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.

Inter- and intra-fraction geometric errors in daily image-guided radiotherapy of free-breathing breast cancer patients measured with continuous portal imaging.

BACKGROUND: Daily image-guided radiotherapy (IGRT) using two orthogonal setup images may be inaccurate for breast cancer patients treated in free breathing because the setup images may capture the patient in a breathing phase that is not representative of the mean anatomy. The aim of this study was to quantify the setup errors in breast radiotherapy after image-guided setup correction based on two orthogonal setup images acquired in free breathing. METHODS AND MATERIALS: For 16 breast cancer patients with daily image-pair based IGRT, continuous portal imaging (7.5 Hz) were acquired at each treatment fraction during the delivery of the two tangential fields. For each portal image, the chest wall position relative to the planned position was determined in the imager direction orthogonal to the cranio-caudal direction. It yielded the time resolved setup error in this direction throughout the 16 treatment courses. RESULTS: The mean absolute setup error exceeded 5 mm in 0.9% (first field) and 1.8% (last field) of the treatments. The group mean error (M) and the standard deviations of the random (σ) and systematic (Σ) setup errors were M=-0.7 mm, Σ=1.1 mm, σ=1.5 mm (first field) and M=-0.2 mm, Σ=1.4 mm, σ=1.7 mm (last field). The negative sign of M indicates that less lung than planned was included in the treatment fields. Intra-field peak-to-peak chest wall motion amplitudes were patient dependent with patient mean values of 2.0±0.7 mm [range 1.1-3.2 mm]. The largest observed intra-field motion amplitude was 8 mm. CONCLUSION: Image-guided setup based on orthogonal planar images acquired in free breathing without synchronization with the respiratory phase was found to result in accurate tangential breast radiotherapy with only few outliers.

Clinical use of iterative 4D-cone beam computed tomography reconstructions to investigate respiratory tumor motion in lung cancer patients.

BACKGROUND: Cone beam computed tomography (CBCT) provides means for respiratory resolved volumetric imaging of the thorax. However, merely sorting the acquired projections into respiratory phases and performing a series of conventional three-dimensional (3D) reconstructions lead to clinically prohibitive reconstruction artifacts. This problem can be mitigated by iterative 4D reconstruction. We present a clinical evaluation of two iterative 4D-CBCT reconstruction algorithms during stereotactic body radiation therapy. MATERIAL AND METHODS: Two types of iterative 4D-CBCT reconstructions were performed utilizing: 1) total variation (TV) minimization; and 2) optical flow (OF) based deformable registration between phases. The reconstructions were initially evaluated on a lung phantom with a moveable target insert. Subsequently, 4D-CBCT reconstructions were performed for 19 patients on 2-3 CBCT projection datasets previously acquired for conventional 3D-CBCT reconstruction (∼650 half-fan projections per scan in a full one-minute gantry rotation). The 4D reconstructions were imported into a treatment planning system, where the gross tumor volume (GTV) was delineated and used to extract the tumor motion amplitude. RESULTS: For both phantom and patient scans, the iterative 4D-CBCT reconstructions had sufficient quality for GTV delineation when the breathing period was faster than 3.5 seconds (15 of 19 patients), but not for slower breathing periods (4 patients). The 3D tumor motion amplitude for the patients was significantly lower (p = 10(-6), Wilcoxon signed rank test) in the OF reconstructions (mean 4.0 mm) than in the TV reconstructions (mean 5.3 mm). CONCLUSION: TV and OF iterative 4D-CBCT reconstruction of the thorax in a lung phantom and for 19 patients was demonstrated from standard CBCT scans and used to estimate the daily lung tumor motion.

A method for selection of beam angles robust to intra-fractional motion in proton therapy of lung cancer.

BACKGROUND: Proton therapy offers the potential for sparing the normal tissue surrounding the target. However, due to well-defined proton ranges around the Bragg peak, dose deposition is more sensitive to changes in the water equivalent path length (WEPL) than with photons. In this study, we assess WEPL variations caused by breathing-induced motion for all possible beam angles in a series of lung cancer patients. By studying the association between measures for WEPL variation and breathing-induced target dose degradation we aimed to develop and explore a tool to identify beam angles that are robust to patient-specific patterns of intra-fractional motion. MATERIAL AND METHODS: Using four-dimensional computed tomography (4DCT) images of three lung cancer patients we evaluated the impact of the WEPL changes on target dose coverage for a series of coplanar single-beam plans. The plans were optimised for the internal target volume (ITV) at the maximum intensity projection (MIP) CT for every 3° gantry interval. The plans were transferred to the ten 4DCT phases and the average reduction in ITV V95 over the ten phases, relative to the original MIP CT calculation, was quantified. The target dose reduction was associated with the mean difference between the WEPL and the phase-averaged WEPL computed for all beam rays across all possible gantry-couch angle combinations. RESULTS: The gantry-couch angle maps showed areas of both high and low WEPL variation, with overall quite similar patterns yet with individual differences reflecting differences in tumour position and breathing-induced motion. The coplanar plans showed a strong association between WEPL changes and ITV V95 reduction, with a correlation coefficient ranging between 0.92 and 0.98 for the three patients (p < 0.01). CONCLUSION: We have presented a 4DCT-based method to quantify WEPL changes during the breathing cycle. The method identified proton field gantry-couch angle combinations that were either sensitive or robust to WEPL changes. WEPL variations along the beam path were associated with target under-dosage.

Time-resolved dose reconstruction by motion encoding of volumetric modulated arc therapy fields delivered with and without dynamic multi-leaf collimator tracking.

BACKGROUND: Organ motion during treatment delivery in radiotherapy (RT) may lead to deterioration of the planned dose, but can be mitigated by dynamic multi-leaf collimator (DMLC) tracking. The purpose of this study was to implement and experimentally validate a method for time-resolved motion including dose reconstruction for volumetric modulated arc therapy (VMAT) treatments delivered with and without DMLC tracking. MATERIAL AND METHODS: Tracking experiments were carried out on a linear accelerator (Trilogy, Varian) with a prototype DMLC tracking system. A motion stage carrying a biplanar dosimeter phantom (Delta4PT, Scandidos) reproduced eight representative clinical tumor trajectories (four lung, four prostate). For each trajectory, two single-arc 6 MV VMAT treatments with low and high modulation were delivered to the moving phantom with and without DMLC tracking. An existing in-house developed program that adds target motion to treatment plans was extended with the ability to split an arc plan into any number of sub-arcs, allowing the calculated dose for different parts of the treatment to be examined individually. For each VMAT sub-arc, reconstructed and measured doses were compared using dose differences and 3%/3 mm γ-tests. RESULTS: For VMAT sub-arcs the reconstructed dose distributions had a mean root-mean-square (rms) dose difference of 2.1% and mean γ failure rate of 2.0% when compared with the measured doses. For final accumulated doses the mean rms dose difference was 1.6% and the γ failure rate was 0.7%. CONCLUSION: The time-resolved motion including dose reconstruction was experimentally validated for complex tracking and non-tracking treatments with patient-measured tumor motion trajectories. The reconstructed dose will be of high value for evaluation of treatment plan robustness facing organ motion and adaptive RT.

Variations in magnitude and directionality of respiratory target motion throughout full treatment courses of stereotactic body radiotherapy for tumors in the liver.

PURPOSE: To investigate the stability of target motion amplitude and motion directionality throughout full stereotactic body radiotherapy (SBRT) treatments of tumors in the liver. MATERIAL AND METHODS: Ten patients with gold markers implanted in the liver received 11 courses of 3-fraction SBRT on a conventional linear accelerator. A four-dimensional computed tomography (4DCT) scan was obtained for treatment planning. The time-resolved marker motion was determined throughout full treatment field delivery using the kV and MV imagers of the accelerator. The motion amplitude and motion directionality of all individual respiratory cycles were determined using principal component analysis (PCA). The variations in motion amplitude and directionality within the treatment courses and the difference from the motion in the 4DCT scan were determined. RESULTS: The patient mean (± 1 standard deviation) peak-to-peak 3D motion amplitude of individual respiratory cycles during a treatment course was 7.9 ± 4.1 mm and its difference from the 4DCT scan was -0.8 ± 2.5 mm (max, 6.6 mm). The mean standard deviation of 3D respiratory cycle amplitude within a treatment course was 2.0 ± 1.6 mm. The motion directionality of individual respiratory cycles on average deviated 4.6 ± 1.6° from the treatment course mean directionality. The treatment course mean motion directionality on average deviated 7.6 ± 6.5° from the directionality in the 4DCT scan. A single patient-specific oblique direction in space explained 97.7 ± 1.7% and 88.3 ± 10.1% of all positional variance (motion) throughout the treatment courses, excluding and including baseline shifts between treatment fields, respectively. CONCLUSION: Due to variable breathing amplitudes a single 4DCT scan was not always representative of the mean motion amplitude during treatment. However, the motion was highly directional with a fairly stable direction throughout treatment, indicating a potential for more optimal individualized motion margins aligned to the preferred direction of motion.

Dosimetric verification of complex radiotherapy with a 3D optically based dosimetry system: dose painting and target tracking.

BACKGROUND: The increasing complexity of radiotherapy (RT) has motivated research into three-dimensional (3D) dosimetry. In this study we investigate the use of 3D dosimetry with polymerizing gels and optical computed tomography (optical CT) as a verification tool for complex RT: dose painting and target tracking. MATERIALS AND METHODS: For the dose painting studies, two dosimeters were irradiated with a seven-field intensity modulated radiotherapy (IMRT) plan with and without dose prescription based on a hypoxia image dataset of a head and neck patient. In the tracking experiments, two dosimeters were irradiated with a volumetric modulated arc therapy (VMAT) plan with and without clinically measured prostate motion and a third with both motion and target tracking. To assess the performance, 3D gamma analyses were performed between measured and calculated stationary dose distributions. RESULTS: Gamma pass-rates of 95.3% and 97.3% were achieved for the standard and dose-painted IMRT plans. Gamma pass-rates of 91.4% and 54.4% were obtained for the stationary and moving dosimeter, respectively, while tracking increased the pass-rate for the moving dosimeter to 90.4%. CONCLUSIONS: This study has shown that the 3D dosimetry system can reproduce and thus verify complex dose distributions, also when influenced by motion.

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.

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.

Robust automatic segmentation of multiple implanted cylindrical gold fiducial markers in cone-beam CT projections.

PURPOSE: Implanted fiducial markers, which are used to correct for day-to-day variations, may potentially also be used to correct for intrafraction motion measurements. However, before any treatment can make use of, and react to, the position of the inserted markers they have to be segmented, either manually through expert user intervention or automatically from an imaging system. In the current study, we aimed to establish a robust and autonomous segmentation method for implanted cylindrical gold markers in a single set of projections from a cone-beam computed tomography (CBCT). METHODS: Multiple cylindrical gold markers were segmented in the projection images of CBCT scans by five sequential steps. Initially, marker candidates were identified in all projections with a blob detection routine, and then traced in subsequent projections. Traces inconsistent with a 3D marker position were rejected, and the best remaining traces were identified and used for the construction of a 3D marker constellation model, consisting of the size, position and orientation of the markers. Finally, projections of the model were used to generate templates for the final template-based marker segmentation. Hereby, challenging situations such as overlap of markers and low contrast regions were taken into account. The segmentation method was tested in 63 CBCT scans from 11 patients with 2-4 cylindrical gold markers implanted in the prostate and for 62 CBCT scans from six patients each with 2-3 cylindrical gold markers implanted in the liver and up to two cylindrical markers placed externally on the abdomen. After segmentation all projections of the 125 scans were manually inspected, and a successful segmentation was registered if the segmented position was within the projection of the marker. RESULTS: For prostate markers, the segmentation was successful in 99.8% of the projections. For the liver patients, liver markers and external markers were segmented successfully in 99.9 and 99.8% of the projections, respectively. All markers were identified in the 3D marker constellation model. The most common source of segmentation error was low contrast and motion of markers relative to each other, which resulted in a discrepancy between the template and actual projection appearance during marker overlap. Markers were overlapping in 20, 2.7, and 0.1% of the projections for prostate, liver, and external, respectively. CONCLUSIONS: We have successfully implemented a new method that, without prior knowledge on marker size, position, orientation, and number, autonomously segments cylindrical gold markers from CBCT projections with a high success rate, despite overlap, motion, and low contrast.

Geometric accuracy of dynamic MLC tracking with an implantable wired electromagnetic transponder.

BACKGROUND: Tumor motion during radiotherapy delivery can substantially deteriorate the target dose distribution. A promising method to overcome this problem is dynamic multi-leaf collimator (DMLC) tracking. The purpose of this phantom study was to integrate a wired electromagnetic (EM) transponder localization system with DMLC tracking and to investigate the geometric accuracy of the integrated system. MATERIAL AND METHODS: DMLC tracking experiments were performed on a Trilogy accelerator with a prototype DMLC tracking system. A wired implantable EM transponder was mounted on a motion stage with a 3 mm tungsten sphere used for target visualization in continuous portal images. The three dimensional (3D) transponder position signal was used for DMLC aperture adaption. The motion stage was programmed to reproduce eight representative patient-measured trajectories for prostate and for lung tumors. The tracking system latency was determined and prediction was used for the lung tumor trajectories to account for the latency. For each trajectory, three conformal fields with a 10 cm circular MLC aperture and 72 s treatment duration were delivered: (1) a 358° arc field; (2) an anterior static field; and (3) a lateral static field. The tracking error was measured as the difference between the marker position and the MLC aperture in the portal images. RESULTS: The tracking system latency was 140 ms. The mean root-mean-square (rms) of the 3D transponder localization error was 0.53/0.54 mm for prostate/lung tumor trajectories. The mean rms of the two dimensional (2D) tracking error was 0.69 mm (prostate) and 0.98 mm (lung tumors) with tracking and 3.4 mm (prostate) and 5.3 mm (lung tumors) without tracking. CONCLUSIONS: DMLC tracking was integrated with a wired EM transponder localization system and investigated for arc and static field delivery. The system provides sub-mm geometrical errors for most trajectories.

Clinical validation of a 4D-CT based method for lung ventilation measurement in phantoms and patients.

BACKGROUND: Lung cancer patients referred to radiotherapy (RT) often present with regional lung function deficits, and it is therefore of interest to image their lung function prior to treatment. In this study a method was developed that uses a deformable image registration (DIR) between the peak-inhale and peak-exhale phases of a thoracic four-dimensional computed tomography (4D-CT) scan to extract ventilation information. The method calculates the displacement vector fields (DVFs) resulting from the DIR using the Jacobian map approach in order to extract information regarding regional lung volume change. MATERIAL AND METHODS: The DVFs resulting from DIRs were analysed to compute the Jacobian determinant of vectors in the field, thus obtaining a map of the vector gradients of the entire registered CT image, i.e. voxel-wise local volume change. Geometric and quantitative validation was achieved using images of both phantoms and patients. In the phantom studies, translations and deformations of known size and direction were introduced to validate both the DIR algorithm and the method as a whole. Furthermore, five patients underwent 4D-CT for planning of stereotactic body RT (SBRT). The patients were immobilised in a stereotactic body frame (SBF) and for each patient, two thoracic 4D-CT scans were acquired, one scan with respiration restricted by an abdominal compression plate and the other under free breathing. RESULTS: In the phantom studies deformation errors were found to be of the order of the expected precision of 3 mm, corresponding to the image slice distance, in lateral and vertical directions. For the longitudinal direction a more pronounced discrepancy was observed, with the algorithm predicting displacement lengths of less than half of the physically introduced deformation. Qualitatively the method performed as expected. In the patient study an inverse consistency test showed deviations of up to 5.8 mm, i.e. almost twice the image slice separation. Jacobian maps of the patient images indicated well-ventilated areas as anatomically expected. CONCLUSION: The established method provides a means of using a (commercially available) DIR algorithm to obtain a quantitative measure of local lung volume change. With further phantom and patient validation studies, quantitative maps of specific ventilation should be possible to produce and use in a clinical setting.

Tracking latency in image-based dynamic MLC tracking with direct image access.

PURPOSE: Target tracking is a promising method for motion compensation in radiotherapy. For image-based dynamic multileaf collimator (DMLC) tracking, latency has been shown to be the main contributor to geometrical errors in tracking of respiratory motion, specifically due to slow transfer of image data from the image acquisition system to the tracking system via image file storage on a hard disk. The purpose of the current study was to integrate direct image access with a DMLC tracking system and to quantify the tracking latency of the integrated system for both kV and MV image-based tracking. METHOD: A DMLC tracking system integrated with a linear accelerator was used for tracking of a motion phantom with an embedded tungsten marker. Real-time target localization was based on x-ray images acquired either with a portal imager or a kV imager mounted orthogonal to the treatment beam. Images were processed directly without intermediate disk access. Continuous portal images and system log files were stored during treatment delivery for detailed offline analysis of the tracking latency. RESULTS: The mean tracking system latency for kV and MV image-based tracking as function of the imaging interval ΔT(image) increased linearly with ΔT(image) as 148 ms + 0.58 * ΔT(image) (kV) and 162 ms + 1.1 * ΔT(image) (MV). The latency contribution from image acquisition and image transfer for kV image-based tracking was independent on ΔT(image) at 103 ± 14 ms. For MV-based tracking, it increased with ΔT(image) as 124 ms + 0.44 * ΔT(image). For ΔT(image) = 200 ms (5 Hz imaging), the total latency was reduced from 550 ms to 264 ms for kV image-based tracking and from 500 ms to 382 ms for MV image-based tracking as compared to the previously used indirect image transfer via image file storage on a hard disk. CONCLUSION: kV and MV image-based DMLC tracking was successfully integrated with direct image access. It resulted in substantial tracking latency reductions compared with image-based tracking without direct image access.

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.

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.

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.

Dynamic MLC tracking of moving targets with a single kV imager for 3D conformal and IMRT treatments.

BACKGROUND: Tumor motion during radiotherapy is a major challenge for accurate dose delivery, in particular for hypofractionation and dose painting. The motion may be compensated by dynamic multileaf collimator (DMLC) tracking. Previous work has demonstrated that a single kV imager can accurately localize moving targets for DMLC tracking during rotational delivery, however this method has not been investigated for the static gantry geometry used for conformal and IMRT treatments. In this study we investigate the accuracy of single kV-imager based DMLC tracking for static-gantry delivery. MATERIAL AND METHODS: A 5-field treatment plan with circular field shape and 200 MU per field was delivered in 20 s per field to a moving phantom with an embedded gold marker. Fluoroscopic kV images were acquired at 5 Hz perpendicular to the treatment beam axis during a 120° pre-treatment gantry rotation, during treatment delivery, and during inter-field gantry rotations. The three-dimensional marker position was estimated from the kV images and used for MLC adaptation. Experiments included 12 thoracic/abdominal tumor trajectories and five prostate trajectories selected from databases with 160 and 548 trajectories, respectively. The tracking error was determined as the mismatch between the marker position and the MLC aperture center in portal images. Simulations extended the study to all trajectories in the databases and to treatments with prolonged duration of 60 s per field. RESULTS: In the experiments, the mean root-mean-square (rms) tracking error was 0.9 mm (perpendicular to MLC) and 1.1 mm (parallel to MLC) for thoracic/abdominal tumor trajectories and 0.6 mm (perpendicular) and 0.5 mm (parallel) for prostate trajectories. Simulations of these experiments agreed to within 0.1 mm. Simulations of all trajectories in the databases resulted in mean rms tracking errors of 0.6 mm (perpendicular) and 0.9 mm (parallel) for thorax/abdomen tumors and 0.4 mm (perpendicular) and 0.2 mm (parallel) for prostate for both 20 s and 60 s per field. CONCLUSION: Single kV imager DMLC tracking, which is fully compatible with IMRT, was demonstrated for static fields. The mean tracking error was sub-2 mm for most tumor trajectories with respiratory motions and sub-1 mm for most prostate trajectories.

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.

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.