-
Cancers Jul 2021To quantitatively assess target and organs-at-risk (OAR) dose rate based on three proposed proton PBS dose rate metrics and study FLASH intensity-modulated proton...
To quantitatively assess target and organs-at-risk (OAR) dose rate based on three proposed proton PBS dose rate metrics and study FLASH intensity-modulated proton therapy (IMPT) treatment planning using transmission beams. An in-house FLASH planning platform was developed to optimize transmission (shoot-through) plans for nine consecutive lung cancer patients previously planned with proton SBRT. Dose and dose rate calculation codes were developed to quantify three types of dose rate calculation methods (dose-averaged dose rate (DADR), average dose rate (ADR), and dose-threshold dose rate (DTDR)) based on both phantom and patient treatment plans. Two different minimum MU/spot settings were used to optimize two different dose regimes, 34-Gy in one fraction and 45-Gy in three fractions. The OAR sparing and target coverage can be optimized with good uniformity (hotspot < 110% of prescription dose). ADR, accounting for the spot dwelling and scanning time, gives the lowest dose rate; DTDR, not considering this time but a dose-threshold, gives an intermediate dose rate, whereas DADR gives the highest dose rate without considering any time or dose-threshold. All three dose rates attenuate along the beam direction, and the highest dose rate regions often occur on the field edge for ADR and DTDR, whereas DADR has a better dose rate uniformity. The differences in dose rate metrics have led a large variation for OARs dose rate assessment, posing challenges to FLASH clinical implementation. This is the first attempt to study the impact of the dose rate models, and more investigations and evidence for the details of proton PBS FLASH parameters are needed to explore the correlation between FLASH efficacy and the dose rate metrics.
PubMed: 34298762
DOI: 10.3390/cancers13143549 -
Cancer Feb 2002It has been claimed that external radiation, as a treatment modality for malignant diseases, partly induces apoptosis. It is not known, however, whether therapeutic...
BACKGROUND
It has been claimed that external radiation, as a treatment modality for malignant diseases, partly induces apoptosis. It is not known, however, whether therapeutic low-dose and low-dose-rate radiation are able to induce apoptosis.
METHODS
The effect of low-dose radiation on apoptosis induction in HeLa Hep2 cells was studied, and quantitation of the apoptotic cells was performed by immunocytochemistry using TdT-mediated dUtp-x Nick End Labeling (TUNEL) technology and the M30 CytoDEATH antibody method.
RESULTS
When TUNEL staining was used to quantify apoptosis in untreated HeLa Hep2 cells kept in culture, approximately 5 plus minus 3% of the cells showed positive staining without any treatment. In the first experiment, the HeLa Hep2 cells were exposed to gamma radiation (i.e., 0.5, 1, 2, 5, 10, and 15 grays [Gy]) from a cobalt-60 radiation source delivering a dose rate of 0.80 Gy/min. The radiated cells were cultivated for 5, 10, 24, 48, 72 and 168 hours after irradiation. Radiation doses below 2 Gy did not cause any significant apoptosis, but between 5 and 15 Gy significant apoptosis was observed, with peak values at 5 Gy (P < 0.001). Up to 60% of the investigated cells were shown to display apoptosis. Time to this peak value was 168 hours after irradiation. The HeLa Hep2 cells were exposed to doses of 2, 5, and 10 Gy at a 10-fold lower dose rate (0.072 Gy/min). The cells that achieved a dose below 2 Gy did not present increased apoptosis. At doses above 2 Gy, however, the cells again demonstrated significant apoptosis. Up to 24 hours following irradiation, no apoptosis could be documented, whereas beyond 24 and up to 168 hours a highly significant apoptosis induction was observed. Significant cytotoxicity was confirmed by chromium-51 release from the cells at 5 Gy.
CONCLUSIONS
Low-dose and low-dose-rate radiation are able to induce significant apoptosis, and apoptosis may be one of the mechanisms by which low-dose radiation causes growth inhibition.
Topics: Apoptosis; Cell Survival; Dose-Response Relationship, Radiation; HeLa Cells; Humans; Radiation Dosage; Radioimmunotherapy; Tumor Cells, Cultured
PubMed: 11877747
DOI: 10.1002/cncr.10287 -
Cancers Jul 2023Proton pencil-beam scanning (PBS) Bragg peak FLASH combines ultra-high dose rate delivery and organ-at-risk (OAR) sparing. This proof-of-principle study compared...
Proton pencil-beam scanning (PBS) Bragg peak FLASH combines ultra-high dose rate delivery and organ-at-risk (OAR) sparing. This proof-of-principle study compared dosimetry and dose rate coverage between PBS Bragg peak FLASH and PBS transmission FLASH in head and neck reirradiation. PBS Bragg peak FLASH plans were created via the highest beam single energy, range shifter, and range compensator, and were compared to PBS transmission FLASH plans for 6 GyE/fraction and 10 GyE/fraction in eight recurrent head and neck patients originally treated with quad shot reirradiation (14.8/3.7 CGE). The 6 GyE/fraction and 10 GyE/fraction plans were also created using conventional-rate intensity-modulated proton therapy techniques. PBS Bragg peak FLASH, PBS transmission FLASH, and conventional plans were compared for OAR sparing, FLASH dose rate coverage, and target coverage. All FLASH OAR V40 Gy/s dose rate coverage was 90-100% at 6 GyE and 10 GyE for both FLASH modalities. PBS Bragg peak FLASH generated dose volume histograms (DVHs) like those of conventional therapy and demonstrated improved OAR dose sparing over PBS transmission FLASH. All the modalities had similar CTV coverage. PBS Bragg peak FLASH can deliver conformal, ultra-high dose rate FLASH with a two-millisecond delivery of the minimum MU per spot. PBS Bragg peak FLASH demonstrated similar dose rate coverage to PBS transmission FLASH with improved OAR dose-sparing, which was more pronounced in the 10 GyE/fraction than in the 6 GyE/fraction. This feasibility study generates hypotheses for the benefits of FLASH in head and neck reirradiation and developing biological models.
PubMed: 37568644
DOI: 10.3390/cancers15153828 -
Materials (Basel, Switzerland) Aug 2021Ultrashort pulse laser machining is subject to increase the processing speeds by scaling average power and pulse repetition rate, accompanied with higher dose rates of...
Ultrashort pulse laser machining is subject to increase the processing speeds by scaling average power and pulse repetition rate, accompanied with higher dose rates of X-ray emission generated during laser-matter interaction. In particular, the X-ray energy range below 10 keV is rarely studied in a quantitative approach. We present measurements with a novel calibrated X-ray detector in the detection range of 2-20 keV and show the dependence of X-ray radiation dose rates and the spectral emissions for different laser parameters from frequently used metals, alloys, and ceramics for ultrafast laser machining. Our investigations include the dose rate dependence on various laser parameters available in ultrafast laser laboratories as well as on industrial laser systems. The measured X-ray dose rates for high repetition rate lasers with different materials definitely exceed the legal limitations in the absence of radiation shielding.
PubMed: 34442920
DOI: 10.3390/ma14164397 -
Journal of Applied Clinical Medical... Oct 2022Interventional cardiology involves catheter-based treatment of heart disease, generally through fluoroscopically guided interventional procedures. Patients can be...
Interventional cardiology involves catheter-based treatment of heart disease, generally through fluoroscopically guided interventional procedures. Patients can be subject to considerable radiation dose due to prolonged fluoroscopy time and radiographic exposure, and therefore efforts to minimize patient dose should always be undertaken. Developing standardized, effective quality control programs for these systems is a difficult task owing to cross-vendor differences and automated control of imaging protocols. Furthermore, analyses of radiation dose should be performed in the context of its associated effects on image quality. The aim of the study is to investigate radiation dose and image quality in two fluoroscopic systems used for interventional cardiology procedures. Image quality was assessed in terms of spatial resolution and modulation transfer function, signal-to-noise and contrast-to-noise ratios, and spatial-temporal resolution of fluoroscopy and cineradiography images with phantoms simulating various patient thicknesses under routine cardiology protocols. The entrance air kerma (or air kerma rate) was measured and used to estimate entrance surface dose (or dose rate) in the phantoms.
Topics: Humans; Radiation Dosage; Fluoroscopy; Phantoms, Imaging
PubMed: 35950644
DOI: 10.1002/acm2.13741 -
International Journal of Radiation... Jun 2022To investigate a plasmid DNA nicking assay approach for isolating and quantifying the DNA-damaging effects of ultrahigh-dose-rate (ie, FLASH) irradiation relative to...
PURPOSE
To investigate a plasmid DNA nicking assay approach for isolating and quantifying the DNA-damaging effects of ultrahigh-dose-rate (ie, FLASH) irradiation relative to conventional dose-rate irradiation.
METHODS AND MATERIALS
We constructed and irradiated phantoms containing plasmid DNA to nominal doses of 20 Gy and 30 Gy using 16 MeV electrons at conventional (0.167 Gy/s) and FLASH (46.6 Gy/s and 93.2 Gy/s) dose rates. We delivered conventional dose rates using a standard clinical Varian iX linear accelerator and FLASH dose rates (FDRs) using a modified Varian 21EX C-series linear accelerator. We ran the irradiated DNA and controls (0 Gy) through an agarose gel electrophoresis procedure that sorted and localized the DNA into bands associated with single strand breaks (SSBs), double strand breaks (DSBs), and undamaged DNA. We quantitatively analyzed the gel images to compute the relative yields of SSBs and DSBs and applied a mathematical model of plasmid DNA damage as a function of dose to compute the relative biological effectiveness (RBE) of SSB and DSB (RBE and RBE) damage for a given endpoint and FDR.
RESULTS
Both RBE and RBE were less than unity with the FDR irradiations, indicating FLASH sparing. With regard to the more deleterious DNA DSB damage, the DSB RBEs of FLASH beams at dose rates of 46.6 Gy/s and 93.2 Gy/s relative to the conventional 16 MeV beam dose rate were 0.54 ± 0.15 and 0.55 ± 0.17, respectively.
CONCLUSIONS
This study demonstrated the feasibility of using a DNA-based phantom to isolate and assess the FLASH sparing effect on DNA. We also found that FLASH irradiation causes less damage to DNA compared with a conventional dose rate. This result supports the notion that the protective effect of FLASH irradiation occurs at least partially via fundamental biochemical processes.
Topics: DNA; DNA Damage; Electrons; Humans; Particle Accelerators; Plasmids; Relative Biological Effectiveness
PubMed: 35124135
DOI: 10.1016/j.ijrobp.2022.01.049 -
Nihon Hoshasen Gijutsu Gakkai Zasshi Jan 2016In equipment used for interventional radiology (IVR), automatic exposure control (AEC) is incorporated to obtain the X-ray output suitable for the treatment of targeted...
In equipment used for interventional radiology (IVR), automatic exposure control (AEC) is incorporated to obtain the X-ray output suitable for the treatment of targeted lesions. For the AEC, users select a region as the signal sensing region (measuring field, MF) in the flat panel detector; MFs with various sizes and shapes were pre-defined and prepared in the system. The aim of this study was to examine the change of measured dose rate with the selection of MFs, the type of dosimeters (the ionization chamber dosimeter and the semiconductor dosimeter), and the dosimeter placement relative to the direction of X-ray tube (from cathode to anode). The IVR equipment was Allura Xper FD20/10 (Philips Medical Systems), and six kinds of built-in MFs were used. It was found that dose rate measured by the ionization chamber dosimeter showed a variation of -2 mGy/min with the MFs and the ionization chamber dosimeter placement. The dose rate measured by the semiconductor dosimeter showed more variation than the ionization chamber dosimeter. The change of dose rate with the dosimeter placement would be caused by the MF overlapping the dosimeter which would affect the AEC (the X-ray output). Also, the change of dose rate with the dosimeter placement was considered to be related to the heel effect of the X-ray beam. When performing dose rate measurements, we should notice that the selection of MFs, the type of dosimeters, and the dosimeter placement would affect the measured values.
Topics: Radiology, Interventional; Radiometry
PubMed: 26796935
DOI: 10.6009/jjrt.2016_JSRT_72.1.63 -
Cancers Oct 2023Meeting dose prescription is critical to control tumors in radiation therapy. Interfraction dose variations (IDVs) from the prescribed dose in high dose rate...
Meeting dose prescription is critical to control tumors in radiation therapy. Interfraction dose variations (IDVs) from the prescribed dose in high dose rate brachytherapy (HDR) would cause the target dose to deviate from the prescription but their clinical effect has not been widely discussed in the literature. Our previous study found that IDVs followed a left-skewed distribution. The clinical effect of the IDVs in 100 cervical cancer HDR patients will be addressed in this paper. An in-house Monte Carlo (MC) program was used to simulate clinical outcomes by convolving published tumor dose response curves with IDV distributions. The optimal dose and probability of risk-free local control (RFLC) were calculated using the utility model. The IDVs were well-fitted by the left-skewed Beta distribution, which caused a 3.99% decrease in local control probability and a 1.80% increase in treatment failure. Utility with respect to IDV uncertainty increased the RFLC probability by 6.70% and predicted an optimal dose range of 83 Gy-91 Gy EQD2. It was also found that a 10 Gy dose escalation would not affect toxicity. In conclusion, HRCTV IDV uncertainty reduced LC probabilities and increased treatment failure rates. A dose escalation may help mitigate such effects.
PubMed: 37835556
DOI: 10.3390/cancers15194862 -
Dose-response : a Publication of... 2018A previous study showed that continuous low-dose-rate irradiation promoted the growth of silkworm larvae. This study aimed to confirm that finding, determine the optimal...
A previous study showed that continuous low-dose-rate irradiation promoted the growth of silkworm larvae. This study aimed to confirm that finding, determine the optimal dose rate for growth promotion, and compare low- and high-dose-rate irradiation in silkworms, while also investigating the effects of the radiation-emitting sheet on growth and tumor transplantability in mice. Silkworm eggs were placed on low-dose-emitting sheets with 4 different dose rates (γ-ray rate: 1.7 -22.4 μSv/hour) or on control sheets. The other groups of silkworm larvae received single whole-body X-irradiation (0.1-50 Gy), and subsequent body weight changes were monitored. Starting at 3 weeks old, Balb/c mice were bred on the same sheets, and body weight change was measured. Seven weeks later, the mice were used to investigate the transplantability of EMT6 tumor cells cultured in vitro. The silkworms bred on the 13.4- and 22.4-μSv/hour sheets became larger than the control. Single 50-Gy irradiation suppressed the growth of silkworms. An increase in the time to EMT6 tumor development was observed in low-dose-rate-irradiated mice. This study confirmed growth promotion of silkworms by continuous low-dose radiation and demonstrated growth suppression at a high dose rate. Growth promotion was not observed in mice; further studies using higher dose-rate sheets may be warranted.
PubMed: 30479589
DOI: 10.1177/1559325818811753 -
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