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Radiation Protection Dosimetry Sep 2023Extremely high dose rate radiation delivery (FLASH) for cancer treatment has been shown to produce less damage to normal tissues while having the same radiotoxic effect...
Extremely high dose rate radiation delivery (FLASH) for cancer treatment has been shown to produce less damage to normal tissues while having the same radiotoxic effect on tumor tissue (referred to as the FLASH effect). Research on the FLASH effect has two very pertinent implications for the field of biodosimetry: (1) FLASH is a good model to simulate delivery of prompt radiation from the initial moments after detonating a nuclear weapon and (2) the FLASH effect elucidates how dose rate impacts the biological mechanisms that underlie most types of biological biodosimetry. The impact of dose rate will likely differ for different types of biodosimetry, depending on the specific underlying mechanisms. The greatest impact of FLASH effects is likely to occur for assays based on biological responses to radiation damage, but the consequences of differential effects of dose rates on the accuracy of dose estimates has not been taken into account.
Topics: Biological Assay; Nuclear Weapons
PubMed: 37721059
DOI: 10.1093/rpd/ncad062 -
Cancers Jul 2023Radiotherapy (RT) using ultra-high dose rate (UHDR) radiation, known as FLASH RT, has shown promising results in reducing normal tissue toxicity while maintaining tumor... (Review)
Review
Radiotherapy (RT) using ultra-high dose rate (UHDR) radiation, known as FLASH RT, has shown promising results in reducing normal tissue toxicity while maintaining tumor control. However, implementing FLASH RT in clinical settings presents technical challenges, including limited depth penetration and complex treatment planning. Monte Carlo (MC) simulation is a valuable tool for dose calculation in RT and has been investigated for optimizing FLASH RT. Various MC codes, such as EGSnrc, DOSXYZnrc, and Geant4, have been used to simulate dose distributions and optimize treatment plans. Accurate dosimetry is essential for FLASH RT, and radiation detectors play a crucial role in measuring dose delivery. Solid-state detectors, including diamond detectors such as microDiamond, have demonstrated linear responses and good agreement with reference detectors in UHDR and ultra-high dose per pulse (UHDPP) ranges. Ionization chambers are commonly used for dose measurement, and advancements have been made to address their response nonlinearities at UHDPP. Studies have proposed new calculation methods and empirical models for ion recombination in ionization chambers to improve their accuracy in FLASH RT. Additionally, strip-segmented ionization chamber arrays have shown potential for the experimental measurement of dose rate distribution in proton pencil beam scanning. Radiochromic films, such as Gafchromic EBT3, have been used for absolute dose measurement and to validate MC simulation results in high-energy X-rays, triggering the FLASH effect. These films have been utilized to characterize ionization chambers and measure off-axis and depth dose distributions in FLASH RT. In conclusion, MC simulation provides accurate dose calculation and optimization for FLASH RT, while radiation detectors, including diamond detectors, ionization chambers, and radiochromic films, offer valuable tools for dosimetry in UHDR environments. Further research is needed to refine treatment planning techniques and improve detector performance to facilitate the widespread implementation of FLASH RT, potentially revolutionizing cancer treatment.
PubMed: 37568699
DOI: 10.3390/cancers15153883 -
Physics in Medicine and Biology Jul 2023This work aims at investigating the response of various thermally stimulated luminescence detectors (TLDs) and optically stimulated luminescence detectors (OSLDs) for...
This work aims at investigating the response of various thermally stimulated luminescence detectors (TLDs) and optically stimulated luminescence detectors (OSLDs) for dosimetry of ultra-high dose rate electron beams. The study was driven by the challenges of dosimetry at ultra-high dose rates and the importance of dosimetry for FLASH radiotherapy and radiobiology experiments.Three types of TLDs (LiF:Mg,Ti; LiF:Mg,Cu,P; CaF:Tm) and one type of OSLD (AlO:C) were irradiated in a 15 MeV electron beam with instantaneous dose rates in the (1-324) kGy srange. Reference dosimetry was carried out with an integrating current transformer, which was calibrated in absorbed dose to water against a reference ionization chamber. Additionally, dose rate independent BeO OSLDs were employed as a reference. Beam non-uniformity was addressed using a matrix of TLDs/OSLDs.The investigated TLDs were shown to be dose rate independent within the experimental uncertainties, which take into account the uncertainty of the dosimetry protocol and the irradiation uncertainty. The relative deviation between the TLDs and the reference dose was lower than 4 % for all dose rates. A decreasing response with the dose rate was observed for AlO:C OSLDs, but still within 10 % from the reference dose.The precision of the investigated luminescence detectors make them suitable for dosimetry of ultra-high dose rate electron beams. Specifically, the dose rate independence of the TLDs can support the investigation of the beam uniformity as a function of the dose rate, which is one of the challenges of the employed beam. AlO:C OSLDs provided high precision measurements, but the decreasing response with the dose rate needs to be confirmed by additional experiments.
Topics: Electrons; Radiometry; Luminescence; Water
PubMed: 37336230
DOI: 10.1088/1361-6560/acdfb2 -
Brain Tumor Research and Treatment Oct 2023FLASH radiotherapy (FLASH RT) is a technique to deliver ultra-high dose rate in a fraction of a second. Evidence from experimental animal models suggest that FLASH RT... (Review)
Review
FLASH radiotherapy (FLASH RT) is a technique to deliver ultra-high dose rate in a fraction of a second. Evidence from experimental animal models suggest that FLASH RT spares various normal tissues including the lung, gastrointestinal track, and brain from radiation-induced toxicity (a phenomenon known as FLASH effect), which is otherwise commonly observed with conventional dose rate RT. However, it is not simply the ultra-high dose rate alone that brings the FLASH effect. Multiple parameters such as instantaneous dose rate, pulse size, pulse repetition frequency, and the total duration of exposure all need to be carefully optimized simultaneously. Furthermore it is critical to validate FLASH effects in an experimental model system. The exact molecular mechanism responsible for this FLASH effect is not yet understood although a number of hypotheses have been proposed including oxygen depletion and less reactive oxygen species (ROS) production by FLASH RT, and enhanced ability of normal tissues to handle ROS and labile iron pool compared to tumors. In this review, we briefly overview the process of ionization event and history of radiotherapy and fractionation of ionizing radiation. We also highlight some of the latest FLASH RT reviews and results with a special interest to neurocognitive protection in rodent model with whole brain irradiation. Lastly we discuss some of the issues remain to be answered with FLASH RT including undefined molecular mechanism, lack of standardized parameters, low penetration depth for electron beam, and tumor hypoxia still being a major hurdle for local control. Nevertheless, researchers are close to having all answers to the issues that we have raised, hence we believe that advancement of FLASH RT will be made more quickly than one can anticipate.
PubMed: 37953445
DOI: 10.14791/btrt.2023.0026 -
Vaccine Jul 2023Safety data on simultaneous vaccination (SV) with primary series monovalent COVID-19 vaccines and other vaccines are limited. We describe SV with primary series COVID-19...
INTRODUCTION
Safety data on simultaneous vaccination (SV) with primary series monovalent COVID-19 vaccines and other vaccines are limited. We describe SV with primary series COVID-19 vaccines and assess 23 pre-specified health outcomes following SV among persons aged ≥5 years in the Vaccine Safety Datalink (VSD).
METHODS
We utilized VSD's COVID-19 vaccine surveillance data from December 11, 2020-May 21, 2022. Analyses assessed frequency of SV. Rate ratios (RRs) were estimated by Poisson regression when the number of outcomes was ≥5 across both doses, comparing outcome rates between COVID-19 vaccinees receiving SV and COVID-19 vaccinees receiving no SV in the 1-21 days following COVID-19 vaccine dose 1 and 1-42 days following dose 2 by SV type received ("All SV", "Influenza SV", "Non-influenza SV").
RESULTS
SV with COVID-19 vaccines was not common practice (dose 1: 0.7 % of 8,455,037 persons, dose 2: 0.3 % of 7,787,013 persons). The most frequent simultaneous vaccines were influenza, HPV, Tdap, and meningococcal. Outcomes following SV with COVID-19 vaccines were rare (total of 56 outcomes observed after dose 1 and dose 2). Overall rate of outcomes among COVID-19 vaccinees who received SV was not statistically significantly different than the rate among those who did not receive SV (6.5 vs. 6.8 per 10,000 persons). Statistically significant elevated RRs were observed for appendicitis (2.09; 95 % CI, 1.06-4.13) and convulsions/seizures (2.78; 95 % CI, 1.10-7.06) in the "All SV" group following dose 1, and for Bell's palsy (2.82; 95 % CI, 1.14-6.97) in the "Influenza SV" group following dose 2.
CONCLUSION
Combined pre-specified health outcomes observed among persons who received SV with COVID-19 vaccine were rare and not statistically significantly different compared to persons who did not receive SV with COVID-19 vaccine. Statistically significant adjusted rate ratios were observed for some individual outcomes, but the number of outcomes was small and there was no adjustment for multiple testing.
Topics: Humans; COVID-19 Vaccines; COVID-19; Influenza Vaccines; Influenza, Human; Vaccination; Bacterial Vaccines
PubMed: 37344264
DOI: 10.1016/j.vaccine.2023.06.042 -
Physics in Medicine and Biology Sep 2023dosimetry (IVD) is an important tool in external beam radiotherapy (EBRT) to detect major errors by assessing differences between expected and delivered dose and to... (Review)
Review
dosimetry (IVD) is an important tool in external beam radiotherapy (EBRT) to detect major errors by assessing differences between expected and delivered dose and to record the received dose by individual patients. Also, in intraoperative radiation therapy (IORT), IVD is highly relevant to register the delivered dose. This is especially relevant in low-risk breast cancer patients since a high dose of IORT is delivered in a single fraction. In contrast to EBRT, online treatment planning based on intraoperative imaging is only under development for IORT. Up to date, two commercial treatment planning systems proposed intraoperative ultrasound or in-room cone-beam CT for real-time IORT planning. This makes IVD even more important because of the possibility for real-time treatment adaptation. Here, we summarize recent developments and applications of IVD methods for IORT in clinical practice, highlighting important contributions and identifying specific challenges such as a treatment planning system for IORT. HDR brachytherapy as a delivery technique was not considered. We add IVD for ultrahigh dose rate (FLASH) radiotherapy that promises to improve the treatment efficacy, when compared to conventional radiotherapy by limiting the rate of toxicity while maintaining similar tumour control probabilities. To date, FLASH IORT is not yet in clinical use.
Topics: Humans; Female; Brachytherapy; Breast Neoplasms; Radiation Oncology; Cone-Beam Computed Tomography; Probability
PubMed: 37607566
DOI: 10.1088/1361-6560/acf2e4 -
The British Journal of Radiology Aug 2023Ultra-high dose-rate (UHDR) irradiations, known as FLASH radiotherapy (RT), rely on delivery of therapeutic doses at instantaneous dose-rates several orders of magnitude... (Review)
Review
Ultra-high dose-rate (UHDR) irradiations, known as FLASH radiotherapy (RT), rely on delivery of therapeutic doses at instantaneous dose-rates several orders of magnitude higher than those currently used in conventional radiotherapy. It has been shown that such an extremely short delivery of radiation leads to remarkable reduction of normal tissue toxicity with respect to conventional dose-rate RT. However, dosimetry at UHDRs is complicated and it is essential to understand the effects that will influence detector response. To date, FLASH RT research has been focused on finding pragmatic solutions that allow the use of UHDR beams in the research setting, but there has been limited focus on absolute dosimetry utilizing primary and secondary standard devices. However, very recently, the data on existing standard dosimeters and novel solutions which could serve as secondary standard devices in UHDR dosimetry started emerging. This review provides an overview of the studies that have been conducted employing calorimeters and innovative solutions utilizing ionization chambers.
Topics: Humans; Radiometry; Radiotherapy Dosage; Radiotherapy
PubMed: 37086074
DOI: 10.1259/bjr.20220560 -
Physics in Medicine and Biology Sep 2023Ultra-high-dose-rate radiotherapy, referred to as FLASH therapy, has been demonstrated to reduce the damage of normal tissue as well as inhibiting tumor growth compared...
Ultra-high-dose-rate radiotherapy, referred to as FLASH therapy, has been demonstrated to reduce the damage of normal tissue as well as inhibiting tumor growth compared with conventional dose-rate radiotherapy. The transient hypoxia may be a vital explanation for sparing the normal tissue. The heterogeneity of oxygen distribution for different doses and dose rates in the different radiotherapy schemes are analyzed. With these results, the influence of doses and dose rates on cell survival are evaluated in this work.The two-dimensional reaction-diffusion equations are used to describe the heterogeneity of the oxygen distribution in capillaries and tissue. A modified linear quadratic model is employed to characterize the surviving fraction at different doses and dose rates.The reduction of the damage to the normal tissue can be observed if the doses exceeds a minimum dose threshold under the ultra-high-dose-rate radiation. Also, the surviving fraction exhibits the 'plateau effect' under the ultra-high dose rates radiation, which signifies that within a specific range of doses, the surviving fraction either exhibits minimal variation or increases with the dose. For a given dose, the surviving fraction increases with the dose rate until tending to a stable value, which means that the protection in normal tissue reaches saturation.The emergence of the 'plateau effect' allows delivering the higher doses while minimizing damage to normal tissue. It is necessary to develop appropriate program of doses and dose rates for different irradiated tissue to achieve more efficient protection.
Topics: Humans; Neoplasms; Radiotherapy Dosage; Oxygen; Hypoxia; Radiotherapy
PubMed: 37586385
DOI: 10.1088/1361-6560/acf112 -
Cancers Sep 2023(1) Background: to report on the use of high-dose-rate (HDR) interventional radiotherapy (brachytherapy, IRT) as a salvage treatment for patients with regionally...
(1) Background: to report on the use of high-dose-rate (HDR) interventional radiotherapy (brachytherapy, IRT) as a salvage treatment for patients with regionally relapsed head and neck cancers. (2) Methods: A retrospective study of 60 patients treated with HDR-IRT for loco-regionally relapsed head and neck cancers at our institution (2016-2020). Treatment procedure, results, and related toxicities were collected. Local and overall survival outcomes were analyzed. (3) Results: The median follow-up was 22.4 months. Twenty-nine (48.3%) patients had locoregional recurrences with a median time of 28.9 months. The local-recurrence free-survival was 88.1% and 37.3% at 3 years and 5 years. At the last follow-up, 21 patients were alive and the median time to death was 24 months. The overall survival was 39.2% and 16.6% at 3 years and 5 years. Collectively, there were 28 events of grade ≥ 3 late toxicities recorded in 21 patients (35%). (4) Conclusions: Salvage HDR-IRT combined with surgery offers a second-line curative treatment option for regionally relapsed head and neck cancers with acceptable outcomes and toxicities.
PubMed: 37760518
DOI: 10.3390/cancers15184549 -
International Journal of Radiation... Nov 2023Compared with conventional dose rate irradiation (CONV), ultrahigh dose rate irradiation (UHDR) has shown superior normal tissue sparing. However, a clinically relevant...
PURPOSE
Compared with conventional dose rate irradiation (CONV), ultrahigh dose rate irradiation (UHDR) has shown superior normal tissue sparing. However, a clinically relevant widening of the therapeutic window by UHDR, termed "FLASH effect," also depends on the tumor toxicity obtained by UHDR. Based on a combined analysis of published literature, the current study examined the hypothesis of tumor isoefficacy for UHDR versus CONV and aimed to identify potential knowledge gaps to inspire future in vivo studies.
METHODS AND MATERIALS
A systematic literature search identified publications assessing in vivo tumor responses comparing UHDR and CONV. Qualitative and quantitative analyses were performed, including combined analyses of tumor growth and survival data.
RESULTS
We identified 66 data sets from 15 publications that compared UHDR and CONV for tumor efficacy. The median number of animals per group was 9 (range 3-15) and the median follow-up period was 30.5 days (range 11-230) after the first irradiation. Tumor growth assays were the predominant model used. Combined statistical analyses of tumor growth and survival data are consistent with UHDR isoefficacy compared with CONV. Only 1 study determined tumor-controlling dose (TCD) and reported statistically nonsignificant differences.
CONCLUSIONS
The combined quantitative analyses of tumor responses support the assumption of UHDR isoefficacy compared with CONV. However, the comparisons are primarily based on heterogeneous tumor growth assays with limited numbers of animals and short follow-up, and most studies do not assess long-term tumor control probability. Therefore, the assays may be insensitive in resolving smaller response differences, such as responses of radioresistant tumor subclones. Hence, tumor cure experiments, including additional TCD experiments, are needed to confirm the assumption of isoeffectiveness in curative settings.
Topics: Animals; Neoplasms; Knowledge; Probability; Research Design; Radiotherapy Dosage
PubMed: 37276928
DOI: 10.1016/j.ijrobp.2023.05.045