Patient Dose Distributions Research Articles

Commissioning of GPU–Accelerated Monte Carlo Code FRED for Clinical Applications in Proton Therapy

We present commissioning and validation of Fred, a graphical processing unit (GPU)–accelerated Monte Carlo code, for two proton beam therapy facilities of different beam line design: CCB (Krakow, IBA) and EMORY (Atlanta, Varian). We followed clinical acceptance tests required to approve the certified treatment planning system for clinical use. We implemented an automated and efficient procedure to build a parameter library characterizing the clinical proton pencil beam. Beam energy, energy spread, lateral propagation model, and a dosimetric calibration factor were parametrized based on measurements performed during the facility start-up. The Fred beam model was validated against commissioning and supplementary measurements performed with and without range shifter. We obtained 1) submillimeter agreement of Bragg peak shapes in water and lateral beam profiles in air and slab phantoms, 2) <2% dose agreement for spread out Bragg peaks of different ranges, 3) average gamma index (2%/2 mm) passing rate of >95% for >1000 patient verification measurements using a two-dimensional array of ionization chambers, and 4) gamma index passing rate of >99% for three-dimensional dose distributions computed with Fred and measured with an array of ionization chambers behind an anthropomorphic phantom. The results of example treatment planning study on >100 patients demonstrated that Fred simulations in computed tomography enable an accurate prediction of dose distribution in patient and application of Fred as second patient quality assurance tool. Computation of a patient treatment in a CT using 104 protons per pencil beam took on average 2′30 min with a tracking rate of 2.9×105p+/s. Fred was successfully commissioned and validated against the clinical beam model, showing that it could potentially be used in clinical routine. Thanks to high computational performance due to GPU acceleration and an automated beam model implementation method, the application of Fred is now possible for research or quality assurance purposes in most of the proton facilities.

Implementation of a Compact Spot-Scanning Proton Therapy System in a GPU Monte Carlo Code to Support Clinical Routine

The purpose of this work was to implement a fast Monte Carlo dose calculation tool, Fred, in the Maastro proton therapy center in Maastricht (Netherlands) to complement the clinical treatment planning system. Fred achieves high accuracy and computation speed by using physics models optimized for radiotherapy and extensive use of GPU technology for parallelization. We implemented the beam model of the Mevion S250i proton beam and validated it against data measured during commissioning and calculated with the clinical TPS. The beam exits the accelerator with a pristine energy of around 230 MeV and then travels through the dynamically extendable nozzle of the device. The nozzle contains the range modulation system and the multi-leaf collimator system named adaptive aperture. The latter trims the spots laterally over the 20 × 20 cm2 area at the isocenter plane. We use a single model to parameterize the longitudinal (energy and energy spread) and transverse (beam shape) phase space of the non-degraded beam in the default nozzle position. The range modulation plates and the adaptive aperture are simulated explicitly and moved in and out of the simulation geometry dynamically by Fred. Patient dose distributions recalculated with Fred were comparable with the TPS and met the clinical criteria. Calculation time was on the order of 10–15 min for typical patient cases, and future optimization of the simulation statistics is likely to improve this further. Already now, Fred is fast enough to be used as a tool for plan verification based on machine log files and daily (on-the-fly) dose recalculations in our facility.

Development of generalized time-dependent TCP model and the investigation of the effect of repopulation and weekend breaks in fractionated external beam therapy

We developed a tumor control probability (TCP) model that incorporates variable time intervals between fractions and a kick-off time (Tk) for radiation-induced accelerated tumor proliferation. The resulting Lee-Rosen model, TCPLR, was used to compute TCPs for treatment courses with and without weekend treatment for tumors with different proliferation rates – slow (prostate), moderate (breast), and rapid (head and neck). TCPs were computed using ideal uniform dose distributions and actual patient plans. The doses for the uniform plans were the mean doses for the prostate and breast cases and the minimum tumor dose for the head and neck case. The TCPLR model predictions agreed with expectations that TCP increases with increasing Tk in all cases. For standard fractionation, as Tk increased from 0 to 4 weeks, TCP increased for the patient distributions by 74.7% for the head and neck cancer, by 6.2% for the breast cancer, and by 2.4% for the prostate cancers. For the uniform dose distributions, the increases were 79.2%, 5.7%, and 2.3%, respectively. TCP increased as the number of weekend breaks decreased. The effect of weekend breaks decreased as the tumor proliferation rate decreased. For the head and neck tumor, notable decreases in TCP of 6.0% (uniform dose distribution) and 6.8% (actual plan dose distribution) were observed with Friday starts compared to Monday starts for the standard 5 fx/wk schedule (Tk = 4 wk). The 7 fx/wk schedule produced increases in TCP of 17.0% and 20.5% for the uniform and patient dose distributions, respectively, compared to the standard schedule. For the breast cancer, starting the 5 fx/wk schedule on Friday decreased the TCP by 0.2% (Tk = 4 wk) compared to a Monday start. The 7 fx/wk schedule produced increases of 0.3% and 0.4% in TCP compared to the standard schedule for the uniform and patient dose distributions, respectively (Tk = 4 wk). For the prostate cancer, the change in TCP for 5 fx/wk schedules starting on different days was 0.1%. The 7 fx/wk schedule increased TCP by 0.8% compared to the standard schedule (Tk = 4 wk). TCP values for the uniform dose distributions for the standard schedule (Tk = 4 wk) agreed with the TCP values for the actual dose distributions within 4.5% for the head and neck tumor and within 0.2% for the breast and prostate tumors. This good agreement suggests that the doses chosen for the uniform dose distributions were good approximations to the clinical doses. The results for head and neck tumors support, in part, the current practice of hyperfractionated/accelerated radiotherapy. They also suggest that shortening the overall treatment time for conventional fractions by eliminating weekend breaks might be beneficial. The predicted effect on TCP of the various schedules studied was insignificant for prostate and breast tumors, suggesting that a weekend treatment might not be necessary for patients starting radiotherapy on a Friday. There is significant uncertainty in the values of the model parameters chosen for these calculations, and no consideration was given to the potential effects of these various schedules on normal tissues.

Dose quantification in carbon ion therapy using in-beam positron emission tomography

This work presents an iterative method for the estimation of the absolute dose distribution in patients undergoing carbon ion therapy, via analysis of the distribution of positron annihilations resulting from the decay of positron-emitting fragments created in the target volume. The proposed method relies on the decomposition of the total positron-annihilation distributions into profiles of the three principal positron-emitting fragment species - 11C, 10C and 15O. A library of basis functions is constructed by simulating a range of monoenergetic 12C ion irradiations of a homogeneous polymethyl methacrylate phantom and measuring the resulting one-dimensional positron-emitting fragment profiles and dose distributions. To estimate the dose delivered during an arbitrary polyenergetic irradiation, a linear combination of factors from the fragment profile library is iteratively fitted to the decomposed positron annihilation profile acquired during the irradiation, and the resulting weights combined with the corresponding monoenergetic dose profiles to estimate the total dose distribution. A total variation regularisation term is incorporated into the fitting process to suppress high-frequency noise. The method was evaluated with 14 different polyenergetic 12C dose profiles in a polymethyl methacrylate target: one which produces a flat biological dose, 10 with randomised energy weighting factors, and three with distinct dose maxima or minima within the spread-out Bragg peak region. The proposed method is able to calculate the dose profile with mean relative errors of 0.8%, 1.0% and 1.6% from the 11C, 10C, 15O fragment profiles, respectively, and estimate the position of the distal edge of the SOBP to within an average of 0.7 mm, 1.9 mm and 1.2 mm of its true location.

17P Comparison of dose distribution in the postoperative breast cancer patients irradiated with the technique of deep inspiratory breath hold and dynamic techniques

17P Comparison of dose distribution in the postoperative breast cancer patients irradiated with the technique of deep inspiratory breath hold and dynamic techniques

Monte Carlo simulation of the effect of magnetic fields on brachytherapy dose distributions in lung tissue material.

The aim of this work was to use TOPAS Monte Carlo simulations to model the effect of magnetic fields on dose distributions in brachytherapy lung treatments, under ideal and clinical conditions. Idealistic studies were modeled consisting of either a monoenergetic electron source of 432 keV, or a polyenergetic electron source using the spectrum of secondary electrons produced by 192Ir gamma-ray irradiation. The electron source was positioned in the center of a homogeneous, lung tissue phantom (ρ = 0.26 g/cm3). Conversely, the clinical study was simulated using the VariSource VS2000 192Ir source in a patient with a lung tumor. Three contoured volumes were considered: the tumor, the planning tumor volume (PTV), and the lung. In all studies, dose distributions were calculated in the presence or absence of a constant magnetic field of 3T. Also, TG-43 parameters were calculated for the VariSource and compared with published data from EGS-brachy (EGSnrc) and PENELOPE. The magnetic field affected the dose distributions in the idealistic studies. For the monoenergetic and poly-energetic studies, the radial distance of the 10% iso-dose line was reduced in the presence of the magnetic field by 64.9% and 24.6%, respectively. For the clinical study, the magnetic field caused differences of 10% on average in the patient dose distributions. Nevertheless, differences in dose-volume histograms were below 2%. Finally, for TG-43 parameters, the dose-rate constant from TOPAS differed by 0.09% ± 0.33% and 0.18% ± 0.33% with respect to EGS-brachy and PENELOPE, respectively. The geometry and anisotropy functions differed within 1.2% ± 1.1%, and within 0.0% ± 0.3%, respectively. The Lorentz forces inside a 3T magnetic resonance machine during 192Ir brachytherapy treatment of the lung are not large enough to affect the tumor dose distributions significantly, as expected. Nevertheless, large local differences were found in the lung tissue. Applications of this effect are therefore limited by the fact that meaningful differences appeared only in regions containing air, which is not abundant inside the human.

Analysis of cardiac substructure dose in a large, multi-centre danish breast cancer cohort (the DBCG HYPO trial): Trends and predictive modelling

Background and purposeRadiotherapy for breast cancer can increase the risks of heart disease. Patient-specific risk assessment may be improved with the inclusion of doses to cardiac substructures. The purpose of this work was to use automatic segmentation to evaluate substructure doses and develop predictive models for these based on the dose to the whole heart. Material and methodsAutomatic segmentation was used to delineate cardiac substructures in a Danish breast cancer trial (DBCG HYPO) dataset comprising over 1500 Danish women treated between 2009 and 2014. Trends in contouring practices and cardiac doses over time were investigated, and models to predict substructure doses from whole heart dose parameters were fit to the data. ResultsManual contouring consistency improved over the study period when compared with automatic segmentation; systematic differences between automatically and manually defined heart volume decreased from 106 cm3 to 12.0 cm3. Doses to the heart and cardiac substructures also decreased. Mean whole heart doses for left-sided treatments in 2009 and 2014 were 1.94±1.19 Gy and 1.29±0.69 Gy (average ± SD), respectively. Prediction of mean substructure doses is accurate, with R2 scores in the range 0.45–0.95 (average 0.77), depending on the particular structure. ConclusionThis study reports heart and cardiac substructure doses in a large breast cancer cohort. Predictive models generated in this work can be used to estimate mean cardiac substructure doses for datasets where patient imaging and dose distributions are not available, provided the tangential field techniques are consistent with those used in the trial.

A Retrospective Analysis of Dose Distribution and Toxicity in Patients with Left Breast Cancer Treated with Adjuvant Intensity-Modulated Radiotherapy: Comparison with Three-Dimensional Conformal Radiotherapy.

BackgroundA better understanding of the organs-at-risk (OAR) dose metrics and the related toxicity induced by radiotherapy (RT) for left breast cancer (BC) will improve the quality of life. This study addressed the issue for left-BC patients treated with intensity-modulated radiotherapy (IMRT) compared to three-dimensional conformal radiotherapy (3D-CRT).Patients and MethodsBetween 2012 and 2018, 308 left-BC patients underwent adjuvant RT at our hospital. Before June 2015, 134 patients were treated with 3D-CRT. Thereafter, 174 patients underwent IMRT. The patient’s characteristics in the IMRT group did not significantly different compared to those in the 3D-CRT group.ResultsAmong the total study population, the incidence of ≥grade 2 radiation dermatitis (RID) was 17.3%. Higher volumes receiving 105% (≥5.7%) and 107% (≥1%) of prescribed dose and 3D-CRT technique were associated with a higher risk of RID. Regarding lung toxicity, the mean lung dose (≥10.2Gy) and V20 (≥20%) of ipsilateral lung were significantly associated with the incidence of RT-induced pulmonary changes. By dosimetry analysis, IMRT achieved better dose conformity and delivered lower mean doses to heart and ipsilateral lung compared to 3D-CRT. Furthermore, propensity sore and multivariate analysis showed that IMRT technique helped to reduce RT-induced dermatitis and lung toxicity.ConclusionOur data suggest that the volume of OAR exposed to higher doses is a predictor of RT-induced toxicity. Adjuvant RT with IMRT technique offered better dose conformity and spared high-dose levels to OARs to reduce radiation-related morbidity for BC patients.

Quantification of internal dosimetry in PET patients: individualized Monte Carlo vs generic phantom-based calculations.

PurposeThe purpose of this work is to calculate individualized dose distributions in patients undergoing 18F‐FDG PET/CT studies through a methodology based on full Monte Carlo (MC) simulations and PET/CT patient images, and to compare such values with those obtained by employing nonindividualized phantom‐based methods.MethodsWe developed a MC‐based methodology for individualized internal dose calculations, which relies on CT images (for organ segmentation and dose deposition), PET images (for organ segmentation and distributions of activities), and a biokinetic model (which works with information provided by PET and CT images) to obtain cumulated activities. The software vGATE version 8.1. was employed to carry out the Monte Carlo calculations. We also calculated deposited doses with nonindividualized phantom‐based methods (Cristy–Eckerman, Stabin, and ICRP‐133).ResultsMedian MC‐calculated dose/activity values are within 0.01–0.03 mGy/MBq for most organs, with higher doses delivered especially to the bladder wall, major vessels, and brain (medians of 0.058, 0.060, 0.066 mGy/MBq, respectively). Comparison with values obtained with nonindividualized phantom‐based methods has shown important differences in many cases (ranging from −80% to + 260%). These differences are significant (p < 0.05) for several organs/tissues, namely, remaining tissues, adrenals, bladder wall, bones, upper large intestine, heart, pancreas, skin, and stomach wall.ConclusionsThe methodology presented in this work is a viable and useful method to calculate internal dose distributions in patients undergoing medical procedures involving radiopharmaceuticals, individually, with higher accuracy than phantom‐based methods, fulfilling the guidelines provided by the European Council directive 2013/59/Euratom.

Dose prediction using a deep neural network for accelerated planning of rectal cancer radiotherapy

PurposeTo apply a deep neural network to predict dose distributions of rectal cancer patients for accelerated volume modulated arc technique (VMAT) planning. Materials and methodsComputed tomography scans and approved VMAT plans together with Doseapproved of 187 patients treated from February 2018 to April 2019 were randomly selected for this retrospective study. The deep neural network DeepLabv3+ was applied for dose distribution prediction. A prior dose information-aided planning scheme was introduced. Prediction precision was evaluated by mean square error (MSE), normalized dose difference (δD), and dose–volume histogram (DVH) indices using a paired t test. Information-aided and experienced replanning were performed by 1-year and 6-year experienced dosimetrists, respectively. Replanning time and DVH indices were evaluated by two-way variance analysis. ResultsThe DeepLabv3+ prediction results (DoseDeepLabv3+) were all clinically acceptable. Taking Doseapproved as the baseline, the MSE was 0.001 and mean δD was 0.40% with an inter-quartile range of 0.079%–0.30% for DoseDeepLabv3+. No significant differences were found for the planning target volume quantitative parameters between Doseapproved and DoseDeepLabv3+, except for the conformality index. For the two-way variance analysis, a significantly different replanning time was found between the information-aided and experienced replanning with maximum time-saving of 15.76 min. Information-aided replans had the advantage of lower maximum dose, higher minimum dose, and lower homogeneity index, and the disadvantage of lower conformality index and higher machine unites with significant differences. ConclusionDeepLabv3+ successfully predicted rectal cancer dose distribution, and the predicted prior information helped save planning times for multi-level experienced dosimetrists.

Impact of interfractional anatomical variation and setup correction methods on interfractional dose variation in IMPT and VMAT plans for pancreatic cancer patients: A planning study.

PurposeTo investigate the impact of interfractional anatomical changes and setup correction methods on dose distributions in pancreatic cancer patients under breath‐hold conditions.MethodsThree intensity‐modulated proton therapy (IMPT) plans with different beam arrangements and one volumetric‐modulated arc therapy (VMAT) plan prescribing 54 Gy in 30 fractions were created for 10 patients who underwent three additional CT scans performed at an interval of 1–2 weeks. The additional CT sets were rigidly registered to the simulation CT set using both bone‐matching (BM) and organ‐matching (OM) methods in each patient. Recalculated dose distributions and dose–volume indices on the additional CT sets using either the BM or the OM method were compared with the simulation values.ResultsDifferences in the gross tumor volume D98% value from the simulation sets ranged from −0.8 to −5.9% on average. In addition, the variations were larger with OM compared with BM for two IMPT plans. Meanwhile, differences in the D98% value in the region isotropically enlarged by 5 mm from the gross tumor volume were significantly improved with OM on two IMPT plans and the VMAT plan. Among the organs at risk, the dose–volume indices were significantly improved with OM only in the duodenum on all plans.ConclusionOrgan‐matching may be a better setup correction technique than BM for both photon therapy and IMPT plans. However, in some beam arrangements of IMPT, the dose distribution may be somewhat worse using OM, due to interfractional anatomical variation. Therefore, it is important to choose beam angles that are less likely to be influenced by changes in the gastrointestinal gas volume, especially in IMPT plans.

Associations between voxel-level accumulated dose and rectal toxicity in prostate radiotherapy.

Associations between dose and rectal toxicity in prostate radiotherapy are generally poorly understood. Evaluating spatial dose distributions to the rectal wall (RW) may lead to improvements in dose-toxicity modelling by incorporating geometric information, masked by dose-volume histograms. Furthermore, predictive power may be strengthened by incorporating the effects of interfraction motion into delivered dose calculations.Here we interrogate 3D dose distributions for patients with and without toxicity to identify rectal subregions at risk (SRR), and compare the discriminatory ability of planned and delivered dose. Daily delivered dose to the rectum was calculated using image guidance scans, and accumulated at the voxel level using biomechanical finite element modelling. SRRs were statistically determined for rectal bleeding, proctitis, faecal incontinence and stool frequency from a training set (n=139), and tested on a validation set (n=47). SRR patterns differed per endpoint. Analysing dose to SRRs improved discriminative ability with respect to the full RW for three of four endpoints. Training set AUC and OR analysis produced stronger toxicity associations from accumulated dose than planned dose. For rectal bleeding in particular, accumulated dose to the SRR (AUC 0.76) improved upon dose-toxicity associations derived from planned dose to the RW (AUC 0.63). However, validation results could not be considered significant. Voxel-level analysis of dose to the RW revealed SRRs associated with rectal toxicity, suggesting non-homogeneous intra-organ radiosensitivity. Incorporating spatial features of accumulated delivered dose improved dose-toxicity associations. This may be an important tool for adaptive radiotherapy in the future.

Evaluation of the effect of mechanical deformation on beam isocenter properties of the SC200 scanning beam delivery system

For proton pencil beam scanning (PBS) technology, the accuracy of the dose distribution in a patient is sensitive to the properties of the incident beam. However, mechanical deformation of the proton therapy facility may occur, and this could be an important factor affecting the proton dose distribution in patients. In this paper, we investigated the effect of deformation on an SC200 proton facility's beam isocenter properties. First, mechanical deformation of the PBS nozzle, L-shape plate, and gantry were simulated using a Finite Element code, ANSYS. Then, the impact of the mechanical deformation on the beam's isocenter properties was evaluated using empirical formulas. In addition, we considered the simplest case that could affect the properties of the incident beam (i.e. if only the bending magnet (BG3) has an error in its mounting alignment), and the effect of the beam optics offset on the isocenter characteristics was evaluated. The results showed that the deformation of the beam position in the X and Y direction was less than 0.27 mm, which meets the structural design requirements. Compared to the mechanical deformation of the L-shape plate, the deformation of the gantry had more influence on the beam's isocenter properties. When the error in the mounting alignment of the BG3 is equal to or more than 0.3 mm, the beam deformation at the isocenter exceeds the maximum accepted deformation limits. Generally speaking, for the current design of the SC200 scanning beam delivery system, the effects of mechanical deformation meet the maximum accepted beam deformation limits. In order to further study the effect of the incident beam optics on the isocenter properties, a fine-scale Monte Carlo model including factors relating to the PBS nozzle and the BG3 should be developed in future research.

Neurointerventionalist and Patient Radiation Doses in Endovascular Treatment of Acute Ischemic Stroke.

To evaluate the patient and the neurointerventionalist radiation dose levels during endovascular treatment of acute ischemic stroke, and to analyze factors affecting doses. From October 2017 to January 2019, we prospectively collected patient radiation data and neurointerventionalist data from real-time dosimetry from all consecutive thrombectomies. Multivariate analysis was performed to analyze patient total dose area product (DAP) and neurointerventionalist dose variability in terms of clinical characteristics and the technical parameters of thrombectomies. Local dose reference levels (RL) were derived as the 75th percentile of the patient dose distributions. A total of 179 patients were treated during the study period and included in this study. Local dose RL for thrombectomy was derived for total DAP to 34Gycm2, cumulative air kerma of 242mGy and fluoroscopy time of 12min. The mean neurointerventionalist dose for thrombectomy was 7.7 ± 7.4µSv. Height (P = 0.018), weight (P = 0.004), body mass index (P = 0.015), puncture to recanalisation (P < 0.001), fluoro time (P < 0.001), number of passes (P < 0.001), thrombolysis in cerebral infarction 2b/3 recanalisation (P = 0.034) and aspiration thrombectomy (P < 0.001) were independent factors affecting patient total DAP, whereas baseline National Institutes of Health Stroke Scale (P = 0.043), puncture to recanalisation (P = 0.003), fluoroscopy time (P = 0.009) and number of passes (P = 0.009) were factors affecting the neurointerventionalist dose. New reference patient doses lower than those in previously published studies were defined. However, the operator's doses were higher than those in the only available study reporting on operator's dose during cerebral interventions.

Impact of Intra-Fractional Motion on Dose Distributions in Lung IMRT.

To investigate the impact of intra-fractional motion on dose distribution in patients treated with intensity-modulated radiation therapy (IMRT) for lung cancer. Twenty patients who had undergone IMRT for non-small cell lung cancer were selected for this retrospective study. For each patient, a four-dimensional computed tomography (CT) image set was acquired and clinical treatment plans were developed using the average CT. Dose distributions were then re-calculated for each of the 10 phases of respiratory cycle and combined using deformable image registration to produce cumulative dose distributions that were compared with the clinical treatment plans. Intra-fractional motion reduced planning target volume (PTV) coverage in all patients. The median reduction of PTV volume covered by the prescription isodose was 3.4%; D98 was reduced by 3.1 Gy. Changes in the mean lung dose were within ±0.7 Gy. V20 for the lung increased in most patients; the median increase was 1.6%. The dose to the spinal cord was unaffected by intra-fractional motion. The dose to the heart was slightly reduced in most patients. The median reduction in the mean heart dose was 0.22 Gy, and V30 was reduced by 2.5%.The maximum dose to the esophagus was also reduced in most patients, by 0.74 Gy, whereas V50 did not change significantly. The median number of points in which dose differences exceeded 3%/3 mm was 6.2%. Intra-fractional anatomical changes reduce PTV coverage compared to the coverage predicted by clinical treatment planning systems that use the average CT for dose calculation. Doses to organs at risk were mostly over-predicted.

Nuclear halo measurements for accurate prediction of field size factor in a Varian ProBeam proton PBS system.

PurposeFor pencil‐beam scanning proton therapy systems, in‐air non‐Gaussian halo can significantly impact output at small field sizes and low energies. Since the low‐intensity tail of spot profile (halo) is not necessarily modeled in treatment planning systems (TPSs), this can potentially lead to significant differences in patient dose distribution. In this work, we report such impact for a Varian ProBeam system.MethodsWe use a pair magnification technique to measure two‐dimensional (2D) spot profiles of protons from 70 to 242 MeV at the treatment isocenter and 30 cm upstream of the isocenter. Measurements are made with both Gafchromic film and a scintillator detector coupled to a CCD camera (IBA Lynx). Spot profiles are measured down to 0.01% of their maximum intensity. Field size factors (FSFs) are compared among calculation using measured 2D profiles, calculation using a clinical treatment planning algorithm (Raystation 8A clinical Monte Carlo), and a CC04 small‐volume ion chamber. FSFs were measured for square fields of proton energies ranging from 70 to 242 MeV.ResultsAll film and Lynx measurements agree within 1 mm for full width at half maximum beam intensity. The measured radial spot profiles disagree with simple Gaussian approximations, which are used for modeling in the TPS. FSF measurements show the magnitude of disagreements between beam output in reality and in the TPS without modeling halo. We found that the clinical TPS overestimated output by as much as 6% for small field sizes of 2 cm at the lowest energy of 70 MeV while the film and Lynx measurements agreed within 4% and 1%, respectively, for this FSF.ConclusionsIf the in‐air halo for low‐energy proton beams is not fully modeled by the TPS, this could potentially lead to under‐dosing small, shallow treatment volumes in PBS treatment plans.

MLC parameters from static fields to VMAT plans: an evaluation in a RT-dedicated MC environment (PRIMO)

BackgroundPRIMO is a graphical environment based on PENELOPE Monte Carlo (MC) simulation of radiotherapy beams able to compute dose distribution in patients, from plans with different techniques. The dosimetric characteristics of an HD-120 MLC (Varian), simulated using PRIMO, were here compared with measurements, and also with Acuros calculations (in the Eclipse treatment planning system, Varian).Materials and methodsA 10 MV FFF beam from a Varian EDGE linac equipped with the HD-120 MLC was used for this work. Initially, the linac head was simulated inside PRIMO, and validated against measurements in a water phantom. Then, a series of different MLC patterns were established to assess the MLC dosimetric characteristics. Those tests included: i) static fields: output factors from MLC shaped fields (2 × 2 to 10 × 10 cm2), alternate open and closed leaf pattern, MLC transmitted dose; ii) dynamic fields: dosimetric leaf gap (DLG) evaluated with sweeping gaps, tongue and groove (TG) effect assessed with profiles across alternate open and closed leaves moving across the field. The doses in the different tests were simulated in PRIMO and then compared with EBT3 film measurements in solid water phantom, as well as with Acuros calculations. Finally, MC in PRIMO and Acuros were compared in some clinical cases, summarizing the clinical complexity in view of a possible use of PRIMO as an independent dose calculation check.ResultsStatic output factor MLC tests showed an agreement between MC calculated and measured OF of 0.5%. The dynamic tests presented DLG values of 0.033 ± 0.003 cm and 0.032 ± 0.006 cm for MC and measurements, respectively. Regarding the TG tests, a general agreement between the dose distributions of 1–2% was achieved, except for the extreme patterns (very small gaps/field sizes and high TG effect) were the agreement was about 4–5%. The analysis of the clinical cases, the Gamma agreement between MC in PRIMO and Acuros dose calculation in Eclipse was of 99.5 ± 0.2% for 3%/2 mm criteria of dose difference/distance to agreement.ConclusionsMC simulations in the PRIMO environment were in agreement with measurements for the HD-120 MLC in a 10 MV FFF beam from a Varian EDGE linac. This result allowed to consistently compare clinical cases, showing the possible use of PRIMO as an independent dose calculation check tool.

The Impact of CBCT Imaging and Setup Accuracy on Spinal Cord Dose in SBRT Treatment

IGRT is an integral aspect of spine SBRT treatment delivery, allowing for accurate patient positioning and high dose to tumor while sparing dose to critical nerves. Meanwhile, intrafraction imaging with kV CBCT introduces additional radiation dose to the peripheral tissues, bone, and spinal cord, which is unaccounted for in treatment planning, with implications particularly for pediatric patients or those at high risk of myelopathy in setting of reirradiation. IGRT to verify our institutional tolerance of 1 mm and 1° between arcs may prolong treatment time and introduce further setup uncertainty. To optimize the imaging workflow (prioritizing KV-2D-3D vs KV-CBCT if sufficient) for achieving practical set up accuracy while limiting the imaging dose received, the cumulative CBCT imaging dose to the spinal cord and the dose perturbation induced by patient setup error were investigated. CBCT imaging dose to spinal cord was derived by correlating our institutional CTDI QA assessment on 4 linear accelerators and 3 C-Series LINACs with the reference value provided in the current literature. The clinical pelvis protocol CTDI was measured with the ACR torso phantom with 10cm pencil chamber, 125kVp, 1080mAs on liner accelerators and 125kVp, 80mA, 13ms on C-Series, respectively. Dosimetry change from setup uncertainty was analyzed by shifting the VMAT plan isocenter by 1 mm in Y direction and 1° couch rotation from the original planning isocenter on 5 spine SBRT patients, prescribed a course of 30Gy in 5 fractions. Dose differences were evaluated in terms of the target volume coverage D95, the spinal cord D0.035cc, D0.1cc and Dmax by re-calculating the plan with the same beam geometry, MLC motion, and MUs as the original plans. Differences between measured and vendor specified CTDI was 14% ± 11%SD (n = 7). Correlating the CBCT imaging dose reference based on Rando phantom measurement and Monte Carlo simulation in the literature, imaging dose to the spinal cord in our clinic was estimated as 3 - 4cGy per pelvis protocol CBCT. Dosimetry change with respect to target D95 showed an average deviation of 0.2% prescription dose with 1mm and 1° positioning uncertainty from the planning intents (n = 5). In the worst-case, the spinal cord with 1mm expansion had a max dose (D0.035cc) increase by an average of 132cGy (4.4% Rx) and with a max of 245cGy (8.2% Rx). CBCT dose from multiple scans (conventionally initial, mid and post) contribute to the total dose of the spinal cord. Mid-CBCTs may also prolong the treatment and introduce additional uncertainty. Our current patient positioning accuracy, effectively achieved with use of multiple 2D-3D kV images and minimized CBCT verification scans per fraction, does not produce any significant change in patient dose distributions in the target or spinal cord. Customized CBCT protocols, optical monitoring system (OSMS), or use of MR-LINAC could potentially further reduce imaging dose related to intrafraction monitoring for spine SBRT.

The Value of Troponin T Level Change During Chemoradiation in Esophageal Cancer Patients

Cardiac adverse events are common in esophageal cancer patients who received chemoradiation (CRT). However, reliable marker is lacking to predict these cardiac events. Troponin T (TnT) is a marker of myocardial necrosis, which is widely used in diagnosis of acute coronary syndromes. The relationship between TnT level change during CRT and cardiac injury is unknown. We hypothesized that the TnT level change during CRT is associated with acute cardiac adverse events and long-term survival outcomes. We retrospectively reviewed 113 esophageal cancer patients who received definitive or neoadjuvant CRT from 2010-2016. All patients consented on a prospective blood collection protocol where samples are drawn at baseline before, once during, at the end of CRT, and at each follow up timepoints. Irradiation dose parameters for the whole heart and each chamber were recorded from the treatment plan. TnT levels were quantified using the Elecsys® TnT-high sensitive assay (Roche Diagnostic). TnT level change was defined as CRT end level divided by baseline level. Logistic regression was used to evaluate the correlation between TnT change and acute cardiac adverse events. Kaplan-Meier method was used to compare survival outcomes in different TnT level change groups. The median TnT level gradually increased from baseline, to mid treatment course, and at the end of CRT: 6.27, 8.56, and 10.63 pg/ml, respectively. The median TnT level change was 1.48 (IQR, 1.12-2.01). For the whole heart, left ventricle (LV), right ventricle (RV), and right atrium (RA), the dose distribution was different between IMRT and proton: IMRT mainly contributed to low dose level (<30Gy), while in high dose regions (>40Gy), proton using passive scattering approach had significantly higher dose than IMRT. The TnT level change was strongly correlated to LV and RV dose percentage from V5 to V50 in proton patients (p<0.01), but not in IMRT patients. Male, lower BMI and lower tumor location were associated with higher TnT increase, while TnT level change could not predict acute cardiac adverse events during CRT or postoperative cardiac complications. There was no significant correlation of TnT levels and survival outcomes. There was significant correlation of TnT levels and cardiac dose distribution in proton patients that was not seen in IMRT patients. Whether TnT level alterations with treatment could correlate with late cardiac events specifically in proton patients requires longer term follow up.

Dosimetry needs for MRI-linacs

The pursuit of real-time image-guided radiotherapy has prompted the development of hybrid devices coupling MRI scanners with radiotherapy treatment units, usually linear accelerators (linacs). One of the challenges in MRI-linac technology is the magnetic field impact on the dose deposition. Dose deposition effects have to be considered in the radiation therapy chain as they alter the dose distribution in patients and influence the response of many commonly used radiation detectors. In this presentation specific issues of dosimetry for MRI-linacs will be reviewed and illustrated with examples from the Australian MRI-linac commissioning process.