Treatment Planning Dataset
An existing RT structure set from a previously-treated radiosurgery patient was chosen for the purpose of this study. The six metastatic lesions were modified in size in the CT data set (0.74 × 0.74 × 1.25 mm voxels) so that a range of targets with diameters from 6–25 mm could be treated. Target locations included lesions sufficiently far apart to measure up to 5.6 cm from isocenter to test the effects of rotational uncertainties on localization accuracy across the brain. The locations of the targets are shown in Fig. 1. In addition, a larger target was included for dose normalization purposes.
Phantom Design
The endpoint of this study was to assess accurate localization and dosimetry in an anatomically realistic measurement. Therefore, it was crucial to perform 3D dosimetry, which is possible with a gel dosimeter. The RTsafe PseudoPatient™ gel phantom produced by RTsafe P.C., (Athens, Greece) was used in this study as has been described in the literature9− 10. This dosimeter was chosen because it is a 3D dosimeter that can be cast in nearly any form, allowing for measurement in a patient-specific geometry. A modified composition of VIPAR polymer gels was used constituting of a mixture of the monomer N - vinylpyrrolidone in 6% weight fraction (wf), the cross-linker N, N' - methylene-bisacrylamide in 4% wf, gelatine of type A in 5% wf, deionized water in 85% wf, and 7 mM THPC6,11− 12. The primary advantage of gel dosimetry in an anthropomorphic phantom is that, unlike other patient-specific QA, it does not rely on a recalculation of the plan on a phantom nor on the process with which to reconstruct a 3D dose distribution. Rather, the measurement in this phantom can be directly compared with the patient’s calculated dose distribution as was demonstrated by Makris et al13. Finally, for the most realistic execution of an end-to-end test, an anthropomorphic phantom is the best substitute to approximate the entire process.
For the purposes of this study, three phantoms were produced by RTsafe based on the actual CT data set bony anatomy and external contour of our reference patient. The first was filled with the aforementioned dosimetric gel so that 3D dose measurements could be obtained. In addition, the other two phantoms were modified to accommodate placement of the other detectors. One had an insert for a one of two point dosimeters: Standard Imaging (Middleton, WI, USA) Exradin A16 or A26 ionization chamber (inside diameters of 2.4 and 3.3 mm respectively with collecting volumes of 0.007 and 0.015 cm3 respectively) or PTW (Freiburg, Germany) microdiamond detector (sensitive volume of 0.004 mm3). The other was designed with a holder for a Gafchromic film (Ashland, Bridgewater, NJ, USA). The point dosimeter and film cassette were situated to coincide with the center of the larger dose normalization target. By making point dosimeter measurements in a larger target less sensitive to small field dosimetry complications, the absolute dose accuracy can be shown with the point and film dosimetry and relative dose distribution characterized by gel dosimetry.
A planning template for HDRS delivery was devised in the Monaco version 5.11.02 treatment planning system (Elekta, Stockholm, Sweden) at UT Health San Antonio. This template consists of a set of beam geometries, prescription, and optimization objectives to be used across all institutions. The isocenter was set at the centroid of the targets. Five non-coplanar VMAT arcs were set up in the template (right and left lateral arcs with table at nominal 0°, right and left lateral oblique arcs with the table at 315° and 45°, and a vertex arc). As the dose linearity of the gel dosimeter breaks down above 12 Gy, the targets were assigned a prescription dose of 8 Gy with maximum doses remaining under 12 Gy. In all metastases, the dose was allowed to peak up to 12 Gy, while a homogeneous dose of 8 Gy was planned in the dose normalization target. No normal tissue objectives were defined and instead conformality at 8 Gy and 4 Gy was pursued. Target penalty, quadratic overdose and conformality objectives were used for optimization. A 1 mm dose calculation grid spacing was used with 1% statistical uncertainty per calculation of dose to medium. In the five single arcs, 180 control points were allowed with 0.5 cm minimum segment width. Medium fluence smoothing was used. For the multi-institutional study, the CT data set, RT structures and Monaco planning template, as well as the phantoms encompassing the point dosimeter and the Gafchromic cassette insert, were shared between all institutions in the study for the purposes of consistency of application. Upon receiving this data, institutions created their own treatment plans following the planning template.
Treatment Delivery
Patient data was sent to the Versa HD linear accelerator for delivery. The gel phantom was treated first and was localized with an XVI VolumeView™ cone-beam CT scan, which was fused with the reference CT data set. An example image of the phantom set up for plan delivery is shown in Fig. 2. The grey value (T + R) (translation and rotation) algorithm in XVI was used with a clipbox placed such that the entire brain was covered. The correction reference was placed at the isocenter. 6D corrections were applied using the HexaPOD tabletop prior to delivery. The process was repeated for the point dosimeter and film measurements.
Film dosimetry and uncertainty
Gafchromic EBT3 film was used for the film phantom measurement. The 14 × 8 cm2 Gafchromic EBT3 films were calibrated at the Secondary Standard Dosimetry Lab of the Greek Atomic Energy Commission and follows AAPM Task Group 55 in water equivalent material14. Film was shipped to each institution and evaluated upon return providing dose maps in absolute Gy values. Since it can take varying durations for an institution to perform the irradiations, the time-dependent calibration curve was built using films scanned at 24 and 72 hours, as well as 5 and 8 days after irradiation. An EPSON (Seiko Epson Corp., Japan) V850 PRO flatbed scanner was used with 150 dpi digitization and 48-bit depth. More details are presented in our previous work on end-to-end accuracy at a single institution6.
The main source of the uncertainties involved in EBT3 film measurements is the calibration procedure and specifically the calibration curve fitting process15. An estimation of the range of the combined 1σ dosimetric uncertainties was performed by following the methodology described in Pappas et al. (2017)16 for triple channel film dosimetry since the calibration component is dose dependent15. Optical density measurement reproducibility, optical scanner homogeneity and film calibration, statistical and systematic dose uncertainties were included in the final estimation. A combined 1σ dosimetric uncertainty of 2.3% was estimated for the dose level of 8 Gy which was the prescription dose. According to Pappas et al. (2017)16 study, a spatial 1σ uncertainty of 1.5 mm is resulting from the spatial registration procedure between scanned film images and the CT dataset of the film phantom following a registration technique described elsewhere13,16.
Dose extraction from Gel phantom
The gel phantoms were scanned on the MRI units of each institution one day after irradiation. Gel dose read-outs were performed using a variety of MRI units including, GE 1.5T Sigma HDX and 3T Optima 750 MW, Siemens 1.5T Espree and Sonata Vision and 3T Trio Tim, as well as Phillips 1.5T Ingenia. A 2D, multi-slice, multi-echo, Half Fourier Single Shot Turbo Spin Echo (HASTE) proton density to T2-weighted sequence was implemented sequentially using the head coil. Averaging was set to n = 14 to improve signal-to-noise ratio. MR-related geometric distortion was reduced with a bandwidth set to 1220 Hz/pixel. The MR protocol used is the one developed and recommended by the gel producer (RTsafe P.C.). Since the relaxation rate (R2 = 1/T2) of the polymer gel is directly proportional to absorbed dose, the MR scan was compared with the patient-derived planning CT data set for dose analysis. The acquired MR images were spatially co-registered with the corresponding CT datasets by performing bone-rigid registration using Monaco since the phantoms provide adequate bone and soft tissue signal in both CT and MR images. Doses were normalized at each site to an appropriate ROI in the larger dose normalization PTV. 3D gamma analysis and dose profile comparisons were performed for analysis.
The linear relationship between measured R2 relaxation rates and delivered dose up to 12 Gy has been verified in previous studies for the same gel formulation used in this work11,17 and for a time window from 24 hours up to 15 days between gel irradiation and MRI scanning11,18. The gel dose uncertainty component, regarding the duration between the gel fabrication and irradiation for a time interval of 6 days has been found less than 2%18. For the purposes of this study, only relative gel dose measurements were performed in order to avoid any potential sources of uncertainty that affect absolute gel dosimetry19. uncertainty level from the fitting procedure (linear fit) was calculated based on Papadakis et al (2007)12 methodology. An estimation of the main sources of uncertainties for relative dose measurements was performed, revealing a dosimetric 1σ uncertainty less than 3%. Moreover, taking into account the spatial resolution of the MR images and the registration technique between MR gel data and CT dataset of the gel-filled phantom, a spatial 1σ uncertainty less than 2 mm.
Data analysis (phantom evaluation)
Point dosimeter measurements were evaluated by comparing to the average dose in a region of interest (ROI) indicating the position of a point dosimeter’s sensitive volume in the plan calculation. Each institution followed standard dosimetry protocols in the conversion of measured charge to absorbed dose using kq and other correction factors from a previous machine calibration. The point dosimetry measurement established the absolute dose levels for the gel dosimetry. Measured 2D and 3D doses were compared to the planned dose distribution after following a rigid image registration procedure using the film fiducials for the film analysis and using the cranial anatomy for the MRI scan. From this point, direct dose profile comparisons can be made. 3D gamma analysis for both the film and gel dosimeter was conducted by utilizing global gamma analysis with various passing criteria. Gamma analysis was performed in the film plane ROI and in the region of individual targets for the 3D gel analysis using the DICOM RTStruct file. In both dosimetric systems, the measured dose distribution was set as the reference one and the TPS calculated as the evaluated during gamma calculations applying a dose threshold of 20%. Finally, consortium-wide plots of sample dose profiles were evaluated and consortium-wide dose volume histograms (DVHs) were assessed to demonstrate the relative difference between the shapes of planned and delivered DVH.