ABSTRACT
Objective To systematically evaluate the efficacy and safety of high-dose dual therapy(HDDT)versus quadruple ther-apy(QT)for the first-line helicobacter pylori(Hp)infection.Methods The randomized controlled trial(RCT)about HDDT versus QT for the first-line treatment of Hp infection were searched from CNKI,VIP,Wanfang,CBM,PubMed,Embase,Cochrane Library and other databases from the establishment of databases to 3 July 2022.RevMan 5.4 and Stata 17.0software were used for Meta-analysis.Results A total of 1l studies with 4015 patients were included.The results of Meta-analysis showed that:the eradication rate of HDDT was statistically superior to that of QT(RR=1.04,95%CI:1.01-1.06,P<0.01)in the intention-to-treat analysis;the eradica-tion rate of the two groups was not statistically significant(RR=1.02,95%CI:1.00-1.04,P=0.08)in the coincidence protocol a-nalysis.HDDT had a significantly lower rate of adverse reactions than QT(RR=0.47,95%CI:0.36-0.61,P<0.01);but HDDT and QT both had achieved a similar eradication rate(RR=1.01,95%CI:1.00-1.02,P=0.06)in the per-protocol analysis.Conclusion The efficacy of HDDT in eradicating Hp infection for the first time is better than that of QT,and the safety is better,so it can be used as a first-line treatment in clinic.
ABSTRACT
OBJECTIVE To explore the effects of 5,10-methylenetetetrahydrofolate reductase (MTHFR) gene polymorphism on the adverse reactions in patients with osteosarcoma after the first high-dose methotrexate (HD-MTX) treatment. METHODS A prospective study was conducted to include 53 patients with osteosarcoma treated with HD-MTX at the first admission in General Hospital of Eastern Theater Command. The dose of MTX was evaluated according to the polymorphism of rs1801133 in the METHFR gene and demographic factors, then whole pharmaceutical monitoring was conducted. The data on liver toxicity, renal toxicity, hematological toxicity, and gastrointestinal reaction were collected after the first chemotherapy cycle. Single factor analysis and binary Logistic regression analysis were used to analyze the correlation between MTX dose, 24 h blood drug concentration, and rs1801133 locus genotype with four adverse reactions. RESULTS The MTX dosage in patients with CC wild type was significantly higher than that in TT mutant type (7.97 g/m2 vs. 6.98 g/m2, P=0.030), but this difference did not affect the 0 h and 24 h blood drug concentrations of MTX. The above four adverse reactions were not related to the dose of MTX. The results of binary Logistic regression analysis showed that carrying one T allele increased the risk of developing hematological toxicity by 4.13 times(95% confidence interval:1.35-12.62,P=0.013). When 24 h plasma concentration threshold of MTX was set to 2.65 µmol/L, the sensitivity and specificity of predicting liver function damage were 53.33% and 86.96%, respectively; when the threshold was set to 7.28 μmol/L, the sensitivity and specificity of predicting renal damage were 100% and 81.63%. CONCLUSIONS The polymorphism of the rs1801133 in the MTHFR gene is associated with hematological toxicity of MTX. Patients who take HD-MTX for the first time and carry the T allele have a high risk of hematological toxicity. The 24 h plasma concentration of MTX is related to liver toxicity and renal toxicity. In addition, monitoring the 24 h blood drug concentration can predict liver and renal toxicity, and take early intervention.
ABSTRACT
At present,precise radiotherapy has been widely used through the development with many years,but the existing technique still is limited by the limitation of tolerance dose of normal tissues,which cannot achieve the optimal goal of treating tumor.Flash radiotherapy(Flash-RT)is one kind of radiotherapy technique that uses the beam with ultra-high dose rate(UHDR)to conduct irradiation,which can furthest treat tumors while significantly reduce radiation injury of normal tissues.But until now,the biological mechanism,key physical parameters and triggering mechanism of Flash-RT are still unclear,and its principle and clinical translational application are still in the stage of research.This review clarified the technological advance and clinical translational application of Flash-RT research through summarized the relevant research of Flash-RT.
ABSTRACT
The Flash radiotherapy(Flash-RT),which is the key breakthrough in the basic field of radiotherapy technique,which is expected to cause a new major transformation in the field of radiotherapy.In this paper,we reviewed the latest research advances of the application and the mechanism exploration of Flash-RT in tumor treatment.Current studies have found that both the Flash-RT with electron beams and photon and the Flash-RT with proton can reduce injury of normal tissue than radiotherapy with conventional dose-rate,but the relevant mechanisms are not yet clearly understood,which includes but not limited to oxygen depletion,DNA damage,cellular senescence,apoptosis and immune response.The difference of Flash-RT injury between tumor tissue and normal tissue further reduces the limitations of radiotherapy,and reduces the adverse reaction and complication compared with conventional radiotherapy,which has wide application prospects.
ABSTRACT
Radiotherapy is an important means to treat lung cancer,but it is easy to cause lung injury and reduce the quality of life of patients.Flash radiotherapy(FLASH-RT)has attracted attention due to its extremely short radiation duration and high dose rate,which can reduce toxicity of normal tissue while ensures treatment intensity of tumor.Whether Flash-RT can reduce radiation-induced lung injury has become an important research topic in recent years.Based on the literature analysis method,this review systematically assessed the effects and mechanisms of Flash-RT and radiotherapy with conventional dose rate on lung injury through searching relevant literatures at home and abroad,so as to provide scientific basis for the treatment of patients with lung cancer by reviewing the comparisons about the effects and mechanisms between Flash-RT and radiotherapy with conventional dose rate on lung injury.Compared with radiotherapy with conventional radiation rate,Flash-RT can significantly reduce lung injury and improve quality of life of patients.It is still demanded to explore the Flash-RT mechanism in future,so as to develop the Flash-RT instrument that is suitable for different tumors and to conduct larger-scale clinical researches.
ABSTRACT
Objective:To study and design one kind of flash radiotherapy(Flash-RT)equipment with ultra-high dose rate,which can be used in the mechanism research of Flash-RT with ultra-high dose rate.Methods:Based on the technique roadmap of high-power petal accelerator,the Flash-RT equipment can realize the requirement of Flash-RT for ultra-high dose rate and multiple irradiation angles.The corresponding design and research work were carried out on the basis of the overall design of the equipment,the main components and characteristics,the dynamics design of beam,the construction of movable and preliminary experimental platform,etc.Result:The dose rate of the designed equipment can reach to 100 Gy/s at a distance of 0.8 meters from the target point,which is easy to realize the radiotherapy method with multi angles.Conclusion:The designed X-ray equipment based on the technique roadmap of high-power petal accelerator can realize the research for the mechanism of medical Flash-RT equipment with ultra-high dose rate.
ABSTRACT
Objective:To conduct a comparative analysis of the radiation damage to zebrafish embryos and the associated biological mechanism after ultra-high dose rate (FLASH) and conventional dose rate irradiation.Methods:Zebrafish embryos at 4 h post-fertilization were exposed to conventional and FLASH irradiation (9 MeV electron beam). The mortality and hatchability of zebrafish after radiation exposure were recorded. Larvae at 96 h post-irradiation underwent morphological scoring, testing of reactive oxygen species (ROS) levels, and analysis of changes in oxidative stress indicators.Results:Electron beam irradiation at doses of 2-12 Gy exerted subtle effects on the mortality and hatchability of zebrafish embryos. However, single high-dose irradiation (≥ 6 Gy) could lead to developmental malformation of larvae, with conventional irradiation showing the most significant effects ( t = 0.87-9.75, P < 0.05). In contrast, after FLASH irradiation (≥ 6 Gy), the ROS levels in zebrafish and its oxidative stress indicators including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were significantly reduced ( t = 0.42-15.19, P < 0.05). There was no statistically significant difference in ROS levels in incubating solutions after conventional and FLASH irradiation ( P > 0.05). Conclusions:Compared to conventional irradiation, FLASH irradiation can reduce radiation damage to zebrafish embryos, and this is in a dose-dependent manner. The two irradiation modes lead to different oxidative stress levels in zebrafish, which might be a significant factor in the reduction of radiation damage with FLASH irradiation.
ABSTRACT
Objective:To investigate whether ultra-high dose rate (FLASH) irradiation can reduce radiation-induced intestinal injuries of mice compared to conventional dose rate (CONV) irradiation.Methods:Both FLASH and CONV irradiation were delivered with electron beam, with dose rates of 750 Gy/s and 0.5G y/s, respectively. A total of 105 mice were randomly divided into groups using a simple randomization method. Twenty-one mice were selected for weight observation, 7 mice in each group. After 9 Gy FLASH and CONV irradiation on the abdomen, the weight changes of mice were measured every other day, and compared among three groups. Twenty-four mice were selected for pathological examination including 5 mice in the control group. Three-and-a-half-day days after 12 Gy FLASH ( n=10) and CONV irradiation ( n=9) on the abdomen, the intestines of the mice were taken. Pathological sections were stained with hematoxylin-eosin (HE) to compare the number and percentage of regenerated crypts of the small intestine between two groups. After 12 Gy FLASH ( n=10) and CONV irradiation ( n=10) on the abdomen, the survival of 20 mice was observed. After FLASH using 4.5 Gy×2 times ( n=10) and CONV irradiation at 9 Gy×1 time ( n=10) on the abdomen, the weight changes were observed. After FLASH using 6 Gy×2 times ( n=10) and CONV irradiation at 12 Gy×1 time ( n=10) on the abdomen, the survival of mice was observed. The time interval between two irradiation was 1 min. EBT3 film was employed to monitor the actual exposure dose of the mice. The variables conforming to normal distribution were expressed by Mean±SD. Inter group comparison was performed by independent t-test. The survival of mice among different groups was compared by log-rank test. Results:After 9 Gy of abdominal irradiation, the mean weight of mice in the FLASH group was significantly higher than that in the CONV group. The weight of mice in the FLASH and CONV groups was (19.8±0.8) g and (18.0±1.8)g ( P=0.036) at 7 days after irradiation, (22.0±1.0)g and (21.2±0.5)g ( P=0.075) at 15 days after irradiation, and (24.2±1.4)g and (22.0±1.2)g ( P=0.012) at 25 days after irradiation, respectively. After 12 Gy irradiation, the mean survival of mice in FLASH and CONV groups was 4 days and 4.7 days ( P=0.029). After 12 Gy total abdominal irradiation, the mean number of intestinal regenerative crypts in the FLASH and CONV groups was 2.9/mm and 1.2/mm ( P=0.041), and the percentage of intestinal regenerative crypts was 34.1% and 14.1%, respectively. The survival of mice irradiated by FLASH using 6 Gy×2 times was longer compared with that of mice after CONV irradiation at 12 Gy×1 time. The weight of mice after 4.5 Gy×2 times irradiation was higher than that of mice after CONV irradiation at 9 Gy×1 time. Conclusion:Weight, survival and the number of intestinal regenerative crypts in the FLASH group are higher than those in the CONV group after irradiation, indicating that radiation-induced intestinal injury caused by FLASH irradiation is slighter than that of CONV irradiation.
ABSTRACT
Objective:To compare the effects on DNA strand break induced by ultra-high dose rate (FLASH) electron beam and conventional irradiation, and investigate whether FLASH effect was correlated with a reduction of radiation response.Methods:Aqueous pBR322 plasmid was treated with FLASH (125 Gy/s) and conventional irradiation (0.05 Gy/s) under physioxia (4% O 2) and normoxia (21% O 2). Open circle DNA and linear DNA were detected by agarose gel electrophoresis, and the plasmid DNA damage was quantified with an established mathematical model to calculate the relative biological effect (RBE) of DNA damage. In some experiments, Samwirin A (SW) was applied to scavenge free radicals generated by ionizing radiation. Results:Under physioxia, the yields of DNA strand breakage induced by both FLASH and conventional irradiation had a dose-dependent manner. FLASH irradiation could significantly decrease radiation-induced linear DNA compared with conventional irradiation ( t=5.28, 5.79, 7.01, 7.66, P<0.05). However, when the aqueous plasmid was pretreated with SW, there was no difference of DNA strand breakage between FLASH and conventional irradiation ( P>0.05). Both of the yields of open circle DNA and linear DNA had no difference caused by FLASH and conventional radiotherapy at normoxia, but were significantly higher than those under physioxia. In addition, the yields of linear DNA and open circle DNA induced by FLASH irradiation per Gy were (2.78±0.03) and (1.85±0.17) times higher than those of conventional irradiation, respectively. Conclusions:FLASH irradiation attenuated radiation-induced DNA damage since a low production yield of free radical in comparison with conventional irradiation, and hence the FLASH effect was correlated with oxygen content.
ABSTRACT
Objective:To study the effects of FLASH irradiation (FLASH-RT) and conventional irradiation (CONV-RT) on gene expression profile in mouse liver, in order to provide theoretical basis of the potential mechanism of FLASH-RT.Methods:A total of 11 C57BL/6J male mice were divided into healthy control group (Ctrl group), CONV-RT group and FLASH-RT group according to random number table method. Mouse abdomen was treated with 12 Gy CONV-RT or FLASH-RT. Then the mice were killed by neck removal, and the liver tissues were collected to extract total RNA for transcriptome sequencing (RNA-Seq) that was then analyzed by bio-informatics analysis to investigate the changes of gene expression profiles. The mRNA expression levels of Stat1, Irf9 and Rela were verified by quantitative real-time PCR assay.Results:1 762 differentially expressed genes (DEGs) were identified in group FLASH-RT vs. CONV-RT. Among them, 660 genes were up-regulated and 1 102 genes were down-regulated. 1 918 DEGs were identified in groups FLASH-RT vs. Ctrl. Among them, 728 genes were up-regulated and 1 190 genes were down-regulated. 1 569 DEGs were identified in group CONV-RT vs. Ctrl. Among them, 1 046 genes were up-regulated and 523 genes were down-regulated. According to Gene Ontology (GO) analysis, these DEGs from groups FLASH-RT vs. CONV-RT were involved in various functions including defense response to virus, other organisms in cell components, adenylyltransferase activity in molecular function activity. These DEGs from group FLASH-RT vs. Ctrl were involved in various functions including defense response to other oranisms, endoplasmic reticulum chaperone complex, double-stranded RNA binding and so on. These DEGs from group FLASH-RT vs. CONV-RT were involved in several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including influenza A, Herpes simplex infection and so on. These DEGs from group FLASH-RT vs. Ctrl were involved in several KEGG pathways including influenza A, NOD-like receptor signaling pathway. Stat1 was likely to be activated by FLASH radiation. The quantitative real-time PCR assay showed that FLASH-RT obviously increased the mRNA expressions of Stat1, Irf9 and Rela ( t=6.62, 2.11, 1.67, P<0.05). Conclusions:FLASH-RT and CONV-RT could alter gene expression profiles in mouse liver tissues, and these DEGs are involved in multiple radiobiological functional pathways. In comparison with CONV-RT, FLASH-RT induces a low level of liver injury, which may due to hypoxia radiation resistance.
ABSTRACT
Objective:To evaluate the usability of Gafchromic HD-V2 film for dose dosimetry in the ultra-high dose-rate (UD) electron beam from a modified medical linac, and to investigate the response between the energy and dose-rate dependence to the film.Methods:The HD-V2 film was utilized to measure the average dose-rate of the UD electron beam. The measured result was compared with those by advanced Markus chamber and alanine pellets. And characteristics of the UD electron beam were also measured by HD-V2 film. Energy dependence of HD-V2 film at three beam energies (6 MV X-ray, 9 MeV and 16 MeV electron beam) was investigated by obtaining and comparing the calibration curves based on the clinical linear accelerator in the dose range of 10-300 Gy. The dose-rate dependence of HD-V2 film was also studied by varying the dose rate among 0.03 Gy/s, 0.06 Gy/s and 0.1 Gy/s, and range of 100-200 Gy/s.Results:The measured average maximum dose-rate of 9 MeV UD electron beam at source skin distance (SSD) 100 cm was approximately 121 Gy/s using HD-V2 film, consistent with the results by advanced Markus chamber and alanine pellets. The measured percentage depth dose (PDD) curve parameters of the UD electron beam were similar to the conventional 9 MeV beam. The off-axis dose distribution of the UD electron beam showed the highest central axis, and the dose was gradually decreased with the increase of off-axis distance. The energy dependence of HD-V2 film had no dependency of 6 MV and 9, 16 MeV while measuring the dose in the range from 20 to 300 Gy. The HD-V2 film had no significant dose-rate dependency at the dose rate of 0.03 Gy/s, 0.06 Gy/s and 0.1 Gy/s for the clinical linear accelerator. Likewise, there was also no dose-rate dependence in the range 100-200 Gy/s in the modified machine.Conclusion:HD-V2 film is suitable for measuring ultra-high dose rate electron beam, independent of energy and dose rate.
ABSTRACT
In recent years, ultra-high dose rate (FLASH) radiotherapy has become one of the most advanced research topics in the field of radiotherapy. Experimental data indicate that FLASH radiotherapy can significantly reduce the irradiation damage in normal tissues while being as effective as clinical conventional dose rate radiotherapy in tumor control. The oxygen depletion hypothesis is considered as one of the key mechanisms underlying the FLASH effect. In this article, research progress on the discovery, experimental evidence and reaction principle of oxygen depletion was reviewed, the measurement methods and biological effect modeling methods of the oxygen depletion hypothesis were summarized, and the oxygen depletion difference between normal tissue and tumor was also discussed.
ABSTRACT
Objective:To conduct a meta-analysis to analyze the efficacy and adverse reactions of fractionated high dose rate brachytherapy (HDR-BT) as monotherapy for localized prostate cancer.Methods:Relevant databases were searched to collect the clinical trials on HDR-BT as monotherapy in patients with localized prostate cancer. Included studies were limited to full-text publications of fractionated HDR-BT as monotherapy with a median follow-up of at least 5 years, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis.Results:According to the inclusion and exclusion criteria, a total of 11 clinical trials involving 2 683 patients with prostate cancer were included in this meta-analysis. The results of the meta-analysis showed that 5-year biochemical recurrence-free survival (bRFS) rate and overall survival (OS) rate were 94% (95% CI: 93% - 96%) and 96% (95% CI: 94% - 98%), respectively. Long-term (≥5 years) cancer-specific survival (CSS) rate and distant metastasis-free survival (DMFS) rate were 99% (95% CI: 98% - 100%) and 98% (95% CI: 98% - 99%), respectively. Long-term (≥5 years) late grade ≥3 grade gastrointestinal and genitourinary adverse reactions rates were 2% (95% CI: 1% - 3%) and 9% (95% CI: 6% - 13%), respectively. Conclusions:Fractionated HDR-BT as monotherapy is an effective treatment for patients with localized prostate cancer. Its long-term efficacy is encouraging, and the treatment is well tolerated and safe.
ABSTRACT
OBJECTIVE To discuss the factors affecting the blood concentration of high-dose methotrexate (HD-MTX) and the occurrence of adverse drug reactions (ADR) when treating lymphoma with HD-MTX. METHODS From July 2020 to November 2021, the information of HD-MTX patients who had been monitored for HD-MTX blood drug concentration in the First Affiliated Hospital of Guangdong Pharmaceutical University was collected by retrospective analysis, such as medical record number, age, sex, height, body mass, chemotherapy plan, dosage; test indexes such as alanine transaminase, aspartate transaminase, total bilirubin, creatinine clearance (CrCl), albumin (ALB) and other indexes were also collected before and after administration. The blood concentrations (c6 h, c24 h, c48 h) of HD-MTX were recorded, drug information of proton pump inhibitors (PPIs) was extracted and used, and ADR occurring within 48 h after administration were all evaluated. Single factor analysis, multiple linear regression and χ2 test were used to analyze the influential factors. RESULTS A total of 133 patients were included in this paper. The results of the single factor analysis of HD-MTX blood drug concentration showed that age, CrCl had an effect on c 6 h (P<0.05); age, CrCl and ALB had an effect on c24 h (P<0.05); age, body mass index (BMI), CrCl, combined use of PPIs and ALB had an effect on c48 h (P<0.05). The results of multiple linear regression analysis showed that age and CrCl had no effect on c 6 h (P>0.05), age was the main influential factor of c 24 h (P<0.05), and CrCl and combined use of PPIs were the main influential factors of c48 h (P<0.05); the coefficient of variance expansion was between 1 and 3.5, indicating that the analysis results were acceptable. The overall incidence of adverse reactions was 51.13%, of which the blood and lymphatic system reactions were the most common. The results of the influential factors of ADR showed that age, BMI, liver function and CrCl had effect on the incidence of ADR (P<0.05). CONCLUSIONS During the process of HD-MTX in the treatment of lymphoma, the patient’s age, CrCl and combined use of PPIs should be considered, and the patient’s blood concentration should be monitored; at the same time, the age of patients, BMI, liver function and CrCl have an impact on the incidence of ADR.
ABSTRACT
Man in his 70s, who had suffered from idiopathic thrombocytopenic purpura (ITP), was admitted to our hospital with chest pain at rest. Coronary angiography revealed obstruction of the right coronary artery and triple vessel disease. Because a bleeding tendency was expected during coronary artery bypass grafting, we performed percutaneous coronary intervention to the culprit lesion first, and then intravenous immunoglobulin and high dose dexamethasone were tried. His platelet count rose from 49,000 to 103,000/mm3, so we performed coronary artery bypass grafting. The patient had no postoperative hemorrhagic complications. We believe that high dose dexamethasone therapy is useful for patients with ITP who need surgery immediately.
ABSTRACT
Objective:To investigate the effects of ultra-high dose rate radiation (FLASH-RT) and conventional radiation (CONV-RT) on plasma metabolites in glioma mice.Methods:Tocally 21 male C57BL/6J mice bearing intracranial glioma xenograft were randomly divided into healthy control group ( n=3), CONV-RT group ( n=9) and FLASH-RT group ( n=9). The CONV-RT group was administered a single dose of 24 Gy radiation on the head of mice at a dose rate of 0.4 Gy/s, and the FLASH-RT group was administered a single dose of 24 Gy radiation on the head of mice at a dose rate of 60 Gy/s, and the healthy control group was given 0 Gy pseudoradiation under the same condition. Mice blood was collected through the inner canthus vein for plasma separation at 1, 3 and 7 d after radiation in the two radiation groups, and the blood plasma of healthy control group was collected at 7 days after sham radiation. The changes in plasma metabolites were detected by the non-targeted metabolomics based on liquid chromatography mass spectrometry tandem platform. Results:After irradiation, the metabolites in plasma of two irradiation groups had significant difference. Compared with the healthy control group, 12 and 5 differential metabolites were screened out in the FLASH-RT group and CONV-RT group at three time points, respectively. The difference of plasma metabolites had the largest value at 1 day and decreased at 3 and 7 d after radiation. The arachidonic acid and isovaleric acid, involving arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, and tyrosine metabolism pathways were screened in both FLASH-RT group and CONV-RT group, and the 10 differential metabolites, mainly involving energy metabolism and redox reactions, only existed in the FLASH-RT group.Conclusions:Arachidonic acid and isovaleric acid may be the common sensitive biomarkers to different radiation patterns, which provides ideas for further exploring the molecular mechanism of FLASH-RT in the treatment of glioma.
ABSTRACT
Objective:To compare the radiation chemistry effects on water molecules after ultra-high dose rate (FLASH) and conventional irradiation.Methods:Both FLASH and conventional irradiation were applied to ultrapure water, with the hydroxyl radical yield in the homogeneous phase detected using electron paramagnetic resonance (EPR) and the hydrogen peroxide (H 2O 2) yield in the diffusion phase analyzed uuxing fluorescence probe. The liposome model was then established to investigate the radiation chemistry effect of FLASH and conventional irradiation in inducing lipid peroxidation. Results:Radiation chemistry reactions were observed in water molecules after irradiation. In the homogeneous phase, the yield of free radicals using FLASH irradiation is similar to those from conventional irradiation ( P>0.05). In the diffusion phase, the amount of H 2O 2 produced by FLASH irradiation was significantly lower than those from conventional irradiation ( t=0.49-12.81, P<0.05). The liposome model confirmed that conventional irradiation could significantly induce lipid peroxidation through the radiation chemistry effect in water molecules as compared with FLASH irradiation ( t=0.31-11.73, P<0.05). Conclusions:The radiation chemistry effect in water molecules after FLASH irradiation was significantly lower than that from conventional irradiation. This could be one of the mechanisms of FLASH effect.
ABSTRACT
Objective:To compare the efficacy and safety of high- and standard-dose radiotherapy (HD-RT vs. SD-RT) during definitive concurrent chemoradiotherapy (dCCRT) for esophageal cancer (EC), aiming to assess the advantages and disadvantages of these two radiotherapy doses when using modern radiotherapy techniques. Methods:Literature review was conducted from PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang database, and abstracts of the American Society of Radiation Oncology (ASTRO) and the European Society of Radiotherapy and Oncology (ESTRO). Randomized controlled trials (RCT) comparing high-dose radiotherapy (HD-RT: ≥59.4 Gy,1.8 Gy per time) with standard-dose radiotherapy (SD-RT: 50 Gy, 2 Gy per time, or 50.4 Gy, 1.8 Gy per time) during dCCRT for EC were included. The retrieval time was from the establishment of the database to January 1, 2023. The meta-analysis was performed using Stata 16.0 software.Results:A total of 1 158 patients from 5 RCT that meet the inclusion criteria were finally included. In 4 RCT, subgroup analysis of 940 patients using modern radiotherapy techniques were performed. Patients in the HD-RT and SD-RT groups had similar 1-, 2-, and 3-year overall survival (OS)( RR=1.03, 95% CI=0.86-1.22, P=0.757; RR=1.05, 95% CI=0.94-1.17, P=0.433; RR=1.05, 95% CI=0.96-1.14, P=0.314; respectively) and 2- and 3-year locoregional progression-free survival (LRPFS) ( RR=0.94, 95% CI=0.82-1.08, P=0.390; RR=0.96, 95% CI=0.86-1.09, P=0.560; respectively). Patients in the HD-RT group had a higher incidence of grade ≥ 3 treatment-related adverse reactions rates ( OR=1.35, 95% CI=1.03-1.77, P=0.029) and treatment-related death rates ( OR=1.66, 95% CI=0.97-2.83, P=0.062) compared with their counterparts in the SD-RT group. In the subgroup analysis using modern radiotherapy techniques, HD-RT did not improve LRPFS compared to SD-RT, but increased the incidence of adverse reactions, and yielded no OS benefit. Conclusions:Whether modern precision radiation therapy is employed or not, SD-RT yields similar LRPFS and OS, and lower grade ≥ 3 treatment-related adverse reactions rates compared with HD-RT. Therefore, standard-dose (50 Gy, 2 Gy per time, or 50.4 Gy, 1.8 Gy per time) should be considered as the recommended dose in dCCRT for EC. Further RCT are needed to verify our conclusions.
ABSTRACT
@#AIM:To study the effect of vitamin E on the injury of human retinal pigment epithelial(hRPE)cells induced by high-dose blue light, and provide experimental evidence for intercepting blue light damaged hRPE cells. <p>METHODS: The hRPE cell injury model was established with 3000±150Lx blue light. The apoptosis rate and reactive oxygen species(ROS)of the six groups of hRPE cells were detected by flow cytometry at 0, 3, 6, 9, 12 and 24h respectively. Apoptosis and ROS in hRPE cells were detected by cytometry in 0h-irradiation group, 6h-irradiation group, and vitamin E added groups(vitamin E concentration 10, 50, 100μmol/L)before or after 6h-irradiation. The fluorescence intensity of hRPE cells was observed under a fluorescence microscope using Hoechst 33258 staining reagent.<p>RESULTS: Compared with the 0h-irradiation group, the relative amount of reactive oxygen species increased significantly in 3, 6, 9, 12 and 24h groups(all <i>P</i><0.01), the apoptosis rate of hRPE cells increased significantly in 6, 9, 12 and 24h groups(all <i>P</i><0.01), the apoptosis rate of the 3h-irradiation group was not statistically significantly increased(<i>P</i>=0.46). Compared with the 6h-irradiation group, the relative amounts of ROS and apoptotic rate of the six groups of hRPE cells added vitamin E were significantly decreased, and the blue fluorescence of Hoechst 33258 released in the cells gradually decreased, which was concentration dependent(all <i>P</i><0.01),except for apoptosis rate of hRPE cells in the 10 μmol/L vitamin E group before irradiation(<i>P</i>=0.66). Compared with the 0h-irradiation group, the difference in the relative amount of ROS and apoptosis rate of hRPE cells in added groups were statistically significant(all <i>P</i><0.01). At the same concentration of vitamin E, the relative amount of ROS and apoptosis rate of hRPE cells added vitamin E after irradiation were significantly lower than those added vitamin E before irradiation(all <i>P</i><0.01), except for apoptosis rate of hRPE cells in the 10 μmol/L vitamin E group, which had no difference between added before and after irradiation(<i>P</i>=0.08).<p>CONCLUSION: After hRPE cells had been irradiated by blue light, the increase in the relative amount of intracellular ROS was earlier than that of apoptosis. Elimination of intracellular ROS is the idea of intercepting high doses of blue light induced hRPE cell injury. Vitamin E protects RPE cell against damage induced by high doses of blue light, and the effect becomes stronger as the concentration of vitamin E increases, which is better when added after irradiating. However, it doesn't take effect until the concentration reaches a certain level. And the damage can't be completely repaired.