Objective:To investigate the differences in acute intestinal injury and regulatory mechanisms in mice following carbon ion FLASH radiotherapy (FLASH-RT) and conventional dose rate radiotherapy (CONV-RT).Methods:Healthy C57BL/6J mice were randomly divided into three groups: control group, FLASH-RT group (100 Gy/s), and CONV-RT group (0.1 Gy/s), with 9 mice in each group. All mice received carbon ion whole abdominal radiotherapy. DNA double-strand breaks (DSB) and cell proliferation were evaluated by measuring the expression of phosphorylated histone H2AX (γ-H2AX) and nuclear-associated antigen 67 (Ki67) using immunohistochemistry; apoptosis was analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL); transcriptome sequencing was used to analyze the differences in molecular pathways between FLASH-RT and CONV-RT.Results:Compared with the CONV-RT group, the FLASH-RT group showed significantly reduced intestinal γ-H2AX signal at 3 h after radiotherapy ( t=3.80, P<0.01), significantly increased expression of Ki67 at the base of intestinal crypts at 6 h after radiotherapy ( t=4.30, P<0.001), and a significantly decreased number of TUNEL-positive cells at 12 h after radiotherapy ( t=3.08, P<0.01). Transcriptome sequencing analysis showed that FLASH-RT specifically activated the insulin-like growth factor (IGF) pathway, avoiding the excessive activation of CONV-RT-induced nuclear factor-κB and B cell receptor inflammatory pathways as well as the inhibition of energy metabolism. Conclusions:Compared with CONV-RT, carbon ion FLASH-RT can reduce DSB damage, preserve the proliferative activity of intestinal stem cells, activate the IGF pathway, and regulate inflammatory, immune, and metabolic pathways, thereby significantly alleviating acute intestinal epithelial injury. Specifically, the regulation of repair pathways mediated by reduced DSB and the inhibition of inflammatory pathways are potential protective mechanisms for normal tissues.

FLASH irradiation (FLASH-IR) is one of the cutting-edge research directions in the field of tumor radiotherapy. Previous studies have demonstrated that FLASH-IR can effectively eradicate tumors while significantly reducing damage to normal tissues, exhibiting unique biological effects characterized by high efficiency and low toxicity. Monte Carlo simulation at the microscopic scale is a critical method for studying radiobiological effects and has been widely applied in conventional radiotherapy research. In recent years, its application in microscopic reaction analysis and mechanistic exploration of FLASH-IR has grown rapidly. This article systematically reviews the latest advances and key challenges in microscopic Monte Carlo simulation studies of FLASH-IR, aiming to provide theoretical insights and method ological guidance for future research.

Objective:To investigate the differences in acute intestinal injury and regulatory mechanisms in mice following carbon ion FLASH radiotherapy (FLASH-RT) and conventional dose rate radiotherapy (CONV-RT).Methods:Healthy C57BL/6J mice were randomly divided into three groups: control group, FLASH-RT group (100 Gy/s), and CONV-RT group (0.1 Gy/s), with 9 mice in each group. All mice received carbon ion whole abdominal radiotherapy. DNA double-strand breaks (DSB) and cell proliferation were evaluated by measuring the expression of phosphorylated histone H2AX (γ-H2AX) and nuclear-associated antigen 67 (Ki67) using immunohistochemistry; apoptosis was analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL); transcriptome sequencing was used to analyze the differences in molecular pathways between FLASH-RT and CONV-RT.Results:Compared with the CONV-RT group, the FLASH-RT group showed significantly reduced intestinal γ-H2AX signal at 3 h after radiotherapy ( t=3.80, P<0.01), significantly increased expression of Ki67 at the base of intestinal crypts at 6 h after radiotherapy ( t=4.30, P<0.001), and a significantly decreased number of TUNEL-positive cells at 12 h after radiotherapy ( t=3.08, P<0.01). Transcriptome sequencing analysis showed that FLASH-RT specifically activated the insulin-like growth factor (IGF) pathway, avoiding the excessive activation of CONV-RT-induced nuclear factor-κB and B cell receptor inflammatory pathways as well as the inhibition of energy metabolism. Conclusions:Compared with CONV-RT, carbon ion FLASH-RT can reduce DSB damage, preserve the proliferative activity of intestinal stem cells, activate the IGF pathway, and regulate inflammatory, immune, and metabolic pathways, thereby significantly alleviating acute intestinal epithelial injury. Specifically, the regulation of repair pathways mediated by reduced DSB and the inhibition of inflammatory pathways are potential protective mechanisms for normal tissues.

FLASH irradiation (FLASH-IR) is one of the cutting-edge research directions in the field of tumor radiotherapy. Previous studies have demonstrated that FLASH-IR can effectively eradicate tumors while significantly reducing damage to normal tissues, exhibiting unique biological effects characterized by high efficiency and low toxicity. Monte Carlo simulation at the microscopic scale is a critical method for studying radiobiological effects and has been widely applied in conventional radiotherapy research. In recent years, its application in microscopic reaction analysis and mechanistic exploration of FLASH-IR has grown rapidly. This article systematically reviews the latest advances and key challenges in microscopic Monte Carlo simulation studies of FLASH-IR, aiming to provide theoretical insights and method ological guidance for future research.

Objective To evaluate the quality of treatment planning(TP)and re-optimization planning(RP)of radiotherapy for rectal cancer using PlanIQ software,thereby providing methods and tools for the screening and optimization of radiotherapy plans.Methods Twenty patients with rectal cancer who received radiotherapy were selected retrospectively,with 10 cases of intensity-modulated radiotherapy(IMRT)and 10 of volumetric modulated arc therapy(VMAT).(1)TP:IMRT plan involved 5-field irradiation,and VMAT plan involved two 360°arcs.The prescription doses were 50 Gy/25 f for PTV1 and 45 Gy/25 f for PTV2.All plans underwent direct machine parameter optimization and required 95%isodose lines to cover 100%of the target volume.Organs-at-risk(OAR)were limited by reference to tolerated dose standards.After the planning was completed,the plans were reviewed and confirmed by a physician,and the treatment was implemented after dose verification.(2)RP:a physicist with 10 years of experience re-optimized the 20 TP plans,with the irradiation technique and field setting unchanged.The re-optimization involved adjusting planning conditions and parameters based on individual experience until the dose to OAR was minimized while without affecting PTV coverage.The quality of TP plans and RP plans were quantitatively evaluated using PlanIQ software.Non-parametric Wilcoxon signed rank test was performed for dose-volume histogram parameters and plan quality index between two groups.Results The dose-volume histogram parameters in RP plans were superior to those in TP plans,and the differences in the Dmax of PTV1,the V45 Gy and Dmax of small intestine,and the V45 Gy of colon were statistically significant(P<0.05).The quality scores of RP plans for IMRT group,VMAT group and all patients were significantly higher than those of TP plans(P<0.05),with plan quality index of 88.55±3.35 vs 86.61±4.63(P=0.005),89.72±3.15 vs 87.21±3.04(P=0.028),and 89.14±3.22 vs 86.91±3.22(P=0.001),respectively.Conclusion RP can further improve the quality of radiotherapy plan for rectal cancer.PlanIQ software serves as an effective tool for quality control and screening of radiotherapy planning.

Objective To assess inter-observer variations(IOV)in the delineation of target volumes and organs-at-risk(OAR)for intensity-modulated radiotherapy(IMRT)of nasopharyngeal carcinoma(NPC)among physicians from different levels of cancer centers,thereby providing a reference for quality control in multi-center clinical trials.Methods Twelve patients with NPC of different TMN stages were randomly selected.Three physicians from the same municipal cancer center manually delineated the target volume(GTVnx)and OAR for each patient.The manually modified and confirmed target volume(GTVnx)and OAR delineation structures by radiotherapy experts from the regional cancer center were used as the standard delineation.The absolute volume difference ratio(△V_diff),maximum/minimum volume ratio(MMR),coefficient of variation(CV),and Dice similarity coefficient(DSC)were used to compare the differences in organ delineation among physicians from different levels of cancer centers and among the 3 physicians from the same municipal cancer center.Furthermore,the IOV of GTVnx and OAR among physicians from different levels cancer centers were compared across different TMN stages.Results Significant differences in the delineation of GTVnx were observed among physicians from different levels of cancer centers.Among the 3 physicians,the maximum values of △V_diff,MMR,and CV were 97.23%±83.45%,2.19±0.75,and 0.31±0.14,respectively,with an average DSC of less than 0.7.Additionally,there were considerable differences in the delineation of small-volume OAR such as the left and right optic nerves,chiasm,and pituitary,with average MMR>2.8,CV>0.37,and DSC<0.51.However,relatively smaller differences were observed in the delineation of large-volume OAR such as the brainstem,spinal cord,left and right eyeballs,and left and right mandible,with average△V_diff<42%,MMR<1.55,and DSC>0.7.Compared with the differences among physicians from different levels cancer centers,the differences among the 3 physicians from the municipal cancer center were slightly reduced.Furthermore,there were also differences in the delineation of target volumes for NPC among physicians from different levels cancer centers,depending on the staging of the disease.Compared with the delineation of target volumes for earlier stage patients(stages I or II),the differences among physicians in the delineation of target volumes for advanced stage patients(stages III or IV)were smaller,with average △V_diff and DSC of 98.31%±67.36%vs 69.38%±72.61%(P<0.05)and 0.55±0.08 vs 0.72±0.12(P<0.05),respectively.Conclusion There are differences in the delineation of GTVnx and OAR in radiation therapy for NPC among physicians from different levels of cancer centers,especially in the delineation of target volume(GTVnx)and small-volume OAR for early-stage patients.To ensure the accuracy of multicenter clinical trials,it is recommended to provide unified training to physicians from different levels of cancer centers and review their delineation results to reduce the effect of differences on treatment outcomes.

Female ; Humans ; Pregnancy ; Septate Uterus ; Uterus/surgery* ; Hysteroscopy/methods* ; Estrogens ; Tissue Adhesions/surgery* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

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.

Purpose: This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients. Materials and Methods: Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/ International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010. Results: With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index ≥ 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase ≥ 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group. Conclusion Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients.