to comply to their prescription doses. If the normal tissue dose limits were respected in the treatment planning dose, the MC recalculated dose did not exceed these limits in over 97% of the plans. Comparison of RAT and recalculated-MC doses confirmed the overestimation of RAT doses observed in previous studies. An inverse correlation between the RAT/MC dose ratio and the target size was also found to be statistically significant (p<10 -4 ), consistent with other studies. In addition, the inaccuracy and variability in target coverage incurred from dose calculations using RAT without heterogeneity corrections was demonstrated. On average, no clinically relevant differences were observed between MC-calculated dose-to-water and dose-to-medium for all tissues investigated (⩽1%). Patients receiving a dose D 95% larger than 119 Gy in EQD2 10 (or ≈52 Gy in 3 fractions) as recalculated by MC were observed to have significantly superior loco-regional progression-free survival rates (p=0.02) with a hazard ratio of 3.45 (95%CI: 1.14-10.5)., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Introduction: Trajectory-based volumetric modulated arc therapy (tr-VMAT) treatment plans enable the option for noncoplanar delivery yielding steeper dose gradients and increased sparing of critical structures compared to conventional treatment plans. The addition of translational couch motion to shorten the effective source-to-axis distance (SAD) may result in improved delivery precision and an increased effective dose rate. In this work, tr-VMAT treatment plans using a noncoplanar "baseball stitch" trajectory were implemented, applied to patients presented with cranial targets, and compared to the clinical treatment plans., Methods: A treatment planning workflow was implemented: (a) beamlet doses were calculated for control points defined along a baseball stitch trajectory using a collapsed-cone convolution-superposition algorithm; (b) VMAT treatment plans were optimized using the column generation approach; (c) a final dose distribution was calculated in Varian Eclipse using the analytical anisotropic algorithm by importing the optimized treatment plan parameters. Tr-VMAT plans were optimized for ten patients presented with cranial targets at both standard and shortened SAD, and compared to the clinical treatment plans through isodose distributions, dose-volume histograms, and dosimetric indices. The control point specifications of the optimized tr-VMAT plans were used to estimate the delivery time., Results: The optimized tr-VMAT plans with both shortened and standard SAD delivery yielded a comparable plan quality to the clinical treatment plans. A statistically significant benefit was observed for dose gradient index and monitor unit efficiency for shortened SAD tr-VMAT plans, while improved target volume conformity was observed for the clinical treatment plan (P ≤ 0.05). A clear dosimetric benefit was not demonstrated between tr-VMAT delivery at shortened SAD compared to standard SAD, but shortened SAD delivery yielded a fraction size-dependent reduction in the estimated delivery time., Conclusion: The implementation of "baseball stitch" tr-VMAT treatment plans to patients presented with cranial targets demonstrated comparable plan quality to clinical treatment plans. The delivery at shortened SAD produced a fraction size-dependent decrease in estimated delivery time., (© 2020 American Association of Physicists in Medicine.)

Purpose: Trajectory-based treatment planning involves the combination of a gantry-couch trajectory with volumetric modulated arc therapy (VMAT) treatment plan optimization. This work presents the implementation of an optimization methodology that generates a trajectory simultaneous with treatment plan optimization (simTr-VMAT)., Methods: The optimization algorithm is based on the column generation approach, in which a treatment plan is iteratively constructed through the solution of a subproblem called the "pricing problem." The property of the pricing problem to rank candidate apertures based on their associated price is leveraged to select an optimal aperture while simultaneously determining the trajectory path. A progressively increasing gantry-couch grid resolution is used to provide an initial coarse sampling of the angular solution space while maintaining fine control point spacing with the final treatment plan. The trajectory optimization was applied and compared to coplanar VMAT treatment plans for a lung patient, a glioblastoma patient, and a prostate patient. Algorithm validation was performed through the generation of 5000 random trajectories and optimization using column generation VMAT for each patient case, representing the solution space for the trajectory optimization problem. The simTr-VMAT trajectories were compared against these random trajectories based on a quality metric that prefers trajectories with few control points and low objective function value over long, inefficient trajectories., Results: For the lung patient, the simTr-VMAT plan resulted in a decrease of the mean dose of 1.5 and 1.0 Gy to the heart and ipsilateral lung, respectively. For the glioblastoma patient, the simTr-VMAT plan resulted in improved planning target volume coverage with a decrease in mean dose to the eyes, lens, nose, and contralateral temporal lobe between 2 and 7 Gy. The prostate patient showed no clinically relevant dosimetric improvement. The simTr-VMAT treatment plans ranked at the 99.6, 96.3, and 99.4 percentiles compared to the distribution of randomly generated trajectories for the lung, glioblastoma, and prostate patients, respectively., Conclusion: The simTr-VMAT optimization methodology resulted in treatment plans with equivalent or improved dosimetric outcomes compared to coplanar VMAT treatment plans, with the trajectories resulting from the optimization ranking among the optimal trajectories for each patient case., (© 2020 American Association of Physicists in Medicine.)

We calculate differential and integrated cross sections for the Compton interaction as well as mass attenuation ([Formula: see text]), mass energy-transfer ([Formula: see text]), and mass energy-absorption ([Formula: see text]) coefficients, within the relativistic impulse approximation (RIA) using Compton profiles (CPs) obtained from unrestricted Hartree-Fock electron densities. We investigate the impact of using molecular as opposed to atomic CPs on dosimetric photon interaction coefficients for air, water and graphite, and compare our cross sections to the simpler Waller-Hartree (WH) and Klein-Nishina (KN) formalisms. We find that differences in [Formula: see text] and [Formula: see text] resulting from the choice of CPs within the RIA are small relative to the differences between the RIA, WH, and KN calculations. Surprisingly, although the WH binding corrections seem accurate when considering [Formula: see text], there are significant discrepancies between the WH and RIA results when we look at [Formula: see text]. The WH theory can differ substantially from the predictions of KN and the RIA in the tens of keV range (e.g. 6%-10% at 20 keV), when Compton scattering becomes the dominant interaction mechanism. For lower energies, the disagreement further grows to about one order of magnitude at 1 keV. However, since the photoelectric effect transfers more energy than the Compton interaction in the tens of keV range and below, the differences in the total [Formula: see text] values resulting from the choice of Compton models (KN, WH, or RIA) are not larger than 0.4%, and the differences between WH and the other two theories are no longer prominent.

The in-phantom calibration method for radiotherapy kilovoltage x-ray beams requires ionization chamber correction factors. The overall ionization chamber correction factor accounts for changes in the chamber response due to the displacement of water by the chamber cavity and wall, the presence of the stem and the change in incident photon energy and angular distribution in the phantom to that in air. A waterproof sheath, if required, is accounted for in a sheath correction factor. The aim of this study is to determine chamber correction factors through Monte Carlo (MC) simulations and water calorimetry measurements. Correction factors are determined for the PTW TM30013, NE2571, IBA FC65-G, IBA FC65-P and Exradin A12 ionization chambers. They are compared to experimental values obtained at the German national metrology institute Physikalisch-Technische Bundesanstalt (PTB) with their water calorimetry-based absorbed dose to water primary standard and at other national metrological institutes. An uncertainty analysis considers the contributions to the uncertainty on the chamber correction factors from the field size, photon cross sections, photon fluence spectra and chamber wall and central electrode dimensions. The MC calculated chamber correction factors are within 2.2% of unity with a standard uncertainty of 0.3%. For the 50 kV and 100 - 140 kV radiation beam qualities, the calculated correction factors deviate from the measured correction factors (with a standard uncertainty of 1%) by up to 2.6%. The calculated chamber correction factors for the PTW TM30013 and Exradin A12 are consistent with those derived from the BIPM kilovoltage primary standard. The inconsistencies between the calculated and experimental chamber correction factors indicate the need to further investigate the accuracy of kilovoltage absorbed dose to water primary standards and the use of MC simulations to determine kilovoltage beam chamber correction factors.

Currently, the American Association of Physicists in Medicine (AAPM) TG-21 is the conventional protocol currently used for the calibration of the Leksell Gamma Knife ® (LGK) (despite the publication of the AAPM TG-51 protocol). However, this protocol is based on the air-kerma standards requiring an elaborate conversion process resulting in an increase in the possibility of errors in the clinic. The International Atomic Energy Agency (IAEA) Technical Reports Series (TRS)-483 Code of Practice provides new recommendations on the dosimetry of small static fields and correction factor data for the calibration of the LGK unit. The purpose of this study is to experimentally validate previously calculated [Formula: see text] factors for the calibration of the LGK Perfexion/Icon unit in the context of the TRS-483 protocol. An experimental comparison between three protocols (TG-51, TG-21 and TRS-483 with the aforementioned correction factors) for calibration of the LGK unit is provided. Dose-rate measurements were performed on a LGK Icon unit using three ionization chambers and three phantoms with different orientations of the chambers with respect to the LGK unit. The dose rate was determined following the three calibration protocols. The standard deviation on the mean dose rate over all phantoms and chambers in different orientations determined using TG-51, TG-21 and TRS-483 protocols were 0.9%, 0.5% and 0.4%, respectively. The mean dose rate calculated using TG-51 protocol was 1.6% and 1.2% lower comparing to the TG-21 and TRS-483 protocols respectively. Applying the [Formula: see text] values calculated in Mirzakhanian et al (2018) to the measured dose rates in LGK unit for all chambers and phantoms resulted in dose rates that are consistent to within 0.4%. The TRS-483 protocol improves the consistency of the results especially when the chamber was positioned in different orientations with respect to the LGK (from 1.6% when using TG-51 or TG-21 protocols to 0.2% when using TRS-483 protocol) since the other protocols do not correct for the different chamber orientations.

Purpose: In this work, the fabrication, operation, and evaluation of a probe-format graphite calorimeter - herein referred to as Aerrow - as an absolute clinical dosimeter of high-energy photon beams while in the presence of a B = 1.5 T magnetic field is described. Comparable to a cylindrical ionization chamber (IC) in terms of utility and usability, Aerrow has been developed for the purpose of accurately measuring absorbed dose to water in the clinic with a minimum disruption to the existing clinical workflow. To our knowledge, this is the first reported application of graphite calorimetry to magnetic resonance imaging (MRI)-guided radiotherapy., Methods: Based on a previously numerically optimized and experimentally validated design, an Aerrow prototype capable of isothermal operation was constructed in-house. Graphite-to-water dose conversions as well as magnetic field perturbation factors were calculated using Monte Carlo, while heat transfer and mass impurity corrections and uncertainties were assessed analytically. Reference dose measurements were performed in the absence and presence of a B = 1.5 T magnetic field using Aerrow in the 7 MV FFF photon beam of an Elekta MRI-linac and were directly compared to the results obtained using two calibrated reference-class IC types. The feasibility of performing solid phantom-based dosimetry with Aerrow and the possible influence of clearance gaps is also investigated by performing reference-type dosimetry measurements for multiple rotational positions of the detector and comparing the results to those obtained in water., Results: In the absence of the B-field, as well as in the parallel orientation while in the presence of the B-field, the absorbed dose to water measured using Aerrow was found to agree within combined uncertainties with those derived from TG-51 using calibrated reference-class ICs. Statistically significant differences on the order of (2-4)%, however, were observed when measuring absorbed dose to water using the ICs in the perpendicular orientation in the presence of the B-field. Aerrow had a peak-to-peak response of about 0.5% when rotated within the solid phantom regardless of whether the B-field was present or not., Conclusions: This work describes the successful use of Aerrow as a straightforward means of measuring absolute dose to water for large high-energy photon fields in the presence of a 1.5 T B-field to a greater accuracy than currently achievable with ICs. The detector-phantom air gap does not appear to significantly influence the response of Aerrow in absolute terms, nor does it contribute to its rotational dependence. This work suggests that the accurate use of solid phantoms for absolute point dose measurement is possible with Aerrow., (© 2019 American Association of Physicists in Medicine.)

Background and Purpose: Previous literature suggests that the dose proximally outside the PTV could have an impact on the incidence of distant metastasis (DM) after SBRT in stage I NSCLC patients. We investigated this observation (along with local failure) in deliveries made by different treatment modalities: robotic mounted linac SBRT (CyberKnife) vs conventional SBRT (VMAT/CRT)., Materials and Methods: This study included 422 stage I NSCLC patients from 2 institutions who received SBRT: 217 treated conventionally and 205 with CyberKnife. The dose behavior outside the PTV of both sub-cohorts were compared by analyzing the mean dose in continuous shells extending 1, 2, 3, …, 100 mm from the PTV. Kaplan-Meier analysis was performed between the two sub-cohorts with respect to DM-free survival and local progression-free survival. A multivariable Cox proportional hazards model was fitted to the combined cohort (n = 422) with respect to DM incidence and local failure., Results: The shell-averaged dose fall-off beyond the PTV was found to be significantly more modest in CyberKnife plans than in conventional SBRT plans. In a 30 mm shell around the PTV, the mean dose delivered with CyberKnife (38.1 Gy) is significantly larger than with VMAT/CRT (22.8 Gy, p<10 -8 ). For 95% of CyberKnife plans, this region receives a mean dose larger than the 21 Gy threshold dose discovered in our previous study. In contrast, this occurs for only 75% of VMAT/CRT plans. The DM-free survival of the entire CyberKnife cohort is superior to that of the 25% of VMAT/CRT patients receiving less than the threshold dose (VMAT/CRT <21Gy ), with a hazard ratio of 5.3 (95% CI: 3.0-9.3, p<10 -8 ). The 2 year DM-free survival rates were 87% (95% CI: 81%-91%) and 44% (95% CI: 28%-58%) for CyberKnife and the below-threshold dose conventional cohorts, respectively. A multivariable analysis of the combined cohort resulted in the confirmation that threshold dose was a significant predictor of DM(HR = 0.28, 95% CI: 0.15-0.55, p<10 -3 ) when adjusted for other clinical factors. CyberKnife was also found to be superior to the entire VMAT/CRT with respect to local control (HR = 3.44, CI: 1.6-7.3). The 2-year local progression-free survival rates for the CyberKnife cohort and the VMAT/CRT cohort were 96% (95% CI: 92%-98%) and 88% (95% CI: 82%-92%) respectively., Conclusions: In standard-of-care CyberKnife treatments, dose distributions that aid distant control are achieved 95% of the time. Although similar doses could be physically achieved by conventional SBRT, this is not always the case with current prescription practices, resulting in worse DM outcomes for 25% of conventional SBRT patients. Furthermore, CyberKnife was found to provide superior local control compared to VMAT/CRT., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In radiation oncology, Machine Learning classification publications are typically related to two outcome classes, e.g. the presence or absence of distant metastasis. However, multi-class classification problems also have great clinical relevance, e.g., predicting the grade of a treatment complication following lung irradiation. This work comprised two studies aimed at making work in this domain less prone to statistical blindsides. In multi-class classification, AUC is not defined, whereas correlation coefficients are. It may seem like solely quoting the correlation coefficient value (in lieu of the AUC value) is a suitable choice. In the first study, we illustrated using Monte Carlo (MC) models why this choice is misleading. We also considered the special case where the multiple classes are not ordinal, but nominal, and explained why Pearson or Spearman correlation coefficients are not only providing incomplete information but are actually meaningless. The second study concerned surrogate biomarkers for a clinical endpoint, which have purported benefits including potential for early assessment, being inexpensive, and being non-invasive. Using a MC experiment, we showed how conclusions derived from surrogate markers can be misleading. The simulated endpoint was radiation toxicity (scale of 0-5). The surrogate marker was the true toxicity grade plus a noise term. Five patient cohorts were simulated, including one control. Two of the cohorts were designed to have a statistically significant difference in toxicity. Under 1000 repeated experiments using the biomarker, these two cohorts were often found to be statistically indistinguishable, with the fraction of such occurrences rising with the level of noise., (Copyright © 2020 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Dose calculation plays an important role in the accuracy of radiotherapy treatment planning and beam delivery. The Monte Carlo (MC) method is capable of achieving the highest accuracy in radiotherapy dose calculation and has been implemented in many commercial systems for radiotherapy treatment planning. The objective of this task group was to assist clinical physicists with the potentially complex task of acceptance testing and commissioning MC-based treatment planning systems (TPS) for photon and electron beam dose calculations. This report provides an overview on the general approach of clinical implementation and testing of MC-based TPS with a specific focus on models of clinical photon and electron beams. Different types of beam models are described including those that utilize MC simulation of the treatment head and those that rely on analytical methods and measurements. The trade-off between accuracy and efficiency in the various source-modeling approaches is discussed together with guidelines for acceptance testing of MC-based TPS from the clinical standpoint. Specific recommendations are given on methods and practical procedures to commission clinical beam models for MC-based TPS., (© 2019 American Association of Physicists in Medicine.)

Purpose: To demonstrate the strength of an innovative knowledge-based model-building method for radiotherapy planning using hypofractionated, multi-target prostate patients., Material and Methods: An initial RapidPlan model was trained using 48 patients who received 60 Gy to prostate (PTV60) and 44 Gy to pelvic nodes (PTV44) in 20 fractions. To improve the model's goodness-of-fit, an intermediate model was generated using the dose-volume histograms of best-spared organs-at-risk (OARs) of the initial model. Using the intermediate model and manual tweaking, all 48 cases were re-planned. The final model, trained using these re-plans, was validated on 50 additional patients. The validated final model was used to determine any planning advantage of using three arcs instead of two on 16 VMAT cases and tested on 25 additional cases to determine efficacy for single-PTV (PTV60-only) treatment planning., Results: For model validation, PTV V 95% of 99.9% was obtained by both clinical and knowledge-based planning. D 1% was lower for model plans: by 1.23 Gy (PTV60, CI = [1.00, 1.45]), and by 2.44 Gy (PTV44, CI = [1.72, 3.16]). OAR sparing was superior for knowledge-based planning: ΔD mean  = 3.70 Gy (bladder, CI = [2.83, 4.57]), and 3.22 Gy (rectum, CI = [2.48, 3.95]); ΔD 2%  = 1.17 Gy (bowel bag, CI = [0.64, 1.69]), and 4.78 Gy (femoral heads, CI = [3.90, 5.66]). Using three arcs instead of two, improvements in OAR sparing and PTV coverage were statistically significant, but of magnitudes < 1 Gy. The model failed at reliable DVH predictions for single PTV plans., Conclusions: Our knowledge-based model delivers efficient, consistent plans with excellent PTV coverage and improved OAR sparing compared to clinical plans., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

The combination of radiation with immune checkpoint inhibitors was reported in some cancers to have synergic effects both locally and distally. Our aim was to assess this combined therapy on both radiated and nonradiated bladder tumors and to characterize the immune landscape within the tumor microenvironment. Murine bladder cancer cells (MB49) were injected subcutaneously in both flanks of C57BL/6 mice. Mice were randomly assigned to the following treatments: placebo, anti-PD-L1 (four intraperitoneal injections over 2 weeks), radiation to right flank (10 Gy in two fractions), or radiation+anti-PD-L1. Tumor digestion, flow cytometry, and qPCR were performed. Log-rank analysis was used for statistical significance. Radiation+anti-PD-L1 group demonstrated statistically significant slower tumor growth rate both in the radiated and nonirradiated tumors ( P < 0.001). Survival curves demonstrated superior survival in the combination group compared with each treatment alone ( P = 0.02). Flow cytometry showed increased infiltration of immunosuppressive cells as well as CTL in the radiation and combination groups ( P = 0.04). Ratio of immunosuppressive cells to CTL shifted in favor of cytotoxic activity in the combination arm ( P < 0.001). The qPCR analysis revealed downregulation of immunosuppressive genes ( CCL22, IL22 , and IL13 ), as well as upregulation of markers of CTL activation ( CXCL9 , GZMA , and GZMB ) within both the radiated and distant tumors within the combination group. Combining radiation with immune checkpoint inhibitor provided better response in the radiated tumors and also the distant tumors along with a shift within the tumor microenvironment favoring cytotoxic activity. These findings demonstrate a possible abscopal effect in urothelial carcinoma with combination therapy., (©2019 American Association for Cancer Research.)

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.

Purpose : The intent of this work was to evaluate the ability of our 200 kV kilovoltage arc therapy (KVAT) system to treat realistic lung tumors without exceeding dose constraints to organs-at-risk (OAR). Methods and Materials : Monte Carlo (MC) methods and the McO optimization framework generated and inversely optimized KVAT treatment plans for 3 SABR lung cancer patients. The KVAT system was designed to treat deep-seated lesions with kilovoltage photons. KVAT delivers dose to roughly spherical PTVs and therefore non-spherical PTVs were divided into spherical sub-volumes. A prescription dose of 12 Gy/fx × 4 fractions was planned to 90% of the PTV volume. KVAT plans were compared to VMC++ calculated, 6 MV stereotactic ablative radiotherapy (SABR) treatment plans. Dose distributions, dose volume histograms, gradient index (GI), planned mean doses and plan treatment times were calculated. Dose constraints for organs-at-risk (OAR) were taken from RTOG 101. Results : All plans, with the exception of the rib dose calculated in one of the KVAT plans for a peripheral lesion, were within dose-constraints. In general, KVAT plans had higher planned doses to OARs. KVAT GI values were 5.7, 7.2 and 8.9 and SABR values were 4.6, 4.1, and 4.7 for patient 1, 2 and 3, respectively. KVAT plan treatment times were 49, 65 and 17 min for patients 1, 2 and 3, respectively. Conclusions : Inverse optimization and MC methods demonstrated the ability of KVAT to produce treatment plans without exceeding TG 101 dose constraints to OARs for 2 out of 3 investigated lung cancer patients., (© 2019 IOP Publishing Ltd.)

Purpose: To introduce a model that reproducibly linearizes the response from radiochromic film (RCF) dosimetry systems at extended dose range. To introduce a correction method, generated from the same scanned images, which corrects for scanner temporal response variation and scanner bed inhomogeneity., Methods: Six calibration curves were established for different lot numbers of EBT3 GAFCHROMIC™ film model based on four EPSON scanners [10000XL (2 units), 11000XL, 12000XL] at three different centers. These films were calibrated in terms of absorbed dose to water based on TG51 protocol or TRS398 with dose ranges up to 40 Gy. The film response was defined in terms of a proposed normalized pixel value ( n P V RGB ) as a summation of first-order equations based on information from red, green, and blue channels. The fitting parameters of these equations are chosen in a way that makes the film response equal to dose at the time of calibration. An integrated set of correction factors (one per color channel) was also introduced. These factors account for the spatial and temporal changes in scanning states during calibration and measurements. The combination of n P V RGB and this "fingerprint" correction formed the basis of this new protocol and it was tested against net optical density ( n e t O D X = R , G , B ) single-channel dosimetry in terms of accuracy, precision, scanner response variability, scanner bed inhomogeneity, noise, and long-term stability., Results: Incorporating multichannel features (RGB) into the normalized pixel value produced linear response to absorbed dose (slope of 1) in all six RCF dosimetry systems considered in this study. The "fingerprint" correction factors of each of these six systems displayed unique patterns at the time of calibration. The application of n P V RGB to all of these six systems could achieve a level of accuracy of ± 2.0% in the dose range of interest within modeled uncertainty level of 2.0%-3.0% depending on the dose level. Consistent positioning of control and measurement film pieces and integrating the multichannel correction into the response function formalism mitigated possible scanner response variations of as much as ± 10% at lower doses and scanner bed inhomogeneity of ± 8% to the established level of uncertainty at the time of calibration. The system was also able to maintain the same level of accuracy after 3 and 6 months post calibration., Conclusions: Combining response linearity with the integrated correction for scanner response variation lead to a sustainable and practical RCF dosimetry system that mitigated systematic response shifts and it has the potential to reduce errors in reporting relative information from the film response., (© 2019 American Association of Physicists in Medicine.)

An understanding of the cellular uptake and trafficking of nanoparticles is important for the design of efficient nanoparticle-based nanomedicines. Herein we compare the uptake and cytotoxicity of diamond-shape, lanthanide upconverting nanoparticles (LiYF 4 :Tm 3+ /Yb 3+ UCNPs) with different surface properties. Coating the UCNP with a supported lipid bilayer yielded negligible cytotoxicity on A549 human lung cancer cells, albeit with a lower, but still significant, UCNP uptake compared to oleate-capped and oleate-free UCNPs. Using inhibition studies and cellular imaging we demonstrate that the UCNPs are internalized by endocytosis and energy independent pathways and trafficked to the endoplasmic reticulum, Golgi apparatus, and lamellar and lipid bodies. Upon incorporation of a photostimulus within the bilayer coating, release of a Nile red as a hydrophobic drug model was demonstrated.

Purpose: The purpose of this study is to create an organ dose database for pediatric individuals undergoing chest, abdomen/pelvis, and head computed tomography (CT) examinations, and to report the differences in absorbed organ doses, when anatomical differences exist for pediatric patients., Methods: The GATE Monte Carlo (MC) toolkit was used to model the GE BrightSpeed Elite CT model. The simulated scanner model was validated with the standard Computed Tomography Dose Index (CTDI) head phantom. Twelve computational models (2.1-14 years old) were used. First, contributions to effective dose and absorbed doses per CTDI vol and per 100 mAs were estimated for all organs. Then, doses per CTDI vol were correlated with patient model weight for the organs inside the scan range for chest and abdomen/pelvis protocols. Finally, effective doses per dose-length product (DLP) were estimated and compared with the conventional conversion k-factors., Results: The system was validated against experimental CTDI w measurements. The doses per CTDI vol and per 100 mAs for selected organs were estimated. The magnitude of the dependency between the dose and the anatomical characteristics was calculated with the coefficient of determination at 0.5-0.7 for the internal scan organs for chest and abdomen/pelvis protocols. Finally, effective doses per DLP were compared with already published data, showing discrepancies between 13 and 29% and were correlated strongly with the total weight (R 2  > 0.8) for the chest and abdomen protocols., Conclusions: Big differences in absorbed doses are reported even for patients of similar age or same gender, when anatomical differences exist on internal organs of the body., (Copyright © 2019 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Radiotherapy (RT) causes morbidity and long-term side effects. A challenge in RT is to maximize cancer cells killing while minimizing damage to normal tissue. The ideal radio-protector selectively improves survival and limits damage to normal tissues while reducing survival of cancer cells. Muscle-derived dipeptide, L-carnosine (CAR) is a potent antioxidant, with radio-protective, but also anticancer properties, affecting the cell cycle of cancer cells. We tested CAR effects in lung cancer cells, differentiated and undifferentiated normal cells. We hypothesized that CAR antioxidant properties will confer protection to the two normal cell lines against RT, while preventing lung cancer cell proliferation, and that CAR may act as a radiosensitizer of lung cancer cells due to its effects on cell-cycle progression of cancer cells. Under the experimental conditions reported here, we found that CAR increased radio-sensitivity of lung (A549) cancer cells by increasing the percentage of cells in G2/M (radiosensitive) phase of cell cycle, it negatively affected their bioenergetics, therefore reduced their viability, and DNA-double strand break repair capacity. CAR had either no effect or reduced RT-induced damage in normal cells, depending on the cell type. CAR is a versatile natural occurring compound, that could improve RT-induced lung cancer cells killing, while reducing the damage to normal differentiated and undifferentiated cells.

In this work we report on the thermoluminescence (TL) and optically stimulated luminescence (OSL) properties of β-Na(Gd,Lu)F 4 :Tb 3+ nanophosphors prepared via a standard high-temperature coprecipitation route. Irradiating this phosphor with X-rays not only produces radioluminescence but also leads to a bright green afterglow that is detectable up to hours after excitation has stopped. The storage capacity of the phosphor was found to be (2.83 ± 0.05) × 10 16 photons/gram, which is extraordinarily high for nano-sized particles and comparable to the benchmark bulk phosphor SrAl 2 O 4 :Eu 2+ ,Dy 3+ . By combining TL with OSL, we show that the relatively shallow traps, which dominate the TL glow curves and are responsible for the bright afterglow, can also be emptied optically using 808 or 980 nm infrared light while the deeper traps can only be emptied thermally. This OSL at therapeutically relevant radiation doses is of high interest to the medical dosimetry community, and is demonstrated here in uniform, solution-processable nanocrystals.