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Physica Medica : PM : An International... Dec 2022To characterize an experimental setup for ultra-high dose rate (UHDR) proton irradiations, and to address the challenges of dosimetry in millimetre-small pencil proton...
PURPOSE
To characterize an experimental setup for ultra-high dose rate (UHDR) proton irradiations, and to address the challenges of dosimetry in millimetre-small pencil proton beams.
METHODS
At the PSI Gantry 1, high-energy transmission pencil beams can be delivered to biological samples and detectors up to a maximum local dose rate of ∼9000 Gy/s. In the presented setup, a Faraday cup is used to measure the delivered number of protons up to ultra-high dose rates. The response of transmission ion-chambers, as well as of different field detectors, was characterized over a wide range of dose rates using the Faraday cup as reference.
RESULTS
The reproducibility of the delivered proton charge was better than 1 % in the proposed experimental setup. EBT3 films, AlO:C optically stimulated luminescence detectors and a PTW microDiamond were used to validate the predicted dose. Transmission ionization chambers showed significant volume ion-recombination (>30 % in the tested conditions) which can be parametrized as a function of the maximum proton current density. Over the considered range, EBT3 films, inorganic scintillator-based screens and the PTW microDiamond were demonstrated to be dose rate independent within ±3 %, ±1.8 % and ±1 %, respectively.
CONCLUSIONS
Faraday cups are versatile dosimetry instruments that can be used for dose estimation, field detector characterization and on-line dose verification for pre-clinical experiments in UHDR proton pencil beams. Among the tested detectors, the commercial PTW microDiamond was found to be a suitable option to measure real time the dosimetric properties of narrow pencil proton beams for dose rates up to 2.2 kGy/s.
Topics: Protons; Reproducibility of Results
PubMed: 36395638
DOI: 10.1016/j.ejmp.2022.10.019 -
Acta Medica Okayama Apr 2021The forced swim test (FST) induces immobility in mice. Low-dose (high-dose-rate) X-irradiation inhibits FSTinduced immobility in mice due to its antioxidative function....
The forced swim test (FST) induces immobility in mice. Low-dose (high-dose-rate) X-irradiation inhibits FSTinduced immobility in mice due to its antioxidative function. We evaluated the effects of low-dose γ-irradiation at a low-dose-rate on the FST-induced depletion of antioxidants in mouse organs. Mice received whole-body low-dose-rate (0.6 or 3.0 mGy/h) of low-dose γ-irradiation for 1 week, followed by daily FSTs (5 days). The immobility rate on day 2 compared to day 1 was significantly lower in the 3.0 mGy/h irradiated mice than in sham irradiated mice. The FST significantly decreased the catalase (CAT) activity and total glutathione (t-GSH) content in the brain and kidney, respectively. The superoxide dismutase (SOD) activity and t-GSH content in the liver of the 3.0 mGy/h irradiated mice were significantly lower than those of the non-FST-treated mice. The CAT activity in the lungs of mice exposed to 3.0 mGy/h γ-irradiation was higher than that of non-FST treated mice and mice treated with FST. However, no significant differences were observed in the levels of these antioxidant markers between the sham and irradiated groups except for the CAT activity in lungs. These findings suggest that the effects of low-dose-rate and low-dose γ-irradiation on FST are highly organ-dependent.
Topics: Animals; Antioxidants; Dose-Response Relationship, Radiation; Gamma Rays; Immobilization; Mice; Oxidative Stress; Swimming; X-Rays
PubMed: 33953424
DOI: 10.18926/AMO/61896 -
Applied Radiation and Isotopes :... Aug 2023Multi-facility nuclear sites with research reactors have several environmental area gamma monitors in a network as a part of their surveillance capability. However, the...
Multi-facility nuclear sites with research reactors have several environmental area gamma monitors in a network as a part of their surveillance capability. However, the routine release of low levels of Ar gas from the reactor is prone to interfere with the recorded gamma dose rate and mask the genuine processes being monitored at the network's central control room. As a potential solution, machine learning techniques have been used in this study to autonomously identify and discriminate the genuine processes, viz., the radioactive consignment loading and its movement, at an interim radiopharmaceutical facility located close to a research reactor. To increase the richness of the recorded univariate dose rate time series, several additional features were created. A labelled dataset of process and non-process dose rate sub-sequences or segments was generated by subject matter experts, based on practical knowledge of the facility, and aided by k-means clustering algorithm. The labelled dataset was used to train several supervised classification models and the random forest class of models gave superior performance. The optimised random forest model was able to identify process sub-sequences with a precision of 82.35% and a specificity of 97.11%. The overall balanced accuracy of the model was 91% with a f1 score of 82%. This machine learning approach proved useful to autonomously identify genuine process driven sub-sequences in the univariate dose rate time series. It has an application in reducing the false alarms at exit portal monitors, especially at those sites where there is a potential for external interference in the monitored dose rate.
Topics: Radiopharmaceuticals; Time Factors; Machine Learning; Algorithms; Random Forest
PubMed: 37247508
DOI: 10.1016/j.apradiso.2023.110878 -
Translational Cancer Research Jul 2021Non-small cell lung cancer (NSCLC) is the most commonly diagnosed solid tumor. While it has been established that stereotactic body radiotherapy for NSCLC plays an...
Impact of high-dose rate radiotherapy on B and natural killer (NK) cell polarization in peripheral blood mononuclear cells (PBMCs) via inducing non-small cell lung cancer (NSCLC)-derived exosomes.
BACKGROUND
Non-small cell lung cancer (NSCLC) is the most commonly diagnosed solid tumor. While it has been established that stereotactic body radiotherapy for NSCLC plays an important role in antitumor immune response, the possible effects of the dose rate on this response has not been fully clarified.
METHODS
, A549 cells were irradiated on a Varian TrueBeam Linear Accelerator with dose and dose rate escalation using the flattening filter-free (FFF) technique, which was followed by coculturing with peripheral blood mononuclear cells (PBMCs). The exosomes from irradiated A549 cells were isolated and then cocultured with PBMCs. Flow cytometry was performed to analyze the proportion of lymph cell clusters in PBMCs.
RESULTS
The proportion of CD3- immune cell clusters in PBMCs was significantly higher in the 10 Gy treatment group than in the nonirradiated group and other lower-dose (2, 6 Gy) treatment groups at the dose rate of 1,000 MU/min. However, no influence was observed on the proportion of CD3+ T cell subsets. Further results showed that both natural killer (NK) and B cell proportions reached peaks in the 14 Gy treatment group when a dose rate of 1,200 MU/min was used. Notably, the peak values of these two cell proportions were reached at a lower radiation dose of 10 Gy when a greater dose rate, ranging from 1,600 to 2,400 MU/min, was used. We further found that a single, high dose of irradiation (10 Gy), as compared with a single, low dose of irradiation (2 Gy), could markedly stimulate the A549-related exosome secretion in a radiation dose rate-dependent manner. The ultrahigh dose rate radiation-derived exosomes contributed to the polarization of B and NK cell subsets in PBMCs.
CONCLUSIONS
The optimized radiation regime, which depends on the appropriate radiation dose and dose rate, results in the production of exosomes derived from NSCLC cells and eventually the redistribution of immune cells in PBMCs.
PubMed: 35116657
DOI: 10.21037/tcr-21-536 -
Medical Physics Mar 2024Radiotherapy with charged particles at high dose and ultra-high dose rate (uHDR) is a promising technique to further increase the therapeutic index of patient...
BACKGROUND
Radiotherapy with charged particles at high dose and ultra-high dose rate (uHDR) is a promising technique to further increase the therapeutic index of patient treatments. Dose rate is a key quantity to predict the so-called FLASH effect at uHDR settings. However, recent works introduced varying calculation models to report dose rate, which is susceptible to the delivery method, scanning path (in active beam delivery) and beam intensity.
PURPOSE
This work introduces an analytical dose rate calculation engine for raster scanned charged particle beams that is able to predict dose rate from the irradiation plan and recorded beam intensity. The importance of standardized dose rate calculation methods is explored here.
METHODS
Dose is obtained with an analytical pencil beam algorithm, using pre-calculated databases for integrated depth dose distributions and lateral penumbra. Dose rate is then calculated by combining dose information with the respective particle fluence (i.e., time information) using three dose-rate-calculation models (mean, instantaneous, and threshold-based). Dose rate predictions for all three models are compared to uHDR helium ion beam (145.7 MeV/u, range in water of approximatively 14.6 cm) measurements performed at the Heidelberg Ion Beam Therapy Center (HIT) with a diamond-detector prototype. Three scanning patterns (scanned or snake-like) and four field sizes are used to investigate the dose rate differences.
RESULTS
Dose rate measurements were in good agreement with in-silico generated distributions using the here introduced engine. Relative differences in dose rate were below 10% for varying depths in water, from 2.3 to 14.8 cm, as well as laterally in a near Bragg peak area. In the entrance channel of the helium ion beam, dose rates were predicted within 7% on average for varying irradiated field sizes and scanning patterns. Large differences in absolute dose rate values were observed for varying calculation methods. For raster-scanned irradiations, the deviation between mean and threshold-based dose rate at the investigated point was found to increase with the field size up to 63% for a 10 mm × 10 mm field, while no significant differences were observed for snake-like scanning paths.
CONCLUSIONS
This work introduces the first dose rate calculation engine benchmarked to instantaneous dose rate, enabling dose rate predictions for physical and biophysical experiments. Dose rate is greatly affected by varying particle fluence, scanning path, and calculation method, highlighting the need for a consensus among the FLASH community on how to calculate and report dose rate in the future. The here introduced engine could help provide the necessary details for the analysis of the sparing effect and uHDR conditions.
Topics: Humans; Helium; Radiotherapy Planning, Computer-Assisted; Benchmarking; Monte Carlo Method; Proton Therapy; Radiotherapy Dosage; Ions; Water
PubMed: 37847027
DOI: 10.1002/mp.16793 -
The New England Journal of Medicine May 2022On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth...
BACKGROUND
On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19).
METHODS
Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day.
RESULTS
The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks.
CONCLUSIONS
Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.
Topics: BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Humans; Israel; SARS-CoV-2
PubMed: 35381126
DOI: 10.1056/NEJMoa2201570 -
Cancer Radiotherapie : Journal de La... Oct 2019Literature review reporting results of salvage brachytherapy and stereotactic body radiotherapy for prostate recurrence only after radiotherapy for prostate cancer. (Review)
Review
PURPOSE
Literature review reporting results of salvage brachytherapy and stereotactic body radiotherapy for prostate recurrence only after radiotherapy for prostate cancer.
MATERIALS AND METHODS
A total of 38 studies (including at least 15 patients per study) were analysed: 19 using low-dose-rate brachytherapy, nine high-dose-rate brachytherapy and ten stereotactic body radiotherapy. Only five studies were prospective. The median numbers of patients were 30 for low-dose-rate brachytherapy, 34 for high-dose-rate brachytherapy, and 30 for stereotactic body radiotherapy. The median follow-up were 47months for low-dose-rate brachytherapy, 36months for high-dose-rate brachytherapy and 21months for stereotactic body radiotherapy.
RESULTS
Late genitourinary toxicity rates ranged, for grade 2: from 4 to 42% for low-dose-rate brachytherapy, from 7 to 54% for high-dose-rate brachytherapy and from 3 to 20% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 24% for low-dose-rate brachytherapy, from 0 to 13% for high-dose-rate brachytherapy and from 0 to 3% for grade 3 or above (except 12% in one study) for stereotactic body radiotherapy. Late gastrointestinal toxicity rates ranged, for grade 2: from 0 to 6% for low-dose-rate brachytherapy, from 0 to 14% for high-dose-rate brachytherapy and from 0 to 11% for stereotactic body radiotherapy, and for grade 3 or above: from 0 to 6% for low-dose-rate brachytherapy, and from 0 to 1% for high-dose-rate brachytherapy and stereotactic body radiotherapy. The 5-year biochemical disease-free survival rates ranged from 20 to 77% for low-dose-rate brachytherapy and from 51 to 68% for high-dose-rate brachytherapy. The 2- and 3-year disease-free survival rates ranged from 40 to 82% for stereotactic body radiotherapy. Prognostic factors of biochemical recurrence have been identified.
CONCLUSION
Despite a lack of prospective data, salvage reirradiation for prostate cancer recurrence can be proposed to highly selected patients and tumours. Prospective comparative studies are needed.
Topics: Brachytherapy; Humans; Male; Neoplasm Recurrence, Local; Prostatic Neoplasms; Radiosurgery; Re-Irradiation; Salvage Therapy
PubMed: 31421999
DOI: 10.1016/j.canrad.2019.07.125 -
Journal of Applied Clinical Medical... Oct 2021A signal dependence on dose rate was reported for the ArcCHECK array due to recombination processes within the diodes. The purpose of our work was to quantify the...
PURPOSE
A signal dependence on dose rate was reported for the ArcCHECK array due to recombination processes within the diodes. The purpose of our work was to quantify the necessary correction and apply them to quality assurance measurements.
METHODS
Static 10 × 10 cm 6-MV fields delivered by a linear accelerator were applied to the detector array while decreasing the average dose rate, that is, the pulse frequency, from 500 to 30 MU/min. An ion chamber was placed inside the ArcCHECK cavity as a reference. Furthermore, the instantaneous dose rate dependence (DRD) was studied. The position of the detector was adjusted to change the dose-per-pulse, varying the distance between the focus and the diode closest to the focus between 69.6 and 359.6 cm. Reference measurements were performed with an ion chamber placed inside a PMMA slab phantom at the same source-to-detector distances ( . Exponential saturation functions were fitted to the data, with different parameters to account for two generations of ArcCHECK detectors (types 2 and 3) and both DRDs. Corrections were applied to 12 volumetric modulated arc therapy plans.
RESULTS
The sensitivity decreased by up to 2.8% with a decrease in average dose rate and by 9% with a decrease in instantaneous dose rate. Correcting the average DRD, the mean gamma pass rates (2%/2-mm criterion) of the treatment plans were improved by 5 percentage points (PP) for diode type 3 and 0.4 PP for type 2. Correcting the instantaneous DRD, the improvement was 8.4 PP for type 3 and 0.9 PP for type 2.
CONCLUSIONS
The instantaneous DRD was identified as the prevailing effect on the diode sensitivity. We developed and validated a method to correct this behavior. The number of falsely not passed treatment plans could be considerably reduced.
Topics: Humans; Particle Accelerators; Quality Assurance, Health Care; Radiometry; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Silicon
PubMed: 34519437
DOI: 10.1002/acm2.13409 -
Physics in Medicine and Biology Apr 2021FLASH irradiation has been shown to reduce significantly normal tissue toxicity compared to conventional irradiation, while maintaining tumor control probability at...
FLASH irradiation has been shown to reduce significantly normal tissue toxicity compared to conventional irradiation, while maintaining tumor control probability at similar level. Clinical translation of FLASH irradiation necessitates comprehensive laboratory studies to elucidate biological effects as well as pertinent technological and physical requirements. At present, FLASH research employs complex accelerator technologies of limited accessibilities. Here, we study the feasibility of a novel self-shielded x-ray irradiation cabinet system, as an enabling technology to enhance the preclinical research capabilities. The proposed system employs two commercially available high capacity 150 kVp fluoroscopy x-ray sources with rotating anode technology in a parallel-opposed arrangement. Simulation was performed with the GEANT4 Monte-Carlo platform. Simulated dosimetric properties of the x-ray beam for both FLASH and conventional dose-rate irradiations were characterized. Dose and dose rate from a single kV x-ray fluoroscopy source in solid water phantom were verified with measurements using Gafchromic films. The parallel-opposed x-ray sources can deliver over 50 Gy doses to a 20 mm thick water equivalent medium at ultrahigh dose-rates of 40-240 Gy s. A uniform depth-dose rate (±5%) is achieved over 8-12 mm in the central region of the phantom. Mirrored beams minimize heel effect of the source and achieve reasonable cross-beam uniformity (±3%). Conventional dose-rate irradiation (≤0.1 Gy s) can also be achieved by reducing the tube current and increasing the distance between the phantom and tubes. The rotating anode x-ray source can be used to deliver both FLASH and conventional dose-rate irradiations with the field dimensions well suitable for small animal and cell-culture irradiations. For FLASH irradiation using parallel-opposed sources, entrance and exit doses can be higher by 30% than the dose at the phantom center. Beam angling can be employed to minimize the high surface doses. Our proposed system is amendable to self-shielding and enhance research in regular laboratory setting.
Topics: Animals; Monte Carlo Method; Radiometry; Radiotherapy Dosage; Research; X-Rays
PubMed: 33780922
DOI: 10.1088/1361-6560/abf2fa -
Nuclear Medicine and Biology 2022Targeted radionuclide therapy (TRT) is used to treat disseminated or metastatic tumours in which conventional external beam radiotherapy (EBRT) would have unacceptable... (Review)
Review
Targeted radionuclide therapy (TRT) is used to treat disseminated or metastatic tumours in which conventional external beam radiotherapy (EBRT) would have unacceptable side effects. Unlike EBRT, TRT delivers low doses at a continuous low dose rate. In EBRT, the effect increases progressively with the dose rate, and biological effects (tumour control and normal tissue damage) are related to the dose according to a sigmoid curve model. This model is part of the so-called quantitative radiobiology that is mostly based on the target cell theory, according to which cell death is due to (lethal) radiation hits to vital cellular targets. This model was developed for EBRT, but was adapted to low dose-rate situations by including a parameter that reflects the time needed to repair tissue damage. However, a growing body of evidence indicates that the model should take into account also the biological effects, which are due to intercellular communications (bystander effects) and amplify the effects of radiation, as well as the immune system. Moreover, extranuclear targets must be considered, although induced intracellular and intercellular signalling pathways may ultimately result in DNA damage. It is likely that bystander effects and immune response always contribute to the overall response to TRT at different levels, and that dose and dose rate are key parameters in controlling their real contribution. We hypothesize that the dose rate is the key determinant in the balance between the physical and DNA-centred response on one side, and the biological response that integrates all subcellular compartments and intercellular signalling pathways on the other side.
Topics: DNA Damage; Humans; Neoplasms; Radiobiology; Radioisotopes; Signal Transduction
PubMed: 34922279
DOI: 10.1016/j.nucmedbio.2021.11.005