Animal Study of a Newly Designed Metal Airway Brachytherapy Stent Loaded with Radioactive 125I Seeds

Aim: To evaluate dynamic tissue changes after airway stenting (AS) with a newly designed metal brachytherapy stent (BS) loaded with radioactive 125I seeds in normal rabbits.Method: Forty-five normal New Zealand white rabbits were divided into three groups (Group A: stent without seeds; Group B: stent with 0.4 mCi active seeds; Group C: stent with 0.8 mCi active seeds) and underwent AS under C-arm guidance. Then, 5 rabbits were sacrificed from each group at 2, 4, and 8 weeks for further examination. Laboratory tests (including routine blood tests, liver function, kidney function, electrolytes and ROS levels), gross observations, and tissue changes of Masson/hematoxylin-eosin staining, plus immunohistochemistry of α-SMA, NOX4, and TGF-β were performed at each time point.Result: All animals underwent AS successfully without procedure-related death, but one animal died at 6 weeks due to severe pulmonary infection in Group C. Apart from a transient increase in white blood cells (P < 0.05) and a gradual increase in ROS levels (P < 0.05), other blood test items showed no significant changes (P > 0.05). The brachytherapy injury score increased with irradiation dose accumulation (P < 0.05), but tissue hyperplasia at the stent end in Group C was less severe than that in Groups A and B (P < 0.05). Airway lateral fibrosis was observed in all groups by histopathologic analysis; however, fibrosis in Group C was more severe than that in Groups A and B (P < 0.05).Conclusion: The brachytherapy injury score increased with irradiation dose accumulation, while granulation tissue hyperplasia at the stent end was inhibited by 125I brachytherapy within 8 weeks.

A new DOSXYZnrc method for Monte Carlo simulations of 4D dose distributions

The purpose of this study is to present a novel method for generating Monte Carlo 4D dose distributions in a single DOSXYZnrc simulation. During a standard simulation, individual energy deposition events are summed up to generate a 3D dose distribution and their associated temporal information is discarded. This means that in order to determine dose distributions as a function of time, separate simulations would have to be run for each interval of interest. Consequently, it has not been clinically feasible until now to routinely perform Monte Carlo simulations of dose rate, time-resolved dose accumulation, or EPID cine-mode images for VMAT plans. To overcome this limitation, we modified DOSXYZnrc and defined new input and output variables that allow a time-like parameter associated with each particle history to be binned in a user-defined manner. Under the new code version, computation times are the same as for a standard simulation, and the time-integrated 4D dose is identical to the standard 3D dose. We present a comparison of scintillator measurements and Monte Carlo simulations for dose rate during a VMAT beam delivery, a study of dose rate in a VMAT Total Body Irradiation plan, and simulations of transit (through-patient) EPID cine-mode images.

Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma

Glioma represents a fast proliferating and highly invasive brain tumor which is resistant to current therapies and invariably recurs. Despite some advancements in anti-glioma therapies, patients’ prognosis remains poor. Toll-like receptors (TLRs) act as the first line of defense in the immune system being the detectors of those associated with bacteria, viruses, and danger signals. In the glioma microenvironment, TLRs are expressed on both immune and tumor cells, playing dual roles eliciting antitumoral (innate and adaptive immunity) and protumoral (cell proliferation, migration, invasion, and glioma stem cell maintenance) responses. Up to date, several TLR-targeting therapies have been developed aiming at glioma bulk and stem cells, infiltrating immune cells, the immune checkpoint axis, among others. While some TLR agonists exhibited survival benefit in clinical trials, it attracts more attention when they are involved in combinatorial treatment with radiation, chemotherapy, immune vaccination, and immune checkpoint inhibition in glioma treatment. TLR agonists can be used as immune modulators to enhance the efficacy of other treatment, to avoid dose accumulation, and what brings more interests is that they can potentiate immune checkpoint delayed resistance to PD-1/PD-L1 blockade by upregulating PD-1/PD-L1 overexpression, thus unleash powerful antitumor responses when combined with immune checkpoint inhibitors. Herein, we focus on recent developments and clinical trials exploring TLR-based treatment to provide a picture of the relationship between TLR and glioma and their implications for immunotherapy.

Cone beam CT-based dose accumulation and analysis of delivered dose to the dominant intraprostatic lesion in primary radiotherapy of prostate cancer

Background Evaluation of delivered dose to the dominant intraprostatic lesion (DIL) for moderately hypofractionated radiotherapy of prostate cancer by cone beam computed tomography (CBCT)-based dose accumulation and target coverage analysis. Methods Twenty-three patients with localized prostate cancer treated with moderately hypofractionated prostate radiotherapy with simultaneous integrated boost (SIB) between December 2016 and February 2020 were retrospectively analyzed. Included patients were required to have an identifiable DIL on bi-parametric planning magnetic resonance imaging (MRI). After import into the RayStation treatment planning system and application of a step-wise density override, the fractional doses were computed on each CBCT and were consecutively mapped onto the planning CT via a deformation vector field derived from deformable image registration. Fractional doses were accumulated for all CBCTs and interpolated for missing CBCTs, resulting in the delivered dose for PTVDIL, PTVBoost, PTV, and the organs at risk. The location of the index lesions was recorded according to the sector map of the Prostate Imaging Reporting and Data System (PIRADS) Version 2.1. Target coverage of the index lesions was evaluated and stratified for location. Results In total, 338 CBCTs were available for analysis. Dose accumulation target coverage of PTVDIL, PTVBoost, and PTV was excellent and no cases of underdosage in DMean, D95%, D02%, and D98% could be detected. Delivered rectum DMean did not significantly differ from the planned dose. Bladder mean DMean was higher than planned with 19.4 ± 7.4 Gy versus 18.8 ± 7.5 Gy, p < 0.001. The penile bulb showed a decreased delivered mean DMean with 29.1 ± 14.0 Gy versus 29.8 ± 14.4 Gy, p < 0.001. Dorsal DILs, defined as DILs in the posterior medial peripheral zone of the prostate, showed a significantly lower delivered dose with a mean DMean difference of 2.2 Gy (95% CI 1.3–3.1 Gy, p < 0.001) compared to ventral lesions. Conclusions CBCT-based dose accumulation showed an adequate delivered dose to the dominant intraprostatic lesion and organs at risk within planning limits. Cautious evaluation of the target coverage for index lesions adjacent to the rectum is warranted to avoid underdosage.

Dynamic Biasing for Improved On-Orbit Total-Dose Lifetimes of Commercial Electronic Devices

The survivability of microelectronic devices in ionizing radiation environments drives spacecraft design, capability, mission scope, and cost. This work exploits the periodic nature of many space radiation environments to extend device lifetimes without additional shielding or modifications to the semiconductor architecture. We propose a technique for improving component lifetimes through reduced total-dose accumulation by modulating device bias during periods of intense irradiation. Simulation of this ``dynamic biasing" technique applied to single-transistor devices in a typical low-Earth orbit results in an increase of component life from 114 days to 477 days (318% improvement) at the expense of 5% down time (95% duty cycle). The biasing technique is also experimentally demonstrated using gamma radiation to study three commercial devices spanning a range of integrated circuit complexity in 109 rad/min and 256 rad/min dose rate conditions. The demonstrated improvements in device lifetimes using the proposed dynamic biasing technique lays a foundation for more effective use of modern microelectronics for space applications. Analogous to the role real-time temperature monitoring plays in maximizing modern processor performance, the proposed dynamic biasing technique is a means of intelligently responding to the radiation environment and capable of becoming an integral tool in optimizing component lifetimes in space.

LEUKOCYTAL INDICES AND OCCUPATIONAL EXTERNAL GAMMA-EXPOSURE

Background: The hematopoietic system is classified as the most radiosensitive body system. Research of occupational radiation-induced hematological shifts continues to be a relevant question of occupational radiation safety. Aim: Analysis of leukocytal indices dynamics depending on the accumulated dose of occupational external gamma-exposure. Methods: The database «Leukemia in the cohort of Mayak Production Association workers hired in 1948-1958» was used as the material. Leukocytal indices were estimated based on 19592 peripheral blood analyses; dynamics of hematological shifts was traced according to accumulation of absorbed doses of occupational external gamma-radiation; comparative analysis of hemogramms with a group of workers without oncohematological pathology was carried out. Nonparametric statistical methods were applied. Results: The period of dose accumulation at the same total dose of occupational external gamma-exposure was much different in the study groups, it was much shorter for individuals who later died of leukemia. Leukocytal indices in groups were most different in the range of accumulated absorbed doses of external gamma exposure equal to 2 – 2.5 Gy and had the largest amplitude of values among the workers diagnosed for leukemia later. Conclusion: The estimation of leukocytal indices may be used as the tool for early detection of adverse hematological shifts in cell lines and may be the indicator of pathologic hemapoiesis in the exposed workers before clinical manifestation of hematological pathology.