Ricky O’Brien

The first clinical implementation of electromagnetic transponder-guided MLC tracking

PURPOSE We report on the clinical process, quality assurance, and geometric and dosimetric results of the first clinical implementation of electromagnetic transponder-guided MLC tracking which occurred on 28 November 2013 at the Northern Sydney Cancer Centre. METHODS An electromagnetic transponder-based positioning system (Calypso) was modified to send the target position output to in-house-developed MLC tracking code, which adjusts the leaf positions to optimally align the treatment beam with the real-time target position. Clinical process and quality assurance procedures were developed and performed. The first clinical implementation of electromagnetic transponder-guided MLC tracking was for a prostate cancer patient being treated with dual-arc VMAT (RapidArc). For the first fraction of the first patient treatment of electromagnetic transponder-guided MLC tracking we recorded the in-room time and transponder positions, and performed dose reconstruction to estimate the delivered dose and also the dose received had MLC tracking not been used. RESULTS The total in-room time was 21 min with 2 min of beam delivery. No additional time was needed for MLC tracking and there were no beam holds. The average prostate position from the initial setup was 1.2 mm, mostly an anterior shift. Dose reconstruction analysis of the delivered dose with MLC tracking showed similar isodose and target dose volume histograms to the planned treatment and a 4.6% increase in the fractional rectal V60. Dose reconstruction without motion compensation showed a 30% increase in the fractional rectal V60 from that planned, even for the small motion. CONCLUSIONS The real-time beam-target correction method, electromagnetic transponder-guided MLC tracking, has been translated to the clinic. This achievement represents a milestone in improving geometric and dosimetric accuracy, and by inference treatment outcomes, in cancer radiotherapy.

Toward the development of intrafraction tumor deformation tracking using a dynamic multi-leaf collimator.

PURPOSE Intrafraction deformation limits targeting accuracy in radiotherapy. Studies show tumor deformation of over 10 mm for both single tumor deformation and system deformation (due to differential motion between primary tumors and involved lymph nodes). Such deformation cannot be adapted to with current radiotherapy methods. The objective of this study was to develop and experimentally investigate the ability of a dynamic multi-leaf collimator (DMLC) tracking system to account for tumor deformation. METHODS To compensate for tumor deformation, the DMLC tracking strategy is to warp the planned beam aperture directly to conform to the new tumor shape based on real time tumor deformation input. Two deformable phantoms that correspond to a single tumor and a tumor system were developed. The planar deformations derived from the phantom images in beams eye view were used to guide the aperture warping. An in-house deformable image registration software was developed to automatically trigger the registration once new target image was acquired and send the computed deformation to the DMLC tracking software. Because the registration speed is not fast enough to implement the experiment in real-time manner, the phantom deformation only proceeded to the next position until registration of the current deformation position was completed. The deformation tracking accuracy was evaluated by a geometric target coverage metric defined as the sum of the area incorrectly outside and inside the ideal aperture. The individual contributions from the deformable registration algorithm and the finite leaf width to the tracking uncertainty were analyzed. Clinical proof-of-principle experiment of deformation tracking using previously acquired MR images of a lung cancer patient was implemented to represent the MRI-Linac environment. Intensity-modulated radiation therapy (IMRT) treatment delivered with enabled deformation tracking was simulated and demonstrated. RESULTS The first experimental investigation of adapting to tumor deformation has been performed using simple deformable phantoms. For the single tumor deformation, the A(u)+A(o) was reduced over 56% when deformation was larger than 2 mm. Overall, the total improvement was 82%. For the tumor system deformation, the A(u)+A(o) reductions were all above 75% and the total A(u)+A(o) improvement was 86%. Similar coverage improvement was also found in simulating deformation tracking during IMRT delivery. The deformable image registration algorithm was identified as the dominant contributor to the tracking error rather than the finite leaf width. The discrepancy between the warped beam shape and the ideal beam shape due to the deformable registration was observed to be partially compensated during leaf fitting due to the finite leaf width. The clinical proof-of-principle experiment demonstrated the feasibility of intrafraction deformable tracking for clinical scenarios. CONCLUSIONS For the first time, we developed and demonstrated an experimental system that is capable of adapting the MLC aperture to account for tumor deformation. This work provides a potentially widely available management method to effectively account for intrafractional tumor deformation. This proof-of-principle study is the first experimental step toward the development of an image-guided radiotherapy system to treat deforming tumors in real-time.

The first patient treatment of electromagnetic-guided real time adaptive radiotherapy using MLC tracking for lung SABR.

BACKGROUND AND PURPOSE Real time adaptive radiotherapy that enables smaller irradiated volumes may reduce pulmonary toxicity. We report on the first patient treatment of electromagnetic-guided real time adaptive radiotherapy delivered with MLC tracking for lung stereotactic ablative body radiotherapy. MATERIALS AND METHODS A clinical trial was developed to investigate the safety and feasibility of MLC tracking in lung. The first patient was an 80-year old man with a single left lower lobe lung metastasis to be treated with SABR to 48Gy in 4 fractions. In-house software was integrated with a standard linear accelerator to adapt the treatment beam shape and position based on electromagnetic transponders implanted in the lung. MLC tracking plans were compared against standard ITV-based treatment planning. MLC tracking plan delivery was reconstructed in the patient to confirm safe delivery. RESULTS Real time adaptive radiotherapy delivered with MLC tracking compared to standard ITV-based planning reduced the PTV by 41% (18.7-11cm3) and the mean lung dose by 30% (202-140cGy), V20 by 35% (2.6-1.5%) and V5 by 9% (8.9-8%). CONCLUSION An emerging technology, MLC tracking, has been translated into the clinic and used to treat lung SABR patients for the first time. This milestone represents an important first step for clinical real-time adaptive radiotherapy that could reduce pulmonary toxicity in lung radiotherapy.

Real-time estimation of prostate tumor rotation and translation with a kV imaging system based on an iterative closest point algorithm

Previous studies have shown that during cancer radiotherapy a small translation or rotation of the tumor can lead to errors in dose delivery. Current best practice in radiotherapy accounts for tumor translations, but is unable to address rotation due to a lack of a reliable real-time estimate. We have developed a method based on the iterative closest point (ICP) algorithm that can compute rotation from kilovoltage x-ray images acquired during radiation treatment delivery. A total of 11 748 kilovoltage (kV) images acquired from ten patients (one fraction for each patient) were used to evaluate our tumor rotation algorithm. For each kV image, the three dimensional coordinates of three fiducial markers inside the prostate were calculated. The three dimensional coordinates were used as input to the ICP algorithm to calculate the real-time tumor rotation and translation around three axes. The results show that the root mean square error was improved for real-time calculation of tumor displacement from a mean of 0.97 mm with the stand alone translation to a mean of 0.16 mm by adding real-time rotation and translation displacement with the ICP algorithm. The standard deviation (SD) of rotation for the ten patients was 2.3°, 0.89° and 0.72° for rotation around the right-left (RL), anterior-posterior (AP) and superior-inferior (SI) directions respectively. The correlation between all six degrees of freedom showed that the highest correlation belonged to the AP and SI translation with a correlation of 0.67. The second highest correlation in our study was between the rotation around RL and rotation around AP, with a correlation of -0.33. Our real-time algorithm for calculation of rotation also confirms previous studies that have shown the maximum SD belongs to AP translation and rotation around RL. ICP is a reliable and fast algorithm for estimating real-time tumor rotation which could create a pathway to investigational clinical treatment studies requiring real-time measurement and adaptation to tumor rotation.

Optimizing 4D cone beam computed tomography acquisition by varying the gantry velocity and projection time interval.

Four dimensional cone beam computed tomography (4DCBCT) is an emerging clinical image guidance strategy for tumour sites affected by respiratory motion. In current generation 4DCBCT techniques, both the gantry rotation speed and imaging frequency are constant and independent of the patients breathing which can lead to projection clustering. We present a mixed integer quadratic programming (MIQP) model for respiratory motion guided-4DCBCT (RMG-4DCBCT) which regulates the gantry velocity and projection time interval, in response to the patients respiratory signal, so that a full set of evenly spaced projections can be taken in a number of phase, or displacement, bins during the respiratory cycle. In each respiratory bin, an image can be reconstructed from the projections to give a 4D view of the patients anatomy so that the motion of the lungs, and tumour, can be observed during the breathing cycle. A solution to the full MIQP model in a practical amount of time, 10 s, is not possible with the leading commercial MIQP solvers, so a heuristic method is presented. Using parameter settings typically used on current generation 4DCBCT systems (4 min image acquisition, 1200 projections, 10 respiratory bins) and a sinusoidal breathing trace with a 4 s period, we show that the root mean square (RMS) of the angular separation between projections with displacement binning is 2.7° using existing constant gantry speed systems and 0.6° using RMG-4DCBCT. For phase based binning the RMS is 2.7° using constant gantry speed systems and 2.5° using RMG-4DCBCT. The optimization algorithm presented is a critical step on the path to developing a system for RMG-4DCBCT.

Stereotactic prostate adaptive radiotherapy utilising kilovoltage intrafraction monitoring: the TROG 15.01 SPARK trial

BackgroundThis paper describes the multi-institutional prospective phase II clinical trial, SPARK: Stereotactic Prostate Adaptive Radiotherapy utilizing Kilovoltage Intrafraction Monitoring (KIM). KIM is a real-time image guided radiotherapy technology being developed and clinically pioneered for prostate cancer treatment in Australia. It has potential for widespread use for target radiotherapy treatment of cancers of the pelvis, thorax and abdomen.MethodsIn the SPARK trial we will measure the cancer targeting accuracy and patient outcomes for 48 prostate cancer patients who will be treated in five treatment sessions as opposed to the conventional 40 sessions. The reduced number of treatment sessions is enabled by the KIM’s increased cancer targeting accuracy.DiscussionReal-time imaging in radiotherapy has the potential to decrease the time taken during cancer treatment and reduce the imaging dose required. With the imaging being acquired during the treatment, and the analysis being automated, there is potential for improved throughput. The SPARK trial will be conducted under the auspices of the Trans-Tasman Radiation Oncology Group (TROG).Trial registrationThis trial was registered on ClinicalTrials.gov on 09 March 2015. The identifier is: NCT02397317

Optimizing 4DCBCT projection allocation to respiratory bins

4D cone beam computed tomography (4DCBCT) is an emerging image guidance strategy used in radiotherapy where projections acquired during a scan are sorted into respiratory bins based on the respiratory phase or displacement. 4DCBCT reduces the motion blur caused by respiratory motion but increases streaking artefacts due to projection under-sampling as a result of the irregular nature of patient breathing and the binning algorithms used. For displacement binning the streak artefacts are so severe that displacement binning is rarely used clinically. The purpose of this study is to investigate if sharing projections between respiratory bins and adjusting the location of respiratory bins in an optimal manner can reduce or eliminate streak artefacts in 4DCBCT images. We introduce a mathematical optimization framework and a heuristic solution method, which we will call the optimized projection allocation algorithm, to determine where to position the respiratory bins and which projections to source from neighbouring respiratory bins. Five 4DCBCT datasets from three patients were used to reconstruct 4DCBCT images. Projections were sorted into respiratory bins using equispaced, equal density and optimized projection allocation. The standard deviation of the angular separation between projections was used to assess streaking and the consistency of the segmented volume of a fiducial gold marker was used to assess motion blur. The standard deviation of the angular separation between projections using displacement binning and optimized projection allocation was 30%-50% smaller than conventional phase based binning and 59%-76% smaller than conventional displacement binning indicating more uniformly spaced projections and fewer streaking artefacts. The standard deviation in the marker volume was 20%-90% smaller when using optimized projection allocation than using conventional phase based binning suggesting more uniform marker segmentation and less motion blur. Images reconstructed using displacement binning and the optimized projection allocation algorithm were clearer, contained visibly fewer streak artefacts and produced more consistent marker segmentation than those reconstructed with either equispaced or equal-density binning. The optimized projection allocation algorithm significantly improves image quality in 4DCBCT images and provides, for the first time, a method to consistently generate high quality displacement binned 4DCBCT images in clinical applications.

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.

Audiovisual biofeedback breathing guidance for lung cancer patients receiving radiotherapy: a multi-institutional phase II randomised clinical trial

BackgroundThere is a clear link between irregular breathing and errors in medical imaging and radiation treatment. The audiovisual biofeedback system is an advanced form of respiratory guidance that has previously demonstrated to facilitate regular patient breathing. The clinical benefits of audiovisual biofeedback will be investigated in an upcoming multi-institutional, randomised, and stratified clinical trial recruiting a total of 75 lung cancer patients undergoing radiation therapy.Methods/DesignTo comprehensively perform a clinical evaluation of the audiovisual biofeedback system, a multi-institutional study will be performed. Our methodological framework will be based on the widely used Technology Acceptance Model, which gives qualitative scales for two specific variables, perceived usefulness and perceived ease of use, which are fundamental determinants for user acceptance. A total of 75 lung cancer patients will be recruited across seven radiation oncology departments across Australia. Patients will be randomised in a 2:1 ratio, with 2/3 of the patients being recruited into the intervention arm and 1/3 in the control arm. 2:1 randomisation is appropriate as within the interventional arm there is a screening procedure where only patients whose breathing is more regular with audiovisual biofeedback will continue to use this system for their imaging and treatment procedures. Patients within the intervention arm whose free breathing is more regular than audiovisual biofeedback in the screen procedure will remain in the intervention arm of the study but their imaging and treatment procedures will be performed without audiovisual biofeedback. Patients will also be stratified by treating institution and for treatment intent (palliative vs. radical) to ensure similar balance in the arms across the sites. Patients and hospital staff operating the audiovisual biofeedback system will complete questionnaires to assess their experience with audiovisual biofeedback. The objectives of this clinical trial is to assess the impact of audiovisual biofeedback on breathing motion, the patient experience and clinical confidence in the system, clinical workflow, treatment margins, and toxicity outcomes.DiscussionThis clinical trial marks an important milestone in breathing guidance studies as it will be the first randomised, controlled trial providing the most comprehensive evaluation of the clinical impact of breathing guidance on cancer radiation therapy to date. This study is powered to determine the impact of AV biofeedback on breathing regularity and medical image quality. Objectives such as determining the indications and contra-indications for the use of AV biofeedback, evaluation of patient experience, radiation toxicity occurrence and severity, and clinician confidence will shed light on the design of future phase III clinical trials.Trial registrationThis trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), its trial ID is ACTRN12613001177741.

The impact of leaf width and plan complexity on DMLC tracking of prostate intensity modulated arc therapy

PURPOSE Intensity modulated arc therapy (IMAT) is commonly used to treat prostate cancer. The purpose of this study was to evaluate the impact of leaf width and plan complexity on dynamic multileaf collimator (DMLC) tracking for prostate motion management during IMAT treatments. METHODS Prostate IMAT plans were delivered with either a high-definition MLC (HDMLC) or a Millennium MLC (M-MLC) (0.25 and 0.50 cm central leaf width, respectively), with and without DMLC tracking, to a dosimetric phantom that reproduced four prostate motion traces. The plan complexity was varied by applying leaf position constraints during plan optimization. A subset of the M-MLC plans was converted for delivery with the HDMLC, isolating the effect of the different leaf widths. The gamma index was used for evaluation. Tracking errors caused by target localization, leaf fitting, and leaf adjustment were analyzed. RESULTS The gamma pass rate was significantly improved with DMLC tracking compared to no tracking (p < 0.001). With DMLC tracking, the average gamma index pass rate was 98.6% (range 94.8%-100%) with the HDMLC and 98.1% (range 95.4%-99.7%) with the M-MLC, using 3%, 3 mm criteria and the planned dose as reference. The corresponding pass rates without tracking were 87.6% (range 76.2%-94.7%) and 91.1% (range 81.4%-97.6%), respectively. Decreased plan complexity improved the pass rate when static target measurements were used as reference, but not with the planned dose as reference. The main cause of tracking errors was leaf fitting errors, which were decreased by 42% by halving the leaf width. CONCLUSIONS DMLC tracking successfully compensated for the prostate motion. The finer leaf width of the HDMLC improved the tracking accuracy compared to the M-MLC. The tracking improvement with limited plan complexity was small and not discernible when using the planned dose as reference.