This study selected patients who fulfilled the following inclusion criteria:
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Known primary extracranial malignancy displaying clinical and diagnostic imaging compatible with brain metastasis
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MRI of the brain showing a limited number of brain metastatic lesions (no more than four lesions)
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Each intracranial tumor size less than 3 cm and at least 5 mm from critical structures (brainstem and optic apparatus)
Patients who participated in this study were subjected to computed tomography simulation (CT SIM) by applying 1-mm slice thickness. SRS-system mask (R406-1 SRS mask, Klarity, China) was used for non-invasive immobilization (Figure 1). MRI was registered into the CT SIM dataset to define targets and for delineation of the organs at risk (OARs).
Target
Gross tumor volume (GTV) was delineated by contouring the contrast-enhancing lesions observed on T1 gadolinium-weighted MRI images. No margin was added to create the clinical target volume (CTV). The planning treatment volume (PTV) was defined by 2 mm isotropic expansion of the GTV.
Organs at risk (OARs)
The whole brain, hippocampi, optic nerves, optic chiasm, pituitary gland, brainstem, both cochlea, bilateral globes, and the lens were contoured.
Virtual structures and treatment evaluation
Virtual structures and help organs were created following the method of Soisson et al (8). Help structures were created for Tomotherapy and VMAT which were inverse planning, whereas the cylindrical collimator was not. The clinical sub-volume (CSV) was created at the centroid of the GTV with a diameter of 2 mm (Figure 2). To create a steep dose gradient, the dose constraint to at least 1% volume of CSV was prescribed at 120% of the prescription dose to target. The surrounding dose was then compressed by the ring. These structures (rings) expanded by 5 mm and 10 mm from the PTV. The 5% volume of these 5 mm and 10 mm rings structures were constrained at 80%-85% and at 50% of the prescription dose, respectively. For all of the plans, the dose coverage was accepted for at least 75% of the maximal dose for Tomotherapy and VMAT, whereas the cylindrical collimator was accepted at 50% of the maximal dose. The prescription dose had to cover at least 99% volume of the PTV, while the distance of the dose gradient from 50–100% of the prescription dose had to be within 10 mm for the single lesion.
Treatment Planning
Treatment planning systems were composed of HT, VMAT, and Cone-based SRS. In our institution, the commissioning in VMAT was performed and SRS was initiated to deliver radiation treatments on December, 2018. Therefore, all patients that had experienced limited-brain metastasis before 2019 were actually treated by HT. After that point, patients received treatment by VMAT. Every contouring dataset was re-planned in order to create each radiation dosimetry for all three treatment systems (HT, VMAT, and Cone-based).
Helical Tomotherapy (HT)
Tomotherapy (Hi-Art equipped dynamic jaws, Tomotherapy, USA) delivers radiation by way of a helical megavoltage fan beam. Accuray® Planning System (HiArt® version 5.1.4, Tomotherapy, Inc) administers treatment plans through employment of the helical treatment mode. The field width was set to ten millimeters in the fixed jaw mode. Modulation factor and pitch were set to 1.800-2.500 and 0.125, respectively. Based on the helical fan beam, a single coplanar was used in all treatment plans. The finest calculation grid was selected (1.95⋅1.95 mm2) for dose calculation.
Volumetric Modulated Arc Therapy (VMAT)
Treatment plans were performed with use of the Monaco® version 5.11.03 (Elekta, Inc) treatment planning system. Modulated broad beam in Linear accelerator (Synergy, Elekta, USA) was used with five millimeters of leaf width at the isocenter. All plans were created using the non-coplanar, single isocenter technique. Two full arcs (300 degrees) with a perpendicular collimator angle between each arc were used at zero degree of the couch angle. Specifically, 120 degrees of the treatment arc was used for three different couch angles (45°, 270°, 315°). The increment of the gantry angle was 10° for all arc beams. The dose optimization was calculated through the 2.00x2.00 mm2 grid size whereas the fineness calculation grid (1.00 x 1.00 mm2) was selected for the dose calculation.
Cone-based LINAC radiosurgery (Cone-based)
Treatment plans were carried out using the Monaco® version 5.11.03 (Elekta, Inc) treatment planning system. Different sizes (5-15 mm diameters) of the pencil beams in Linear accelerator (Synergy, Elekta, USA) were used in the non-coplanar technique. The directions of the arc beam were set in a half sphere and intersections between each beam were avoided through multiple isocenters in the targets. The weighting radiation dose of each isocenter was applied according to the experience of the planner. The finest calculation grid (1.00⋅1.00 mm2) was selected to establish the dose calculation.
Dosimetric Comparison
Conformity index (CI), homogeneity index (HI), and gradient index were analyzed to compare the three techniques (9, 10, 11). Relevant formulars were as follows:
CI (9) = Vpres/VPTV
Vpres: volume covered by prescribed dose
VPTV: PTV volume
HI (10) = Dmax/DRx
DMAX: maximum dose in the PTV
DRX: prescription dose
CI50 = V50%Rx/VPTV
V50%Rx: volume of 50% prescription isodose volume
VPTV: PTV volume
CGI (11) = 100-100x([Reff,50%Rx-Reff,Rx]-0.3 cm)
Reff,50%Rx: effective radius of 50% of prescription isodose enclosing PTV
Reff,Rx: the prescription isodose enclosing PTV
Beam On Time Calculation
HT represents the beam-on time (BoT) value of the unit of second, whereas the others were determined by the monitor unit (MU). The MU of the Cone-based SRS was converted to the unit of second by dividing the dose rate. The highest dose rate of our Cone-based approach provided 10 MU/sec. In the case of this approach, the dose rate could directly divide the total MU of each plan. In the VMAT technique, various dose rates were used in each plan. The treatment planning system (TPS) can be used to estimate BoT, but it is dependent upon the resolution of the calculation. A resolution of 2 mm was used in the optimization process to accelerate the optimization time, but a resolution of 1 mm was used to re-calculate the final absorbed dose. The result, then, was representative of the minimum BoT value, whereas various other dose rates were ignored in the VMAT technique.
Decision Score Analysis
The decision score was used to evaluate the performance among the different SRS techniques. The HT and VMAT approaches were benchmarked by applying the Cone-based technique. Significant differences of the plan quality indexes and dosimetric parameters were considered for the scoring procedure. Either plus one or minus one was granted to both the indexes and the parameters, which was indicative of either better or lesser performance than the Cone-based approach, respectively. The indexes and parameters received no score when no significant differences were observed.
Statistical Analysis
Descriptive analyses were summarized as medians with interquartile range (IQR) for continuous characteristics and as frequencies and proportions for categorical characteristics. The Friedman test was used to compare the dosimetric parameters and radiation painting to OARs, which were non-normally distributed between HT, VMAT, and the Cone-based planning techniques. A pairwise comparison was made and results were analyzed using Wilcoxon Signed Rank Test. The p value reports were two-tailed with an alpha level of 0.05 to establish statistical significance. All analyses were conducted using Stata version 16 (StataCorp LP, College Station, TX, USA).