Simulation positioning equipment and Planning system
An integrated immobilization plate (Macromedics, Sweden) and thermoplastic mesh (Cleridian, Guangzhou, China) were used to immobilize the patient in the body position. The patients underwent scanning utilizing the Discovery large-aperture CT scanner (GE, USA), with the resulting images subsequently transferred to the uRT-TPOIS planning system (Shanghai United Imaging Healthcare , China) for the generation of radiotherapy and in vivo dose verification (hereafter referred to as In vivo) plans.
Linear Accelerator and Electronic Portal Imaging Device
The uRT-linac 506c linear accelerator (Shanghai United Imaging Healthcare , China) represents an innovative radiation therapy device that incorporates a 24-row diagnostic-grade fan-beam CT on the back of a 6 MV X-ray linear accelerator. The head of the accelerator is equipped with 60 pairs of multileaf collimators, including 40 pairs in the center with 0.5 cm leaf thickness and 20 pairs on both sides with 1 cm leaf thickness, with a maximum field of 40 cm × 40 cm. sIMRT (static IMRT), dIMRT (dynamic IMRT), and uARC (volume-rotation-intensity-modulated radiation therapy) are supported by the device. Moreover, the linear accelerator is equipped with an electron portal imaging device (EPID) composed of amorphous silicon. The EPID boasts an effective detection area of 40.96 cm × 40.96 cm, with a source image distance of 145 cm and a resolution of 1024 × 1024 pixels in 1 × 1 binning mode, featuring a pixel size of 0.4 mm and a spatial resolution of 0.27 mm at the isocenter plane, with a maximum frame rate of 15 frames per second (fps). In addition to image guidance, the EPID device is equipped with in vivo dose verification 2D evaluation (hereafter referred to as In vivo 2D) and 3D reconstruction dose (hereafter referred to as In vivo 3D) evaluation functions.
In Vivo Dose Verification Function
(1) In vivo 2D function: The process of calculating transit images involves utilizing a Monte Carlo algorithm combined with patient CT images. On the basis of accurate modeling of the accelerator, particle sampling is completed, and each particle is accurately tracked by combining patient CT information. The signal response of electrons and photons with different energies at different angles of incidence is obtained by accurate modeling of EPID[12-13], and the "pseudo-dose" image of particle deposition on a flat plate is calculated. Subsequently, particle scattering and energy deposition on the detector were modeled using the energy point spread function of the particles, resulting in the expected image for In vivo 2D. During actual treatment, treatment rays traverse the patient, depositing energy on the EPID and generating a measured image. This measured image then undergoes correction for flat gain, geometry, and any imperfections to produce a final grayscale image suitable for the clinical use. A threshold is established to compare the expected and measured images, with the degree of conformity assessed by the γ-passing rate.
(2) In vivo 3D function: During plan execution, details such as the positions of the multileaf collimator and collimator openings, as well as the actual beam intensity of the machine, are depicted in the In vivo 2D measurement images. The In vivo 3D reconstruction algorithm model relies on the In vivo 2D images acquired during treatment. Flux maps utilized in the reconstruction of dose calculations are integrated with patient CT data to derive the patient's reconstructed dose field. This process utilizes the fast Monte Carlo Dose Algorithm developed by United Imaging Healthcare, a Monte Carlo dosimetry algorithm[14] to calculate the patient's In vivo 3D reconstruction dose field.
Patient in vivo dose validation study workflow
Since May 2022, our unit has been officially implementing EPID in vivo dose validation for post-breast-conserving radiotherapy in early breast cancer patients using the uRT-linac 506c (Jinhua Hospital affiliated to Zhejiang University School of Medicine Ethical Approval No. 48, 2022). The patient in vivo dose validation process comprises three primary phases: treatment planning, patient treatment, and 3D dose reconstruction (Figure 1).
(1) Treatment Plan: Twenty-six patients diagnosed with early-stage breast cancer (with a mean age of 54 years and a median age: of 50 years) underwent postoperative radiotherapy at our institution from May 2022 to March 2023. These patients had a pathological stage of T1-2M0N0, with 16 cases involving left breast cancer and 10 cases involving right breast cancer. All patients were immobilized using a thermoplastic body mesh during treatment. Imaging was conducted using the GE Discovery RT localization CT scanner, and volumetric rotational intensity-modulated radiotherapy plans (referred to as CT plans) were generated using the Union Image uRT-TPOIS (R001) planning system from Shanghai United Imaging Healthcare, China. The prescribed dose was PGTV 6000 cGy/25f for the tumor bed area target and PTV 5000 cGy/25f for the breast target, with a dose calculation grid of 2.5 mm. Prior to treatment, the CT plans were validated through pre-treatment planning. In vivo 2D expected images were calculated based on the planned CT, also known as plan prediction images.
(2) Patient Treatment: The CT plan is sent to the linear accelerator system, where the patient is then positioned and treated according to the specifications of the CT plan. Prior to the first treatment and weekly thereafter, the patient was subjected to guidance using FBCT. EPID was utilized for real-time dose acquisition during each treatment session. The criteria for the 2Dγ-pass rate approach include a dose difference and distance to agreement (DTA) of 3% and 3 mm, respectively. The Gamma analysis threshold was set at 10%, with points below 10% of the maximum dose being excluded. Throughout the treatment process, calculated images from the planning system were compared with measured images captured by EPID. This comparison was performed using the In vivo 2D function, focusing on user-selected arcs, to determine the 2Dγ-pass rate results for the current arc.
(3) 3D Dose Reconstruction: In the retrospective analysis phase, 3D dose reconstruction is conducted. In our study, FBCT images used for IGRT were delineated by a senior radiotherapist for both the target area and organs at risk. Maintaining the parameters of the planned CT (such as shot field arc segment, monitor units, subfields, etc.), the planned CT data was transferred to the FBCT images to generate an FBCT image-based plan (referred to as FBCT plan). Subsequently, prediction images based on FBCT images were obtained using the In vivo 2D function and compared with the measured treatment images. Dosimetric differences were analyzed, and 3D γ-pass rates were compared by conducting 3D dose reconstruction on both the planned CT images and FBCT images using the In vivo 3D function.
Organs at Risk relative change and target area deformation analysis
Relative change in ROI (region of interest): We compared the ROIs delineated for critical organs, primarily the lungs and heart, on the FBCT images with those on the original CT planning images. Equation 1 was employed for the calculation, resulting in relative error values for the ROIs. A relative error value close to 0 indicates that affected side lung and heart ROIs on the FBCT image closely matches that of the original planned image.
where Vi refers to the ROI volume of the split FBCT images of the day; V0 refers to the ROI volume of the scheduled CT images
Target-area deformation: Drawing on the conformal index concept, we have proposed a deformation index for the Planning Target Volume (PTV) to characterize the disparity between the PTV of the FBCT image and that of the CT planning image. We have duplicated the PTV from the planned CT image onto the FBCT image and create their intersection using a functional function, as described in equation 2. The PTV deformation index is calculated. The closer the PTV deformation index of the target area is to 1, the closer the FBCT image is to the volume of the target area of the planned image.
where PTVCT refers to the PTV outlined on the program CT image; and PTVFBCT refers to the PTV copied to the FBCT image.
Comparison of in vivo dose validation pass rates
The 2D/3Dγ-pass rate results for all treatment fractions were grouped into the ALL category. The results from treatment fractions without IGRT were categorized into the N-IGRT group, while those with IGRT were placed in the IGRT group. The results calculated using FBCT images from the same day were designated as the FBCT group. The criteria for comparing the 2D/3Dγ-pass rates across these groups were set at 3 mm 3% and 3 mm 5%.
Comparison of dose distribution
To obtain the actual dose distribution received by the patient, the measured images obtained via EPID were utilized to reconstruct the three-dimensional dose on the FBCT images taken on the same day using the In vivo 3D function. This process yields the patient's dose distribution under the FBCT images of the day, referred to as FBCT in vivo. Subsequently, this distribution was compared with the patient's CT plan and the dose distribution of the FBCT plan, respectively. For target areas, we counted PGTV D95, PGTV D2, PTV D95, PTV D90; for critical organs, we counted Heart Dmean, V5, lung Dmean, V20, V5.
Statistical analysis
SPSS 19. 0 software was used to test all data for normality. In vivo dose validation 2D/3Dγpass rate data is represented as the median and quartile values, denoted by [M (P25, P75)]. For non-normally distributed data, the Wilcoxon rank sum test was employed. Paired-design signed rank sum test was conducted for data with the same sample size, while grouped-design two-sample rank sum test was utilized for data with different sample sizes. p < 0.05 was considered statistically significant.