Tumor Motion Amplitude Research Articles

Development of a novel 3D-printed dynamic anthropomorphic thorax phantom for evaluation of four-dimensional computed tomography

Background and purposeIn radiotherapy, the image quality of four-dimensional computed tomography (4DCT) is often degraded by artifacts resulting from breathing irregularities. Quality assurance mostly employ simplistic phantoms, not fully representing complexities and dynamics in patients. 3D-printing allows for design of highly customized phantoms. This study aims to validate the proof-of-concept of a realistic dynamic thorax phantom and its 4DCT application. Materials and methodsUsing 3D-printing, a realistic thorax phantom was produced with tissue-equivalent materials for soft tissue, bone, and compressible lungs, including bronchi and tumors. Lung compression was facilitated by motors simulating customized breathing curves with an added platform for application of monitoring systems. The phantom contained three tumors which were assessed in terms of tumor motion amplitude. Three 4DCT sequences and repeated static images for different lung compression levels were acquired to evaluate the reproducibility. Moreover, more complex patient-specific breathing patterns with irregularities were simulated. ResultsThe phantom showed a reproducibility of ±0.2 mm and ±0.4 mm in all directions for static 3DCT images and 4DCT images, respectively. Furthermore, the tumor close to the diaphragm showed higher amplitudes in the inferior/superior direction (13.9 mm) than lesions higher in the lungs (8.1 mm) as observed in patients. The more complex breathing patterns demonstrated commonly seen 4DCT artifacts. ConclusionThis study developed a dynamic 3D-printed thorax phantom, which simulated customized breathing patterns. The phantom represented a realistic anatomy and 4DCT scanning of it could create realistic artifacts, making it beneficial for 4DCT quality assurance or protocol optimization.

Respiratory motion tracking of spine stereotactic radiotherapy in prone position.

The CyberKnife system is a specialized device for non-coplanar irradiation; however, it possesses the geometric restriction that the beam cannot be irradiated from under the treatment couch. Prone positioning is expected to reduce the dose to normal lung tissue in spinal stereotactic body radiotherapy (SBRT) owing to the efficiency of beam arrangement; however, respiratory motion occurs. Therefore, the Xsight spine prone tracking (XSPT) system is used to reduce the effects of respiratory motion. The purpose of this study was to evaluate the motion-tracking error of the spine in the prone position. Data from all 25 patients who underwent spinal SBRT at our institution between April 2020 and February 2022 using CyberKnife (VSI, version 11.1.0) with the XSPT tracking system were retrospectively analyzed using log files. The tumor motion, correlation, and prediction errors for each patient were examined. Furthermore, to assess the potential relationships between the parameters, the relationships between the tumor-motion amplitudes and correlation or prediction errors were investigated using linear regression. The tumor-motion amplitudes in each direction were as follows: superior-inferior (SI), 0.51±0.39mm; left-right (LR), 0.37±0.29mm; and anterior-posterior (AP), 3.43±1.63mm. The overall mean correlation and prediction errors were 0.66±0.48mm and 0.06±0.07mm, respectively. The prediction errors were strongly correlated with the tumor-motion amplitudes, whereas the correlation errors were not. This study demonstrated that the correlation error of spinal SBRT in the prone position is sufficiently small to be independent of the tumor-motion amplitude. Furthermore, the prediction error is small, contributing only slightly to the tracking error. These findings will improve the understanding of how to compensate for respiratory-motion uncertainty in the prone position.

Quantification of Lung Tumor Motion and Optimization of Treatment.

Mobility of lung tumors is induced by respiration and causes inadequate dose coverage. This study quantified lung tumor motion, velocity, and stability for small (≤5 cm) and large (>5 cm) tumors to adapt radiation therapy techniques for lung cancer patients. In this retrospective study, 70 patients with lung cancer were included that 50 and 20 patients had a small and large gross tumor volume (GTV). To quantify the tumor motion and velocity in the upper lobe (UL) and lower lobe (LL) for the central region (CR) and a peripheral region (PR), the GTV was contoured in all ten respiratory phases, using 4D-CT. The amplitude of tumor motion was greater in the LL, with motion in the superior-inferior (SI) direction compared to the UL, with an elliptical motion for small and large tumors. Tumor motion was greater in the CR, rather than in the PR, by 63% and 49% in the UL compared to 50% and 38% in the LL, for the left and right lung. The maximum tumor velocity for a small GTV was 44.1 mm/s in the LL (CR), decreased to 4 mm/s for both ULs (PR), and a large GTV ranged from 0.4 to 9.4 mm/s. The tumor motion and velocity depend on the tumor localization and the greater motion was in the CR for both lobes due to heart contribution. The tumor velocity and stability can help select the best technique for motion management during radiation therapy.

A Simulation Study of Tolerance of Breathing Amplitude Variations in Radiotherapy of Lung Cancer Using 4DCT and Time-Resolved 4DMRI.

As patient breathing irregularities can introduce a large uncertainty in targeting the internal tumor volume (ITV) of lung cancer patients, and thereby affect treatment quality, this study evaluates dose tolerance of tumor motion amplitude variations in ITV-based volumetric modulated arc therapy (VMAT). A motion-incorporated planning technique was employed to simulate treatment delivery of 10 lung cancer patients' clinical VMAT plans using original and three scaling-up (by 0.5, 1.0, and 2.0 cm) motion waveforms from single-breath four-dimensional computed tomography (4DCT) and multi-breath time-resolved 4D magnetic resonance imaging (TR-4DMRI). The planning tumor volume (PTV = ITV + 5 mm margin) dose coverage (PTV D95%) was evaluated. The repeated waveforms were used to move the isocenter in sync with the clinical leaf motion and gantry rotation. The continuous VMAT arcs were broken down into many static beam fields at the control points (2°-interval) and the composite plan represented the motion-incorporated VMAT plan. Eight motion-incorporated plans per patient were simulated and the plan with the native 4DCT waveform was used as a control. The first (D95% ≤ 95%) and second (D95% ≤ 90%) plan breaching points due to motion amplitude increase were identified and analyzed. The PTV D95% in the motion-incorporated plans was 99.4 ± 1.0% using 4DCT, closely agreeing with the corresponding ITV-based VMAT plan (PTV D95% = 100%). Tumor motion irregularities were observed in TR-4DMRI and triggered D95% ≤ 95% in one case. For small tumors, 4 mm extra motion triggered D95% ≤ 95%, and 6-8 mm triggered D95% ≤ 90%. For large tumors, 14 mm and 21 mm extra motions triggered the first and second breaching points, respectively. This study has demonstrated that PTV D95% breaching points may occur for small tumors during treatment delivery. Clinically, it is important to monitor and avoid systematic motion increase, including baseline drift, and large random motion spikes through threshold-based beam gating.

Dosimetric robustness of lung tumor photon radiotherapy evaluated from multiple event CT imaging

Purpose:Intrafractional respiratory motion is a concern for lung tumor radiotherapy but full evaluation of its impact is hampered by the lack of images representing the true motion. This study presents a novel evaluation using free-breathing images acquired over realistic treatment times to study the dosimetric impact of respiratory motion in photon radiotherapy. Methods:Cine-CT images of 14 patients with lung cancer acquired during eight minutes of free-breathing at three occasions were used to simulate dose tracking of four different planning methods. These methods aimed to deliver 54 Gy in three fractions to D50% of the target and were denoted as robust 4D (RB4), homogeneous fluence to the ITV (FLU) and an isodose prescription to the ITV with a high central dose (ISD), concurrently renormalized (IRN). Differences in dose coverage probability and homogeneity between the methods were quantified. Correlations between underdosage and attributes regarding the tumor and its motion were investigated. Results:Despite tumor motion amplitudes being larger than in the 4DCT all but FLU achieved the intended CTV D50% for the cohort average. For all methods but IRN at least 93% of the patients would have received 95% of the intended dose. No differences in D50% were found between RB4 and ISD nor IRN. However, RB4 led to better homogeneity. Conclusions:Tumor motion in free-breathing not covered by the 4DCT had a small impact on dose. The RB4 is recommended for planning of free-breathing treatments. No factor was found that consistently correlated dose degradation with patient or motion attributes.

Dosimetric effects of respiratory motion during stereotactic body radiation therapy of lung tumors

Background Respiratory-induced lung tumor motion may affect the delivered dose in stereotactic body radiation therapy (SBRT). Previous studies are often based on phantom studies for one specific treatment technique. In this study, the dosimetric effect of tumor motion was quantified in real patient geometries for different modulated treatments and tumor motion amplitudes for lung-SBRT. Material and Methods A simulation method using deformable image registrations and 4-dimensional computed tomographies (4DCT) was developed to assess the dosimetric effects of tumor motion. The method was evaluated with ionization chamber and Gafchromic film measurements in a thorax phantom and used to simulate the effect for 15 patients with lung tumors moving 7.3–27.4 mm. Four treatment plans with different complexities were created for each patient and the motion-induced dosimetric effect to the gross tumor volume (GTV) was simulated. The difference between the planned dose to the static tumor and the simulated delivered dose to the moving tumor was quantified for the near minimum (D98%), near maximum (D2%) and mean dose (Dmean) to the GTV as well as the largest observed local difference within the GTV (Maxdiff). Results No correlation was found between the dose differences and the tumor motion amplitude or plan complexity. However, the largest deviations were observed for tumors moving >15.0 mm. The simulated delivered dose was within 2.5% from the planned dose for D98% (tumors moving <15 mm) and within 3.3% (tumors moving >15 mm). The corresponding values were 1.7% vs. 6.4% (D2%); 1.7% vs. 2.4% (Dmean) and 8.9% vs. 35.2% (Maxdiff). Using less complex treatment techniques minimized Maxdiff for tumors moving >15.0 mm. Conclusion The dosimetric effects of respiratory-induced motion during lung SBRT are patient and plan specific. The magnitude of the dosimetric effect cannot be assessed solely based upon tumor motion amplitude or plan complexity.

Synthetic 4DCT(MRI) lung phantom generation for 4D radiotherapy and image guidance investigations.

PurposeRespiratory motion is one of the major challenges in radiotherapy. In this work, a comprehensive and clinically plausible set of 4D numerical phantoms, together with their corresponding “ground truths,” have been developed and validated for 4D radiotherapy applications.MethodsThe phantoms are based on CTs providing density information and motion from multi‐breathing‐cycle 4D Magnetic Resonance imagings (MRIs). Deformable image registration (DIR) has been utilized to extract motion fields from 4DMRIs and to establish inter‐subject correspondence by registering binary lung masks between Computer Tomography (CT) and MRI. The established correspondence is then used to warp the CT according to the 4DMRI motion. The resulting synthetic 4DCTs are called 4DCT(MRI)s. Validation of the 4DCT(MRI) workflow was conducted by directly comparing conventional 4DCTs to derived synthetic 4D images using the motion of the 4DCTs themselves (referred to as 4DCT(CT)s). Digitally reconstructed radiographs (DRRs) as well as 4D pencil beam scanned (PBS) proton dose calculations were used for validation.ResultsBased on the CT image appearance of 13 lung cancer patients and deformable motion of five volunteer 4DMRIs, synthetic 4DCT(MRI)s with a total of 871 different breathing cycles have been generated. The 4DCT(MRI)s exhibit an average superior–inferior tumor motion amplitude of 7 ± 5 mm (min: 0.5 mm, max: 22.7 mm). The relative change of the DRR image intensities of the conventional 4DCTs and the corresponding synthetic 4DCT(CT)s inside the body is smaller than 5% for at least 81% of the pixels for all studied cases. Comparison of 4D dose distributions calculated on 4DCTs and the synthetic 4DCT(CT)s using the same motion achieved similar dose distributions with an average 2%/2 mm gamma pass rate of 90.8% (min: 77.8%, max: 97.2%).ConclusionWe developed a series of numerical 4D lung phantoms based on real imaging and motion data, which give realistic representations of both anatomy and motion scenarios and the accessible “ground truth” deformation vector fields of each 4DCT(MRI). The open‐source code and motion data allow foreseen users to generate further 4D data by themselves. These numeric 4D phantoms can be used for the development of new 4D treatment strategies, 4D dose calculations, DIR algorithm validations, as well as simulations of motion mitigation and different online image guidance techniques for both proton and photon radiation therapy.

Evaluation of Lung Tumor Target Volume in a Large Sample: Target and Clinical Factors Influencing the Volume Derived From Four-Dimensional CT and Cone Beam CT.

Background and PurposeThis study aimed to systematically evaluate the influence of target-related and clinical factors on volume differences and the similarity of targets derived from four-dimensional computed tomography (4DCT) and cone beam computed tomography (CBCT) images in lung stereotactic body radiation therapy (SBRT).Materials and Methods4DCT and CBCT image data of 210 tumors from 195 patients were analyzed. The internal gross target volume (IGTV) derived from the maximum intensity projection (MIP) of 4DCT (IGTV-MIP) and the IGTV from CBCT (IGTV-CBCT) were compared with the reference IGTV from 10 phases of 4DCT (IGTV-10). The target size, tumor motion, and the similarity between IGTVs were measured. The influence of target-related and clinical factors on the adequacy of IGTVs derived from 4DCT MIP and CBCT images was evaluated.ResultsThe mean tumor motion amplitude in the 3D direction was 6.5 ± 5 mm. The mean size ratio of IGTV-CBCT and IGTV-MIP compared to IGTV-10 in all patients was 0.71 ± 0.21 and 0.8 ± 0.14, respectively. Female sex, greater BSA, and larger target size were protective factors, while the Karnofsky Performance Status, body mass index, and motion were risk factors for the similarity between IGTV-MIP and IGTV-10. Older age and larger target size were protective factors, while adhesion to the heart, coexistence with cardiopathy, and tumor motion were risk factors for the similarity between IGTV-CBCT and IGTV-10.ConclusionClinical factors should be considered when using MIP images for defining ITV, and when using CBCT images for verifying treatment targets.

Study on Motion Management of Pancreatic Cancer Treated by CyberKnife.

PurposeWe investigated the movement characteristics of pancreas and the clinical accuracy of tracking pancreas with the Synchrony Respiratory Tracking System (SRTS) during the CyberKnife treatment. These data provide a clinical data basis for the expansion margins of pancreatic tumor target.Methods and MaterialsForty-two patients with pancreatic cancer treated by CyberKnife were retrospectively studied. The pancreatic displacement calculated from the x-ray images collected during the time interval between two consecutive movements constituted a data set.ResultsThe total mean motion amplitudes and standard deviations of pancreatic tumors in SI, LR, AP, and radial directions were 3.66 ± 1.71 mm, 0.97 ± 0.62 mm, 1.52 ± 1.02 mm, and 1.36 ± 0.49 mm, respectively. The overall mean correlation errors and standard deviations were 0.82 ± 0.46 mm, 0.47 ± 0.33 mm, 0.41 ± 0.24 mm, and 0.98 ± 0.37 mm, respectively. The overall mean prediction errors and standard deviations were 0.57 ± 0.14 mm, 0.62 ± 0.28 mm, 0.39 ± 0.17 mm, and 1.58 ± 0.36 mm, respectively. The correlation errors and prediction errors of pancreatic tumors at different anatomical positions in SI, LR, and AP directions were statistically significant (p < 0.05).ConclusionsThe tumor motion amplitude, the tumor location, and the treatment time are the main factors affecting the tracking accuracy. The pancreatic tumors at different anatomical locations should be treated differently to ensure sufficient dose coverage of the pancreatic target area.

Lung Stereotactic Body Radiotherapy (SBRT) Using Spot-Scanning Proton Arc (SPArc) Therapy: A Feasibility Study

We developed a 4D interplay effect model to quantitatively evaluate breathing-induced interplay effects and assess the feasibility of utilizing spot-scanning proton arc (SPArc) therapy for hypo-fractionated lung stereotactic body radiotherapy (SBRT). The model was then validated by retrospective application to clinical cases.A digital lung 4DCT phantoms was used to mimic targets in diameter of 3cm with breathing motion amplitudes: 5, 10, 15, and 20 mm, respectively. Two planning groups based on robust optimization were generated: (1) Two-field Intensity Modulated Proton Therapy (IMPT) plans and (2) SPArc plans via a partial arc. 5000 cGy was prescribed to the internal target volume (ITV) in 5 fractions. To quantitatively assess the breathing induced interplay effect, the 4D dynamic dose was calculated by synchronizing the breathing pattern with the simulated proton machine delivery sequence, including IMPT, Volumetric repainting (IMPTvolumetric), iso-layered repainting (IMPTlayer) and SPArc. Ten lung patients' 4DCT previously treated with VMAT SBRT, were used to validate the digital lung tumor model. Normal tissue complicated probability (NTCP) of chestwall toxicity was calculated.Target dose were degraded as the tumor motion amplitude increased. The 4D interplay effect phantom model indicated that motion mitigation effectiveness using SPArc was about five times of IMPTvolumetric or IMPTlayer using maximum MU/spot as 0.5 MU at 20 mm motion amplitude. The retrospective study showed that SPArc has an advantage in normal tissue sparing. The probability of chestwall's toxicity were significantly improved from 40.2% ± 29.0% (VMAT) (P = 0.01) and 16.3% ± 12.0% (IMPT) (P = 0.01) to 10.1% ± 5.4% (SPArc). SPArc significantly mitigated the interplay effect compared to IMPT, where the average target D99 in single fraction 4D dynamic dose throughout patients was 4876 ± 107 cGy[RBE] (IMPT) vs. 4913 ± 64 cGy[RBE] (SPArc) (P < 0.01).SPArc is an efficient treatment modality capable of effectively mitigating the interplay effect in lung SBRT compared to IMPT with repainting. Such a technique has the potential to further reduce the normal tissue complexity compared to the VMAT.G. Liu: None. L. Zhao: None. A. Qin: None. R.L. Deraniyagala: None. C.W. Stevens: None. D. Yan: None. X. Li: None. X. Ding: None.

Dosimetric study of the interplay effect using three-dimensional motion phantom in proton pencil beam scanning treatment of moving thoracic tumours

Abstract Aim: The dosimetric and clinical advantages offered by implementation of pencil beam scanning (PBS) proton therapy for moving thoracic tumours is hindered by interplay effect. The purpose of this study is to evaluate the impact of large proton beam spot size along with adaptive aperture (AA) and various motion mitigation techniques on the interplay effect for a range of motion amplitudes in a three-dimensional (3D) respiratory motion phantom. Materials and Methods: Point doses using ionisation chamber (IC) and planner dose distributions with radiochromic film were compared against the corresponding treatment planning system (TPS) information. A 3D respiratory motion phantom was scanned either for static or 4D computed tomographic (CT) technique for 6-, 10- and 14-mm motion amplitudes in SI direction. For free breathing (FB) treatment, a tumour was contoured on maximum intensity projection scan and an average scan was used for treatment planning. Each FB treatment was delivered with one, three and five volumetric repaintings (VRs). Three phases (CT40–60%) were extracted from the 4D-CT scans of each motion amplitude for the respiratory-gated treatment and were used for the treatment planning and delivery. All treatment plans were made using AA and robustly optimised with 5-mm set-up and 3·5% density uncertainty. A total of 26 treatment plans were delivered to IC and film using static, dynamic and respiratory-gated treatments combinations. A percent dose difference between IC and TPS for the point dose and gamma indices for film–TPS planner dose comparison was used. Results: The dose profile of film and TPS for the static phantom matched well, and percent dose difference between IC and TPS was 0·4%. The percent dose difference for all the gated treatments were below 3·0% except 14-mm motion amplitude-gated treatment. The gamma passing rate was more than 95% for film–TPS comparison for all gated treatment for the investigated gamma acceptance criteria. For FB treatments, the percent dose difference for 6-, 10- and 14-mm motion amplitude was 1·4%, −2·7% and −4·1%, respectively. As the number of VR increased, the percent difference between measured and calculated values decreased. The gamma passing rate met the required tolerance for different acceptance criteria except for the 14-mm motion amplitude FB treatment. Conclusion: The PBS technique for the FB thoracic treatments up to 10-mm motion amplitude can be implemented with an acceptable accuracy using large proton beam spot size, AA and robust optimisation. The impact of the interplay effect can be reduced with VR and respiratory-gated treatment and extend the treatable tumour motion amplitude.

Reducing the impact on renal function of kidney SABR through management of respiratory motion.

Stereotactic ablative body radiotherapy (SABR) is as a viable treatment option to treat kidney cancer. This study quantifies dose reduction to non-tumour ipsilateral kidney and estimated renal function gain from elimination of respiratory motion. We reviewed 62 previously treated kidney SABR patients. The gross tumour volume (GTV) was segmented in each phase of a four-dimensional CT (4DCT). Tumour motion amplitude (TMA) was obtained from the GTV centroid on each phase. Low modulation, motion managed (MM) plans were generated on the exhale phase image. Internal target volume (ITV)-based plans were generated on the 4DCT average intensity projection. To estimate delivered kidney dose, the ITV-based plan was copied ten times to the exhale phase image, with isocentre located at the GTV centroid position in each phase. The dose was calculated and averaged to result in non-motion managed plans. Difference in ipsilateral kidney volume receiving 50% of the prescription dose (V50%) and estimated glomerular filtration rate (GFR) change were compared between ITV and MM plans. The mean±st.dev. TMA was 0.79±0.49cm. Removing respiratory motion reduced ipsilateral kidney V50% (slope of the difference=12cc/cm of TMA, Pearson-r=0.69, p-value <10-9), and estimated GFR was improved (slope=4.4 %/cm of TMA, Pearson-r=0.85, p-value<10-10). We have quantified the improvement in healthy kidney dose when removing respiratory motion from kidney SABR plans, and demonstrated an expected gain in GFR of 4.4 %/cm of motion removed.

Technical Note: Multiple energy extraction techniques for synchrotron-based proton delivery systems may exacerbate motion interplay effects in lung cancer treatments.

The multiple energy extraction (MEE) delivery technique for synchrotron-based proton delivery systems reduces beam delivery time by decelerating the beam multiple times during one accelerator spill, but this might cause additional plan quality degradation due to intrafractional motion. We seek to determine whether MEE causes significantly different plan quality degradation compared to single energy extraction (SEE) for lung cancer treatments due to the interplay effect. Ten lung cancer patients treated with IMPT at our institution were nonrandomly sampled based on a representative range of tumor motion amplitudes, tumor volumes, and respiratory periods. Dose-volume histogram (DVH) indices from single-fraction SEE and MEE four-dimensional (4D) dynamic dose distributions were compared using the Wilcoxon signed-rank test. Distributions of monitor units (MU) to breathing phases were investigated for features associated with plan quality degradation. SEE and MEE DVH indices were compared in fractionated deliveries of the worst-case patient treatment scenario to evaluate the impact of fractionation. There were no clinically significant differences in target mean dose, target dose conformity, or dose to organs-at-risk between SEE and MEE in single-fraction delivery. Three patients had significantly worse dose homogeneity with MEE compared to SEE (single-fraction mean D5% -D95% increased by up to 9.6% of prescription dose), and plots of MU distribution to breathing phases showed synchronization patterns with MEE but not SEE. However, after 30 fractions the patient in the worst-case scenario had clinically acceptable target dose homogeneity and coverage with MEE (mean D5% -D95% increased by 1% compared to SEE). For some patients with breathing periods close to the mean spill duration, MEE resulted in significantly worse single-fraction target dose homogeneity compared to SEE due to the interplay effect. However, this was mitigated by fractionation, and target dose homogeneity and coverage were clinically acceptable after 30 fractions with MEE.

Tumour motion analysis from planning to end of treatment course for a large cohort of peripheral lung SBRT targets

Background The aim is to quantify and analyse tumour motion during a course of treatment for lung SBRT patients. Material and methods Peak-to-peak motion of 483 tumours in 441 patients treated with peripheral lung SBRT at a single institution over a two year period was measured on planning CT and at all treatment fractions. Planning 4D-CT scans were analysed using our clinical workflow involving deformable propagation of the delineated target to all phases. Similarly, acquisition of the 4D-CBCT data followed the clinical workflow based on XVI 5.0 available on Elekta linacs. Differences and correlations of the peak-to-peak motion on the planning CT and at treatment were analysed. Results On the planning CT, a total of 81.4% of the tumours had a peak-to-peak motion <10 mm, and 96.1% had <20 mm. The largest motion was observed in the CC direction, with largest amplitude for tumours located in the caudal posterior part of the lung. The difference in amplitude in CC between planning CT and first fraction had a mean and standard deviation of 0.3 mm and 3.5 mm, respectively, and the largest differences were observed in the caudal posterior part of the lung. Patients with a difference in tumour motion amplitude exceeding two standard deviations (>7 mm) at the first fraction were evaluated individually, and they all had poor 4DCT image quality. The difference between the first and second/third fractions had a mean and standard deviation of 0.4 mm/0.5 mm and 2.0 mm/1.9 mm. Conclusion Tumour motion at first treatment was similar to motion at planning, and motion at subsequent treatments was very similar to motion at first treatment. Large tumour motions are located towards the caudal posterior tumour locations. Patients with poor 4D-CT image quality should be closely followed at the first treatment to verify the motion.

Quantification of the geometric uncertainty when using implanted markers as a surrogate for lung tumor motion

Fiducial markers are used as surrogates for tumor location during radiation therapy treatment. Developments in lung fiducial marker and implantation technology have provided a means to insert markers endobronchially for tracking of lung tumors. This study quantifies the surrogacy uncertainty (SU) when using endobronchially implanted markers as a surrogate for lung tumor position. We evaluated SU for 17 patients treated in a prospective electromagnetic-guided MLC tracking trial. Tumor and markers were segmented on all phases of treatment planning 4DCTs and all frames of pretreatment kilovoltage fluoroscopy acquired from lateral and frontal views. The difference in tumor and marker position relative to end-exhale position was calculated as the SU for both imaging methods and the distributions of uncertainties analyzed. The mean (range) tumor motion amplitude in the 4DCT scan was 5.9mm (1.7-11.7mm) in the superior-inferior (SI) direction, 2.2mm (0.9-5.5mm) in the left-right (LR) direction, and 3.9mm (1.2-12.9mm) in the anterior-posterior (AP) direction. Population-based analysis indicated symmetric SU centered close to 0mm, with maximum 5th/95th percentile values over all axes of -2.0mm/2.1mm with 4DCT, and -2.3/1.3mm for fluoroscopy. There was poor correlation between the SU measured with 4DCT and that measured with fluoroscopy on a per-patient basis. We observed increasing SU with increasing surrogate motion. Based on fluoroscopy analysis, the mean (95% CI) SU was 5% (2%-8%) of the motion magnitude in the SI direction, 16% (6%-26%) of the motion magnitude in the LR direction, and 33% (23%-42%) of the motion magnitude in the AP direction. There was no dependence of SU on marker distance from the tumor. We have quantified SU due to use of implanted markers as surrogates for lung tumor motion. Population 95th percentile range are up to 2.3mm, indicating the approximate contribution of SU to total geometric uncertainty. SU was relatively small compared with the SI motion, but substantial compared with LR and AP motion. Due to uncertainty in estimations of patient-specific SU, it is recommended that population-based margins are used to account for this component of the total geometric uncertainty.

Lung Stereotactic Body Radiotherapy (SBRT) Using Spot-Scanning Proton Arc (SPArc) Therapy: A Feasibility Study.

PurposeWe developed a 4D interplay effect model to quantitatively evaluate breathing-induced interplay effects and assess the feasibility of utilizing spot-scanning proton arc (SPArc) therapy for hypo-fractionated lung stereotactic body radiotherapy (SBRT). The model was then validated by retrospective application to clinical cases.Materials and MethodsA digital lung 4DCT phantoms was used to mimic targets in diameter of 3cm with breathing motion amplitudes: 5, 10, 15, and 20 mm, respectively. Two planning groups based on robust optimization were generated: (1) Two-field Intensity Modulated Proton Therapy (IMPT) plans and (2) SPArc plans via a partial arc. 5,000 cGy relative biological effectiveness (RBE) was prescribed to the internal target volume (ITV) in five fractions. To quantitatively assess the breathing induced interplay effect, the 4D dynamic dose was calculated by synchronizing the breathing pattern with the simulated proton machine delivery sequence, including IMPT, Volumetric repainting (IMPTvolumetric), iso-layered repainting (IMPTlayer) and SPArc. Ten lung patients’ 4DCT previously treated with VMAT SBRT, were used to validate the digital lung tumor model. Normal tissue complicated probability (NTCP) of chestwall toxicity was calculated.ResultTarget dose were degraded as the tumor motion amplitude increased. The 4D interplay effect phantom model indicated that motion mitigation effectiveness using SPArc was about five times of IMPTvolumetric or IMPTlayer using maximum MU/spot as 0.5 MU at 20 mm motion amplitude. The retrospective study showed that SPArc has an advantage in normal tissue sparing. The probability of chestwall’s toxicity were significantly improved from 40.2 ± 29.0% (VMAT) (p = 0.01) and 16.3 ± 12.0% (IMPT) (p = 0.01) to 10.1 ± 5.4% (SPArc). SPArc could play a significant role in the interplay effect mitigation with breathing-induced motion more than 20 mm, where the target D99 of 4D dynamic dose for patient #10 was improved from 4,514 ± 138 cGy [RBE] (IMPT) vs. 4,755 ± 129 cGy [RBE] (SPArc) (p = 0.01).ConclusionSPArc effectively mitigated the interplay effect for proton lung SBRT compared to IMPT with repainting and was associated with normal tissue sparing. This technology may make delivery of proton SBRT more technically feasible and less complex with fewer concerns over underdosing the target compared to other proton therapy techniques.

Combining rescanning and gating for a time-efficient treatment of mobile tumors using pencil beam scanning proton therapy

Background and purposeRespiratory motion during proton therapy can severely degrade dose distributions, particularly due to interplay effects when using pencil beam scanning. Combined rescanning and gating treatments for moving tumors mitigates dose degradation, but at the cost of increased treatment delivery time. The objective of this study was to identify the time efficiency of these dose degradation-motion mitigation strategies for different range of motions. Materials and methodsSeventeen patients with thoracic or abdominal tumors were studied. Tumor motion amplitudes ranged from 2–30 mm. Deliveries using different combinations of rescanning and gating were simulated with a dense dose spot grid (4 × 4 × 2.5 mm3) for all patients and a sparse dose spot grid (8 × 8 × 5 mm3) for six patients with larger tumor movements (>8 mm). The resulting plans were evaluated in terms of CTV coverage and time efficiency. ResultsBased on the studied patient cohort, it has been shown that for amplitudes up to 5 mm, no motion mitigation is required with a dense spot grid. For amplitudes between 5 and 10 mm, volumetric rescanning should be applied while maintaining a 100% duty cycle when using a dense spot grid. Although gating could be envisaged to reduce the target volume for intermediate motion, it has been shown that the dose to normal tissues would only be reduced marginally. Moreover, the treatment time would increase. Finally, for larger motion amplitudes, both volumetric rescanning and respiratory gating should be applied with both spot grids. In addition, it has been shown that a dense spot grid delivers better CTV dose coverage than a sparse dose grid. ConclusionVolumetric rescanning and/or respiratory gating can be used in order to effectively and efficiently mitigate dose degradation due to tumor movement.

Quantification of Intrafraction and Interfraction Tumor Motion Amplitude and Prediction Error for Different Liver Tumor Trajectories in Cyberknife Synchrony Tracking

To research the fiducial-based, real-time tracking intrafraction (during the fraction [intra-]) and interfraction (between fractions [inter-]) tumor respiration amplitude, motion trajectory, and prediction error and quantify their relationships for different types of motion trajectories during Cyberknife-based stereotactic ablation radiotherapy. Twelve patients with liver tumors were treated using a Cyberknife system, and 58 fractions were involved in this study. Real-time target motion tracking data were extracted and transformed from the robot coordinate system into the patient coordinate system by the rotation matrix. Only the time sessions of the beam on were studied according to the data information generated from the Cyberknife motion tracking system. The motion correlation model between the external marker signal and internal fiducial position was built to present the type of motion trajectory. Using the correlation model as a function of external marker signal and internal fiducial position, we knew 4 motion trajectories mainly existed for liver cancer patients as follows: perfect linearity (group I), simple linearity (group II), hysteresis (group III), and area respiratory (group IV) patterns. More than half of the patients had a linear breathing trajectory. Analyzing all patients together, the intra-amplitudes were slightly less than those of the inter-amplitudes. The amplitude from large to small was in the superior-inferior, left-right and anterior-posterior directions, regardless of inter- and intra-amplitudes. Then, patients with a larger peak-to-peak have a larger standard deviation of amplitude and a larger amplitude in all fractions/sessions. The prediction errors of the linear motion trajectory were generally less than 1 mm. The prediction errors of the regular hysteresis breathing model were smaller than those of the irregular hysteresis model. Scattered breathing would result in a larger tracking error, such as the area respiratory trajectory. It was logical that prediction errors were larger for patients who showed much variation in their breathing amplitude. This paper showed that the liver motion trajectory model included perfect linearity, sample linearity, hysteresis, and area. The linear motion trajectory presented the minimum tracking error and the best stability, and the hysteresis and area trajectory were the worst. Therefore, breathing management, including respiration training, control, and evaluation of motion trajectory in all directions, was significantly necessary during liver SABR treatment.

Impact of lung tumor motion on dose delivered to organ at risk in lung stereotactic body radiation therapy

To evaluate the amplitude of lung tumor motion and impact of tumor motion on dose delivered to the organs at risk (OARs) during lung stereotactic body radiation therapy (SBRT). This study included 55 patients (30 males and 25 females) with lung cancer who had a small gross tumor volume (GTV). SBRT lung cancer patients were treated with a prescribed dose of 60 Gy in 4 to 8 fractions. Radiotherapy plans were planned in Pinnacle 9.10 with two partial dynamic conformal arcs (DCAs) for the peripheral region (PR) and three to four partial DCAs for the central region (CR). The amplitude of tumor motion and their impact on the maximum dose delivered (Dmax) to the OARs were evaluated in the upper lobe (UL) and lower lobe (LL) in cases of CR and PR tumor’s localizations. The median tumor motions between CR and PR were 4.5 vs 2.2 mm in the UL and 12.5 vs 7.0 mm in the LL. Max dose delivered to the OARs between CR and PR in the UL and LL were as follows: 6.7 vs 8.9 Gy and 9.1 vs 11.7 Gy for the spinal cord; 15.2 vs 0.6 Gy and 22.4 vs 7.6 Gy for the heart; and 11.7 vs 10.8 Gy and 14.8 vs 9.8 Gy for the esophagus, respectively. The dose received by the OARs depends on the amplitude of tumor motion and is relative to the OAR’s location and motion, due to patient respiration and heart contribution.

Time-resolved magnetic resonance fingerprinting for radiotherapy motion management.

This study aims to develop a novel time-resolved magnetic resonance fingerprinting (TR-MRF) technique for respiratory motion imaging applications. The TR-MRF technique consists of repeated MRF acquisitions using an unbalanced steady-state free precession sequence with spiral-in-spiral-out trajectory. Time-resolved magnetic resonance fingerprinting was first tested via computer simulation using a four-dimensional (4D) extended cardiac-torso (XCAT) phantom for both regular and irregular breathing profiles, and was tested in three healthy volunteers. Parametric TR-MRF maps at different respiratory phases were subsequently estimated using our TR-MRF sorting and reconstruction techniques. The resulting TR-MRF maps were evaluated using a set of metrices related to radiotherapy applications, including absolute difference in motion amplitude, error in the amplitude of diaphragm motion (ADM), tumor volume error (TVE), signal-to-noise ratio (SNR), and tumor contrast. TR-MRF maps with regular and irregular breathing were successfully generated in XCAT phantom. Numerical simulations showed that the TVE were 1.6±2.7% and 1.3±2.2%, the average absolute differences in tumor motion amplitude were 0.3±0.7mm and 0.3±0.6mm, and the ADM were 4.1±0.9% and 3.5±0.9% for irregular and regular breathing, respectively. The SNR of the T1 and T2 maps of the liver and the tumor were generally higher for regular breathing compared to irregular breathing, whereas tumor-to-liver contrast is similar between the two breathing patterns. The proposed technique was successfully implemented on the healthy volunteers. We have successfully demonstrated in both digital phantom and healthy subjects a novel TR-MRF technique capable of imaging respiratory motions with simultaneous quantification of MR multiparametric maps.