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Ophthalmology Science 2024To describe a pilot study on the use of single-session, high-dose-rate, Food and Drug Administration-cleared, yttrium-90 (Y) plaque brachytherapy for iris and...
PURPOSE
To describe a pilot study on the use of single-session, high-dose-rate, Food and Drug Administration-cleared, yttrium-90 (Y) plaque brachytherapy for iris and iridociliary melanoma.
DESIGN
A single-center, clinical case series.
PARTICIPANTS
Six consecutive patients were included in this study. Each was diagnosed with an iris or iridociliary melanoma based on clinical examination with or without biopsy.
METHODS
Each tumor was staged according to the American Joint Committee on Cancer criteria and received Y eye plaque brachytherapy. The main variables were tumor size, patient age, sex, and method of diagnosis (clinical or biopsy). Surgical techniques, treatment durations, and ocular side effects were recorded. Local control was defined as a lack of tumor growth or regression determined by clinical examinations, including slit-lamp and gonio photography, as well as high-frequency ultrasound measurements. Toxicity parameters included acute and short-term corneal/scleral change, anterior segment inflammation, and cataract progression.
MAIN OUTCOME MEASURES
Local and systemic cancer control, tumor regression, visual acuity, as well as radiation-related normal tissue toxicity.
RESULTS
High-dose-rate Y plaque brachytherapy was used to treat small (American Joint Committee on Cancer cT1) category melanomas. Single-surgery high-dose-rate irradiations were performed under anesthesia. Because of short treatment durations, high-dose-rate Y did not require the additional procedures used for low-dose-rate plaque (e.g., sutures, amniotic membrane epicorneal buffering, Gunderson flaps, and second surgeries for plaque removal). Only conjunctival recession was used to avoid normal tissue irradiation. High-dose-rate Y treatment durations averaged 8.8 minutes (median, 7.9; range, 5.8-12.9). High-dose-rate Y brachytherapy was associated with no periorbital, corneal (Descemet folds), or conjunctival edema. There was no acute or short-term anterior uveitis, secondary cataract, scleropathy, radiation retinopathy, maculopathy, or optic neuropathy. The follow-up was a mean of 16.0 (range 12-24) months. Evidence of local control included a lack of expansion of tumor borders ( = 6, 100%), darkening with or without atrophy of the tumor surface ( = 5/6, 83%), and a mean 24.5% reduction in ultrasonographically measured tumor thickness. There were no cases of metastatic disease.
CONCLUSIONS
High-dose-rate Y brachytherapy allowed for single-surgery, minimally invasive, outpatient irradiation of iris and iridociliary melanomas.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
PubMed: 38840779
DOI: 10.1016/j.xops.2024.100513 -
Mutation Research. Genetic Toxicology... Sep 2022Ionizing radiation (IR) kills cells mainly through induction of DNA damages and the surviving cells may suffer from mutations. Transgenerational effects of IR are well...
Ionizing radiation (IR) kills cells mainly through induction of DNA damages and the surviving cells may suffer from mutations. Transgenerational effects of IR are well documented, but the exact mechanisms underlying them are less well understood; they include induction of mutations in germ cells and epigenetic inheritance. Previously, effects in the offspring of mice and zebrafish exposed to IR have been reported. A few studies also showed indications of transgenerational effects of radiation in humans, particularly in nuclear power workers. In the present project, short- and long-term effects of low-dose-rate (LDR; 50 and 97 mGy/h) and high-dose-rate (HDR; 23.4, 47.1 and 495 Gy/h) IR in Drosophila embryos were investigated. The embryos were irradiated at different doses and dose rates and radiosensitivity at different developmental stages was investigated. Also, the survival of larvae, pupae and adults developed from embryos irradiated at an early stage (30 min after egg laying) were studied. The larval crawling and pupation height assays were applied to investigate radiation effects on larval locomotion and pupation behavior, respectively. In parallel, the offspring from 3 Gy irradiated early-stage embryos were followed up to 12 generations and abnormal phenotypes were studied. Acute exposure of embryos at different stages of development showed that the early stage embryo is the most sensitive. The effects on larval locomotion showed no significant differences between the dose rates but a significant decrease of locomotion activity above 7 Gy was observed. The results indicate that embryos exposed to the low dose rates have shorter eclosion times. At the same cumulative dose (1 up to 7 Gy), HDR is more embryotoxic than LDR. We also found a radiation-induced depigmentation on males (A5 segment of the dorsal abdomen, A5pig) that can be transmitted up to 12 generations. The phenomenon does not follow the classical Mendelian laws of segregation.
Topics: Animals; Dose-Response Relationship, Radiation; Drosophila; Embryonic Development; Gamma Rays; Humans; Larva; Male; Radiation, Ionizing; Zebrafish
PubMed: 36031335
DOI: 10.1016/j.mrgentox.2022.503523 -
Radiation Research Nov 2020Internal contamination by radionuclides may constitute a major source of exposure and biological damage after radiation accidents and potentially in a dirty bomb or...
Internal contamination by radionuclides may constitute a major source of exposure and biological damage after radiation accidents and potentially in a dirty bomb or improvised nuclear device scenario. We injected male C57BL/6 mice with radiolabeled cesium chloride solution (137CsCl) to evaluate the biological effects of varying cumulative doses and dose rates in a two-week study. Injection activities of 137CsCl were 5.71, 6.78, 7.67 and 9.29 MBq, calculated to achieve a target dose of 4 Gy at days 14, 7, 5 and 3, respectively. We collected whole blood samples at days 2, 3, 5, 7 and 14 so that we can publish the issue in Decemberfrom all injection groups and measured gene expression using Agilent Mouse Whole Genome microarrays. We identified both dose-rate-independent and dose-rate-dependent gene expression responses in the time series. Gene Ontology analysis indicated a rapid and persistent immune response to the chronic low-dose-rate irradiation, consistent with depletion of radiosensitive B cells. Pathways impacting platelet aggregation and TP53 signaling appeared activated, but not consistently at all times in the study. Clustering of genes by pattern and identification of dose-rate-independent and -dependent genes provided insight into possible drivers of the dynamic transcriptome response in vivo, and also indicated that TP53 signaling may be upstream of very different transcript response patterns. This characterization of the biological response of blood cells to internal radiation at varying doses and dose rates is an important step in understanding the effects of internal contamination after a nuclear event.
Topics: Animals; Cesium Radioisotopes; DNA Repair; Gene Ontology; Male; Mice; Radiation Dosage
PubMed: 32931585
DOI: 10.1667/RADE-20-00041 -
Applied Radiation and Isotopes :... Feb 2023In this paper, a portable gamma-ray spectrometer for real-time and in-situ gamma-ray detection applications is presented. By combining a quasi-hemispherical CdZnTe (CZT)...
In this paper, a portable gamma-ray spectrometer for real-time and in-situ gamma-ray detection applications is presented. By combining a quasi-hemispherical CdZnTe (CZT) semiconductor detector and a Geiger-Muller (GM) counter together, a wide dose rate range is achieved, ranging from 0.1 μSv/h to 100 mSv/h with a relative error of less than 10%. The GM counter is used to measure dose rate from 1 mSv/h to 100 mSv/h. With CZT, the spectrometer can provide a high energy resolution spectrum for nuclide identification and a high precision dose rate at low dose rates. The full width half maximum (FWHM) resolution is 2.2% at 662 keV below 70 μSv/h and is better than 3.3% at 3.8 mSv/h. The weight of the spectrometer is 3.2 kg for handheld and the runtime is up to 12 h without charging. For preliminary applications, the spectrometer was used to measure the gamma radiation around the Back-n white neutron beam line at China Spallation Neutron Source and around the steam generator in the nuclear power plant at Daya Bay Nuclear Power Station.
Topics: Gamma Rays; Radiometry; Neutrons; Tellurium
PubMed: 36444786
DOI: 10.1016/j.apradiso.2022.110572 -
Journal of Radiation Research Mar 2022Intestinal organoids are an in vitro cultured tissue model generated from intestinal stem cells, and they contain a mixture of epithelial cell types. We previously...
Intestinal organoids are an in vitro cultured tissue model generated from intestinal stem cells, and they contain a mixture of epithelial cell types. We previously established an efficient 'one cell/well' sorting method, and defined organoid-forming potential (OFP) as a useful index to evaluate the stemness of individual cells. In this study, we assessed the response to radiation dose and dose-rate by measuring both OFP and the percentage of stem cells in the crypts. After high-dose-rate (HDR, 0.5 Gy/min) irradiation in vivo, the percentage of stem cells in the harvested crypt cells decreased, and the replenishment of cycling stem cells originating from dormant cells was enhanced, but OFP increased in cells irradiated with a total dose of >1 Gy. In contrast, at a total dose of 0.1 Gy the percentage of stem cells reduced slightly, but neither replenishment rate nor OFP changed. Furthermore, the response to 1 Gy of low-dose-rate (LDR) irradiation was similar to the response to 0.1 Gy HDR irradiation. These results suggest that 0.1 Gy HDR irradiation or 1 Gy LDR irradiation does not alter stemness. Additionally, the OFP increase in the colon in response to irradiation was smaller than that in the duodenum, similar to the percentage of stem cells. Understanding the differences in the response of stem cells between the colon and the duodenum to radiation is important to clarify the mechanisms underlying the development of radiation-associated intestinal cancers.
Topics: Dose-Response Relationship, Radiation; Intestines; Organoids; Radiation Dosage; Radiation, Ionizing; Stem Cells
PubMed: 34977948
DOI: 10.1093/jrr/rrab120 -
Neurosurgery Dec 2019Gamma Knife radiosurgery (GKRS; Elekta AB) remains a well-established treatment modality for vestibular schwannomas. Despite highly effective tumor control, further...
BACKGROUND
Gamma Knife radiosurgery (GKRS; Elekta AB) remains a well-established treatment modality for vestibular schwannomas. Despite highly effective tumor control, further research is needed toward optimizing long-term functional outcomes. Whereas dose-rate effects may impact post-treatment toxicities given tissue dose-response relationships, potential effects remain largely unexplored.
OBJECTIVE
To evaluate treatment outcomes and potential dose-rate effects following definitive GKRS for vestibular schwannomas.
METHODS
We retrospectively reviewed 419 patients treated at our institution between 1998 and 2015, characterizing baseline demographics, pretreatment symptoms, and GKRS parameters. The cohort was divided into 2 dose-rate groups based on the median value (2.675 Gy/min). Outcomes included clinical tumor control, radiographic progression-free survival, serviceable hearing preservation, hearing loss, and facial nerve dysfunction (FND). Prognostic factors were assessed using Cox regression.
RESULTS
The study cohort included 227 patients with available follow-up. Following GKRS 2-yr and 4-yr clinical tumor control rates were 98% (95% CI: 95.6%-100%) and 96% (95% CI: 91.4%-99.6%), respectively. Among 177 patients with available radiographic follow-up, 2-yr and 4-yr radiographic progression-free survival rates were 97% (95% CI: 94.0%-100.0%) and 88% (95% CI: 81.2%-95.0%). The serviceable hearing preservation rate was 72.2% among patients with baseline Gardner-Robertson class I/II hearing and post-treatment audiological evaluations. Most patients experienced effective relief from prior headaches (94.7%), tinnitus (83.7%), balance issues (62.7%), FND (90.0%), and trigeminal nerve dysfunction (79.2%), but not hearing loss (1.0%). Whereas GKRS provided effective tumor control independently of dose rate, GKRS patients exposed to lower dose rates experienced significantly better freedom from post-treatment hearing loss and FND (P = .044).
CONCLUSION
Whereas GKRS provides excellent tumor control and effective symptomatic relief for vestibular schwannomas, dose-rate effects may impact post-treatment functional outcomes. Further research remains warranted.
Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Female; Follow-Up Studies; Hearing; Hearing Loss; Hearing Tests; Humans; Male; Middle Aged; Neuroma, Acoustic; Radiation Dosage; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 31270543
DOI: 10.1093/neuros/nyz229 -
Current Issues in Molecular Biology Aug 2023The output constancy of the accelerator used for boron neutron capture therapy (BNCT) is essential to ensuring anti-tumor efficacy and safety. BNCT as currently...
The output constancy of the accelerator used for boron neutron capture therapy (BNCT) is essential to ensuring anti-tumor efficacy and safety. BNCT as currently practiced requires a wide variety of beam quality assessments to ensure that RBE dose errors are maintained within 5%. However, the necessity of maintaining a constant beam dose rate has not been fully discussed. We therefore clarified the effect of different physical dose rates of the accelerator BNCT on biological effects. SAS and A172 cells exposed to B-boronophenylalanine were irradiated using a neutron beam (normal operating current, 100 μA) at the Aomori Quantum Science Center. Thermal neutron flux was attenuated to 50.0 ± 0.96% under 50 μA irradiation compared to that under 100 μA irradiation. Cells were given physical doses of 1.67 and 3.36 Gy at 30 and 60 mC, respectively, and survival was significantly increased after 50 μA irradiation for both cell types ( = 0.0052 for SAS; = 0.046 for A172, for 60 mC). Differences in accelerator BNCT beam dose rates have non-negligible effects on biological effects. Dose rate fluctuations and differences should not be easily permitted to obtain consistent biological effects.
PubMed: 37754225
DOI: 10.3390/cimb45090441 -
Journal of Radiation Research Mar 2023While epidemiological data have greatly contributed to the estimation of the dose and dose-rate effectiveness factor (DDREF) for human populations, studies using animal... (Review)
Review
While epidemiological data have greatly contributed to the estimation of the dose and dose-rate effectiveness factor (DDREF) for human populations, studies using animal models have made significant contributions to provide quantitative data with mechanistic insights. The current article aims at compiling the animal studies, specific to rodents, with reference to the dose-rate effects of cancer development. This review focuses specifically on the results that explain the biological mechanisms underlying dose-rate effects and their potential involvement in radiation-induced carcinogenic processes. Since the adverse outcome pathway (AOP) concept together with the key events holds promise for improving the estimation of radiation risk at low doses and low dose-rates, the review intends to scrutinize dose-rate dependency of the key events in animal models and to consider novel key events involved in the dose-rate effects, which enables identification of important underlying mechanisms for linking animal experimental and human epidemiological studies in a unified manner.
Topics: Animals; Humans; Radiation Dosage; Neoplasms, Radiation-Induced; Risk Assessment; Radiation Exposure; Models, Animal; Liver; Lung; Hematopoietic System; Dose-Response Relationship, Radiation
PubMed: 36773331
DOI: 10.1093/jrr/rrad003 -
Radiation Protection Dosimetry Oct 2022External dose rates were measured 1 m away from 230 Lu-177 patients to characterise the variability in normalised dose rates as a function of administered activity,...
External dose rates were measured 1 m away from 230 Lu-177 patients to characterise the variability in normalised dose rates as a function of administered activity, body mass index (BMI) and sex. The largest dose rate observed was 0.07 mSv/h associated with an administered activity of 7.2 GBq. Substantial variability was found in the distribution of the normalised dose rate associated that had an average of 0.0037 mSv/h per GBq and a 95% confidence interval of 0.0024-0.0058 mSv/h per GBq. Based on this study, estimating the patient dose rate based on the Lu-177 gamma exposure factor overestimates the dose rate by a factor of 2. A statistically significant inverse relationship was found between the patient dose rate and patient BMI and an empirically derived equation relating these two quantities was reported. On average, male patient dose rates were 3.5% lower than female dose rates, which may be attributed to the larger average BMI of the male patient group.
Topics: Humans; Male; Female; Lutetium; Radioisotopes; Body Mass Index; Cohort Studies
PubMed: 36138119
DOI: 10.1093/rpd/ncac187 -
Scientific Reports May 2024The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We...
The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We developed and characterized a dedicated dose monitor for uHDR-scanned carbon-ion beams. Furthermore, a simple measurable dose rate (dose rate per spot (DR)) was suggested by using the developed dose monitor and experimentally validating quantities relevant to the uHDR scanned carbon-ion beam. A large plane-parallel ionization chamber (IC) with a smaller electrode spacing was used to reduce uHDR recombination effects, and a dedicated operational amplifier was manufactured for the uHDR-scanned carbon-ion beam. The dose linearity of the IC was within ± 1% in the range of 1.8-12.3 Gy. The spatial inhomogeneity of the dose response of the IC was ± 0.38% inside the ± 40-mm detector area, and a systematic deviation of approximately 2% was measured at the edge of the detector. uHDR irradiation with beam scanning was tested and verified for different doses at the corresponding dose rates (in terms of both the average dose rate and DR). We confirmed that the dose monitor can highlight the characteristics (i.e., dose, dose rate, and dose profile) of uHDR-scanned carbon-ion beams at several dose levels in the monochromatic beam mode.
PubMed: 38773165
DOI: 10.1038/s41598-024-62148-2