Efficacy of various nanoparticle types in dose enhancement during low energy X-ray IORT: A Monte Carlo simulation study
Introduction
Up to now, different modalities have been developed for cancer treatment. Radiotherapy is one of the most important treatment methods which can be employed either as a sole or adjuvant approach in conjunction with other treatment types such as surgery, chemotherapy, immunotherapy, etc. (Baskar et al., 2012; Wang et al., 2018; Chen et al., 2017; Hennequin et al., 2019). Radiotherapy can be mainly divided into two major types of external beam radiotherapy (EBRT) and brachytherapy (Skowronek, 2017; Shirato et al., 2018). The selection of each type of radiotherapy depends on its dedicated features as well as the considered indications for patient treatment. Besides the above-mentioned radiotherapy techniques, intraoperative radiotherapy (IORT) using dedicated facilities has been also introduced in recent years (Shamsabadi et al., 2020a; Thomas and Small, 2018; Pilar et al., 2017).
Generally, IORT means delivering a high single fraction of radiation dose to the anesthetized patient immediately after the surgery inside the operating theatre (Baghani et al., 2019a; Williams et al., 2014). The most widely utilized methods for IORT implementation are intraoperative electron radiotherapy (IOERT) and low energy X-ray IORT (low-kV IORT). Efficacy of these IORT methods, especially in breast cancer irradiation after the breast-conserving surgery, has been confirmed by some popular clinical trials such as TARGIT-A and ELIOT (Vaidya et al., 2010; Veronesi et al., 2013). The last method (low-kV IORT) has gained great attention in breast cancer treatment and is widely employed for intraoperative breast irradiation, as a complementary treatment, after breast-conserving surgery (Harris and Small, 2017; Kraus-Tiefenbacher et al., 2006; Tuschy et al., 2013).
At the moment, two dedicated machines known as INTRABEAM (Carl Zeiss, Inc.) and Xsoft/Axxent (iCAD, Inc.) have been provided for low-kV IORT of breast cancer which can produce low energy X-rays (up to 50 kV nominal energy) for intraoperative radiotherapy (Valente et al., 2017; White et al., 2016).
INTRABEAM machine is equipped with a bare probe that acts as a small tube for X-ray production. In addition to the bare probe, some dedicated spherical applicators with various diameters (ranging from 1.5 cm to 5 cm) have been also provided for this machine during the breast intraoperative irradiation. The breast treatment procedure with this machine can be briefly described as follows. After the tumor resection, an appropriate spherical applicator diameter is selected to fill the created lumpectomy cavity during breast surgery. Then, the bare probe is inserted into the applicator utilizing a shank, so that its tip is exactly located at the center of the spherical applicator. Finally, the remaining tumor bed (including residual microscopic tumor cells) after the surgery is irradiated by emitted low energy X-rays from the probe tip (Baghani et al., 2019b). The presence of each spherical applicator diameter can provide a conformal radiotherapy situation through adopting the geometry of the tumor bed with isotropically emitted X-rays from the bare probe (Eaton, 2012; Nairz et al., 2006; Bouzid et al., 2015).
One of the main limitations of the low kV-IORT with the INTRABEAM machine is the long treatment time. In general, the treatment time depends on the size of the employed spherical applicator and increments with an increase in applicator diameter (Kraus-Tiefenbacher et al., 2011). For example, with increasing the applicator diameter from 1.5 cm to 5 cm, the treatment time for delivering the 20 Gy dose at the surface of spherical applicator increments from 7 min to about 50 min (Kraus-Tiefenbacher et al., 2011). Such long irradiation times may be of concern from both clinical and technical aspects. Firstly, increasing the treatment time can increase the risk of infection in anesthetized patient with an open wound. Secondly, this increased treatment time can reduce the lifetime of the brae probe and finally limit the active time of machine availability at the treatment center. To overcome these unprofitable issues and reduce the treatment time, one should improve the machine dose rate inside the treatment volume. One solution in this regard is employing the nanoparticles (NPs) to enhance the absorbed dose by the irradiated volume.
Gold (Au) nanoparticles are the most widely proposed ones for dose enhancement purposes during radiotherapy. The physical dose enhancement and energy transfer to the irradiated medium by the X-rays, in presence of Gold NPs, have been extensively evaluated through conducted experiments by Guo and his colleagues (Carter et al., 2007; Lee et al., 2012; Davidson and Guo, 2014; Sharmah et al., 2016). Nevertheless, other NP types such as Silver (Ag), Bismuth (Bi), Iron (Fe), Gadolinium (Gd), Hafnium (Hf), Platinum (Pt), and Titanium (Ti) have been also introduced for dose enhancement purpose during the photon radiotherapy (Su et al., 2014; Babaei and Ganjalikhani, 2014; Shiryaeva et al., 2019). Apart from Au, Ag, Bi, and Fe which have been recently evaluated by Moradi et al. (2020) and Omyan et al. (2020) studies, the clinical efficacy of other mentioned NP types in dose enhancement during low-kV IORT technique has not been still evaluated. Therefore, the current study aims to evaluate and compare the efficiency of all the above-mentioned NP types in dose enhancement during the intraoperative radiotherapy by low energy X-rays through the Monte Carlo simulation and introduce the most efficient NP type in this regard.
Section snippets
INTRABEAM machine
As mentioned previously, INTRABEAM is a dedicated facility for implementing the low kV-IORT. The core section of this machine is a bare probe which includes a 10 cm length evacuated hollow tube with 3.2 mm diameter. The primary electrons will be accelerated across 30, 40, or 50 kV accelerating potential and then impinge on a very thin layer of Gold target (0.5 μm thickness) which is coated on the inner surface of the probe tip. During this process X-rays with corresponding nominal energies of
Results and discussion
The comparison between the simulated and measured PDD curves related to the 2 cm and 4 cm diameter spherical applicators has been shown in Fig. 3.
As declared by Fig. 3, reasonable accordance would be observed between the obtained results, such that the gamma index values are less than unity at all of the studied depths for both considered spherical applicator diameters. Nevertheless, a more favorable agreement is seen in the case of 4 cm applicator diameter because the gamma index values are
Conclusion
The clinical efficacy of various nanoparticle types in dose enhancement during intraoperative radiotherapy was evaluated through a Monte Carlo simulation approach at the current study. To doing so, at first, the bare probe of the INTRABEAM machine, a dedicated facility for low-kV IORT implementation, along with 2 cm and 4 cm diameter spherical applicators were simulated by MCNPX Monte Carlo code. Then, the dose enhancement factor (DEF) in the presence of each considered NP type was evaluated
CRediT authorship contribution statement
Hamid Reza Baghani: Conceptualization, Methodology, Formal analysis, Investigation, Writing – original draft, Writing – review & editing, Project administration, Supervision. Shiva Nasrollahi: Software, Validation, Formal analysis, Resources, Investigation, Formal analysis, Resources, Visualization.
Declaration of competing interest
We wish to confirm that there are no known conflicts of interest associated with this publication between the contributing authors and also there has been no significant financial support for this work that could have influenced its outcome. The manuscript has been read and approved by all named authors.
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