Extension of matRad with a modified microdosimetric kinetic model for carbon ion treatment planning: Comparison with Monte Carlo calculation.

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 (DRBE ) 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). DRBE 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.

Evaluation of robustness in hybrid intensity-modulated radiation therapy plans generated by commercial software for automated breast planning.

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.

Systematic quantitative evaluation of Plan-IQ for intensity-modulated radiation therapy after modified radical mastectomy.

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.

Analysis of the Dose Drop at the Edge of the Target Area in Heavy Ion Radiotherapy.

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.

Daily waiting and treatment times at an advanced radiation oncology setup: A 4-year audit of consecutive patients from single institution.

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.

Lung Cancer Radiotherapy: Simulation and Analysis Based on a Multicomponent Mathematical Model.

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.

Treatment Volume, Dose Prescription and Delivery Techniques for Dose-intensification in Rectal Cancer: A National Survey.

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.

Comparing two radiotherapy techniques of whole central nervous system tumors, considering tumor and critical organs' dose provided by treatment planning system and direct measurement.

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.

Effect of Surgical Mask on Setup Error in Head and Neck Radiotherapy.

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.

Statistical Analysis of Treatment Planning Parameters for Prediction of Delivery Quality Assurance Failure for Helical Tomotherapy.

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.

A novel and fast methodology to calculate doses in LDR brachytherapy.

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.

Intensity-Modulated Radiation Therapy Optimization for Acceptable and Remaining-One Unacceptable Dose-Volume and Mean-Dose Constraint Planning.

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.

On the three-objective static unconstrained leaf sequencing in IMRT.

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.

Modeling the Impact of Cardiopulmonary Irradiation on Overall Survival in NRG Oncology Trial RTOG 0617.

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.

An IAEA survey of radiotherapy practice including quality assurance extent and depth.

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.

Isotoxic dose prescription level strategies for stereotactic liver radiotherapy: the price of dose uniformity.

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.

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

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

The influence of errors in small field dosimetry on the dosimetric accuracy of treatment plans.

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 cm2) 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.

Development and validation of a novel MR imaging predictor of response to induction chemotherapy in locoregionally advanced nasopharyngeal cancer: a randomized controlled trial substudy (NCT01245959).

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 (pinteraction <  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 (pinteraction = 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.