Six-degrees-of-freedom pelvic bone monitoring on 2D kV intrafraction images to enable multi-target tracking for locally advanced prostate cancer.

BACKGROUND: Patients with locally advanced prostate cancer require the prostate and pelvic lymph nodes to be irradiated simultaneously during radiation therapy treatment. However, relative motion between treatment targets decreases dosimetric conformity. Current treatment methods mitigate this error by having large treatment margins and often prioritize the prostate at patient setup at the cost of lymph node coverage. PURPOSE: Treatment accuracy can be improved through real-time multi-target adaptation which requires simultaneous motion monitoring of both the prostate and lymph node targets. This study developed and evaluated an intrafraction pelvic bone motion monitoring method as a surrogate for pelvic lymph node displacement to be combined with prostate motion monitoring to enable multi-target six-degrees-of-freedom (6DoF) tracking using 2D kV projections acquired during treatment. MATERIAL AND METHODS: A method to monitor pelvic bone translation and rotation was developed and retrospectively applied to images from 20 patients treated in the TROG 15.01 Stereotactic Prostate Ablative Radiotherapy with Kilovoltage Intrafraction Monitoring (KIM) trial. The pelvic motion monitoring method performed template matching to calculate the 6DoF position of the pelvis from 2D kV images. The method first generated a library of digitally reconstructed radiographs (DRRs) for a range of imaging angles and pelvic rotations. The normalized 2D cross-correlations were then calculated for each incoming kV image and a subset of DRRs and the DRR with the maximum correlation coefficient was used to estimate the pelvis translation and rotation. Translation of the pelvis in the unresolved direction was calculated using a 3D Gaussian probability estimation method. Prostate motion was measured using the KIM marker tracking method. The pelvic motion monitoring method was compared to the ground truth obtained from a 6DoF rigid registration of the CBCT and CT. RESULTS: The geometric errors of the pelvic motion monitoring method demonstrated sub-mm and sub-degree accuracy and precision in the translational directions ( T LR ${{T}_{{\mathrm{LR}}}}$ , T SI ${{T}_{{\mathrm{SI}}}}$ , T AP ${{T}_{{\mathrm{AP}}}}$ ) and rotational directions ( R LR ${{R}_{{\mathrm{LR}}}}$ , R SI ${{R}_{{\mathrm{SI}}}}$ , R AP ${{R}_{{\mathrm{AP}}}}$ ). The 3D relative displacement between the prostate and pelvic bones exceeded 2, 3, 5, and 7 mm for approximately 66%, 44%, 12%, and 7% of the images. CONCLUSIONS: Accurate intrafraction pelvic bone motion monitoring in 6DoF was demonstrated on 2D kV images, providing a necessary tool for real-time multi-target motion-adapted treatment.

Quantifying dose perturbations in high-risk prostate radiotherapy due to translational and rotational motion of prostate and pelvic lymph nodes.

BACKGROUND: Radiotherapy of the prostate and the pelvic lymph nodes (LN) is a part of the standard of care treatment for high-risk prostate cancer. The independent translational and rotational (i.e., six-degrees-of-freedom, [6DoF]) motion of the prostate and LN target during and between fractions can perturb the dose distribution. However, no standard dose reconstruction method accounting for differential 6DoF target motion is available. PURPOSE: We present a framework for monitoring motion-induced dose perturbations for two independently moving target volumes in 6DoF. The framework was used to determine the dose perturbation for the prostate and the LN target caused by differential 6DoF motion for a cohort of high-risk prostate cancer patients. As a potential first step toward real-time dose-guided high-risk prostate radiotherapy, we furthermore investigated if the dose reconstruction was fast enough for real-time application for both targets. METHODS: Twenty high-risk prostate cancer patients were treated with 3-arc volumetric modulated arc therapy (VMAT). Kilovoltage intrafraction monitoring (KIM) with triggered kilovoltage (kV) images acquired every 3 throughout 7-10 fractions per patient was used for retrospective 6DoF intrafraction prostate motion estimation. The 6DoF interfraction LN motion was determined from a pelvic bone match between the planning CT and a post-treatment cone beam CT (CBCT). Using the retrospectively extracted motion, real-time 6DoF motion-including dose reconstruction was simulated using the in-house developed software DoseTracker. A data stream with the 6DoF target positions and linac parameters was broadcasted at a 3-Hz frequency to DoseTracker. In a continuous loop, DoseTracker calculated the target dose increments including the specified motion and, for comparison, without motion. The motion-induced change in D99.5% for the prostate CTV (ΔD99.5%) and in D98% for the LN CTV (ΔD98%) was calculated using the final cumulative dose of each fraction and averaged over all imaged fractions. The real-time reconstructed dose distribution of DoseTracker was benchmarked against a clinical treatment planning system (TPS) and it was investigated whether the calculation speed was fast enough to keep up with the incoming data stream. RESULTS: Translational motion was largest in cranio-caudal (CC) direction (prostate: [-5.9, +8.4] mm; LN: [-9.9; +11.0] mm) and anterior-posterior (AP) direction (prostate:[-5.6; +6.9] mm; LN: [-9.6; +11.0] mm). The pitch was the largest rotation (prostate: [-22.5; +25.2] deg; LN: [-3.9; +5.5] deg). The prostate CTV ΔD99.5% was [-16.2; +2.5]% for single fractions and [-3.0; +1.7]% when averaged over all imaged fractions. The LN CTV ΔD98% was [-19.8; +1.2]% for single fractions and [-3.1; +0.9]% after averaging. Mean (Standard deviation) absolute dose errors in DoseTracker of 107.8% (Std: 1.9%) for the prostate and 105.5% (Std:1.4%) for the LN were corrected during dose reconstruction by automatically calculated normalization factors. It resulted in accurate calculation of the motion-induced dose errors with relative differences between DoseTracker and TPS dose calculations of -0.1% (Std: 0.5%) (prostate CTV ΔD99.5%) and -0.2% (Std: 0.5%) (LN CTV ΔD98%). The DoseTracker calculation was fast enough to keep up with the incoming inputs for all but two out of 107 184 dose calculations. CONCLUSION: Using the developed framework for dose perturbation monitoring, we found that the differential 6DoF target motion caused substantial dose perturbation for individual fractions, which largely averaged out after several fractions. The framework was shown to provide reliable dose calculations and a sufficiently high-dose reconstruction speed to be applicable in real-time.

Dose perturbations in proton pencil beam delivery investigated by dynamically deforming silicone-based radiochromic dosimeters.

Objective.Proton therapy with pencil beam delivery enables dose distributions that conform tightly to the shape of a target. However, proton therapy dose delivery is sensitive to motion and deformation, which especially occur in the abdominal and thoracic regions. In this study, the dose perturbation caused by dynamic motion with and without gating during proton pencil beam deliveries were investigated using deformable three-dimensional (3D) silicone-based radiochromic dosimeters.Approach.A spread-out Bragg peak formed by four proton spots with different energies was delivered to two dosimeter batches. All dosimeters were cylindrical with a 50 mm diameter and length. The dosimeters were irradiated stationary while uncompressed and during dynamic compression by sinusoidal motion with peak-to-peak amplitudes of 20 mm in one end of the dosimeter and 10 mm in the other end. Motion experiments were made without gating and with gating near the uncompressed position. The entire experiment was video recorded and simulated in a Monte Carlo (MC) program.Main results.The 2%/2 mm gamma index analysis between the dose measurements and the MC dose simulations had pass rates of 86%-94% (first batch) and 98%-99% (second batch). Compared to the static delivery, the dose delivered during motion had gamma pass rates of 99%-100% when employing gating and 68%-87% without gating in the experiments whereas for the MC simulations it was 100% with gating and 66%-82% without gating.Significance.This study demonstrated the ability of using deformable 3D dosimeters to measure dose perturbations in proton pencil beam deliveries caused by dynamic motion and deformation.

Experimental investigation of dynamic real-time rotation-including dose reconstruction during prostate tracking radiotherapy.

BACKGROUND: Hypofractionation in prostate radiotherapy is of increasing interest. Steep dose gradients and a large weight on each individual fraction emphasize the need for motion management. Real-time motion management techniques such as multileaf collimator (MLC) tracking or couch tracking typically adjust for translational motion while rotations remain uncompensated with unknown dosimetric impact. PURPOSE: The purpose of this study is to demonstrate and validate dynamic real-time rotation-including dose reconstruction during radiotherapy experiments with and without MLC and couch tracking. METHODS: Real-time dose reconstruction was performed using the in-house developed software DoseTracker. DoseTracker receives streamed target positions and accelerator parameters during treatment delivery and uses a pencil beam algorithm with water density assumption to reconstruct the dose in a moving target. DoseTracker's ability to reconstruct motion-induced dose errors in a dynamically rotating and translating target was investigated during three different scenarios: (1) no motion compensation and translational motion correction with (2) MLC tracking and (3) couch tracking. In each scenario, dose reconstruction was performed online and in real time during delivery of two dual-arc volumetric-modulated arc therapy prostate plans with a prescribed fraction dose of 7 Gy to the prostate and simultaneous intraprostatic lesion boosts with doses of at least 8 Gy, but up to 10 Gy as long as the organs at risk dose constraints were fulfilled. The plans were delivered to a pelvis phantom that replicated three patient-measured motion traces using a rotational insert with 21 layers of EBT3 film spaced 2.5 mm apart. DoseTracker repeatedly calculated the actual motion-including dose increment and the planned static dose increment since the last calculation in 84 500 points in the film stack. The experiments were performed with a TrueBeam accelerator with MLC and couch tracking based on electromagnetic transponders embedded in the film stack. The motion-induced dose error was quantified as the difference between the final cumulative dose with motion and without motion using the 2D 2%/2 mm γ-failure rate and the difference in dose to 95% of the clinical target volume (CTV ΔD95% ) and the gross target volume (GTV ΔD95% ) as well as the difference in dose to 0.1 cm3 of the urethra, bladder, and rectum (ΔD0.1CC ). The motion-induced errors were compared between dose reconstructions and film measurements. RESULTS: The dose was reconstructed in all calculation points at a mean frequency of 4.7 Hz. The root-mean-square difference between real-time reconstructed and film-measured motion-induced errors was 3.1%-points (γ-failure rate), 0.13 Gy (CTV ΔD95% ), 0.23 Gy (GTV ΔD95% ), 0.19 Gy (urethra ΔD0.1CC ), 0.09 Gy (bladder ΔD0.1CC ), and 0.07 Gy (rectum ΔD0.1CC ). CONCLUSIONS: In a series of phantom experiments, online real-time rotation-including dose reconstruction was performed for the first time. The calculated motion-induced errors agreed well with film measurements. The dose reconstruction provides a valuable tool for monitoring dose delivery and investigating the efficacy of advanced motion-compensation techniques in the presence of translational and rotational motion.

Real-time dose-guidance in radiotherapy: Proof of principle.

PURPOSE: The outcome of radiotherapy is a direct consequence of the dose delivered to the patient. Yet image-guidance and motion management to date focus on geometrical considerations as a practical surrogate for dose. Here, we propose real-time dose-guidance realized through continuous motion-including dose reconstructions and demonstrate this new concept in simulated liver stereotactic body radiotherapy (SBRT) delivery. MATERIALS AND METHODS: During simulated liver SBRT delivery, in-house developed software performed real-time motion-including reconstruction of the tumor dose delivered so far and continuously predicted the remaining fraction tumor dose. The total fraction dose was estimated as the sum of the delivered and predicted doses, both with and without the emulated couch correction that maximized the predicted final CTV D95% (minimum dose to 95% of the clinical target volume). Dose-guided treatments were simulated for 15 liver SBRT patients previously treated with tumor motion monitoring, using both sinusoidal tumor motion and the actual patient-measured motion. A dose-guided couch correction was triggered if it improved the predicted final CTV D95% with 3, 4 or 5 %-points. The final CTV D95% of the dose-guidance strategy was compared with simulated treatments using geometry guided couch corrections (Wilcoxon signed-rank test). RESULTS: Compared to geometry guidance, dose-guided couch corrections improved the median CTV D95% with 0.5-1.5 %-points (p < 0.01) for sinusoidal motions and with 0.9 %-points (p < 0.01, 3 %-points trigger threshold), 0.5 %-points (p = 0.03, 4 %-points threshold) and 1.2 %-points (p = 0.09, 5 %-points threshold) for patient-measured tumor motion. CONCLUSION: Real-time dose-guidance was proposed and demonstrated to be superior to geometrical adaptation in liver SBRT simulations.

First experimental evaluation of multi-target multileaf collimator tracking during volumetric modulated arc therapy for locally advanced prostate cancer.

PURPOSE: Locally advanced and oligometastatic cancer patients require radiotherapy treatment to multiple independently moving targets. There is no existing commercial solution that can simultaneously track and treat multiple targets. This study experimentally implemented and evaluated a real-time multi-target tracking system for locally advanced prostate cancer. METHODS: Real-time multi-target MLC tracking was integrated with 3D x-ray image guidance on a standard linac. Three locally advanced prostate cancer treatment plans were delivered to a static lymph node phantom and dynamic prostate phantom that reproduced three prostate trajectories. Treatments were delivered using multi-target MLC tracking, single-target MLC tracking, and no tracking. Doses were measured using Gafchromic film placed in the dynamic and static phantoms. Dosimetric error was quantified by the 2%/2 mm gamma failure rate. Geometric error was evaluated as the misalignment between target and aperture positions. The multi-target tracking system latency was measured. RESULTS: The mean (range) gamma failure rates for the prostate and lymph nodes, were 18.6% (5.2%, 28.5%) and 7.5% (1.1%, 13.7%) with multi-target tracking, 7.9% (0.7%, 15.4%) and 37.8% (18.0%, 57.9%) with single-target tracking, and 38.1% (0.6%, 75.3%) and 37.2% (29%, 45.3%) without tracking. Multi-target tracking had the lowest geometric error with means and standard deviations within 0.2 ± 1.5 for the prostate and 0.0 ± 0.3 mm for the lymph nodes. The latency was 730 ± 20 ms. CONCLUSION: This study presented the first experimental implementation of multi-target tracking to independently track prostate and lymph node displacement during VMAT. Multi-target tracking reduced dosimetric and geometric errors compared to single-target tracking and no tracking.

Adapting to the motion of multiple independent targets using multileaf collimator tracking for locally advanced prostate cancer: Proof of principle simulation study.

PURPOSE: For patients with locally advanced cancer, multiple targets are treated simultaneously with radiotherapy. Differential motion between targets can compromise the treatment accuracy, yet there are currently no methods able to adapt to independent target motion. This study developed a multileaf collimator (MLC) tracking algorithm for differential motion adaptation and evaluated it in simulated treatments of locally advanced prostate cancer. METHODS: A multi-target MLC tracking algorithm was developed that consisted of three steps: (a) dividing the MLC aperture into two possibly overlapping sections assigned to the prostate and lymph nodes, (b) calculating the ideally shaped MLC aperture as a union of the individually translated sections, and (c) fitting the MLC positions to the ideal aperture shape within the physical constraints of the MLC leaves. The multi-target tracking method was evaluated and compared with two existing motion management methods: single-target tracking and no tracking. Treatment simulations of six locally advanced prostate cancer patients with three prostate motion traces were performed for all three motion adaptation methods. The geometric error for each motion adaptation method was calculated using the area of overexposure and underexposure of each field. The dosimetric error was estimated by calculating the dose delivered to the prostate, lymph nodes, bladder, rectum, and small bowel using a motion-encoded dose reconstruction method. RESULTS: Multi-target MLC tracking showed an average improvement in geometric error of 84% compared to single-target tracking, and 83% compared to no tracking. Multi-target tracking maintained dose coverage to the prostate clinical target volume (CTV) D98% and planning target volume (PTV) D95% to within 4.8% and 3.9% of the planned values, compared to 1.4% and 0.7% with single-target tracking, and 20.4% and 31.8% with no tracking. With multi-target tracking, the node CTV D95%, PTV D90%, and gross tumor volume (GTV) D95% were within 0.3%, 0.6%, and 0.3% of the planned values, compared to 9.1%, 11.2%, and 21.1% for single-target tracking, and 0.8%, 2.0%, and 3.2% with no tracking. The small bowel V57% was maintained within 0.2% to the plan using multi-target tracking, compared to 8% and 3.5% for single-target tracking and no tracking, respectively. Meanwhile, the bladder and rectum V50% increased by up to 13.6% and 5.2%, respectively, using multi-target tracking, compared to 2.7% and 1.9% for single-target tracking, and 11.2% and 11.5% for no tracking. CONCLUSIONS: A multi-target tracking algorithm was developed and tracked the prostate and lymph nodes independently during simulated treatments. As the algorithm optimizes for target coverage, tracking both targets simultaneously may increase the dose delivered to the organs at risk.

Is multileaf collimator tracking or gating a better intrafraction motion adaptation strategy? An analysis of the TROG 15.01 stereotactic prostate ablative radiotherapy with KIM (SPARK) trial.

PURPOSE: Stereotactic Ablative Radiotherapy (SABR) has recently emerged as a favourable treatment option for prostate cancer patients. With higher doses delivered over fewer fractions, motion adaptation is a requirement for accurate delivery of SABR. This study compared the efficacy of multileaf collimator (MLC) tracking vs. gating as a real-time motion adaptation strategy for prostate SABR patients enrolled in a clinical trial. METHODS: Forty-four prostate cancer patients treated over five fractions in the TROG 15.01 SPARK trial were analysed in this study. Forty-nine fractions were treated using MLC tracking and 166 fractions were treated using beam gating and couch shifts. A time-resolved motion-encoded dose reconstruction method was used to evaluate the dose delivered using each motion adaptation strategy and compared to an estimation of what would have been delivered with no motion adaptation strategy implemented. RESULTS: MLC tracking and gating both delivered doses closer to the plan compared to when no motion adaptation strategy was used. Differences between MLC tracking and gating were small with differences in the mean discrepancy from the plan of -0.3% (CTV D98%), 1.4% (CTV D2%), 0.4% (PTV D95%), 0.2% (rectum V30Gy) and 0.0% (bladder V30Gy). On average, 0.5 couch shifts were required per gated fractions with a mean interruption duration of 1.8 ± 2.6 min per fraction treated using gating. CONCLUSION: Both MLC tracking and gating were effective strategies at improving the accuracy of the dose delivered to the target and organs at risk. While dosimetric performance was comparable, gating resulted in interruptions to treatment. CLINICAL TRIAL REGISTRATION NUMBER: NCT02397317.

Isotoxic dose prescription level strategies for stereotactic liver radiotherapy: the price of dose uniformity.

Introduction: To find the optimal dose prescription strategy for liver SBRT, this study investigated the tradeoffs between achievable target dose and healthy liver dose for a range of isotoxic uniform and non-uniform prescription level strategies.Material and methods: Nine patients received ten liver SBRT courses with intrafraction motion monitoring during treatment. After treatment, five VMAT treatment plans were made for each treatment course. The PTV margin was 5 mm (left-right, anterior-posterior) and 10 mm (cranio-caudal). All plans had a mean CTV dose of 56.25 Gy in three fractions, while the PTV was covered by 50%, 67%, 67 s% (steep dose gradient outside CTV), 80%, and 95% of this dose, respectively. The 50%, 67 s%, 80%, and 95% plans were then renormalized to be isotoxic with the standard 67% plan according to a Lyman-Kutcher-Burman normal tissue complication probability model for radiation induced liver disease. The CTV D98 and mean dose of the iso-toxic plans were calculated both without and with the observed intrafraction motion, using a validated method for motion-including dose reconstruction.Results: Under isotoxic conditions, the average [range] mean CTV dose per fraction decreased gradually from 21.2 [20.5-22.7] Gy to 15.5 [15.0-16.6] Gy and the D98 dose per fraction decreased from 20.4 [19.7-21.7] Gy to 15.0 [14.5-15.5] Gy, as the prescription level to the PTV rim was increased from 50% to 95%. With inclusion of target motion the mean CTV dose was 20.5 [16.5-22.5] Gy (50% PTV rim dose) and 15.4 [13.9-16.7] Gy (95% rim dose) while D98 was 17.8 [7.4-20.6] Gy (50% rim dose) and 14.6 [8.8-15.7] Gy (95% rim dose).Conclusion: Requirements of a uniform PTV dose come at the price of excess normal tissue dose. A non-uniform PTV dose allows increased CTV mean dose at the cost of robustness toward intrafraction motion. The increase in planned CTV dose by non-uniform prescription outbalanced the dose deterioration caused by motion.

Dose-response of deformable radiochromic dosimeters for spot scanning proton therapy.

Intrafractional motion and deformation influence proton therapy delivery for tumours in the thorax, abdomen and pelvis. This study aimed to test the dose-response of a compressively strained three-dimensional silicone-based radiochromic dosimeter during proton beam delivery. The dosimeter was read-out in its relaxed state using optical computed tomography and calibrated for the linear energy transfer, based on Monte Carlo simulations. A three-dimensional gamma analysis showed a 99.3% pass rate for 3%/3 mm and 93.9% for 2%/2 mm, for five superimposed measurements using deformation-including Monte Carlo dose calculations as reference. We conclude that the dosimeter's dose-response is unaffected by deformations.

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

PURPOSE: To 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. METHODS: Six 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. RESULTS: MLC 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). CONCLUSIONS: Intrafraction 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.

Setup strategies and uncertainties in esophageal radiotherapy based on detailed intra- and interfractional tumor motion mapping.

BACKGROUND AND PURPOSE: Detailed knowledge of target motion is important for improved accuracy and decreased toxicity of esophageal cancer radiotherapy. This study uses the 3D trajectories of implanted markers during setup CBCT scans to investigate the intra- and interfractional tumor motion in esophageal cancer radiotherapy. MATERIAL AND METHODS: For 21 esophageal cancer patients with implanted fiducial markers, 60-s 3D marker trajectories were estimated from the 2D marker positions in the projections of daily setup CBCT scans by a probability-based method. The motion was separated into respiratory and cardiac components by frequency analysis and motion magnitude (2nd-98th percentile) was extracted for each marker. The mean motion was calculated over all markers. The daily mean setup interfraction error for bony-anatomy and soft-tissue setup was used to estimate the margin accounting for interfractional motion. RESULTS: A total of 1036 marker trajectories were extracted using 427 CBCT scans and 63 markers. The mean motion magnitude over all markers was 2.9 mm (left-right (LR)), 8.8 mm (cranio-caudal (CC)) and 4.1 mm (anterior-posterior (AP)) for the full motion during CBCT acquisition with mean magnitudes of 2.7 mm (LR), 8.4 mm (CC) and 3.5 mm (AP) for respiratory motion and 1.0 mm (LR), 1.5 mm (CC) and 1.4 mm (AP) for cardiac motion. Substantial daily marker shifts relative to bones resulted in margins of 8.9 mm (LR), 9.5 mm (CC), and 7.3 mm (AP). Soft-tissue based setup in and near the CTV combined with rescanning of patients with anatomical changes reduced the margins to 6.9 mm (LR), 6.8 mm (CC), and 5.6 mm (AP). CONCLUSIONS: Esophageal tumor motion was mapped with unprecedented detail throughout the radiotherapy course. Respiratory motion dominated and was largest in the CC direction. Soft-tissue matching and an adaptive strategy reduced interfractional margins by 2-3 mm compared to bony-anatomy matching.

Validation of fast motion-including dose reconstruction for proton scanning therapy in the liver.

This study validates a method of fast motion-including dose reconstruction for proton pencil beam scanning in the liver. The method utilizes a commercial treatment planning system (TPS) and calculates the delivered dose for any translational 3D target motion. Data from ten liver patients previously treated with photon radiotherapy with intrafraction tumour motion monitoring were used. The dose reconstruction method utilises an in-house developed program to incorporate beam's-eye-view tumour motion by shifting each spot in the opposite direction of the tumour and in-depth motion as beam energy changes for each spot. The doses are then calculated on a single CT phase in the TPS. Two aspects of the dose reconstruction were assessed: (1) The accuracy of reconstruction, by comparing dose reconstructions created using 4DCT motion with ground truth doses obtained by calculating phase specific doses in all 4DCT phases and summing up these partial doses. (2) The error caused by assuming 4DCT motion, by comparing reconstructions with 4DCT motion and actual tumour motion. The CTV homogeneity index (HI) and the root-mean-square (rms) dose error for all dose points receiving >70%, >80% and >90% of the prescribed dose were calculated. The dose reconstruction resulted in mean (range) absolute CTV HI errors of 1.0% (0.0-3.0)% and rms dose errors of 2.5% (1.0%-5.3%), 2.1% (0.9%-4.5%), and 1.8% (0.7%-3.7%) for >70%, >80% and >90% doses, respectively, when compared with the ground truth. The assumption of 4DCT motion resulted in mean (range) absolute CTV HI errors of 5.9% (0.0-15.0)% and rms dose errors of 6.3% (3.9%-12.6%), 5.9% (3.4%-12.5%), and 5.4% (2.6%-12.1%) for >70%, >80% and >90% doses, respectively. The investigated method allows tumour dose reconstruction with the actual tumour motion and results in significantly smaller dose errors than those caused by assuming that motion at treatment is identical to the 4DCT motion.

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

PURPOSE: 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. METHODS: 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%/3 mm 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. RESULTS: In total, 181,120 dose reconstructions and 5,237 γ-evaluations were performed online and in real time with median computation times of 30 ms and 1.2 s, 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. CONCLUSIONS: 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 2 s with high sensitivity and specificity.

Review of Real-Time 3-Dimensional Image Guided Radiation Therapy on Standard-Equipped Cancer Radiation Therapy Systems: Are We at the Tipping Point for the Era of Real-Time Radiation Therapy?

PURPOSE: To review real-time 3-dimensional (3D) image guided radiation therapy (IGRT) on standard-equipped cancer radiation therapy systems, focusing on clinically implemented solutions. METHODS AND MATERIALS: Three groups in 3 continents have clinically implemented novel real-time 3D IGRT solutions on standard-equipped linear accelerators. These technologies encompass kilovoltage, combined megavoltage-kilovoltage, and combined kilovoltage-optical imaging. The cancer sites treated span pelvic and abdominal tumors for which respiratory motion is present. For each method the 3D-measured motion during treatment is reported. After treatment, dose reconstruction was used to assess the treatment quality in the presence of motion with and without real-time 3D IGRT. The geometric accuracy was quantified through phantom experiments. A literature search was conducted to identify additional real-time 3D IGRT methods that could be clinically implemented in the near future. RESULTS: The real-time 3D IGRT methods were successfully clinically implemented and have been used to treat more than 200 patients. Systematic target position shifts were observed using all 3 methods. Dose reconstruction demonstrated that the delivered dose is closer to the planned dose with real-time 3D IGRT than without real-time 3D IGRT. In addition, compromised target dose coverage and variable normal tissue doses were found without real-time 3D IGRT. The geometric accuracy results with real-time 3D IGRT had a mean error of <0.5 mm and a standard deviation of <1.1 mm. Numerous additional articles exist that describe real-time 3D IGRT methods using standard-equipped radiation therapy systems that could also be clinically implemented. CONCLUSIONS: Multiple clinical implementations of real-time 3D IGRT on standard-equipped cancer radiation therapy systems have been demonstrated. Many more approaches that could be implemented were identified. These solutions provide a pathway for the broader adoption of methods to make radiation therapy more accurate, impacting tumor and normal tissue dose, margins, and ultimately patient outcomes.

A Prospective Cohort Study of Gated Stereotactic Liver Radiation Therapy Using Continuous Internal Electromagnetic Motion Monitoring.

PURPOSE: Intrafraction motion can compromise the treatment accuracy in liver stereotactic body radiation therapy (SBRT). Respiratory gating can improve treatment delivery; however, gating based on external motion surrogates is inaccurate. The present study reports the use of Calypso-based internal electromagnetic motion monitoring for gated liver SBRT. METHODS AND MATERIALS: Fifteen patients were included in a study of 3-fraction respiratory gated liver SBRT guided by 3 implanted electromagnetic transponders. The planning target volume was created by a 5-mm axial and 7-mm (n = 12) or 10-mm (n = 3) craniocaudal expansion of the clinical target volume (CTV) and covered with 67% of the prescribed CTV mean dose. Treatment was gated to the end-exhale phase of the respiratory cycle with beam-on when the target deviated <3 mm (left-right/anteroposterior) and 4 mm (craniocaudal) from the planned position, according to the monitored (25-Hz) transponder centroid position. The couch was adjusted remotely if baseline drifts >1 to 2 mm occurred. Log files of transponder motion were used to determine the geometric error and reconstruct the delivered CTV dose in the actual gated treatments and in simulated nongated treatments. RESULTS: No severe side effects were observed in relation to transponder implantation. All 45 treatment fractions were successfully guided using the Calypso system. The mean number of couch corrections during each gated fraction was 2.8 (range 0-7). The mean duty cycle during gated treatment was 62.5% (range 29.1%-84.9%). Without gating, the mean 3-dimensional geometric error during a fraction would have been 5.4 mm (range 2.7-12.1). Gating reduced this error to 2.0 mm (range 1.2-3.0). The patient mean reduction in minimum dose to 95% of the CTV relative to the planned dose was 6.0 percentage points (range 0.7-22.0) without gating and 0.8 percentage point (range 0.2-2.0) with gating. CONCLUSIONS: Gating using internal motion monitoring was successfully applied for liver SBRT. It markedly improved the geometric and dosimetric accuracy compared with nongated standard treatment.

Electromagnetic-Guided MLC Tracking Radiation Therapy for Prostate Cancer Patients: Prospective Clinical Trial Results.

PURPOSE: To report on the primary and secondary outcomes of a prospective clinical trial of electromagnetic-guided multileaf collimator (MLC) tracking radiation therapy for prostate cancer. METHODS AND MATERIALS: Twenty-eight men with prostate cancer were treated with electromagnetic-guided MLC tracking with volumetric modulated arc therapy. A total of 858 fractions were delivered, with the dose per fraction ranging from 2 to 13.75 Gy. The primary outcome was feasibility, with success determined if >95% of fractions were successfully delivered. The secondary outcomes were (1) the improvement in beam-target geometric alignment, (2) the improvement in dosimetric coverage of the prostate and avoidance of critical structures, and (3) no acute grade ≥3 genitourinary or gastrointestinal toxicity. RESULTS: All 858 planned fractions were successfully delivered with MLC tracking, demonstrating the primary outcome of feasibility (P < .001). MLC tracking improved the beam-target geometric alignment from 1.4 to 0.90 mm (root-mean-square error). MLC tracking improved the dosimetric coverage of the prostate and reduced the daily variation in dose to critical structures. No acute grade ≥3 genitourinary or gastrointestinal toxicity was observed. CONCLUSIONS: Electromagnetic-guided MLC tracking radiation therapy for prostate cancer is feasible. The patients received improved geometric targeting and delivered dose distributions that were closer to those planned than they would have received without electromagnetic-guided MLC tracking. No significant acute toxicity was observed.

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.

Online 4D ultrasound guidance for real-time motion compensation by MLC tracking.

PURPOSE: With the trend in radiotherapy moving toward dose escalation and hypofractionation, the need for highly accurate targeting increases. While MLC tracking is already being successfully used for motion compensation of moving targets in the prostate, current real-time target localization methods rely on repeated x-ray imaging and implanted fiducial markers or electromagnetic transponders rather than direct target visualization. In contrast, ultrasound imaging can yield volumetric data in real-time (3D + time = 4D) without ionizing radiation. The authors report the first results of combining these promising techniques-online 4D ultrasound guidance and MLC tracking-in a phantom. METHODS: A software framework for real-time target localization was installed directly on a 4D ultrasound station and used to detect a 2 mm spherical lead marker inside a water tank. The lead marker was rigidly attached to a motion stage programmed to reproduce nine characteristic tumor trajectories chosen from large databases (five prostate, four lung). The 3D marker position detected by ultrasound was transferred to a computer program for MLC tracking at a rate of 21.3 Hz and used for real-time MLC aperture adaption on a conventional linear accelerator. The tracking system latency was measured using sinusoidal trajectories and compensated for by applying a kernel density prediction algorithm for the lung traces. To measure geometric accuracy, static anterior and lateral conformal fields as well as a 358° arc with a 10 cm circular aperture were delivered for each trajectory. The two-dimensional (2D) geometric tracking error was measured as the difference between marker position and MLC aperture center in continuously acquired portal images. For dosimetric evaluation, VMAT treatment plans with high and low modulation were delivered to a biplanar diode array dosimeter using the same trajectories. Dose measurements with and without MLC tracking were compared to a static reference dose using 3%/3 mm and 2%/2 mm γ-tests. RESULTS: The overall tracking system latency was 172 ms. The mean 2D root-mean-square tracking error was 1.03 mm (0.80 mm prostate, 1.31 mm lung). MLC tracking improved the dose delivery in all cases with an overall reduction in the γ-failure rate of 91.2% (3%/3 mm) and 89.9% (2%/2 mm) compared to no motion compensation. Low modulation VMAT plans had no (3%/3 mm) or minimal (2%/2 mm) residual γ-failures while tracking reduced the γ-failure rate from 17.4% to 2.8% (3%/3 mm) and from 33.9% to 6.5% (2%/2 mm) for plans with high modulation. CONCLUSIONS: Real-time 4D ultrasound tracking was successfully integrated with online MLC tracking for the first time. The developed framework showed an accuracy and latency comparable with other MLC tracking methods while holding the potential to measure and adapt to target motion, including rotation and deformation, noninvasively.