Dosimetric effect of rotational setup errors in stereotactic radiosurgery with HyperArc for single and multiple brain metastases

Abstract Purpose In stereotactic radiosurgery (SRS) with single‐isocentric treatments for brain metastases, rotational setup errors may cause considerable dosimetric effects. We assessed the dosimetric effects on HyperArc plans for single and multiple metastases. Methods For 29 patients (1–8 brain metastases), HyperArc plans with a prescription dose of 20–24 Gy for a dose that covers 95% (D95%) of the planning target volume (PTV) were retrospectively generated (Ref‐plan). Subsequently, the computed tomography (CT) used for the Ref‐plan and cone‐beam CT acquired during treatments (Rot‐CT) were registered. The HyperArc plans involving rotational setup errors (Rot‐plan) were generated by re‐calculating doses based on the Rot‐CT. The dosimetric parameters between the two plans were compared. Results The dosimetric parameters [D99%, D95%, D1%, homogeneity index, and conformity index (CI)] for the single‐metastasis cases were comparable (P > 0.05), whereas the D95% for each PTV of the Rot‐plan decreased 10.8% on average, and the CI of the Rot‐plan was also significantly lower than that of the Ref‐plan (Ref‐plan vs Rot‐plan, 0.93 ± 0.02 vs 0.75 ± 0.14, P < 0.01) for the multiple‐metastases cases. In addition, for the multiple‐metastases cases, the Rot‐plan resulted in significantly higher V10Gy (P = 0.01), V12Gy (P = 0.02), V14Gy (P = 0.02), and V16Gy (P < 0.01) than those in the Ref‐plan. Conclusion The rotational setup errors for multiple brain metastases cases caused non‐negligible underdosage for PTV and significant increases of V10Gy to V16Gy in SRS with HyperArc.


| INTRODUCTION
Brain metastases are one of the most frequent neurological complications of systemic cancer. 1 It has been estimated that 20%-40% of cancer patients will develop brain metastases during their disease. 2 For brain metastasis, various treatment options are available, such as surgical resection, whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and dexamethasone supportive therapy. 3 The optimal option should be chosen after considering patient factors (such as age and performance status), tumor factors (such as extracranial cancer activity, number, size, and location), and outcomes (such as survival, tumor control, and quality of life). 3 Regarding radiotherapy, WBRT has been the mainstay for brain metastases treatment, but WBRT causes local damage or necrosis of normal tissue within 1 yr with 100% probability and deterioration of cognitive function resulting in poor quality of life. 4 In contrast, SRS can expose normal tissues to less radiation, preserve neurocognitive function, and minimize radiation-associated hair loss. [3][4][5][6][7][8][9] Therefore, SRS has received increased attention as a treatment option for brain metastases.
Lately, advances in technology permit linear accelerator (LINAC)based SRS. Especially volumetric-modulated arc therapy (VMAT) technique provides faster, safer, and more accurate treatment than conventional treatment. 10 Liu et al. demonstrated that modern LINACs could simultaneously deliver shaped doses to multiple targets and achieve accuracy and precision as high as those of the Gamma Knife ® because of the availability of image-guided radiation therapy, advances in computers, and improvement in tools, such as high-definition multileaf collimators (MLC). 11 A new commercially available SRS treatment approach, named HyperArc™, was recently released. This approach is based on the seminal work of a group from the University of Alabama 12,13 and automatically sets the location of the single-isocenter, noncoplanar beam arrangement and collimator angle. The HyperArc can provide a steeper dose gradient for targets while minimizing doses to surrounding normal tissues as much as possible with a lesser workload than that of the conventional SRS technique of VMAT. 12 In addition, single-isocentric irradiation for multiple metastases can reduce treatment time compared with conventional multi-isocentric irradiation treatment devices, such as the Gamma Knife and CyberKnife ® . [12][13][14][15][16][17][18][19][20] In SRS, setup errors are important considerations. 18,21 Especially, single-isocentric SRS for multiple targets is not robust regarding rotational setup errors. 18 According to a report by Guckenberger et al., the rotational setup error around the three axes in each of 98 patients who had undergone LINAC-based SRS was ≤1.7°± 0.8°on average, with a 4.0°maximum. 21 Roper et al. simulated the effect of rotational setup errors for single-isocentric VMAT-based SRS for multitargets and showed that the errors could compromise target coverage, especially for small targets far from the isocenter. 18 The single-isocentric irradiation using HyperArc plans with a steep dose gradient may be considerably affected by rotational setup errors, and the dose coverage of targets far from the isocenter can be worse.
The aim of this study was to determine the dosimetric effects of rotational setup errors in stereotactic radiosurgery with HyperArc for brain metastases in a clinical setting. A retrospective analysis of 29 patients was performed by comparing two plans: one without rotational setup errors and one with rotational setup errors.

2.A | Patients and clinical treatment
This study included 29 patients with 1-8 brain metastases who had Hounsfield unit values equivalent to those of a conventional CT scan (120 kVp), 22 was reconstructed and used for treatment plans.
The gross tumor volume (GTV) was delineated on the CT image by referring to gadolinium-enhanced T1-weighted magnetic resonance imaging sets and using a treatment planning system (TPS) Eclipse (version 13.7; Varian Medical Systems, Palo Alto, CA). A clinical target volume (CTV) with a 2-mm margin was generated from the GTV, and a planning target volume (PTV) was generated by adding an isotropic margin of 1 mm to the CTV. For multiple-metastases cases, a structure, named PTV all , was defined as the union of each PTV in a patient.
The prescription dose was 20-24 Gy for a 95% volume of the PTV for the single-metastasis cases or PTV all for multiple-metastases cases in a single fraction. Before each treatment, a kilo-voltage cone-beam CT (CBCT) scan was acquired, and bone-matching corrections were performed between the pCT and the CBCT.

2.B | HyperArc plans
The pCT sets and structure sets used for original treatment were retrospectively imported to the prototype TPS Eclipse (version 15.5) with beam data from the TrueBeam STx (Varian Medical Systems), which equips a 2.5-mm leaf-width MLC. HyperArc plans based on these sets were generated for each patient. The isocenter position is automatically set based on the selected target structures. These structures were used for collimator angle optimization. Arc geometry (four arc fields; one full coplanar arc with a 0°couch and three half noncoplanar arc fields a 315°, 45°, and 90°or 270°couch) arranged with a single isocenter automatically located on the basis of the distance between each lesion. 20,23 The prescription dose was the same SAGAWA ET AL.
| 85 as that of the clinical treatment plan for 95% volume of the PTV all , and 6-MV flattening filter-free photon beams were used. In the optimization process, the minimum dose in the target structures was set at the prescription dose. An analytical anisotropic algorithm was used in dose calculations of all plans with a 1.25-mm grid size. The HyperArc plan generated by this process was designated as the ref-

2.C | HyperArc with rotational setup errors
As done against the Ref-plan, we generated the HyperArc plan with rotational setup errors (Rot-plan) for each patient (Fig. 1) The distance between the position of the isocenter (x i , y i , z i ) and that of each target (x t , y t , z t ) (ITD) was calculated according to the following formula.
Further, a 3-dimensional rotation setup error (RSE 3D ) was defined by [Eq. (2)], where RSE p , RSE y , and RSE r were the rotational setup errors for pitch, yaw, and roll axis, respectively.

2.D | Data analysis
In this study, we compared the dosimetric parameters between the in the same way. The HI was defined according to Eq. (3): where D max and D prescribed were the maximum and prescribed doses, respectively. 24 The CI was defined by Paddick as follows, where PTV PD was the volume of PTV covered by the prescription dose, and V PD was the prescription isodose volume. 25 The relative dose error (RDE) between the Ref-plan and Rot-plan was calculated as follows: where     fractions. 27 In this study, the mean rotational setup errors were  cally. 26 If the 6DOF was not in use, an additional margin, which compensates for rotational setup error, may be needed for targets located far from the isocenter to avoid underdosage for the target.
Related to the OAR, the Rot-plan for multiple-metastases cases caused a significant increase in normal brain tissues in the range of V 10Gy to V 16Gy . Blonigen et al. reported that the V values in the range of V 8Gy to V 16Gy were the best predictors for the incidence of brain radionecrosis in LINAC-based SRS. 32

| CONCLUSION
Although the HyperArc plans for the single-metastasis cases were robust with respect to rotational setup errors, the errors for the multiple brain metastases cases caused statistically significant underdosage for PTV in SRS using the HyperArc. Furthermore, for normal brain tissues, significant increases in the V 10Gy to V 16Gy values were induced, which are predictors of brain radionecrosis. Consequently, we think that the correction of rotational setup errors is imperative to deliver an adequate dose for multiple-metastases cases.

This study was supported by a JSPS KAKENHI Grant (Grant-in-Aid
for Young Scientists (B) 17K15816).

CONFLI CT OF INTEREST
The authors are involved in an ongoing collaboration with Varian Medical Systems and financial support was provided.