LR Directions Research Articles

Reducing planning target volume margins decreases dose to parotid glands in head and neck cancers - a dosimetric analysis

Introduction: Radiotherapy in head and neck cancers is treated for several weeks and daily setup and reproducibility is a challenge. This daily variability causes setup errors which accounts planning target volume margins. Reduced PTV margins have to be taken to decrease the dose to the parotid glands, without compromising on loco regional control rates. The present study is done to identify setup errors and see the feasibility to decrease the PTV margins by creating dummy radiotherapy plans in order to decrease dose to parotid glands. Material and Methods: 420 portal images were evaluated for setup errors in three dimensions (Antero Posterior, Left to Right and Superior to Inferior) which were performed in ten patients of oropharyngeal squamous cell carcinoma. All patients were treated in supine position using immobilization cast. After target volume delineation a PTV margin of 7mm was given. Dosimetric parameters of PTV and organs at risk were assessed. PTV margins were calculated according to three methods proposed by Stroom, Van Herk and ICRU 62. Dummy radiotherapy plans were generated using new PTV margins and compared with 7mm PTV margins. The data was analyzed using 3-way ANNOVA test for statistical significance. Results: The optimum PTV margins were 4mm in LR and SI direction and 7mm in AP direction. The PTV parameters (V95, D95, Dmax, Dmean, HI and CI) had no significant difference among different radiotherapy plans with different PTV margins. There was a significant decrease in the dose to right parotid (39.12 Gy to 32.88Gy; p-0.04), left parotid (37.90 to 31.21Gy; p-0.03) and parotid combined (38.65 to 31.45 Gy; p-0.01) when 7mm PTV margins were reduced to 4mm PTV margins. The results of dummy radiotherapy plans using asymmetric PTV margins (LR-4mm, SI-4mm and AP-7mm) and symmetrical PTV margins (4mm in all directions) are compared with PTV margins (7mm in all directions), in terms of PTV and OAR dosimetric parameters. Conclusion: The decreased PTV margins of 4mm decreases the dose to the parotid significantly. The implementation of radiotherapy plans needs to be supplemented by daily IGRT.

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

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

Real-time direct diaphragm tracking using kV imaging on a standard linear accelerator.

As the predominant driver of respiratory motion, the diaphragm represents a key surrogate for motion management during the irradiation of thoracic cancers. Existing approaches to diaphragm tracking often produce phase-based estimates, suffer from lateral side failures or are not executable in real-time. In this paper, we present an algorithm that continuously produces real-time estimates of three-dimensional (3D) diaphragm position using kV images acquired on a standard linear accelerator. Patient-specific 3D diaphragm models were generated via automatic segmentation on end-exhale four-dimensional-computed tomography (4D-CT) images. The estimated trajectory of diaphragmatic motion, referred to as the principal motion vector, was obtained by registering end-exhale to end-inhale 4D-CT images. Two-dimensional (2D) diaphragm masks were generated by forward-projecting 3D models over the complement of angles spanned during kV image acquisition. For each kV image, diaphragm position was determined by shifting angle-matched 2D masks along the principal motion vector and selecting the position of highest contrast on a vertical difference image. Retrospective analysis was performed using 22 cone beam CT (CBCT) image sequences for six lung cancer patients across two datasets. Given the current lack of objective ground truth for diaphragm position, our algorithm was evaluated by examining its ability to track implanted markers. Simple linear regression was used to construct 3D marker motion models and estimation errors were computed as the difference between estimated and ground truth marker positions. Additionally, Pearson correlation coefficients were used to characterize diaphragm-marker correlation. The mean±standard deviation of the estimation errors across all image sequences was -0.1±0.7mm, -0.1±1.8mm and 0.2±1.4mm in the LR, SI, and AP directions respectively. The 95th percentile of the absolute errors ranged over 0.5-3.1mm, 1.6-6.7mm, and 1.2-4.0mm in the LR, SI, and AP directions, respectively. The mean±standard deviation of diaphragm-marker correlations over all image sequences was -0.07±0.57, 0.67±0.49, and 0.29±0.52 in the LR, SI, and AP directions, respectively. Diaphragm-marker correlation was observed to be highly dependent on marker position. Mean correlation along the SI axis ranged over 0.91-0.93 for markers situated in the lower lobes of the lung, while correlations ranging over -0.51-0.79 were observed for markers situated in the upper and middle lobes. This work advances a new approach to real-time direct diaphragm tracking in realistic treatment scenarios. By achieving continuous estimates of diaphragmatic motion, the proposed method has applications for both markerless tumor tracking and respiratory binning in 4D-CBCT.

Impact of daily soft-tissue image guidance to prostate on pelvic lymph node (PLN) irradiation for prostate patients receiving SBRT.

PurposeTo determine the impact of using fiducial match for daily image‐guidance on pelvic lymph node (PLN) coverage for prostate cancer patients receiving stereotactic body radiation therapy (SBRT).MethodsThirty patients underwent SBRT treatment to the prostate and PLN from 2014 to 2016. Each patient received either 800cGy × 5 or 500cGy × 5 to the prostate and 500cGy × 5 to the PLN. A 5 mm clinical target volume (CTV)‐to‐planning target volume (PTV) margin around the PLN was used for planning. Two registrations with planning computed tomography (PCT) for each of the daily cone beam CTs (CBCTs) were performed: a rigid registration to fiducials and to the bony anatomy. The average translational difference between fiducial and bony match as well as percentage of fractions with differences > 5mm were calculated. Changes in bladder and rectal volume as well as center‐of‐mass (COM) position from simulation parameters, and their correlation with translational difference were also evaluated. The dosimetric impact of the translational differences was calculated by shifting the plan isocenter.ResultsThe average translational difference between fiducial and bony match was 0.06 ± 0.82, 2.1 ± 4.1, −2.8 ± 4.3, and 5.5 ± 4.2 mm for lateral, vertical, longitudinal, and vector directions. The average change in bladder and rectal volume from simulation was −67.2 ± 163.04 cc (−12 ± 52%) and −1.6 ± 18.75 (−2 ± 30%) cc. The average change in COM of bladder from the simulation position was 0.34 ± 2.49, 4.4 ± 8.1, and −3.9 ± 7.5 mm along the LR, AP, and SI directions. The corresponding COM change for the rectum was 0.17 ± 1.9, 1.34 ± 3.5, and −0.6 ± 5.2 mm.ConclusionsThe 5 mm margin covered ~75% of fractions receiving PLN irradiation with SBRT, daily CBCT and fiducial‐guided setup. The dosimetric impact on PLN coverage was significant in 19% of fractions or 25% of patients. A larger translational shift was due to variation in rectal volume and changes in COM position of the bladder and rectum. A consistent bladder positioning and/or rectum filling compared with presimulation volume were essential for adequate coverage of PLN in a hypofractionated treatment regime.

A six-degree-of-freedom robotic motion system for quality assurance of real-time image-guided radiotherapy

In this study we develop and characterise a six degree-of-freedom (6 DoF) robotic motion system for quality assurance of real-time image-guided radiotherapy techniques. The system consists of a commercially available robotic arm, an acrylic phantom with embedded Calypso markers, a custom base plate to mount the robot to the treatment couch, and control software implementing the appropriate sequence of transformations to reproduce measured tumour motion traces. The robotic motion system was evaluated in terms of the set-up and motion trace repeatability, static localization accuracy and dynamic localization accuracy. Four prostate, two liver and three lung motion traces, representing a range of tumor motion trajectories recorded in real patient treatments, were executed using the robotic motion system and compared with motion measurements from the clinical Calypso motion tracking system. System set-up and motion trace repeatability was better than 0.5 deg and 0.3 mm for rotation and translation, respectively. The static localization accuracy of the robotic motion system in the LR, SI and AP directions was 0.09 mm, 0.08 mm and 0.02 mm for translations, respectively, and 0.2°, 0.06° and 0.06° for rotations, respectively. The dynamic localization accuracy of the robotic motion system was <0.2 mm and <0.6° for translations and rotations, respectively. Thus, we have demonstrated the ability to accurately mimic rigid-body tumor motion using a robotically controlled phantom to provide precise geometric QA for advanced radiotherapy delivery approaches.

A Prospective Study to Investigate the Placement of Setup Skin Markings for Larger Breasted Women Undergoing External Beam Radiotherapy (RT) for Breast Cancer

Background: The technique of placing all three skin marks (reference skin marks) on a single position during CT simulation for setup of patients undergoing conventional breast radiotherapy becomes a challenge when presented with larger breasted women (bra cup size ≥ D). A new way of using skin marks in setting these patients up has been developed where three skin marks are made on the patient (one on the sternum and two lateral skin marks more inferiorly beneath the breasts) for setup as against the departmental standard of using only a single skin mark on the sternum, and employing an SSD (Source to Skin Distance) technique. This study therefore reviewed the placement of the skin markings for larger breasted women undergoing external beam radiotherapy for breast cancer by quantifying treatment field alignment errors and setup errors between the two different setup techniques. Method: 36 patients were used in this study. Out of this number, 18 were setup using three reference skin marks and the remaining 18 were setup using one reference anterior skin mark. With an acceptable patient treatment field alignment error of 2 degrees, portal images (AP and lateral) of the different skin mark techniques were analysed for field alignment errors using an Iview GT system. More so, portal images (AP and lateral) of setup for both techniques were analysed for systematic (Σ) and random (σ) errors. Results:The AP images of the single skin mark setup and the three skin mark setup yielded no significant difference as they recorded a p- value (p&lt;0.05) of 0.089 and 0.110 respectively when compared to the treatment field alignment threshold error of 2 degrees. The lateral images of the three skin mark also yielded no significant difference as a p- value (p&lt;0.05) of 0.091 was recorded. The lateral images of the single skin mark yielded a significant difference with a p- value (p&lt;0.05) of 0.026. Secondly, mean comparisons of the field alignment errors between the two setup techniques yielded no significant difference in the AP images as a p- value (p&lt;0.05) of 0.089 was detected. On the contrary, a p- value (p&lt;0.05) of 0.026 was recorded in the field alignment errors of the lateral images. This difference is significant. Lastly, random errors were reduced in all directions (AP- anterior-posterior, SI- superior-inferior and LR- Left-right) in the three skin mark setup (4.5mm AP, 4.9mm SI and 2.4mm LR) as compared to the single skin mark setup (4.7mm AP, 5.2mm SI and 2.6mm LR). Systematic errors were also reduced in the three skin mark setup (1.7mm AP and 1.8mm SI) compared to the single skin mark setup (2.0mm AP, 2.1mm SI). Systematic errors in the LR direction on the other hand increased from 2.0mm in the single skin mark to 2.2mm in the three skin marks. Conclusion For setup of larger breasted women undergoing external beam radiotherapy for breast cancer, the three skin mark setup technique is superior to the single skin mark setup technique.

2 Clinical use of 4D CBCT: ITV volume and amplitude study

Introduction After the validation of the respiratory correlated CBCT using a dynamic thorax phantom, investigations on the accuracy of the 4D CBCT were made on clinical data (i.e. patients 4D CBCT). A first study consisted in the evaluation of the difference in terms of positioning corrections between 3D CBCT and 4D CBCT images. Then, a second study compared the ITV volume between different imaging modalities (4D CT, 3D CBCT and 4D CBCT) and estimated the interfraction changes in breathing amplitude. Materials and Methods Five patients with a lung tumor treated in ITV strategy were included in the first study. They had both 3D CBCT and 4D CBCT pre-treatment images. A total of 44 CBCT images were retrospectively analyzed. A 4D CBCT image was first acquired and a 3D region-of-interest (ROI) mask registration was computed and applied in order to pre-position the patient. A 3D-CBCT image was then acquired and 3D ROI mask registration was computed but not applied. Only the patients treated with SBRT were included in the second study. A physician delineated ITV on different average images (4D CT, 3D CBCT and 4D CBCT) using a MonacoSim (Elekta) workstation. These contours were compared using a dice coefficient. Tumor motion amplitude from daily 4D CBCT was directly obtained with the on-line reconstruction software Symmetry (Elekta) and the amplitude variation was then computed. Results The average residual positioning corrections between 4D and 3D CBCT images were 0.06, 0.08 and 0.07 cm for LR, SI and AP direction respectively; and were respectively 0.41, 0.62, 0.21° for pitch, roll and yaw. From our preliminary results, the dice coefficients found were 0.77 ± 0.13, 0.70 ± 0.14 and 0.84 ± 0.11 between 4D CT and 4D CBCT, 4D CT and 3D CBCT and 3D CBCT and 4D CBCT images respectively. Interfraction changes in breathing amplitude were negligible in the LR and AP directions. The average breathing amplitude variation was 0.31 cm in SI direction (maximum of 0.44 cm). Conclusion Similar positioning corrections were found using a 3D ROI registration on either a 3D CBCT image or a 4D CBCT image. Since 4D CBCT allows a better visual inspection, it is now systematically used for lung SBRT patient positioning. ITV contours study suggests an overestimation of the ITV from 4D CT images compared to 4D CBCT images. The dice coefficient showed a better correspondence between ITV from 4D CT compared to 4D CBCT than between ITV from 4D CT and 3D CBCT. However, a satisfying correlation between 3D CBCT and 4D CBCT ITV contours was found. Interfractional changes in breathing amplitudes need to be further investigated and compared to treatment margins.

Target Site Analysis of Set-up and Positioning Accuracy for Head and Neck Stereotactic Ablative Radiation Therapy (SABR)

Stereotactic ablative radiotherapy (SABR) is utilized to address recurrent and/or previously irradiated head and neck cancers (HNC) and requires high set-up accuracy. We previously demonstrated excellent results with our custom cushion/mask/bite-block (CMB) immobilization system. Here, we compare set-up and positioning accuracy across different head and neck tumor locations to further optimize PTV margins for SABR treatment planning and delivery. We analyzed 375 treatment sessions across 73 patients with recurrent HNC treated with SABR using our custom CMB immobilization system. Initial set-up was performed using ExacTrac infrared tracking, and interfractional error was determined by comparing initial X-ray to the treatment plan. Patients were then shifted using ExacTrac and the residual set-up error was measured with repeat X-ray verification. Next, cone-beam CT (CBCT) was obtained and compared to ExacTrac for 3-dimensional positioning agreement. Finally, intrafractional positioning errors were measured by taking pre-beam X-ray. The data was stratified based on treatment site: paranasal sinus, nasopharynx, skull base (SB), cervical and parotid nodes (Neck), and oropharynx, oral cavity, larynx (Mucosal). The median dose and volume were 45Gy in 5 fractions (range: 27-47.5Gy, 3-5 fractions) and 17.12cm3 (range: 1.47-69.20cm3). There were no significant differences in the mean age, treatment volume, or monitor units (MU) between groups. The initial translational set-up errors were -0.3 ± 1.1mm, 0.3 ± 1.5mm, and -0.2 ± 1.4mm in the AP, CC, and LR directions, respectively. Site-specific mean 3D interfractional vectors were 2.2 ± 1.2mm (SB; P<0.00001 vs others), 2.9 ± 1.4mm (Neck), and 2.5 ± 1.7mm (Mucosal). Overall, the mean ExacTrac-CBCT agreement was between -0.1 and 0.1mm in translational and rotation directions, and overall residual errors were -0.1 ± 0.2mm, 0.0 ± 0.2mm, and 0.0 ± 0.2mm in the AP, CC, and LR directions, respectively. Site-specific mean 3D residual vectors were 0.4 ± 0.3mm (SB), 0.7 ± 0.7mm (Neck), and 0.5 ± 0.3mm (Mucosal), with a residual 3D vector >1.0mm occurring in 5.4% of SB patients compared to 26.1% (Neck) and 26.7% (Mucosal)(P=0.013). Intrafractional errors showed a mean 3D vector of 0.7 ± 0.5mm (SB; P<0.05 vs others), 1.3 ± 0.9mm (Neck), and 1.4 ± 1.5mm (Mucosal). An intrafractional 3D vector >1.0mm occurred in 16.2% of SB patients compared to 52.2% (Neck) and 46.7% (Mucosal) (P<0.0001). The calculated PTV margin for each site was ≤1.3mm (Skull Base), ≤2.2mm (Neck), and ≤3.4mm (Mucosal). In a large comparison of set-up and positioning accuracy for head and neck SABR, PTV treatment margins can be optimized depending on the treatment site. The error magnitude is significantly smaller for skull base targets and a 2-mm PTV margin may be sufficient. For mucosal targets, a 4-mm PTV margin may be necessary to account for internal organ motion.

Geometric Reproducibility of Fiducial Markers and Efficacy of a Patient-Specific Margin Design Using Active Breath Hold for Pancreas Stereotactic Body Radiation Therapy

In patients undergoing SBRT for pancreatic adenocarcinoma using an active breathing control (ABC), the reproducibility of fiducial positioning between breath-holds is unclear. We characterized this variation by acquiring multiple breath-hold CTs at time of simulation and analyzed whether a patient-specific margin based on this variation would help account for intra-fraction variation at time of treatment. We analyzed five pancreatic cancer patients who underwent SBRT for pancreatic adenocarcinoma and who were treated with ABC. At time of simulation, 3-additional breath-hold scans were acquired immediately after the primary contrast-enhanced planning CT with 2-mm slice thickness. To characterize the variability in tumor position between breath-holds, fiducial centroids from the planning CT were used as the reference and compared to the fiducial centroids from the additional breath-hold CTs. Both the average excursions in fiducial position (Sim Varavg) and the maximum excursions in fiducial position (Sim Varmax) were calculated. For treatment planning for each patient, the amount of variation in each direction between breath-holds was applied as a margin to the GTV, followed by an additional 2-mm margin to determine the final PTV. The difference in volume between this method versus directly expanding the GTV by a uniform 2-mm expansion was calculated. During 5-fraction treatment, 20-27 breath-hold CBCTs were acquired for each patient. The intrafraction variation in fiducial position was calculated using the same method as above, using the initial CBCT for that fraction as the reference CT and using similar metrics to characterize fiducial position variation (Tx Varavg and Tx Varmax). The adequacy of a direct 2-mm expansion on the GTV was analyzed by evaluating the percentage of fiducial locations within 2-mm of variability on CBCTs. Table 1 summarizes the breath-hold reproducibility averaged over all five patients at CT sim and treatment. By applying the variation seen during multiple breath-holds at time of simulation to the GTV volume before further expanding by 2 mm, the final PTV volume increased by 19.5 ± 7.0% as compared to a uniform 2-mm expansion off of the GTV. However, by using this patient-specific margin, 95% of the all fiducial locations during treatment were encompassed within this volume, while a uniform 2-mm expansion only covered the fiducials 80% in both LR and AP directions and 60% in the SI direction.Abstract SU_18_2175; Table 1Inter-BH reproducibilityLR (mm)AP (mm)SI (mm)Sim Varavg0.8 ± 0.51.0 ± 0.41.5 ± 0.7Sim Varmax1.2 ± 0.71.4 ± 0.52.3 ± 0.6Tx Varavg1.2 ± 0.51.4 ± 0.62.1 ± 0.4Tx Varmax4.7 ± 2.15.5 ± 3.06.4 ± 2.4 Open table in a new tab Variation in tumor position exists between breath-holds when treating with ABC. Acquiring multiple breath-hold CTs during simulation can help quantify inter-breath-hold reproducibility and can provide a patient specific margin design to compensate for the variation in tumor position between breath-holds at time of treatment.

Feasibility of MR-Generated Synthetic CT Images for Planning Stereotactic Radiosurgery of Brain Metastases

Frameless Linac-based stereotactic radiosurgery (SRS) treatment planning typically involves spatial registration of MR and CT images. A solely MR-guided workflow would eliminate the burdens of CT scanning and associated time as well as alignment errors, but would require dose calculations and patient positioning based on MR-derived information. The feasibility of MR-guided SRS of brain metastases was investigated. Specifically, it was hypothesized that synthetic CT images (MRCTs) could be used to generate plans and reference images for positioning that would not differ from SRS using a traditional CT-guided technique. MR and CT images were acquired for 19 patients undergoing SRS for brain metastases. Following rigid image alignment, PTV and OAR contours were delineated. MRCT image volumes were generated using a voxel-based probabilistic classification technique and aligned rigidly to their respective CT scans. The CT structures were transferred onto the MRCT volumes. CT-based plans were created with the intent to deliver 99.5% of the prescription dose to the PTV and avoid excess doses to the OARs. The fluences from the CT plans then were used for dose calculations on a “maskless” CT plan (in which the attenuation of the immobilization device was removed) and MRCT images. PTV D99.5 and OAR D0.1 cc values were compared. OARs (brainstem, optic nerves/chiasm, eyes, lenses, cochleae) typically defined on CT were drawn on the source MR (T1- and T2-weighted image volumes) images and compared to the original CT volumes. Cone beam CT (CBCT) volumes used for positioning at treatment were aligned to the MRCT and CT volumes, and resulting transforms compared. A total of 43 PTVs were studied with a mean prescription dose of 21.1 Gy (range 12 to 30 Gy). The mean difference in PTV D99.5 between the CT versus maskless CT was 0.0 % (range -0.0 to 0.1 %) and CT versus MRCT was 0.0 % (range -0.1 to 0.0 %) of the prescription doses. Dose metrics for a total of 185 OARs were calculated. OAR D0.1 cc difference between the CT versus maskless CT was 0.0 Gy (range -0.1 to 0.0 Gy) and CT versus MRCT was 0.0 Gy (range -0.2 to 0.7 Gy). For OAR volumes larger than 1 cc (n=64), the mean Dice coefficient between CT and MR structures was 0.82 (range 0.17 to 0.93). Mean differences in alignment between the CBCT volumes and MRCT and CT volumes resulted in isocenter positioning differences of 0.0 mm (range -0.2 to 0.1 mm), 0.0 mm (range -0.5 to 0.4 mm), and 0.1 mm (range -0.2 to 0.5 mm) in the LR, AP, and CC directions. The accuracy of delineation, calculated doses, and patient positioning indicate that MR-guided frameless SRS is feasible. Future investigations will explore generation of reference image volumes for alignment that combine MR and synthesized CT contrasts. Supported by NIH R01EB016079.

Impact of immobilization base plates composed of various materials on the imaging quality of MR simulation during radiotherapy

Objective To compare the impact of immobilization base plates composed of 7 types of materials on the MR-simulation imaging quality used for radiotherapy, aiming to provide reference data for clinical applications. Methods Using identical T1 and T2 sequences of Siemens MR-simulator, the MR images of ACR Large Phantom were acquired on the Orfit carbon fiber laminate, polycarbonate (PC), high precision base plate (HP), Jinan Huayuxin BR, WR, KP and SP materials, respectively. The imaging quality without any plate was used as the baseline data. The following metrics were compared: 1.High-contrast spatial resolution: the sharpness of 3 pairs of hole arrays was observed, which represented resolutions of 1.1 mm, 1.0 mm and 0.9 mm on the LR and AP directions; 2.Image intensity uniformity in terms of percent integral uniformity (PIU): PIU=100×[1-((high-low)/(high+ low)]; 3. Low-contrast resolution: distinguishable spokes representing resolutions of 5.1%, 3.6%, 2.5% and 1.4% were recorded. According to ACR recommendations, high-contrast resolution of 1.0 mm, PIU of T1WI and T2>82%and low-contrast spoke difference<3 were considered as clinically acceptable. Results High-contrast T1WI and T2WI resolutions of no plate, PC plate, HP plate and KP material were all 0.9 mm, and those of the remaining materials were worse than 0.9 mm. The T1WI and T2WI PIU of no plate was>87%, and the PIU of carbon fiber plate was reduced by> 25%. The PIU decrease of remaining materials was within ±4%. Except the carbon fiber plate, the low-contrast spokes of the remaining materials were within ±3 compared with the reference. Conclusions In clinical settings, carbon fiber plate exerts the most significant effect upon the MR-simulation imaging quality, which is unsuitable for MR simulation. Imaging quality of PC and HP plates are consistent with that of no plate. BR and KP materials exert slight effect upon MR signal. The remaining materials are of potential values for the manufacture of immobilization devices and accessories. Key words: Magnetic resonance simulation image; Immobilization device material; Imaging quality; Quality assurance

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

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

How much margin do we need for pelvic lymph nodes irradiation in the era of IGRT?

Background and purpose: Image guided radiotherapy (IGRT) without 6 degree of freedom couch can only correct the translational setup errors of pelvic radiotherapy. But errors introduced by rotation and deformation of CTV can't be adjusted in most of IGRT systems. This article is to evaluate these errors and to provide recommendations on the margin needed in the era of IGRT.Material and methods: 218 patients who received pelvic radiotherapy in PUMC Hospital from 2012 to 2014 were included. A simulation CT and a CBCT were acquired for every patient. 3D and 6D registrations of CT and CBCT were applied. 9 bony landmarks were marked and distances of each landmark between CT and CBCT were measured in three directions.Results: Without image guidance, movements of landmarks in the directions of LR, AP and SI were 0.4 ± 2.5 mm, 1.3 ± 3.8 mm and 1.5 ± 5.0 mm respectively, with 3D-registration, movements were 0.0 ± 1.5 mm, 0.7± 2.8 mm and 0.6± 3.2 mm, and with 6D-registration, movements were 0.0 ± 0.5 mm, 0.2 ± 1.0 mm and 0.2 ± 1.1 mm in each direction.Conclusions: IGRT could reduce setup errors. IGRT with 6D treatment couches could further reduce setup errors compared to 3D couches. For centers without IGRT, we suggest CTV-PTV margins of 6 mm, 9 mm and 12 mm in LR, AP and SI directions respectively, margins of 3 mm, 6.5 mm and 7 mm for the use of daily IGRT with 3D couch and 2 mm, 3 mm and 3 mm for 6D couch.

Comparison of gross tumor volume of primary oesophageal cancer based on contrast-enhanced three-dimensional, four-dimensional, and cone beam computed tomography.

BackgroundTo explore motion information included in 3DCT, 4DCT and CBCT by comparing volumetric and positional differences of GTV.ResultsIndependent of tumor location, significant differences were observed among volumes [IGTV10 > (IGTVCBCT or IGTVMIP) > (GTV3D or GTV4D50)]. The underestimations or overestimations between IGTV10 and IGTVCBCT were larger than those between IGTV10 and IGTVMIP (p < 0.001–0.011; p < 0.001–0.023). For upper oesophageal tumors, GTV4D50/IGTVCBCT negatively correlated with motion vector (r = –0.756, p = 0.011). In AP direction, the centroid coordinates of IGTVCBCT differed from GTV3D, GTV4D50, IGTVMIP and IGTV10 (p = 0.006, 0.013, 0.038, and 0.010). For middle oesophageal tumors, IGTV10/IGTVCBCT positively correlated with motion vector (r = 0.695, p = 0.006). The centroid coordinates of IGTVCBCT differed from those of IGTV10 (p = 0.046) in AP direction. For distal oesophageal tumors, the centroid coordinates of IGTVCBCT showed significant differences to those of IGTVMIP (p = 0.042) in LR direction. For both middle and distal tumors, the degrees of associations of IGTV10 outside IGTVCBCT significantly correlated with the motion vector (r = 0.540, p = 0.046; r = 0.678, p = 0.031).Materials and MethodsThirty-four oesophageal cancer patients underwent 3DCT, 4DCT and CBCT. GTV3D, GTV4D50, internal GTVMIP (IGTVMIP) and IGTVCBCT were delineated on 3DCT, 4DCT50, 4DCTMIP and CBCT. GTVs from 10 respiratory phases were combined to produce GTV10. Differences in volume, position for different targets, correlation between volume ratio and motion vector were evaluated. The motion vector was the spatial moving of the target centroid position.ConclusionsIGTVCBCT encompasses more motion information than GTV3D and GTV4D50 for upper oesophageal tumors, but slightly less than IGTV10 for middle and distal oesophageal tumors. IGTVCBCT incorporated similar motion information to IGTVMIP. However, motion information encompassed in CBCT and MIP cannot replace each other.

Intrafractional Prostate Motion and Dose Variation during Radiation Therapy for Prostate Cancer Using 4D-TPUS

More recently, noninvasive 4D transperineal ultrasound (4D-TPUS) has been introduced in tracking intrafractional prostate motion in radiotherapy. Compared to other tracking method, the ultrasound has its own advantage in precise identification of soft tissue without invasive procedure or extra radiation dose. In this study, we investigated the prostate motion model and dose variation during radiotherapy using a transperineal autoscan ultrasound system (Clarity®, Elekta Inc., Sweden). From July 2014 through December 2016, 57 prostate cancer patients were enrolled with a median age of 74 years (range 61-85). All patients were asked to have a full bladder and empty rectum before each treatment. A simultaneous CT and TPUS simulation was conducted to provide a fused CT/US reference. Before radiation delivery, prostates were localized using CBCT to determine setup offsets relative to the patients’ skin tattoos. During the treatment, real-time ultrasound images were acquired and data was collected for direct monitoring of 3D motion of the prostate. Then dose distributions were recalculated with the isocenter shifts relative to the simulation CT images according to the real-time data using the leaf sequences/MUs based on the original treatment plan. The doses were compared with the original doses planned on the simulation CT using the clinical acceptance criteria. A total of 1207 fractions were evaluated. The mean (±SD) of the infraction displacements were [mm]: I(+)/S: (0.03 ± 0.92); L(+)/R: (0.12 ± 1.03); and A(+)/P: (-0.01 ± 1.37), respectively. There were 41/1207 (3.4%), 29/1207 (2.4%), and 66/1207 (5.5%) fractions with deviation exceeded 3 mm in the IS, LR, and AP directions, respectively. The A/P direction has the largest extent of prostate displacement. The percentage of time with displacements 0-1mm, 1-2mm, 2-3mm and larger than 3 mm was 88.1%, 9.8%, 1.7% and 0.4% in the IS direction, 89.3%, 8.9%, 1.5% and 0.3 % in the LR direction, 84.5%, 11.1%, 3.7%, and 0.7% in the AP direction. We classified our patients into three groups according to the motion model: stable (n=50), irregular (n=3) and intention (n=4). The intention group was defined as persistent deviation to the same direction (the maximal displacement should exceed 3 mm) that repeated in at least 50% fractions. All these patients had obviously anxiety and urinary frequency and/or urgency. Recalculated dose distributions showed that all the 4 patients in the intention group did not meet our criterion of D95% of PTV prostate> 8000 cGy or V70 of rectum< 20%, which may leading to insufficient treatment and increased toxicity. The present study demonstrated that for over 90% of fractions, a CTV-PTV margin of 3 mm would be good coverage with the planned prescribed dose. However, it is important to identify the patients belonging to the intention group. Pre-treatment with anti-anxiety drugs and α receptor blocker may be useful in relief the prostate motion.

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

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

The Novel Method to Reconstruct Three-Dimensional Target Motion From Body Surface Motion for Dynamic Moving Phantom

We have developed the new dynamic moving phantom (DMP) with three axis drives to reproduce three-dimensional(3D) target motion plus one axis drive for body surface motion. The motion data for operating this phantom is able to be acquired by rehearsing dynamic tracking therapy (DTT) of a patient. In this study, the novel approach which reconstructs the 3D long time information from respiratory motion (RPM) data on the body surface during planning CT and the target motion measured by 4DCT is developed. First, the RPM data on body surface during planning CT in each patient was obtained by laser ranger (u(t)). Then, the average wave of u(t) when 4DCT are scanned was calculated and 3D target motion was obtained by analyzing 4DCT. Next, correlation functions between average wave and 3D target motion in LR, AP and SI directions were created. Finally, long time 3D target motion was generated by the correlation function with u(t) in each patient. Two different correlation models were tested. One is dual polynomial model which is composed of polynomial functions separated by inspiratory and expiratory phases (P(u(t))). Another one is simple linear fitting function (L(u(t))). RPM data of 8 lung cancer patients who participated in clinical trial with DTT using gimbaled linac were used in this study. The average absolute difference between actual target position that was already known from tracking log data and reconstructed position were calculated to evaluate two correlation models. The significance between the average absolute difference of L (u (t)) and that of P (u (t)) were evaluated by Wilcoxon’s signed rank one-sided test. Table summarizes the result of the average of absolute difference in each patient. The difference between actual target position and reconstructed position by L(u(t)) in LR, AP and SI were 0.12±0.08 mm, 0.53±0.29 mm, 0.31±0.18 mm, respectively. On the other hand, those by P(u(t)) in LR, AP and SI were 0.23±0.14 mm, 0.87±0.54 mm, 0.69±0.40 mm, respectively (p = 0.018, 0.005, 0.027). The novel approach which reconstructs the 3D target motion from RPM data during planning CT and 3D target motion measured by 4DCT were shown. Dual polynomial model that we investigated in this study was better to reconstruct 3D target motion.Abstract 3619Pt.No.Dual polynomial modelLinear modelLR (mm)SI (mm)AP (mm)LR (mm)SI (mm)AP (mm)AVSDAVSDAVSDAVSDAVSDAVSD10.070.040.300.150.140.100.090.070.300.240.400.2720.220.130.490.300.390.250.220.130.520.351.070.5930.020.010.440.200.100.080.050.020.680.360.420.2740.130.060.480.270.060.060.220.090.630.360.160.1250.060.050.690.430.480.290.340.191.860.941.440.7460.200.170.530.250.210.140.540.320.500.290.430.2470.100.060.420.350.270.140.130.091.040.780.300.1680.120.130.870.420.840.410.270.171.400.981.290.81AV0.120.080.530.290.310.180.230.140.870.540.690.40 Open table in a new tab

Analysis of components of variance determining probability of setup errors in CBCT‐guided stereotactic radiotherapy of lung tumors

Online tumor matching for SABR lung setup requires margins for inaccuracies due to intra-fraction variability of breathing-averaged tumor position (BATP) and CBCT image guidance. We studied intra-fraction variability during SABR delivery using VMAT, corrected these for measurement inaccuracies, and quantified the CBCT image-guidance uncertainties. For 193 fractions in 38 patients positioned without immobilization devices, CBCT scans were acquired before and after 2 arcs of a RapidArc treatment. A hidden marker test was performed to determine the accuracy of the CBCT system and an inter-observer test was performed to measure registration accuracy. Intra-fraction variability was calculated after correction for these components of variance, and the prediction interval for setup inaccuracies was determined. Correction for measurement inaccuracies reduced the intra-fraction variability of the BATP from 1.9 to 1.6 mm in AP, from 1.7 to 1.4 mm in SI and from 1.5 to 1.1 mm in LR direction (1 SD). Intra-fraction variability in bony anatomy after correction was ≤ 1 mm (1 SD). The 95% prediction interval to account for CBCT image-guidance uncertainties and intra-fraction variability was determined, and was found to be within our institutional PTV margins of 5 mm. Our findings show that it is essential to account for measurement and system inaccuracies when obtaining data for validating PTV margins from online CBCT image guidance.

P2.05-039 Assessment of Lung Tumor Motion Comparing 4DCT, 4DCBCT and Motion of Implanted Beacons during Imaging and Irradiation: Topic: RT Techniques

Moving lung tumors exceeding the observed motion from planning 4D computed tomography (4DCT) can result in reduced dose coverage in stereotactic ablative body radiation therapy (SABR). 4D cone-beam CT (4DCBCT) facilitates verification of tumor trajectories before each treatment fraction. Using implanted Calypso beacons in the lung as ground truth, this work aims to assess how well 4DCT and 4DCBCT represent the actual motion range during imaging and irradiation. 4DCBCT was reconstructed for 1-2 fractions of 6 patients (three implanted Calypso beacons) receiving lung SABR from the projections acquired for treatment setup CBCT. Two reconstructions per projection set were created using the prior image constrained compressed sensing (PICCS) method based on the Calypso motion trajectories or an external respiratory signal (Philips Bellows). Calypso beacons were segmented for all 10 bins of the 4DCT and 4DCBCT sets and the centroid position calculated. Beacon centroid motion as seen on the 4DCT and 4DCBCT with respect to reference phase (end-exhale) was extracted and compared with the actual beacon centroid motion during CBCT acquisition and during irradiation. Both methods for 4DCBCT reconstruction failed to capture sudden motion peaks during scanning (see Fig. 1), but performed similar to the 4DCT. In general, 4DCT and 4DCBCT underestimated the actual beacon centroid motion. In the SI direction 22-27% of the actual motion exceeded the motion range from 4DCT and 4DCBCT imaging. In AP and LR direction up to 39-58% of the motion exceeded the observed motion range from 4D imaging. Both 4DCT and 4DCBCT failed to represent the full tumor motion range. For a safe treatment delivery this needs to be accounted for either by sufficient margins or more preferably real-time treatment adaptation directly tackling motion peaks and unpredictable motion.

Annual ring orientation effect on bending strength of subfossil elm wood

The effect of annual rings’ orientation on bending strength was examined on subfossil elm wood. Elm is extremely rarely found as subfossil wood, and during the last 50–60 years it has almost disappeared from natural forest stands of south-eastern Europe, due to the Elm Dutch disease. The samples were cut from approximately 670 years old subfossil elm trunk retrieved from the bed of the river Sava in the area between the villages Grebnice and Domaljevac in north Bosnia. The wood was identified to the genus level based on optical microscopy analysis of three wood sections—transverse, tangential and radial. Bending strength was determined by the three-point bending test. The load was applied to the longitudinal–tangential surface (LT) and to the longitudinal–radial surface (LR). The bending strength values of subfossil elm do not differ from the values of recent elm, despite the 700-year resting in anoxic river conditions. Bending strength in LT direction was slightly higher than bending strength in LR direction. The coefficient of variation and the standard deviation of the arithmetical mean were higher for LT direction. It was found that the measured bending strength for both directions follows Weibull distribution. Coefficient of determination of Weibull functions was close to 1 for both directions. The Weibull shape parameter was higher for LR direction.