Kilovoltage Intrafraction Monitoring Research Articles

The first clinical implementation of real-time 6 degree-of-freedom image-guided radiotherapy for liver SABR patients

PurposeMultiple survey results have identified a demand for improved motion management for liver cancer IGRT. Until now, real-time IGRT for liver has been the domain of dedicated and expensive cancer radiotherapy systems. The purpose of this study was to clinically implement and characterise the performance of a novel real-time 6 degree-of-freedom (DoF) IGRT system, Kilovoltage Intrafraction Monitoring (KIM) for liver SABR patients. Methods/MaterialsThe KIM technology segmented gold fiducial markers in intra-fraction x-ray images as a surrogate for the liver tumour and converted the 2D segmented marker positions into a real-time 6DoF tumour position. Fifteen liver SABR patients were recruited and treated with KIM combined with external surrogate guidance at three radiotherapy centres in the TROG 17.03 LARK multi-institutional prospective clinical trial. Patients were either treated in breath-hold or in free breathing using the gating method. The KIM localisation accuracy and dosimetric accuracy achieved with KIM + external surrogate were measured and the results were compared to those with the estimated external surrogate alone. ResultsThe KIM localisation accuracy was 0.2±0.9 mm (left–right), 0.3±0.6 mm (superior-inferior) and 1.2±0.8 mm (anterior-posterior) for translations and −0.1◦±0.8◦ (left–right), 0.6◦±1.2◦ (superior-inferior) and 0.1◦±0.9◦ (anterior-posterior) for rotations. The cumulative dose to the GTV with KIM + external surrogate was always within 5% of the plan. In 2 out of 15 patients, >5% dose error would have occurred to the GTV and an organ-at-risk with external surrogate alone. ConclusionsThis work demonstrates that real-time 6DoF IGRT for liver can be implemented on standard radiotherapy systems to improve treatment accuracy and safety. The observations made during the treatments highlight the potential false assurance of using traditional external surrogates to assess tumour motion in patients and the need for ongoing improvement of IGRT technologies.

Study protocol of the LARK (TROG 17.03) clinical trial: a phase II trial investigating the dosimetric impact of Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring

BackgroundStereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR.MethodsForty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured.DiscussionLiver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR.Trial registrationThis trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566.

Improvement of kilovoltage intrafraction monitoring accuracy through gantry angles selection

Kilovoltage intrafraction monitoring (KIM) is a method allowing to precisely infer the tumour trajectory based on cone beam computed tomography (CBCT) 2D-projections. However, its accuracy is deteriorated in the case of highly mobile tumours involving hysteresis. A first adaptation of KIM consisting of a prior amplitude based binning step has been developed in order to minimize the errors of the original model (phase-KIM). In this work, we propose enhanced methods (KIMsub-arc optim and phase-KIMsub-arc optim) to improve the accuracy of KIM and phase-KIM which relies on the selection of the optimal starting CBCT gantry angle. Aiming at demonstrating the interest of our approach, we carried out a simulation study and an experimental study: we compared the accuracy of the conventional versus sub-arc optim methods on simulated realistic tumour motions with amplitudes ranging from 5 to 30 mm in 1 mm increments. The same approach was performed using a lung dynamic phantom generating a 30 mm amplitude sinusoidal motion. The results show that for in-silico simulated motions of 10, 20 and 30 mm amplitude, the three-dimensional root mean square error (3D-RMSE) can be reduced by 0.67 mm, 0.91 mm, 0.94 mm and 0.18 mm, 0.25 mm, 0.28 mm using KIMsub-arc optim and phase-KIMsub-arc optim respectively. Considering all in-silico simulated trajectories, the percentage of errors larger than 1 mm decreases from 21.9% down to 1.6% for KIM (p < 0.001) and from 6.6% down to 1.2% for phase-KIM (p < 0.001). Experimentally, the 3D-RMSE is lowered by 0.5732 mm for KIM and by 0.1 mm for phase-KIM. The percentage of errors larger than 1 mm falls from 39.7% down to 18.5% for KIM and from 23.2% down to 11.1% for phase-KIM. In conclusion, our method efficiently anticipates CBCT gantry angles associated with a significantly better accuracy by using KIM and phase-KIM.

Real-Time Image Guided Ablative Prostate Cancer Radiation Therapy: Results From the TROG 15.01 SPARK Trial

Kilovoltage intrafraction monitoring (KIM) is a novel software platform implemented on standard radiation therapy systems and enabling real-time image guided radiation therapy (IGRT). In a multi-institutional prospective trial, we investigated whether real-time IGRT improved the accuracy of the dose patients with prostate cancer received during radiation therapy. Forty-eight patients with prostate cancer were treated with KIM-guided SABR with 36.25 Gy in 5 fractions. During KIM-guided treatment, the prostate motion was corrected for by either beam gating with couch shifts or multileaf collimator tracking. A dose reconstruction method was used to evaluate the dose delivered to the target and organs at risk with and without real-time IGRT. Primary outcome was the effect of real-time IGRT on dose distributions. Secondary outcomes included patient-reported outcomes and toxicity. Motion correction occurred in ≥1 treatment for 88% of patients (42 of 48) and 51% of treatments (121 of 235). With real-time IGRT, no treatments had prostate clinical target volume (CTV) D98% dose 5% less than planned. Without real-time IGRT, 13 treatments (5.5%) had prostate CTV D98% doses 5% less than planned. The prostate CTV D98% dose with real-time IGRT was closer to the plan by an average of 1.0% (range, -2.8% to 20.3%). Patient outcomes showed no change in the 12-month patient-reported outcomes compared with baseline and no grade ≥3 genitourinary or gastrointestinal toxicities. Real-time IGRT is clinically effective for prostate cancer SABR.

Kilovoltage intrafraction monitoring during normofractionated prostate cancer radiotherapy

PurposeDuring radiotherapy (RT) for prostate cancer (PCa), interfraction and intrafraction movements can lead to decreased target dose coverage and unnecessary over-exposure of organs at risk. New image-guided RT techniques accuracy allows planning target volume (PTV) margins reduction. We aim to assess the feasibility of a kilovoltage intrafraction monitoring (KIM) to track the prostate during RT. Methods and materialsBetween November 2017 and April 2018, 44 consecutive patients with PCa were included in an intrafraction prostate motion study using the Truebeam Auto Beam Hold® tracking system (Varian Medical Systems, United State) triggered by gold fiducials localization on kilovoltage (kV) imaging. A 5-mm PTV was considered. A significant gating event (SGE) was defined as the occurrence of an automatic beam interruption requiring patient repositioning following the detection of one fiducial outside a 5-mm target area around the marker during more than 45seconds. ResultsSix patients could not benefit from the KIM because of technical issues (loss of one fiducial marker=1, hip prosthesis=4, morbid obesity causing table movements=1). The mean rate of SGE per patient was 14±19%, and the fraction average delivery time was increased by 146±86seconds. For a plan of 39 fractions of 2Gy, the additional radiation dose increased by 0.13±0.09Gy. The mean rates of SGE were 2% and 18% (P=0.002) in patients with planned fraction<90 and>90seconds respectively, showing that duration of the session strongly interfered with prostate intrafraction movements. No other significant clinical and technical parameter was correlated with the occurrence of SGE. ConclusionAutomated intrafraction kV imaging can effectively perform autobeam holds due to intrafraction movement of the prostate in the large majority of patients. The additional radiation dose and delivery time are acceptable. This technique may be a cost-effective alternative to electromagnetic transponder guidance.

Simulated multileaf collimator tracking for stereotactic liver radiotherapy guided by kilovoltage intrafraction monitoring: Dosimetric gain and target overdose trends

PurposeTo investigate the potential benefit of multileaf collimator (MLC) tracking guided by kilovoltage intrafraction monitoring (KIM) during stereotactic body radiotherapy (SBRT) in the liver, and to understand trends of target overdose with MLC tracking. MethodsSix liver SBRT patients with 2–3 implanted gold markers received SBRT delivered with volumetric modulated arc therapy (VMAT) in three fractions using daily cone-beam CT setup. The CTV-to-PTV margins were 5 mm in the axial plane and 10 mm in the cranio-caudal directions, and the plans were designed to give minimum target doses of 95% (CTV) and 67% (PTV). The three-dimensional marker trajectory estimated by post-treatment analysis of kV fluoroscopy images acquired throughout treatment delivery was assumed to represent the tumor motion. MLC tracking guided by real-time KIM was simulated. The reduction in CTV D95 (minimum dose to 95% of the clinical target volume) relative to the planned D95 (ΔD95) was compared between actual non-tracking and simulated MLC tracking treatments. ResultsMLC tracking maintained a high CTV dose coverage for all 18 fractions with ΔD95 (mean: 0.2 percentage points (pp), range: −1.7 to 1.9 pp) being significantly lower than for the actual non-tracking treatments (mean: 6.3 pp range: 0.6–16.0 pp) (p = 0.002). MLC tracking of large target motion perpendicular to the MLC leaves created dose artifacts with regions of overdose in the CTV. As a result, the mean dose in spherical volumes centered in the middle of the CTV was on average 2.4 pp (5 mm radius sphere) and 1.3 pp (15 mm radius sphere) higher than planned (p = 0.002). ConclusionsIntrafraction tumor motion can deteriorate the CTV dose of liver SBRT. The planned CTV dose coverage may be restored with KIM-guided MLC tracking. However, MLC tracking may have a tendency to create hotspots in the CTV.

The accuracy and precision of the KIM motion monitoring system used in the multi-institutional TROG 15.01 Stereotactic Prostate Ablative Radiotherapy with KIM (SPARK) trial.

Kilovoltage intrafraction monitoring (KIM) allows for real-time image guidance for tracking tumor motion in six-degrees-of-freedom (6DoF) on a standard linear accelerator. This study assessed the geometric accuracy and precision of KIM used to guide patient treatments in the TROG 15.01 multi-institutional Stereotactic Prostate Ablative Radiotherapywith KIM trial and investigated factors affecting accuracy and precision. Fractions from 44 patients with prostate cancer treated using KIM-guided SBRT were analyzed across four institutions, on two different linear accelerator models and two different beam models (6 MVand 10MV FFF). The geometric accuracy and precision of KIM was assessed from over 33000images (translation) and over 9000 images (rotation) by comparing the real-time measured motion to retrospective kV/MV triangulation. Factors potentially affecting accuracy, including contrast-to-noise ratio (CNR) of kV images and incorrect marker segmentation, were also investigated. The geometric accuracy and precision did not depend on treatment institution, beam model or motion magnitude, but was correlated with gantry angle. The centroid geometric accuracy and precision of the KIM system for SABR prostate treatments was 0.0±0.5, 0.0±0.4 and 0.1±0.3mm for translation, and-0.1±0.6°, -0.1±1.4° and-0.1±1.0° for rotation in the AP, LR and SI directions respectively. Centroid geometric error exceeded 2mm for 0.05% of this dataset. No significant relationship was found between large geometric error and CNR or marker segmentation correlation. This study demonstrated the ability of KIM to locate the prostate with accuracy below other uncertainties in radiotherapy treatments, and the feasibility for KIM to be implemented across multiple institutions.

Kilovoltage Intrafraction Monitoring (KIM) Real-Time Tracking Improves Patient Dose Distributions: Interim Primary Hypothesis Results from the First 20 Patients on the TROG 15.01 Stereotactic Prostate Ablative Radiation Therapy SPARK Trial

Kilovoltage Intrafraction Monitoring (KIM) Real-Time Tracking Improves Patient Dose Distributions: Interim Primary Hypothesis Results from the First 20 Patients on the TROG 15.01 Stereotactic Prostate Ablative Radiation Therapy SPARK Trial

Knowledge-Based Planning as a Real Time Review Quality Assurance Feedback Tool in the TROG 1501 SPARK Trial

Quality assurance (QA) in radiotherapy (RT) clinical trials is essential to ensure protocol compliance, patient safety and trial quality. However, protocol compliance does not necessarily ensure optimal plan generation. This study aimed to demonstrate the feasibility and impact of Knowledge-Based Planning (KBP) feedback as part of the Real Time Review (RTR) process for the TROG 1501 SPARK trial (Stereotactic Prostate Adaptive RT Utilising Kilovoltage Intrafraction Monitoring). A knowledge based dose-volume histogram (DVH) estimation model and automated planning routine were created using 34 SPARK RT plans that had previously been submitted as part of the TROG QA program. The KBP routine was applied to 5 subsequent patients pre-treatment. A feedback report comparing the KBP generated DVH versus the initial plan was collated using a customised script and sent to the site within 24 hours. Centres were asked to review the report and decide whether they would amend their clinical plan. Of the 5 patients, 4 were protocol compliant and 1 case was replanned due to a major protocol deviation. As a result of KBP feedback 2/4 (50%) cases which were originally protocol compliant, were nevertheless replanned. Protocol dose constraints for all 5 cases were calculated and an average for each metric was generated. The mean dose-volume metrics were then compared between the initial submission, resubmission and KBP generated plans. Overall, the rectum, bladder, penile bulb and urethra planning risk volume (PRV) demonstrated that an improved dose-volume relationship could be achieved compared to the initial submission and was implemented in practice for the 3 resubmitted cases. Variable results were observed for the femoral heads, demonstrating a potential dose trade off (Table 1).Abstract TU_36_3254: Table 1Organ at Risk (OAR)ConstraintInitial N=5KBP N=5Initial (Resubmitted) N=3Resubmitted N = 3RectumV18.13Gy ≤50%21.6 (15.5 - 29.3)12.7 (8.8 – 20.9)23.1 (15.5 – 29.3)15.0 (10.8 – 19.2)V32.63Gy ≤5%2.6 (0.4 - 4.9)1.7 (0.0 – 3.9)2.0 (0.4 – 4.6)1.4 (0.1 – 3.1)BladderV18.13Gy ≤50%15.6 (3.5 - 29.6)14.7 (4.4 – 32.2)21.1 (16.1 – 29.6)19.5 (9.4 – 32.4)V32.63Gy ≤10%4.7 (0.9 - 8.5)4.8 (1.0 – 10.4)5.8 (3.6 – 8.5)5.4 (2.0 – 9.1)Urethra PRVD0.1cc ≤38.78Gy37.6 (37.1 - 37.9)37.0 (36.6 – 37.7)37.4 (37.1 – 37.5)37.2 (37.0 – 37.5)Penile BulbD0.1cc ≤36.25Gy13.4 (3.7 - 25.3)12.2 (3.5 – 21.5)14.4 (4.9 – 25.3)12.1 (6.3 – 20.1)Left FemHeadD0.1cc ≤30Gy15.5 (12.1 – 17.3)15.6 (13.6 – 17.5)14.8 (12.1 – 16.5)16.7 (14.3 – 20.0)Right FemHeadD0.1cc ≤30Gy16.2 (14.3 – 18.1)16.8 (14.4 – 20.1)16.2 (14.3 – 18.1)18.4 (13.5 – 21.5) Open table in a new tab KBP feedback was successfully incorporated into the RTR process for the SPARK trial and demonstrated that both improvements to and validation of plan quality for OAR dosimetry could be achieved. Further prospective investigation of the role of KBP in TROG clinical trials is planned.

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

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. 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. 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%/2mm criteria with adaptation for static shifts and periodic motion. 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.

First online real-time evaluation of motion-induced 4D dose errors during radiotherapy delivery.

In radiotherapy, dose deficits caused by tumor motion often far outweigh the discrepancies typically allowed in plan-specific quality assurance (QA). Yet, tumor motion is not usually included in present QA. We here present a novel method for online treatment verification by real-time motion-including four-dimensional (4D) dose reconstruction and dose evaluation and demonstrate its use during stereotactic body radiotherapy (SBRT) delivery with and without MLC tracking. Five volumetric-modulated arc therapy (VMAT) plans were delivered with and without MLC tracking to a motion stage carrying a Delta4 dosimeter. The VMAT plans have previously been used for (nontracking) liver SBRT with intratreatment tumor motion recorded by kilovoltage intrafraction monitoring (KIM). The motion stage reproduced the KIM-measured tumor motions in three dimensions (3D) while optical monitoring guided the MLC tracking. Linac parameters and the target position were streamed to an in-house developed software program (DoseTracker) that performed real-time 4D dose reconstructions and 3%/3mm γ-evaluations of the reconstructed cumulative dose using a concurrently reconstructed planned dose without target motion as reference. Offline, the real-time reconstructed doses and γ-evaluations were validated against 4D dosimeter measurements performed during the experiments. In total, 181,120 dose reconstructions and 5,237 γ-evaluations were performed online and in real time with median computation times of 30ms and 1.2s, respectively. The mean (standard deviation) difference between reconstructed and measured doses was -1.2% (4.9%) for transient doses and -1.5% (3.9%) for cumulative doses. The root-mean-square deviation between reconstructed and measured motion-induced γ-fail rates was 2.0%-point. The mean (standard deviation) sensitivity and specificity of DoseTracker to predict γ-fail rates above a given threshold was 96.8% (3.5%) and 99.2% (0.4%), respectively, for clinically relevant thresholds between 1% and 30% γ-fail rate. Real-time delivery-specific QA during radiotherapy of moving targets was demonstrated for the first time. It allows supervision of treatment accuracy and action on treatment discrepancy within 2s with high sensitivity and specificity.

Automatic online and real-time tumour motion monitoring during stereotactic liver treatments on a conventional linac by combined optical and sparse monoscopic imaging with kilovoltage x-rays (COSMIK)

The purpose of this study was to develop, validate and clinically demonstrate fully automatic tumour motion monitoring on a conventional linear accelerator by combined optical and sparse monoscopic imaging with kilovoltage x-rays (COSMIK).COSMIK combines auto-segmentation of implanted fiducial markers in cone-beam computed tomography (CBCT) projections and intra-treatment kV images with simultaneous streaming of an external motion signal. A pre-treatment CBCT is acquired with simultaneous recording of the motion of an external marker block on the abdomen. The 3-dimensional (3D) marker motion during the CBCT is estimated from the auto-segmented positions in the projections and used to optimize an external correlation model (ECM) of internal motion as a function of external motion. During treatment, the ECM estimates the internal motion from the external motion at 20 Hz. KV images are acquired every 3 s, auto-segmented, and used to update the ECM for baseline shifts between internal and external motion. The COSMIK method was validated using Calypso-recorded internal tumour motion with simultaneous camera-recorded external motion for 15 liver stereotactic body radiotherapy (SBRT) patients. The validation included phantom experiments and simulations hereof for 12 fractions and further simulations for 42 fractions. The simulations compared the accuracy of COSMIK with ECM-based monitoring without model updates and with model updates based on stereoscopic imaging as well as continuous kilovoltage intrafraction monitoring (KIM) at 10 Hz without an external signal. Clinical real-time tumour motion monitoring with COSMIK was performed offline for 14 liver SBRT patients (41 fractions) and online for one patient (two fractions).The mean 3D root-mean-square error for the four monitoring methods was 1.61 mm (COSMIK), 2.31 mm (ECM without updates), 1.49 mm (ECM with stereoscopic updates) and 0.75 mm (KIM).COSMIK is the first combined kV/optical real-time motion monitoring method used clinically online on a conventional accelerator. COSMIK gives less imaging dose than KIM and is in addition applicable when the kV imager cannot be deployed such as during non-coplanar fields.

The first clinical implementation of real-time image-guided adaptive radiotherapy using a standard linear accelerator

PurposeUntil now, real-time image guided adaptive radiation therapy (IGART) has been the domain of dedicated cancer radiotherapy systems. The purpose of this study was to clinically implement and investigate real-time IGART using a standard linear accelerator. Materials/methodsWe developed and implemented two real-time technologies for standard linear accelerators: (1) Kilovoltage Intrafraction Monitoring (KIM) that finds the target and (2) multileaf collimator (MLC) tracking that aligns the radiation beam to the target. Eight prostate SABR patients were treated with this real-time IGART technology. The feasibility, geometric accuracy and the dosimetric fidelity were measured. ResultsThirty-nine out of forty fractions with real-time IGART were successful (95% confidence interval 87–100%). The geometric accuracy of the KIM system was −0.1 ± 0.4, 0.2 ± 0.2 and −0.1 ± 0.6 mm in the LR, SI and AP directions, respectively. The dose reconstruction showed that real-time IGART more closely reproduced the planned dose than that without IGART. For the largest motion fraction, with real-time IGART 100% of the CTV received the prescribed dose; without real-time IGART only 95% of the CTV would have received the prescribed dose. ConclusionThe clinical implementation of real-time image-guided adaptive radiotherapy on a standard linear accelerator using KIM and MLC tracking is feasible. This achievement paves the way for real-time IGART to be a mainstream treatment option.

The accuracy and precision of Kilovoltage Intrafraction Monitoring (KIM) six degree-of-freedom prostate motion measurements during patient treatments

Background and purposeTo perform a quantitative analysis of the accuracy and precision of Kilovoltage Intrafraction Monitoring (KIM) six degree-of-freedom (6DoF) prostate motion measurements during treatments. Material and methodsReal-time 6DoF prostate motion was acquired using KIM for 14 prostate cancer patients (377 fractions). KIM outputs the 6DoF prostate motion, combining 3D translation and 3D rotational motion information relative to its planning position. The corresponding groundtruth target motion was obtained post-treatment based on kV/MV triangulation. The accuracy and precision of the 6DoF KIM motion estimates were calculated as the mean and standard deviation differences compared with the ground-truth. ResultsThe accuracy ± precision of real-time 6DoF KIM−measured prostate motion were 0.2 ± 1.3° for rotations and 0.1 ± 0.5 mm for translations, respectively. The magnitude of KIM-measured motion was well-correlated with the magnitude of ground-truth motion resulting in Pearson correlation coefficients of ≥0.88 in all DoF. ConclusionsThe results demonstrate that KIM is capable of providing the real-time 6DoF prostate target motion during patient treatments with an accuracy ± precision of within 0.2 ± 1.3° and 0.1 ± 0.5 mm for rotation and translation, respectively. As KIM only requires a single X-ray imager, which is available on most modern cancer radiotherapy devices, there is potential for widespread adoption of this technology.

The First Clinical Implementation of Real-time Adaptive Radiation Therapy Using a Standard Linear Accelerator

Until now, real-time adaptive radiotherapy has been the domain of expensive dedicated cancer radiotherapy systems. The purpose of this study was to clinically implement and investigate real-time adaptive radiotherapy using a standard linear accelerator. The hypothesis is that real-time adaptive radiotherapy using a standard linear accelerator is feasible. We led an international consortium of universities and hospitals that developed two real-time image guidance technologies for standard linear accelerators: (1) Kilovoltage Intrafraction Monitoring (KIM) which finds the target position in real-time during radiotherapy and (2) multileaf collimator (MLC) tracking which aligns the radiation beam to the moving target. Together, KIM and MLC tracking enable real-time adaptive radiotherapy using a standard linear accelerator without any additional hardware. These two technologies have been clinically implemented independently, but have not been used together to treat patients. To test the real-time radiotherapy technology, prostate SABR patients enrolled on the TROG 15.01 SPARK (NCT02397317) clinical trial were treated. The feasibility hypothesis was tested using maximum likelihood estimates assuming a binomial distribution of success. The geometric accuracy of the real-time adaptive technology was measured by kV/MV triangulation. The dosimetric impact was assessed by dose reconstruction. Ten of 10 clinical treatments with real-time adaptation using the KIM and MLC tracking technologies were successful. The hypothesis test yielded a probability estimate of 1.0, with 95% confidence intervals of [0.69, 1.0]. For the fraction with the largest observed motion, up to 9mm, the geometric accuracy of the KIM system was -0.19±0.49, 0.17±0.26 and 0.08±0.64 mm in the LR, SI, and AP directions, respectively. The dose reconstruction results showed that real-time adaptation faithfully reproduced the planned dose in the presence of intrafraction motion. For the largest motion fraction, with real-time adaptation 98% of the CTV received the prescription dose; without real-time adaptation only 94% of the CTV would have received the prescription dose. With real-time tracking the rectal V70% increased from 10% planned to 12% delivered; without real-time adaptation the rectal V70% would have been 23%. The clinical implementation of real-time adaptive radiotherapy using a standard linear accelerator using KIM and MLC tracking is feasible. This milestone paves the way for this technology to be tested more broadly, enabling more accurate radiotherapy on widely available linear accelerators, and ushering in the era of real-time radiotherapy as a mainstream treatment option.

Quantifying the accuracy and precision of a novel real-time 6 degree-of-freedom kilovoltage intrafraction monitoring (KIM) target tracking system

Target rotation can considerably impact the delivered radiotherapy dose depending on the tumour shape. More accurate tumour pose during radiotherapy treatment can be acquired through tracking in 6 degrees-of-freedom (6 DoF) rather than in translation only. A novel real-time 6 DoF kilovoltage intrafraction monitoring (KIM) target tracking system has recently been developed. In this study, we experimentally evaluated the accuracy and precision of the 6 DoF KIM implementation. Real-time 6 DoF KIM motion measurements were compared against the ground truth motion retrospectively derived from kV/MV triangulation for a range of lung and prostate tumour motion trajectories as well as for various static poses using a phantom. The accuracy and precision of 6 DoF KIM were calculated as the mean and standard deviation of the differences between KIM and kV/MV triangulation for each DoF, respectively. We found that KIM is able to provide 6 DoF motion with sub-degree and sub-millimetre accuracy and precision for a range of realistic tumour motion.

The first clinical implementation of a real-time six degree of freedom target tracking system during radiation therapy based on Kilovoltage Intrafraction Monitoring (KIM)

PurposeWe present the first clinical implementation of a real-time six-degree of freedom (6DoF) Kilovoltage Intrafraction Monitoring (KIM) system which tracks the cancer target translational and rotational motions during treatment. The method was applied to measure and correct for target motion during stereotactic body radiotherapy (SBRT) for prostate cancer. MethodsPatient: A patient with prostate adenocarcinoma undergoing SBRT with 36.25Gy, delivered in 5 fractions was enrolled in the study. 6DoF KIM technology: 2D positions of three implanted gold markers in each of the kV images (125kV, 10mA at 11Hz) were acquired continuously during treatment. The 2D→3D target position estimation was based on a probability distribution function. The 3D→6DoF target rotation was calculated using an iterative closest point algorithm. The accuracy and precision of the KIM method was measured by comparing the real-time results with kV-MV triangulation. ResultsOf the five treatment fractions, KIM was utilised successfully in four fractions. The intrafraction prostate motion resulted in three couch shifts in two fractions when the prostate motion exceeded the pre-set action threshold of 2mm for more than 5s. KIM translational accuracy and precision were 0.3±0.6mm, −0.2±0.3mm and 0.2±0.7mm in the Left-Right (LR), Superior-Inferior (SI) and Anterior-Posterior (AP) directions, respectively. The KIM rotational accuracy and precision were 0.8°±2.0°, −0.5°±3.3° and 0.3°±1.6° in the roll, pitch and yaw directions, respectively. ConclusionThis treatment represents, to the best of our knowledge, the first time a cancer patient’s tumour position and rotation have been monitored in real-time during treatment. The 6 DoF KIM system has sub-millimetre accuracy and precision in all three translational axes, and less than 1° accuracy and 4° precision in all three rotational axes.

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

Kilovoltage intrafraction monitoring for real-time image guided adaptive radiotherapy reduces total dose for lung SABR

This study presents estimation of typical kV fluoroscopic imaging doses for image-guided real-time adaptive radiotherapy. For a cohort of 10 lung SABR patients the estimated imaging dose to ipsi-lateral lung with real-time adaptation is 9.9–15.1cGy, which is less than the extra lung dose from treatment with potentially larger ITV-based PTV approach.

TH-AB-202-10: Quantifying the Accuracy and Precision of Six Degree-Of-Freedom Motion Estimation for Use in Real-Time Tumor Motion Monitoring During Radiotherapy

Purpose: Kilovoltage intrafraction monitoring (KIM) scheme has been successfully used to simultaneously monitor 3D tumor motion during radiotherapy. Recently, an iterative closest point (ICP) algorithm was implemented in KIM to also measure rotations about three axes, enabling real-time tracking of tumor motion in six degrees-of-freedom (DoF). This study aims to evaluate the accuracy of the six DoF motion estimates of KIM by comparing it with the corresponding motion (i) measured by the Calypso; and (ii) derived from kV/MV triangulation. Methods: (i) Various motions (static and dynamic) were applied to a CIRS phantom with three embedded electromagnetic transponders (Calypso Medical) using a 5D motion platform (HexaMotion) and a rotating treatment couch while both KIM and Calypso were used to concurrently track the phantom motion in six DoF. (ii) KIM was also used to retrospectively estimate six DoF motion from continuous sets of kV projections of a prostate, implanted with three gold fiducial markers (2 patients with 80 fractions in total), acquired during the treatment. Corresponding motion was obtained from kV/MV triangulation using a closed form least squares method based on three markers’ positions. Only the frames where all three markers were present were used in the analysis. The mean differences between the corresponding motion estimates were calculated for each DoF. Results: Experimental results showed that the mean of absolute differences in six DoF phantom motion measured by Calypso and KIM were within 1.1° and 0.7 mm. kV/MV triangulation derived six DoF prostate tumor better agreed with KIM estimated motion with the mean (s.d.) difference of up to 0.2° (1.36°) and 0.2 (0.25) mm for rotation and translation, respectively. Conclusion: These results suggest that KIM can provide an accurate six DoF intrafraction tumor during radiotherapy.