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.

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.

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.

Objective:To evaluate the dosimetric characteristics, safety and effectiveness of magnetic resonance-guided fractionated stereotactic radiotherapy (FSRT) for brain tumors.Methods:Clinical data of 8 brain tumor patients treated with magnetic resonance-guided FSRT in the Radiotherapy Department of the First Medical Center of the PLA General Hospital from July 2023 to February 2024 were retrospectively analyzed. Online adaptive radiotherapy was adopted for all patients. Adapt-to-position (ATP) or adapt-to-shape (ATS) radiotherapy was chosen by radiologists. Each adaptation was initiated after the radiotherapy plan was re-examined. The radiotherapy fractionation plan was 21-30 Gy/3-5 F. Clinical characteristics, radiotherapy plans and plan parameters were analyzed by statistical description. Median ( Q1， Q3) was used to describe continuous data and percentage was used to describe categorical data. Results:In this study, 9 lesions were treated a total of 41 times, including 20 times (49%) of ATP plan and 21 times (51%) of ATS plan. The median target area coverage rate was 95.1% (95%, 99.8%), the median target area maximum dose rate was 1.15 (1.07, 1.31), the median conformity index (CI) was 0.75 (0.69, 0.86), the median homogeneity index (HI) was 1.09 (1.06, 1.21), and the median gradient index (GI) was 4.73 (3.36, 8.45), respectively. After ATS plan, the median reduction in gross target volume (GTV) was 8.22 cm3 (1.2, 10.1 cm3), and the median reduction in brain tissue V12 Gy was 30.46 cm3 (8.34, 31.13 cm3).The median follow-up was 3.2 months (1.4, 6.1 months). No radiation necrosis was found in any patient. There were 2 cases of acute brain edema during radiotherapy (both were mild). Except for 1 case who died due to systemic disease progression, the remaining patients had no local recurrence, and achieved good quality of life. Conclusions:The parameters of the treatment plan of magnetic resonance-guided FSRT are generally acceptable. The adaptive plan can effectively reduce the dose of normal brain tissues. It is safe and feasible to use the magnetic resonance-guided FSRT for brain tumors.

Objective:To investigate the regulatory role of mesenchymal stem cells(MSCs)on radiation-induced lung injury in mice by the ferroptosis pathway.Methods:The mice were divided into normal control group,MSCs-treated group(MSCs group),single irradiation group(IR group)and IR combined with MSCs group(IR+MSCs group)according to random number table method before irradiation.A mouse model of radiation-induced lung injury was constructed using whole thorax irradiation with cobalt 60(60Co)(20Gy each time),and TNF-α and IL-6 levels of mouse were detected by enzyme-linked immunosorbent assay(ELISA).The injury of lung tissue in mice was assessed using hematoxylin eosin(HE)staining and Masson staining.Western Blot was used to examine the expression levels of ferroptosis-related proteins in lung tissue,including nuclear factor erythroid NF-E2 related factor 2(Nrf2),4-Hydroxynonenal(4-HNE)and glutathione peroxidase 4(GPX4).The expression level of prostaglandin-endoperoxide synthase 2 Gene(PTGS2)in the lung tissue of mice was detected by using quantitative polymerase chain reaction(qPCR),and the level of reactive oxygen species(ROS)in the lung tissue of mice was detected after radiation by using dihydroethidium(DHE),and the level of malondialdehyde(MDA)content in the lung tissue was detected after radiation.And then,the level of oxidative damage in the lung tissue of mice was assessed.Results:Elisa results showed the serum TNF-α and IL-6 levels in mice after irradiation in IR group were significantly higher than those in normal control group(F=53.60,10.65,P＜0.05),respectively.The HE and MSCs staining of pathological analysis showed that MSCs treatment could significantly relieve both early radiation-induced pneumonitis and advanced pulmonary fibrosis.After radiation,the 4-HNE expression level was upregulation and the Nrf2 expression level was downregulation in the lung tissues of mice,whereas MSCs were able to significantly reduce the 4-HNE expression and upregulate the Nrf2 expression.The mRNA expression level and MDA content of the ferroptosis gene PTGS2 were significantly increased,which were significantly higher than those of normal control group,while MSCs were able to significantly reduce its expression,and the differences were statistically significant(F=105.8,7.693,P＜0.05).Conclusion:MSCs is able to relieve significantly ionizing radiation-induced ferroptosis of lung epithelial cells,thereby relieve radiation-induced lung injury.

Objective:To evaluate the dosimetric characteristics of Zap-X system and CyberKnife (CK) G4 system of stereotactic radiosurgery (SRS) for single brain metastasis.Methods:Twelve patients with single brain metastasis had been treated with CK were selected retrospectively. The prescribed dose of planning target volume (PTV) was 18-24 Gy for 1-3 fractions. The PTV was ranged from 0.44 to 11.52 cm 3. The 12 patients were re-planned in the Zap-X planning system using the same prescription dose and organs at risk constraints, and the prescription dose of PTV was normalized to 70% for both Zap-X and CK. The planning parameters and dosimetric parameters of PTV and organs at risk were compared and evaluated between two plans. All data were read at MIM Maestro. A paired Wilcoxon' signed-rank test was adopted for statistical analysis. A P value of less than 0.05 was considered as statistical significance. Results:For the target coverage, CK was significantly higher than Zap-X (99.14±0.57% vs. 97.55±1.34%, P<0.01), but Zap-X showed a higher conformity index (0.81±0.05 vs. 0.77±0.07, P<0.05), a lower Paddick gradient index (2.98±0.24 vs. 3.15±0.38), and a higher gradient score index (GSI) than CK. The total monitor unit (MU) of Zap-X was significantly lower than that of CK (11 627.63 ±5 039.53 vs. 23 522.16 ±4 542.12, P<0.01) and the treatment time was shorter than that of CK [(25.08 ±6.52) vs. (38.08 ±4.74) min, P<0.01]. Zap-X had lower dose volumes than CK for the dose of brain ( P<0.05). Zap-X had a lower D mean and D max of brainstem (both P<0.05), but a higher value of eyes and lens. For optic nerves and optic chiasm, there were no significant differences between two groups. In addition, for the protection of skin (V 22.5 Gy), Zap-X seemed better than CK [(4.15±4.48) vs. (4.37±4.50) cm 3, P<0.05]. Conclusions:For SRS treating single brain metastasis, Zap-X could provide a high quality plan equivalent to or even better than CK, especially reducing the treatment time. With continuous improvement and upgrading of Zap-X system, it may become a new SRS platform for the treatment of brain metastasis.

Objective:To compare the dosimetric characteristics of beams between Zap-X and G4 CyberKnife and provide reference for clinical application of Zap-X.Methods:PTW three-dimensional water tank and dosimetry diode ionization chamber were used to measure the two orthogonal off-axis ratio and field size at isocenter of 7 different collimators (5 mm, 7.5 mm, 10 mm, 12.5 mm, 15 mm, 20 mm and 25 mm) of Zap-X and CyberKnife at the water depth of maximum dose, 50 mm, 100 mm, and 200 mm. The penumbra, flatness, symmetry and field size under each parameter condition were analyzed by using PTW supporting software PTW MEPHYSTO (version 5.1). Data analysis and graph were performed using Origin 2021 software.Results:With the same collimator, the dose plateau area of Zap-X was wider than that of G4 CyberKnife, and the dose fall-off at the field edge of Zap-X system was faster. With the increase of the collimator, the penumbra of Zap-X and CyberKnife tended to become larger, and the flatness tended to become smaller, the penumbra and flatness of Zap-X were significantly smaller than those of CyberKnife. Both of them had excellent symmetry (<1%), and the symmetry results of CyberKnife (<0.39%) were better than that of Zap-X (0.99%). The accuracy of Zap-X collimator size at isocenter was better than that of CyberKnife.Conclusion:Compared with G4 CyberKnife, Zap-X system has smaller penumbra, better flatness and higher accuracy of collimator size, which is suitable for stereotactic radiosurgery.

To study an automatic plan(AP) method for radiotherapy after breast-conserving surgery based on TiGRT system and and compare with manual plan (MP). The dosimetry parameters of 10 patients and the evaluation of scoring table were analyzed, it was found that the targets dose of AP were better than that of MP, but there was no statistical difference except for CI, The V5, V20 and V30 of affected lungs and whole lungs in AP were lower than all that in MP, the Dmean of hearts was slightly higher than that of MP, but the difference was not statistically significant, the MU of AP was increase by 16.1% compared with MP, the score of AP evaluation was increase by 6.1% compared with MP. So the AP could be programmed and automated while ensuring the quality of the plan, and can be used to design the plans for radiotherapy after breast-conserving surgery.
Breast Neoplasms/surgery* ; Female ; Humans ; Mastectomy, Segmental ; Organs at Risk ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Intensity-Modulated

Image-guided radiation therapy using magnetic resonance imaging (MRI) is a new technology that has been widely studied and developed in recent years. The technology combines the advantages of MRI imaging, and can offer online real-time tracking of tumor and adjacent organs at risk, as well as real-time optimization of radiotherapy plan. In order to provide a comprehensive understanding of this technology, and to grasp the international development and trends in this field, this paper reviews and summarizes related researches, so as to make the researchers and clinical personnel in this field to understand recent status of this technology, and carry out corresponding researches. This paper summarizes the advantages of MRI and the research progress of MRI linear accelerator (MR-Linac), online guidance, adaptive optimization, and dosimetry-related research. Possible development direction of these technologies in the future is also discussed. It is expected that this review can provide a certain reference value for clinician and related researchers to understand the research progress in the field.
Magnetic Resonance Imaging ; Particle Accelerators ; Radiometry ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Image-Guided

Objective:To explore the regulatory effect of glutathione S-transferase P1(GSTP1) on the radiosensitivity of mouse Lewis lung cancer (LLC) cells.Methods:GSTP1-shRNA lentivirus and negative control lentivirus were used to respectively infect the LLC cells, and stable transgenic strains were selected. Real-time PCR and Western blot were conducted to quantitatively measure the expression levels of GSTP1 mRNA and protein in the LLC cells to verify the knockdown effect. The cell counting kit-8(CCK-8) assay was used to detect cell viability after irradiation. The colony formation assay was utilized to assess the cell proliferation ability after irradiation. Flow cytometry was performed to assess the level of cell apoptosis after irradiation. The tumor-bearing mice were established and irradiated to detect the changes in the tumor volume after irradiation. TUNEL staining was employed to detect the level of tumor apoptosis after irradiation. Immunofluorescence was used to detect the number of CD 4+ CD 8+ T cells in the tumor after irradiation. Results:Real-time PCR and Western blot showed that after shRNA lentivirus interference, the expression levels of GSTP1 mRNA and protein were significantly down-regulated. Down-regulation of GSTP1 reduced cell viability and proliferation, and increased the rate of cell apoptosis after irradiation. The tumor volume of the tumor-bearing mice after irradiation in the GSTP1 knockdown group was significantly smaller than that in the NC group, whereas the tumor apoptosis rate was significantly higher and the number of infiltrating CD 4+ CD 8+ T cells in the tumor was remarkably higher compared with those in the control group. Conclusion:Knockdown of GSTP1 can significantly increase the radiosensitivity of LLC cells and enhance the infiltration of lymphocytes in tumor tissues.