Evaluation of Set-Up Accuracy in Stereotactic Radio Surgery and Stereotactic Radio Therapy of Intracranial Lesions
Prathima Ramachandran *1, B. Krishnamoorthy Reddy 1, Vinay Manoor Ural 1, Prasanna Kumar 1,
Arun L. Naik 2
1. Dept of Radiation Oncology, Apollo Cancer Center, Bangalore, India.
2. Dept of Neurosurgery, Apollo Hospitals, Bangalore, India.
Corresponding Author: Prathima Ramachandran, Dept of Radiation Oncology, Apollo Cancer Center, Bangalore, India.
Copy Right: © 2023 Prathima Ramachandran, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received Date: February 07, 2023
Published Date: March 01, 2023
Abstract
Purpose: To evaluate the set-up accuracy of frameless immobilization system using relocatable head mask, stereoscopic X-ray imaging and robotic couch in treating different intracranial lesions – benign and malignant using Brain Lab and Exactrac.
Materials and Methods: Forty patients with benign intracranial lesions and brain metastases were treated at Apollo Cancer Center, Bangalore. All patients were treated using frameless head mask using Image Guided Radio – Surgery (IGRS) and Cone Beam Computed Tomography (CBCT) on Truebeam STx with 6D robotic couch and residual shifts obtained were analysed. Clinically the patients were also analysed for side effects.
Results: The mean of the shifts in each dimension was compared between ExacTrac and CBCT. The Root Mean Square (RMS) of shifts obtained by ExacTrac were ≤0.5 mm (translational) and ≤0.5? (rotational) and by CBCT were ≤0.0009 (translational) and ≤0.012? (rotational), keeping in accordance with the tolerance limits of the imaging system.
Conclusion: SRS and SRT are progressively becoming a choice of treatment for benign and malignant intracranial lesions for which reproducibility of accuracy is imperative. The relocatable mask, orthogonal stereoscopic imager and robotic couch used in combination form an accurate repositioning system in SRS and SRT of intracranial lesions, with much less radiation induced toxicity compared to fractionated radiotherapy.
Introduction
The American Society for Radiation Oncology (ASTRO) describes Stereotactic Radiosurgery (SRS) as a “distinct discipline that utilizes externally generated ionizing radiation to inactivate or eradicate definite target(s) in the head without the need to make an incision” [1]. SRS is A high dose of External Beam Radiation Therapy (EBRT) delivered in one to five fractions via stereotactic guidance, with approximately 1 millimetre targeting accuracy to intracranial targets and selected tumours around the base of the skull. If an intra-cranial lesion is irradiated using stereotactic guidance in more than 5 fractions, it is termed as Stereotactic Radiotherapy (SRT). For all other targets outside the cranium, the dedicated term Stereotactic Body Radiotherapy (SBRT) is used [2].
In the earlier years of practice of SRS, stereotactic fixed frames were predominantly used as a form of immobilization. These frames were fixed to the patient with screws driven in to the skull. The fixation of frames to the skull was a tedious procedure that was done under anaesthesia. These stereotactic fixed frames gave an excellent target accuracy of ≤1 millimetre and were hence regarded as gold standard for SRS for a long period of time.
Over the past few decades, with the evolution of high-quality and precise imaging devices, it has been possible to progress from fixed frames to lesser invasive immobilization devices. There has been a paradigm shift towards non-invasive and relocatable immobilization techniques in the recent era where patients can undergo multiple sessions of LINAC based radiotherapy with excellent accuracy of localizing the target.
Immobilization of patients during SRS/SRT has been broadly divided in to two types – Frame- based and Frameless. Each of these systems is different with respect to material of the stereotactic frame, design, assembly with localizer and positioner for accuracy of repositioning.
A few of the Frame based immobilization systems include:
Frameless Immobilization include:
Owing to the feasibility of non-invasive and effective immobilization techniques and accurate localization of the target, SRS and SRT have become a routine practice in the treatment of several conditions of the brain – both benign and malignant – throughout the world.
The American College of Radiologists (ACR) and American Society for Radiation Oncology (ASTRO) have laid down guidelines for the clinical practice of SRS [2] [3]. As SRS is delivered with a large dose in a single or limited number of fractions, it warrants an extremely steep dose fall-off to ensure that minimal radiation dose is received by the surrounding normal organs while maximum dose is delivered to the target. In order to minimize the radiation-induced damage to normal tissues, a nominal setup boundary of the target is warranted. Conversely, a small setup margin although reduces the dose to normal structures, which may also result in under-dosing or over-dosing the target leading to poor clinical outcomes. Thus, an accurate system of imaging and immobilization technique is mandatory in the treatment of SRS and SRT.
In this study we evaluated the accuracy of the frameless immobilization system at the Department of Radiotherapy, Apollo Cancer Centre, Bengaluru in the treatment of intra-cranial lesions.
Materials and Methods
This prospective study was conducted in the Department of Radiation Oncology, Apollo Cancer Centre, between January 2018 and April 2019 after acquiring the approval from the Institutional Scientific Review Board and Ethical Committee. A detailed informed consent was taken from each of the patients recruited for this study.
Patient Selection
Patients selected for the study were selected based on the inclusion criteria:
Patients with metal implants, non-MRI competent pacemakers and claustrophobia were excluded from the study as MRI was a necessary tool.
Sample Size
After consulting with statistician, sample size was calculated to 39 using ANOVA (Analysis Of Variance) test (g Power Version 3.1). However, Forty patients were recruited for this study between January 2018 and April 2019.
Patient Immobilization
All patients were immobilized with a white Thermoplastic relocatable mask by BrainLABTM.
The relocatable head mask consists of five components viz.,
The patients were made to lie down with head in neutral position while they were subjected to the preparation of the mask. The processing time for moulding was around 30-45 minutes.
Patient imaging and Simulation
After the mask was prepared, patients were positioned in the in-house diagnostic Computed Tomography (CT) scanner (Philips TruFlight Select 64-slice) along with BrainLABTM CT localizer box. The CT simulation protocol for this study utilized 1 millimeter thick slices for Radiation Planning CT scan. CT images were obtained in both plain and contrast sequences. Along with the CT simulation, patients were also subjected to Magnetic Resonance (MR) simulation with the same protocol of 1 mm thick slices. MR images were obtained in our in-house MRI scanner (Philips 1.5 Tesla Achieva) with axial sections in the following sequences:
Contouring and Planning
The CT and MR images were registered and fused in iPlan (version 5.0) by BrainLAB. These images were then transferred to the Eclipse (version 11) on which contouring was done. MR images were used for accurate delineation of the Gross Tumour Volume (GTV). Two of the forty patients were treated for vascular malformations for which the interventional radiologist performed Digital Subtraction Angiography (DSA) to determine the nidus. Contouring and planning was done on plain CT images.
All doses were prescribed to the Planning Target Volume (PTV). The GTV to PTV margin was set at 0-1 millimetre for patients who underwent SRS (1-5 fractions) and up to 2-3 millimetres for those who underwent SRT (up to 30 fractions). All patients were planned using Eclipse with Volumetric Modulated Arc Therapy (VMAT) using 6 MV photons.
Apart from the daily QA tests performed for the LINAC (TrueBeam STx by Varian), individual plan QAs were performed for dosimetry. A Winston Lutz test was performed for as a part of imager QA prior to each patient’s treatment delivery.
Treatment Procedure
All patients were treated on Truebeam STx version 2.5 by Varian. The processing time from simulation to commencement of treatment delivery was 2-7 days. At the time of delivery, patients were positioned with their respective 5-layered mask on the six Degree of Freedom (6 – DoF) robotic couch by Novalis. The imaging and planning co-ordinates were set to align with the isocenter. A localizer frame from BrainLAB with an array of 6 Infrared (IR) markers was fixed over the mask. The movements of the target (patient) were monitored by the IR cameras.
Patient positioning and imaging
The initial set-up imaging was done using the ExacTrac imaging system which consists of two floor mounted kilo Volt (kV) X-ray tubes with two ceiling-mounted detectors. The orthogonal imaging by ExacTrac utilizes bony landmarks in the cranium using a 6D registration algorithm with quadratic convergence based on pixel values of the images. Shifts are calculated in 6 dimensions – Translational (lateral, longitudinal, vertical) and Rotational (pitch, roll, yaw). In keeping with our institutional protocol of image guidance system and resolution, the tolerance limit was set to 0.7 millimetre for translational shift and 0.7? for rotational dimensions. Shifts calculated by the system were displayed on the monitor and acceptable shifts were applied from console through an integrated communication system with the couch. If shifts were beyond 5 millimetre, the patient was repositioned manually and same was repeated.
Following this, On–Board Imaging (OBI) using Cone Beam Computed Tomography (CBCT) was performed to verify the positioning. Residual shifts obtained with CBCT imaging were not applied. A CBCT has an advantage of using both soft tissues and bony landmarks in matching the region of interest. Ideally, the residual shifts measured by CBCT should not exceed ExacTrac values. If residual shifts on CBCT were within tolerance limits, it was ignored. If the shifts were beyond tolerance limits, patient was repositioned and the same was repeated.
Once images were matched satisfactorily, radiation was delivered. Following the completion of treatment delivery, an ExacTrac imaging was done at the end of each fraction to look for intra- fraction motion of target.
Statistical Analysis:
All the means and Root Mean Square (RMS) of residual shifts from ExacTrac imaging and CBCT were tabulated and studied. The difference in means and Root Mean Squares (RMS) were analysed using a paired t-test using SPSS version 25. A p-value of <0.05 was considered statistically significant
Results
Patient characteristics:
Forty patients were treated for different intracranial lesions on TrueBeam STx, of which twenty-one were females and nineteen were males. Patient characteristics are tabulated below.
40 patients with 58 lesions were treated to a total of 413 fractions on TrueBeam STx with Novalis 6 Degree of Freedom couch, CBCT and ExacTrac. The patients were immobilized on the couch and set-up verification was done with ExacTrac and the shifts were applied and computed. Based on the bony landmarks, shift is calculated by the system in all 6 dimensions and is displayed on the screen – this is the initial shift. If shifts were within 0.5 mm and 0.5?, they were applied from console.
If the shifts were beyond these values, the patient was manually repositioned and a repeat ExacTrac imaging was done to verify. After the initial shift was applied, an ExacTrac imaging was done to see the residual shift. These values were tabulated for the study as residual shift errors from ExacTrac. The mean and Standard Deviation (SD) of residual shifts as measured on ExacTrac are as follows:
Analysis of the residual shifts of ExacTrac with CBCT
After final verification of the residual shift was done using ExacTrac, a CBCT was done using the On-Board Imager (OBI), the shifts on CBCT were calculated by matching the bony anatomy along with the soft tissue in the region of interest. The residual shifts measured by CBCT were only used for verification but not applied. The shifts were within our tolerance limits, however, as per our protocol if the residual shifts were to appear greater than those on ExacTrac, a manual repositioning was done and the entire process was repeated. The shifts calculated by CBCT are as tabulated below:
Comparison of the residual shifts by ExacTrac with CBCT
The two modalities of imaging were tabulated and a paired t-test was performed on the means of residual shifts using the software SPSS version 25. A p value of <0.05 was considered significant.
The mean shifts noted on ExacTrac were : Translational (mm): lateral -0.10 (SD = 0.36), longitudinal 0.06 (SD = 0.49), vertical -0.05 (SD=0.51); Rotational (?) : pitch -0.066 (SD = 0.56), yaw -0.22 (SD = 0.35), roll -0.0175 (SD = 0.50).
The mean of shifts noted on CBCT were: Translational (mm): lateral -0.02 (SD = 0.35), longitudinal -0.03 (SD = 0.37), vertical -0.02 (SD=0.36); Rotational (? ) : pitch -0.07 (SD = 0.4), yaw -0.14 (SD = 0.35), roll -0.06 (SD = 0.46). We ran a paired t-test on the two sets of values and noted that the shifts by ExacTrac and CBCT were statistically insignificant.
Root Mean Square (RMS)
A Root Mean Square (RMS) was also performed to the shifts obtained from ExacTrac and CBCT for ease of comparison with a paired t-test.
The RMS of residual shifts on ExacTrac were – Translational (mm) – Lateral : 0.37 (SD = 0.15), Longitudinal 0.48 (SD = 0.43), Vertical 0.5 (SD = 0.32); Rotational (?) – Pitch 0.56 (SD = 0.9), Yaw 0.4 (SD = 0.22), Roll 0.5 (SD = 0.32).
The RMS of residual shifts on CBCT were – Translational (mm) – Lateral : 0.0006 (SD = 0.17), Longitudinal 0.0009 (SD = 0.2), Vertical 0.0005 (SD = 0.16); Rotational (?) – Pitch 0.004 (SD = 0.01), Yaw 0.012 (SD = 0.19), Roll 0.003 (SD = 0.2).
Intrafraction Motion
An ExacTrac image was taken at the end of treatment for every patient to look for intra-fraction motion of the target. For patients who underwent non-coplanar treatment, the couch was brought back to 0? and an ExacTrac image was taken and the shifts obtained were noted.
These values were computed and the difference of shifts obtained were: Lateral 0.06 mm (SD=0.36 mm), Longitudinal -0.21 mm (SD=0.72 mm), Vertical -0.12 mm (SD=0.72 mm), Pitch 0.13? (SD = 0.42?), Yaw = -0.17? (SD= 0.32?), Roll 0.019? (SD= 0.29?).
The maximum recorded shifts were: lateral -0.475 mm, longitudinal -0.69 mm, vertical -0.63 mm, pitch -0.6?, yaw -0.61?, roll -0.59?. The shifts were marginally more in the patients who underwent non-coplanar treatment indicating that couch movements count for sub millmetric shifts. The shifts were in accordance with the isocenter accuracy as tested at our set up. The couch, gantry and collimator tested to an accuracy of 0.63 mm (cut-off of 0.75 mm as per Varian). The combination of couch and gantry together gave an accuracy of 0.374 mm (cut-off of 0.5 mm by Varian).
Discussion
Stereotactic Radiosurgery and Stereotactic Radiotherapy have increasingly become a routine in the treatment of intracranial lesions in radiation centres across the world. For a successful frameless SRS and SRT, a vital prerequisite is the patient immobilization and accuracy of imaging and treatment delivery. In the previous decades, SRS was performed using Stereotactic fixed head frames which gave excellent accuracy but were invasive and cumbersome [6]. However, these frames come with their own limitations. Patient inconvenience, frame slippage and distortion may hinder the accuracy of target localization in SRS [7, 8]. With the frame-based set up even though the patient may be exposed only to a single fraction of radiation, but is required to stay in the hospital under constant care and anaesthesia. However, with the evolution of imaging technology, it has been possible to progress from invasive frame-based system to the non-invasive and relocatable head masks. Not only have these masks been proved to have equal accuracy as their frame-based counterparts, additionally, they can be used in repeated fractions with no compromise in accuracy. LINACs have also advanced over the last few decades with respect to dose delivery, image guidance and target accuracy with dedicated immobilization techniques where SRS can be performed with an equal accuracy as a Gamma Knife Unit [23].
Hence it has been possible to bring in the concept of Stereotactic Radiotherapy (more than 5 fractions) in the treatment of intracranial lesions. Bednarz et al [24] compared the accuracy of a fixed frame-based radiosurgery and radiosurgery using a frameless mask and ExacTrac. The study showed that frame-based immobilization had slightly better accuracy (gold standard). However, for the practice of Stereotactic Radiotherapy (more than 5 fractions), a daily kV imaging is recommended by the author.
In our study, we evaluated the accuracy and its reproducibility in our centre in the treatment of 58 intracranial lesions using BrainLAB’s relocatable head mask, Novalis’s 6 DoF couch, ExacTrac’s stereoscopic X-ray imaging for patients treated on TrueBeam STx. We verified the shifts obtained on ExacTrac with CBCT. The RMS of ExacTrac shifts of our study showed ≤0.5 mm in translational and <0.6? in rotational shifts. The individual values were: 0.37 mm lateral (SD = 0.15 mm), 0.48 mm longitudinal (SD = 0.43 mm), 0.5 mm vertical (SD = 0.32 mm), 0.56? pitch (SD = 0.97?), 0.4? roll (SD = 0.22?), 0.5? yaw (SD = 0.32?). In a study done by Oh SA and group [5], 107 patients were treated with intracranial SRS and ExacTrac shifts were compared with online CBCT in the study. The RMS of the shifts produced were ≤0.25 mm (translational) and ≤0.25? (rotational) for ExacTrac shifts alone.
For the CBCT variations, our study showed RMS of: 0.32 mm lateral (SD= 0.15 mm), 0.48 mm longitudinal (SD=0.43 mm), 0.5 mm vertical (SD = 0.32 mm), 0.56? pitch (SD = 0.97?), 0.41? yaw (SD = 0.22?), 0.5? roll (SD= 0.32?). The shifts were ≤0.5 mm in translational and <0.6? in rotational, consistent with the values obtained from ExacTrac. In the same study by Oh SA [5] the RMS of shifts obtained on CBCT were ≤0.4 mm in translational and <0.5? in rotational, which was consistent with our study.
Ma et al [9] evaluated the set-up differences between ExacTrac and CBCT in head phantoms and patients undergoing intracranial SRS and they reported an RMS <0.5 mm & <0.2? in translational and rotational dimensions respectively for phantoms. On the patients, they recorded an RMS of <1.5 mm and <1? in translational and rotational respectively. These values were consistent with our study.
In another similar study, Chang et al [10], in the treatment of 16 patients with spinal lesions by SRS retrospectively studied the residual set-up errors between ExacTrac and CBCT in anthropometric phantoms and patients individually. Using phantoms, the discrepancy between the two modalities were <1 mm in translational and <1? in rotational, while in patients the discrepancies were <2 mm and <1.5? in translational and rotational respectively.
Rahimian et al [11] provided a thorough analysis on the set-up error components, with Root Mean Square (RMS) analysis for patients treated for Trigeminal Neuralgia using Novalis ExacTrac. This study confirms the total clinical accuracy of the Novalis system when used with the invasive head frames. The RMS deviation for the system was calculated at 0.66 mm when the couch error is corrected and 0.9 mm when couch errors are included. The measured SD was up to 0.7 mm. The data was based on the measurements of treatments planned using seven noncoplanar arcs, deviations ensuing from the couch and gantry rotations respectively were partially averaged out. Other bases of errors with regard to patients viz., possible frame slippage or distortion resulting from time lapse between frame fixation and treatment were not accounted for. The Novalis IGRT, X-ray verification and correction were accomplished with high-speed computing in less than 1 minute.
Several frameless stereotactic immobilization systems have been implemented in routine practice in recent era, viz., the Infrared (IR) tracking system [12], implanted fiducial marker [13,14] and mask fixation system [15] with equal accuracy as the fixed frames. While Hong et al [16] investigated the setup errors using only kV image verification along with a BrainLAB thermoplastic head face mask for immobilization in the treatment of cranial stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) of 57 brain lesions in 42 patients. The mean and SD of the couch shift were 0.0±0.9, 0.1±1.4, and 0.3 ±0.8 mm in the vertical, longitudinal and lateral directions respectively. The average of the shifts in trans[lational approached unity. However, the rotational shifts were not assessed in this study.
Kataria et al [17] evaluated the shifts by using a kV-CBCT alone for patients with brain, head and neck, thorax and pelvic lesions. They performed a daily image with kV-CBCT to see if the PTV margin could be reduced if daily online verification could be done and analysed the residual errors obtained. For the 15 patients treated for brain lesions, the mean displacement of the target was found to be 0.18 cm which was acceptable as the isotropic expansion to PTV was 0.3 cm.
Wurm et al [4], published their study stating that phantom tests showed an overall system accuracy of 1.04 ± 0.47 mm. The average deviation of 0.02 ± 0.96 mm in lateral and 0.02 ± 0.7 mm in longitudinal. With an ExacTrac setup, the overall mean translational deviation by the stereoscopic x-ray system of verification was 1.5 ± 1.3 mm, and mean rotational deviation was 1 ± 0.8?.
Infusino et al [18] estimated setup errors for SRS performed intracranial lesions on 15 patients with the ExacTrac X-Ray 6D system treated to a dose of 30 Gy in 3 fractions, the verification of setup errors on ExacTrac alone was < 2 mm in all directions i.e., -0.9 mm, -1.6 mm, -1.8°, -0.4°, and -1.8° for the lateral, vertical, pitch, roll, and yaw dimensions, respectively.
Minniti et al [19], studied the accuracy of frameless SRS for patients treated for brain metastases. They analysed data from 102 patients with the on-board imaging CBCT. They reported a mean isocenter displacements at 0.12 mm (SD = 0.35 mm) in lateral, 0.2 mm (SD = 0.4 mm) in longitudinal and 0.4 mm (SD = 0.6 mm) in vertical dimensions. The maximum displacement was 2.1 mm seen in longitudinal direction. The mean 3D displacement was 0.5 mm (SD = 0.7 mm).
In a study conducted by Dhaban and group [20], the set up accuracy was verified in 28 patients immobilized with head ring and U-frame treated for 38 targets in 63 fractions, the mean of shifts in translational were 0.2 mm, 0.3 mm and 0.4 mm in the lateral, vertical and longitudinal and rotational were 0.1°, 0.2° and 0.1° in pitch, roll, and yaw respectively using CBCT alone. The accuracy was attributed to the planning CT scans that were done with a slice thickness of 0.625 mm.
Gaevert et al [21] performed frameless SRS on 40 patients with 66 brain metastases using 6DoF couch and the mean of residual shifts were 1.91 mm (SD, 1.25 mm). The rotational errors were larger in longitudinal (mean, 0.23?; SD, 0.82?) direction compared with lateral (mean, 0.09?; SD, 0.72?) and vertical (mean, 0.10?; SD, 1.03?) directions (p < 0.05). The mean three-dimensional intrafraction shift was 0.58 mm (SD, 0.42 mm). The mean intra-fractional rotational errors were comparable with the vertical, longitudinal, and lateral directions:0.01? (SD= 0.35?), 0.03? (SD= 0.31?), and 0.03? (SD= 0.33?), respectively.
Chang et al [76] measured the repositioning accuracy in CyberKnife system for intracranial lesions and found that the radiosurgery system had a clinically relevant accuracy of 1.1 ± 0.3 mm while we report an accuracy of 0.9 ± 0.3 mm in our system. Smith et al [77] report an average residual setup accuracy of 0.48 mm in patients who were treated with GammaKnife Perfexion for intracranial lesions while we report an average accuracy of 0.46 mm in our system at our center.
Follow-up:
Twelve out of the forty patients were followed up during the study period.
Six out of twenty-one patients treated for brain metastases with different primaries were assessed radiologically:
Among the subjects of this study one patient, treated for brain metastases, expired due to multi- organ failure 6 months following the procedure.
In Minniti’s study [19], nine out of the hundred and two patients reported local recurrence.
With this study we hypothesize the fact that high accuracy in the treatment of intracranial lesions can translate to improved clinical and radiological outcomes. However, we need longer follow-up period and more frequent radiological imaging to verify the same.
Conclusion
Our study aimed at evaluating the set-up accuracy of the frameless immobilization system which is a combination of the relocatable head mask, 6 DoF robotic couch and stereoscopic kV X-ray imaging. We verified the residual shifts measured by ExacTrac with CBCT using the mean and RMS of residual shifts using a paired t-test. The shifts in all directions were statistically insignificant.
The reproducibility of accuracy is a major challenge, especially when it comes to fractionated treatments of the brain lesions which was deemed possible in our study. Thus, we conclude that the thermoplastic head mask along with localizer box (relocatable head mask), 6 Degree of Freedom (DoF) couch and stereoscopic imaging work in unison to form an accurate frameless immobilization system in the treatment of various benign lesions and brain metastases undergoing single or multi-fractionated radiotherapy.
Abbreviations Used
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