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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 -
Radiological Physics and Technology Mar 2024FLASH radiotherapy (FLASH-RT) has great potential to improve patient outcomes. It delivers radiation doses at an ultra-high dose rate (UHDR: ≥ 40 Gy/s) in a... (Review)
Review
FLASH radiotherapy (FLASH-RT) has great potential to improve patient outcomes. It delivers radiation doses at an ultra-high dose rate (UHDR: ≥ 40 Gy/s) in a single instant or a few pulses. Much higher irradiation doses can be administered to tumors with FLASH-RT than with conventional dose rate (0.01-0.40 Gy/s) radiotherapy. UHDR irradiation can suppress toxicity in normal tissues while sustaining antitumor efficiency, which is referred to as the FLASH effect. However, the mechanisms underlying the effects of the FLASH remain unclear. To clarify these mechanisms, the development of simulation models that can contribute to treatment planning for FLASH-RT is still underway. Previous studies indicated that transient oxygen depletion or augmented reactions between secondary reactive species produced by irradiation may be involved in this process. To discuss the possible mechanisms of the FLASH effect and its clinical potential, we summarized the physicochemical, chemical, and biological perspectives as well as the development of simulation modeling for FLASH-RT.
Topics: Humans; Computer Simulation; Radiotherapy Dosage; Radiotherapy
PubMed: 38184508
DOI: 10.1007/s12194-023-00770-x -
International Journal of Radiation... May 2024Preclinical studies have shown a preferential normal tissue sparing effect of FLASH radiation therapy with ultra-high dose rates. The aim of the present study was to use...
PURPOSE
Preclinical studies have shown a preferential normal tissue sparing effect of FLASH radiation therapy with ultra-high dose rates. The aim of the present study was to use a murine model of acute skin toxicity to investigate the biologic effect of varying dose rates, time structure, and introducing pauses in the dose delivery.
METHODS AND MATERIALS
The right hind limbs of nonanaesthetized mice were irradiated in the entrance plateau of a pencil beam scanning proton beam with 39.3 Gy. Experiment 1 was with varying field dose rates (0.7-80 Gy/s) without repainting, experiment 2 was with varying field dose rates (0.37-80 Gy/s) with repainting, and in experiment 3, the dose was split into 2, 3, 4, or 6 identical deliveries with 2-minute pauses. In total, 320 mice were included, with 6 to 25 mice per group. The endpoints were skin toxicity of different levels up to 25 days after irradiation.
RESULTS
The dose rate, which is the dose rate to induce a response in 50% of the animals, depended on the level of skin toxicity, with the higher toxicity levels displaying a FLASH effect at 0.7-2 Gy/s. Repainting resulted in higher toxicity for the same field dose rate. Splitting the dose into 2 deliveries reduced the FLASH effect, and for 3 or more deliveries, the FLASH effect was almost abolished for lower grades of toxicity.
CONCLUSIONS
The dose rate that induced a FLASH effect varied for different skin toxicity levels, which are characterized by a differing degree of sensitivity to radiation dosage. Conclusions on a threshold for the dose rate needed to obtain a FLASH effect can therefore be influenced by the dose sensitivity of the used endpoint. Splitting the total dose into more deliveries compromised the FLASH effect. This can have an impact for fractionation as well as for regions where 2 or more FLASH fields overlap within the same treatment session.
PubMed: 38750904
DOI: 10.1016/j.ijrobp.2024.04.071 -
Physics in Medicine and Biology Jul 2023FLASH radiation therapy with ultrahigh dose rates (UHDR) has the potential to reduce damage to normal tissue while maintaining anti-tumor efficacy. However, rapid and...
FLASH radiation therapy with ultrahigh dose rates (UHDR) has the potential to reduce damage to normal tissue while maintaining anti-tumor efficacy. However, rapid and precise dose distribution measurements remain difficult for FLASH radiation therapy with proton beams. To solve this problem, we performed luminescence imaging of water following irradiation by a UHDR proton beam captured using a charge-coupled device camera.. We used 60 MeV proton beams with dose rates of 0.03-837 Gy sfrom a cyclotron. Therapeutic 139.3 MeV proton beams with dose rates of 0.45-4320 Gy sdelivered by a synchrotron-based proton therapy system were also tested. The luminescent light intensity induced by the UHDR beams was compared with that produced by conventional beams to compare the dose rate dependency of the light intensity and its profile.. Luminescence images of water were clearly visualized under UHDR conditions, with significantly shorter exposure times than those with conventional beams. The light intensity was linearly proportional to the delivered dose, which is similar to that of conventional beams. No significant dose-rate dependency was observed for 0.03-837 Gy s. The light-intensity profiles of the UHDR beams agreed with those of conventional beams. The results did not differ between accelerators (synchrotron or cyclotron) and beam energies.. Luminescence imaging of water is achievable with UHDR proton beams as well as with conventional beams. The proposed method should be suitable for rapid and easy quality assurance investigations for proton FLASH therapy, because it facilitates real-time, filmless measurements of dose distributions, and is useful for rapid feedback.
Topics: Humans; Protons; Luminescence; Water; Proton Therapy; Light; Radiotherapy Dosage; Radiation Injuries
PubMed: 37429310
DOI: 10.1088/1361-6560/ace60b -
Clinical Oncology (Royal College of... Jun 2024Interstitial high-dose-rate brachytherapy (HDR-BT) is an effective therapy modality for patients with localized prostate carcinoma. The objectives of the study were to...
AIMS
Interstitial high-dose-rate brachytherapy (HDR-BT) is an effective therapy modality for patients with localized prostate carcinoma. The objectives of the study were to optimise the therapy regime variables using two models: response surface methodology (RSM) and artificial neural network (ANN).
MATERIALS AND METHODS
Thirty-one studies with 5651 patients were included (2078 patients presented as low-risk, 3077 patients with intermediate-risk, and 496 patients with high-risk). A comparison of these therapy schedules was carried out using an effective biologically effective dose (BED) that was calculated assuming the number of treatment days and dose (D) per day. The modelling and optimization of therapy parameters (BED and risk level) in order to obtain the maximum biochemical free survival (BFS) were carried out by the RSM and ANN models.
RESULTS
An optimal treatment schedule (BFS = 97%) for patients presented with low-risk biochemical recurrence would be D = 26 Gy applied in one application, 2 fractions at least 6 h apart, within an overall treatment time of 1 day (BED = 251 Gy) by the RSM and ANN model. For patients presented with intermediate- or high-risk an optimal treatment regime (BFS = 94% and 90%, respectively) would be D = 38 Gy applied in one application, 4 fractions at least 6 h apart, with an overall treatment time of 2 days (BED = 279 Gy) by the RSM and ANN models.
CONCLUSIONS
The RSM and ANN models determine almost the same optimal values for the set of predicted therapy parameters that make a feasible selection of an optimal treatment regime.
Topics: Humans; Male; Brachytherapy; Prostatic Neoplasms; Radiotherapy Dosage; Algorithms; Neural Networks, Computer
PubMed: 38584072
DOI: 10.1016/j.clon.2024.03.009 -
Radiotherapy and Oncology : Journal of... Jul 2024
Topics: Humans; Radiation Protection; Radiotherapy Dosage; Patient Safety; Neoplasms; Radiotherapy
PubMed: 38648991
DOI: 10.1016/j.radonc.2024.110291 -
Cancers May 2024To explore the most suitable dosage regimen for limited-stage small cell lung cancer (LS-SCLC) and provide references for clinical selection, strict inclusion criteria... (Review)
Review
To explore the most suitable dosage regimen for limited-stage small cell lung cancer (LS-SCLC) and provide references for clinical selection, strict inclusion criteria were applied, and studies were screened from Pubmed, Embase, and Web of Science. Subsequently, data on two-year overall survival rates and dosage regimens were collected, and scatter plots were constructed to provide a comprehensive perspective. The survival benefits of various dosage regimens were evaluated, and a linear quadratic equation was utilized to fit the relationship between the biologically effective dose (BED10) and the two-year overall survival rate. Among the five randomized controlled trials, the two-year overall survival rate of ConvTRT regimens with BED10 > 60 Gy (rough value) was only at or below the median of all ConvTRT regimens or all included study regimens, indicating that increasing the number and total dose of ConvTRT does not necessarily lead to better prognosis. In the exploration of HypoTRT regimens, there was a linear positive correlation between BED10 and the two-year overall survival rate ( < 0.0001), while the exploration of HyperTRT regimens was relatively limited, with the majority focused on the 45 Gy/30 F regimen. However, the current 45 Gy/30 F regimen is not sufficient to control LS-SCLC, resulting in a high local recurrence rate. High-dose ConvTRT regimens have long treatment durations and may induce tumor regrowth which may cause reduced efficacy. Under reasonable toxicity reactions, HyperTRT or HypoTRT with higher radiotherapy doses is recommended for treating LS-SCLC.
PubMed: 38791986
DOI: 10.3390/cancers16101908 -
BMC Urology Mar 2024The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a meta-analysis to investigate the efficacy and safety of low-dose corticosteroids plus leflunomide for progressive IgA nephropathy.
METHODS
Eligible studies were obtained from PubMed, Embase, and Cochrane Library databases. We also searched the references of the included studies. Our protocol followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Eligibility criteria were defined using a PICOS framework.
RESULTS
Our study included three articles presenting 342 patient cases. Findings revealed that low-dose corticosteroids combined with the leflunomide group were effective in relieving urine protein excretion (UPE) [mean difference (MD) = -0.35, 95% confidence interval (CI): -0.41 to -0.30, P < 0.00001] compared with the full-dose corticosteroids group. Regarding serum creatinine (SCr), estimated glomerular filtration rate (eGFR), complete remission rate, and overall response rate, there was no difference between the groups (p > 0.05). Regarding safety, low-dose corticosteroids combined with leflunomide significantly reduced the risk of serious adverse events [odds ratio (OR): 0.11, 95% CI: 0.01 to 0.91, P = 0.04]. Besides, no significant differences were observed between the two groups in the incidence of respiratory infection, abnormal liver function, diarrhea, herpes zoster, alopecia, pruritus, insomnia, pneumonia, diabetes, and urinary tract infection (P > 0.05).
CONCLUSIONS
Low-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy.
TRIAL REGISTRATION
The PROSPERO registration number is CRD42022361883.
Topics: Humans; Leflunomide; Glomerulonephritis, IGA; Immunosuppressive Agents; Adrenal Cortex Hormones; Glomerular Filtration Rate
PubMed: 38468247
DOI: 10.1186/s12894-024-01438-3 -
International Journal of Radiation... Nov 2023To take full advantage of FLASH dose rate (40 Gy/s) and high-dose conformity, we introduce a novel optimization and delivery technique, the spot-scanning proton arc...
PURPOSE
To take full advantage of FLASH dose rate (40 Gy/s) and high-dose conformity, we introduce a novel optimization and delivery technique, the spot-scanning proton arc therapy (SPArc) + FLASH (SPLASH).
METHODS AND MATERIALS
SPLASH framework was implemented in an open-source proton planning platform (MatRad, Department of Medical Physics in Radiation Oncology, German Cancer Research Center). It optimizes with the clinical dose-volume constraint based on dose distribution and the dose-average dose rate by minimizing the monitor unit constraint on spot weight and accelerator beam current sequentially, enabling the first dynamic arc therapy with voxel-based FLASH dose rate. This new optimization framework minimizes the overall cost function value combined with plan quality and voxel-based dose-rate constraints. Three representative cases (brain, liver, and prostate cancer) were used for testing purposes. Dose-volume histogram, dose-rate-volume histogram, and dose-rate map were compared among intensity modulated proton radiation therapy (IMPT), SPArc, and SPLASH.
RESULTS
SPLASH/SPArc could offer superior plan quality over IMPT in terms of dose conformity. The dose-rate-volume histogram results indicated SPLASH could significantly improve V Gy/s in the target and region of interest for all tested cases compared with SPArc and IMPT. The optimal beam current per spot is simultaneously generated, which is within the existing proton machine specifications in the research version (<200 nA).
CONCLUSIONS
SPLASH offers the first voxel-based ultradose-rate and high-dose conformity treatment using proton beam therapy. Such a technique has the potential to fit the needs of a broad range of disease sites and simplify clinical workflow without applying a patient-specific ridge filter, which has never before been demonstrated.
Topics: Male; Humans; Proton Therapy; Protons; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Prostatic Neoplasms
PubMed: 37196836
DOI: 10.1016/j.ijrobp.2023.05.012 -
Physics in Medicine and Biology Sep 2023. Commercial electron FLASH platforms deliver ultra-high dose rate doses at discrete combinations of pulse parameters including pulse width (PW), pulse repetition...
. Commercial electron FLASH platforms deliver ultra-high dose rate doses at discrete combinations of pulse parameters including pulse width (PW), pulse repetition frequency (PRF) and number of pulses (), which dictate unique combinations of dose and dose rates. Additionally, collimation, source to surface distance, and airgaps also vary the dose per pulse (DPP). Currently, obtaining pulse parameters for the desired dose and dose rate is a cumbersome manual process involving creating, updating, and looking up values in large spreadsheets for every treatment configuration. This work presents a pulse parameter optimizer application to match intended dose and dose rate precisely and efficiently.. Dose and dose rate calculation methods have been described for a commercial electron FLASH platform. A constrained optimization for the dose and dose rate cost function was modelled as a mixed integer problem in MATLAB (The MathWorks Inc., Version9.13.0 R2022b, Natick, Massachusetts). The beam and machine data required for the application were acquired using GafChromic film and alternating current current transformers (ACCTs). Variables for optimization included DPP for every collimator, PW and PRF measured using ACCT and airgap factors.. Using PW, PRF,and airgap factors as parameters, a software was created to optimize dose and dose rate, reaching the closest match if exact dose and dose rates are not achievable. Optimization took 20 s or less to converge to results. This software was validated for accuracy of dose calculation and precision in matching prescribed dose and dose rate.. A pulse parameter optimization application was built for a commercial electron FLASH platform to increase efficiency in dose, dose rate, and pulse parameter prescription process. Automating this process reduces safety concerns associated with manual look up and calculation of these parameters, especially when many subjects at different doses and dose rates are to be safely managed.
Topics: Humans; Electrons; Electricity; Heart Rate; Software
PubMed: 37735967
DOI: 10.1088/1361-6560/acf63e