Spatial accuracy of dose delivery significantly impacts the planning target volume margin in linear accelerator-based intracranial stereotactic radiosurgery

Spatial accuracy of dose delivery significantly impacts the planning target volume margin in linear accelerator-based intracranial stereotactic radiosurgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Spatial accuracy of dose delivery significantly impacts the planning target volume margin in linear accelerator-based intracranial stereotactic radiosurgery Yuta Takahashi, Riki Oshika, Rie Tachibana, Katsuyuki Shirai, and 24 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5336613/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 29 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract The impact of three-dimensional (3D) dose delivery accuracy of C-arm linacs on the planning target volume (PTV) margin was evaluated for non-coplanar intracranial stereotactic radiosurgery (SRS). A multi-institutional 3D starshot test using beams from seven directions was conducted at 22 clinics using Varian and Elekta linacs with X-ray CT-based polymer gel dosimeters. Variability in dose delivery accuracy was observed, with the distance between the imaging isocenter and each beam exceeding 1 mm at one institution for Varian and nine institutions for Elekta. The calculated PTV margins for Varian and Elekta linacs that could cover the gross tumor volume with 95% probability at 95% of the institutions were 2.3 and 3.5 mm, respectively, in the superior–inferior direction. However, with multifactorial system management (i.e., high-accuracy 3D dose delivery with rigorous linac quality assurance, strict patient immobilization, and high intra-fractional positioning accuracy), these margins could be reduced to 1.0 mm and 1.5 mm, respectively. The findings indicate significant millimeter-level variability in 3D dose delivery accuracy among linacs installed in clinical settings, but effective system management can achieve PTV margins below 2 mm, suitable for SRS applications. Health sciences/Oncology/Cancer/Cancer therapy/Radiotherapy Health sciences/Oncology/Cancer/Cns cancer SRS linac three-dimensional dose delivery accuracy margin size gel dosimeter multi-institution Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) using a medical linear accelerator (linac) have largely replaced whole-brain irradiation as a treatment for multiple brain metastases. 1 – 6 For such applications, SRS and SRT commonly use non-coplanar, intensity-modulated irradiation. 7 , 8 The targets are often smaller than a few centimeters, and treatment is planned with a small planning target volume (PTV) margin of 0–2 mm. 9 – 11 This margin size is also recommended by the working group on stereotactic radiotherapy of the German Society of Radiation Oncology. 12 These facts highlight the need for radiation delivery with submillimeter accuracy. Minimizing irradiation positional errors relative to the imaging isocenter is therefore becoming increasingly important. Variations in linac dose delivery accuracy may also affect clinical outcomes of intracranial SRS/SRT. Several guidelines for SRS require a geometric accuracy within 1 mm in an end-to-end (E2E) test. 13 – 15 The E2E test includes the accuracy of contouring and registration 15 . Thus, the guidelines require the delivery accuracy of the linac to be less than 1 mm. To compensate for systematic and random errors in patient positioning, 16 van Herk et al. designed a margin determination method that does not depend on the three-dimensional (3D) dose delivery accuracy of the linac. 17 In contrast, Takakura et al. suggested a method for estimating overall geometric uncertainty from uncertainties in both the patient position and linac dose delivery. 18 Moreover, Zhang et al. suggested a method to derive the optimal PTV margin for intracranial SRS by taking into account the distance between the imaging and radiation isocenters and the residual setup error after image guidance. 19 , 20 If the impact of the 3D dose delivery accuracy on the margin is high, the approach proposed by Zhang et al. and Takakura et al. is considered ideal. To correctly derive the margin, the 3D dose delivery accuracy of the linac must be measured with low measurement uncertainties. To appropriately determine the margin for intracranial SRS/SRT and provide treatment with sufficient target coverage, we should directly assess and manage the 3D radiation delivery accuracy relative to the imaging isocenter by performing quality assurance (QA) procedures with minimal measurement uncertainties. Conventionally, two-dimensional (2D) planar images are obtained for each beam in QA tests, and the mechanical isocenter with some setup uncertainties is commonly used as the reference, especially for the Winston–Lutz (WL) test. 15 , 21 , 22 Thus, these tests include the measurement uncertainties derived from the mechanical isocenter to obtain 3D information from the 2D images. Uncertainties in a QA test may therefore contribute to the PTV margin size because the spatial dose delivery accuracy of linacs affects geometric uncertainties in the GTV. Recently, a new 3D starshot (3D-SS) test using a polymer gel dosimeter has been reported to solve the above-mentioned problems in verifying geometric accuracy. 23 – 25 This approach allows a direct, comprehensive 3D evaluation of spatial radiation accuracy relative to the imaging isocenter. 25 The trajectories of radiation beams through the dosimeter are visualized using kilovoltage cone-beam computed tomography (kV-CBCT), and the imaging isocenter is thus obtained from the resulting kV-CBCT image. Human errors derived from QA phantom setup and laser indication adjustment do not affect the measurement accuracy. The 3D-SS test may be superior to the conventional QA methods because it eliminates uncertainties associated with those methods, and the measurement uncertainty of the 3D-SS test has been found to be 0.2–0.3 mm 25 . The geometric uncertainties in patient setup and dose delivery may vary among institutions and manufacturers. The 3D dose delivery accuracy should be included in the PTV margin size if the uncertainties significantly affect the margin. This 3D dose delivery accuracy should be measured with low uncertainty, because the guidelines have recommended that each institution aim to achieve a PTV margin of 2 mm in intracranial SRS. 12 In contrast to conventional QA tests of spatial dose delivery, which may over- or underestimate the margin, 3D-SS analysis is effective for this purpose because it provides such spatial information free from measurement uncertainties associated with the setup. However, only the methodology has so far been proposed, and no information is available on variations in 3D dose delivery accuracy among commercially available linacs. While there are numerous studies focusing on patient setup accuracy 26 – 29 , there is a notable lack of research addressing linac precision, particularly with respect to differences between manufacturers and individual units. Furthermore, it remains unclear whether the PTV margin obtained for linac-based intracranial SRS via 3D-SS analysis will satisfy the recommended 2 mm limit. 12 To correctly evaluate the impact of the spatial dose delivery accuracy of linacs on the PTV margin in intracranial SRS, we performed a multi-institutional study using linacs from two vendors using the 3D-SS test. We also developed a method for calculating the margin for the 3D-SS test. Furthermore, on the basis of the 3D-SS test results, we investigated whether the PTV margin could be constrained within 2 mm by implementing advanced image guidance (real-time video-based 3D optical surface imaging and 2D kV stereoscopic imaging) and rigorous linac quality management. 2. Materials and Methods 2.1. Institution Selection Twenty-two institutions that performed intracranial stereotactic radiotherapy in clinical practices participated in this study. All institutions used a medical C-arm linac attached to an on-board imager enabling kV-CBCT. Seven institutions used a TrueBeam system (Varian Medical Systems, Inc., Palo Alto, CA, USA), four used a TrueBeamSTx system (Varian Medical Systems), four used a VersaHD system (Elekta AB, Stockholm, Sweden), three used an Infinity system (Elekta AB), and four used a Synergy system (Elekta AB). We verified that a geometric QA test was regularly performed at all facilities in accordance with guidelines published by task groups 142 and 198 of the American Association of Physicists in Medicine. 21 , 22 2.2. Assessment of 3D linac accuracy using the 3D-SS test The 3D-SS test is robust with low measurement uncertainties for evaluating 3D dose delivery accuracy. 25 All institutions followed the 3D-SS test procedure described below. In total, 22 jars each containing an X-ray computed tomography (CT)-based polymer gel dosimeter called dGEL™ (Triangle Products Co., Ltd., Kashiwa, Japan) were used in this study. 30 Treatment was planned using the treatment planning system installed at each institution. A common dGEL™ CT dataset, acquired using an Aquilion ONE system (Canon Medical Systems, Otawara, Japan), was sent to all institutions. A 10 MV flattening filter photon beam or a 6 or 10 MV flattening filter-free photon beam was used. Symmetric fields with a minimum size of 0.5 × 0.5 cm² for Varian systems and 0.6 × 0.6 cm² for Elekta systems were used. Table 1 shows gantry, couch, and collimator angle settings for radiation beams based on the study by Pant et al. 23 A machine output between 6000 and 8000 monitor units was determined for each beam to create an isodose line of 20 Gy in the beam path (Fig. 1 A). A dose of 20 Gy was selected on the basis of our preliminary study 25 , which showed that this dose resulted in a sufficient contrast-to-noise ratio for each beam to perform the analysis using our in-house software. The software uses algorithms that determine a 3D vector with a point in the CBCT coordinate system that defines the beam axis by maximizing the contrast-to-noise ratio. 25 Each jar including the gel dosimeter was sent to its respective institution. The jar was placed with the center of its sensitive volume located approximately at the mechanical isocenter indicated by the room laser. The gel dosimeter was placed on the couch and secured in place using adhesive tape to prevent movement. A pre-irradiation kV-CBCT image was obtained using the image acquisition and reconstruction parameters in Table 2 . Subsequently, the gel dosimeter was irradiated with seven narrow beams using gantry and couch rotations (Fig. 1 B), and post-irradiated kV-CBCT images were acquired using the same parameters as above (Fig. 1 C). For analysis, the image datasets of pre-irradiated and post-irradiated gel dosimeters were imported into our in-house program 25 . The analysis quantified the minimum distance ( \(\:{d}_{\text{m}\text{i}\text{n}}\) ) between each radiation beam and the origin of the imaging coordinate system (imaging isocenter, \(\:\text{i}\text{I}\text{C}\) ), the distance ( \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) ) between the radiation isocenter ( \(\:\text{r}\text{I}\text{C}\) ) and the \(\:\text{i}\text{I}\text{C}\) , and the radius ( \(\:r\) ) of the smallest sphere that intersects all beams. 25 Table 1 Gantry, couch, and collimator angles of beams used in this study, following International Electrotechnical Commission standard 61217. Beam No. Gantry [degree] Couch [degree] Collimator [degree] 1 45 0 0 2 135 0 0 3 180 0 0 4 270 0 0 5 45 45 0 6 45 90 0 7 45 270 0 Table 2 Kilovoltage cone-beam CT image acquisition and reconstruction parameters used for the three-dimensional starshot analysis. parameter Varian (iCBCT) Varian (FBP) Elekta Tube voltage [kV] 80 80 70 Tube current-exposure time product [mAs] 1080 1080 2112 Frame rate [frames/sec] 15 15 5.5 Gantry speed [degree/sec] 1 1 0.6 Rotational angle [degree - degree] 180–180 (CCW) 180–180 (CCW) 180–180 (CCW) Fan type Full Full Full Trajectory Full Full Full Reconstruction iCBCT FBP Feldkamp Matrix size 512 x 512 512 x 512 512 x 512 Slice thickness[mm] 1 1 1 The other reconstruction parameters Smooth reconstruction filter: standard denoise: Medium Smooth reconstruction filter: Auto Reconstruction filter: Wiener Interpolation: strong (set as Partial2) Scatter Correction: Uniform (set the factor as 0.24) Pre Filter: Median (strong) Projection Down Size Factor: 1 (best quality) Abbreviations: iCBCT = iterative cone-beam computed tomography; FBP = filtered back projection; CCW = counterclockwise. The values of \(\:{d}_{\text{m}\text{i}\text{n}}\) , \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) , and \(\:r\) were obtained at all institutions. An inter-manufacturer comparison was made for these values. For \(\:{d}_{\text{m}\text{i}\text{n}}\) and \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) , the comparison was made for each direction of the image (DICOM) coordinate system and for the resultant vector. 2.3. Impact of 3D linac accuracy on SRS We assessed the impact of the spatial dose delivery accuracy on the PTV margins in intracranial SRS. PTV margins were derived using the 3D-SS analysis results. Zhang et al. proposed a method to calculate the optimal PTV margin for single-fraction intracranial SRS that incorporates the linac spatial dose delivery error and the residual patient setup error after image guidance. 19 , 20 The method provides an anisotropic margin for intracranial SRS that ensures with 95% probability that the clinical target volume receives the prescribed dose. In this study, we developed the method by inputting the 3D dose delivery accuracy derived from the 3D-SS test as the linac spatial dose delivery error, building on a previously reported study 20 . After calculating the optimal PTV margins, inter-institution and inter-manufacturer comparisons were made. The formulas are $$\:{C}_{i}={W}_{0i}+{b}_{1}\left({W}_{0i}\right){\sigma\:}_{i}+{b}_{2}\left({W}_{0i}\right){\sigma\:}_{i}^{2}$$ 1 , $$\:{b}_{1}\left({W}_{0i}\right)={2.331-1.425W}_{0i}+2.296{W}_{0i}^{2}-1.539{W}_{0i}^{3}+0.374{W}_{0i}^{4}$$ 2 , $$\:{b}_{2}\left({W}_{0i}\right)={0.434W}_{0i}-0.917{W}_{0i}^{2}+0.676{W}_{0i}^{3}-0.171{W}_{0i}^{4}$$ 3 , were \(\:{C}_{i}\) represents the PTV margin for the i = X , Y , and Z directions in the DICOM coordinate system; \(\:{W}_{0i}={V}_{s0i}+{V}_{r0i}\) , where \(\:{V}_{s0i}\) represents the systematic error in the imaging isocenter and radiation isocenter along each axis; \(\:{V}_{r0i}\) denotes the average residual error in patient setup after image guidance; and \(\:{\sigma\:}_{i}\) is a function of the standard deviation of the residual error in patient setup ( \(\:{SD}_{\text{s}\text{e}\text{t}\text{u}\text{p},i}\) ). In this study, we added fluctuations in the radiation beam position (random error in the radiation isocenter) to \(\:{\sigma\:}_{i}\) : $$\:{\sigma\:}_{i}=\sqrt{{SD}_{\text{s}\text{e}\text{t}\text{u}\text{p},i}^{2}+{\left(0.683\times\:r\right)}^{2}}$$ 4 , where the term \(\:0.683\times\:r\) corresponds to the standard deviation of the radiation isocenter error, which was assumed to follow a normal distribution. In this study, \(\:{V}_{s0i}\) was directly set equal to \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) , which includes the influence of couch rotation. The values of \(\:{V}_{r0i}\) and \(\:{SD}_{\text{s}\text{e}\text{t}\text{u}\text{p},i}\) were taken from the studies of Zhang et al. 20 and Ong et al. 26 and are shown in Supplementary Table A1. The values of the former and the latter were defined as the larger and smaller residual patient setup errors. 2.4. Impact of QA procedures on SRS accuracy We evaluated the impact of implementing advanced image guidance systems for patient positioning and rigorous geometric QA of the linac. This study assumed that advanced image guidance systems, which include widely installed video-based 3D optical surface imaging and 2D kV stereoscopic imaging, were implemented. During non-coplanar irradiation in clinical settings, we also assumed that intra-fraction patient motion caused by treatment couch shifts during couch rotation could be monitored and corrected by these imaging modalities. For example, we hypothesized that current surface-guided radiation therapy systems could detect a couch walk-out of < 1 mm. 31 Furthermore, the value of \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) was treated as a systematic error for linacs that could be minimized by a geometric calibration test performed by the user. These assumptions form the basis for the further analysis conducted in this study. Therefore, this study assumed that in clinical practice, the user’s efforts can reduce the impact of these two factors on geometric accuracy to nearly zero. Based on this assumption, the PTV margin was recalculated by replicating the situation using the following procedure: 3D dose delivery accuracy was recalculated using only the co-planar beams, and the new values of \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) and \(\:r\) were measured. Subsequently, \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) was set to zero to account for the error contribution of the geometric calibration of the linac. Finally, the PTV margin was recalculated using equations 1 – 4 and the above value of \(\:r\) . 2.5. Statistical analysis Statistical analyses were performed to examine inter-manufacturer differences and inter-axis differences in various parameters. The Kruskal–Wallis test and Mann–Whitney U test were used to compare the results from more than two institutions and vendors, respectively. The Steel–Dwass post hoc test was used to make pair-wise comparisons. All statistical analyses were conducted using EZR (version 1.62, Saitama Medical Center, Jichi Medical University, Saitama, Japan). A value of p < 0.05 was considered statistically significant. 3. Results Figure 2 categorizes the values of \(\:{d}_{\text{m}\text{i}\text{n}}\) , \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) , and \(\:r\) for non-coplanar irradiation for each institution according to the linac manufacturer, and the raw data for these parameters are summarized in Supplements B, C, and D, respectively. For the seven beams used at each institution, \(\:{d}_{\text{m}\text{i}\text{n}}\:\) showed variability among institutions and between manufacturers (Fig. 2 A and Supplements B1, B2). As shown in Fig. 2 A, the positional errors in the beam paths of the Elekta systems were significantly larger than those of the Varian systems in the X ( \(\:p\:\) < 0.001), Y ( \(\:p\) < 0.001), and Z ( \(\:p\) < 0.05) directions. There were no significant differences in the positional errors among any of the X , Y , and Z directions for Varian systems, whereas the Elekta systems had a significantly larger error in the Z direction compared with those in the X and Y directions ( \(\:p\) < 0.001). In terms of the resultant vector, the Elekta systems had a significantly larger positional error in the beam path than the Varian systems \(\:(p\:\) < 0.05), as shown in Fig. 2 B, and the numbers of institutions for which the value exceeded 1 mm were one and nine for Varian and Elekta systems, respectively. These 10 institutions exceeded the 1 mm tolerance proposed for the E2E test by the Medical Physics Practice Guidelines developed by the American Association of Physicists in Medicine and also proposed in the consensus statement from the working groups for radiosurgery and stereotactic radiotherapy of the German Society for Radiation Oncology and for physics and technology in stereotactic radiotherapy of the German Society for Medical Physics. 13 , 15 The value of \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) , which includes the influence of couch rotation, was evaluated. As shown in Fig. 2 C and Supplement C, the values of \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) for the Varian systems were within ± 0.32 mm in all directions, and the median values were within 0.1 mm. No significant differences were observed among the values of \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) in the X , Y , and Z directions. In contrast, the Elekta systems had a maximum \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) of 1.21 mm in the Y direction, with median values in the X , Y , and Z directions of 0.16, 0.39, and − 0.42 mm, respectively. Furthermore, \(\:{d}_{\text{i}\text{I}\text{C}-\text{r}\text{I}\text{C}}\) was significantly larger in the Z (longitudinal) direction than in the X ( p < 0.05) and Y ( p < 0.01) directions. The displacements for the Elekta systems were significantly larger than those for the Varian systems ( \(\:p\) < 0.001), as shown in Fig. 2 D and Supplement C. The radius of the smallest sphere intersecting all radiation beams, which includes the effect of couch rotation, is presented in Fig. 2 E and Supplement D. The Elekta linacs had a significantly larger radius ( \(\:p\:\) < 0.001) than the Varian linacs. Figure 3 and Supplement E show the PTV margins derived from 3D-SS analysis of dose delivery error and from residual patient setup errors after image guidance. The PTV margins varied among institutions and between manufacturers. The minimum and maximum PTV margins were 1.0 and 3.4 mm, respectively, regardless of manufacturer or coordinate axis. Significant differences in the PTV margins between the Varian and Elekta systems were measured in the X ( \(\:p\) < 0.01), Y ( \(\:p\) < 0.01), and Z ( \(\:p\) < 0.001) directions. Assuming that the PTV margins calculated for the institutions sampled follow a normal distribution, the cumulative frequency distributions of the PTV margins were calculated for each manufacturer (Fig. 4 ). The probability of exceeding a 2 mm margin was higher for Elekta systems than for Varian systems. Table 3 shows the PTV margins that could cover the GTV in the X , Y , and Z directions with 95% probability at 95% of the institutions. A PTV margin of 2 mm was achievable for the Varian systems if the smaller setup errors reported by Ong et al. 26 were assumed. The margin for Elekta systems was unachievable under all conditions assumed in this study, with a 3.5 mm margin being required in the Z direction in the worst case. Table 3 Planning target volume (PTV) margins for Varian and Elekta linear accelerators that could cover the gross tumor volume with 95% probability at 95% of the institutions. The margins in three directions are shown, and they were derived from a three-dimensional starshot (3D-SS) test of the dose delivery accuracy and the residual setup errors reported by Ong et al. 26 and Zhang et al. 20 Manufacturer Direction PTV margin size [mm] Ong Zhang Varian X 1.7 1.9 Y 1.6 1.6 Z 1.6 2.3 Elekta X 2.4 2.6 Y 2.8 2.8 Z 2.6 3.5 Assuming that high-accuracy 3D dose delivery, strict patient immobilization and intra-fractional positioning, and rigorous linac QA could improve 3D geometric accuracy, the isocentricity \(\:r\) was reduced from 0.81 to 0.32 mm for Varian systems and from 1.45 to 0.76 mm for Elekta systems (cf. Supplements D and F). Being less than 1 mm, these values met the proposed tolerance level. 13 , 15 PTV margins for all institutions are shown in Supplement G, and those margins that could cover the GTV with 95% probability at 95% of the institutions are shown in Table 4 . Even when a larger residual patient setup error was assumed, the margin size for all institutions using Varian systems remained below 2 mm, and the PTV margins that could cover the GTV with 95% probability at 95% of the institutions were 1.5, 1.1, and 2.0 mm in the X , Y , and Z directions, respectively. When a smaller residual patient setup error was assumed, the PTV margin size for all institutions using Elekta systems remained below 2 mm, and the margins that could cover the GTV with 95% probability at 95% of the institutions were 1 mm for Varian Systems and 1.5 mm for Elekta Systems in all directions. Table 4 PTV margins for Varian and Elekta linear accelerators that could cover the gross tumor volume with 95% probability at 95% of the institutions, determined assuming that the distance between the imaging and radiation isocenters is zero owing to rigorous QA implementation and that the intra-fraction error caused by treatment couch rotation is zero owing to implementation of a positional monitoring system such as surface image guidance. The margins in three directions are shown, and they were derived from 3D-SS analysis of the dose delivery accuracy and the residual setup errors reported by Ong et al. 26 and Zhang et al. 20 Manufacturer Direction Reduced PTV margin size [mm] Ong Zhang Varian X 1.0 1.5 Y 1.0 1.1 Z 1.0 2.0 Elekta X 1.5 1.9 Y 1.5 1.6 Z 1.5 2.3 4. Discussion To our knowledge, this is the first multi-institutional study to combine 3D-SS analysis with an X-ray CT-based polymer gel dosimeter to evaluate the 3D dose delivery accuracy, including couch rotation accuracy, of commercially available linacs broadly in clinical use. Moreover, institution- and manufacturer-specific PTV margins for intracranial SRS were derived from 3D-SS analysis of dose delivery accuracy. This report will serve as a useful reference for institutions seeking to objectively evaluate their own dose delivery accuracy and to determine the PTV margin for intracranial SRS. This study made several important findings. First, it provides generally achievable values for linacs from each manufacturer. Pant et al. proposed a 3D-SS method that minimizes measurement uncertainties. However, there is no information on variations in 3D dose delivery accuracy among commercially available linacs. Second, we found that one Varian and nine Elekta linacs exceeded the 1 mm tolerance of SRS guidelines on spatial irradiation accuracy, even if conventional WL tests and timings were followed. In a previous study, there were discrepancies of < 0.4 mm in the resulting coincidence of each beam obtained via the conventional WL test and 3D-SS test. 25 Thus, these results imply that conventional QA methods may underestimate 3D dose delivery errors. A 3D QA procedure with low measurement uncertainties, such as the 3D-SS test, should be performed to achieve dose delivery errors of no more than 1 mm in 3D coordinates. Third, non-coplanar irradiation for intracranial SRS performed without any image guidance system may need more than a 2 mm PTV margin when a larger residual patient setup error is assumed. Several studies have reported that the PTV margin can be reduced without affecting the clinical outcome 9 , 11 . However, it is unclear whether similar results can be obtained at other institutions because our findings indicate that the accuracy of irradiation is institution-dependent. In this study, the margin was in the 1.0–3.4 mm range. This considerable variation indicates that universal determination and reduction of the PTV margin should be approached cautiously. The limitation of this study is that we used the values of residual setup error from other studies. Institution-specific residual setup error ideally may be input to the formula of the margin calculation. In contrast, a common margin from research papers and some protocols from clinical trials may be used in many institutions. In this study, two kinds of residual setup errors from the literature 20 , 26 were used, and we evaluated the impact on the PTV margin. Institution-specific residual setup errors should be evaluated to determine a more accurate margin. In this study, we used linacs for intracranial stereotactic radiotherapy in clinical practice. Although the Elekta linac models used in this study belong to different generations, there are no differences in the structure and function of the linacs across the three models. The couch systems differ among the three models. However, only the yaw rotation of the couch was used in this study, and we considered that there was no significant difference in the accuracy of the yaw rotation among the models. Finally, this study highlights the importance of precise management of the 3D dose delivery accuracy by medical physicists. Radiation oncology departments should also introduce a real-time monitoring system capable of correcting patient displacement due to body movement and couch rotation. Moreover, therapists must improve patient immobilization and verification of position accuracy. The margin could be reduced to within the recommended 2 mm limit by assuring high-accuracy 3D dose delivery, strict patient immobilization and intra-fractional positioning, and rigorous linac QA. 12 Our multi-institutional study showed that it is possible to limit the PTV margin size for intracranial SRS to 1.0 mm for Varian systems and 1.5 mm for Elekta systems in all directions. 5. Conclusion The 3D dose delivery accuracy of linacs currently in operation largely varied at the millimeter level in this study. The accuracy of current radiotherapy technology should not be overestimated, and it is essential to rigorously determine the 3D dose delivery accuracy and estimate the PTV margins. A geometric QA test with low measurement uncertainties should be performed to ensure the PTV margin is within 2 mm. During treatment, the patient’s intra-fractional setup error should be limited using advanced image guidance systems. Finally, for intracranial SRS, one should ensure that the irradiation margins remain within 2 mm. Abbreviations iCBCT iterative cone-beam computed tomography FBP filtered back projection CCW counterclockwise. Declarations Author Contributions Statement H. T. conceptualized the study, helped interpret the data, and provided expertise in manuscript preparation. Y. T, R. O., and H. T developed the study design and supervised the authors throughout the study. Y. T. analyzed data. R. T. provided study materials. H. A., M. M., T. S., S. T., T. K., H. K., S. N., H. N., Y. I., M. U., K. K., D. K., K. S., Y. N., K. H., T. K., H. E., Y. M., H. I., M. I., S. K., R. H., D. H., and Y. T. performed 3D star shot analyses at various institutions. H. T. and K. S. critically revised the manuscript. Competing Interests Y. T. received study materials from Triangle Products Co. Ltd. H. T. received a research grant from Triangle Products Co. Ltd. R. T. holds stock in Triangle Products Co. Ltd. There are no other commercial or financial relationships that might lead to a perceived conflict of interest. All the remaining authors declare no conflict of interest. Author Contribution H. T. conceptualized the study, helped interpret the data, and provided expertise in manuscript preparation. Y. T., R. O., and H. T. developed the study design and supervised the authors throughout the study. Y. T. analyzed data. R. T. provided study materials. H. A., M. M., T. S., S. T., T. K., H. K., S. N., H. N., Y. I., M. U., K. K., D. K., K. S., Y. N., K. H., T. K., H. E., Y. M., H. I., M. I., S. K., R. H., D. H., and Y. T. performed 3D star shot analyses at various institutions. H. T. and K. S. critically revised the manuscript. Acknowledgement We thank Triangle Products Co. Ltd. (www.triangle-products.jp) for free provision of X-ray CT-based polymer gel dosimeters. We also thank Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript. Data Availability Research data are stored in an institutional repository and will be shared upon request to the corresponding author. References Yamamoto M, Serizawa T, Shuto T, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): A multi-institutional prospective observational study. Lancet Oncol . 2014;15:387-395. doi:10.1016/S1470-2045(14)70061-0 Gu Lei, Qing S, Zhu X, et al. Stereotactic radiation therapy (SRT) for brain metastases of multiple primary tumors: A single institution retrospective analysis. Front Oncol . 2019;9:1352. doi:10.3389/fonc.2019.01352 Vogelbaum MA, Brown PD, Messersmith H, et al. Treatment for brain metastases: ASCO-SNO-ASTRO guideline. J Clin Oncol . 2022;40:492-516. doi:10.1200/JCO.21.02314. Chen WC, Baal UH, Baal JD, et al. Efficacy and safety of stereotactic radiosurgery for brainstem metastases: A systematic review and meta-analysis. JAMA Oncol . 2021;7:1033-1040. doi:10.1001/jamaoncol.2021.1262 Schiff D, Messersmith H, Brastianos PK, et al. Radiation Therapy for Brain Metastases: ASCO Guideline Endorsement of ASTRO Guideline. J Clin Oncol. 2022;40(20):2271-2276. doi:10.1200/JCO.22.00333 Gondi V, Bauman G, Bradfield L, et al. Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline. Pract Radiat Oncol. 2022;12(4):265-282. doi:10.1016/j.prro.2022.02.003 Hartgerink D, Swinnen A, Roberge D, et al. LINAC based stereotactic radiosurgery for multiple brain metastases: guidance for clinical implementation. Acta Oncol . 2019;58: 1275-1282. doi:10.1080/0284186X.2019.1633016 Raza GH, Capone L, Tini P, Giraffa M, Gentile P, Minniti G. Single-isocenter multiple-target stereotactic radiosurgery for multiple brain metastases: dosimetric evaluation of two automated treatment planning systems. Radiat Oncol . 2022;17:116. doi:10.1186/s13014-022-02086-3 Badloe J, Mast M, Petoukhova A, et al. Impact of PTV margin reduction (2 mm to 0 mm) on pseudoprogression in stereotactic radiotherapy of solitary brain metastases. Tech Innov Patient Support Radiat Oncol . 2021;17:40-47. doi:10.1016/j.tipsro.2021.02.008 Redmond KJ, Gui C, Benedict S, et al. Tumor control probability of radiosurgery and fractionated stereotactic radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys . 2021;110:53-67. doi:10.1016/j.ijrobp.2020.10.034 Kirkpatrick JP, Wang Z, Sampson JH, et al. Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: Results of a randomized trial. Int J Radiat Oncol Biol Phys . 2015;91:100-108. doi:10.1016/j.ijrobp.2014.09.004 Kocher M, Wittig A, Piroth MD, et al. Stereotactic radiosurgery for treatment of brain metastases. A report of the DEGRO Working Group on Stereotactic Radiotherapy. Strahlenther Onkol. 2014;190(6):521-532. doi:10.1007/s00066-014-0648-7 Guckenberger M, Baus WW, Blanck O, et al. Definition and quality requirements for stereotactic radiotherapy: consensus statement from the DEGRO/DGMP Working Group Stereotactic Radiotherapy and Radiosurgery. Strahlenther Onkol. 2020;196(5):417-420. doi:10.1007/s00066-020-01603-1 Schmitt D, Blanck O, Gauer T, et al. Technological quality requirements for stereotactic radiotherapy : Expert review group consensus from the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy. Strahlenther Onkol. 2020;196(5):421-443. doi:10.1007/s00066-020-01583-2 Halvorsen PH, Cirino E, Das IJ, et al. AAPM-RSS Medical Physics Practice Guideline 9.a. for SRS-SBRT. J Appl Clin Med Phys . 2017;18(5):10-21. doi:10.1002/acm2.12146 International Commission on Radiation Units and Measurements (ICRU) Report 62, Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50). Bethesda, USA: ICRU Publications; 1999. van Herk M, Remeijer P, Rasch C, Lebesque JV. The probability of correct target dosage: dose-population histograms for deriving treatment margins in radiotherapy. Int J Radiat Oncol Biol Phys . 2000;47:1121-1135. doi:10.1016/s0360-3016(00)00518-6 Takakura T, Mizowaki T, Nakata M, et al. The geometric accuracy of frameless stereotactic radiosurgery using a 6D robotic couch system. Phys Med Biol . 2010;55:1-10. doi:10.1088/0031-9155/55/1/001 Zhang Q, Chan, MF, Song, Y, Burman, C. Three dimensional expansion of margins for single fraction treatments: Stereotactic radiosurgery brain cases. Int J Med Phys Clin Eng Radiat Oncol . 2012;1:15-22. doi: 10.4236/ijmpcero.2012.12003 Zhang Q, Chan MF, Burman C, Song Y, Zhang M. Three independent one-dimensional margins for single-fraction frameless stereotactic radiosurgery brain cases using CBCT. Med Phys . 2013;40:121715. doi:10.1118/1.4829517 Klein EE, Hanley J, Bayouth J, et al. Task group 142 report: Quality assurance of medical accelerators. Med Phys . 2009;36:4197-4212. doi:10.1118/1.3190392 Hanley J, Dresser S, Simon W, et al. AAPM Task Group 198 Report: An implementation guide for TG 142 quality assurance of medical accelerators. Med Phys . 2021;48:e830-e885. doi:10.1002/mp.14992 Pant K, Umeh C, Oldham M, Floyd S, Giles W, Adamson J. Comprehensive radiation and imaging isocenter verification using NIPAM kV-CBCT dosimetry. Med Phys . 2020;47:927-936. doi:10.1002/mp.14008 Kim JH, Kim B, Shin WG, et al. 3D star shot analysis using MAGAT gel dosimeter for integrated imaging and radiation isocenter verification of MR-linac system. J Appl Clin Med Phys . 2022;23:e13615. doi:10.1002/acm2.13615 Oshika R, Tachibana R, Seki K, et al. Technical Notes: Robustness of three-dimensional treatment and imaging isocenter testing using a new gel dosimeter and kilovoltage CBCT. J Appl Clin Med Phys. 2025;e14439. Doi:10.1002/acm2.14439 Ong, C., Giaj-Levra, N., Nicosia, L. et al. Intra-fraction and inter-fraction analysis of a dedicated immobilization device for intracranial radiation treatment. Radiat Oncol . 2020;15:200. doi:10.1186/s13014-020-01639-8 Babic S, Lee Y, Ruschin M, et al. To frame or not to frame? Cone-beam CT-based analysis of head immobilization devices specific to linac-based stereotactic radiosurgery and radiotherapy. Journal of Applied Clinical Medical Physics . 2018;19(2). doi:10.1002/acm2.12251 Seravalli E, van Haaren PM, van Der Toorn PP, Hurkmans CW. A comprehensive evaluation of treatment accuracy, including end-to-end tests and clinical data, applied to intracranial stereotactic radiotherapy. Radiother Oncol . 2015;116:131-138. doi: 10.1016/j.radonc.2015.06.004 Sykes JR, Brettle DS, Magee DR, Thwaites DI. Investigation of uncertainties in image registration of cone beam CT to CT on an image-guided radiotherapy system. Physics in Medicine and Biology . 2009;54(24). doi:10.1088/0031-9155/54/24/002 Tachibana H, Oshika R, Tachibana R, Seki K. Toward “on-line” X-ray computed tomography-based dosimetry using a new polymer gel with rapid response. Radiat Phys and Chem . 2024;218:111570. doi:10.1016/j.radphyschem.2024.111570 Al-Hallaq HA, Cerviño L, Gutierrez AN, et al. AAPM task group report 302: Surface-guided radiotherapy. Med Phys. 2022;49(4):e82-e112. doi:10.1002/mp.15532 Additional Declarations Competing interest reported. Y. T. received study materials from Triangle Products Co. Ltd. H. T. received a research grant from Triangle Products Co. Ltd. R. T. holds stock in Triangle Products Co. Ltd. There are no other commercial or financial relationships that might lead to a perceived conflict of interest. All the remaining authors declare no conflict of interest. Supplementary Files 04SupplementA.pdf 04SupplementB.pdf 04SupplementC.pdf 04SupplementD.pdf 04SupplementE.pdf 04SupplementF.pdf 04SupplementG.pdf Cite Share Download PDF Status: Published Journal Publication published 29 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 27 Dec, 2024 Reviews received at journal 26 Dec, 2024 Reviewers agreed at journal 26 Dec, 2024 Reviews received at journal 05 Dec, 2024 Reviewers agreed at journal 29 Nov, 2024 Reviewers invited by journal 28 Nov, 2024 Editor assigned by journal 28 Nov, 2024 Editor invited by journal 18 Nov, 2024 Submission checks completed at journal 16 Nov, 2024 First submitted to journal 26 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5336613","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":386530871,"identity":"3a140404-7cec-44f9-b4e2-ff2bfb2e0b3e","order_by":0,"name":"Yuta Takahashi","email":"","orcid":"","institution":"Jichi Medical University Saitama Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yuta","middleName":"","lastName":"Takahashi","suffix":""},{"id":386530872,"identity":"f2f019c6-25d2-436c-b197-a0c2ebc36611","order_by":1,"name":"Riki Oshika","email":"","orcid":"","institution":"National Cancer Center Hospital East","correspondingAuthor":false,"prefix":"","firstName":"Riki","middleName":"","lastName":"Oshika","suffix":""},{"id":386530874,"identity":"748ca817-c4c9-4d63-b8ca-4ca038d4ade0","order_by":2,"name":"Rie Tachibana","email":"","orcid":"","institution":"Triangle Products Co. Ltd","correspondingAuthor":false,"prefix":"","firstName":"Rie","middleName":"","lastName":"Tachibana","suffix":""},{"id":386530876,"identity":"157edfc8-789c-48c6-8d85-58190b508b4a","order_by":3,"name":"Katsuyuki Shirai","email":"","orcid":"","institution":"Jichi Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Katsuyuki","middleName":"","lastName":"Shirai","suffix":""},{"id":386530877,"identity":"fd6bf295-24cf-496f-8e55-3b1f796ee74c","order_by":4,"name":"Hiroshi Asakura","email":"","orcid":"","institution":"Dokkyo Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Asakura","suffix":""},{"id":386530878,"identity":"2405aa63-1eab-4e68-b7ca-8c39bcfbc5ba","order_by":5,"name":"Masayoshi Miyazaki","email":"","orcid":"","institution":"Osaka International Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Masayoshi","middleName":"","lastName":"Miyazaki","suffix":""},{"id":386530879,"identity":"f1bc1649-b35c-49e7-9779-3cace8e45641","order_by":6,"name":"Tomohiro Sagawa","email":"","orcid":"","institution":"Osaka International Cancer Institute","correspondingAuthor":false,"prefix":"","firstName":"Tomohiro","middleName":"","lastName":"Sagawa","suffix":""},{"id":386530880,"identity":"4900f919-1385-4406-93ab-037ce014d19a","order_by":7,"name":"Shinichi Takahashi","email":"","orcid":"","institution":"National Cancer Center Hospital East","correspondingAuthor":false,"prefix":"","firstName":"Shinichi","middleName":"","lastName":"Takahashi","suffix":""},{"id":386530881,"identity":"34d64228-62b6-4806-b3d1-7f78a3e2d42a","order_by":8,"name":"Tsunekazu Kuwae","email":"","orcid":"","institution":"Yuuai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Tsunekazu","middleName":"","lastName":"Kuwae","suffix":""},{"id":386530882,"identity":"3e4f734e-0a7b-4fd6-940c-cd5ad362ef3c","order_by":9,"name":"Hironori Kojima","email":"","orcid":"","institution":"Kanazawa University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hironori","middleName":"","lastName":"Kojima","suffix":""},{"id":386530884,"identity":"d7f4ca54-6173-4208-b0e8-212019dc2d33","order_by":10,"name":"Shiro Nishiyama","email":"","orcid":"","institution":"Saiseikai Kawaguchi General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shiro","middleName":"","lastName":"Nishiyama","suffix":""},{"id":386530889,"identity":"4619549a-3a5d-4eaf-9ea9-9342aa8d9734","order_by":11,"name":"Hikaru Nemoto","email":"","orcid":"","institution":"University of Yamanashi","correspondingAuthor":false,"prefix":"","firstName":"Hikaru","middleName":"","lastName":"Nemoto","suffix":""},{"id":386530892,"identity":"dbdae716-655d-4855-99cd-0108884db2e9","order_by":12,"name":"Yoshitomo Ishihara","email":"","orcid":"","institution":"Japanese Red Cross Wakayama Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yoshitomo","middleName":"","lastName":"Ishihara","suffix":""},{"id":386530893,"identity":"1877a17f-4293-48fa-9966-d207f0d21fd5","order_by":13,"name":"Mariko Umeda","email":"","orcid":"","institution":"Saitama Medical University","correspondingAuthor":false,"prefix":"","firstName":"Mariko","middleName":"","lastName":"Umeda","suffix":""},{"id":386530894,"identity":"59631d22-fde9-429f-8487-3642910130be","order_by":14,"name":"Kotaro Kijima","email":"","orcid":"","institution":"NHO Saitama Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kotaro","middleName":"","lastName":"Kijima","suffix":""},{"id":386530895,"identity":"b54492df-4ba0-48f2-bb82-64ff9c32af3b","order_by":15,"name":"Daisuke Kobayashi","email":"","orcid":"","institution":"University of Tsukuba Hospital","correspondingAuthor":false,"prefix":"","firstName":"Daisuke","middleName":"","lastName":"Kobayashi","suffix":""},{"id":386530896,"identity":"9efd7219-a03f-4439-a781-9780f7aa1653","order_by":16,"name":"Keiji Suzuki","email":"","orcid":"","institution":"University of Tsukuba Hospital","correspondingAuthor":false,"prefix":"","firstName":"Keiji","middleName":"","lastName":"Suzuki","suffix":""},{"id":386530897,"identity":"39bcca77-5a55-4108-ab03-2b910a06ecc5","order_by":17,"name":"Yuki Nozawa","email":"","orcid":"","institution":"The University of Tokyo Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuki","middleName":"","lastName":"Nozawa","suffix":""},{"id":386530898,"identity":"77249cf4-527a-4841-8d1f-ec4a05c6837c","order_by":18,"name":"Kento Hoshida","email":"","orcid":"","institution":"Kurume University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kento","middleName":"","lastName":"Hoshida","suffix":""},{"id":386530899,"identity":"b9178b16-b280-4015-8dcd-4369bdf6a9fc","order_by":19,"name":"Tomoki Kitagawa","email":"","orcid":"","institution":"Aichi Cancer Center Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tomoki","middleName":"","lastName":"Kitagawa","suffix":""},{"id":386530900,"identity":"88c27429-e6c9-453e-9b6b-27d33b933055","order_by":20,"name":"Hiromitsu Endo","email":"","orcid":"","institution":"Southern TOHOKU General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hiromitsu","middleName":"","lastName":"Endo","suffix":""},{"id":386530901,"identity":"4c1fff55-dab9-4cec-a61e-1944bff8010c","order_by":21,"name":"Yuki Matsunaga","email":"","orcid":"","institution":"Fukuoka Tokushukai Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuki","middleName":"","lastName":"Matsunaga","suffix":""},{"id":386530902,"identity":"1251c0bc-2cbc-4dcd-874c-a5bf099a1e31","order_by":22,"name":"Hiroya Itagaki","email":"","orcid":"","institution":"Niigata City General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hiroya","middleName":"","lastName":"Itagaki","suffix":""},{"id":386530903,"identity":"14295379-64a8-41bf-9ff2-ed9c26e988be","order_by":23,"name":"Mayumi Ishida","email":"","orcid":"","institution":"JCHO Osaka Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mayumi","middleName":"","lastName":"Ishida","suffix":""},{"id":386530904,"identity":"1864f94b-f1e1-4fab-8850-aeea27038345","order_by":24,"name":"Shigeru Kanahara","email":"","orcid":"","institution":"Kawasaki Medical School General Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Shigeru","middleName":"","lastName":"Kanahara","suffix":""},{"id":386530905,"identity":"ebee6e08-ecf6-4199-accb-646d021790e3","order_by":25,"name":"Ryo Horita","email":"","orcid":"","institution":"Nagoya City University East Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ryo","middleName":"","lastName":"Horita","suffix":""},{"id":386530906,"identity":"f7586f01-6ab2-48a9-8990-e1b16625fda4","order_by":26,"name":"Daisuke Hori","email":"","orcid":"","institution":"Japanese Red Cross Nagasaki Genbaku Hospital","correspondingAuthor":false,"prefix":"","firstName":"Daisuke","middleName":"","lastName":"Hori","suffix":""},{"id":386530907,"identity":"a3d5e8e9-75ef-4349-b5f4-ac72e41b6912","order_by":27,"name":"Hidenobu Tachibana","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYBACAyBmZjA4wMCPKs6DRwsbVItkA5B3gHgtQLUGB1C04AHm8s0PPxcU3JE3Pt78+PMHhjvy/A3sFx8wyNzBqcWyjc1YeobBM8NtZ46ZSRxgeGY44wBPsQEDzzPcDjvGYMbMY3CYcduNBDOgww4nAJWnSTDwHMajhf0bSIv95vnPP38gUgsP2JbEDRI8BhIQLezHCGjJKZbmMXiWPONMTpnEGYPDhjMO8zAbJODzy+HjGz/z/Llj299+fPOHiorD8vzt7Q8ffOzBHWLoJgAx0J0MiT0HiNUCBuwPGBh+kKZlFIyCUTAKhjUAAOm9Vz5/7MNcAAAAAElFTkSuQmCC","orcid":"","institution":"National Cancer Center Hospital East","correspondingAuthor":true,"prefix":"","firstName":"Hidenobu","middleName":"","lastName":"Tachibana","suffix":""}],"badges":[],"createdAt":"2024-10-26 09:08:28","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5336613/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5336613/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-87769-z","type":"published","date":"2025-01-29T15:58:05+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":72299042,"identity":"ec247b73-d9c3-4668-b61b-28d2d9d13bee","added_by":"auto","created_at":"2024-12-25 00:59:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":524438,"visible":true,"origin":"","legend":"\u003cp\u003eThree-dimensional starshot (3D-SS) treatment planning (A), irradiated gel dosimeter (B), and cone-beam computed tomography (CT) images of the post-irradiated gel dosimeter (C) used in this study. Red linesin panel A indicate the 20 Gy isodose line.\u003c/p\u003e","description":"","filename":"03FIG1.png","url":"https://assets-eu.researchsquare.com/files/rs-5336613/v1/44359fff4faff90f30072ad2.png"},{"id":72299267,"identity":"c19d4603-dfff-4ab9-b779-6c691651bc33","added_by":"auto","created_at":"2024-12-25 01:07:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":33252,"visible":true,"origin":"","legend":"\u003cp\u003eBox and whisker plots of the 3D-SS test performed using Varian and Elekta machines at 22 institutions (bold line, median; cross, mean; boxes, first and third quartiles; whiskers, 5th and 95th percentiles; circles, outliers). (A) Minimum distance (dmin) of the seven beams from the imaging isocenter in three directions. (B) Value of d_min for the seven beams, expressed in terms of the resultant vector. (C) Distance between the imaging isocenter and radiation isocenter (diIC-rIC) in three directions. (D) Value of diIC-rIC expressed in terms of the resultant vector. (E) Radius (r) of the smallest sphere that intersects all radiation beams. Notation: n.s. = not significant; *p \u0026lt; 0.05; **p \u0026lt; 0.01; ***p \u0026lt; 0.001.\u003c/p\u003e","description":"","filename":"03FIG2mod.png","url":"https://assets-eu.researchsquare.com/files/rs-5336613/v1/496c8e2590df8d0d83fbd380.png"},{"id":72299044,"identity":"1c33d8f2-231e-4097-a44d-16ca2b2e4e04","added_by":"auto","created_at":"2024-12-25 00:59:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":96538,"visible":true,"origin":"","legend":"\u003cp\u003eBox and whisker plots of the planning target volume (PTV) margins (Ci; i = X, Y, Z) for intracranial single-fraction stereotactic radiosurgery at 22 institutions. The margin was derived from 3D-SS analysis of the dose delivery accuracy and from residual setup errors reported by Ong et al.26 and Zhang et al.20 Notation: *p \u0026lt; 0.05; **p \u0026lt; 0.01; ***p \u0026lt; 0.001.\u003c/p\u003e","description":"","filename":"03FIG3.png","url":"https://assets-eu.researchsquare.com/files/rs-5336613/v1/b292c3827283d2305b750bc0.png"},{"id":72299045,"identity":"ddacab9f-48d4-4a12-b84c-2344a699ee07","added_by":"auto","created_at":"2024-12-25 00:59:19","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":326394,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative frequency distributions of the PTV margins for Varian and Elekta systems used in this study. The margin sizes in three directions are shown, and they were derived from 3D-SS analysis of the dose delivery accuracy and from residual setup errors reported by Ong et al.\u003csup\u003e26\u003c/sup\u003e and Zhang et al.\u003csup\u003e20\u003c/sup\u003e\u003c/p\u003e","description":"","filename":"03FIG4.png","url":"https://assets-eu.researchsquare.com/files/rs-5336613/v1/62f8be67009cb496df3136ad.png"},{"id":75351333,"identity":"10869d40-74bf-4a0b-9ee9-921dba28abe0","added_by":"auto","created_at":"2025-02-03 16:09:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1945213,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5336613/v1/08612964-9b3d-48d6-9ecc-a2aadf9ca8ea.pdf"},{"id":72299268,"identity":"2066b5d7-c0e2-48a0-b716-01db876df7cb","added_by":"auto","created_at":"2024-12-25 01:07:19","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":86270,"visible":true,"origin":"","legend":"","description":"","filename":"04SupplementA.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5336613/v1/2523bcd74cdc95fa29e0eff5.pdf"},{"id":72299269,"identity":"956f457c-efe0-4e60-97a9-900785b152ed","added_by":"auto","created_at":"2024-12-25 01:07:19","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":371304,"visible":true,"origin":"","legend":"","description":"","filename":"04SupplementB.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5336613/v1/baca35375286aa16db46f498.pdf"},{"id":72299048,"identity":"b8d02976-6791-4b10-bf4b-b6f920e41d2a","added_by":"auto","created_at":"2024-12-25 00:59:19","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":75232,"visible":true,"origin":"","legend":"","description":"","filename":"04SupplementC.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5336613/v1/966dd06286c8615b3a4bf5f6.pdf"},{"id":72299270,"identity":"11f8d494-b09d-442d-bb88-1b03d2482b9c","added_by":"auto","created_at":"2024-12-25 01:07:19","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":125174,"visible":true,"origin":"","legend":"","description":"","filename":"04SupplementD.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5336613/v1/666d8717c8eb399333753e2b.pdf"},{"id":72299049,"identity":"4e371e85-76ed-4846-bb6f-2b7b6d33e277","added_by":"auto","created_at":"2024-12-25 00:59:19","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":134655,"visible":true,"origin":"","legend":"","description":"","filename":"04SupplementE.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5336613/v1/feababd9468de85ec42e2cc5.pdf"},{"id":72299052,"identity":"f48142c7-2722-40aa-b0eb-0333852849e5","added_by":"auto","created_at":"2024-12-25 00:59:19","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":154550,"visible":true,"origin":"","legend":"","description":"","filename":"04SupplementF.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5336613/v1/af7964dfb709fc41e1a15967.pdf"},{"id":72299051,"identity":"a164a1a4-aa8f-424a-a5ce-9ee01852ac1b","added_by":"auto","created_at":"2024-12-25 00:59:19","extension":"pdf","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":157815,"visible":true,"origin":"","legend":"","description":"","filename":"04SupplementG.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5336613/v1/d2a9daf6eb48d109e018204c.pdf"}],"financialInterests":"Competing interest reported. Y. T. received study materials from Triangle Products Co. Ltd. H. T. received a research grant from Triangle Products Co. Ltd. R. T. holds stock in Triangle Products Co. Ltd. There are no other commercial or financial relationships that might lead to a perceived conflict of interest. All the remaining authors declare no conflict of interest.","formattedTitle":"Spatial accuracy of dose delivery significantly impacts the planning target volume margin in linear accelerator-based intracranial stereotactic radiosurgery","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eStereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) using a medical linear accelerator (linac) have largely replaced whole-brain irradiation as a treatment for multiple brain metastases.\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e For such applications, SRS and SRT commonly use non-coplanar, intensity-modulated irradiation.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e The targets are often smaller than a few centimeters, and treatment is planned with a small planning target volume (PTV) margin of 0\u0026ndash;2 mm.\u003csup\u003e\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e This margin size is also recommended by the working group on stereotactic radiotherapy of the German Society of Radiation Oncology.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e These facts highlight the need for radiation delivery with submillimeter accuracy. Minimizing irradiation positional errors relative to the imaging isocenter is therefore becoming increasingly important. Variations in linac dose delivery accuracy may also affect clinical outcomes of intracranial SRS/SRT. Several guidelines for SRS require a geometric accuracy within 1 mm in an end-to-end (E2E) test.\u003csup\u003e\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e The E2E test includes the accuracy of contouring and registration\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Thus, the guidelines require the delivery accuracy of the linac to be less than 1 mm.\u003c/p\u003e \u003cp\u003eTo compensate for systematic and random errors in patient positioning,\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e van Herk et al. designed a margin determination method that does not depend on the three-dimensional (3D) dose delivery accuracy of the linac.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e In contrast, Takakura et al. suggested a method for estimating overall geometric uncertainty from uncertainties in both the patient position and linac dose delivery.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Moreover, Zhang et al. suggested a method to derive the optimal PTV margin for intracranial SRS by taking into account the distance between the imaging and radiation isocenters and the residual setup error after image guidance.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e If the impact of the 3D dose delivery accuracy on the margin is high, the approach proposed by Zhang et al. and Takakura et al. is considered ideal. To correctly derive the margin, the 3D dose delivery accuracy of the linac must be measured with low measurement uncertainties.\u003c/p\u003e \u003cp\u003eTo appropriately determine the margin for intracranial SRS/SRT and provide treatment with sufficient target coverage, we should directly assess and manage the 3D radiation delivery accuracy relative to the imaging isocenter by performing quality assurance (QA) procedures with minimal measurement uncertainties. Conventionally, two-dimensional (2D) planar images are obtained for each beam in QA tests, and the mechanical isocenter with some setup uncertainties is commonly used as the reference, especially for the Winston\u0026ndash;Lutz (WL) test.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Thus, these tests include the measurement uncertainties derived from the mechanical isocenter to obtain 3D information from the 2D images. Uncertainties in a QA test may therefore contribute to the PTV margin size because the spatial dose delivery accuracy of linacs affects geometric uncertainties in the GTV.\u003c/p\u003e \u003cp\u003eRecently, a new 3D starshot (3D-SS) test using a polymer gel dosimeter has been reported to solve the above-mentioned problems in verifying geometric accuracy.\u003csup\u003e\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e This approach allows a direct, comprehensive 3D evaluation of spatial radiation accuracy relative to the imaging isocenter.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e The trajectories of radiation beams through the dosimeter are visualized using kilovoltage cone-beam computed tomography (kV-CBCT), and the imaging isocenter is thus obtained from the resulting kV-CBCT image. Human errors derived from QA phantom setup and laser indication adjustment do not affect the measurement accuracy. The 3D-SS test may be superior to the conventional QA methods because it eliminates uncertainties associated with those methods, and the measurement uncertainty of the 3D-SS test has been found to be 0.2\u0026ndash;0.3 mm\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe geometric uncertainties in patient setup and dose delivery may vary among institutions and manufacturers. The 3D dose delivery accuracy should be included in the PTV margin size if the uncertainties significantly affect the margin. This 3D dose delivery accuracy should be measured with low uncertainty, because the guidelines have recommended that each institution aim to achieve a PTV margin of 2 mm in intracranial SRS.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e In contrast to conventional QA tests of spatial dose delivery, which may over- or underestimate the margin, 3D-SS analysis is effective for this purpose because it provides such spatial information free from measurement uncertainties associated with the setup. However, only the methodology has so far been proposed, and no information is available on variations in 3D dose delivery accuracy among commercially available linacs. While there are numerous studies focusing on patient setup accuracy\u003csup\u003e\u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, there is a notable lack of research addressing linac precision, particularly with respect to differences between manufacturers and individual units. Furthermore, it remains unclear whether the PTV margin obtained for linac-based intracranial SRS via 3D-SS analysis will satisfy the recommended 2 mm limit.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eTo correctly evaluate the impact of the spatial dose delivery accuracy of linacs on the PTV margin in intracranial SRS, we performed a multi-institutional study using linacs from two vendors using the 3D-SS test. We also developed a method for calculating the margin for the 3D-SS test. Furthermore, on the basis of the 3D-SS test results, we investigated whether the PTV margin could be constrained within 2 mm by implementing advanced image guidance (real-time video-based 3D optical surface imaging and 2D kV stereoscopic imaging) and rigorous linac quality management.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003e2.1. Institution Selection\u003c/h2\u003e\n \u003cp\u003eTwenty-two institutions that performed intracranial stereotactic radiotherapy in clinical practices participated in this study. All institutions used a medical C-arm linac attached to an on-board imager enabling kV-CBCT. Seven institutions used a TrueBeam system (Varian Medical Systems, Inc., Palo Alto, CA, USA), four used a TrueBeamSTx system (Varian Medical Systems), four used a VersaHD system (Elekta AB, Stockholm, Sweden), three used an Infinity system (Elekta AB), and four used a Synergy system (Elekta AB). We verified that a geometric QA test was regularly performed at all facilities in accordance with guidelines published by task groups 142 and 198 of the American Association of Physicists in Medicine.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003e2.2. Assessment of 3D linac accuracy using the 3D-SS test\u003c/h2\u003e\n \u003cp\u003eThe 3D-SS test is robust with low measurement uncertainties for evaluating 3D dose delivery accuracy.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e All institutions followed the 3D-SS test procedure described below. In total, 22 jars each containing an X-ray computed tomography (CT)-based polymer gel dosimeter called dGEL\u0026trade; (Triangle Products Co., Ltd., Kashiwa, Japan) were used in this study.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eTreatment was planned using the treatment planning system installed at each institution. A common dGEL\u0026trade; CT dataset, acquired using an Aquilion ONE system (Canon Medical Systems, Otawara, Japan), was sent to all institutions. A 10 MV flattening filter photon beam or a 6 or 10 MV flattening filter-free photon beam was used. Symmetric fields with a minimum size of 0.5 \u0026times; 0.5 cm\u0026sup2; for Varian systems and 0.6 \u0026times; 0.6 cm\u0026sup2; for Elekta systems were used. Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e shows gantry, couch, and collimator angle settings for radiation beams based on the study by Pant et al.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e A machine output between 6000 and 8000 monitor units was determined for each beam to create an isodose line of 20 Gy in the beam path (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA). A dose of 20 Gy was selected on the basis of our preliminary study\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e, which showed that this dose resulted in a sufficient contrast-to-noise ratio for each beam to perform the analysis using our in-house software. The software uses algorithms that determine a 3D vector with a point in the CBCT coordinate system that defines the beam axis by maximizing the contrast-to-noise ratio.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Each jar including the gel dosimeter was sent to its respective institution. The jar was placed with the center of its sensitive volume located approximately at the mechanical isocenter indicated by the room laser. The gel dosimeter was placed on the couch and secured in place using adhesive tape to prevent movement. A pre-irradiation kV-CBCT image was obtained using the image acquisition and reconstruction parameters in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Subsequently, the gel dosimeter was irradiated with seven narrow beams using gantry and couch rotations (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB), and post-irradiated kV-CBCT images were acquired using the same parameters as above (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eC). For analysis, the image datasets of pre-irradiated and post-irradiated gel dosimeters were imported into our in-house program\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. The analysis quantified the minimum distance (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{m}\\text{i}\\text{n}}\\)\u003c/span\u003e\u003c/span\u003e) between each radiation beam and the origin of the imaging coordinate system (imaging isocenter, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\text{i}\\text{I}\\text{C}\\)\u003c/span\u003e\u003c/span\u003e), the distance (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e) between the radiation isocenter (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\text{r}\\text{I}\\text{C}\\)\u003c/span\u003e\u003c/span\u003e) and the \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\text{i}\\text{I}\\text{C}\\)\u003c/span\u003e\u003c/span\u003e, and the radius (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:r\\)\u003c/span\u003e\u003c/span\u003e) of the smallest sphere that intersects all beams.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eGantry, couch, and collimator angles of beams used in this study, following International Electrotechnical Commission standard 61217.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBeam No.\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGantry [degree]\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCouch\u003c/p\u003e\n \u003cp\u003e[degree]\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCollimator\u003c/p\u003e\n \u003cp\u003e[degree]\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eKilovoltage cone-beam CT image acquisition and reconstruction parameters used for the three-dimensional starshot analysis.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eparameter\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVarian (iCBCT)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVarian (FBP)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eElekta\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTube voltage [kV]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTube current-exposure time product [mAs]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2112\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFrame rate [frames/sec]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGantry speed [degree/sec]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRotational angle\u003c/p\u003e\n \u003cp\u003e[degree - degree]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e180\u0026ndash;180 (CCW)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e180\u0026ndash;180 (CCW)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e180\u0026ndash;180 (CCW)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFan type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrajectory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFull\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReconstruction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eiCBCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFBP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFeldkamp\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMatrix size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e512 x 512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e512 x 512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e512 x 512\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSlice thickness[mm]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThe other reconstruction parameters\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmooth reconstruction filter: standard\u003c/p\u003e\n \u003cp\u003edenoise: Medium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmooth reconstruction filter: Auto\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReconstruction filter: Wiener\u003c/p\u003e\n \u003cp\u003eInterpolation: strong (set as Partial2)\u003c/p\u003e\n \u003cp\u003eScatter Correction: Uniform (set the factor as 0.24)\u003c/p\u003e\n \u003cp\u003ePre Filter: Median (strong)\u003c/p\u003e\n \u003cp\u003eProjection Down Size Factor: 1 (best quality)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eAbbreviations: iCBCT = iterative cone-beam computed tomography; FBP = filtered back projection; CCW = counterclockwise.\u003c/p\u003e\n \u003cp\u003eThe values of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{m}\\text{i}\\text{n}}\\)\u003c/span\u003e\u003c/span\u003e, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e, and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:r\\)\u003c/span\u003e\u003c/span\u003e were obtained at all institutions. An inter-manufacturer comparison was made for these values. For \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{m}\\text{i}\\text{n}}\\)\u003c/span\u003e\u003c/span\u003e and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e, the comparison was made for each direction of the image (DICOM) coordinate system and for the resultant vector.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e2.3. Impact of 3D linac accuracy on SRS\u003c/h2\u003e\n \u003cp\u003eWe assessed the impact of the spatial dose delivery accuracy on the PTV margins in intracranial SRS. PTV margins were derived using the 3D-SS analysis results. Zhang et al. proposed a method to calculate the optimal PTV margin for single-fraction intracranial SRS that incorporates the linac spatial dose delivery error and the residual patient setup error after image guidance.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e The method provides an anisotropic margin for intracranial SRS that ensures with 95% probability that the clinical target volume receives the prescribed dose.\u003c/p\u003e\n \u003cp\u003eIn this study, we developed the method by inputting the 3D dose delivery accuracy derived from the 3D-SS test as the linac spatial dose delivery error, building on a previously reported study\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. After calculating the optimal PTV margins, inter-institution and inter-manufacturer comparisons were made.\u003c/p\u003e\n \u003cp\u003eThe formulas are\u003c/p\u003e\n \u003cdiv id=\"Equ1\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equ1\" name=\"EquationSource\"\u003e$$\\:{C}_{i}={W}_{0i}+{b}_{1}\\left({W}_{0i}\\right){\\sigma\\:}_{i}+{b}_{2}\\left({W}_{0i}\\right){\\sigma\\:}_{i}^{2}$$\u003c/div\u003e\n \u003cdiv class=\"EquationNumber\"\u003e1\u003c/div\u003e\n \u003c/div\u003e,\u003cdiv id=\"Equ2\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equ2\" name=\"EquationSource\"\u003e$$\\:{b}_{1}\\left({W}_{0i}\\right)={2.331-1.425W}_{0i}+2.296{W}_{0i}^{2}-1.539{W}_{0i}^{3}+0.374{W}_{0i}^{4}$$\u003c/div\u003e\n \u003cdiv class=\"EquationNumber\"\u003e2\u003c/div\u003e\n \u003c/div\u003e,\u003cdiv id=\"Equ3\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equ3\" name=\"EquationSource\"\u003e$$\\:{b}_{2}\\left({W}_{0i}\\right)={0.434W}_{0i}-0.917{W}_{0i}^{2}+0.676{W}_{0i}^{3}-0.171{W}_{0i}^{4}$$\u003c/div\u003e\n \u003cdiv class=\"EquationNumber\"\u003e3\u003c/div\u003e\n \u003c/div\u003e,\u003cp\u003ewere \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{C}_{i}\\)\u003c/span\u003e\u003c/span\u003e represents the PTV margin for the \u003cem\u003ei\u003c/em\u003e\u0026thinsp;=\u0026thinsp;\u003cem\u003eX\u003c/em\u003e, \u003cem\u003eY\u003c/em\u003e, and \u003cem\u003eZ\u003c/em\u003e directions in the DICOM coordinate system; \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{W}_{0i}={V}_{s0i}+{V}_{r0i}\\)\u003c/span\u003e\u003c/span\u003e, where \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{V}_{s0i}\\)\u003c/span\u003e\u003c/span\u003e represents the systematic error in the imaging isocenter and radiation isocenter along each axis; \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{V}_{r0i}\\)\u003c/span\u003e\u003c/span\u003e denotes the average residual error in patient setup after image guidance; and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\sigma\\:}_{i}\\)\u003c/span\u003e\u003c/span\u003e is a function of the standard deviation of the residual error in patient setup (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{SD}_{\\text{s}\\text{e}\\text{t}\\text{u}\\text{p},i}\\)\u003c/span\u003e\u003c/span\u003e). In this study, we added fluctuations in the radiation beam position (random error in the radiation isocenter) to \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{\\sigma\\:}_{i}\\)\u003c/span\u003e\u003c/span\u003e:\u003c/p\u003e\n \u003cdiv id=\"Equ4\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equ4\" name=\"EquationSource\"\u003e$$\\:{\\sigma\\:}_{i}=\\sqrt{{SD}_{\\text{s}\\text{e}\\text{t}\\text{u}\\text{p},i}^{2}+{\\left(0.683\\times\\:r\\right)}^{2}}$$\u003c/div\u003e\n \u003cdiv class=\"EquationNumber\"\u003e4\u003c/div\u003e\n \u003c/div\u003e,\u003cp\u003ewhere the term \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:0.683\\times\\:r\\)\u003c/span\u003e\u003c/span\u003e corresponds to the standard deviation of the radiation isocenter error, which was assumed to follow a normal distribution.\u003c/p\u003e\n \u003cp\u003eIn this study, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{V}_{s0i}\\)\u003c/span\u003e\u003c/span\u003e was directly set equal to \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e, which includes the influence of couch rotation. The values of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{V}_{r0i}\\)\u003c/span\u003e\u003c/span\u003e and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{SD}_{\\text{s}\\text{e}\\text{t}\\text{u}\\text{p},i}\\)\u003c/span\u003e\u003c/span\u003e were taken from the studies of Zhang et al.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e and Ong et al.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e and are shown in Supplementary Table A1. The values of the former and the latter were defined as the larger and smaller residual patient setup errors.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003e2.4. Impact of QA procedures on SRS accuracy\u003c/h2\u003e\n \u003cp\u003eWe evaluated the impact of implementing advanced image guidance systems for patient positioning and rigorous geometric QA of the linac. This study assumed that advanced image guidance systems, which include widely installed video-based 3D optical surface imaging and 2D kV stereoscopic imaging, were implemented. During non-coplanar irradiation in clinical settings, we also assumed that intra-fraction patient motion caused by treatment couch shifts during couch rotation could be monitored and corrected by these imaging modalities. For example, we hypothesized that current surface-guided radiation therapy systems could detect a couch walk-out of \u0026lt;\u0026thinsp;1 mm.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e Furthermore, the value of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e was treated as a systematic error for linacs that could be minimized by a geometric calibration test performed by the user. These assumptions form the basis for the further analysis conducted in this study. Therefore, this study assumed that in clinical practice, the user\u0026rsquo;s efforts can reduce the impact of these two factors on geometric accuracy to nearly zero. Based on this assumption, the PTV margin was recalculated by replicating the situation using the following procedure: 3D dose delivery accuracy was recalculated using only the co-planar beams, and the new values of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:r\\)\u003c/span\u003e\u003c/span\u003e were measured. Subsequently, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e was set to zero to account for the error contribution of the geometric calibration of the linac. Finally, the PTV margin was recalculated using equations \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and the above value of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:r\\)\u003c/span\u003e\u003c/span\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003e2.5. Statistical analysis\u003c/h2\u003e\n \u003cp\u003eStatistical analyses were performed to examine inter-manufacturer differences and inter-axis differences in various parameters. The Kruskal\u0026ndash;Wallis test and Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e test were used to compare the results from more than two institutions and vendors, respectively. The Steel\u0026ndash;Dwass post hoc test was used to make pair-wise comparisons. All statistical analyses were conducted using EZR (version 1.62, Saitama Medical Center, Jichi Medical University, Saitama, Japan). A value of \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e categorizes the values of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{m}\\text{i}\\text{n}}\\)\u003c/span\u003e\u003c/span\u003e, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e, and \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:r\\)\u003c/span\u003e\u003c/span\u003e for non-coplanar irradiation for each institution according to the linac manufacturer, and the raw data for these parameters are summarized in Supplements B, C, and D, respectively.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor the seven beams used at each institution, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{m}\\text{i}\\text{n}}\\:\\)\u003c/span\u003e\u003c/span\u003eshowed variability among institutions and between manufacturers (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA and Supplements B1, B2). As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA, the positional errors in the beam paths of the Elekta systems were significantly larger than those of the Varian systems in the \u003cem\u003eX\u003c/em\u003e (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:p\\:\\)\u003c/span\u003e\u003c/span\u003e\u0026lt; 0.001), \u003cem\u003eY\u003c/em\u003e (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:p\\)\u003c/span\u003e\u003c/span\u003e \u0026lt; 0.001), and \u003cem\u003eZ\u003c/em\u003e (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:p\\)\u003c/span\u003e\u003c/span\u003e \u0026lt; 0.05) directions. There were no significant differences in the positional errors among any of the \u003cem\u003eX\u003c/em\u003e, \u003cem\u003eY\u003c/em\u003e, and \u003cem\u003eZ\u003c/em\u003e directions for Varian systems, whereas the Elekta systems had a significantly larger error in the \u003cem\u003eZ\u003c/em\u003e direction compared with those in the \u003cem\u003eX\u003c/em\u003e and \u003cem\u003eY\u003c/em\u003e directions (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:p\\)\u003c/span\u003e\u003c/span\u003e \u0026lt; 0.001). In terms of the resultant vector, the Elekta systems had a significantly larger positional error in the beam path than the Varian systems \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:(p\\:\\)\u003c/span\u003e\u003c/span\u003e\u0026lt; 0.05), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB, and the numbers of institutions for which the value exceeded 1 mm were one and nine for Varian and Elekta systems, respectively. These 10 institutions exceeded the 1 mm tolerance proposed for the E2E test by the Medical Physics Practice Guidelines developed by the American Association of Physicists in Medicine and also proposed in the consensus statement from the working groups for radiosurgery and stereotactic radiotherapy of the German Society for Radiation Oncology and for physics and technology in stereotactic radiotherapy of the German Society for Medical Physics.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe value of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e, which includes the influence of couch rotation, was evaluated. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eC and Supplement C, the values of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e for the Varian systems were within \u0026plusmn;\u0026thinsp;0.32 mm in all directions, and the median values were within 0.1 mm. No significant differences were observed among the values of \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e in the \u003cem\u003eX\u003c/em\u003e, \u003cem\u003eY\u003c/em\u003e, and \u003cem\u003eZ\u003c/em\u003e directions. In contrast, the Elekta systems had a maximum \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e of 1.21 mm in the \u003cem\u003eY\u003c/em\u003e direction, with median values in the \u003cem\u003eX\u003c/em\u003e, \u003cem\u003eY\u003c/em\u003e, and \u003cem\u003eZ\u003c/em\u003e directions of 0.16, 0.39, and \u0026minus;\u0026thinsp;0.42 mm, respectively. Furthermore, \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:{d}_{\\text{i}\\text{I}\\text{C}-\\text{r}\\text{I}\\text{C}}\\)\u003c/span\u003e\u003c/span\u003e was significantly larger in the \u003cem\u003eZ\u003c/em\u003e (longitudinal) direction than in the \u003cem\u003eX\u003c/em\u003e (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and \u003cem\u003eY\u003c/em\u003e (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01) directions. The displacements for the Elekta systems were significantly larger than those for the Varian systems (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:p\\)\u003c/span\u003e\u003c/span\u003e \u0026lt; 0.001), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD and Supplement C.\u003c/p\u003e \u003cp\u003eThe radius of the smallest sphere intersecting all radiation beams, which includes the effect of couch rotation, is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE and Supplement D. The Elekta linacs had a significantly larger radius (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:p\\:\\)\u003c/span\u003e\u003c/span\u003e\u0026lt; 0.001) than the Varian linacs.\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Supplement E show the PTV margins derived from 3D-SS analysis of dose delivery error and from residual patient setup errors after image guidance. The PTV margins varied among institutions and between manufacturers. The minimum and maximum PTV margins were 1.0 and 3.4 mm, respectively, regardless of manufacturer or coordinate axis. Significant differences in the PTV margins between the Varian and Elekta systems were measured in the \u003cem\u003eX\u003c/em\u003e (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:p\\)\u003c/span\u003e\u003c/span\u003e \u0026lt; 0.01), \u003cem\u003eY\u003c/em\u003e (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:p\\)\u003c/span\u003e\u003c/span\u003e \u0026lt; 0.01), and \u003cem\u003eZ\u003c/em\u003e (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:p\\)\u003c/span\u003e\u003c/span\u003e \u0026lt; 0.001) directions. Assuming that the PTV margins calculated for the institutions sampled follow a normal distribution, the cumulative frequency distributions of the PTV margins were calculated for each manufacturer (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The probability of exceeding a 2 mm margin was higher for Elekta systems than for Varian systems. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the PTV margins that could cover the GTV in the \u003cem\u003eX\u003c/em\u003e, \u003cem\u003eY\u003c/em\u003e, and \u003cem\u003eZ\u003c/em\u003e directions with 95% probability at 95% of the institutions. A PTV margin of 2 mm was achievable for the Varian systems if the smaller setup errors reported by Ong et al.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e were assumed. The margin for Elekta systems was unachievable under all conditions assumed in this study, with a 3.5 mm margin being required in the \u003cem\u003eZ\u003c/em\u003e direction in the worst case.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePlanning target volume (PTV) margins for Varian and Elekta linear accelerators that could cover the gross tumor volume with 95% probability at 95% of the institutions. The margins in three directions are shown, and they were derived from a three-dimensional starshot (3D-SS) test of the dose delivery accuracy and the residual setup errors reported by Ong et al.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e and Zhang et al.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eManufacturer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDirection\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003ePTV margin size [mm]\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOng\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eZhang\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVarian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElekta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAssuming that high-accuracy 3D dose delivery, strict patient immobilization and intra-fractional positioning, and rigorous linac QA could improve 3D geometric accuracy, the isocentricity \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:r\\)\u003c/span\u003e\u003c/span\u003e was reduced from 0.81 to 0.32 mm for Varian systems and from 1.45 to 0.76 mm for Elekta systems (cf. Supplements D and F). Being less than 1 mm, these values met the proposed tolerance level.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e PTV margins for all institutions are shown in Supplement G, and those margins that could cover the GTV with 95% probability at 95% of the institutions are shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Even when a larger residual patient setup error was assumed, the margin size for all institutions using Varian systems remained below 2 mm, and the PTV margins that could cover the GTV with 95% probability at 95% of the institutions were 1.5, 1.1, and 2.0 mm in the \u003cem\u003eX\u003c/em\u003e, \u003cem\u003eY\u003c/em\u003e, and \u003cem\u003eZ\u003c/em\u003e directions, respectively. When a smaller residual patient setup error was assumed, the PTV margin size for all institutions using Elekta systems remained below 2 mm, and the margins that could cover the GTV with 95% probability at 95% of the institutions were 1 mm for Varian Systems and 1.5 mm for Elekta Systems in all directions.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePTV margins for Varian and Elekta linear accelerators that could cover the gross tumor volume with 95% probability at 95% of the institutions, determined assuming that the distance between the imaging and radiation isocenters is zero owing to rigorous QA implementation and that the intra-fraction error caused by treatment couch rotation is zero owing to implementation of a positional monitoring system such as surface image guidance. The margins in three directions are shown, and they were derived from 3D-SS analysis of the dose delivery accuracy and the residual setup errors reported by Ong et al.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e and Zhang et al.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eManufacturer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDirection\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eReduced PTV margin size [mm]\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOng\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eZhang\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVarian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElekta\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eZ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eTo our knowledge, this is the first multi-institutional study to combine 3D-SS analysis with an X-ray CT-based polymer gel dosimeter to evaluate the 3D dose delivery accuracy, including couch rotation accuracy, of commercially available linacs broadly in clinical use. Moreover, institution- and manufacturer-specific PTV margins for intracranial SRS were derived from 3D-SS analysis of dose delivery accuracy. This report will serve as a useful reference for institutions seeking to objectively evaluate their own dose delivery accuracy and to determine the PTV margin for intracranial SRS.\u003c/p\u003e \u003cp\u003eThis study made several important findings. First, it provides generally achievable values for linacs from each manufacturer. Pant et al. proposed a 3D-SS method that minimizes measurement uncertainties. However, there is no information on variations in 3D dose delivery accuracy among commercially available linacs.\u003c/p\u003e \u003cp\u003e Second, we found that one Varian and nine Elekta linacs exceeded the 1 mm tolerance of SRS guidelines on spatial irradiation accuracy, even if conventional WL tests and timings were followed. In a previous study, there were discrepancies of \u0026lt;\u0026thinsp;0.4 mm in the resulting coincidence of each beam obtained via the conventional WL test and 3D-SS test.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Thus, these results imply that conventional QA methods may underestimate 3D dose delivery errors. A 3D QA procedure with low measurement uncertainties, such as the 3D-SS test, should be performed to achieve dose delivery errors of no more than 1 mm in 3D coordinates.\u003c/p\u003e \u003cp\u003eThird, non-coplanar irradiation for intracranial SRS performed without any image guidance system may need more than a 2 mm PTV margin when a larger residual patient setup error is assumed. Several studies have reported that the PTV margin can be reduced without affecting the clinical outcome\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. However, it is unclear whether similar results can be obtained at other institutions because our findings indicate that the accuracy of irradiation is institution-dependent. In this study, the margin was in the 1.0\u0026ndash;3.4 mm range. This considerable variation indicates that universal determination and reduction of the PTV margin should be approached cautiously.\u003c/p\u003e \u003cp\u003eThe limitation of this study is that we used the values of residual setup error from other studies. Institution-specific residual setup error ideally may be input to the formula of the margin calculation. In contrast, a common margin from research papers and some protocols from clinical trials may be used in many institutions. In this study, two kinds of residual setup errors from the literature\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e were used, and we evaluated the impact on the PTV margin. Institution-specific residual setup errors should be evaluated to determine a more accurate margin.\u003c/p\u003e \u003cp\u003eIn this study, we used linacs for intracranial stereotactic radiotherapy in clinical practice. Although the Elekta linac models used in this study belong to different generations, there are no differences in the structure and function of the linacs across the three models. The couch systems differ among the three models. However, only the yaw rotation of the couch was used in this study, and we considered that there was no significant difference in the accuracy of the yaw rotation among the models.\u003c/p\u003e \u003cp\u003eFinally, this study highlights the importance of precise management of the 3D dose delivery accuracy by medical physicists. Radiation oncology departments should also introduce a real-time monitoring system capable of correcting patient displacement due to body movement and couch rotation. Moreover, therapists must improve patient immobilization and verification of position accuracy. The margin could be reduced to within the recommended 2 mm limit by assuring high-accuracy 3D dose delivery, strict patient immobilization and intra-fractional positioning, and rigorous linac QA.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Our multi-institutional study showed that it is possible to limit the PTV margin size for intracranial SRS to 1.0 mm for Varian systems and 1.5 mm for Elekta systems in all directions.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThe 3D dose delivery accuracy of linacs currently in operation largely varied at the millimeter level in this study. The accuracy of current radiotherapy technology should not be overestimated, and it is essential to rigorously determine the 3D dose delivery accuracy and estimate the PTV margins. A geometric QA test with low measurement uncertainties should be performed to ensure the PTV margin is within 2 mm. During treatment, the patient\u0026rsquo;s intra-fractional setup error should be limited using advanced image guidance systems. Finally, for intracranial SRS, one should ensure that the irradiation margins remain within 2 mm.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eiCBCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eiterative cone-beam computed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFBP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efiltered back projection\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCCW\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecounterclockwise.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eAuthor Contributions Statement\u003c/h2\u003e \u003cp\u003eH. T. conceptualized the study, helped interpret the data, and provided expertise in manuscript preparation. Y. T, R. O., and H. T developed the study design and supervised the authors throughout the study. Y. T. analyzed data. R. T. provided study materials. H. A., M. M., T. S., S. T., T. K., H. K., S. N., H. N., Y. I., M. U., K. K., D. K., K. S., Y. N., K. H., T. K., H. E., Y. M., H. I., M. I., S. K., R. H., D. H., and Y. T. performed 3D star shot analyses at various institutions. H. T. and K. S. critically revised the manuscript.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e\u003ch2\u003eCompeting Interests\u003c/h2\u003e\u003cp\u003eY. T. received study materials from Triangle Products Co. Ltd. H. T. received a research grant from Triangle Products Co. Ltd. R. T. holds stock in Triangle Products Co. Ltd. There are no other commercial or financial relationships that might lead to a perceived conflict of interest. All the remaining authors declare no conflict of interest.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eH. T. conceptualized the study, helped interpret the data, and provided expertise in manuscript preparation. Y. T., R. O., and H. T. developed the study design and supervised the authors throughout the study. Y. T. analyzed data. R. T. provided study materials. H. A., M. M., T. S., S. T., T. K., H. K., S. N., H. N., Y. I., M. U., K. K., D. K., K. S., Y. N., K. H., T. K., H. E., Y. M., H. I., M. I., S. K., R. H., D. H., and Y. T. performed 3D star shot analyses at various institutions. H. T. and K. S. critically revised the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe thank Triangle Products Co. Ltd. (www.triangle-products.jp) for free provision of X-ray CT-based polymer gel dosimeters. We also thank Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eResearch data are stored in an institutional repository and will be shared upon request to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eYamamoto M, Serizawa T, Shuto T, et al. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): A multi-institutional prospective observational study. \u003cem\u003eLancet Oncol\u003c/em\u003e. 2014;15:387-395. doi:10.1016/S1470-2045(14)70061-0\u003c/li\u003e\n \u003cli\u003eGu Lei, Qing S, Zhu X, et al. Stereotactic radiation therapy (SRT) for brain metastases of multiple primary tumors: A single institution retrospective analysis. \u003cem\u003eFront Oncol\u003c/em\u003e. 2019;9:1352. doi:10.3389/fonc.2019.01352\u003c/li\u003e\n \u003cli\u003eVogelbaum MA, Brown PD, Messersmith H, et al. Treatment for brain metastases: ASCO-SNO-ASTRO guideline.\u003cem\u003e\u0026nbsp;J Clin Oncol\u003c/em\u003e. 2022;40:492-516. doi:10.1200/JCO.21.02314.\u003c/li\u003e\n \u003cli\u003eChen WC, Baal UH, Baal JD, et al. Efficacy and safety of stereotactic radiosurgery for brainstem metastases: A systematic review and meta-analysis. \u003cem\u003eJAMA Oncol\u003c/em\u003e. 2021;7:1033-1040. doi:10.1001/jamaoncol.2021.1262\u003c/li\u003e\n \u003cli\u003eSchiff D, Messersmith H, Brastianos PK, et al. Radiation Therapy for Brain Metastases: ASCO Guideline Endorsement of ASTRO Guideline. J Clin Oncol. 2022;40(20):2271-2276. doi:10.1200/JCO.22.00333\u003c/li\u003e\n \u003cli\u003eGondi V, Bauman G, Bradfield L, et al. Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline. Pract Radiat Oncol. 2022;12(4):265-282. doi:10.1016/j.prro.2022.02.003\u003c/li\u003e\n \u003cli\u003eHartgerink D, Swinnen A, Roberge D, et al. LINAC based stereotactic radiosurgery for multiple brain metastases: guidance for clinical implementation. \u003cem\u003eActa Oncol\u003c/em\u003e. 2019;58: 1275-1282. doi:10.1080/0284186X.2019.1633016\u003c/li\u003e\n \u003cli\u003eRaza GH, Capone L, Tini P, Giraffa M, Gentile P, Minniti G. Single-isocenter multiple-target stereotactic radiosurgery for multiple brain metastases: dosimetric evaluation of two automated treatment planning systems. \u003cem\u003eRadiat Oncol\u003c/em\u003e. 2022;17:116. doi:10.1186/s13014-022-02086-3\u003c/li\u003e\n \u003cli\u003eBadloe J, Mast M, Petoukhova A, et al. Impact of PTV margin reduction (2 mm to 0 mm) on pseudoprogression in stereotactic radiotherapy of solitary brain metastases. \u003cem\u003eTech Innov Patient Support Radiat Oncol\u003c/em\u003e. 2021;17:40-47. doi:10.1016/j.tipsro.2021.02.008\u003c/li\u003e\n \u003cli\u003eRedmond KJ, Gui C, Benedict S, et al. Tumor control probability of radiosurgery and fractionated stereotactic radiosurgery for brain metastases. \u003cem\u003eInt J Radiat Oncol Biol Phys\u003c/em\u003e. 2021;110:53-67. doi:10.1016/j.ijrobp.2020.10.034\u003c/li\u003e\n \u003cli\u003eKirkpatrick JP, Wang Z, Sampson JH, et al. Defining the optimal planning target volume in image-guided stereotactic radiosurgery of brain metastases: Results of a randomized trial. \u003cem\u003eInt J Radiat Oncol Biol Phys\u003c/em\u003e. 2015;91:100-108. doi:10.1016/j.ijrobp.2014.09.004\u003c/li\u003e\n \u003cli\u003eKocher M, Wittig A, Piroth MD, et al. Stereotactic radiosurgery for treatment of brain metastases. A report of the DEGRO Working Group on Stereotactic Radiotherapy. Strahlenther Onkol. 2014;190(6):521-532. doi:10.1007/s00066-014-0648-7\u003c/li\u003e\n \u003cli\u003eGuckenberger M, Baus WW, Blanck O, et al. Definition and quality requirements for stereotactic radiotherapy: consensus statement from the DEGRO/DGMP Working Group Stereotactic Radiotherapy and Radiosurgery. Strahlenther Onkol. 2020;196(5):417-420. doi:10.1007/s00066-020-01603-1\u003c/li\u003e\n \u003cli\u003eSchmitt D, Blanck O, Gauer T, et al. Technological quality requirements for stereotactic radiotherapy : Expert review group consensus from the DGMP Working Group for Physics and Technology in Stereotactic Radiotherapy. Strahlenther Onkol. 2020;196(5):421-443. doi:10.1007/s00066-020-01583-2\u003c/li\u003e\n \u003cli\u003eHalvorsen PH, Cirino E, Das IJ, et al. AAPM-RSS Medical Physics Practice Guideline 9.a. for SRS-SBRT. \u003cem\u003eJ Appl Clin Med Phys\u003c/em\u003e. 2017;18(5):10-21. doi:10.1002/acm2.12146\u003c/li\u003e\n \u003cli\u003eInternational Commission on Radiation Units and Measurements (ICRU) Report 62, Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50). Bethesda, USA: ICRU Publications; 1999.\u003c/li\u003e\n \u003cli\u003evan Herk M, Remeijer P, Rasch C, Lebesque JV. The probability of correct target dosage: dose-population histograms for deriving treatment margins in radiotherapy. \u003cem\u003eInt J Radiat Oncol Biol Phys\u003c/em\u003e. 2000;47:1121-1135. doi:10.1016/s0360-3016(00)00518-6\u003c/li\u003e\n \u003cli\u003eTakakura T, Mizowaki T, Nakata M, et al. The geometric accuracy of frameless stereotactic radiosurgery using a 6D robotic couch system. \u003cem\u003ePhys Med Biol\u003c/em\u003e.\u0026nbsp;2010;55:1-10. doi:10.1088/0031-9155/55/1/001\u003c/li\u003e\n \u003cli\u003eZhang Q, Chan, MF, Song, Y, Burman, C. Three dimensional expansion of margins for single fraction treatments: Stereotactic radiosurgery brain cases. \u003cem\u003eInt J Med Phys Clin Eng Radiat Oncol\u003c/em\u003e. 2012;1:15-22. doi: 10.4236/ijmpcero.2012.12003\u003c/li\u003e\n \u003cli\u003eZhang Q, Chan MF, Burman C, Song Y, Zhang M. Three independent one-dimensional margins for single-fraction frameless stereotactic radiosurgery brain cases using CBCT. \u003cem\u003eMed Phys\u003c/em\u003e. 2013;40:121715. doi:10.1118/1.4829517\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eKlein EE, Hanley J, Bayouth J, et al. Task group 142 report: Quality assurance of medical accelerators. \u003cem\u003eMed Phys\u003c/em\u003e. 2009;36:4197-4212. doi:10.1118/1.3190392\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eHanley J, Dresser S, Simon W, et al. AAPM Task Group 198 Report: An implementation guide for TG 142 quality assurance of medical accelerators. \u003cem\u003eMed Phys\u003c/em\u003e. 2021;48:e830-e885. doi:10.1002/mp.14992\u0026nbsp;\u003c/li\u003e\n \u003cli\u003ePant K, Umeh C, Oldham M, Floyd S, Giles W, Adamson J. Comprehensive radiation and imaging isocenter verification using NIPAM kV-CBCT dosimetry. \u003cem\u003eMed Phys\u003c/em\u003e.\u0026nbsp;2020;47:927-936. doi:10.1002/mp.14008\u003c/li\u003e\n \u003cli\u003eKim JH, Kim B, Shin WG, et al. 3D star shot analysis using MAGAT gel dosimeter for integrated imaging and radiation isocenter verification of MR-linac system. \u003cem\u003eJ Appl Clin Med Phys\u003c/em\u003e. 2022;23:e13615. doi:10.1002/acm2.13615\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eOshika R, Tachibana R, Seki K, et al. Technical Notes: Robustness of three-dimensional treatment and imaging isocenter testing using a new gel dosimeter and kilovoltage CBCT. J Appl Clin Med Phys. 2025;e14439. Doi:10.1002/acm2.14439\u003c/li\u003e\n \u003cli\u003eOng, C., Giaj-Levra, N., Nicosia, L. et al. Intra-fraction and inter-fraction analysis of a dedicated immobilization device for intracranial radiation treatment. \u003cem\u003eRadiat Oncol\u003c/em\u003e. 2020;15:200. doi:10.1186/s13014-020-01639-8\u003c/li\u003e\n \u003cli\u003eBabic S, Lee Y, Ruschin M, et al. To frame or not to frame? Cone-beam CT-based analysis of head immobilization devices specific to linac-based stereotactic radiosurgery and radiotherapy. \u003cem\u003eJournal of Applied Clinical Medical Physics\u003c/em\u003e. 2018;19(2). doi:10.1002/acm2.12251\u003c/li\u003e\n \u003cli\u003eSeravalli E, van Haaren PM, van Der Toorn PP, Hurkmans CW. A comprehensive evaluation of treatment accuracy, including end-to-end tests and clinical data, applied to intracranial stereotactic radiotherapy. \u003cem\u003eRadiother Oncol\u003c/em\u003e. 2015;116:131-138. doi: 10.1016/j.radonc.2015.06.004\u003c/li\u003e\n \u003cli\u003eSykes JR, Brettle DS, Magee DR, Thwaites DI. Investigation of uncertainties in image registration of cone beam CT to CT on an image-guided radiotherapy system. \u003cem\u003ePhysics in Medicine and Biology\u003c/em\u003e. 2009;54(24). doi:10.1088/0031-9155/54/24/002\u003c/li\u003e\n \u003cli\u003eTachibana H, Oshika R, Tachibana R, Seki K. Toward \u0026ldquo;on-line\u0026rdquo; X-ray computed tomography-based dosimetry using a new polymer gel with rapid response. \u003cem\u003eRadiat Phys and Chem\u003c/em\u003e. 2024;218:111570. doi:10.1016/j.radphyschem.2024.111570\u003c/li\u003e\n \u003cli\u003eAl-Hallaq HA, Cervi\u0026ntilde;o L, Gutierrez AN, et al. AAPM task group report 302: Surface-guided radiotherapy. Med Phys. 2022;49(4):e82-e112. doi:10.1002/mp.15532\u003cstrong\u003e\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"SRS, linac, three-dimensional dose delivery accuracy, margin size, gel dosimeter, multi-institution","lastPublishedDoi":"10.21203/rs.3.rs-5336613/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5336613/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe impact of three-dimensional (3D) dose delivery accuracy of C-arm linacs on the planning target volume (PTV) margin was evaluated for non-coplanar intracranial stereotactic radiosurgery (SRS). A multi-institutional 3D starshot test using beams from seven directions was conducted at 22 clinics using Varian and Elekta linacs with X-ray CT-based polymer gel dosimeters. Variability in dose delivery accuracy was observed, with the distance between the imaging isocenter and each beam exceeding 1 mm at one institution for Varian and nine institutions for Elekta. The calculated PTV margins for Varian and Elekta linacs that could cover the gross tumor volume with 95% probability at 95% of the institutions were 2.3 and 3.5 mm, respectively, in the superior\u0026ndash;inferior direction. However, with multifactorial system management (i.e., high-accuracy 3D dose delivery with rigorous linac quality assurance, strict patient immobilization, and high intra-fractional positioning accuracy), these margins could be reduced to 1.0 mm and 1.5 mm, respectively. The findings indicate significant millimeter-level variability in 3D dose delivery accuracy among linacs installed in clinical settings, but effective system management can achieve PTV margins below 2 mm, suitable for SRS applications.\u003c/p\u003e","manuscriptTitle":"Spatial accuracy of dose delivery significantly impacts the planning target volume margin in linear accelerator-based intracranial stereotactic radiosurgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-25 00:59:14","doi":"10.21203/rs.3.rs-5336613/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-12-27T19:27:05+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-26T20:39:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"6911959153541863226721635786376937200","date":"2024-12-26T15:43:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-12-05T07:34:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"167069109922128464380849326092506681079","date":"2024-11-30T03:23:02+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-28T18:45:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-11-28T18:42:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-11-18T11:54:40+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-11-16T06:24:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-10-26T09:01:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"53534bf5-2a05-404c-8961-8796a31b4d2c","owner":[],"postedDate":"December 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":41185792,"name":"Health sciences/Oncology/Cancer/Cancer therapy/Radiotherapy"},{"id":41185793,"name":"Health sciences/Oncology/Cancer/Cns cancer"}],"tags":[],"updatedAt":"2025-02-03T16:03:53+00:00","versionOfRecord":{"articleIdentity":"rs-5336613","link":"https://doi.org/10.1038/s41598-025-87769-z","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-01-29 15:58:05","publishedOnDateReadable":"January 29th, 2025"},"versionCreatedAt":"2024-12-25 00:59:14","video":"","vorDoi":"10.1038/s41598-025-87769-z","vorDoiUrl":"https://doi.org/10.1038/s41598-025-87769-z","workflowStages":[]},"version":"v1","identity":"rs-5336613","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5336613","identity":"rs-5336613","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}