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Background: Treatment planning is essential for in silico particle therapy studies. matRad is an open-source research treatment planning system (TPS) based on the local effect model, which is a type of relative biological effectiveness (RBE) model., Purpose: This study aims to implement a microdosimetric kinetic model (MKM) in matRad and develop an automation algorithm for Monte Carlo (MC) dose recalculation using the TOPAS code. In addition, we provide the developed MKM extension as open-source tool for users., Methods: Carbon beam data were generated using TOPAS MC pencil beam irradiation. We parameterized the TOPAS MC beam data with a double-Gaussian fit and modeled the integral depth doses and lateral spot profiles in the range of 100-430 MeV/u. To implement the MKM, the specific energy data table for Z = 1-6 and integrated depth-specific energy data were acquired based on the Kiefer-Chatterjee track structure and TOPAS MC simulation, respectively. Generic data were integrated into matRad, and treatment planning was performed based on these data. The optimized plan parameters were automatically converted into MC simulation input. Finally, the matRad TPS and TOPAS MC simulations were compared using the RBE-weighted dose calculation results. A comparison was made for three geometries: homogeneous water phantom, inhomogeneous phantom, and patient., Results: The RBE-weighted dose (D RBE ) distribution agreed with TOPAS MC within 1.8% for all target sizes for the homogeneous phantom. For the inhomogeneous phantom, the relative difference in the range of 80% of the prescription dose in the distal fall-off region (R80) between the matRad TPS and TOPAS MC was 0.6% (1.1 mm). D RBE between the TPS and the MC was within 4.0%. In the patient case, the difference in the dose-volume histogram parameters for the target volume between the TPS and the MC was less than 2.7%. The relative difference in R80 was 0.7% (1.2 mm)., Conclusions: The MKM was successfully implemented in matRad TPS, and the RBE-weighted dose was comparable to that of TOPAS MC. The MKM-implemented matRad was released as an open-source tool. Further investigations with MC simulations can be conducted using this tool, providing a good option for carbon ion research., (© 2023 American Association of Physicists in Medicine.)

This study aimed to evaluate the robustness against geometric uncertainties in the hybrid intensity-modulated radiation therapy (IMRT) plans generated by commercially available software for automated breast planning (ABP). The ABP plans were compared with commonly used forward-planned field-in-field (FIF) technique plans. The planning computed tomography datasets of 20 patients who received left-sided breast-conserving surgery were used for both the ABP and FIF plans. Geometric uncertainties were simulated by shifting beam isocenters by 2, 3, 5, and 10 mm in the six directions: anterior/posterior, left/right, and superior/inferior. A total of 500 plans (20 patients and 25 scenarios, including the original plan) were created for each of the ABP and FIF plans. The homogeneity index of the target volume in the ABP plans was significantly better (p < 0.001) than the value in the FIF plans in the scenarios of shifting beam isocenters by 2, 3, and 5 mm. Mean heart dose and percentage volume of lungs receiving a dose more than 20 Gy were clinically acceptable in all scenarios. The hybrid IMRT plans generated by commercially available ABP software provided better robustness against geometric uncertainties than forward-planned FIF plans., (© 2022. The Author(s).)

Background: The dose distribution of heavy ions at the edge of the target region will have a steep decay during radiotherapy, which can better protect the surrounding organs at risk., Objective: To analyze the dose decay gradient at the back edge of the target region during heavy ion radiotherapy., Methods: Treatment planning system (TPS) was employed to analyze the dose decay at the edge of the beam under different incident modes and multiple dose segmentation conditions during fixed beam irradiation. The dose decay data of each plan was collected based on the position where the rear edge of the beam began to fall rapidly. Uniform scanning mode was selected in heavy ion TPS. Dose decay curves under different beam setup modes were drawn and compared., Results: The dose decay data analysis showed that in the case of single beam irradiation, the posterior edge of the beam was 5 mm away, and the posterior dose could drop to about 20%. While irradiation in opposite direction, the posterior edge of the beam was 5 mm away, and the dose could drop to about 50%. In orthogonal irradiation of two beams, the posterior edge of the beam could drop to about 30-38% in a distance of 5 mm. Through the data analysis in the TPS, the sharpness of the dose at the back edge of the heavy ion beam is better than that at the lateral edge, but the generated X-ray contamination cannot be ignored., Conclusions: The effect of uneven CT value on the dose decay of heavy ion beam should also be considered in clinical treatment., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Xiaoyun Ma et al.)

Radiotherapy (RT) is one of the main treatment strategies of breast cancer. It is challenging to design RT plans that can completely cover the target area while protecting organs at risk (OAR). The Plan-IQ feasibility tool can estimate the best sparing dose of OAR before optimizing the Plan. A systematic quantitative evaluation of the quality change of intensity-modulated radiation therapy (IMRT) using the Plan-IQ feasibility tool was performed for modified radical mastectomy in this study. We selected 50 patients with breast cancer treated with IMRT. All patients received the same dose in the planning target volume (PTV). The plans are categorized into two groups, with each patient having one plan in each group: the clinically accepted normal plan group (NP group) and the repeat plan group (RP group). An automated planning strategy was generated using a Plan-IQ feasibility dose volume histogram (FDVH) in RP group. These plans were assessed according to the dosimetry parameters. A detailed scoring strategy was based on the RTOG9804 report and 2018 National Comprehensive Cancer Network guidelines, combined with clinical experience. PTV coverage in both groups was achieved at 100% of the prescribed dose. Except for the thyroid coverage, the dose limit of organs at risk (OAR) in RP group was significantly better than that in NP group. In the scoring analysis, the total scores of RP group decreased compared to that of NP group (P < 0.05), and the individual scores of PTV and OAR significantly changed. PTV scores in RP group decreased (P < 0.01); however, OAR scores improved (P < 0.01). The Plan-IQ FDVH was useful for evaluating a class solution for IMRT planning. Plan-IQ can automatically help physicians design the best OAR protection plan, which sacrifices part of PTV, but still meets clinical requirements., (© 2021. The Author(s).)

Background: Lung cancer has been one of the most deadly illnesses all over the world, and radiotherapy can be an effective approach for treating lung cancer. Now, mathematical model has been extended to many biomedical fields to give a hand for analysis, evaluation, prediction, and optimization., Methods: In this paper, we propose a multicomponent mathematical model for simulating the lung cancer growth as well as radiotherapy treatment for lung cancer. The model is digitalized and coded for computer simulation, and the model parameters are fitted with many research and clinical data to provide accordant results along with the growth of lung cancer cells in vitro., Results: Some typical radiotherapy plans such as stereotactic body radiotherapy, conventional fractional radiotherapy, and accelerated hypofractionated radiotherapy are simulated, analyzed, and discussed. The results show that our mathematical model can perform the basic work for analysis and evaluation of the radiotherapy plan., Conclusion: It will be expected that in the near future, mathematical model will be a valuable tool for optimization in personalized medical treatment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wen-song Hong et al.)

Purpose: We present our data for every single fraction for every patient treated at our center for the past 4 years, analyzing the waiting and treatment times., Materials and Methods: Between January 2014 and February 2018, all patients and their corresponding recorded measurements of waiting time and machine treatment time were analyzed. Times recorded included actual arrival time, designated arrival time, linac entry time, and last beam treatment time. The complete waiting time information was divided into two categories (1) first day treatments and (2) subsequent day treatments. SPSS version 18 was used for statistical calculations, correlations, and assessing significance., Results: First day treatments - of 1982 patients following treatments were carried out; 1557 volumetric-modulated arc therapy (78.6%), 88 three-dimensional conformal radiotherapy (RT) (4.4%), 14 electron (0.7%), 10 intensity-modulated RT (0.5%), 264 stereotactic irradiation (13.3%), 17 stereotactic body RT (0.7%), and 32 total body irradiation (1.6%). The mean (± standard deviation) times for early/late time, total spent time (TST), wait time gross (WTG), and wait time net (WTN) were 11.0 ± 49.6 min, 74.7 ± 44.8 min, 47.46 ± 43.9 min, and 24.1 ± 44.4 min, respectively. Subsequent day treatments - a total of 34,438 sessions of treatment delivery were recorded. Overall average WTG was 37.4 ± 32.7 min. Overall WTN was 12.1 ± 62.7 min. Overall mean total spent time (TST) was 52.4 ± 33.0 min, overall mean setup and treatment time was 15.1 ± 10.9 min., Conclusion: We have presented our results of patient-related times during RT. Our study covers the daily waiting times before RT as well as the actual treatment times during modern-day RT. This consecutive patient data from a large series shall be an important resource tool for future planners and policymakers., Competing Interests: None

Background/aim: The aim of the study was to investigate boost volume definition, doses, and delivery techniques for rectal cancer dose intensification., Patients and Methods: An online survey was made on 25 items (characteristics, simulation, imaging, volumes, doses, planning and treatment)., Results: Thirty-eight radiation oncologists joined the study. Twenty-one delivered long-course radiotherapy with dose intensification. Boost volume was delineated on diagnostic magnetic resonance imaging (MRI) in 18 centres (85.7%), and computed tomography (CT) and/or positron emission tomography-CT in 9 (42.8%); 16 centres (76.2%) performed co-registration with CT-simulation. Boost dose was delivered on gross tumor volume in 10 centres (47.6%) and on clinical target volume in 11 (52.4%). The most common total dose was 54-55 Gy (71.4%), with moderate hypofractionation (85.7%). Intensity-modulated radiotherapy (IMRT) was used in all centres, with simultaneous integrated boost in 17 (80.8%) and image-guidance in 18 (85.7%)., Conclusion: A high quality of treatment using dose escalation can be inferred by widespread multidisciplinary discussion, MRI-based treatment volume delineation, and radiation delivery relying on IMRT with accurate image-guided radiation therapy protocols., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We present the concept of a new methodology for faster simulation of the doses in brachytherapy with permanent implants, based on the knowledge of the seeds arrangement, adding previously simulated doses in an equivalent medium in terms of the atomic composition of the organ in question. To perform the doses calculations we use Monte Carlo simulations. We simulated a cylindrical I-125 seed and compared our results against published data. Our proposal is to have the doses simulated previously in different arrangement of seed-absorbents, and then, considering the spacial positions of the seeds after the implants, these doses can be directly added, obtaining a very fast computation of the total dose. Two phantoms of prostates with permanent implant seeds in 2D and 3D arrangements were simulated. The results of the proposed methodology were compared with two complete Monte Carlo simulations in 2D and 3D designs. Differences in doses were analysed, obtaining statistical discrepancies of less than 1% and reducing the simulation time by more than 4 orders of magnitude. With the proposed methodology, it is possible to perform rapid dose calculations in brachytherapy, using laptop or desktop computers., (Copyright © 2020. Published by Elsevier Ltd.)

Aims: In central nervous system (CNS) tumors, surgery combined with radiotherapy may cure many tumors. The basic technique in conventional radiotherapy is craniospinal radiotherapy; in this technique, spinal cord can be treated with electron or photon beams. This study was aimed to compare two radiotherapy techniques in craniospinal radiotherapy, (a) treatment of spine with a single photon beam and (b) with a combination of photon and electron beams., Materials and Methods: The two techniques were planned. In the first technique, both brain and spine were irradiated with 6 MV photon beams. In the second technique, brain was irradiated with 6 MV photon and spine with 18 MeV electron beams. To compensate the dose deficiency in lumbar area, an anterior field of 15 MV photon beam was also applied in the second technique. The dose to target volume and organ at risks (OARs) were measured by thermoluminescent dosimeter and compared with the corresponding values calculated by Isogray treatment planning system., Results: OARs including heart, mandible, thyroid, and lungs received lower dose from technique 2 compared with technique 1; kidneys were exceptions which received higher dose in the technique 2., Conclusions: The dose to thyroid, mandible, heart, and lungs were lower in technique 2, while kidneys received higher dose in technique 2. This was caused by using the anterior 15 MV photon beam. Based on these results, for children, instead of photon beam for treatment of spinal cord, it is wiser to use electron beam., Competing Interests: None

We give a novel approach for obtaining an intensity-modulated radiation therapy (IMRT) optimization solution based on the idea of continuous dynamical methods. The proposed method, which is an iterative algorithm derived from the discretization of a continuous-time dynamical system, can handle not only dose-volume but also mean-dose constraints directly in IMRT treatment planning. A theoretical proof for the convergence to an equilibrium corresponding to the desired IMRT planning is given by using the Lyapunov stability theorem. By introducing the concept of "acceptable," which means the existence of a nonempty set of beam weights satisfying the given dose-volume and mean-dose constraints, and by using the proposed method for an acceptable IMRT planning, one can resolve the issue that the objective and evaluation are different in the conventional planning process. Moreover, in the case where the target planning is totally unacceptable and partly acceptable except for one group of dose constraints, we give a procedure that enables us to obtain a nearly optimal solution close to the desired solution for unacceptable planning. The performance of the proposed approach for an acceptable or unacceptable planning is confirmed through numerical experiments simulating a clinical setup., Competing Interests: The authors declare no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Ryosei Nakada et al.)

Purpose: To quantitatively predict the impact of cardiopulmonary dose on overall survival (OS) after radiotherapy for locally advanced non-small cell lung cancer., Experimental Design: We used the NRG Oncology/RTOG 0617 dataset. The model building procedure was preregistered on a public website. Patients were split between a training and a set-aside validation subset ( N = 306/131). The 191 candidate variables covered disease, patient, treatment, and dose-volume characteristics from multiple cardiopulmonary substructures (atria, lung, pericardium, and ventricles), including the minimum dose to the hottest x% volume (Dx%[Gy]), mean dose of the hottest x% (MOHx%[Gy]), and minimum, mean (Mean[Gy]), and maximum dose. The model building was based on Cox regression and given 191 candidate variables; a Bonferroni-corrected P value threshold of 0.0003 was used to identify predictors. To reduce overreliance on the most highly correlated variables, stepwise multivariable analysis (MVA) was repeated on 1000 bootstrapped replicates. Multivariate sets selected in ≥10% of replicates were fit to the training subset and then averaged to generate a final model. In the validation subset, discrimination was assessed using Harrell c -index, and calibration was tested using risk group stratification., Results: Four MVA models were identified on bootstrap. The averaged model included atria D45%[Gy], lung Mean[Gy], pericardium MOH55%[Gy], and ventricles MOH5%[Gy]. This model had excellent performance predicting OS in the validation subset ( c = 0.89)., Conclusions: The risk of death due to cardiopulmonary irradiation was accurately modeled, as demonstrated by predictions on the validation subset, and provides guidance on the delivery of safe thoracic radiotherapy., (©2020 American Association for Cancer Research.)

Algorithms are an essential part of radiation therapy planning, which includes three optimizations problems: beam angle configuration, fluence map, and realization. This study addresses the third one, also called the leaf sequencing problem, which arises for each chosen irradiation angle, given the optimized fluence map. It consists in defining a sequence of configurations of a device (called multileaf collimator) that correctly delivers radiation to the patient. A usual model for this problem is the decomposition of a matrix into a weighted sum of (0,1)-matrices, called segments, in which the ones in each row appear consecutively. Each (0,1)-matrix corresponds to a configuration of the device. The realization problem has three objectives. The first one is to minimize the sum of weights assigned to the (0,1)-matrices. The second is to minimize the number of segments. Finally, the third one is to find the best order to apply those configurations. This study presents a greedy and randomized algorithm to this problem and compares it with other algorithms presented previously in the literature. Statistical tests show that our algorithm outperformed the previous ones regarding the quality indicators investigated. Graphical Abstract a Illustrates how the IMRT realization is modelled to a mathematical problem. b Shows a decomposition example of the IMRT realization. c The scheme of the algorithm that is proposed on this work, called GRA-SRA.

Background: The IAEA recommends a quality assurance program in radiotherapy to ensure safe and effective treatments. In this study, radiotherapy departments were surveyed on their current practice including the extent and depth of quality assurance activities. Methods: Radiotherapy departments were voluntarily surveyed in three stages, firstly, in basic facility information, secondly, in quality assurance activities and treatment techniques, and thirdly, in a snapshot of quality assurance, departmental and treatment activities. Results: The IAEA received completed surveys from 381 radiotherapy departments throughout the world with 100 radiotherapy departments completing all three surveys. Dominant patterns were found in linac-based radiotherapy with access to treatment planning systems for 3D-CRT and 3D imaging. Staffing levels for major staff groups were on average in the range recommended by the IAEA. The modal patient workload per EBRT unit was as expected in the range of 21-30 patients per day, however significant instances of high workload (more than 50 patients per day per treatment unit) were reported. Staffing levels were found to correlate with amount of treatment equipment and patient workload. In a self-assessment of quality assurance performance, most radiotherapy departments reported that they would perform at least 60% of the quality assurance activities itemized in the second survey, with particular strength in equipment quality control. In a snapshot survey of quality assurance performance, again equipment quality control practice was well developed, particularly for the treatment equipment. Conclusions: The IAEA surveys provide a snapshot of current radiotherapy practice including quality assurance activities.

Introduction: To find the optimal dose prescription strategy for liver SBRT, this study investigated the tradeoffs between achievable target dose and healthy liver dose for a range of isotoxic uniform and non-uniform prescription level strategies. Material and methods: Nine patients received ten liver SBRT courses with intrafraction motion monitoring during treatment. After treatment, five VMAT treatment plans were made for each treatment course. The PTV margin was 5 mm (left-right, anterior-posterior) and 10 mm (cranio-caudal). All plans had a mean CTV dose of 56.25 Gy in three fractions, while the PTV was covered by 50%, 67%, 67 s% (steep dose gradient outside CTV), 80%, and 95% of this dose, respectively. The 50%, 67 s%, 80%, and 95% plans were then renormalized to be isotoxic with the standard 67% plan according to a Lyman-Kutcher-Burman normal tissue complication probability model for radiation induced liver disease. The CTV D98 and mean dose of the iso-toxic plans were calculated both without and with the observed intrafraction motion, using a validated method for motion-including dose reconstruction. Results: Under isotoxic conditions, the average [range] mean CTV dose per fraction decreased gradually from 21.2 [20.5-22.7] Gy to 15.5 [15.0-16.6] Gy and the D98 dose per fraction decreased from 20.4 [19.7-21.7] Gy to 15.0 [14.5-15.5] Gy, as the prescription level to the PTV rim was increased from 50% to 95%. With inclusion of target motion the mean CTV dose was 20.5 [16.5-22.5] Gy (50% PTV rim dose) and 15.4 [13.9-16.7] Gy (95% rim dose) while D98 was 17.8 [7.4-20.6] Gy (50% rim dose) and 14.6 [8.8-15.7] Gy (95% rim dose). Conclusion: Requirements of a uniform PTV dose come at the price of excess normal tissue dose. A non-uniform PTV dose allows increased CTV mean dose at the cost of robustness toward intrafraction motion. The increase in planned CTV dose by non-uniform prescription outbalanced the dose deterioration caused by motion.

Background: Dosimetric effects of inaccuracies of output factors (OFs) implemented in treatment planning systems (TPSs) were investigated. Materials and methods: Modified beam models (MBM) for which the OFs of small fields (down to 1 × 1 cm 2 ) were increased by up to 12% compared to the original beam models (OBM) were created for two TPSs. These beam models were used to recalculate treatment plans of different complexity. Treatment plans using stereotactic 3D-conformal (s3D-CRT) for brain metastasis as well as VMAT plans for head and neck and prostate cancer patients were generated. Dose distributions calculated with the MBM and the OBM were compared to measured dose distributions acquired using film dosimetry and a 2D-detector-array. For the s3D-CRT plans the calculated and measured dose at the isocenter was evaluated. For VMAT, gamma pass rates (GPRs) were calculated using global gamma index with 3%/3 mm, 2%/3 mm, 1%/3 mm and 2%/2 mm with a 20% threshold. Contribution of small fields to the total fluence was expressed as the ratio (F) of fluence trough leaf openings smaller than 2 cm to the total fluence. Results: Using film dosimetry for the s3D-CRT plans, the average of the ratio of calculated dose to measured dose at the isocenter was 1.01 and 1.06 for the OBM and MBM model, respectively. A significantly lower GPR of the MBM compared to the OBM was only found for the localized prostate cases ( F  = 12.4%) measured with the 2D-detector-array and an acceptance criterion of 1%/3 mm. Conclusion: The effects of uncertainties in small field OFs implemented in TPSs are most pronounced for s3D-CRT cases and can be clearly identified using patient specific quality assurance. For VMAT these effects mainly remain undetected using standard patient specific quality assurance. Using tighter acceptance criteria combined with an analysis of the fluence generated by small fields can help identifying inaccuracies of OFs implemented in TPSs.

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

Purpose: This study aimed to investigate the parameters with a significant impact on delivery quality assurance (DQA) failure and analyze the planning parameters as possible predictors of DQA failure for helical tomotherapy., Methods: In total, 212 patients who passed or failed DQA measurements were retrospectively included in this study. Brain (n = 43), head and neck (n = 37), spinal (n = 12), prostate (n = 36), rectal (n = 36), pelvis (n = 13), cranial spinal irradiation and a treatment field including lymph nodes (n = 24), and other types of cancer (n = 11) were selected. The correlation between DQA results and treatment planning parameters were analyzed using logistic regression analysis. Receiver operating characteristic (ROC) curves, areas under the curves (AUCs), and the Classification and Regression Tree (CART) algorithm were used to analyze treatment planning parameters as possible predictors for DQA failure., Results: The AUC for leaf open time (LOT) was 0.70, and its cut-off point was approximately 30%. The ROC curve for the predicted probability calculated when the multivariate variable model was applied showed an AUC of 0.815. We confirmed that total monitor units, total dose, and LOT were significant predictors for DQA failure using the CART., Conclusions: The probability of DQA failure was higher when the percentage of LOT below 100 ms was higher than 30%. The percentage of LOT below 100 ms should be considered in the treatment planning process. The findings from this study may assist in the prediction of DQA failure in the future.

Purpose: With the widespread prevalence of Corona Virus Disease 2019 (COVID-19), cancer patients are suggested to wear a surgical mask during radiation treatment. In this study, cone beam CT (CBCT) was used to investigate the effect of surgical mask on setup errors in head and neck radiotherapy., Methods: A total of 91 patients with head and neck tumors were selected. CBCT was performed to localize target volume after patient set up. The images obtained by CBCT before treatment were automatically registered with CT images and manually fine-tuned. The setup errors of patients in 6 directions of Vrt, Lng, Lat, Pitch, Roll and Rotation were recorded. The patients were divided into groups according to whether they wore the surgical mask, the type of immobilization mask used and the location of the isocenter. The setup errors of patients were calculated. A t -test was performed to detect whether it was statistically significant., Results: In the 4 groups, the standard deviation in the directions of Lng and Pitch of the with surgical mask group were all higher than that in the without surgical mask group. In the head-neck-shoulder mask group, the mean in the Lng direction of the with surgical mask group was larger than that of the without surgical mask group. In the lateral isocenter group, the mean in the Lng and Pitch directions of the with surgical mask group were larger than that of the without surgical mask group. The t -test results showed that there was significant difference in the setup error between the 2 groups ( p = 0.043 and p = 0.013, respectively) only in the Lng and Pitch directions of the head-neck-shoulder mask group. In addition, the setup error of 6 patients with immobilization open masks exhibited no distinguished difference from that of the patients with regular immobilization masks., Conclusion: In the head and neck radiotherapy patients, the setup error was affected by wearing surgical mask. It is recommended that the immobilization open mask should be used when the patient cannot finish the whole treatment with a surgical mask.

Purpose: Lymphedema after regional nodal irradiation is a severe complication that could be minimized without significantly compromising nodal coverage if the anatomic region(s) associated with lymphedema were better defined. This study sought to correlate dose-volume relationships within subregions of the axilla with lymphedema outcomes to generate treatment planning guidelines for reducing lymphedema risk., Methods and Materials: Women with stage II-III breast cancer who underwent breast surgery with axillary assessment and regional nodal irradiation were identified. Nodal targets were prospectively contoured per Radiation Therapy Oncology Group guidelines for field design. The axilla was divided into 8 distinct subregions that were retrospectively contoured. Lymphedema outcomes were assessed by arm circumferences. Multivariate Cox proportional hazards regression assessed patient, surgical, and dosimetric predictors of lymphedema outcomes., Results: Treatment planning computed tomography scans for 265 women treated between 2013 and 2017 were identified. Median post-radiation therapy follow-up was 3 years (interquartile range [IQR], 1.9-3.6). Dose to the axillary-lateral thoracic vessel juncture (ALTJ; superior to level I) was most associated with lymphedema risk (maximally selected rank statistic = 6.3, P < .001). The optimal metric was ALTJ minimum dose (D min ) <38.6 Gy (3-year lymphedema rate 5.7% vs 37.4%, P <.001), although multiple parameters relating to sparing of the ALTJ were highly correlated. Multivariate analysis confirmed ALTJ D min <38.6 Gy (hazard ratio [HR], 0.13; P < .001), body mass index (HR, 1.06/unit; P = .002), and number of lymph nodes removed (HR, 1.08/node; P < .001) as significant predictors. Women with ALTJ D min <38.6 Gy maintained median V 45Gy of 99% in the supraclavicular (IQR, 94-100%), 100% in level III (IQR, 97%-100%), 98% in level II (IQR, 86%-100%), and 91% in level I (IQR, 75%-98%) nodal basins., Conclusions: Anatomic studies suggest the ALTJ region is typically traversed by arm lymphatics and appears to be an organ at risk in breast radiation therapy. Ideally, avoidance of the ALTJ may be feasible while simultaneously encompassing breast-draining nodal basins. Confirmation of this finding in future prospective studies is needed., (Copyright © 2019. Published by Elsevier Inc.)

Background: In locoregionally advanced nasopharyngeal carcinoma (LANPC) patients, variance of tumor response to induction chemotherapy (ICT) was observed. We developed and validated a novel imaging biomarker to predict which patients will benefit most from additional ICT compared with chemoradiotherapy (CCRT) alone., Methods: All patients, including retrospective training (n = 254) and prospective randomized controlled validation cohorts (a substudy of NCT01245959, n = 248), received ICT+CCRT or CCRT alone. Primary endpoint was failure-free survival (FFS). From the multi-parameter magnetic resonance images of the primary tumor at baseline, 819 quantitative 2D imaging features were extracted. Selected key features (according to their interaction effect between the two treatments) were combined into an Induction Chemotherapy Outcome Score (ICTOS) with a multivariable Cox proportional hazards model using modified covariate method. Kaplan-Meier curves and significance test for treatment interaction were used to evaluate ICTOS, in both cohorts., Results: Three imaging features were selected and combined into ICTOS to predict treatment outcome for additional ICT. In the matched training cohort, patients with a high ICTOS had higher 3-year and 5-year FFS in ICT+CCRT than CCRT subgroup (69.3% vs. 45.6% for 3-year FFS, and 64.0% vs. 36.5% for 5-year FFS; HR = 0.43, 95% CI = 0.25-0.74, p = 0.002), whereas patients with a low ICTOS had no significant difference in FFS between the subgroups (p = 0.063), with a significant treatment interaction (p interaction  <  0.001). This trend was also found in the validation cohort with high (n = 73, ICT+CCRT 89.7% and 89.7% vs. CCRT 61.8% and 52.8% at 3-year and 5-year; HR = 0.17, 95% CI = 0.06-0.51, p <  0.001) and low ICTOS (n = 175, p = 0.31), with a significant treatment interaction (p interaction  = 0.019). Compared with 12.5% and 16.6% absolute benefit in the validation cohort (3-year FFS from 69.9 to 82.4% and 5-year FFS from 63.4 to 80.0% from additional ICT), high ICTOS group in this cohort had 27.9% and 36.9% absolute benefit. Furthermore, no significant survival improvement was found from additional ICT in both groups after stratifying low ICTOS patients into low-risk and high-risks groups, by clinical risk factors., Conclusion: An imaging biomarker, ICTOS, as proposed, identified patients who were more likely to gain additional survival benefit from ICT+CCRT (high ICTOS), which could influence clinical decisions, such as the indication for ICT treatment., Trial Registration: ClinicalTrials.gov , NCT01245959 . Registered 23 November 2010.

Purpose: The ongoing phase 2/3 PRODIGE 26/CONCORDE trial compares chemoradiation therapy with and without dose escalation in patients with locally advanced or unresectable esophageal cancer. The results of a benchmark case procedure are reported here to evaluate the protocol compliance of participating centers as part of quality assurance for radiation therapy., Methods and Materials: Volume delineation, target coverage, and dose constraints to the organs at risk (OARs) were assessed on treatment plans of a common benchmark case performed by each participating center. The centers were classified in 3 categories: per protocol, minor acceptable deviation (MiD), or major unacceptable deviation (MaD). A plan was rejected if ≥4 MiDs or 1 MaD were found., Results: Thirty-5 centers submitted 43 plans. Among them, 14 (32.6%) were per protocol, 19 (44.2%) presented at least 1 MiD, 2 (4.6%) presented at least 1 MaD, and 8 (18.6%) presented both MiD and MaD. Overall, 11 (25.6%) plans were rejected. Only 1 plan was rejected because gross tumor volume was not correctly delineated. The OAR delineation was respected in all cases. Dose constraints to the OARs were respected in the majority of cases except for the heart, where one-third of the plans presented a deviation. As for the target volume, 3 plans (5.8%) had a major underdosage and 1 plan (1.9%) had a major overdosage. Overall, 58% of all treatments were planned with intensity modulated radiation therapy, whereas 42% were planned with 3-dimensional chemoradiation therapy. Significantly more plans in the intensity modulated radiation therapy group were accepted compared with the 3-dimensional chemoradiation therapy group (P = .03)., Conclusion: The high frequency of protocol deviations underlines the importance of a quality assurance program in clinical trials. Further work should assess the impact of quality assurance for radiation therapy on patient outcomes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Inter-observer variability (IOV) in target volume delineation is a well-documented source of geometric uncertainty in radiotherapy. Such variability has not yet been explored in the context of adaptive re-delineation based on imaging data acquired during treatment. We compared IOV in the pre- and mid-treatment setting using expert primary gross tumour volume (GTV) and clinical target volume (CTV) delineations in locoregionally advanced head-and-neck squamous cell carcinoma (HNSCC) and (non-)small cell lung cancer [(N)SCLC]. Material and methods: Five and six observers participated in the HNSCC and (N)SCLC arm, respectively, and provided delineations for five cases each. Imaging data consisted of CT studies partly complemented by FDG-PET and was provided in two separate phases for pre- and mid-treatment. Global delineation compatibility was assessed with a volume overlap metric (the Generalised Conformity Index), while local extremes of IOV were identified through the standard deviation of surface distances from observer delineations to a median consensus delineation. Details of delineation procedures, in particular, GTV to CTV expansion and adaptation strategies, were collected through a questionnaire. Results: Volume overlap analysis revealed a worsening of IOV in all but one case per disease site, which failed to reach significance in this small sample ( p -value range .063-.125). Changes in agreement were propagated from GTV to CTV delineations, but correlation could not be formally demonstrated. Surface distance based analysis identified longitudinal target extent as a pervasive source of disagreement for HNSCC. High variability in (N)SCLC was often associated with tumours abutting consolidated lung tissue or potentially invading the mediastinum. Adaptation practices were variable between observers with fewer than half stating that they consistently adapted pre-treatment delineations during treatment. Conclusion: IOV in target volume delineation increases during treatment, where a disparity in institutional adaptation practices adds to the conventional causes of IOV. Consensus guidelines are urgently needed.

The benefits of integrating MRI into the radiotherapy pathway are well published, however there is little consensus in guidance on how to commission or implement its use. With a view to developing consensus guidelines for the use of MRI in external beam radiotherapy (EBRT) treatment planning in the UK, a survey was undertaken by an Institute of Physics and Engineering in Medicine (IPEM) working-party to assess the current landscape of MRI use in EBRT in the UK. A multi-disciplinary working-party developed a survey to understand current practice using MRI for EBRT treatment planning; investigate how MRI is currently used and managed; and identify knowledge gaps. The survey was distributed electronically to radiotherapy service managers and physics leads in 71 UK radiotherapy (RT) departments (all NHS and private groups). The survey response rate was 87% overall, with 89% of NHS and 75% of private centres responding. All responding centres include EBRT in some RT pathways: 94% using Picture Archiving and Communication System (PACS) images potentially acquired without any input from RT departments, and 69% had some form of MRI access for planning EBRT. Most centres reporting direct access use a radiology scanner within the same hospital in dedicated (26%) or non-dedicated (52%) RT scanning sessions. Only two centres reported having dedicated RT MRI scanners in the UK, lower than reported in other countries. Six percent of radiotherapy patients in England (data not publically available outside of England) have MRI as part of their treatment, which again is lower than reported elsewhere. Although a substantial number of centres acquire MRI scans for treatment planning purposes, most centres acquire less than five patient scans per month for each treatment site. Commissioning and quality assurance of both image registration and MRI scanners was found to be variable across the UK. In addition, staffing models and training given to different staff groups varied considerably across the UK, reflecting the current lack of national guidelines. The primary barriers reported to MRI implementation in EBRT planning included costs (e.g. lack of a national tariff for planning MRI), lack of MRI access and/or capacity within hospitals. Despite these challenges, significant interest remains in increasing MRI-assisted EBRT planning over the next five years.

Purpose: Lung and some digestive tumours move during a respiratory cycle. Four-dimensional scanography (4D-CT) is commonly used in treatment planning to account for respiratory motion. Although many French radiotherapy centres are now equipped, there are no guidelines on this subject to date. We wanted to draw up a description of the use of the 4D-CT for the treatment planning in France., Methods and Material: We conducted a survey in all French radiotherapy centres between March and April 2017., Results: One hundred and seventy-two were contacted. The participation rate was 88.37%. The use of the 4D-CT seems to be common and concerned planning for 15.28% of kidney and adrenal cancers, 19.72% of pancreatic cancers, 27.78% of oesophageal cancers and 73.24% of lung cancers in case of normofractionated treatments. The use of the 4D-CT was also widespread in the case of stereotactic body radiation therapy: with 61.11% in the case of pulmonary irradiation and 34.72% in the case of hepatic irradiation. Many centres declared they carried out several 4D-CT for treatment planning (29, 55% in case of stereotactic body radiation therapy for lung tumours and 20% for liver tumours). Private centres tend to repeat 4D-CT more., Conclusion: Although the use of the 4D-CT appears to be developing, it remains very heterogeneous. To date, the repetition of the 4D-CT has been very poorly studied and could be the subject of clinical studies, allowing to define in which indications and for which populations there is a real benefit., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: Preoperative long-course chemoradiotherapy (CRT) and short-course radiotherapy (SCR) for locally advanced rectal cancer (LARC) were found to have equivalent outcomes in 3 randomized trials. SCR has not been widely adopted in the United States (US). Three-dimensional (3D) treatment planning is standard, whereas intensity-modulated radiotherapy (IMRT) is controversial. In this study, we assessed the economic impact of fractionation scheme and planning method for payers in the US., Materials and Methods: We performed a population-based analysis of the total cost of radiotherapy for LARC in the US annually. The national annual target population was calculated using the Surveillance, Epidemiology, and End Results database. Radiotherapy costs were based on billing codes and 2018 pricing by Medicare's Hospital Outpatient Prospective Payment System., Results: We estimate that 12,945 patients with LARC are treated with radiotherapy annually in the US. The cost of CRT with 3D or IMRT is US $15,882 and $23,745 per patient, respectively. With SCR, the cost with 3D or IMRT is $5,458 and $7,323 per patient, respectively. The use of SCR would lead to 53% to 77% annual savings of $106,168,871 to $232,105,727 compared with CRT. IMRT increases the total cost of treatment by 34% to 50%, and if adopted widely, would lead to an excess cost of $24,152,134 and $101,784,723 annually with SCR and CRT, respectively., Conclusions: SCR may have the potential to save approximately US $106 to t232 million annually in the US, likely without impacting outcomes. Lack of evidence showing benefit with costly IMRT should limit its use to clinical trials. It would be reasonable for public and private payers to consider which type of radiation is most suited to reimbursement., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The use of radiolabeled molecules for tumor targeting constitutes a remarkable technique for the treatment of systemic malignancies. An accurate patient-specific dosimetry in nuclear medicine procedures should be a relevant pre-requisite in order to achieve the required lethal damage to tumor cells while maintaining possible side-effects to normal tissues at tolerable levels. It is desired to assess in vivo the radiopharmaceutical distribution for further estimation of absorbed dose released to target and involved organs. In this context, it was developed a computational toolkit, called DOSIS, in order to perform patient-specific dosimetry based on personalized patient anatomy and biodistribution of radionuclides both obtained by currently available dual PET/CT or SPECT/CT facilities. This work is focused on comparing 3D dose distributions obtained by DOSIS performing full stochastic Monte Carlo simulations versus analogue distributions obtained with analytical approaches like dose point kernel convolution and local energy deposition, when considering non-homogeneous activity or density distributions at different scales. Mathematical virtual phantoms were created for this study in order to compare results with other calculation methods. Some of the beta-emitters radionuclides commonly used for therapy ( 90 Y, 131 I, 177 Lu) were investigated, and emissions of beta-particles, conversion electrons, gamma radiation, and characteristic X-rays were considered. DOSIS implements a novel code devoted to managing radiation transport simulation by means of PENELOPE Monte Carlo general-purpose routines on voxelized geometries defined by 3D mass and activity distributions. Both distributions can be defined through patients-specific images, or pre-defined virtual phantoms. Results preliminary confirmed DOSIS as a reliable and accurate toolkit for personalized internal dosimetry along with highlighting advantages/drawbacks of the different calculation schemes proposed., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We address a non-linear programming problem to find the optimal scheme of dose fractionation in cancer radiotherapy. Using the LQ model to represent the response to radiation of tumour and normal tissues, we formulate a constrained non-linear optimization problem in terms of the variables number and sizes of the dose fractions. Quadratic constraints are imposed to guarantee that the damages to the early and late responding normal tissues do not exceed assigned tolerable levels. Linear constraints are set to limit the size of the daily doses. The optimal solutions are found in two steps: i) analytical determination of the optimal sizes of the fractional doses for a fixed, but arbitrary number of fractions n; ii) numerical simulation of a sequence of the previous optima for n increasing, and for specific tumour classes. We prove the existence of a finite upper bound for the optimal number of fractions. So, the optimum with respect to n is found by means of a finite number of comparisons amongst the optimal values of the objective function at the first step. In the numerical simulations, the radiosensitivity and repopulation parameters of the normal tissue are fixed, while we investigate the behaviour of the optimal solution for wide variations of the tumour parameters, relating our optima to real clinical protocols. We recognize that the optimality of hypo or equi-fractionated treatment schemes depends on the value of the tumour radiosensitivity ratio compared to the normal tissue radiosensitivity. Fast growing, radioresistant tumours may require particularly short optimal treatments., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Institute of Mathematics and its Applications. All rights reserved.)

Purpose: This study aimed to present an innovative approach to quantify, visualize, and predict radiation therapy (RT) process reliability using data captured from a voluntary incident learning system, with an overall aim to improve patient safety outcomes., Methods and Materials: We analyzed 111 reported deviations that were tripped and caught within 159 mapped RT process steps included within 7 major stages of RT delivery, 94 of which were any type of quality assurance (QA) controls. This allowed for us to compute the trip rate and fail-to-catch-rate (FCR) per each QA control with the available data. Next, we used a logistic regression model to identify significant variables predictive of FCRs, predicted FCRs for each QA control without available data, and thus, attempted to quantify RT process reliability expressed as percentage of patients with uncaught deviations after treatment planning, before their first treatment, and during treatment delivery., Results: Using the predicted FCRs, we computed the upper 95% likelihood that a deviation remains uncaught in a patient's course of treatment at the following RT process stages: immediately after treatment planning at 10.26%; before the first treatment at 0.0052%; and throughout treatment delivery at 0.0276%., Conclusions: The results suggest that RT process reliability can be predicted and visualized using data from incident learning systems. If implemented and used as a safety metric, this could help RT clinics to proactively maintain their preoccupation with patient safety. RT process reliability may also help guide future work on standardization and continuous improvement of the design of RT QA programs., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: In prostate cancer treatment with external beam radiation therapy (EBRT), prostate motion and internal changes in tissue distribution can lead to a decrease in plan quality. In most currently used planning methods, the uncertainties due to prostate motion are compensated by irradiating a larger treatment volume. However, this could cause underdosage of the treatment volume and overdosage of the organs at risk (OARs). To reduce this problem, in this proof of principle study we developed and evaluated a novel adaptive planning method. The strategy proposed corrects the dose delivered by each beam according to the actual position of the target in order to produce a final dose distribution dosimetrically as similar as possible to the prescribed one., Material and Methods: Our adaptive planning method was tested on a phantom case and on a clinical case. For the first, a pilot study was performed on an in-silico pelvic phantom. A "library" of intensity modulated RT (IMRT) plans corresponding to possible positions of the prostate during a treatment fraction was generated at planning stage. Then a 3D random walk model was used to simulate possible displacements of the prostate during the treatment fraction. At treatment stage, at the end of each beam, based on the current position of the target, the beam from the library of plans, which could reproduce the best approximation of the prescribed dose distribution, was selected and delivered. In the clinical case, the same approach was used on two prostate cancer patients: for the first a tissue deformation was simulated in-silico and for the second a cone beam CT (CBCT) taken during the treatment was used to simulate an intra-fraction change. Then, dosimetric comparisons with the standard treatment plan and, for the second patient, also with an isocenter shift correction, were performed., Results: For the phantom case, the plan generated using the adaptive planning method was able to meet all the dosimetric requirements and to correct for a misdosage of 13% of the dose prescription on the prostate. For the first clinical case, the standard planning method caused underdosage of the seminal vesicles, respectively by 5% and 4% of the prescribed dose, when the position changes for the target were correctly taken into account. The proposed adaptive planning method corrected any possible missed target coverage, reducing at the same time the dose on the OARs. For the second clinical case, both with the standard planning strategy and with the isocenter shift correction target coverage was significantly worsened (in particular uniformity) and some organs exceeded some toxicity objectives. While with our approach, the most uniform coverage for the target was produced and systematically the lowest toxicity values for the organs at risk were achieved., Conclusions: In our proof of principle study, the adaptive planning method performed better than the standard planning and the isocenter shift methods for prostate EBRT. It improved the coverage of the treatment volumes and lowered the dose to the OARs. This planning method is particularly promising for hypofractionated IMRT treatments in which a higher precision and control on dose deposition are needed. Further studies will be performed to test more extensively the proposed adaptive planning method and to evaluate it at a full clinical level., Competing Interests: We have the following interests. All the authors were employed by Philips Research, when the work has been implemented. Presently, only Peter Prinsen and Alfonso A. Isola are employed by Philips Research. This work is related to an invention previously patented by two of the co-authors (“Radiation therapy system using plural treatment plans”, patent #WO 2017005758 A1, inventors DF and AAI). There are no further patents, products in development or marketed products to declare. The commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials. This work is related to an invention previously patented by two of the co-authors (patent #WO 2017005758 A1, inventors DF and AAI). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: In patients diagnosed with rectal cancer, dose escalation is currently being investigated in a large number of studies. Since there is little known on gross tumor volume (GTV) inter-fraction motion for rectal cancer, a wide variety in margins is used. Purpose of this study is to quantify GTV inter-fraction motion statistics on different timescales and to give estimates of planning target volume (PTV) margins., Material and Methods: Thirty-two patients, diagnosed with rectal cancer, were included. To investigate motion from week-to-week, 16 patients underwent a pretreatment and five weekly MRIs, prior to a radiotherapy (RT) fraction of the chemoradiotherapy treatment. To investigate motion from day-to-day, the remaining 16 patients underwent five daily MRIs before each fraction in one week of RT. GTV was delineated on all scans according to guidelines. Scans were aligned on bony anatomy with the first MRI. For both datasets separately, GTV inter-fraction motion was determined based on center-of-gravity displacement. Therefrom, systematic and random errors were determined in left/right (LR), anterior/posterior and cranial/caudal (CC) direction. PTV margin estimates were calculated and evaluated on GTV coverage., Results: Systematic and random errors were found in the range of 2.3-4.8 mm and 1.5-3.3 mm from week-to-week, and 1.8-4.5 mm and 1.8-4.0 mm from day-to-day, respectively. On both timescales, similar motion patterns were found; the most motion was observed in CC whilst the least motion was observed in LR. On the week-to-week data more systematic and less random motion was observed compared to the day-to-day data. Overall, only slight differences in margin estimates were found. Derived PTV margin estimates were found to give adequate GTV coverage., Conclusion: GTV inter-fraction motion, on a week-to-week and day-to-day timescale, can be accounted for using motion statistics presented in this study.

Background: To assess the impact of training and interprofessional collaboration on the interobserver variation in the delineation of the lung gross tumor volume (GTVp) and lymph node (GTVln)., Material and Methods: Eight target volume delineations courses were organized between 2008 and 2013. Specialists and trainees in radiation oncology were asked to delineate the GTVp and GTVln on four representative CT images of a patient diagnosed with lung cancer individually prior each course (baseline), together as group (interprofessional collaboration) and post-training. The mean delineated volume and local standard deviation (local SD) between the contours for each course group were calculated and compared with the expert delineations., Results: A total 410 delineations were evaluated. The average local SD was lowest for the interprofessional collaboration (GTVp = 0.194 cm, GTVln = 0.371 cm) followed by the post-training (GTVp = 0.244 cm, GTVln = 0.607 cm) and baseline delineations (GTVp = 0.274 cm, GTVln: 0.718 cm). The mean delineated volume was smallest for the interprofessional (GTVp = 4.93 cm 3 , GTVln = 4.34 cm 3 ) followed by the post-training (GTVp = 5.68 cm 3 , GTVln = 5.47 cm 3 ) and baseline delineations (GTVp = 6.65 cm 3 , GTVln = 6.93 cm 3 ). All delineations were larger than the expert for both GTVp and GTVln (p < .001)., Conclusion: Our findings indicate that image interpretational differences can lead to large interobserver variation particularly when delineating the GTVln. Interprofessional collaboration was found to have the greatest impact on reducing interobserver variation in the delineation of the GTVln. This highlights the need to develop a clinical workflow so as to ensure that difficult cases are reviewed routinely by a second radiation oncologist or radiologist so as to minimize the risk of geographical tumor miss and unnecessary irradiation to normal tissue.

Purpose: Robotic stabilization of a therapeutic radiation beam with respect to a dynamically moving tumor target can be accomplished either by moving the radiation source, the patient, or both. As the treatment beam is on during this process, the primary goal is to minimize exposure of normal tissue to radiation as much as possible when moving the target back to the desired position. Due to the complex mechanical structure of 6 degree-of-freedom (6DoF) robots, it is not intuitive as to what 6 dimensional (6D) correction trajectory is optimal in achieving such a goal. With proportional-integrative-derivative (PID) and other controls, the potential exists that the controller may generate a trajectory that is highly curved, slow, or suboptimal in that it leads to unnecessary exposure of healthy tissue to radiation. This work investigates a novel feedback planning method that takes into account a robot's mechanical joint structure, patient safety tolerances, and other system constraints, and performs real-time optimization to search the entire 6D trajectory space in each time cycle so it can respond with an optimal 6D correction trajectory., Methods: Computer simulations were created for two 6DoF robotic patient support systems: a Stewart-Gough platform for moving a patient's head in frameless maskless stereotactic radiosurgery, and a linear accelerator treatment table for moving a patient in prostate cancer radiation therapy. Motion planning was formulated as an optimization problem and solved at real-time speeds using the L-BFGS algorithm. Three planning methods were investigated, moving the platform as fast as possible (platform-D), moving the target along a straight-line (target-S), and moving the target based on the fastest descent of position error (target-D). Both synthetic motion and prior recorded human motion were used as input data and output results were analyzed., Results: For randomly generated 6D step-like and sinusoidal synthetic input motion, target-D planning demonstrated the smallest net trajectory error in all cases. On average, optimal planning was found to have a 45% smaller target trajectory error than platform-D control, and a 44% smaller target trajectory error than target-S planning. For patient head motion compensation, only target-D planning was able to maintain a ≤0.5mm and ≤0.5deg clinical tolerance objective for 100% of the treatment time. For prostate motion, both target-S planning and target-D planning outperformed platform-D control., Conclusions: A general 6D target trajectory optimization framework for robotic patient motion compensation systems was investigated. The method was found to be flexible as it allows control over various performance requirements such as mechanical limits, velocities, acceleration, or other system control objectives., Competing Interests: A patent application titled: SYSTEMS AND METHODS FOR DETERMINING 6DOF CORRECTION TRAJECTORIES IN COMPENSATING MOVEMENT OF A TREATMENT TARGET IN A PATIENT has been submitted by Rodney Wiersma to the US patent office and is currently under review. There are no further patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Purpose: To investigate the dosimetric effect of variable gas volume in esophageal cancer radiation therapy (RT) and whether a density override (DO) in treatment planning can effectively mitigate this dosimetric effect., Material and Methods: Nine patients with gastrointestinal gas pockets in the planning computed tomography (pCT) were retrospectively included. Per patient, the intensity-modulated RT (IMRT) and volumetric-modulated arc therapy (VMAT) plans associated with no DO, DO = 0.5, and DO = 1 in the gas pockets were made. Initial and follow-up gas volumes were assessed from the pCTs and cone-beam CTs (CBCTs), respectively. Fractional CTs were created based on the pCT and CBCTs to calculate the fractional doses using all six plans. We then investigated for all six plans the correlation between the gas volume difference (relative to initial gas volume) and the dose difference (relative to planned dose). We also calculated and compared the accumulated dose by summing the fractional doses using two strategies: single-plan strategy (i.e. using each of the six plans separately) and plan-selection strategy (i.e. selecting one of the three plans depending on the fractional gas volume for IMRT and VMAT planning separately)., Results: The dose difference was approximately linearly correlated to the gas volume difference. Underdoses of >3.5% and overdoses of >7% were found for gas volume decreases >160 mL/330 mL and increases >260 mL/370 mL for IMRT/VMAT planning, respectively. Moreover, for most patients, the single-plan strategy with the use of DO = 0.5 resulted in neither undesired underdose nor much overdose. The plan-selection strategy, however, can always ensure sufficient target coverage and minimize high dose regions to the most extent., Conclusions: The variation in gas volume during the treatment course can result in clinically undesired underdose or overdose. The DO-based plan-selection strategy can effectively mitigate the gas-induced underdose and minimize the overdose for esophageal cancer RT.

Currently, lung cancer is one of the most lethal types of cancer (IARC, 2012), the pathology being detected in advanced stage, when the tumor has considerable volume because the disease in most cases asymptomatic in the early stages (INCA, 2016). Dosimetry analysis of healthy organs under real conditions is not feasible. Therefore, computational simulations are used to aid in dose verification in organs of patients submitted to radiotherapy. The goal of this study was to calculate the equivalent dose, due to photons, in the surrounding of healthy organs of patients submitted to radiotherapy for lung cancer, through computational modeling. The simulation was performed using the MCNPX code (MNCPX, 2006), Rex and Regina phantoms (ICRP 110, 2009), radiotherapy room, Siemens Oncor Expression accelerator operating at 6 MV and treatment protocol adopted at the INCA (National Cancer Institute - Brazil). The results obtained, considering the dose due to photons for both phantoms indicate that organs located inside the thoracic cavity received higher dose, being the bronchi, heart and esophagus more affected, due to their anatomical positioning. Clinical data describe the development of bronchiolitis, esophagitis and cardiomyopathies with decreased cardiopulmonary function as one of the major effects of lung cancer treatment. In the Regina phantom, the second largest dose was in the region of the breasts with 615.73 mSv/Gy, while in the Rex the dose was 514.06 mSv/Gy, event related to the difference of anatomical structure of the organ. A qualitative analysis was performed between the dose deposition profile of the treatment planning system and the simulated treatment through the tmesh command and a similar profile of dose distribution was verified throughout the patient's body., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To measure the impact of contouring on worktime in the adjuvant radiation treatment of breast cancer, and to identify factors that might affect the measurements., Material and Methods: The dates and times of contouring clinical target volumes and organs at risk were recorded by a senior and by two junior radiation oncologists. Outcome measurements were contour times and the time from start to approval. The factors evaluated were patient age, type of surgery, radiation targets and setup, operator, planning station, part of the day and day of the week on which the contouring started. The Welch test was used to comparatively assess the measurements., Results: Two hundred and three cases were included in the analysis. The mean contour time per patient was 34minutes for a mean of 4.72 structures, with a mean of 7.1minutes per structure. The clinical target volume and organs at risk times did not differ significantly. The mean time from start to approval per patient was 29.4hours. Factors significantly associated with longer contour times were breast-conserving surgery (P=0.026), prone setup (P=0.002), junior operator (P<0.0001), Pinnacle planning station (P=0.026), contouring start in the morning (P=0.001), and contouring start by the end of the week (P<0.0001). Factors significantly associated with time from start to approval were age (P=0.038), junior operator (P<0.0001), planning station (P=0.016), and contouring start by the end of the week (P=0.004)., Conclusion: Contouring is a time-consuming process. Each delineated structure influences worktime, and many factors may be targeted for optimization of the workflow. These preliminary data will serve as basis for future prospective studies to determine how to establish a cost-effective solution., (Copyright © 2018 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

During respiratory-gated radiotherapy (RGRT), gate on and off latencies cause deviations of gating windows, possibly leading to delivery of low- and high-dose radiations to tumors and normal tissues, respectively. Currently, there are no RGRT systems that have definite tools to compensate for the delays. To address the problem, we propose a framework consisting of two steps: (1) multistep-ahead prediction and (2) prediction-based gating. For each step, we have devised a specific algorithm to accomplish the task. Numerical experiments were performed using respiratory signals of a phantom and ten volunteers, and our prediction-based RGRT system exhibited superior performance in more than a few signal samples. In some, however, signal prediction and prediction-based gating did not work well, maybe due to signal irregularity and/or baseline drift. The proposed approach has potential applicability in RGRT, and further studies are needed to verify and refine the constituent algorithms.

Conventional radiotherapy is mainly applied by linear accelerators. Although linear accelerators provide dual (electron/photon) radiation beam modalities, both of them are intrinsically produced by a megavoltage electron current. Modern radiotherapy treatment techniques are based on suitable devices inserted or attached to conventional linear accelerators. Thus, precise control of delivered beam becomes a main key issue. This work presents an integral description of electron beam deflection control as required for novel radiotherapy technique based on convergent photon beam production. Theoretical and Monte Carlo approaches were initially used for designing and optimizing device´s components. Then, dedicated instrumentation was developed for experimental verification of electron beam deflection due to the designed magnets. Both Monte Carlo simulations and experimental results support the reliability of electrodynamics models used to predict megavoltage electron beam control., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Using Monte Carlos methods, with the MCNP5 code, a gynecological phantom and a vaginal cylinder were modeled. The spatial distribution of absorbed dose rates in Uterine Cervical Cancer treatment through low dose rate brachytherapy was determined. A liquid water gynecology computational phantom, including a vaginal cylinder applicator made of Lucite, was designed. The applicator has a linear array of four radioactive sources of Cesium 137. Around the vaginal cylinder, 13 water spherical cells of 0.5 cm-diameter were modeled to calculate absorbed dose emulating the procedure made by the treatment planning system. The gamma-ray fluence distribution was estimated, as well as the absorbed doses resulting approximately symmetrical for cells located at upper and lower of vaginal cylinder. Obtained results allow the use of the radioactive decay law to determine dose rate for Uterine Cervical Cancer using low dose rate brachytherapy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Radiotherapy plays an important role in curative and palliative cancer treatment. As a novel radiation delivery technique, stereotactic radiotherapy utilizes three-dimensional-conformal treatment planning, high-precision beam delivery technology, and patient specific position verification to target tumors, often in one to five high-dose fractions. Currently, there is no consensus about best stereotactic radiotherapy practices in veterinary radiotherapy. The objective of this study was to document the breadth of perspectives, techniques, and applications of stereotactic radiotherapy in veterinary medicine. We conducted an online survey of American College of Veterinary Radiology members specializing in radiation oncology to assess how, when, and why stereotactic radiotherapy is being used. Both stereotactic radiotherapy users and nonusers completed the survey. The overall response and survey completion rates were 54% (67/123) and 87% (58/67), respectively. Overall, 55% of respondents reported providing stereotactic radiotherapy at their facility, with a median of 4.5 canine cases and one feline case per month. Delivery methods included C-arm linear accelerator with multi-leaf collimator, helical tomotherapy, and CyberKnife. Nonpituitary intracranial tumors, pituitary tumors, and sinonasal tumors were the most common cancers treated using stereotactic radiotherapy in both species. The most common fractionation scheme was three fractions of 10 Gy/fraction. The results of this survey suggest common availability of stereotactic radiotherapy in veterinary radiation facilities. These results provide valuable information regarding current stereotactic radiotherapy practices in veterinary medicine, and may provide an initial step toward standardizing methods and establishing consensus guidelines., (© 2018 American College of Veterinary Radiology.)

The collimator in volumetric modulated arc therapy (VMAT) planning is rotated to minimize tongue-and-groove effect and interleaf leakage. The aim of this study was to evaluate the effect of collimator angle on the dosimetric results of VMAT plan for patients with lung cancer undergoing stereotactic body radiation therapy (SBRT) treatment. In the present investigation discrepancies between the calculated dose distributions with different collimators rotations have been studied. Six different collimators rotations (0, 10, 20, 30, 45 and 90 degrees), 6 MV x-ray non-flattened from a TrueBeam accelerator equipped with High-Definition 120MLC were used, as well as two planning technique: One full arc and two half arcs. For rotation between 10 and 45 degrees there were not found a significant variation meanwhile collimator rotation of 0 and 90° may impact on dose distribution resulting in unexpected dose variation. The homogeneity, conformity and gradient indexes as well as dose in organs at risk reached their best values with the half arcs technique and collimator angle between 20° and 45°., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This work reports the experimental development of an integral Gd-infused dosimeter suitable for Gd dose enhancement assessment along with Monte Carlo simulations applied to determine the dose enhancement by radioactive and X-ray sources of interest in conventional and electronic brachytherapy. In this context, capability to elaborate a stable and reliable Gd-infused dosimeter was the first goal aimed at direct and accurate measurements of dose enhancement due to Gd presence. Dose-response was characterized for standard and Gd-infused PAGAT polymer gel dosimeters by means of optical transmission/absorbance. The developed Gd-infused PAGAT dosimeters demonstrated to be stable presenting similar dose-response as standard PAGAT within a linear trend up to 13 Gy along with good post-irradiation readout stability verified at 24 and 48 h. Additionally, dose enhancement was evaluated for Gd-infused PAGAT dosimeters by means of Monte Carlo (PENELOPE) simulations considering scenarios for isotopic and X-ray generator sources. The obtained results demonstrated the feasibility of obtaining a maximum enhancement around of (14 ± 1)% for 192 Ir source and an average enhancement of (70 ± 13)% for 241 Am. However, dose enhancement up to (267 ± 18)% may be achieved if suitable filtering is added to the 241 Am source. On the other hand, optimized X-ray spectra may attain dose enhancements up to (253 ± 22) %, which constitutes a promising future alternative for replacing radioactive sources by implementing electronic brachytherapy achieving high dose levels., (Copyright © 2018. Published by Elsevier Ltd.)

Background and Objective: Tracking mobile tumor regions during the treatment is a crucial part of image-guided radiation therapy because of two main reasons which negatively affect the treatment process: (1) a tiny error will lead to some healthy tissues being irradiated; and (2) some cancerous cells may survive if the beam is not accurately positioned as it may not cover the entire cancerous region. However, tracking or delineation of such a tumor region from magnetic resonance imaging (MRI) is challenging due to photometric similarities of the region of interest and surrounding area as well as the influence of motion in the organs. The purpose of this work is to develop an approach to track the center and boundary of tumor region by auto-contouring the region of interest in moving organs for radiotherapy., Methods: We utilize a nonrigid registration method as well as a publicly available RealTITracker algorithm for MRI to delineate and track tumor regions from a sequence of MRI images. The location and shape of the tumor region in the MRI image sequence varies over time due to breathing. We investigate two approaches: the first one uses manual segmentation of the first frame during the pretreatment stage; and the second one utilizes manual segmentation of all the frames during the pretreatment stage., Results: We evaluated the proposed approaches over a sequence of 600 images acquired from 6 patients. The method that utilizes all the frames in the pretreatment stage with moving mesh based registration yielded the best performance with an average Dice Score of 0.89 ± 0.04 and Hausdorff Distance of 3.38 ± 0.10 mm., Conclusions: This study demonstrates a promising boundary tracking tool for delineating the tumor region that can deal with respiratory movement and the constraints of adaptive radiation therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The correlation between the absorbed energy and the induced biological damage still has unclear aspects, especially in the low energy and low dose rate irradiation regimes. From the knowledge of the molecular-induced effects (dissociations), it would be possible to better understand the side effects of radiation, such as induced cancers or damage to healthy tissue. With this in view, this paper presents results of a simulation of a 125 I-seed treatment with an event-by-event MC code (LEPTS) specifically designed to account for the low energy secondary particle interactions, such as electron attachment, vibro-rotational and neutral dissociation interactions. This calculation allowed us to analyze the potential radiation damage not only in connection with the energy deposition, but also in terms of induced molecular dissociations by taking into account ionizing and non-ionizing dissociative processes. We propose that this description of the molecular level damage be the basis for nanodosimetric evaluations., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This paper presents the feasibility study of a novel 3D mesa bridge microdosimeter and its use for BNCT dosimetry. The performance of the microdosimeter was studied using Monte Carlo simulation. The clinical BNCT field at Kyoto University Reactor (KUR) using both thermal and epithermal irradiation modes were used in this study. Results show that this microdosimeter can be utilised as an effective tool to measure microdosimetric spectrum in the BNCT field and experimental validation will follow once KUR is operational., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Fuel configurations for a subcritical neutron multiplier, which was embedded in a beam-shaping assembly and irradiated by electrons from a linear accelerator, were examined to maximize the production of the epithermal neutron flux for boron neutron capture therapy. The epithermal neutron flux at the treatment position increased as the area per uranium fuel plate increased and was estimated to be 2 × 10 9 cm -2 s -1 when the subcritical neutron multiplier was irradiated by a 4.4 kW (0.22 mA) beam of 20 MeV electrons., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

CT scans are an integral component of modern radiotherapy treatments, enabling the accurate localisation of the treatment target and organs-at-risk, and providing the tissue density information required for the calculation of dose in the treatment planning system. For these reasons, it is important to ensure exposures are optimised to give the required clinical image quality with doses that are as low as reasonably achievable. However, there is little guidance in the literature on dose levels in radiotherapy CT imaging either within the UK or internationally. This IPEM topical report presents the results of the first UK wide survey of dose indices in radiotherapy CT planning scans. Patient dose indices were collected for prostate, gynaecological, breast, lung 3D, lung 4D, brain and head and neck scans. Median values per scanner and examination type were calculated and national dose reference levels and 'achievable levels' of CT dose index (CTDI vol ), dose-length-product (DLP) and scan length are proposed based on the third quartile and median values of these distributions, respectively. A total of 68 radiotherapy CT scanners were included in this audit. The proposed dose reference levels for CTDI vol and DLP are; prostate 16 mGy and 570 mGy · cm, gynaecological 16 mGy and 610 mGy · cm, breast 10 mGy and 390 mGy · cm, lung 3D 14 mGy and 550 mGy · cm, lung 4D 63 mGy and 1750 mGy · cm, brain 50 mGy and 1500 mGy · cm and head and neck 49 mGy and 2150 mGy · cm. Significant variations in dose indices were noted, with head and neck and lung 4D yielding a factor of eighteen difference between the lowest and highest dose scanners. There was also evidence of some clustering in the data by scanner manufacturer, which may be indicative of a lack of local optimisation of individual systems to the clinical task. It is anticipated that providing this data to the UK and wider radiotherapy community will aid the optimisation of treatment planning CT scan protocols.

A shielding disk is used for IOERT procedures to absorb radiation behind the target and protect underlying healthy tissues. Setup variation of shielding disk can affect the corresponding in-vivo dose distribution. In this study, the changes of dosimetric parameters due to the disk setup variations is evaluated using EGSnrc Monte Carlo (MC) code. The results can help treatment team to decide about the level of accuracy in the setup procedure and delivered dose to the target volume during IOERT., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Intra-fraction motion represents a crucial issue in the era of precise radiotherapy in several settings, including breast irradiation. To date, only few data exist on real-time measured intra-fraction motion in breast cancer patients. Continuous surface imaging using visible light offers the capability to monitor patient movements in three-dimensional space without any additional radiation exposure. The aim of the present study was to quantify the uncertainties of possible intra-fractional motion during breast radiotherapy., Material and Methods: One hundred and four consecutive patients that underwent postoperative radiotherapy following breast conserving surgery or mastectomy were prospectively evaluated during 2028 treatment sessions. During each treatment session the patients' motion was continuously measured using the Catalyst™ optical surface scanner (C-RAD AB, Sweden) and compared to a reference scan acquired at the beginning of each session. The Catalyst system works through an optical surface imaging with light emitting diode (LED) light and reprojection captured by a charge coupled device (CCD) camera, which provide target position control during treatment delivery with a motion detection accuracy of 0.5 mm. For 3D surface reconstruction, the system uses a non-rigid body algorithm to calculate the distance between the surface and the isocentre and using the principle of optical triangulation. Three-dimensional deviations and relative position differences during the whole treatment fraction were calculated by the system and analyzed statistically., Results: Overall, the maximum magnitude of the deviation vector showed a mean change of 1.93 mm ± 1.14 mm (standard deviation [SD]) (95%-confidence interval: [0.48-4.65] mm) and a median change of 1.63 mm during dose application (beam-on time only). Along the lateral and longitudinal axis changes were quite similar (0.18 mm ± 1.06 mm vs. 0.17 mm ± 1.32 mm), on the vertical axis the mean change was 0.68 mm ± 1.53 mm. The mean treatment session time was 154 ± 53 (SD) seconds and the mean beam-on time only was 55 ± 16 s. According to Friedman's test differences in the distributions of the three possible directions (lateral, longitudinal and vertical) were significant (p < 0.01), in post-hoc analysis there were no similarities between any two of the three directions., Conclusion: The optical surface imaging system is an accurate and easy tool for real-time motion management in breast cancer radiotherapy. Intra-fraction motion was reported within five millimeters in all directions. Thus, intra-fraction motion in our series of 2028 treatment sessions seems to be of minor clinical relevance in postoperative radiotherapy of breast cancer.