Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs). Using Monte Carlo–generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5–14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected. The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to IV administration during external beam radiotherapy. For FDA approved concentrations of CNPs or CBNPs considered, this could allow for additional dose enhancement to tumors via photoelectric mechanism during concomitant chemoradiotherapy.
We predict, for the first time, that by using United States Food and Drug Administration approved concentrations of cisplatin, major radiosensitization may be achieved via photoelectric mechanism during concomitant chemoradiotherapy (CCRT). Our analytical calculations estimate that radiotherapy (RT) dose to cancer cells may be enhanced via this mechanism by over 100% during CCRT. The results proffer new potential for significantly enhancing CCRT via an emerging clinical scenario, where the cisplatin is released in-situ from RT biomaterials loaded with cisplatin nanoparticles.
The purpose of this study is to investigate the feasibility of using cerium oxide nanoparticles (CONPs) as radical scavengers during accelerated partial breast irradiation (APBI) to protect normal tissue. We hypothesize that CONPs can be slowly released from the routinely used APBI balloon applicators—via a degradable coating—and protect the normal tissue on the border of the lumpectomy cavity over the duration of APBI. To assess the feasibility of this approach, we analytically calculated the initial concentration of CONPs required to protect normal breast tissue from reactive oxygen species (ROS) and the time required for the particles to diffuse to various distances from the lumpectomy wall. Given that cerium has a high atomic number, we took into account the possible inadvertent dose enhancement that could occur due to the photoelectric interactions with radiotherapy photons. To protect against a typical MammoSite treatment fraction of 3.4 Gy, 5 ng-g−1 of CONPs is required to scavenge hydroxyl radicals and hydrogen peroxide. Using 2 nm sized NPs, with an initial concentration of 1 mg-g−1, we found that 2–10 days of diffusion is required to obtain desired concentrations of CONPs in regions 1–2 cm away from the lumpectomy wall. The resultant dose enhancement factor (DEF) is less than 1.01 under such conditions. Our results predict that CONPs can be employed for radioprotection during APBI using a new design in which balloon applicators are coated with the NPs for sustained/controlled in-situ release from within the lumpectomy cavity.
Several studies have demonstrated low rates of local recurrence with brachytherapy-based accelerated partial breast irradiation (APBI). However, long-term outcomes on toxicity (e.g. telangiectasia) and cosmesis remain a major concern. The purpose of this study is to investigate the dosimetric feasibility of using targeted non-toxic radiosensitizing gold nanoparticles (GNPs) for localized dose enhancement to the planning target volume (PTV) during electronic brachytherapy APBI while reducing normal tissue toxicity. We propose to incorporate GNPs into a micrometer-thick polymer film on the surface of routinely used lumpectomy balloon applicators and provide subsequent treatment using a 50 kVp Xoft device. An experimentally determined diffusion coefficient was used to determine space-time customizable distribution of GNPs for feasible in-vivo concentrations of 7 mg/g and 43 mg/g. An analytical approach from previously published work was employed to estimate the dose enhancement due to GNPs as a function of distance up to 1 cm from the lumpectomy cavity surface. Clinically significant dose enhancement values of at least 1.2, due to 2 nm GNPs, were found at 1 cm away from the lumpectomy cavity wall when using electronic brachytherapy APBI. Higher customizable dose enhancement was also achieved at other distances as a function of nanoparticle size. Our preliminary results suggest that significant dose enhancement can be achieved to residual tumor cells targeted with GNPs during APBI with electronic brachytherapy.
The aim of this study is to investigate the feasibility of prostate stereotactic body radiation therapy treatment with a newly developed Varian Halcyon TM 2.0 machine by comparing radiotherapy plans with previously delivered CyberKnife G4 plans created with the previous version of CyberKnife Treatment Planning System Multiplan 4.6.1. Methods Fifteen previously treated prostate stereotactic body radiation therapy treatment CyberKnife plans were replanned retrospectively according to the Radiation Therapy Oncology Group 0938 protocol on a Halcyon TM 2.0 machine with a prescription of 3625 cGy in five fractions. Results All re-plans on a Halcyon TM 2.0 were able to meet the Radiation Therapy Oncology Group 0938 protocol goals and constraints. The re-plans decreased the maximum dose to skin and urethra, mean doses to the bladder and rectum, and also improve the conformity index and the Planning Target Volume coverage. However, D1cc to the rectum, D1cc and D10% to the bladder increased with no statistically significant differences (p > 0.05) with the re-plans. Conclusion The Halcyon TM 2.0 can generate stereotactic body radiation therapy treatment prostate plans created based on the Radiation Therapy Oncology Group 0938 protocol by delivering adequate coverage to the target while sparing healthy tissues.
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