Objective To compare the dosimetric difference among TomoDirect (TD) radiotherapy,Helical Tomotherapy(HT) and volumetric modulated arc therapy(VMAT) in the treatment of upper thoracic esophageal carcinoma.Methods A total of 15 patients with cT2-4 N0-1 M0 upper thoracic esophageal squamous cell carcinoma were enrolled.Three plans were generated using the same dose objective for each patient:TD,HT and VMAT.Dose-volume histogram (DVH),homogeneity index (HI),conformal index (CI),dose at organ at risk (OAR),delivery time and monitor unit (MU) were compared among different plans.Results The D2 and D values in the HT and TD plans were significantly lower than those in the VMAT plans.The D98 value in the TD was similar to that in the HT,but lower than that in the VMAT.The HI of HT was significantly better than those of TD and VMAT (F =81.603,P ＜ 0.05).For the CI,there was no significant difference among the three techniques (P ＞ 0.05).For the V15 of lung,HT was significantly higher than TD (t =-2.626,P ＜0.05) and VMAT (t=3.547,P ＜ 0.05).The V20 of lung in TD was similar to that in HT,but higher than that in VMAT (t =2.824,3.052,P ＜ 0.05).The Dmax of spinal cord showed no significant difference among the three techniques.VMAT had a significantly shorter delivery time and lower MU compared with HT and TD (t =21.617,15.693,10.018,7.802,P ＜ 0.05).Conclusions HT and TD could gain a better planning target volume (PTV) coverage and HI than VMAT in the treatment of upper thoracic esophageal carcinoma.However,VMAT achieved the lowest lung V20,the least Mus and the shortest delivery time.HT achieved a better PTV coverage compared with TD,but TD had a lower lung V15 Mus and shorter delivery time compared with HT.

Objective To investigate the hemodynamic,cerebral perfusion and neurological function changes between unilateral symptomatic internal carotid artery occlusion(SICAO)and symptomatic middle cerebral artery occlusion(SMCAO)after superfical temporal artery-middle cerebral artery(STA-MCA)bypass surgery as well as the correlation between relative peak volume of blood flow(rPVOL)in STA measured by carotid Doppler ultrasonography(CDU)and relative cerebral blood flow(rCBF)by CT perfusion(CTP).Methods Retrospective analysis of 112 patients who diagnosed with unilateral SICAO or SMCAO through DSA and/or CT angiography(CTA)and underwent superficial temporal artery-middle cerebral artery(STA-MCA)bypass in the Department of Neurosurgery at First Affiliated Hospital of Soochow University from March 2019 to June 2022.The patients were divided into SICAO group(50 cases)and SMCAO group(62 cases)and followed up for 360 days.General clinical and imaging data of patients in two groups were collected.General clinical information included age,gender,clinical manifestations(stroke,transient ischemic attack[TIA]),hypertension,diabetes,smoking history,blood biochemical indicators(total cholesterol,triacylglycerol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,high-sensitivity C-reactive protein),National Institute of Health stroke scale(NIHSS)scores at admission and 7 days after surgery,and modified Rankin Scale(mRS)scores at admission and 7,180 and 360 days after surgery(mRS scores 2 as good prognosis,＞2 as poor prognosis).Imaging data included hemodynamic parameters(STA diameter[D],resistance index[RI],time-averaged-mean velocity[TAMV],and time-average-peak flow velocity[TAPV])evaluated by CDU within 7 days before and 7,30,180 and 360 days after STA-MCA bypass,as well as CTP parameters(rCBF,relative cerebral blood volume[rCBV],relative mean transit time[rMTT]and relative time to peak[rTTP])of the head region of interest(ROI)before and 7,180 and 360 days after surgery.Patients were observed 1 year after surgery through outpatient or telephone follow-up to determine if they have experienced recurrent stroke(TIA,cerebral infarction,etc.)and other postoperative complications(subdural hematoma,cerebral hemorrhage,etc.).DSA imaging was also performed to determine the patency of vascular anastomosis of patients in SICAO and SMCAO groups.STA hemodynamic parameters,head CTP parameters,NIHSS scores,and mRS scores at different time points before and after STA-MCA bypass surgery were compared between SICAO and SMCAO groups correspondingly;STA hemodynamic parameters,head CTP parameters,and mRS scores were pairwise compared between different time points within each group.A correlation analysis was conducted between rCBF and rPVOL in STA which was measured by CTP and CDU accordingly in the SICAO and SMCAO groups to further determine the consistency of the blood flow through STA and intracranial cerebral blood flow.Results(1)There was no statistically significant difference in general clinical data between the two groups(all P＞0.05).(2)Comparison of STA hemodynamic parameters:D,TAMV,and TAPV of both groups significantly increased at 7,30,180,and 360 days after surgery(all P＜0.05)compared with preoperative,and reaching their peak at 7 days after surgery,and there was no statistically significant difference in D,TAMV,and TAPV among 30,180,and 360days after surgery(all P＞0.05).There was no statistically significant difference in D,TAMV,or TAPV between the two groups at each time point(D:F=2.286,TAMV:F=0.180,TAPV:Wald x=1.709;all P＞0.05).RI of the two groups was significantly reduced at 7,30,180,and 360 days after surgery(all P＜0.05)compared with preoperative,and there was no statistically difference in RI among 7,30,180,and 360 days after surgery(all P＞0.05).There was also no statistically difference in RI between the two groups at each time point(Wald x2=0.788,P＞0.05).(3)Comparison of CTP parameters between two groups:compared to preoperative,rCBF and rCBV in the SICAO group and SMCAO group increased at 7,180,and 360 days after surgery(all P＜0.05),there was no statistically difference in CTP parameters within the two groups at different time points(Wald x2 was 0.177,2.954,respectively,all P＞0.05),and the rMTT and rTTP of both groups decreased at 7,180,and 360 days after surgery(all P＜0.05),there was no significant difference in rMTT and rTTP between the two groups at different time points(Waldx2 was 2.157,1.706,respectively,all P＞0.05),and there was no statistically difference in the parameters of each postoperative time point within each group(all P＞0.05).(4)Comparison of vascular patency between two groups:1 year DSA showed that 91.1％(102/112)of patients were patent,with 92.0％(46/50)in the SICAO group and 90.3％(56/62)in the SMCAO group.There was no statistically difference between the two groups(x2=0.001,P＞0.05).The STA hemodynamics and intracranial CTP parameters of the two groups of patients with patent anastomosis were significantly improved compared to preoperative.A total of 10 patients were non-patent by 1 year DSA,including 4 cases in the SICAO group and 6 cases in the SMCAO group.In 1 non-patent SICAO patient and 3 non-patent SMCAO patients,the STA hemodynamic parameters evaluated by CDU 180 days and 360 days after surgery also showed corresponding improvement compared to preoperative,with an increase in TAMV and TAPV,and a decrease in RI.(5)Comparison of neurological improvement between the two groups:compared with preoperative,the mRS scores of the SICAO group and the SMCAO group significantly decreased at 7,180,and 360days postoperatively(all P＜0.05);there was no statistically difference in the mRS scores within each group at 7,180,and 360 days after surgery(P＞0.05).There was no statistically difference in mRS scores between the two groups at different time points including admission and 7,180 and 360 days after surgery(Wald x2=0.006,P＞0.05).The NIHSS scores of the SICAO group and the SMCAO group decreased at 7 days after surgery compared to admission(Z was 21.040,-5.183,respectively,all P＜0.01),and there was no statistically difference in NIHSS scores between the two groups at admission and 7 days after surgery(both P＞0.05).(6)Spearman rank correlation analysis showed that rPVOL and rCBF were highly positively correlated in the SICAO group(r=0.865,P＜0.01)and in the SMCAO group(r=0.864,P＜0.01).Conclusions Unilateral STA-MCA bypass can improve cerebral perfusion and neurological function in patients with SICAO and SMCAO,and there is no statistical difference between the two groups of patients.The rPVOL measured by CDU was highly correlated with the rCBF in patients after STA-MCA bypass surgery.

Background and objective Radiation therapy is one of the most common treatments for non-small cell lung cancer(NSCLC).However,the insensitivity of some tumor cells to radiation is one of the major reasons for the poor efficacy of radiotherapy and the poor prognosis of patients,and exploring the underlying mechanisms behind radioresistance is the key to solving this clinical challenge.This study aimed to identify the molecules associated with radioresistance in lung ad-enocarcinoma(LUAD),identified thyroid hormone receptor interactor 13(TRIP13)as the main target initially,and explored whether TRIP 13 is related to radioresistance in LUAD and the specific mechanism,with the aim of providing theoretical basis and potential targets for the combination therapy of LUAD patients receiving radiotherapy in the clinic.Methods Three data-sets,GSE18842,GSE19188 and GSE33532,were selected from the Gene Expression Omnibus(GEO)database and screened for differentially expressed genes(|log FC|＞1.5,P＜0.05)in each of the three datasets using the R 4.1.3 software,and then Venn diagram was used to find out the differentially expressed genes common to the three datasets.The screened differential genes were then subjected to protein-protein interaction(PPI)analysis and module analysis with the help of STRING online tool and Cytoscape software,and survival prognosis analysis was performed for each gene with the help of Kaplan-Meier Plotter database,and the TRIP13 gene was identified as the main molecule for subsequent studies.Subsequently,the human LUAD cell line H292 was irradiated with multiple X-rays using a sub-lethal dose irradiation method to construct a radioresistant cell line,H292DR.The radioresistance of H292DR cells was verified using cell counting kit-8(CCK-8)assay and clone formation assay.The expression levels of TRIP 13 in H292 and H292DR cells were measured by Western blot.Small interfering RNA(siRNA)was used to silence the expression of TRIP 13 in H292DR cells and Western blot assay was performed.The clone formation ability and migration ability of H292DR cells were observed after TRIP13 silencing,followed by the detection of changes in the expression levels of proteins closely related to homologous recombination,such as ataxia telangiectasia mutated(ATM)protein.Results Screening of multiple GEO datasets,validation of external datasets and survival analysis revealed that TRIP 13 was highly expressed in LUAD and was associated with poor prognosis in LUAD patients who had received radiation therapy.And the results of gene set enrichment analysis(GSEA)of TRIP13 suggested that TRIP13 might be closely associated with LUAD radioresistance by promoting homologous recombination repair after radiation therapy.Experimentally,TRIP13 expression was found to be upregulated in H292DR,and silencing of TRIP13 was able to increase the sensitivity of H292DR cells to radiation.Conclusion TRIP13 is associated with poor prognosis in LUAD patients treated with radiation,possibly by promoting a homologous recombination repair pathway to mediate resistance of LUAD cells to radiation.

Objective:To investigate the efficacy of different types of neoadjuvant therapy for esophageal cancer.Methods:The clinical data of 542 patients with esophageal squamous cell carcinoma (ESCC) who received neoadjuvant therapy in Anyang Tumor Hospital of Science and Technology from January 2015 to May 2022 were retrospectively analyzed. These patients, consisting of 198 females and 344 males, with 289 cases aging ≤ 65 and 253 cases aging >65, were divided into a neoadjuvant chemoradiotherapy (NCRT) group (137 cases), a neoadjuvant chemotherapy (NCT) group (241 cases), and a neoadjuvant immunotherapy plus chemotherapy (NICT) group (164 cases). In this study, primary endpoints included major pathological response (MPR) and pathologic complete response (pCR) rates, and secondary endpoints comprised overall survival (OS), progression-free survival (PFS), and safety. Survival analysis was performed using the Kaplan-Meier method, and inter-group comparisons were made using the Log-rank test. Furthermore, prognostic factors were analyzed based on the Cox proportional hazards regression model.Results:The NCRT, NCT, and NICT groups exhibited MPR and pCR rates of 66.4% (91/137) and 35.3% (85/241), 63.4% (104/164) and 35.8% (49/137), and 6.6% (16/241) and 31.1% (51/164), respectively ( χ2=1.67, P < 0.001). These groups displayed 1-, 2-, and 3-year OS rates of 89.8%, 85.9%, and 91.9%; 82.3%, 71.4%, and 81.5%; and 72.3%, 61.4%, and 77.8%, respectively, with significant differences ( χ2=9.20, P < 0.01). Furthermore, they exhibited 1-, 2-, and 3-year PFS rates of 81.5%, 75.9%, and 80.1%; 67.9%, 61.0%, and 65.5%; and 66.6%, 53.5%, and 65.3%, respectively, with significant differences ( χ2=4.62, P < 0.05). Multivariate analysis showed that therapeutic modality, T stage, and N stage were independent prognostic factors for OS ( P < 0.05). Additionally, there was no difference in adverse reactions and postoperative complications among the three groups. Conclusions:Compared to NCT, NICT and NCRT feature higher pCR and MPR rates, along with more survival benefits. Therefore, neoadjuvant immunotherapy has the potential to serve as a preoperative therapeutic modality for esophageal cancer, yet large-scale randomized controlled trials are still required for confirmation.

Objective:To evaluate the efficacy and safety of immunotherapy with or without radiotherapy in the treatment of recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC).Methods:A retrospective analysis was conducted on the data of 75 patients with R/M ESCC treated with sintilimab at Anyang Tumor Hospital from January 2020 to October 2021. The patients were divided into the radiotherapy (RT) group ( n=37) and non-radiotherapy (NRT) group ( n=38) based on whether they received radiotherapy. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse effects were compared between two groups. Count data were expressed as composition ratios and analyzed using Chi-square test or Fisher's exact test. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:There was no statistically significant difference in ORR and DCR between the RT and NRT groups (70% vs. 61%, P=0.375; 95% vs. 89%, P=0.414). However, the complete response (CR) rate in the RT group was higher compared to that in the NRT group (19% vs. 3%, P=0.022). The median follow-up duration was 25.4 months. There was no statistically significant difference in the median PFS and OS between the RT and NRT groups (13.8 months vs. 9.9 months, P=0.221; 20.2 months vs. 18.9 months, P=0.214). Subgroup analysis demonstrated that among patients with recurrence or metastasis confined to local and / or ≤3 distant lymph nodes, there was no statistically significant difference in the median PFS between the RT and NRT groups (15.1 months vs. 8.4 months, P=0.115), but the median OS in the RT group was better than that in the NRT group (not reached vs. 12.3 months, P=0.036). Compared to the NRT group, besides an increase in grade 1-2 pneumonitis (41% vs. 18%, P=0.035), no significant increase in treatment-related toxicity was observed in the RT group. Conclusion:Immunotherapy combined with radiotherapy is safe in patients with R/M ESCC, and shows survival benefit in patients with recurrence or metastasis confined to local and / or ≤3 distant lymph nodes.

Objective:To explore the biomarkers of radiochemotherapy sensitivity and potential mechanisms in esophageal squamous cell carcinoma (ESCC), and validate the screened biomarkers at human tissue, animal and cellular levels.Methods:Based on bioinformatics system, clinical and transcriptome data of ESCC were obtained from The Cancer Genome Atlas (TCGA) and GEO databases. HUB genes related to chemoradiotherapy sensitivity were identified by weighted correlation network analysis (WGCNA) and cytoscape software and survival differences were analyzed. CellMiner database was used to predict and screen drugs with strong correlation with HUB genes. The expression levels of HUB genes in clinical tissues was detected by real-time reverse transcription PCR (qRT-PCR). Then, oe-AKR1C1 mouse model, cisplatin-resistant cells and radiation-resistant cells were constructed, and the effects of HUB genes on tumor size and mass, and cell proliferation ability were analyzed.Results:A total of 5 HUB genes were identified, among which NAD(P)H quinone dehydrogenase 1 (NQO1), AKR1C1 and NADH: ubiquinone oxidoreductase core subunit S2 (NDUFS2) were significantly correlated with ESCC survival (all P<0.05). Dacarbazine, alectinib and obatoclax were the anti-tumor drugs predicted to have a strong correlation with HUB genes in this study. Human tissue test results showed that the expression levels of NQO1, AKR1C1 and NDUFS2 were up-regulated in patients with chemoradiotherapy resistance, and AKR1C1 and NDUFS2 had statistical significance (both P<0.05). The results of mouse tumor bearing experiment showed that the tumor volume and mass of oe-AKR1C1 mice after radiotherapy and chemotherapy were significantly higher than those in the control group (both P<0.05). The cell experiment results showed that the expression levels of AKR1C1 and NDUFS2 in radiation-resistant cells and cisplatin-resistant cells were significantly higher than those in control cells ( P<0.05), while there was no statistically significant difference in the relative expression level of NQO1. Conclusion:NQO1, AKR1C1 and NDUFS2 are HUB genes significantly related to the survival of ESCC, which can be used as important therapeutic tumor targets for ESCC.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair