-
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 -
Low and high dose rate heavy ion radiation-induced intestinal and colonic tumorigenesis in APC mice.Life Sciences in Space Research May 2017Ionizing radiation (IR) is a recognized risk factor for colorectal cancer (CRC) and astronauts undertaking long duration space missions are expected to receive IR doses...
Ionizing radiation (IR) is a recognized risk factor for colorectal cancer (CRC) and astronauts undertaking long duration space missions are expected to receive IR doses in excess of permissible limits with implications for colorectal carcinogenesis. Exposure to IR in outer space occurs at low doses and dose rates, and energetic heavy ions due to their high linear energy transfer (high-LET) characteristics remain a major concern for CRC risk in astronauts. Previously, we have demonstrated that intestinal tumorigenesis in a mouse model (APC) of human colorectal cancer was significantly higher after exposure to high dose rate energetic heavy ions relative to low-LET γ radiation. The purpose of the current study was to compare intestinal tumorigenesis in APC mice after exposure to energetic heavy ions at high (50cGy/min) and relatively low (0.33cGy/min) dose rate. Male and female mice (6-8 weeks old) were exposed to either 10 or 50cGy of Si (energy: 300MeV/n; LET: 70keV/μm) or Fe (energy: 1000MeV/n; LET: 148keV/μm) ions at NASA Space Radiation Laboratory in Brookhaven National Laboratory. Mice (n=20 mice/group) were euthanized and intestinal and colon tumor frequency and size were counted 150days after radiation exposure. Intestinal tumorigenesis in male mice exposed to Fe was similar for high and low dose rate exposures. Although male mice showed a decreasing trend at low dose rate relative to high dose rate exposures, the differences in tumor frequency between the two types of exposures were not statistically significant after Si radiation. In female mice, intestinal tumor frequency was similar for both radiation type and dose rates tested. In both male and female mice intestinal tumor size was not different after high and low dose rate radiation exposures. Colon tumor frequency in male and female mice after high and low dose rate energetic heavy ions was also not significantly different. In conclusion, intestinal and colonic tumor frequency and size was similar irrespective of energetic heavy ion radiation dose rate suggesting that carcinogenic potential of energetic heavy ions is independent of dose rate.
Topics: Adenomatous Polyposis Coli Protein; Animals; Carcinogenesis; Colonic Neoplasms; Disease Models, Animal; Dose-Response Relationship, Radiation; Female; Heavy Ion Radiotherapy; Intestinal Neoplasms; Male; Mice; Mice, Inbred C57BL; Neoplasms, Radiation-Induced; Radiation Exposure
PubMed: 28554509
DOI: 10.1016/j.lssr.2017.04.003 -
Clinical Oncology (Royal College of... Mar 2020The management of high-risk prostate cancer is challenging, as patients have a high risk of both local and distant relapse. Although adjuvant systemic treatment remains... (Review)
Review
The management of high-risk prostate cancer is challenging, as patients have a high risk of both local and distant relapse. Although adjuvant systemic treatment remains an important component of management, for those receiving radiotherapy, optimal local treatment should include a brachytherapy boost. This may be given by low dose rate (LDR) or high dose rate (HDR) techniques, but HDR has several advantages over LDR by virtue of more consistent dose optimisation, ability to treat outside the prostate and lower toxicity. A significant body of evidence now supports the use of HDR brachytherapy in addition to supplementary pelvic external beam radiotherapy for men with high-risk disease. Consistent evidence has emerged from randomised clinical trials, meta-analyses, and from institutional and multicentre cohort studies. It has been shown to improve local disease control and possibly reduce metastases and improve cancer-specific survival compared with external beam radiotherapy alone. It should be considered as standard treatment.
Topics: Brachytherapy; Humans; Male; Prostatic Neoplasms; Radiotherapy Dosage
PubMed: 31791573
DOI: 10.1016/j.clon.2019.11.003 -
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 -
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 -
Physics in Medicine and Biology Aug 2020Dose distributions have become more complex with the introduction of image-guided brachytherapy in high-dose-rate (HDR) brachytherapy treatments. Therefore, to correctly...
Dose distributions have become more complex with the introduction of image-guided brachytherapy in high-dose-rate (HDR) brachytherapy treatments. Therefore, to correctly execute HDR, conducting a quality assurance programme for the remote after-loading system and verifying the dose distribution in the patient treatment plan are necessary. The characteristics of the dose distribution of HDR brachytherapy are that the dose is high near the source and rapidly drops when the distance from the source increases. Therefore, a measurement tool corresponding to the characteristic is required. In this study, using an Iridium-192 (Ir-192) source, we evaluated the basic characteristics of a nanoclay-based radio-fluorogenic gel (NC-RFG) dosimeter that is a fluorescent gel dosimeter using dihydrorhodamine 123 hydrochloride as a fluorescent probe. The two-dimensional dose distribution measurements were performed at multiple source positions to simulate a clinical plan. Fluorescence images of the irradiated NC-RFG were obtained at a high resolution (0.04 mm pixel) using a gel scanner with excitation at 465 nm. Good linearity was confirmed up to a dose range of 100 Gy without dose rate dependence. The dose distribution measurement at the five-point source position showed good agreement with the treatment planning system calculation. The pass ratio by gamma analysis was 92.1% with a 2%/1 mm criterion. The NC-RFG dosimeter demonstrates to have the potential of being a useful tool for quality assurance of the dose distribution delivered by HDR brachytherapy. Moreover, compared with conventional gel dosimeters such as polymer gel and Fricke gel dosimeters it solves the problems of diffusion, dose rate dependence and inhibition of oxygen-induced reactions. Furthermore, it facilitates dose data to be read in a short time after irradiation, which is useful for clinical use.
Topics: Brachytherapy; Fluorescent Dyes; Gels; Humans; Iridium Radioisotopes; Radiation Dosage; Radiometry; Radiotherapy Dosage; Rhodamines
PubMed: 32485693
DOI: 10.1088/1361-6560/ab98d2 -
Critical Reviews in Oncology/hematology Jun 2015The intrinsic physical and radiobiological characteristics of High Dose Rate Brachytherapy (HDR-BT) are well suited to the treatment of prostate cancer. HDR-BT was... (Review)
Review
The intrinsic physical and radiobiological characteristics of High Dose Rate Brachytherapy (HDR-BT) are well suited to the treatment of prostate cancer. HDR-BT was initially used as a boost to external beam brachytherapy, but has subsequently been employed as the sole treatment, which is termed HDR monotherapy. This review summarizes the clinical outcomes and toxicity results of the principal studies and discusses the radiobiological basis supporting its use.
Topics: Brachytherapy; Dose Fractionation, Radiation; Humans; Male; Prostatic Neoplasms; Radiotherapy Dosage; Salvage Therapy; Treatment Outcome
PubMed: 25819287
DOI: 10.1016/j.critrevonc.2015.02.003 -
International Journal of Radiation... Apr 2015To investigate in detail the earlier observed combined effect of low dose-rate β-irradiation delivered at a dose-rate of 15 mGy/h and continued intermittent hypoxia...
PURPOSE
To investigate in detail the earlier observed combined effect of low dose-rate β-irradiation delivered at a dose-rate of 15 mGy/h and continued intermittent hypoxia that leads to extensive cell death after approximately 3-6 weeks.
MATERIAL AND METHODS
Continuous low dose-rate β-irradiation at a dose rate of 15, 1.5 or 0.6 mGy/h was given by incorporation of [(3)H]-labelled valine into cellular protein. The cells were cultivated in an atmosphere with 4% O2 using an INVIVO2 hypoxia glove box. Clonogenic capacity, cell-cycle distribution and cellular respiration were monitored throughout the experiments.
RESULTS
After 3-6 weeks most cells died in response to the combined treatment, giving a surviving fraction of only 1-2%. However, on continued cultivation a few cells survived and restarted proliferation as the cellular oxygen supply increased with the reduced cell number. Irradiating the T-47D cells grown in an atmosphere with 4% O2 at dose-rates 10 and 25 times lower than 15 mGy/h did not have a pronounced effect on the clonogenic capacity with surviving fractions of 60-80%.
CONCLUSIONS
Treatment of T-47D cells with low dose-rate β-irradiation leads to a specific effect on intermittent hypoxic cells, inactivating more than 98% of the cells in the population. Given improved oxygen conditions, the few surviving cells can restart their proliferation.
Topics: Cell Hypoxia; Cell Line, Tumor; Cell Survival; DNA Breaks, Double-Stranded; Humans; Radiation Dosage
PubMed: 25510258
DOI: 10.3109/09553002.2014.996262 -
Medical Physics Feb 2017The aim of this study was to assess the suitability of Gafchromic EBT3 films for reference dose measurements in the beam of a prototype high dose-per-pulse linear...
PURPOSE
The aim of this study was to assess the suitability of Gafchromic EBT3 films for reference dose measurements in the beam of a prototype high dose-per-pulse linear accelerator (linac), capable of delivering electron beams with a mean dose-rate (Ḋ ) ranging from 0.07 to 3000 Gy/s and a dose-rate in pulse (Ḋ ) of up to 8 × 10 Gy/s. To do this, we evaluated the overall uncertainties in EBT3 film dosimetry as well as the energy and dose-rate dependence of their response.
MATERIAL AND METHODS
Our dosimetric system was composed of EBT3 Gafchromic films in combination with a flatbed scanner and was calibrated against an ionization chamber traceable to primary standard. All sources of uncertainties in EBT3 dosimetry were carefully analyzed using irradiations at a clinical radiotherapy linac. Energy dependence was investigated with the same machine by acquiring and comparing calibration curves for three different beam energies (4, 8 and 12 MeV), for doses between 0.25 and 30 Gy. Ḋ dependence was studied at the clinical linac by changing the pulse repetition frequency (f) of the beam in order to vary Ḋ between 0.55 and 4.40 Gy/min, while Ḋ dependence was probed at the prototype machine for Ḋ ranging from 7 × 10 to 8 × 10 Gy/s. Ḋ dependence was first determined by studying the correlation between the dose measured by films and the charge of electrons measured at the exit of the machine by an induction torus. Furthermore, we compared doses from the films to independently calibrated thermo-luminescent dosimeters (TLD) that have been reported as being dose-rate independent up to such high dose-rates.
RESULTS
We report that uncertainty below 4% (k = 2) can be achieved in the dose range between 3 and 17 Gy. Results also demonstrated that EBT3 films did not display any detectable energy dependence for electron beam energies between 4 and 12 MeV. No Ḋ dependence was found either. In addition, we obtained excellent consistency between films and TLDs over the entire Ḋ range attainable at the prototype linac confirming the absence of any dose-rate dependence within the investigated range (7 × 10 to 8 × 10 Gy/s). This aspect was further corroborated by the linear relationship between the dose-per-pulse (D ) measured by films and the charge per pulse (C ) measured at the prototype linac exit.
CONCLUSION
Our study shows that the use of EBT3 Gafchromic films can be extended to reference dosimetry in pulsed electron beams with a very high dose rate. The measurement results are associated with an overall uncertainty below 4% (k = 2) and are dose-rate and energy independent.
Topics: Electrons; Feasibility Studies; Film Dosimetry; Humans; Particle Accelerators; Radiation Dosage
PubMed: 28019660
DOI: 10.1002/mp.12066 -
Frontiers in Oncology 2016Nowadays, head and neck squamous cell carcinoma (HNSCC) treatment failure is mostly explained by locoregional progression or intrinsic radioresistance. Radiotherapy (RT)...
Nowadays, head and neck squamous cell carcinoma (HNSCC) treatment failure is mostly explained by locoregional progression or intrinsic radioresistance. Radiotherapy (RT) has recently evolved with the emergence of heavy ion radiations or new fractionation schemes of photon therapy, which modify the dose rate of treatment delivery. The aim of the present study was then to evaluate the in vitro influence of a dose rate variation during conventional RT or carbon ion hadrontherapy treatment in order to improve the therapeutic care of patient. In this regard, two HNSCC cell lines were irradiated with photons or 72 MeV/n carbon ions at a dose rate of 0.5, 2, or 10 Gy/min. For both radiosensitive and radioresistant cells, the change in dose rate significantly affected cell survival in response to photon exposure. This variation of radiosensitivity was associated with the number of initial and residual DNA double-strand breaks (DSBs). By contrast, the dose rate change did not affect neither cell survival nor the residual DNA DSBs after carbon ion irradiation. As a result, the relative biological efficiency at 10% survival increased when the dose rate decreased. In conclusion, in the RT treatment of HNSCC, it is advised to remain very careful when modifying the classical schemes toward altered fractionation. At the opposite, as the dose rate does not seem to have any effects after carbon ion exposure, there is less need to adapt hadrontherapy treatment planning during active system irradiation.
PubMed: 27014633
DOI: 10.3389/fonc.2016.00058