-
Radiotherapy and Oncology : Journal of... Sep 2023Proton radiotherapy (PRT) offers potential benefits over other radiation modalities, including photon and electron radiotherapy. Increasing the rate at which proton...
BACKGROUND AND PURPOSE
Proton radiotherapy (PRT) offers potential benefits over other radiation modalities, including photon and electron radiotherapy. Increasing the rate at which proton radiation is delivered may provide a therapeutic advantage. Here, we compared the efficacy of conventional proton therapy (CONV) to ultrahigh dose-rate proton therapy, FLASH, in a mouse model of non-small cell lung cancers (NSCLC).
MATERIALS AND METHODS
Mice bearing orthotopic lung tumors received thoracic radiation therapy using CONV (<0.05 Gy/s) and FLASH (>60 Gy/s) dose rates.
RESULTS
Compared to CONV, FLASH was more effective in reducing tumor burden and decreasing tumor cell proliferation. Furthermore, FLASH was more efficient in increasing the infiltration of cytotoxic CD8 T-lymphocytes inside the tumor while simultaneously reducing the percentage of immunosuppressive regulatory T-cells (Tregs) among T-lymphocytes. Also, compared to CONV, FLASH was more effective in decreasing pro-tumorigenic M2-like macrophages in lung tumors, while increasing infiltration of anti-tumor M1-like macrophages. Finally, FLASH treatment reduced expression of checkpoint inhibitors in lung tumors, indicating reduced immune tolerance.
CONCLUSIONS
Our results suggest that FLASH dose-rate proton delivery modulates the immune system to improve tumor control and might thus be a promising new alternative to conventional dose rates for NSCLC treatment.
Topics: Animals; Mice; Protons; Radiotherapy Dosage; Lung Neoplasms; Proton Therapy; Carcinoma, Non-Small-Cell Lung
PubMed: 37315577
DOI: 10.1016/j.radonc.2023.109741 -
American Journal of Cardiovascular... Jul 2023The intravenous double-syringe technique (DST) of adenosine administration is the first-line treatment for stable supraventricular tachycardia (SVT). Alternatively, the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The intravenous double-syringe technique (DST) of adenosine administration is the first-line treatment for stable supraventricular tachycardia (SVT). Alternatively, the single-syringe technique (SST) was recently found to be potentially beneficial in several studies. This study aimed to perform a meta-analysis of the SST versus the DST of adenosine administration for the treatment of SVT.
METHODS
We assessed EMBASE, PubMed, Cochrane, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) and non-randomized studies of intervention (NRSIs) comparing the DST to the SST of adenosine administration in patients with SVT. Outcomes included termination rate, termination rate at first dose, total administered dose, adverse effects, and discharge rate.
RESULTS
We included four studies (three RCTs and one NRSI) with a total of 178 patients, of whom 99 underwent the SST of adenosine administration. No significant difference was found between treatment groups regarding termination rate, termination rate restricted to RCTs, total administered dose, and discharge rate. Termination rate at first dose (odds ratio 2.87; confidence interval 1.11-7.41; p = 0.03; I = 0%) was significantly increased in patients who received the SST. Major adverse effects were observed in only one study.
CONCLUSIONS
The SST is probably as safe as the DST and at least as effective for SVT termination, SVT termination at first dose, and discharge rate from the emergency department. However, definitive superiority of one technique is not feasible given the limited sample size.
REGISTRATION
PROSPERO identifier nº CRD42022345125.
Topics: Humans; Adenosine; Syringes; Tachycardia, Supraventricular; Emergency Service, Hospital; Administration, Intravenous
PubMed: 37162718
DOI: 10.1007/s40256-023-00581-w -
BMJ (Clinical Research Ed.) Aug 2023To evaluate the effect of protracted low dose, low dose rate exposure to ionising radiation on the risk of cancer.
OBJECTIVE
To evaluate the effect of protracted low dose, low dose rate exposure to ionising radiation on the risk of cancer.
DESIGN
Multinational cohort study.
SETTING
Cohorts of workers in the nuclear industry in France, the UK, and the US included in a major update to the International Nuclear Workers Study (INWORKS).
PARTICIPANTS
309 932 workers with individual monitoring data for external exposure to ionising radiation and a total follow-up of 10.7 million person years.
MAIN OUTCOME MEASURES
Estimates of excess relative rate per gray (Gy) of radiation dose for mortality from cancer.
RESULTS
The study included 103 553 deaths, of which 28 089 were due to solid cancers. The estimated rate of mortality due to solid cancer increased with cumulative dose by 52% (90% confidence interval 27% to 77%) per Gy, lagged by 10 years. Restricting the analysis to the low cumulative dose range (0-100 mGy) approximately doubled the estimate of association (and increased the width of its confidence interval), as did restricting the analysis to workers hired in the more recent years of operations when estimates of occupational external penetrating radiation dose were recorded more accurately. Exclusion of deaths from lung cancer and pleural cancer had a modest effect on the estimated magnitude of association, providing indirect evidence that the association was not substantially confounded by smoking or occupational exposure to asbestos.
CONCLUSIONS
This major update to INWORKS provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality based on some of the world's most informative cohorts of radiation workers. The summary estimate of excess relative rate solid cancer mortality per Gy is larger than estimates currently informing radiation protection, and some evidence suggests a steeper slope for the dose-response association in the low dose range than over the full dose range. These results can help to strengthen radiation protection, especially for low dose exposures that are of primary interest in contemporary medical, occupational, and environmental settings.
Topics: Humans; United States; Cohort Studies; Neoplasms, Radiation-Induced; Radiation Dosage; Radiation, Ionizing; Industry; United Kingdom; Occupational Exposure; Occupational Diseases; Radiation Exposure
PubMed: 37586731
DOI: 10.1136/bmj-2022-074520 -
Applied Radiation and Isotopes :... Aug 2023Review is provided of a number of low-dose, low dose rate situations that in study require advances in the development of dosimetric facilities. Using a clinical linac...
Review is provided of a number of low-dose, low dose rate situations that in study require advances in the development of dosimetric facilities. Using a clinical linac set up to provide doses down to the few mGy level, the performance of a real-time radioluminescence system has then been illustrated, accommodating pulsed as well as continuous dose delivery. The system gate times provide for tracking of the pattern of dose delivery, allowing detailed account of dose and dose-rate variations. The system has been tested in both x-ray and electron mode dose delivery.
Topics: Radiometry; Radiography; Radiotherapy Dosage; X-Rays
PubMed: 37257265
DOI: 10.1016/j.apradiso.2023.110875 -
Radiation Protection Dosimetry Sep 2023Testing and validation of biodosimetry assays is routinely performed using conventional dose rate irradiation platforms, at a dose rate of approximately 1 Gy/min. In...
Testing and validation of biodosimetry assays is routinely performed using conventional dose rate irradiation platforms, at a dose rate of approximately 1 Gy/min. In contrast, the exposures from an improvised nuclear device will be delivered over a large range of dose rates with a prompt irradiation component, delivered in less than 1 μs, and a protracted component delivered over hours and days. We present preliminary data from a large demographic study we have undertaken for investigation of age, sex and dose rate effects on dicentric and micronucleus yields. Our data demonstrate reduced dicentric and micronucleus yields at very high dose rates. Additionally, we have seen small differences between males and females, with males having slightly fewer micronuclei and slightly more dicentrics than females, at high doses.
Topics: Female; Male; Humans; Cytogenetics; Biological Assay; Cell Nucleus; Cytogenetic Analysis
PubMed: 37721073
DOI: 10.1093/rpd/ncac286 -
Psychiatry Research Sep 2023Sertraline has been shown to be effective in the treatment of depression. However, the relationship between the dosage of sertraline and its efficacy and safety are... (Meta-Analysis)
Meta-Analysis Review
Sertraline has been shown to be effective in the treatment of depression. However, the relationship between the dosage of sertraline and its efficacy and safety are unclear. We identified RCTs that compared sertraline with placebo for the treatment of depression, conducted conventional meta-analyses on the efficacy and safety of sertraline, and assessed the nonlinear dose-response relationship between sertraline dosage and the changes in HAM-D and CGI-S scores, dropout from care for any reason or due to adverse effects, and the rate of adverse effects, using a 1-stage restricted cubic spline regression model. Twenty-one RCTs involving 4,235 patients were included. The pooled mean differences (MD) in the change in HAM-D total score [MD=-2.34, 95% confidence interval (CI) -2.93, -1.76], CGI-S score and MADRS score, but also the dropout rate for adverse effects, and rate of adverse effects were higher in sertraline group. The therapeutic response of sertraline for treating depression increased with the dosage. Meanwhile, the risk of total adverse reactions slightly decreased between 50 and 150 mg, and increased at doses above 150 mg. The dose-dependence of both efficacy and safety need to be considered when choosing the optimal dosage of sertraline.
Topics: Humans; Depression; Randomized Controlled Trials as Topic; Sertraline; Treatment Outcome
PubMed: 37557058
DOI: 10.1016/j.psychres.2023.115391 -
Biomedical Physics & Engineering Express Aug 2023. EDBreast gel is an alternative Fricke gel dosimeter, read by Magnetic Resonance Imaging, in which sucrose is added to lower diffusion effects. This paper aims at...
. EDBreast gel is an alternative Fricke gel dosimeter, read by Magnetic Resonance Imaging, in which sucrose is added to lower diffusion effects. This paper aims at determining the dosimetric characteristics of this dosimeter.. The characterization has been performed in high energy photon beams. The dose-response of the gel has been evaluated as well as its detection limit, its fading effects, the reproducibility of its response and its stability over time. Its energy and dose-rate dependence has been investigated, and the overall dose uncertainty budget established. Once characterized, the dosimetry method has been applied to a simple reference irradiation case in a 6 MV photon beam, with the measurement of the lateral dose profile of a 2 × 2 cmfield. The results have been compared with microDiamond measurements.. In addition to its low diffusivity, the gel presents a high sensitivity, no dose-rate dependence consideringTPR20-10values ranging from 0.66 to 0.79 and an energy response comparable to ionization chambers. However, its non-linear dose-response induces a high uncertainty on the measured dose (8 % (k=1) at 20 Gy) and reproducibility issues. The profile measurements displayed discrepancies compared to the microDiamond due to diffusion effects. The appropriate spatial resolution was estimated using the diffusion coefficient.. EDBreast gel dosimeter presents interesting characteristics for applications in clinics, but the linearity of its dose-response should be improved to lower the uncertainties and to enhance the reproducibility.
Topics: Reproducibility of Results; Radiometry; Diffusion; Radiation Dosimeters; Uncertainty
PubMed: 37236157
DOI: 10.1088/2057-1976/acd942 -
Cancer Science Nov 2023Rectal cancer is a common malignancy that requires multidisciplinary treatment. By utilizing the dose-response relationship in rectal cancer radiotherapy, increasing the... (Review)
Review
Rectal cancer is a common malignancy that requires multidisciplinary treatment. By utilizing the dose-response relationship in rectal cancer radiotherapy, increasing the radiotherapy dose can improve clinical complete remission rates. High-dose rate endorectal brachytherapy (HDREBT) is a novel technique that delivers high doses of radiotherapy directly to the tumor via an endorectal applicator, sparing the adjacent normal tissues from excessive radiation exposure. HDREBT includes contact X-ray brachytherapy and high-dose-rate intracavitary brachytherapy. We introduce the latest developments in applicators and imaging techniques for HDREBT in rectal cancer and summarize the current evidence on the efficacy, safety, and feasibility of HDREBT as a neoadjuvant, definitive, or palliative treatment option for all stages of rectal cancer patients. We also discuss the potential advantages and challenges of HDREBT in achieving organ preservation and improving the quality of life of rectal cancer patients. HDREBT has shown promising results in achieving high complete response rates, enabling nonoperative management, improving organ preservation rates, and providing effective palliation in rectal cancer patients. More studies are needed to optimize its dose and fractionation schemes in different clinical scenarios.
Topics: Humans; Brachytherapy; Quality of Life; Radiotherapy Dosage; Rectal Neoplasms; Rectum
PubMed: 37702196
DOI: 10.1111/cas.15959 -
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 -
Radiation Protection Dosimetry Oct 2023In this study, in some neighborhoods in Kahramanmaraş province of Turkey, indoors and outdoors direct gamma dose rate measurements have been done. All of the gamma dose...
In this study, in some neighborhoods in Kahramanmaraş province of Turkey, indoors and outdoors direct gamma dose rate measurements have been done. All of the gamma dose rate measurements have been made at ground level and at the height of 1 m from the ground. The median values of the gamma dose rates on the ground and 1 m above the ground indoors are 70.34 ± 7.74 and 49.53 ± 5.39 nGy h-1, respectively. Outdoor measurements have been carried out on both soil and asphalt floors. The average values of gamma dose rate on the ground and at a height of 1 m outdoors (soil floor) are 68.16 ± 7.49 and 53.50 ± 5.88 nGy h-1, respectively. The mean values of gamma dose rate on the ground and 1 m above the ground outdoors (asphalt floor) are 61.63 ± 6.77 and 48.69 ± 5.35 nGy h-1, respectively. Indoor and outdoor average gamma dose rates are below the mean world. In addition, using the measured gamma dose rate values, annual effective dose equivalent (AEDE) and excess lifetime cancer risk (ELCR) for adults have been calculated. The total AEDE and ELCR (on soil floors and indoors at 1 m above ground level) are 0.31 ± 0.03 mSv y-1 and 1.08 ± 0.10 × 10-3, respectively. The total AEDE and ELCR (on asphalt floors and indoors at 1 m above ground level) are 0.30 ± 0.03 mSv y-1 and 1.06 ± 0.10 × 10-3, respectively. The AEDE and ELCR for adults living in the neighborhoods within the scope of the study in Kahramanmaraş city center within 1 y are lower than the average world.
PubMed: 37587689
DOI: 10.1093/rpd/ncad223