Joao Seco

Effects of organ motion on IMRT treatments with segments of few monitor units

Interplay between organ (breathing) motion and leaf motion has been shown in the literature to have a small dosimetric impact for clinical conditions (over a 30 fraction treatment). However, previous studies did not consider the case of treatment beams made up of many few-monitor-unit (MU) segments, where the segment delivery time (1-2 s) is of the order of the breathing period (3-5 s). In this study we assess if breathing compromises the radiotherapy treatment with IMRT segments of low number of MUs. We assess (i) how delivered dose varies, from patient to patient, with the number of MU per segment, (ii) if this delivered dose is identical to the average dose calculated without motion over the path of the motion, and (iii) the impact of the daily variation of the delivered dose as a function of MU per segment. The organ motion was studied along two orthogonal directions, representing the left-right and cranial-caudal directions of organ movement for a patient setup in the supine position. Breathing motion was modeled as sin(x), sin4(x), and sin6(x), based on functions used in the literature to represent organ motion. Measurements were performed with an ionization chamber and films. For a systematic study of motion effects, a MATLAB simulation was written to model organ movement and dose delivery. In the case of a single beam made up of one single segment, the dose delivered to point in a moving target over 30 fractions can vary up to 20% and 10% for segments of 10 MU and 20 MU, respectively. This dose error occurs because the tumor spends most of the time near the edges of the radiation beam. In the case of a single beam made of multiple segments with low MU, we observed 2.4%, 3.3%, and 4.3% differences, respectively, for sin(x), sin4(x), and sin6(x) motion, between delivered dose and motion-averaged dose for points in the penumbra region of the beam and over 30 fractions. In approximately 5-10% of the cases, differences between the motion-averaged dose and the delivered 30-fraction dose could reach 6%, 8% and 10-12%, respectively for sin(x), sin4(x), and sin6(x) motion. To analyze a clinical IMRT beam, two patient plans were randomly selected. For one of the patients, the beams showed a likelihood of up to 25.6% that the delivered dose would deviate from the motion-averaged dose by more than 1%. For the second patient, there was a likelihood of up to 62.8% of delivering a dose that differs by more than 1% from the motion-averaged dose and a likelihood of up to approximately 30% for a 2% dose error. For the entire five-beam IMRT plan, statistical averaging over the beams reduces the overall dose error between the delivered dose and the motion-averaged dose. For both patients there was a likelihood of up to 7.0% and 33.9% that the dose error was greater than 1%, respectively. For one of the patients, there was a 12.6% likelihood of a 2% dose error. Daily intrafraction variation of the delivered dose of more than 10% is non-negligible and can potentially lead to biological effects. We observed [for sin(x), sin4(x), and sin6(x)] that below 10-15 MU leads to large daily variations of the order of 15-35%. Therefore, for small MU segments, non-negligible biological effects can be incurred. We conclude that for most clinical cases the effects may be small because of the use of many beams, it is desirable to avoid low-MU segments when treating moving targets. In addition, dose averaging may not work well for hypo-fractionation, where fewer fractions are used. For hypo-fractionation, PDF modeling of the tumor motion in IMRT optimization may not be adequate.

Assessing the effect of electron density in photon dose calculations.

Photon dose calculation algorithms (such as the pencil beam and collapsed cone, CC) model the attenuation of a primary photon beam in media other than water, by using pathlength scaling based on the relative mass density of the media to water. In this study, we assess if differences in the electron density between the water and media, with different atomic composition, can influence the accuracy of conventional photon dose calculations algorithms. A comparison is performed between an electron-density scaling method and the standard mass-density scaling method for (i) tissues present in the human body (such as bone, muscle, etc.), and for (ii) water-equivalent plastics, used in radiotherapy dosimetry and quality assurance. We demonstrate that the important material property that should be taken into account by photon dose algorithms is the electron density, and not the mass density. The mass-density scaling method is shown to overestimate, relative to electrondensity predictions, the primary photon fluence for tissues in the human body and water-equivalent plastics, where 6%-7% and 10% differences were observed respectively for bone and air. However, in the case of patients, differences are expected to be smaller due to the large complexity of a treatment plan and of the patient anatomy and atomic composition and of the smaller thickness of bone/air that incident photon beams of a treatment plan may have to traverse. Differences have also been observed for conventional dose algorithms, such as CC, where an overestimate of the lung dose occurs, when irradiating lung tumors. The incorrect lung dose can be attributed to the.incorrect modeling of the photon beam attenuation through the rib cage (thickness of 2-3 cm in bone upstream of the lung tumor) and through the lung and the oversimplified modeling of electron transport in convolution algorithms. In the present study, the overestimation of the primary photon fluence, using the mass-density scaling method, was shown to be a consequence of the differences in the hydrogen content between the various media studied and water. On the other hand, the electron-density scaling method was shown to predict primary photon fluence in media other than water to within 1%-2% for all the materials studied and for energies up to 5 MeV. For energies above 5 MeV, the accuracy of the electron-density scaling method was shown to depend on the photon energy, where for materials with a high content of calcium (such as bone, cortical bone) or for primary photon energies above 10 MeV, the pair-production process could no longer be neglected. The electron-density scaling method was extended to account for pair-production attenuation of the primary photons. Therefore the scaling of the dose distributions in media other than water became dependent on the photon energy. The extended electron-scaling method was shown to estimate the photon range to within 1% for all materials studied and for energies from 100 keV to 20 MeV, allowing it to be used to scale dose distributions to media other than water and generated by clinical radiotherapy photon beams with accelerator energies from 4 to 20 MV.

CT metal artifact reduction method correcting for beam hardening and missing projections

We present and validate a computed tomography (CT) metal artifact reduction method that is effective for a wide spectrum of clinical implant materials. Projections through low-Z implants such as titanium were corrected using a novel physics correction algorithm that reduces beam hardening errors. In the case of high-Z implants (dental fillings, gold, platinum), projections through the implant were considered missing and regularized iterative reconstruction was performed. Both algorithms were combined if multiple implant materials were present. For comparison, a conventional projection interpolation method was implemented. In a blinded and randomized evaluation, ten radiation oncologists ranked the quality of patient scans on which the different methods were applied. For scans that included low-Z implants, the proposed method was ranked as the best method in 90% of the reviews. It was ranked superior to the original reconstruction (p = 0.0008), conventional projection interpolation (p < 0.0001) and regularized limited data reconstruction (p = 0.0002). All reviewers ranked the method first for scans with high-Z implants, and better as compared to the original reconstruction (p < 0.0001) and projection interpolation (p = 0.004). We conclude that effective reduction of CT metal artifacts can be achieved by combining algorithms tailored to specific types of implant materials.

Conversion of CT numbers into tissue parameters for Monte Carlo dose calculations: a multi-centre study.

The conversion of computed tomography (CT) numbers into material composition and mass density data influences the accuracy of patient dose calculations in Monte Carlo treatment planning (MCTP). The aim of our work was to develop a CT conversion scheme by performing a stoichiometric CT calibration. Fourteen dosimetrically equivalent tissue subsets (bins), of which ten bone bins, were created. After validating the proposed CT conversion scheme on phantoms, it was compared to a conventional five bin scheme with only one bone bin. This resulted in dose distributions D(14) and D(5) for nine clinical patient cases in a European multi-centre study. The observed local relative differences in dose to medium were mostly smaller than 5%. The dose-volume histograms of both targets and organs at risk were comparable, although within bony structures D(14) was found to be slightly but systematically higher than D(5). Converting dose to medium to dose to water (D(14) to D(14wat) and D(5) to D(5wat)) resulted in larger local differences as D(5wat) became up to 10% higher than D(14wat). In conclusion, multiple bone bins need to be introduced when Monte Carlo (MC) calculations of patient dose distributions are converted to dose to water.

Dosimetric impact of motion in free-breathing and gated lung radiotherapy: A 4D Monte Carlo study of intrafraction and interfraction effects

The purpose of this study was to investigate if interfraction and intrafraction motion in free-breathing and gated lung IMRT can lead to systematic dose differences between 3DCT and 4DCT. Dosimetric effects were studied considering the breathing pattern of three patients monitored during the course of their treatment and an in-house developed 4D Monte Carlo framework. Imaging data were taken in free-breathing and in cine mode for both 3D and 4D acquisition. Treatment planning for IMRT delivery was done based on the free-breathing data with the CORVUS (North American Scientific, Chatsworth, CA) planning system. The dose distributions as a function of phase in the breathing cycle were combined using deformable image registration. The study focused on (a) assessing the accuracy of the CORVUS pencil beam algorithm with Monte Carlo dose calculation in the lung, (b) evaluating the dosimetric effect of motion on the individual breathing phases of the respiratory cycle, and (c) assessing intrafraction and interfraction motion effects during free-breathing or gated radiotherapy. The comparison between (a) the planning system and the Monte Carlo system shows that the pencil beam algorithm underestimates the dose in low-density regions, such as lung tissue, and overestimates the dose in high-density regions, such as bone, by 5% or more of the prescribed dose (corresponding to approximately 3-5 Gy for the cases considered). For the patients studied this could have a significant impact on the dose volume histograms for the target structures depending on the margin added to the clinical target volume (CTV) to produce either the planning target (PTV) or internal target volume (ITV). The dose differences between (b) phases in the breathing cycle and the free-breathing case were shown to be negligible for all phases except for the inhale phase, where an underdosage of the tumor by as much as 9.3 Gy relative to the free-breathing was observed. The large difference was due to breathing-induced motion/deformation affecting the soft/lung tissue density and motion of the bone structures (such as the rib cage) in and out of the beam. Intrafraction and interfraction dosimetric differences between (c) free-breathing and gated delivery were found to be small. However, more significant dosimetric differences, of the order of 3%-5%, were observed between the dose calculations based on static CT (3DCT) and the ones based on time-resolved CT (4DCT). These differences are a consequence of the larger contribution of the inhale phase in the 3DCT data than in the 4DCT.

Effects of Hounsfield number conversion on CT based proton Monte Carlo dose calculations.

The Monte Carlo method provides the most accurate dose calculations on a patient computed tomography (CT) geometry. The increase in accuracy is, at least in part, due to the fact that instead of treating human tissues as water of various densities as in analytical algorithms, the Monte Carlo method allows human tissues to be characterized by elemental composition and mass density, and hence allows the accurate consideration of all relevant electromagnetic and nuclear interactions. On the other hand, the algorithm to convert CT Hounsfield numbers to tissue materials for Monte Carlo dose calculation introduces uncertainties. There is not a simple one to one correspondence between Hounsfield numbers and tissue materials. To investigate the effects of Hounsfield number conversion for proton Monte Carlo dose calculations, clinical proton treatment plans were simulated using the Geant4 Monte Carlo code. Three Hounsfield number to material conversion methods were studied. The results were compared in forms of dose volume histograms of gross tumor volume and clinical target volume. The differences found are generally small but can be dosimetrically significant. Further, different methods may cause deviations in the predicted proton beam range in particular for deep proton fields. Typically, slight discrepancies in mass density assignments play only a minor role in the target region, whereas more significant effects are caused by different assignments in elemental compositions. In the presence of large tissue inhomogeneities, for head and neck treatments, treatment planning decisions could be affected by these differences because of deviations in the predicted tumor coverage. Outside the target area, differences in elemental composition and mass density assignments both may play a role. This can lead to pronounced effects for organs at risk, in particular in the spread-out Bragg peak penumbra or distal regions. In addition, the significance of the elemental composition effect (dose to water vs. dose to tissue) is tissue-type dependent and is also affected by nuclear reactions.

Use of a realistic breathing lung phantom to evaluate dose delivery errors

PURPOSE To compare the effect of respiration-induced motion on delivered dose (the interplay effect) for different treatment techniques under realistic clinical conditions. METHODS A flexible resin tumor model was created using rapid prototyping techniques based on a computed tomography (CT) image of an actual tumor. Twenty micro-MOSFETs were inserted into the tumor model and the tumor model was inserted into an anthropomorphic breathing phantom. Phantom motion was programed using the motion trajectory of an actual patient. A four-dimensional CT image was obtained and several treatment plans were created using different treatment techniques and planning systems: Conformal (Eclipse), step-and-shoot intensity-modulated radiation therapy (IMRT) (Pinnacle), step-and-shoot IMRT (XiO), dynamic IMRT (Eclipse), complex dynamic IMRT (Eclipse), hybrid IMRT [60% conformal, 40% dynamic IMRT (Eclipse)], volume-modulated arc therapy (VMAT) [single-arc (Eclipse)], VMAT [double-arc (Eclipse)], and complex VMAT (Eclipse). The complex plans were created by artificially pushing the optimizer to give complex multileaf collimator sequences. Each IMRT field was irradiated five times and each VMAT field was irradiated ten times, with each irradiation starting at a random point in the respiratory cycle. The effect of fractionation was calculated by randomly summing the measured doses. The maximum deviation for each measurement point per fraction and the probability that 95% of the model tumor had dose deviations less than 2% and 5% were calculated as a function of the number of fractions. Tumor control probabilities for each treatment plan were calculated and compared. RESULTS After five fractions, measured dose deviations were less than 2% for more than 95% of measurement points within the tumor model for all plans, except the complex dynamic IMRT, step-and-shoot IMRT (XiO), complex VMAT, and single-arc VMAT plans. Reducing the dose rate of the complex IMRT plans from 600 to 200 MU/min reduced the dose deviations to less than 2%. Dose deviations were less than 5% after five fractions for all plans, except the complex single-arc VMAT plan. CONCLUSIONS Rapid prototyping techniques can be used to create realistic tumor models. For most treatment techniques, the dose deviations averaged out after several fractions. Treatments with unusually complicated multileaf collimator sequences had larger dose deviations. For IMRT treat-ments, dose deviations can be reduced by reducing the dose rate. For VMAT treatments, using two arcs instead of one is effective for reducing dose deviations.

Energy- and time-resolved detection of prompt gamma-rays for proton range verification

In this work, we present experimental results of a novel prompt gamma-ray detector for proton beam range verification. The detection system features an actively shielded cerium-doped lanthanum(III) bromide scintillator, coupled to a digital data acquisition system. The acquisition was synchronized to the cyclotron radio frequency to separate the prompt gamma-ray signals from the later-arriving neutron-induced background. We designed the detector to provide a high energy resolution and an effective reduction of background events, enabling discrete proton-induced prompt gamma lines to be resolved. Measuring discrete prompt gamma lines has several benefits for range verification. As the discrete energies correspond to specific nuclear transitions, the magnitudes of the different gamma lines have unique correlations with the proton energy and can be directly related to nuclear reaction cross sections. The quantification of discrete gamma lines also enables elemental analysis of tissue in the beam path, providing a better prediction of prompt gamma-ray yields. We present the results of experiments in which a water phantom was irradiated with proton pencil-beams in a clinical proton therapy gantry. A slit collimator was used to collimate the prompt gamma-rays, and measurements were performed at 27 positions along the path of proton beams with ranges of 9, 16 and 23 g cm(-2) in water. The magnitudes of discrete gamma lines at 4.44, 5.2 and 6.13 MeV were quantified. The prompt gamma lines were found to be clearly resolved in dimensions of energy and time, and had a reproducible correlation with the proton depth-dose curve. We conclude that the measurement of discrete prompt gamma-rays for in vivo range verification of clinical proton beams is feasible, and plan to further study methods and detector designs for clinical use.

Monte Carlo modelling of a-Si EPID response: The effect of spectral variations with field size and position

This study focused on predicting the electronic portal imaging device (EPID) image of intensity modulated radiation treatment (IMRT) fields in the absence of attenuation material in the beam with Monte Carlo methods. As IMRT treatments consist of a series of segments of various sizes that are not always delivered on the central axis, large spectral variations may be observed between the segments. The effect of these spectral variations on the EPID response was studied with fields of various sizes and off-axis positions. A detailed description of the EPID was implemented in a Monte Carlo model. The EPID model was validated by comparing the EPID output factors for field sizes between 1 x 1 and 26 x 26 cm2 at the isocenter. The Monte Carlo simulations agreed with the measurements to within 1.5%. The Monte Carlo model succeeded in predicting the EPID response at the center of the fields of various sizes and offsets to within 1% of the measurements. Large variations (up to 29%) of the EPID response were observed between the various offsets. The EPID response increased with field size and with field offset for most cases. The Monte Carlo model was then used to predict the image of a simple test IMRT field delivered on the beam axis and with an offset. A variation of EPID response up to 28% was found between the on- and off-axis delivery. Finally, two clinical IMRT fields were simulated and compared to the measurements. For all IMRT fields, simulations and measurements agreed within 3%-0.2 cm for 98% of the pixels. The spectral variations were quantified by extracting from the spectra at the center of the fields the total photon yield (Ytotal), the photon yield below 1 MeV (Ylow), and the percentage of photons below 1 MeV (Plow). For the studied cases, a correlation was shown between the EPID response variation and Ytotal, Ylow, and Plow.

Proton range verification through prompt gamma-ray spectroscopy

We present an experimental study of a novel method to verify the range of proton therapy beams. Differential cross sections were measured for 15 prompt gamma-ray lines from proton-nuclear interactions with (12)C and (16)O at proton energies up to 150 MeV. These cross sections were used to model discrete prompt gamma-ray emissions along proton pencil-beams. By fitting detected prompt gamma-ray counts to these models, we simultaneously determined the beam range and the oxygen and carbon concentration of the irradiated matter. The performance of the method was assessed in two phantoms with different elemental concentrations, using a small scale prototype detector. Based on five pencil-beams with different ranges delivering 5 × 10(8) protons and without prior knowledge of the elemental composition at the measurement point, the absolute range was determined with a standard deviation of 1.0-1.4 mm. Relative range shifts at the same dose level were detected with a standard deviation of 0.3-0.5 mm. The determined oxygen and carbon concentrations also agreed well with the actual values. These results show that quantitative prompt gamma-ray measurements enable knowledge of nuclear reaction cross sections to be used for precise proton range verification in the presence of tissue with an unknown composition.