Introduction
Even with improvements in external beam radiation therapy techniques like volumetric-modulated arc therapy, image-guided radiation therapy, and stereotactic body radiation therapy, brachytherapy continues to be a vital treatment choice for numerous cancer patients [1]. External radiotherapy and brachytherapy are the most effective primary treatment options for patients with invasive vaginal cancer. Brachytherapy, used in conjunction with external radiotherapy, plays a crucial role in ensuring the delivery of a therapeutic dose to the tumor [2,3]. Brachytherapy can be administered through various methods, such as intraluminal, intracavitary, multi-catheter interstitial techniques, and intensity-modulated brachytherapy (IMBT) [4]. While the interstitial approach offers improved precision in dose distribution, it is more invasive and subjective [5]. Dose modulation methods utilizing metal shields have been introduced to protect healthy tissues. Nonetheless, a standardized technique for achieving optimal outcomes remains elusive [6].
The practice of using high-Z materials as a protective barrier for a particular organ at risk (OAR) has been established for quite some time. In recent years, methods involving a shielded applicator or source have been explored to adjust the radiation dose intensity during brachytherapy administration, known as IMBT [7]. To perform IMBT effectively, it is crucial for the shield to be of sufficient thickness to successfully modify the intensity of the radiation source, especially when utilizing high-energy sources such as 60Co. The introduction of the 60Co high dose rate (HDR) after-loading system presents an attractive option. The 60Co HDR source's longer half-life of 5.3 years provides logistical and financial benefits compared to the 192Ir HDR source [8,9].
A notable focus is on creating shielding materials to substitute traditional lightweight and body-safe lead. Among these materials is tungsten-based material, which boasts a high atomic number and superior shielding capabilities compared to lead [10]. Tungsten, a material free of lead, is non-toxic and possesses a higher density and atomic number than lead. Consequently, tungsten offers superior shielding characteristics compared to lead [11]. However, other types of materials need to be taken into account. The properties of nanomaterials indicate that their high surface area to volume ratio enhances the ratio of photon absorption potential [12]. Nanoparticle composites possess the potential to meet the requirements for shielding against radiation in medical and industrial environments. Several research studies and theoretical assessments have delved into the effects of nano-WO3 composite materials on radiation protection [12,13]. However, there is a lack of literature on the application of these nanoparticles in the necessary protection in IMBT techniques. Considering their manufacturability and acceptable weight, the utilization of these nanoparticles can be a feasible option for the required protective materials inside the applicator.
This article introduces our innovative idea of using a cylinder applicator shielded with nano-WO3/epoxy composite to deliver patient-specific intensity-modulated HDR brachytherapy. This approach aims to enhance target coverage compared to current brachytherapy techniques while reducing radiation exposure to organs at risk. The applicator used in this study is based on the redesign of the IMBT commercial cylinder applicator by Elekta Company (Elekta, Stockholm, Sweden).
Materials and Methods
Fig. 1 categorizes the various stages of conducting this study.
1. Patient data selection
The current study included 18 cases of cervical cancer with stages ranging from IB to IVA. The high-risk clinical target volumes (HR-CTV) had volumes ranging from 5.2 to 95.3 cm3, with an average of 36.1 cm3 and a standard deviation of 16.3 cm3. Patients with a history of surgery in the vaginal and cervical region were excluded from the study. A skilled brachytherapy oncologist contoured OARs such as the bladder, sigmoid, rectum, and HR-CTV for all instances using high-resolution computed tomography (CT) scans with a 1 mm slice thickness.
2. IMBT applicator and source design
The vaginal cylinder applicator (Elekta Brachytherapy, Veenendaal, The Netherlands) was redesigned to maximize the IMBT ability in utilizing more amount of shielding in a cylinder tube. To maximize the shield's capacity within the applicator, the internal structure has been redesigned to accommodate a shielding rod with a diameter of 22.1 mm inside a 24.5 mm internal diameter. The overall internal structure consists of a shielding rod and a source channel (with an internal diameter of 1.0 mm and outer diameter 1.3 mm) connected to a rotational system enabling the rotation of structures relative to each other When the outer shell is fixed. The reconstruction of the internal structure of the applicator, such as the repositioning of the source channel and the placement of the shielding cylinder on a rotatable structure, can enable the implementation of dynamic techniques. In the redesigned applicator, some structural features, such as the outer diameter of 25.0 mm and a length of 6.3 cm, have not been modified to maintain consistent clinical usability.
This research employed a simulated form of the 60Co encapsulated source made by Elekta Company. The source was modeled to mimic the Flexisource utilized in the Elekta Flexitron afterloader, a brachytherapy device manufactured by Elekta Brachytherapy [14]. This study used Monte Carlo calculations following the American Association of Physicists in Medicine Task Group No. 229 (TG-229) guidelines to establish the TG-43 parameters of the 192Ir source from Nucletron, Elekta, for high-energy brachytherapy sources. The source's properties, including its geometry, material composition, and densities, were sourced from published materials. Notably, the source is 0.9 mm in diameter and 4.5 mm in length (Fig. 2) [15]. The calculation of total treatment durations utilized a standard activity of 10 Ci for 192Ir and 2 Ci for 60Co.
3. Shielding material simulation
A simulation code based on Geant4 application to tomographic emission (GATE) was employed to model a nano-WO3/epoxy composite. An epoxy resin with a chemical formula of C21H25ClO5 and a density of 1.18 g/cm3 was employed as the matrix. The simulation involved tungsten trioxide, which has a density of 7.16 g/cm3, as the polymer filler in 30 nm dimensions and at a weight percentage of 80 weight%. Previous research indicated that using WO3 filler of this size and weight percentage exhibited promising results in attenuating/absorbing high-energy gamma photons [13,16]. The simulation code was utilized to evenly distribute WO3 particles within the resin polymer matrix as spherical particles measuring 30 nm in diameter. To provide clearer visualization, screenshots of the simulated composite with both micro and nanofiller sizes are presented in Fig. 2.
4. Patient modeling
The anonymized patient data, comprising magnetic resonance images in Digital Imaging and Communications in Medicine (DICOM) format, contours from DICOM radiotherapy structure set files, and dwell positions extracted from DICOM radiotherapy plan files, were imported into the three-dimensional (3D) Slicer software [17]. The CT image had a slice thickness of 1 mm. Each case involved converting the images into voxelized phantoms with a voxel size of 1 × 1 × 1 mm3. Each organ was individually modeled, maintaining its spatial relationships with other organs, and then exported in Stereolithography format. This format facilitated importing the models into the simulation code. Subsequently, each structure was associated with the appropriate material model from the code library within the simulation code. A female pelvic phantom with properties equivalent to water, sized 30 × 30 × 30 cm3, was simulated within a larger air box world measuring 80 × 80 × 80 cm3 using the GATE simulation code based on Geant4. The OARs and HR-CTV models were positioned at the center of the phantom. To evaluate the conventional brachytherapy (CBT) and IMBT treatment planning methods for 18 patients with identical source path geometry, simulations were conducted using the GATE simulation code. The simulations aimed to ensure that the prescribed dose to the HR-CTV met acceptable standards and complied with Groupe Europeen de Curietherapiee-European Society for Radiotherapy and Oncology (GEC-ESTRO) constraints [18]. This approach enabled a comparison of the administered dose to the organs at risk.
5. IMBT plan simulation
The GATE, Geant4-based simulation code was utilized to optimize and streamline the plans. To minimize any potential bias from the planner, all plans were optimized using the same parameters without any manual adjustments thereafter. The optimized dose distributions were fine-tuned to ensure the minimum dose received by 90% of target volume (D90) value for the HR-CTV aligned with the prescribed dose of 5.5 Gy per fraction. This normalization was performed to facilitate a fair comparison across various combinations of modality and radionuclide. Key dosimetric comparisons metrics, such as minimum dose received by the highest 2 cc of organ (D2cc) for organs at risk and D90 for HR-CTV, were derived from the results following the guidelines outlined by the GEC-ESTRO. The statistical significance of dose-volume histogram metrics variations was evaluated using a paired sample t-test, with a significance level set at p < 0.05. In planning conventional and IMBT high-dose-rate plans, the active core materials chosen were 192Ir and 60Co. In the CBT method, the entire procedure was repeated by replacing the nanoparticle shielding material with a water-equivalent Plexiglas applicator, which is a conventional acting applicator. A standard activity level of 10 Ci for 192Ir and 2 Ci for 60Co was considered when calculating the total treatment durations. To ensure uncertainties remained within the range of 1% to 2%, a total of 108 decay events were simulated for each radionuclide at every dwell position, with a voxel resolution of 2 mm3 employed in the GATE simulation. Actors are tools that allow to interact with the simulation. They can collect information during the simulation, such as energy deposit, number of particles created in a given volume, etc. They can also modify the behavior of the simulation. In the GATE simulation code, DoseActors for scoring were defined and linked to all specified organs. The output data format was set as .mhd and .hdr, which were then processed using 3D Slicer and Amide software. In a Monte Carlo simulation, a physics list library refers to a collection of predefined physics processes and models that can be used to simulate the interactions of particles in a simulation. These processes can include electromagnetic interactions, particle decay, hadronic interactions, and more. By choosing and configuring a physics list from the library, users can customize the behavior of particles in the simulation to accurately model the physical processes they are interested in studying. The emstandard_opt3-physics list, recognized for its high precision in electromagnetic interactions, was utilized throughout the research. This physics library encompasses critical radiation-matter interactions essential in dosimetry and radiotherapy applications [19]. The algorithms were run on a high-performance computing system featuring the following configuration: 16 gigabytes of RAM, an Intel CoreTM i7-6700 processor clocked at 3.4 GHz with 8 cores, Mesa Intel HD Graphics, and a GTX 1080 Ti graphics card equipped with 11 gigabytes of GDDR5X memory. This supercomputer operates on a Linux operating system and is situated at the imaging center of Mashhad University of Medical Sciences in Iran.
6. Monte Carlo simulation validation
A quantitative measure called the transmission factor (TF) is defined to assess the alignment of simulated data with measured data. Following the principles of TG-43 [20], we use the polar angle (or zenith angle), denoted as β, which is measured from the z-axis. The azimuthal angle in the x-y plane, denoted as α, is defined as the axis shielding for dose modulation. The distance from the origin is defined as the radius, denoted as r. Fig. 3 provides a visual representation of the coordinate system. TF is calculated as the ratio of the dose at a distance of 2 cm from the center of the tandem on the x-y plane of the shielded side to that of the unshielded side. This parameter has been simulated and measured to determine its value. A 0.6 cm3 Farmer-type ionization chamber manufactured by PTW (Freiburg GmbH, Freiburg, Germany) was inserted into the corresponding point at the water phantom. Due to the offsetting of the central source channel through different applicators, the effect of distance squared has been considered and adjusted to compare the applicators.
Results
The findings from utilizing dynamic IMBT techniques and traditional approaches with cobalt and iridium HDR sources were acquired and assessed, and the essential parameters were extracted and detailed in Table 1. Furthermore, their visual representation can be seen in Fig. 4. There is a slight relative variation of less than 1.0% in the absorbed dose parameter D90 for the target in both techniques using 60Co and 192Ir sources. The plan comparison indices of D2cc (which represents the maximum dose for OARs) decreased by 2.3%–18.7% for dynamic IMBT, as shown in Table 1. Overall, IMBT with 192Ir and 60Co exhibited significant enhancements in sparing organs at risk compared to conventional methods. IMBT also showcased a notable decrease in rectal D2cc compared to CBT while maintaining the same level of HR-CTV D90 coverage. The rectum and bladder D2cc parameter obtained from vaginal IMBT and CBT techniques showed that the dynamic IMBT technique offered greater protection to the rectum and bladder compared to conventional techniques (Fig. 4). Additionally, the level of protection for OARs was slightly higher for the iridium source than for the cobalt source.
The Monte Carlo statistical uncertainties were calculated for the target, rectum, and bladder in the brachytherapy methods. The average statistical uncertainties were obtained by averaging the uncertainties of all voxels in both the IMBT and conventional techniques. All uncertainties were below two percent, with a slightly higher value for the target (1.72%) compared to the organs at risk (0.62%). The TF was used to evaluate the alignment of simulated and measured data for both sources with IMBT applicator. Simulated values were 5.1% and 12.5%, and the measured values were 5.0% and 12.5% for the 192Ir and 60Co sources, respectively, which reports a difference of less than one percent in both sources.
Discussion and Conclusion
This research was carried out to evaluate the effectiveness of a newly designed nanoparticle tungsten-shielded dynamic cylinder applicator in comparison to a traditional applicator for brachytherapy treatment of vaginal cancer, utilizing the GATE Monte Carlo code. In order to conduct IMBT, a shielded applicator with off-center channels is required to offer effective shielding to OARs and administer a precise dose to the target area. The protective capability of OARs was enhanced by utilizing a WO3 nanoparticle material for the main body of the applicator.
Choosing an appropriate and effective shielding material against gamma rays requires great precision in the type and thickness of materials. Factors such as weight, volume, and cost considerations play a significant role in the interconnected analysis for choosing the right material for the protective shield. The primary characteristic of a material’s protective ability lies in its capacity to attenuate gamma radiation, with heavier materials generally exhibiting greater attenuation abilities. The design of a radiation protective shield is influenced by factors such as the radiation source's type and characteristics, the installation type, and the shield material's properties [21].
Numerous factors advocate for the utilization of nanoparticles in the design of radiation shielding. Conventional materials like lead may not always be able to be manufactured in the specific shapes and geometries needed for diverse applications. The drawbacks of traditional metallic lead shields, including toxicity and weight, have prompted researchers to explore alternative radiation shielding materials that are lighter, flexible, moldable, and non-toxic. Nanoparticle-based composites, for instance, have the capability to fulfill the criteria for radiation protection in both medical and industrial settings.
Although the protective properties of various compounds, including bismuth trioxide (Bi2O3), copper (II) oxide, gadolinium oxide, and lead monoxide in powder form, and zirconium ZrO2, against different spectra of radiation, have been investigated, none of these compounds have been specifically applied for the required protection in IMBT technique [22]. Numerous experimental investigations and modeling analyses have explored the impact of nano-WO3 composite materials in radiation shielding, yielding promising findings [16,23-26]. Therefore, in this research, we harnessed this capability in a new application within the field of brachytherapy.
The present research validated that IMBT methods with a redesigned commercial applicator using nano-WO3/epoxy composite surpassed traditional brachytherapy in the treatment of vaginal cancer. Including a shielded segment within the applicator partially blocked the radiation directed toward healthy tissues surrounding the applicator, allowing the targeted area to receive radiation without a significant decrease in its original intensity. Consequently, the IMBT technique could precisely adjust the radiation dose distribution to effectively cover the tumor while also providing adequate protection to OARs. IMBT utilizing 192Ir sources, known for their lower average photon energy, demonstrated superior modulation potential by effectively reducing the radiation dose to OARs, with a more pronounced reduction observed compared to 60Co sources. Dynamic IMBT with 60Co HDR sources led to an 11.1% decrease in the relative D2cc of the bladder and a 12.8% decrease in the rectum compared to conventional applicators. The use of 192Ir HDR sources in IMBT resulted in a 16.6% reduction in the relative D2cc for the bladder and an 18.7% reduction in the rectum. The D2cc of the sigmoid dose exhibited a non-significant decrease with both cobalt and iridium sources, indicating that the lack of significance in dose reduction may be attributed to the organ's location. The ability to modulate doses in IMBT techniques is influenced by various factors, including tumor size, location, and shape; shielding characteristics such as diameter, material, density, availability, and cost; and source energies. Therefore, in order to design and create an efficient IMBT system, it is essential to take into account, examine, validate, and optimize the impact of all these contributing factors.
In the present study, for the first time, the direct incorporation of nano-WO3/epoxy composite in the design of brachytherapy applicators has been utilized. While complete organ protection has not been achieved, a significant reduction in organs at risk doses has occurred. This study marks a promising start in the use of nanoparticle compounds in IMBT that can be further enhanced through more extensive research in this area.
The performance of a newly designed dynamic cylinder applicator shielded with nano-WO3/epoxy composite was simulated and contrasted with a standard applicator using the GATE Monte Carlo code for treating vaginal cancer. This study represents the initial utilization of nano-WO3/epoxy composite directly integrated into the design of brachytherapy applicators. Although full organ protection was not attained, a notable decrease in doses to organs at risk was observed. This research signifies a hopeful beginning in incorporating nanoparticle compounds in IMBT, with the potential for further advancements through additional research in this field.
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