A method for beam's eye view breath-hold monitoring during breast volumetric modulated arc therapy.

Background and purpose: Deep inspiration breath-hold (DIBH) is a technique that is widely utilised to spare the heart and lungs during breast radiotherapy. In this study, a method was developed to validate directly the intrafraction accuracy of DIBH during breast volumetric modulated arc therapy (VMAT) via internal chest wall (CW) monitoring. Materials and methods: In-house software was developed to automatically extract and compare the treatment position of the CW in cine-mode electronic portal image device (EPID) images with the planned CW position in digitally reconstructed radiographs (DRR) for breast VMAT treatments. Feasibility of this method was established by evaluating the percentage of total dose delivered to the target volume when the CW was sufficiently visible for monitoring. Geometric accuracy of the approach was quantified by applying known displacements to an anthropomorphic thorax phantom. The software was used to evaluate (offline) the geometric treatment accuracy for ten patients treated using real-time position management (RPM)-guided DIBH. Results: The CW could be monitored within the tangential sub-arcs which delivered a median 89% (range 73% to 97%) of the dose to target volume. The phantom measurements showed a geometric accuracy within 1 mm, with visual inspection showing good agreement between the software-derived and user-determined CW positions. For the RPM-guided DIBH treatments, the CW was found to be within ±5 mm of the planned position in 97% of EPID frames in which the CW was visible. Conclusion: An intrafraction monitoring method with sub-millimetre accuracy was successfully developed to validate target positioning during breast VMAT DIBH.

Clinical impact of removing respiratory motion during liver SABR.

BACKGROUND: Liver tumors are subject to motion with respiration, which is typically accounted for by increasing the target volume. The prescription dose is often reduced to keep the mean liver dose under a threshold level to limit the probability of radiation induced liver toxicity. A retrospective planning study was performed to determine the potential clinical gains of removal of respiratory motion from liver SABR treatment volumes, which may be achieved with gating or tumor tracking. METHODS: Twenty consecutive liver SABR patients were analysed. The treated PTV included the GTV in all phases of respiration (ITV) with a 5 mm margin. The goal prescription was 50Gy/5# (BED 100 Gy10) but was reduced by 2.5 Gy increments to meet liver dose constraints. Elimination of motion was modelled by contouring the GTV in the expiration phase only, with a 5 mm PTV margin. All patients were replanned using the no-motion PTV and tumor dose was escalated to higher prescription levels where feasible given organ-at-risk constraints. For the cohort of patients with metastatic disease, BED gains were correlated to increases in tumour control probability (TCP). The effect of the gradient of the TCP curve on the magnitude of TCP increase was evaluated by repeating the study for an additional prescription structure, 54Gy/3# (BED 151 Gy10). RESULTS: Correlation between PTV size and prescribed dose exists; PTVs encompassing < 10% of the liver could receive the highest prescription level. A monotonically increasing correlation (Spearman's rho 0.771, p = 0.002) between the degree of PTV size reduction and motion vector magnitude was observed for GTV sizes <100cm3. For 11/13 patients initially planned to a decreased prescription, tumor dose escalation was possible (5.4Gy10-21.4Gy10 BED) using the no-motion PTV. Dose escalation in excess of 20 Gy10 increased the associated TCP by 5% or more. A comparison of TCP gains between the two fractionation schedules showed that, for the same patient geometry, the absolute increase in BED was the overarching factor rather than the gradient of the TCP curve. CONCLUSIONS: In liver SABR treatments unable to be prescribed optimal dose due to exceeding mean liver thresholds, eliminating respiratory motion allowed dose escalation in the majority of patients studied and substantially increased TCP.

Physico-chemical properties and optimization of the deformable FlexyDos3D radiation dosimeter.

Deformable 3D radiation dosimetry is receiving growing interest for the validation of image-guided radiotherapy treatments (IGRT) of moving and deformable targets. Previously, a proof-of-concept of a flexible anthropomorphic 3D dosimeter called 'FlexyDos3D' has been demonstrated. One of the concerns with respect to the FlexyDos3D dosimeter is its dose-response instability. The effect of different formulations of the dosimeter on its stability were investigated. A stable formulation for the dosimeter was found by optimising the ratios of curing agent and base of the silicone matrix between 3% and 4.5% [w/w] curing agent. The effects of elevated curing temperatures and times upon the dosimetric properties were also investigated and the dose-response was found to be independent of curing times for curing times over an hour at 120 °C. 1H NMR spectra of the dosimeter chemical constituents and the effect of radiation dose were determined. The evaporation and diffusion rates of chloroform in the dosimeter were determined and are the likely cause of the dosimeters depth-dose profile uncertainties. A composition for a stable silicone dosimeter which can be cured quickly at elevated temperatures was found, demonstrating the potential for 3D printing of patient-specific dosimeters. However, it is suggested that another radical initiator be used in future formulations of the dosimeter.

Technical Note: Real-time image-guided adaptive radiotherapy of a rigid target for a prototype fixed beam radiotherapy system.

PURPOSE: Fixed beam radiotherapy systems utilize couch movement and rotation instead of gantry rotation in order to simplify linear accelerator design. We investigate the ability to deliver fixed beam treatments with the same level of clinical accuracy as conventional (rotating beam) treatments using real-time image guidance to maintain this accuracy in the presence of rigid target motion. METHODS: A prototype fixed beam radiotherapy system was built using a standard linac with the beam fixed in the vertical position and a computer controlled rotation stage that rotated a rigid phantom about the superior-inferior axis. Kilovoltage Intrafraction Monitoring (KIM) and real-time beam adaptation with MLC tracking was applied to a five-field IMRT treatment plan with motion introduced to the phantom. The same IMRT treatment was also delivered with real-time adaptation using the conventional rotating beam geometry. Film dosimetry was used to measure the dose delivered with a fixed beam compared to a rotating beam, as well as to compare treatments delivered with and without real-time adaptation. RESULTS: The dose distributions were found to be equivalent between the fixed beam and rotating beam geometry for real-time adaptive radiotherapy using KIM and MLC tracking beam adaptation. Gamma analysis on the films showed agreement >98% using a 2%/2 mm criteria with adaptation for static shifts and periodic motion. CONCLUSIONS: Fixed beam treatments with real-time beam adaptation are dosimetrically equivalent to conventional treatments with a rotating beam, even in the presence of rigid target motion. This suggests that, for a rigid target, the high clinical accuracy of real-time adaptive radiotherapy can be achieved with simpler beam geometry.

An interdimensional correlation framework for real-time estimation of six degree of freedom target motion using a single x-ray imager during radiotherapy.

Increasing evidence suggests that intrafraction tumour motion monitoring needs to include both 3D translations and 3D rotations. Presently, methods to estimate the rotation motion require the 3D translation of the target to be known first. However, ideally, translation and rotation should be estimated concurrently. We present the first method to directly estimate six-degree-of-freedom (6DoF) motion from the target's projection on a single rotating x-ray imager in real-time. This novel method is based on the linear correlations between the superior-inferior translations and the motion in the other five degrees-of-freedom. The accuracy of the method was evaluated in silico with 81 liver tumour motion traces from 19 patients with three implanted markers. The ground-truth motion was estimated using the current gold standard method where each marker's 3D position was first estimated using a Gaussian probability method, and the 6DoF motion was then estimated from the 3D positions using an iterative method. The 3D position of each marker was projected onto a gantry-mounted imager with an imaging rate of 11 Hz. After an initial 110° gantry rotation (200 images), a correlation model between the superior-inferior translations and the five other DoFs was built using a least square method. The correlation model was then updated after each subsequent frame to estimate 6DoF motion in real-time. The proposed algorithm had an accuracy (±precision) of -0.03 ± 0.32 mm, -0.01 ± 0.13 mm and 0.03 ± 0.52 mm for translations in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) directions respectively; and, 0.07 ± 1.18°, 0.07 ± 1.00° and 0.06 ± 1.32° for rotations around the LR, SI and AP axes respectively on the dataset. The first method to directly estimate real-time 6DoF target motion from segmented marker positions on a 2D imager was devised. The algorithm was evaluated using 81 motion traces from 19 liver patients and was found to have sub-mm and sub-degree accuracy.

MagicPlate-512: A 2D silicon detector array for quality assurance of stereotactic motion adaptive radiotherapy.

PURPOSE: Spatial and temporal resolutions are two of the most important features for quality assurance instrumentation of motion adaptive radiotherapy modalities. The goal of this work is to characterize the performance of the 2D high spatial resolution monolithic silicon diode array named "MagicPlate-512" for quality assurance of stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) combined with a dynamic multileaf collimator (MLC) tracking technique for motion compensation. METHODS: MagicPlate-512 is used in combination with the movable platform HexaMotion and a research version of radiofrequency tracking system Calypso driving MLC tracking software. The authors reconstruct 2D dose distributions of small field square beams in three modalities: in static conditions, mimicking the temporal movement pattern of a lung tumor and tracking the moving target while the MLC compensates almost instantaneously for the tumor displacement. Use of Calypso in combination with MagicPlate-512 requires a proper radiofrequency interference shielding. Impact of the shielding on dosimetry has been simulated by (GEANT)4 and verified experimentally. Temporal and spatial resolutions of the dosimetry system allow also for accurate verification of segments of complex stereotactic radiotherapy plans with identification of the instant and location where a certain dose is delivered. This feature allows for retrospective temporal reconstruction of the delivery process and easy identification of error in the tracking or the multileaf collimator driving systems. A sliding MLC wedge combined with the lung motion pattern has been measured. The ability of the MagicPlate-512 (MP512) in 2D dose mapping in all three modes of operation was benchmarked by EBT3 film. RESULTS: Full width at half maximum and penumbra of the moving and stationary dose profiles measured by EBT3 film and MagicPlate-512 confirm that motion has a significant impact on the dose distribution. Motion, no motion, and motion with MLC tracking profiles agreed within 1 and 0.4 mm, respectively, for all field sizes tested. Use of electromagnetic tracking system generates a fluctuation of the detector baseline up to 10% of the full scale signal requiring a proper shielding strategy. MagicPlate-512 is also able to reconstruct the dose variation pulse-by-pulse in each pixel of the detector. An analysis of the dose transients with motion and motion with tracking shows that the tracking feedback algorithm used for this experiment can compensate effectively only the effect of the slower transient components. The fast changing components of the organ motion can contribute only to discrepancy of the order of 15% in penumbral region while the slower components can change the dose profile up to 75% of the expected dose. CONCLUSIONS: MagicPlate-512 is shown to be, potentially, a valid alternative to film or 2D ionizing chambers for quality assurance dosimetry in SRS or SBRT. Its high spatial and temporal resolutions allow for accurate reconstruction of the profile in any conditions with motion and with tracking of the motion. It shows excellent performance to reconstruct the dose deposition in real time or retrospectively as a function of time for detailed analysis of the effect of motion in a specific pixel or area of interest.

Determining appropriate imaging parameters for kilovoltage intrafraction monitoring: an experimental phantom study.

Kilovoltage intrafraction monitoring (KIM) utilises the kV imager during treatment for real-time tracking of prostate fiducial markers. However, its effectiveness relies on sufficient image quality for the fiducial tracking task. To guide the performance characterisation of KIM under different clinically relevant conditions, the effect of different kV parameters and patient size on image quality, and quantification of MV scatter from the patient to the kV detector panel were investigated in this study. Image quality was determined for a range of kV acquisition frame rates, kV exposure, MV dose rates and patient sizes. Two methods were used to determine image quality; the ratio of kV signal through the patient to the MV scatter from the patient incident on the kilovoltage detector, and the signal-to-noise ratio (SNR). The effect of patient size and frame rate on MV scatter was evaluated in a homogeneous CIRS pelvis phantom and marker segmentation was determined utilising the Rando phantom with embedded markers. MV scatter incident on the detector was shown to be dependent on patient thickness and frame rate. The segmentation code was shown to be successful for all frame rates above 3 Hz for the Rando phantom corresponding to a kV to MV ratio of 0.16 and an SNR of 1.67. For a maximum patient dimension less than 36.4 cm the conservative kV parameters of 5 Hz at 1 mAs can be used to reduce dose while retaining image quality, where the current baseline kV parameters of 10 Hz at 1 mAs is shown to be adequate for marker segmentation up to a patient dimension of 40 cm. In conclusion, the MV scatter component of image quality noise for KIM has been quantified. For most prostate patients, use of KIM with 10 Hz imaging at 1 mAs is adequate however image quality can be maintained and imaging dose reduced by altering existing acquisition parameters.

FlexyDos3D: a deformable anthropomorphic 3D radiation dosimeter: radiation properties.

Three dimensional radiation dosimetry has received growing interest with the implementation of highly conformal radiotherapy treatments. The radiotherapy community faces new challenges with the commissioning of image guided and image gated radiotherapy treatments (IGRT) and deformable image registration software.A new three dimensional anthropomorphically shaped flexible dosimeter, further called 'FlexyDos3D', has been constructed and a new fast optical scanning method has been implemented that enables scanning of irregular shaped dosimeters. The FlexyDos3D phantom can be actuated and deformed during the actual treatment. FlexyDos3D offers the additional advantage that it is easy to fabricate, is non-toxic and can be molded in an arbitrary shape with high geometrical precision.The dosimeter formulation has been optimized in terms of dose sensitivity. The influence of the casting material and oxygen concentration has also been investigated. The radiophysical properties of this new dosimeter are discussed including stability, spatial integrity, temperature dependence of the dosimeter during radiation, readout and storage, dose rate dependence and tissue equivalence.

Quality assurance for the clinical implementation of kilovoltage intrafraction monitoring for prostate cancer VMAT.

PURPOSE: Kilovoltage intrafraction monitoring (KIM) is a real-time 3D tumor monitoring system for cancer radiotherapy. KIM uses the commonly available gantry-mounted x-ray imager as input, making this method potentially more widely available than dedicated real-time 3D tumor monitoring systems. KIM is being piloted in a clinical trial for prostate cancer patients treated with VMAT (NCT01742403). The purpose of this work was to develop clinical process and quality assurance (QA) practices for the clinical implementation of KIM. METHODS: Informed by and adapting existing guideline documents from other real-time monitoring systems, KIM-specific QA practices were developed. The following five KIM-specific QA tests were included: (1) static localization accuracy, (2) dynamic localization accuracy, (3) treatment interruption accuracy, (4) latency measurement, and (5) clinical conditions accuracy. Tests (1)-(4) were performed using KIM to measure static and representative patient-derived prostate motion trajectories using a 3D programmable motion stage supporting an anthropomorphic phantom with implanted gold markers to represent the clinical treatment scenario. The threshold for system tolerable latency is <1 s. The tolerances for all other tests are that both the mean and standard deviation of the difference between the programmed trajectory and the measured data are <1 mm. The (5) clinical conditions accuracy test compared the KIM measured positions with those measured by kV/megavoltage (MV) triangulation from five treatment fractions acquired in a previous pilot study. RESULTS: For the (1) static localization, (2) dynamic localization, and (3) treatment interruption accuracy tests, the mean and standard deviation of the difference are <1.0 mm. (4) The measured latency is 350 ms. (5) For the tests with previously acquired patient data, the mean and standard deviation of the difference between KIM and kV/MV triangulation are <1.0 mm. CONCLUSIONS: Clinical process and QA practices for the safe clinical implementation of KIM, a novel real-time monitoring system using commonly available equipment, have been developed and implemented for prostate cancer VMAT.

DMLC tracking and gating can improve dose coverage for prostate VMAT.

PURPOSE: To assess and compare the dosimetric impact of dynamic multileaf collimator (DMLC) tracking and gating as motion correction strategies to account for intrafraction motion during conventionally fractionated prostate radiotherapy. METHODS: A dose reconstruction method was used to retrospectively assess the dose distributions delivered without motion correction during volumetric modulated arc therapy fractions for 20 fractions of five prostate cancer patients who received conventionally fractionated radiotherapy. These delivered dose distributions were compared with the dose distributions which would have been delivered had DMLC tracking or gating motion correction strategies been implemented. The delivered dose distributions were constructed by incorporating the observed prostate motion with the patient's original treatment plan to simulate the treatment delivery. The DMLC tracking dose distributions were constructed using the same dose reconstruction method with the addition of MLC positions from Linac log files obtained during DMLC tracking simulations with the observed prostate motions input to the DMLC tracking software. The gating dose distributions were constructed by altering the prostate motion to simulate the application of a gating threshold of 3 mm for 5 s. RESULTS: The delivered dose distributions showed that dosimetric effects of intrafraction prostate motion could be substantial for some fractions, with an estimated dose decrease of more than 19% and 34% from the planned CTVD99% and PTV D95% values, respectively, for one fraction. Evaluation of dose distributions for DMLC tracking and gating deliveries showed that both interventions were effective in improving the CTV D99% for all of the selected fractions to within 4% of planned value for all fractions. For the delivered dose distributions the difference in rectum V65% for the individual fractions from planned ranged from -44% to 101% and for the bladder V65% the range was -61% to 26% from planned. The application of tracking decreased the maximum rectum and bladder V65% difference to 6% and 4%, respectively. CONCLUSIONS: For the first time, the dosimetric impact of DMLC tracking and gating to account for intrafraction motion during prostate radiotherapy has been assessed and compared with no motion correction. Without motion correction intrafraction prostate motion can result in a significant decrease in target dose coverage for a small number of individual fractions. This is unlikely to effect the overall treatment for most patients undergoing conventionally fractionated treatments. Both DMLC tracking and gating demonstrate dose distributions for all assessed fractions that are robust to intrafraction motion.

The effects of radiotherapy treatment uncertainties on the delivered dose distribution and tumour control probability.

Uncertainty in the precise quantity of radiation dose delivered to tumours in external beam radiotherapy is present due to many factors, and can result in either spatially uniform (Gaussian) or spatially non-uniform dose errors. These dose errors are incorporated into the calculation of tumour control probability (TCP) and produce a distribution of possible TCP values over a population. We also study the effect of inter-patient cell sensitivity heterogeneity on the population distribution of patient TCPs. This study aims to investigate the relative importance of these three uncertainties (spatially uniform dose uncertainty, spatially non-uniform dose uncertainty, and inter-patient cell sensitivity heterogeneity) on the delivered dose and TCP distribution following a typical course of fractionated external beam radiotherapy. The dose distributions used for patient treatments are modelled in one dimension. Geometric positioning uncertainties during and before treatment are considered as shifts of a pre-calculated dose distribution. Following the simulation of a population of patients, distributions of dose across the patient population are used to calculate mean treatment dose, standard deviation in mean treatment dose, mean TCP, standard deviation in TCP, and TCP mode. These parameters are calculated with each of the three uncertainties included separately. The calculations show that the dose errors in the tumour volume are dominated by the spatially uniform component of dose uncertainty. This could be related to machine specific parameters, such as linear accelerator calibration. TCP calculation is affected dramatically by inter-patient variation in the cell sensitivity and to a lesser extent by the spatially uniform dose errors. The positioning errors with the 1.5 cm margins used cause dose uncertainty outside the tumour volume and have a small effect on mean treatment dose (in the tumour volume) and tumour control.

Modelling the dosimetric consequences of organ motion at CT imaging on radiotherapy treatment planning.

Treatment planning algorithms usually assume that the correct or at least the mean organ position is derived from the CT imaging procedure, and that this position is reproduced throughout the treatment. In reality a mobile organ is unlikely to be in its exact mean position at the time of imaging, causing the treatment to be planned with an organ off-set from its assumed mean position. This introduces an extra 'CT uncertainty' into the treatment. A Monte Carlo (MC) model is used to simulate organ translations at imaging and evaluate the effect of this uncertainty (above the treatment delivery uncertainties) on the dose distribution. An underdose by 4 Gy in a 60 Gy treatment is calculated in the penumbral region of a single-field dose distribution as a result of the CT uncertainty. The effect is reduced to less then 0.5 Gy when the organ position at planning is derived as the average from multiple pretreatment CT scans. It is shown that a convolution method can be applied to predict the effect of CT uncertainty on the dose distribution for a patient population. Additionally, a variation kernel for a convolution method is derived that incorporates uncertainty at both imaging and treatment.

Improved spatial resolution by MOSFET dosimetry of an x-ray microbeam.

Measurement of the lateral profile of the dose distribution across a narrow x-ray microbeam requires a dosimeter with a micron resolution. We investigated the use of a MOSFET dosimeter in an "edge-on" orientation with the gate insulating oxide layer parallel to the direction of the beam. We compared results using this technique to Gafchromic film measurements of a 200 micrometer wide planar x-ray microbeam. The microbeam was obtained by using a vernier micrometer-driven miniature collimator attached to a Therapax DXT300 x-ray machine operated at 100 kVp. The "edge-on" application allows utilization of the ultra thin sensitive volume of the MOSFET detector. Spatial resolution of both the MOSFET and Gafchromic film dosimeters appeared to be of about 1 micrometer. The MOSFET dosimeter appeared to provide more uniform dose profiles with the advantage of on-line measurements.

Set-up error & organ motion uncertainty: a review.

Conformal radiotherapy allows improvement in the treatment outcome due to increased targeting accuracy through advanced beam shaping techniques to precisely conform radiation dose to the geometry of the tumour. Treatment set-up and organ motion uncertainties are unavoidable factors that are limiting increases in accuracy and have to be accounted for in conformal treatment planning. The magnitudes of set-up errors and organ motion uncertainties for specific sites, and using various set-up techniques, have been quantified in the literature. However, the parameters used with these measurements and the presentation of the data has differed between studies for the same site. The purpose of this paper is to analyse and combine the published material into a uniform format and to display typical reported values of set-up and organ motion uncertainties. Values measured under similar conditions were averaged across studies. The results of this analysis illustrate (1) variability in the parameters used for measurements across studies, (2) typical motion ranges of the prostate, kidneys, liver and diaphragm, (3) typical means and standard deviations for set-up errors associated with the prostate, pelvis, brain, head and neck, thorax, rectum and breast and (4) a brief review of the common methods to lower or account for these uncertainties.

A method to predict the effect of organ motion and set-up variations on treatment plans.

Dose distributions calculated by commercial treatment planning systems do not allow incorporation of the effects of patient position variation or organ motion throughout the course of radiation therapy treatment. We have established a convolution-based method, which enables us to display dose distributions using a commercial treatment planning system that can take into account target movement. An example of the method applied to a prostate treatment plan is presented. For the method to be of clinical use it requires assessment of the parameters leading to target movement in a scientific manner in the same treatment department that it is to be used. It is not sufficient to rely on published data especially that relating to set-up accuracy as this has been shown to vary widely from centre to centre. We believe that with appropriate movement data, a convolution-based approach can lead to more optimal radiation margins around clinical target volumes (CTV). Optimal margins will help prevent geometric misses as well as ensure that the amount of critical late reacting normal tissues surrounding the CTV irradiated is minimised. Optimal margins cannot be guaranteed with the more conventionally used "rule of thumb" techniques for placing a planning target volume around the CTV.

Bremsstrahlung production from a linac target in the presence of external magnetic fields.

A method to increase the photon fluence of the linac is to apply a magnetic field to the bremsstrahlung producing electrons in the target. This field changes the electron paths, and therefore the photon trajectories. In this research Monte Carlo techniques are used to model the effect of three separate magnetic field configurations applied to a tungsten target, on the forward projection of bremsstrahlung created from incident 6 MeV electrons. A radial fluence spectrum is produced for each magnetic field. The maximum increase in fluence is shown to be around 10% for a physically possible field. We conclude that the cost of constructing and installing such magnets (currently) outweighs the small increase in fluence yield.