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EJNMMI Physics Sep 2021The aim of this study was to investigate the safety and efficacy of selective internal radiation therapy (SIRT) with Y resin microspheres for the treatment of...
BACKGROUND
The aim of this study was to investigate the safety and efficacy of selective internal radiation therapy (SIRT) with Y resin microspheres for the treatment of Intrahepatic Cholangiocarcinoma (ICC). A total of 23 SIRT procedures from 18 ICC subjects were analysed to determine a lesion-based dose/response relationship with absorbed dose measures from Y PET and metabolic response as measured on [F]FDG PET. Average absorbed dose (D), minimum dose to 70% of the volume (D), volume receiving at least 50 Gy (V), biological effective dose (BED) and equivalent uniform dose (EUD), were compared to changes in metabolic volume, maximum standardised uptake value (SUV) and total lesion glycolysis (TLG). Dose to normal liver was assessed with changes in liver uptake rate as measured with [Tc]mebrofenin scintigraphy for a cohort of 20 subjects with primary liver malignancy (12 ICC, 8 hepatocellular carcinoma (HCC)).
RESULTS
Thirty-four lesions were included in the analysis. A relationship was found between metabolic response and both D and EUD similar to that seen previously in metastatic colorectal cancer (mCRC), albeit trending towards a lower response plateau. Both dose and SUV coefficient of variation within the lesion (CoV and CoV), baseline TLG and EUD were found to be mildly significant predictors of response. No strong correlation was seen between normal liver dose and change in [Tc]mebrofenin liver uptake rate; low baseline uptake rate was not indicative of declining function following SIRT, and no subjects dropped into the 'poor liver function' category.
CONCLUSIONS
ICC lesions follow a similar dose-response trend as mCRC, however, despite high lesion doses a full metabolic response was rarely seen. The CoV of lesion dose may have a significant bearing on response, and EUD correlated more tightly with metabolic response compared to D. SIRT in primary liver malignancy appears safe in terms of not inducing a clinically significant decline in liver function, and poor baseline uptake rate is not predictive of a reduction in function post SIRT.
PubMed: 34519900
DOI: 10.1186/s40658-021-00406-2 -
Radiation and Environmental Biophysics Aug 2020Many experimental studies are carried out to compare biological effectiveness of high dose rate (HDR) with that of low dose rate (LDR). The rational for this is the...
Many experimental studies are carried out to compare biological effectiveness of high dose rate (HDR) with that of low dose rate (LDR). The rational for this is the uncertainty regarding the value of the dose rate effectiveness factor (DREF) used in radiological protection. While a LDR is defined as 0.1 mGy/min or lower, anything above that is seen as HDR. In cell and animal experiments, a dose rate around 1 Gy/min is usually used as representative for HDR. However, atomic bomb survivors, the reference cohort for radiological protection, were exposed to tens of Gy/min. The important question is whether gamma radiation delivered at very high dose rate (VHDR-several Gy/min) is more effective in inducing DNA damage than that delivered at HDR. The aim of this investigation was to compare the biological effectiveness of gamma radiation delivered at VHDR (8.25 Gy/min) with that of HDR (0.38 Gy/min or 0.79 Gy/min). Experiments were carried out with human peripheral mononuclear cells (PBMC) and the human osteosarcoma cell line U2OS. Endpoints related to DNA damage response were analysed. The results show that in PBMC, VHDR is more effective than HDR in inducing gene expression and micronuclei. In U2OS cells, the repair of 53BP1 foci was delayed after VHDR indicating a higher level of damage complexity, but no VHDR effect was observed at the level of micronuclei and clonogenic cell survival. We suggest that the DREF value may be underestimated when the biological effectiveness of HDR and LDR is compared.
Topics: Adult; Cell Line; Cesium Radioisotopes; DNA Damage; Dose-Response Relationship, Radiation; Female; Gamma Rays; Humans; Leukocytes, Mononuclear; Micronuclei, Chromosome-Defective; Radiation Protection; Relative Biological Effectiveness; Young Adult
PubMed: 32488310
DOI: 10.1007/s00411-020-00852-z -
Physics in Medicine and Biology Jun 2021Cancer radiotherapy (RT) with the irradiation at ultra-high dose rates, namely FLASH-RT, can substantially reduce radiation-induced normal tissue toxicities while...
Cancer radiotherapy (RT) with the irradiation at ultra-high dose rates, namely FLASH-RT, can substantially reduce radiation-induced normal tissue toxicities while maintaining tumor response. Currently, clinical FLASH-RT on deep-seated tumors can only be performed with proton beams. One way to achieve ultra-high dose rates at depth is through the use of high-energy transmission beams (TB), where the Bragg peaks (BP) fall outside the body. However, planning with TB alone does not fully leverage the degrees of freedom for dose shaping as traditional intensity modulated proton therapy (IMPT) which uses the BP of multi-energy proton beams at the tumor target. This work will develop a simultaneous dose and dose rate optimization (SDDRO) method with the joint use of TB and BP, namely SDDRO-Joint. Specifically, BP are placed inside tumor targets to improve the target dose conformality and sparse the normal-tissue dose, while TB primarily cover the tumor boundary to achieve ultra-high dose rate coverage of organs-at-risk (OAR) close to tumor targets. The sparing of OAR and other normal tissues via SDDRO-Joint is jointly by TB and BP, i.e. the FLASH sparing by TB and the dose sparing by BP. The results suggest that the addition of BP substantially increased the target dose conformality for SDDRO. Noticeably SDDRO-Joint also provided slightly higher conformal index values than the conventional IMPT method with BP alone.
Topics: Organs at Risk; Proton Therapy; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated
PubMed: 34010818
DOI: 10.1088/1361-6560/ac02d8 -
Journal of Dairy Science Nov 2021Transition dairy cows experience a decline in immune function that increases the risk of peripartum disease. One strategy to improve peripartum immune function involves...
Transition dairy cows experience a decline in immune function that increases the risk of peripartum disease. One strategy to improve peripartum immune function involves the use of a commercially available cytokine: bovine granulocyte-colony stimulating factor, with the addition of polyethylene glycol to increase duration of effectiveness. Treatment with Imrestor (15 mg pegbovigrastim; Elanco) one week before expected calving date (d -7) and again on the day of calving (d 0) was previously reported to increase the neutrophil number and improve neutrophil function; as a result, the incidence of clinical mastitis was reduced. We conducted 2 experiments over consecutive years to investigate the effect of a lower dose rate (half or quarter dose rate) of Imrestor in grazing dairy cattle and reduced administration frequency: one dose instead of the recommended 2. White blood cell counts were measured to determine changes in relative cell populations in response to treatment. Neutrophil function was assessed by measuring myeloperoxidase activity. Imrestor treatment increased the numbers of neutrophils, band cells, lymphocytes, and monocytes until 14 d postcalving in a dose-dependent manner; it also increased neutrophil myeloperoxidase activity. One dose of Imrestor increased white blood cell counts and myeloperoxidase activity, but the timing, degree, and duration of the response were different relative to the recommended 2 doses and were also dependent upon when Imrestor treatment was given. One dose at d -7 relative to expected calving date did not have a lasting effect postcalving, whereas one dose only on d 0 caused a delayed effect relative to cows that received 2 doses. There was no effect of Imrestor on milk yield or on blood indicators of transition cow health. A lower dose rate of Imrestor or a single dose of Imrestor on the day of calving may be sufficient to improve neutrophil function during the early postpartum in grazing dairy cows. Large-scale field studies are required to determine whether the smaller response from lower dose rates or the timing of the immunological response to drug delivery affect animal health in early lactation.
Topics: Animals; Cattle; Female; Granulocyte Colony-Stimulating Factor; Lactation; Milk; Neutrophils; Recombinant Proteins
PubMed: 34419282
DOI: 10.3168/jds.2021-20630 -
Journal of Medical Virology Jun 2022We analyzed published studies on the efficacy and safety of the third dose of the COVID-19 vaccine in various general population settings. We conducted systematic...
We analyzed published studies on the efficacy and safety of the third dose of the COVID-19 vaccine in various general population settings. We conducted systematic searches of PubMed and EMBASE for series published in the English language through November 15, 2021, using the search terms "third" or "booster" or "three" and "dose" and "COVID-19" or "SARS-CoV-2." All articles were selected according to the MOOSE guidelines. The seroconversion risk after third doses was descriptively expressed as a pooled rate ratio ([seroconversion rate after the third dose]/[seroconversion rate after the second dose]). The search returned 30 studies that included a total of 2 734 437 vaccinated subjects. In more than 2 700 000 Israeli patients extracted from the general population, the reduction in the risk of infection ranged from 88% to 92%. Conversion rates for IgG anti-spike ranged from 95% to 100%. In cancer or immunocompromised patients, mean IgG seroconversion was 39.4% before and 66.6% after third doses. A third dose seems necessary to protect against all COVID-19 infection, severe disease, and death risk.
Topics: Antibodies, Viral; COVID-19; COVID-19 Vaccines; Humans; Immunoglobulin G; SARS-CoV-2; Seroconversion
PubMed: 35118680
DOI: 10.1002/jmv.27644 -
Journal of Environmental Radioactivity Oct 2022In this paper, we have developed a methodology to estimate the spatiotemporal distribution of radiation air dose rates around the Fukushima Daiichi Nuclear Power Plant...
In this paper, we have developed a methodology to estimate the spatiotemporal distribution of radiation air dose rates around the Fukushima Daiichi Nuclear Power Plant (FDNPP). In our exploratory data analysis, we found that (1) the temporal evolution of dose rates is composed of a log-linear decay trend and fluctuations of air dose rates that are spatially correlated among adjacent monitoring posts; and (2) the slope of the log-linear environmental decay trend can be represented as a function of the apparent initial dose rates, coordinate position, land-use type, and soil type. From these observations, we first estimated the log-linear decay trend at each location based on these predictors, using the random forest method. We then developed a modified Kalman filter coupled with a Gaussian process model to estimate the dose-rate time series at a given location and time. We applied this method to the Fukushima evacuation zone (as of March 2017), which included 17 monitoring post locations (with monitoring datasets collected between 2014 and 2018) and generated a time series of dose-rate maps. Our results show that this approach allows us to produce accurate spatial and temporal predictions of radiation dose-rate maps using limited spatiotemporal measurements.
Topics: Air Pollutants, Radioactive; Cesium Radioisotopes; Fukushima Nuclear Accident; Japan; Nuclear Power Plants; Radiation Dosage; Radiation Monitoring
PubMed: 35752033
DOI: 10.1016/j.jenvrad.2022.106946 -
Clinical and Translational Radiation... Sep 2020Modern accelerators have the "flattening filter-free" (FFF) technique to deliver RT with a moderate high-dose rate, currently used in limited clinical indications. No...
INTRODUCTION
Modern accelerators have the "flattening filter-free" (FFF) technique to deliver RT with a moderate high-dose rate, currently used in limited clinical indications. No scientifically established data are currently available on the possible effects of this high dose rate on the anti-tumor immune response. We therefore propose here to study these effects in a preclinical CT26 murine colorectal tumor model.
MATERIAL AND METHODS
, CT26 cells were irradiated on a Varian TrueBeam® linac at 3 different dose rates (4; 12 or 24 Gy/min) using the FFF mode. Activation of the anti-tumor immune response was evaluated by the analysis of induction of genes of the type I interferon pathway by RT-qPCR, and by the study of the induction of immunogenic death biomarkers. , an efficacy study of RT delivering 16.5 Gy at 2 different dose rates was performed in immunocompetent Balb/c mice carrying CT26 syngeneic tumors, as well as an immunomonitoring analysed by flow cytometry and a transcriptomic analysis using RNA sequencing. Statistical analyzes were performed using non-parametric tests.
RESULTS
no significant influence of an increase in FFF dose rate was shown for the induction of genes of the type I interferon pathway as well as for the studied immunogenic death markers (HMGB1 secretion). , no difference in terms of tumor growth retardation between the 2 dose rates used was demonstrated, as well as for the composition of immune cell infiltrates within tumor microenvironment and the expression of immune checkpoints in immunomonitoring and RNAseq.
CONCLUSION
In this study involving the CT26 model, no influence of a moderate high dose rate in FFF technique on the anti-tumor immune response was demonstrated, which would make studies of associations between RT and checkpoint inhibitors fit with this technique of RT. However, further explorations using other cellular models seem to be of interest.
PubMed: 32793819
DOI: 10.1016/j.ctro.2020.07.004 -
Frontiers in Physiology 2023To improve the accuracy of cerebral blood flow (CBF) measurement in mice by accounting for the anesthesia effects. The dependence of CBF on anesthesia dose and time...
To improve the accuracy of cerebral blood flow (CBF) measurement in mice by accounting for the anesthesia effects. The dependence of CBF on anesthesia dose and time was investigated by simultaneously measuring respiration rate (RR) and heart rate (HR) under four different anesthetic regimens. Quantitative CBF was measured by a phase-contrast (PC) MRI technique. RR was evaluated with a mouse monitoring system (MouseOX) while HR was determined using an ultrashort-TE MRI sequence. CBF, RR, and HR were recorded dynamically with a temporal resolution of 1 min in a total of 19 mice. Linear regression models were used to investigate the relationships among CBF, anesthesia dose, RR, and HR. CBF, RR, and HR all showed a significant dependence on anesthesia dose ( < 0.0001). However, the dose in itself was insufficient to account for the variations in physiological parameters, in that they showed a time-dependent change even for a constant dose. RR and HR together can explain 52.6% of the variations in CBF measurements, which is greater than the amount of variance explained by anesthesia dose (32.4%). Based on the multi-parametric regression results, a model was proposed to correct the anesthesia effects in mouse CBF measurements, specifically . We also reported awake-state CBF in mice to be 142.0 ± 8.8 mL/100 g/min, which is consistent with the model-predicted value. The accuracy of CBF measurement in mice can be improved by using a correction model that accounts for respiration rate, heart rate, and anesthesia dose.
PubMed: 37123257
DOI: 10.3389/fphys.2023.1169622 -
Journal of Applied Clinical Medical... Jun 2021To assess dosimetric properties and identify required updates to commonly used protocols (including use of film and ionization chamber) pertaining to a clinical linac...
PURPOSE
To assess dosimetric properties and identify required updates to commonly used protocols (including use of film and ionization chamber) pertaining to a clinical linac configured into FLASH (ultra-high dose rate) electron mode.
METHODS
An 18MV photon beam of a Varian iX linac was converted to FLASH electron beam by replacing the target and the flattening filter with an electron scattering foil. The dose was prescribed by entering the MUs through the console. Fundamental beam properties, including energy, dose rate, dose reproducibility, field size, and dose rate dependence on the SAD, were examined in preparation for radiobiological experiments. Gafchromic EBT-XD film was evaluated for usability in measurements at ultra-high dose rates by comparing the measured dose to the inverse square model. Selected previously reported models of chamber efficiencies were fitted to measurements in a broad range of dose rates.
RESULTS
The performance of the modified linac was found adequate for FLASH radiobiological experiments. With exception of the increase in the dose per MU on increase in the repetition rate, all fundamental beam properties proved to be in line with expectations developed with conventional linacs. The field size followed the theorem of similar triangles. The highest average dose rate (2 × 10 Gy/s) was found next to the internal monitor chamber, with the field size of FWHM = 1.5 cm. Independence of the dose readings on the dose rate (up to 2 × 10 Gy/s) was demonstrated for the EBT-XD film. A model of recombination in an ionization chamber was identified that provided good agreement with the measured chamber efficiencies for the average dose rates up to at least 2 × 10 Gy/s.
CONCLUSION
Dosimetric measurements were performed to characterize a linac converted to FLASH dose rates. Gafchromic EBT-XD film and dose rate-corrected cc13 ionization chamber were demonstrated usable at FLASH dose rates.
Topics: Electrons; Film Dosimetry; Humans; Particle Accelerators; Radiometry; Reproducibility of Results
PubMed: 34028969
DOI: 10.1002/acm2.13270 -
Journal of Radiation Research Mar 2021The biological effects of ionizing radiation, especially those of sparsely ionizing radiations like X-ray and γ-ray, are generally reduced as the dose rate is reduced....
The biological effects of ionizing radiation, especially those of sparsely ionizing radiations like X-ray and γ-ray, are generally reduced as the dose rate is reduced. This phenomenon is known as 'the dose-rate effect'. The dose-rate effect is considered to be due to the repair of DNA damage during irradiation but the precise mechanisms for the dose-rate effect remain to be clarified. Ku70, Ku86 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are thought to comprise the sensor for DNA double-strand break (DSB) repair through non-homologous end joining (NHEJ). In this study, we measured the clonogenic ability of Ku70-, Ku86- or DNA-PKcs-deficient rodent cells, in parallel with respective control cells, in response to high dose-rate (HDR) and low dose-rate (LDR) γ-ray radiation (~0.9 and ~1 mGy/min, respectively). Control cells and murine embryonic fibroblasts (MEF) from a severe combined immunodeficiency (scid) mouse, which is DNA-PKcs-deficient, showed higher cell survival after LDR irradiation than after HDR irradiation at the same dose. On the other hand, MEF from Ku70-/- mice exhibited lower clonogenic cell survival after LDR irradiation than after HDR irradiation. XR-V15B and xrs-5 cells, which are Ku86-deficient, exhibited mostly identical clonogenic cell survival after LDR and HDR irradiation. Thus, the dose-rate effect in terms of clonogenic cell survival is diminished or even inversed in Ku-deficient rodent cells. These observations indicate the involvement of Ku in the dose-rate effect.
Topics: Animals; Cell Line; Cell Survival; Cesium Radioisotopes; Clone Cells; Cobalt Radioisotopes; DNA End-Joining Repair; DNA-Activated Protein Kinase; Dose-Response Relationship, Radiation; Gamma Rays; Ku Autoantigen; Mice, SCID; Mice
PubMed: 33372229
DOI: 10.1093/jrr/rraa128