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.

Investigating the use of comprehensive motion monitoring for intrafraction 3D drift assessment of hypofractionated prostate cancer patients on a 1.5T magnetic resonance imaging radiotherapy system.

This work investigates the use of a multi-2D cine magnetic resonance imaging-based comprehensive motion monitoring (CMM) system for the assessment of prostate intrafraction 3D drifts. The data of six healthy volunteers were analyzed and the values of a clinically-relevant registration quality factor metric exported by CMM were presented. Additionally, the CMM-derived prostate motion was compared to a 3D-based reference and the 2D-3D tracking agreement was reported. Due to the low quality of SI motion tracking (often > 2 mm tracking mismatch between anatomical planes) we conclude that further improvements are desirable prior to clinical introduction of CMM for prostate drift corrections.

Artificial intelligence-based motion tracking in cancer radiotherapy: A review.

Radiotherapy aims to deliver a prescribed dose to the tumor while sparing neighboring organs at risk (OARs). Increasingly complex treatment techniques such as volumetric modulated arc therapy (VMAT), stereotactic radiosurgery (SRS), stereotactic body radiotherapy (SBRT), and proton therapy have been developed to deliver doses more precisely to the target. While such technologies have improved dose delivery, the implementation of intra-fraction motion management to verify tumor position at the time of treatment has become increasingly relevant. Artificial intelligence (AI) has recently demonstrated great potential for real-time tracking of tumors during treatment. However, AI-based motion management faces several challenges, including bias in training data, poor transparency, difficult data collection, complex workflows and quality assurance, and limited sample sizes. This review presents the AI algorithms used for chest, abdomen, and pelvic tumor motion management/tracking for radiotherapy and provides a literature summary on the topic. We will also discuss the limitations of these AI-based studies and propose potential improvements.

Treatment accuracy of standard linear accelerator-based prostate SBRT: the delivered dose assessment of patients treated within two major clinical trials using an in-house position monitoring system.

Background and purpose: The purpose of this study was to assess the dosimetric improvements achieved in prostate stereotactic body radiotherapy (SBRT) treatment within the PROMETHEUS and NINJA trials using an in-house real-time position monitoring system, SeedTracker. Methods and materials: This study considered a total of 127 prostate SBRT patients treated in the PROMETHEUS (ACTRN12615000223538) and NINJA (ACTRN12618001806257) clinical trials. The SeedTracker position monitoring system was utilized for real-time position monitoring with a 3-mm position tolerance. The doses delivered to the clinical target volume (CTV), rectum, and bladder were assessed by incorporating the actual target position during treatment. The dose that would have been delivered without monitoring was also assessed by incorporating the observed position deviations. Results: Treatment with position corrections resulted in a mean (range) CTV D99 difference of -0.3 (-1.0 to 0.0) Gy between the planned and delivered dose. Without corrections, this difference would have been -0.6 (-3.7 to 0.0) Gy. Not correcting for position deviations resulted in a statistically significant difference between the planned and delivered CTV D99 (p < 0.05). The mean (range) dose difference between the planned and delivered D2cc of the rectum and bladder for treatment with position corrections was -0.1 (-3.7 to 4.7) Gy and -0.1 (-1.7 to 0.5) Gy, respectively. Without corrections, these differences would have been -0.6 (-6.1 to 4.7) Gy and -0.2 (-2.5 to 0.9) Gy. Conclusions: SeedTracker improved clinical dose volume compliance in prostate SBRT. Without monitoring and corrections, delivered dose would significantly differ from the planned dose.

Dosimetric impact of intrafraction patient motion on MLC-based 3D-conformal spatially fractionated radiation therapy treatment of large and bulky tumors.

PURPOSE: To evaluate the dosimetric impact on spatially fractionated radiation therapy (SFRT) plan quality due to intrafraction patient motion via multi-field MLC-based method for treating large and bulky (≥8 cm) unresectable tumors. METHODS: For large tumors, a cone beam CT-guided 3D conformal MLC-based SFRT method was utilized with 15 Gy prescription. An MLC GTV-fitting algorithm provided 1 cm diameter apertures with a 2 cm center-to-center distance at the isocenter. This generated a highly heterogeneous sieve-like dose distribution within an hour, enabling same-day SFRT treatment. Fifteen previously treated SFRT patients were analyzed (5 head & neck [H&N], 5 chest and lungs, and 5 abdominal and pelvis masses). For each plan, intrafraction motion errors were simulated by incrementally shifting original isocenters of each field in different x-, y-, and z-directions from 1 to 5 mm. The dosimetric metrics analyzed were: peak-to-valley-dose-ratio (PVDR), percentage of GTV receiving 7.5 Gy, GTV mean dose, and maximum dose to organs-at-risk (OARs). RESULTS: For ±1, ±2, ±3, ±4, and ±5 mm isocenter shifts: PVDR dropped by 3.9%, 3.8%, 4.0%, 4.1%, and 5.5% on average respectively. The GTV(V7.5) remained within 0.2%, and the GTV mean dose remained within 3.3% on average, compared to the original plans. The average PVDR drop for 5 mm shifts was 4.2% for H&N cases, 10% for chest and lung, and 2.2% for abdominal and pelvis cases. OAR doses also increased. The maximum dose to the spinal cord increased by up to 17 cGy in H&N plans, mean lung dose (MLD) changed was small for chest/lung, but the bowel dose varied up to 100 cGy for abdominal and pelvis cases. CONCLUSION: Due to tumor size, location, and characteristics of MLC-based SFRT, isocenter shifts of up to ±5 mm in different directions had moderate effects on PVDR for H&N and pelvic tumors and a larger effect on chest tumors. The dosimetric impact on OAR doses depended on the treatment site. Site-specific patient masks, Vac-Lok bags, and proper immobilization devices similar to SBRT/SRT setups should be used to minimize these effects.

Stereotactic Body Radiotherapy (SBRT) to Localised Prostate Cancer in the Era of MRI-Guided Adaptive Radiotherapy: Doses Delivered in the HERMES Trial Comparing Two- and Five-Fraction Treatments.

HERMES is a phase II trial of MRI-guided daily-adaptive radiotherapy (MRIgART) randomising men with localised prostate cancer to either 2-fractions of SBRT with a boost to the tumour or 5-fraction SBRT. In the context of this highly innovative regime the dose delivered must be carefully considered. The first ten patients recruited to HERMES were analysed in order to establish the dose received by the targets and organs at risk (OARS) in the context of intrafraction motion. A regression analysis was performed to measure how the volume of air within the rectum might further impact rectal dose secondary to the electron return effect (ERE). One hundred percent of CTV target objectives were achieved on the MRI taken prior to beam-on-time. The post-delivery MRI showed that high-dose CTV coverage was achieved in 90% of sub-fractions (each fraction is delivered in two sub-fractions) in the 2-fraction cohort and in 88% of fractions the 5-fraction cohort. Rectal D1 cm3 was the most exceeded constraint; three patients exceeded the D1 cm3 < 20.8 Gy in the 2-fraction cohort and one patient exceeded the D1 cm3 < 36 Gy in the 5-fraction cohort. The volume of rectal gas within 1 cm of the prostate was directly proportional to the increase in rectal D1 cm3, with a strong (R = 0.69) and very strong (R = 0.90) correlation in the 2-fraction and 5-fraction cohort respectively. Dose delivery specified in HERMES is feasible, although for some patients delivered doses to both target and OARs may vary from those planned.

Magnetic resonance image-guided adaptive radiotherapy enables safe CTV-to-PTV margin reduction in prostate cancer: a cine MRI motion study.

Introduction: We aimed to establish if stereotactic body radiotherapy to the prostate can be delivered safely using reduced clinical target volume (CTV) to planning target volume (PTV) margins on the 1.5T MR-Linac (MRL) (Elekta, Stockholm, Sweden), in the absence of gating. Methods: Cine images taken in 3 orthogonal planes during the delivery of prostate SBRT with 36.25 Gray (Gy) in 5 fractions on the MRL were analysed. Using the data from 20 patients, the percentage of radiotherapy (RT) delivery time where the prostate position moved beyond 1, 2, 3, 4 and 5 mm in the left-right (LR), superior-inferior (SI), anterior-posterior (AP) and any direction was calculated. Results: The prostate moved less than 3 mm in any direction for 90% of the monitoring period in 95% of patients. On a per-fraction basis, 93% of fractions displayed motion in all directions within 3 mm for 90% of the fraction delivery time. Recurring motion patterns were observed showing that the prostate moved with shallow drift (most common), transient excursions and persistent excursions during treatment. Conclusion: A 3 mm CTV-PTV margin is safe to use for the treatment of 5 fraction prostate SBRT on the MRL, without gating. In the context of gating this work suggests that treatment time will not be extensively lengthened when an appropriate gating window is applied.

Stereotactic body radiation therapy (SBRT) for prostate cancer: Improving treatment delivery efficiency and accuracy.

Purpose: In stereotactic body radiation therapy (SBRT) for prostate cancer, intrafraction motion is an important source of treatment uncertainty as it could not be completely smoothed through fractionation. Herein, we compared different arrangements and beam qualities for extreme hypofractionated treatments to minimize beam delivery time and so intrafractional errors. Methods: A retrospective dataset of 11 patients was used. Three volumetric modulated arc therapy (VMAT) beam arrangements were compared for a prescription dose of 40 Gy/5 fractions: two full arcs, 6 MV flattening filter free (FFF); one full arc, 6 MV FFF; one full arc, 10 MV FFF. A plan quality index was defined to compare achievement of the planning goals. Plan complexity was evaluated with the modulation factor. Dose delivery accuracy and efficiency were measured with patient-specific quality assurance plans. Results: All treatment plans fulfilled all dose objectives. No statistical differences were found both in plan quality and complexity. Very accurate dose delivery was achieved with the three arrangements, with mean γ passing rates >96.5 % (2 %/2 mm criteria). Slightly but significantly higher γ passing rates were observed with single-arc 6 MV FFF. Contrariwise, statistically significant reductions of the delivery time were obtained with single-arc geometries: the average delivery times were 1.6 min (-46.1 %) and 1.3 min (-56.2 %) for 6 and 10 MV FFF respectively. Conclusions: The high-quality, very fast and accurate dose delivery of single-arc plans confirmed the suitability of this arrangement for prostate SBRT. In particular, the significant reduction of delivery time would improve treatment robustness against intrafraction prostate motion.

Treatment planning evaluation and experimental validation of the magnetic resonance-based intrafraction drift correction.

Background and purpose: MRI-guided online adaptive treatments can account for interfractional variations, however intrafraction motion reduces treatment accuracy. Intrafraction plan adaptation methods, such as the Intrafraction Drift Correction (IDC) or sub-fractionation, are needed. IDC uses real-time automatic monitoring of the tumor position to initiate plan adaptations by repositioning segments. IDC is a fast adaptation method that occurs only when necessary and this method could enable margin reduction. This research provides a treatment planning evaluation and experimental validation of the IDC. Materials and methods: An in silico treatment planning evaluation was performed for 13 prostate patients mid-treatment without and with intrafraction plan adaptation (IDC and sub-fractionation). The adaptation methods were evaluated using dose volume histogram (DVH) metrics. To experimentally verify IDC a treatment was mimicked whereby a motion phantom containing an EBT3 film moved mid-treatment, followed by repositioning of segments. In addition, the delivered treatment was irradiated on a diode array phantom for plan quality assurance purposes. Results: The planning study showed benefits for using intrafraction adaptation methods relative to no adaptation, where the IDC and sub-fractionation showed consistently improved target coverage with median target coverages of 100.0%. The experimental results verified the IDC with high minimum gamma passing rates of 99.1% and small mean dose deviations of maximum 0.3%. Conclusion: The straightforward and fast IDC technique showed DVH metrics consistent with the sub-fractionation method using segment weight re-optimization for prostate patients. The dosimetric and geometric accuracy was shown for a full IDC workflow using film and diode array dosimetry.

Intrafractional motion detection for spine SBRT via X-ray imaging using ExacTrac Dynamic.

Purpose: Due to its close vicinity to critical structures, especially the spinal cord, standards for safety for spine stereotactic body radiotherapy (SBRT) should be high. This study was conducted, to evaluate intrafractional motion during spine SBRT for patients without individualized immobilization (e.g., vacuum cushions) using high accuracy patient monitoring via orthogonal X-ray imaging. Methods: Intrafractional X-ray data were collected from 29 patients receiving 79 fractions of spine SBRT. No individualized immobilization devices were used during the treatment. Intrafractional motion was monitored using the ExacTrac Dynamic (ETD) System (Brainlab AG, Munich, Germany). Deviations were detected in six degrees of freedom (6 DOF). Tolerances for repositioning were 0.7 mm for translational and 0.5° for rotational deviations. Patients were repositioned when the tolerance levels were exceeded. Results: Out of the 925 pairs of stereoscopic X-ray images examined, 138 (15 %) showed at least one deviation exceeding the predefined tolerance values. In all 6 DOF together, a total of 191 deviations out of tolerance were recorded. The frequency of deviations exceeding the tolerance levels varied among patients but occurred in all but one patient. Deviations out of tolerance could be seen in all 6 DOF. Maximum translational deviations were 2.6 mm, 2.3 mm and 2.8 mm in the lateral, longitudinal and vertical direction. Maximum rotational deviations were 1.8°, 2.6° and 1.6° for pitch, roll and yaw, respectively. Translational deviations were more frequent than rotational ones, and frequency and magnitude of deviations showed an inverse correlation. Conclusion: Intrafractional motion detection and patient repositioning during spine SBRT using X-ray imaging via the ETD System can lead to improved safety during the application of high BED in critical locations. When using intrafractional imaging with low thresholds for re-positioning individualized immobilization devices (e.g. vacuum cushions) may be omitted.

Setup and intra-fractional motion measurements using surface scanning in head and neck cancer radiotherapy- A feasibility study.

Background and purpose: Surface-guided radiotherapy (SGRT) is applied to improve patient set-up and to monitor intra-fraction motion. Head and neck cancer (H&N) patients are usually fixated using 5-point thermoplastic masks, that are experienced as uncomfortable or even stressful. Therefore, the feasibility of irradiating H&N patients without a mask by using SGRT was examined. Material and methods: Nineteen H&N patients were included in a simulation study. Once a week, before the standard treatment, a maskless treatment was simulated, using SGRT for setup and intrafraction motion monitoring. Initial patient setup accuracy and intrafraction motion was determined using ConeBeam CT (CBCT) images as well as SGRT before and after the (simulated) treatment. The clinical target volume to planning target volume (CTV-PTV) margin for intrafraction motion was calculated. Using patient questionnaires, the patient-friendliness H&N irradiation with and without mask was determined. Results: Maskless setup with SGRT and CBCT was as accurate as with a mask. SGRT showed that intrafraction motion was gradual during the treatment. The CTV-PTV margin correcting for intrafraction motion was 1.7 mm for maskless treatment without interventions, and 1.2 mm if corrected for motions > 2 mm. For 19 % of fractions, the intrafraction motion, as detected by both SGRT and CBCT, was larger than 2 mm in at least one direction. Sixteen patients preferred maskless treatment, while 3 worried they would move too much. Conclusions: Using SGRT and a standard head rest resulted in a patient-friendly treatment with accurate patient setup and acceptably small intrafraction motion for H&N patients.

Electromagnetic Transmitter-Based Prostate Gating for Dose-Escalated Linac-Based Stereotactic Body Radiation Therapy: An Evaluation of Intrafraction Motion.

BACKGROUND: Stereotactic Body Radiotherapy (SBRT) is as a standard treatment for prostate cancer (PCa). Tight margins and high dose gradients are needed, and the precise localization of the target is mandatory. Our retrospective study reports our experience regarding the evaluation of intrafraction prostate motion during LINAC-based SBRT evaluated with a novel electromagnetic (EM) tracking device. This device consists of an integrated Foley catheter with a transmitter connected to a receiver placed on the treatment table. METHODS: We analyzed 31 patients who received LINAC-based SBRT using flattening filter-free (FFF) volumetric modulated arc therapy (VMAT). The patients were scheduled to be treated for primary (n = 27) or an intraprostatic recurrent PCa (n = 4). A simulation CT scan was conducted while the patients had a filled bladder (100-150 cc) and an empty rectum, and an EM tracking device was used. The same rectal and bladder conditions were employed during the treatment. The patients received 36.25 Gy delivered over five consecutive fractions on the whole prostate and 40 Gy on the nodule(s) visible via MRI, both delivered with a Simultaneous Integrated Boost approach. The CTV-to-PTV margin was 2 mm for both the identified treatment volumes. Patient positioning was verified with XVI ConeBeam-CT (CBCT) matching before each fraction. When the signals exceeded a 2 mm threshold in any of the three spatial directions, the treatment was manually interrupted. A new XVI CBCT was performed if this offset lasted >20 s. RESULTS: We analyzed data about 155 fractions. The median and mean treatment times, calculated per fraction, were 10 m31 s and 12 m44 s (range: 6 m36 s-65 m28 s), and 95% of the fractions were delivered with a maximum time of 27 m48 s. During treatment delivery, the mean and median number of XVI CBCT operations realized during the treatment were 2 and 1 (range: 0-11). During the treatment, the prostate was outside the CTV-to-PTV margin (2 mm), thus necessitating the stoppage of the delivery +/- a reacquisition of the XVI CBCT for 11.2%, 8.9%, and 3.9% of the delivery time in the vertical, longitudinal, and lateral direction, respectively. CONCLUSIONS: We easily integrated an EM-transmitter-based gating for prostate LINAC-based SBRT into our normal daily workflow. Using this system, a 2 mm CTV-to-PTV margin could be safely applied. A small number of fractions showed a motion exceeding the predefined 2 mm threshold, which would have otherwise gone undetected without intrafraction motion management.

Prostate cancer image guided radiotherapy: Why the commotion over rectal volume and motion?

Introduction: Distended rectums on pre-radiotherapy scans are historically associated with poorer outcomes in patients treated with two-dimensional IGRT. Subsequently, strict rectal tolerances and preparation regimes were implemented. Contemporary IGRT, daily online registration to the prostate, corrects interfraction motion but intrafraction motion remains. We re-examine the need for rectal management strategies when using contemporary IGRT by quantifying rectal volume and its effect on intrafraction motion. Materials and methods: Pre and during radiotherapy rectal volumes and intrafraction motion were retrospectively calculated for 20 patients treated in 5-fractions and 20 treated in 20-fractions. Small (rectal volume at planning-CT ≤ median), and large (volume > median) subgroups were formed, and rectal volume between timepoints and subgroups compared. Rectal volume and intrafraction motion correlation was examined using Spearman's rho. Intrafraction motion difference between small and large subgroups and between fractions with rectal volume < or ≥ 90 cm3 were assessed. Results: Median rectal volume was 74 cm3, 64 cm3 and 65 cm3 on diagnostic-MRI, planning-CT and treatment imaging respectively (ns). No significant correlation was found between patient's rectal volume at planning-CT and median intrafraction motion, nor treatment rectal volume and intrafraction motion for individual fractions. No significant difference in intrafraction motion between small and large subgroups presented and for fractions where rectal volume breached 90 cm3, motion during that fraction was not significantly greater. Conclusion: Larger rectal volumes before radiotherapy and during treatment did not cause greater intrafraction motion. Findings support the relaxation of strict rectal diameter tolerances and do not support the need for rectal preparation when delivering contemporary IGRT to the prostate.

MRI-based inter- and intrafraction motion analysis of the pancreatic tail and spleen as preparation for adaptive MRI-guided radiotherapy in neuroblastoma.

BACKGROUND: In pediatric radiotherapy treatment planning of abdominal tumors, dose constraints to the pancreatic tail/spleen are applied to reduce late toxicity. In this study, an analysis of inter- and intrafraction motion of the pancreatic tail/spleen is performed to estimate the potential benefits of online MRI-guided radiotherapy (MRgRT). MATERIALS AND METHODS: Ten randomly selected neuroblastoma patients (median age: 3.4 years), irradiated with intensity-modulated arc therapy at our department (prescription dose: 21.6/1.8 Gy), were retrospectively evaluated for inter- and intrafraction motion of the pancreatic tail/spleen. Three follow-up MRIs (T2- and T1-weighted ± gadolinium) were rigidly registered to a planning CT (pCT), on the vertebrae around the target volume. The pancreatic tail/spleen were delineated on all MRIs and pCT. Interfraction motion was defined as a center of gravity change between pCT and T2-weighted images in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) direction. For intrafraction motion analysis, organ position on T1-weighted ± gadolinium was compared to T2-weighted. The clinical radiation plan was used to estimate the dose received by the pancreatic tail/spleen for each position. RESULTS: The median (IQR) interfraction motion was minimal in LR/AP, and largest in CC direction; pancreatic tail 2.5 mm (8.9), and spleen 0.9 mm (3.9). Intrafraction motion was smaller, but showed a similar motion pattern (pancreatic tail, CC: 0.4 mm (1.6); spleen, CC: 0.9 mm (2.8)). The differences of Dmean associated with inter- and intrafraction motions ranged from - 3.5 to 5.8 Gy for the pancreatic tail and - 1.2 to 3.0 Gy for the spleen. In 6 out of 10 patients, movements of the pancreatic tail and spleen were highlighted as potentially clinically significant because of ≥ 1 Gy dose constraint violation. CONCLUSION: Inter- and intrafraction organ motion results into unexpected constrain violations in 60% of a randomly selected neuroblastoma cohort, supporting further prospective exploration of MRgRT.

Gating and intrafraction drift correction on a 1.5 T MR-Linac: Clinical dosimetric benefits for upper abdominal tumors.

This work reports on the first seven patients treated with gating and baseline drift correction on the high-field MR-Linac system. Dosimetric analysis showed that the active motion management system improved congruence to the planned dose, efficiently mitigating detrimental effects of intrafraction motion in the upper abdomen.

Accelerating 4D image reconstruction for magnetic resonance-guided radiotherapy.

Background and purpose: Physiological motion impacts the dose delivered to tumours and vital organs in external beam radiotherapy and particularly in particle therapy. The excellent soft-tissue demarcation of 4D magnetic resonance imaging (4D-MRI) could inform on intra-fractional motion, but long image reconstruction times hinder its use in online treatment adaptation. Here we employ techniques from high-performance computing to reduce 4D-MRI reconstruction times below two minutes to facilitate their use in MR-guided radiotherapy. Material and methods: Four patients with pancreatic adenocarcinoma were scanned with a radial stack-of-stars gradient echo sequence on a 1.5T MR-Linac. Fast parallelised open-source implementations of the extra-dimensional golden-angle radial sparse parallel algorithm were developed for central processing unit (CPU) and graphics processing unit (GPU) architectures. We assessed the impact of architecture, oversampling and respiratory binning strategy on 4D-MRI reconstruction time and compared images using the structural similarity (SSIM) index against a MATLAB reference implementation. Scaling and bottlenecks for the different architectures were studied using multi-GPU systems. Results: All reconstructed 4D-MRI were identical to the reference implementation (SSIM > 0.99). Images reconstructed with overlapping respiratory bins were sharper at the cost of longer reconstruction times. The CPU  + GPU implementation was over 17 times faster than the reference implementation, reconstructing images in 60 ± 1 s and hyper-scaled using multiple GPUs. Conclusion: Respiratory-resolved 4D-MRI reconstruction times can be reduced using high-performance computing methods for online workflows in MR-guided radiotherapy with potential applications in particle therapy.

Plan robustness analysis for threshold determination of SGRT-based intrafraction motion control in 3DCRT breast cancer radiation therapy.

PURPOSE: The goal of this study was to obtain maximum allowed shift deviations from planning position in six degrees of freedom (DOF), that can serve as threshold values in surface guided radiation therapy (SGRT) of breast cancer patients. METHODS: The robustness of conformal treatment plans of 50 breast cancer patients against 6DOF shifts was investigated. For that, new dose distributions were calculated on shifted computed tomography scans and evaluated with respect to target volume and spinal cord dose. Maximum allowed shift values were identified by imposing dose constraints on the target volume dose coverage for 1DOF, and consecutively, for 6DOF shifts using an iterative approach and random sampling. RESULTS: Substantial decreases in target dose coverage and increases of spinal cord dose were observed. Treatment plans showed highly differing robustness for different DOFs or treated area. The sensitivity was particularly high if clavicular lymph nodes were irradiated, for shifts in lateral, vertical, roll or yaw direction, and showed partly pronounced asymmetries. Threshold values showed similar properties with an absolute value range of 0.8 mm to 5 mm and 1.4° to 5°. CONCLUSION: The robustness analysis emphasized the necessity of taking differences between DOFs and asymmetrical sensitivities into account when evaluating the dosimetric impact of position deviations. It also highlighted the importance of rotational shifts, especially if clavicular lymph nodes were irradiated. A practical approach of determining 6DOF shift limits was introduced and a set of threshold values applicable for SGRT based patient motion control was identified.

Planning CT Identifies Patients at Risk of High Prostate Intrafraction Motion.

Prostate motion (standard deviation, range of motion, and diffusion coefficient) was calculated from 4D ultrasound data of 1791 fractions of radiation therapy in N = 100 patients. The inner diameter of the lesser pelvis was obtained from transversal slices through the pubic symphysis in planning CTs. On the lateral and craniocaudal axes, motility increases significantly (t-test, p < 0.005) with the inner diameter of the lesser pelvis. A diameter of >106 mm (ca. 6th decile) is a good predictor for high prostate intrafraction motion (ca. 9th decile). The corresponding area under the receiver operator curve (AUROC) is 80% in the lateral direction, 68% to 80% in the craniocaudal direction, and 62% to 70% in the vertical direction. On the lateral x-axis, the proposed test is 100% sensitive and has a 100% negative predictive value for all three characteristics (standard deviation, range of motion, and diffusion coefficient). On the craniocaudal z-axis, the proposed test is 79% to 100% sensitive and reaches 95% to 100% negative predictive value. On the vertical axis, the proposed test still delivers 98% negative predictive value but is not particularly sensitive. Overall, the proposed predictor is able to help identify patients at risk of high prostate motion based on a single planning CT.

Stereotactic Body Radiation Therapy for Prostate Cancer Using Tomotherapy With Synchrony Fiducial Tracking.

Numerous prospective and retrospective studies have demonstrated the efficacy and safety of stereotactic body radiation therapy (SBRT) for prostate cancer. Since SBRT utilizes a very tight margin, management of intrafraction prostate motion is necessary. As a real-time motion tracking and correction system (Synchrony; Accuray, Sunnyvale, CA) has been introduced in the newer platform of tomotherapy (Radixact; Accuray), Radixact can deliver tracking SBRT. In the case report, we present the first clinical experience with prostate SBRT using tomotherapy with Synchrony fiducial tracking.

Assessment of intrafraction motion and its dosimetric impact on prostate radiotherapy using an in-house developed position monitoring system.

Purpose: To implement an in-house developed position monitoring software, SeedTracker, for conventional fractionation prostate radiotherapy, and study the effect on dosimetric impact and intrafraction motion. Methods: Thirty definitive prostate radiotherapy patients with implanted fiducial markers were included in the study. All patients were treated with VMAT technique and plans were generated using the Pinnacle planning system using the 6MV beam model for Elekta linear accelerator. The target dose of 60 Gy in 20 fractions was prescribed for 29 of 30 patients, and one patient was treated with the target dose of 78 Gy in 39 fractions. The SeedTracker position monitoring system, which uses the x-ray images acquired during treatment delivery in the Elekta linear accelerator and associated XVI system, was used for online prostate position monitoring. The position tolerance for online verification was progressively reduced from 5 mm, 4 mm, and to 3 mm in 10 patient cohorts to effectively manage the treatment interruptions resulting from intrafraction motion in routine clinical practice. The delivered dose to target volumes and organs at risk in each of the treatment fractions was assessed by incorporating the observed target positions into the original treatment plan. Results: In 27 of 30 patients, at least one gating event was observed, with a total of 177 occurrences of position deviation detected in 146 of 619 treatment fractions. In 5 mm, 4 mm, and 3 mm position tolerance cohorts, the position deviations were observed in 13%, 24%, and 33% of treatment fractions, respectively. Overall, the mean (range) deviation of -0.4 (-7.2 to 5.3) mm, -0.9 (-6.1 to 15.6) mm, and -1.7 (-7.0 to 6.1) mm was observed in Left-Right, Anterior-Posterior, and Superior-Inferior directions, respectively. The prostate CTV D99 would have been reduced by a maximum value of 1.3 Gy compared to the planned dose if position deviations were uncorrected, but with corrections, it was 0.3 Gy. Similarly, PTV D98 would have been reduced by a maximum value of 7.6 Gy uncorrected, with this difference reduced to 2.2 Gy with correction. The V60 to the rectum increased by a maximum of 1.0% uncorrected, which was reduced to 0.5%. Conclusion: Online target position monitoring for conventional fractionation prostate radiotherapy was successfully implemented on a standard Linear accelerator using an in-house developed position monitoring software, with an improvement in resultant dose to prostate target volume.