Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).

Difficulties and advances of incisional hernia repair after hepatobiliary and pancreatic surgery / 中华消化外科杂志

Abdominal incisional hernia is caused by poor healing of myofascial layer of abdominal wall and abdominal visceral organs protruding through the defect after abdominal surgery. The incidence of abdominal incisional hernia is 5.0%?20.0%, even higher after hepato-biliary and pancreatic surgery. Although great progress has been made in the methods of abdominal incision closure, hernia repair technology and materials, the overall incidence, repair effect and prognosis of abdominal incisional hernia are still not significantly improved. The incisional hernias after hepatobiliary and pancreatic surgery are relatively more complex, and the difficult problems of surgical repair are more prominent, including effectively controlling basic diseases, choosing a better surgical method, reasonably using a variety of abdominal wall defect closure and reconstruction techniques, and reducing the risk of postoperative complications. Relevant guidelines for abdominal incisional hernia repair and abdominal closure have been issued and updated all over the world. In order to improve the treatment of incisional hernia after hepatobiliary and pancreatic surgery and improve the prognosis of patients, the authors summarize the difficulties and new progress in the repair of incisional hernia after hepatobiliary and pancreatic surgery.

Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with different doses of whole brain radiotherapy / 中华放射肿瘤学杂志

Objective:To analyze the prognosis and influencing factors of patients with brain metastases from non-small cell lung cancer (NSCLC) treated with different doses of whole brain radiotherapy (WBRT).Methods:A total of 244 NSCLC patients with brain metastases who underwent WBRT in the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different doses of WBRT (EQD 2Gy), they were divided into the 30-39 Gy group ( n= 104) and ≥40 Gy group ( n= 140). The intracranial progression-free survival (iPFS) and overall survival (OS) were compared betweentwo groups. According to the number of brain metastases, GPA score, KPS score, chemotherapy and targeted therapy, the prognosis of different doses of WBRT was further analyzed. Results:The median iPFS and OS of all patients were 6.9 months and 11.8 months, respectively. Univariate survival analysis: the 1-year iPFS and 1-year OS between two groups were 22.5% and 25.4%( P=0.430) and 41.1% and 46.4%( P=0.068), respectively. Multivariate survival analysis: different doses of WBRT were not associated with the improvement of iPFS and OS; independent factors influencing iPFS included local boost, gender, number of brain metastases, chemotherapy and targeted therapy; independent factors influencing OS included gender, number of brain metastases, chemotherapy and targeted therapy. Subgroup analysis: in patients with KPS≥90, the 1-year iPFS and OS of patients with WBRT ≥ 40 Gy were seemingly better than those of their counterparts with 30-39 Gy, but the difference was statistically significant only in OS ( P=0.047), the difference was not statistically significant in iPFS ( P=0.068); in patients with chemotherapy, the 1-year iPFS and OS of patients with WBRT≥40 Gy were better than those of their counterparts with 30-39 Gy ( P=0.017, P=0.012); in patients with targeted therapy, the 1-year iPFS and OS in the WBRT≥40 Gy group were better than those in the 30-39 Gy group ( P=0.012, P=0.045). Conclusions:The 30-39 Gy may be the appropriate dose of WBRT for NSCLC patients with brain metastases. WBRT≥40 Gy does not bring more benefits. WBRT≥40 Gy may benefit NSCLC patients with brain metastases with high KPS score or active systemic therapy.

Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with supplemental radiotherapy under different prognostic scores / 中华放射肿瘤学杂志

Objective:To analyze the prognosis and influencing factors of different radiotherapy modes in patients with brain metastases from non-small cell lung cancer (NSCLC), and to explore the best benefit population with radiotherapy boost under different prognostic scores.Methods:634 patients with brain metastasis from NSCLC admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different radiotherapy modes, they were divided into three groups: no radiotherapy group ( n=330), whole-brain radiotherapy group (WBRT)( n=127) and whole-brain radiotherapy combined with boost group (WBRT+ boost)( n=177). The intracranial progression-free survival (iPFS) and overall survival (OS) were calculated by Kaplan-Meier method. The multivariate prognostic factors were analyzed by the Cox models. Results:The median iPFS and OS of all patients were 6.9 months and 9.0 months, respectively. In the no radiotherapy, WBRT and WBRT+ boost groups, the 1-year iPFS was 15.1%, 16.3% and 40.2%( P=0.002), and the 1-year OS was 33.7%, 38.2% and 48.1%( P<0.001), respectively. Multivariate survival analysis demonstrated that different radiotherapy modes were the independent factors affecting iPFS and OS. Subgroup analysis revealed that for patients with 1-3 brain metastases, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone ( P=0.026, P=0.044) when GPA score was 2.5-4.0; the 1-year OS and iPFSin the WBRT+ boost group were better than those of WBRT alone ( P=0.036, P=0.049) when there was no targeted therapy; for patients with ≥4 brain metastases, the 1-year iPFS in the WBRT+ boost group was better than that of WBRT alone ( P=0.019, P=0.012) when GPA score was 2.5-4.0 and there was no targeted therapy. When the GPA score was 0-2 or there was targeted therapy, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone, but the difference was not statistically significant (all P>0.05). Conclusions:Radiotherapy can significantly improve the iPFS and OS of NSCLC patients with brain metastases. When the number of brain metastases is 1-3, GPA score is 2.5-4.0 or no targeted therapy, boost may improve the iPFS and OS; when the number of brain metastases is more than 4, GPA score is 2.5-4.0 or no targeted therapy, boost may only bring iPFS benefit; when GPA score is 0-2 or targeted therapy, boost may not benefit significantly.

Predictive effect of liver fibrosis score and other factors on the prognosis of liver transplantation for liver cancer / 中华器官移植杂志

Objective:To explore the value of aspartate aminotransferase(AST)and platelet (PLT)ratio index(APRI)in the prognosis of liver transplantation(LT)for hepatocellular carcinoma and establish a nomogram model for evaluating its clinical application potential.Methods:From January 2015 to December 2019, retrospective review was conducted for clinical data of LT for hepatocellular carcinoma(HCC)at First Affiliated Hospital of Zhejiang University School of Medicine and Shulan(Hangzhou)Hospital(601 cases). They were randomized into two groups of modeling (399 cases)and validation(202 cases)and then divided into low and high APRI groups according to the APRI value at Month 1 post-transplantation. The independent risk factors of recurrence and prognosis post-LT were screened in modeling group using univariate and multivariate Cox regression analyses and were further used for constructing a nomogram prediction model. The receiver operating characteristic curve(ROC)and survival curve were utilized for verifying the accuracy of nomogram prediction model.Results:Univariate and multivariate Cox regression analyses revealed that independent risk factors for the prognosis of HCC-LT included cold ischemic time(CIT) >8 h, beyond Hangzhou criteria, surgical bleeding volume >1 000 ml and APRI >1.5. The AUC of HCC-LT recurrence prediction model was 0.734(95%CI: 0.681~0.787)and 0.749(95%CI: 0.671~0.817)in modeling and validation groups; the AUC of HCC-LT mortality prediction model was 0.735(95%CI: 0.679~0.790)and 0.758(95%CI: 0.682~0.834)in modeling and validation groups.Conclusions:APRI>1.5 is an independent risk factor for postoperative recurrence and mortality after HCC-LT. The nomogram prediction model based upon CIT, Hangzhou criteria, intraoperative bleeding volume and APRI can effectively predict the recurrence and overall survival of LT for HCC.

Efficacy of prophylactic irradiation of internal mammary lymph nodes in breast cancer: a Meta-analysis / 中华放射肿瘤学杂志

Objective:To evaluate the effect of prophylactic irradiation of internal mammary lymph nodes in patients with breast cancer in this Meta-analysis.Methods:CNKI, Wanfang Medical network, CBM, PubMed, EMBASE and Web of Science were searched by computer. The controlled clinical studies comparing whether or not internal mammary lymph node irradiation as an intervention were included and the quality of the included literature was evaluated according to Newcastle-Ottawa Scale (NOS). RevMan 5.3 software and Stata 14 software were used for Meta-analysis.Results:A total of 11 original articles were included, and 13 181 patients were included for Meta-analysis. There was no statistically significant difference in the overall survival (OS) between patients with and without internal mammary lymph node irradiation ( P=0.490). The subgroup analysis using the date of treatment and the degree of risk in the enrolled population as criteria showed that 5-year OS was significantly increased after internal mammary area irradiation in high-risk stage Ⅱ-Ⅲ patients (N+ , T 3-T 4 stage) with the date of treatment of after 2000( P=0.003, 0.006). Compared with patients without internal mammary area irradiation, internal mammary irradiation significantly increased the 5-year disease-free survival (DFS)( P<0.001). Conclusion:Under the modern radiotherapy technology, internal mammary lymph node irradiation improves the DFS of patients, and may bring OS benefits to high-risk stage Ⅱ-Ⅲ breast cancer patients (N+ , T 3-T 4 stage).

Comparison of different local treatment patterns in breast cancer with ipsilateral supraclavicular lymph node metastasis / 中华放射肿瘤学杂志

Objective:To explore the optimal local treatment pattern of supraclavicular lymph node in breast cancer patients with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM).Methods:Clinical data of 128 breast cancer patients with sISLM admitted to the Fourth Hospital of Hebei Medical University from 2010 to 2015 were retrospectively analyzed. Among them, 68 cases were treated with supraclavicular lymph node dissection combined with radiotherapy, and 60 cases received radiotherapy alone. The locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were statistically compared between two groups.Results:Univariate analysis demonstrated that the 5-year LRFS, DMFS, PFS and OS did not significantly differ between two groups (all P>0.05). Multivariate analysis revealed that the local treatment pattern of supraclavicular lymph node was an independent prognostic factor for the 5-year DMFS, PFS and OS (all P<0.05). Subgroup analysis showed that when radiotherapy alone was performed, the 5-year OS of patients in the supraclavicular region radiation dose of>50 Gy group were significantly better than that in the 50 Gy group ( P=0.047). When supraclavicular lymph node dissection combined with radiotherapy was delivered, if the number of dissection was less than 10, the 5-year LRFS, DMFS, PFS, OS of patients in the>50 Gy group were all better than those in the 50 Gy group numerically without statistical significance (all P>0.05). If the number of dissection was ≥10, the 5-year LRFS, DMFS, PFS, OS in the 50 Gy group were better than those in the>50 Gy group numerically, whereas significant difference was only found in the 5-year DMFS ( P=0.028). Conclusions:Supraclavicular lymph node dissection combined with radiotherapy may be the optimal local treatment pattern for supraclavicular lymph node. When radiotherapy alone is performed, a radiation boost to the supraclavicular region may improve OS. When supraclavicular lymph node dissection combined with radiotherapy is performed, if the degree of dissection is low, a radiation boost to the supraclavicular region may bring clinical benefits. However, if the degree of dissection is high, a radiation boost to the supraclavicular region may not bring significant clinical benefits.

The value of high frequency ultrasound in the diagnosis of internal mammary lymph node metastasis in breast cancer / 中华超声影像学杂志

Objective:To investigate the ultrasonographic characteristics and risk factors of breast cancer internal mammary lymph node (IMLN) metastasis.Methods:A retrospective analysis of 296 first diagnosed breast cancer patients in the Fourth Hospital of Hebei Medical University from March 2010 to May 2020. IMLN was divided into metastatic group (236 cases) and non-metastatic group (60 cases) based on pathology. Chi-square test and independent sample t test were used to analyze the ultrasound characteristics of IMLN metastasis and factors related to metastasis. ROC curve analysis of IMLNs were plotted to obtain the diagnostic thresholds and their sensitivity and specificity.Univariate and multivariate Logistic analysis was used to analyze the risk factors of IMLN metastasis. Results:①The appearances of IMLN in ultrasound were normal type, thickened-cortex type, unclear hilus structure type and thickened-nodular soft tissue type. ②In the two groups, the differences in IMLN long diameter, thickness diameter, number, and lymphatic hilum structure type were statistically significant (all P<0.05), and there were no significant differences in IMLN long diameter/thickness diameter and IMLN blood supply (all P>0.05). ③The long diameter threshold of IMLN for diagnosis of metastasis was 10.5 mm, the are under the ROC curve(AUC) was 0.825, with sensitivity of 58.5% and specificity 93.3%; thickness and diameter threshold was 4.5 mm, AUC was 0.790, with sensitivity 66.9% and specificity 75.0%. The sensitivity and specificity of the diagnosis of long-diameter combined structure type were 56.3% and 93.3%, respectively; the sensitivity and specificity of the diagnosis of thick-diameter combined structure type were 64.8% and 81.7%, respectively. The cortical thickness threshold was 1.9 mm, and the diagnostic sensitivity and specificity were 91.9% and 86.7%, respectively. ④The risk factors of IMLN metastasis inculded univariate analysis showed tumor length, tumor volume, axillary lymph node long diameter, axillary lymph node metastasis, and clavicle lymph node metastasis. There was a statistically significant difference in the pathology of the lower lymph nodes between the two groups ( P<0.05). Multivariate analysis showed that the long diameter of the tumor and the metastasis of the axillary lymph nodes were independent risk factors of IMLN metastasis. Conclusions:The metastatic IMLN mostly manifest as no lymphatic hilum structure or cortical thickening (≥1.9 mm), and multiple IMLN can help diagnose metastasis.Ultrasound can better assess breast cancer IMLN metastasis, and the diagnostic efficiency of IMLN long-diameter combines structure type is higher.Independent risk factors for IMLN metastasis include tumor size and axillary lymph node metastasis.

Application of 3D printed head film fixation technology in radiotherapy for head tumors / 中华放射肿瘤学杂志

Objective:To customize the individualized 3D printed head film for patients with head tumors undergoing radiotherapy, and to evaluate the physical properties of the material and the precision of this technology compared with the thermoplastic head film.Methods:The 3D printed head film and thermoplastic head film were placed on the solid water surface, and the depth and surface dose were measured at 5 cm by ionization chamber and film, respectively. Thirty patients with head tumors receiving radiotherapy were randomly divided into the control and experimental groups. The patients were fixed with thermoplastic head film and 3D printed head film. The translational and rotational errors in the x, y and z direction were obtained by CBCT.Results:The radiation attenuation rate of two materials at the depth of 5 cm was less than 1%. The dose of thermoplastic head film in the surface position was increased by 27%, and increased by 18% in the 3D printed head film. In two groups, 116 sets of setup errors were collected. The average translational setup errors in the control and experimental groups were 1.29 mm and 1.16 mm, 1.42 mm and 1.24 mm, 1.38 mm and 1.16 mm, respectively, and the average rotational setup errors were 1.29°and 1.08°, 1.02°and 0.96°, 1.01°and 1.00°, respectively. The translational setup errors in the y and z direction and rotational setup errors in the x direction significantly differed between the control and experimental groups (all P<0.05), but no statistical significance was found in the other direction (all P>0.05). Conclusion:The 3D printed head film fixation meets the precise setup requirements of modern radiotherapy, which deserves further application in clinical trials.

Effect of different expression levels of USP28 on apoptosis and related protein expression in esophageal cancer cell ECA109 after irradiation / 中华放射肿瘤学杂志

Objective@#To observe the effect of different expression levels of USP28 on the radiosensitivity of ECA109 cells by gene transfection method, aiming to provide theoretical basis for comprehensive treatment of esophageal cancer.@*Methods@#The expression levels of USP28 and c-Myc in the esophageal epithelial cells Het-1A, ECA109 and ECA109R were quantitatively measured by qRT-PCR. The specific siRNA sequences were designed according to the USP28 and c-Myc genes. The pcDNA-USP28 and pcDNA-c-Myc plasmids were constructed. The esophageal cancer cell ECA109 was transfected with Lipofectamine 2000 to observe the transfection effect and related protein expression. ECA109 and ECA109R cells were exposed to 6 Gy X-ray radiation. The cell apoptosis in each group was detected by flow cytometry. The radiosensitivity was evaluated by clone formation assay.@*Results@#The expression levels of USP28 and c-Myc in ECA109 were significantly higher than those in Het-1A (both P<0.05), and the expression levels of USP28 and c-Myc in ECA109R were remarkably higher than those in ECA109(both P<0.05). The pcDNA-USP28 and pcDNA-c-Myc recombinant plasmids were successfully constructed. Compared with the negative control group, the expression of USP28 at the protein and mRNA levels in the si-USP28 group was significantly down-regulated, whereas those in the pcDNA-USP28 group were remarkably up-regulated. Similar results were obtained in terms of c-Myc. Compared with the control group, the expression level of c-Myc protein was significantly up-regulated in the pcDNA-USP28 group, whereas considerably down-regulated in the si-USP28 group. After 6 Gy irradiation, the apoptosis rate and radiosensitivity of ECA109 cells were significantly declined. The apoptosis rate and radiosensitivity of ECA109R cells were increased in the si-USP28 group.@*Conclusions@#The expression of USP28 protein is closely correlated with the radiosensitivity of esophageal cancer cells. The underlying mechanism may be related to the regulation of c-Myc expression by USP28.

The effect of RNF2 knockdown on the radiosensitivity in transplanted tumor of nude mice of esophageal carcinoma in vivo / 中华放射肿瘤学杂志

Objective To evaluate the effect of RNF2 gene knockdown in ECA109 cells on the radiosensitivity to esophageal cancer cell xenograft in nude mice. Methods Thirty-six male BALB/c/nu nude mice were randomly divided into 6 groups: control group, control+ irradiation group, NC group, NC+irradiation group, RNF2 shRNA group and RNF2 shRNA+ irradiation group. The nude mouse models with transplanted tumors were established by subcutaneous inoculation of EAC109 cells and given with irradiation at a dose of 3 Gy for 5 times. The longest ( a) and shortest ( b) diameters of the transplanted tumor were measured every 2 to 3 day since the fourteenth day after inoculation. The time of tumor formation was recorded. The tumor volume was calculated according to the formula ( ab2/2 ) . The growth curve was delineated. Three nude mice were sacrificed in each group at 24 h after the initial irradiation. The expression of RNF2 at the mRNA and protein levels in transplanted tumor tissues was measured by qRT-PCR and immunohistochemistry, respectively. The growth and tumor volume of the other nude mice in each group were observed. The cell apoptosis of transplanted tumor tissues was detected by TUNEL assay. The expression of Bcl-2 and Bax at the mRNA and protein levels in transplantated tumor tissues was quantitatively measured by qRT-PCR and immunohistochemistry, respectively. Results The tumor growth rate was the highest in the control and NC groups. The knockdown of RNF2 reduced the growth rate of xenografts and the tumor growth rate was the slowest in the RNF2 shRNA+ irradiation group ( P<0.05) . TUNEL assay revealed that the cell apoptosis rates in all groups were significantly increased after irradiation ( all P<0.05) . Before and after irradiation, the apoptosis rate in the RNF2 shRNA group was markedly higher than those in the control and NC groups ( both P<0.05) . Prior to irradiation, the expression levels of RNF2 mRNA and protein in the RNF2 shRNA group were significantly lower compared with those in the control and NC groups ( all P<0.05) , and the tendency became more significant after irradiation. Compared with the control and NC groups, the expression levels of Bcl-2 mRNA and protein were significantly down-regulated in the RNF2 shRNA group before and after irradiation ( all P<0.05) , whereas those of Bax mRNA and protein were considerably up-regulated ( all P<0.05 ) . Conclusions In vivo experiment demonstrates that RNF2 knockdown effectively increases the radiosensitivity of esophageal carcinoma EAC109 cells in nude mouse models with transplanted tumors, which is intimately associated with inducing the cell apoptosis.

Effect of different expression levels of USP28 on apoptosis and related protein expression in esophageal cancer cell ECA109 after irradiation / 中华放射肿瘤学杂志

Objective To observe the effect of different expression levels of USP28 on the radiosensitivity of ECA109 cells by gene transfection method,aiming to provide theoretical basis for comprehensive treatment of esophageal cancer.Methods The expression levels of USP28 and c-Myc in the esophageal epithelial cells Het-1A,ECA109 and ECA109R were quantitatively measured by qRT-PCR.The specific siRNA sequences were designed according to the USP28 and c-Myc genes.The pcDNA-USP28 and pcDNA-c-Myc plasmids were constructed.The esophageal cancer cell ECA109 was transfected with Lipofectamine 2000 to observe the transfection effect and related protein expression.ECA109 and ECA109R cells were exposed to 6 Gy X-ray radiation.The cell apoptosis in each group was detected by flow cytometry.The radiosensitivity was evaluated by clone formation assay.Results The expression levels of USP28 and c-Myc in ECA109 were significantly higher than those in Het-1A (both P＜0.05),and the expression levels of USP28 and c-Myc in ECA109R were remarkably higher than those in ECA109(both P＜0.05).The pcDNA-USP28 and pcDNA-c-Myc recombinant plasmids were successfully constructed.Compared with the negative control group,the expression of USP28 at the protein and mRNA levels in the si-USP28 group was significantly down-regulated,whereas those in the pcDNA-USP28 group were remarkably up-regulated.Similar results were obtained in terms of c-Myc.Compared with the control group,the expression level of c-Myc protein was significantly up-regulated in the pcDNA-USP28 group,whereas considerably down-regulated in the si-USP28 group.After 6 Gy irradiation,the apoptosis rate and radiosensitivity of ECA109 cells were significantly declined.The apoptosis rate and radiosensitivity of ECA109R cells were increased in the si-USP28 group.Conclusions The expression of USP28 protein is closely correlated with the radiosensitivity of esophageal cancer cells.The underlying mechanism may be related to the regulation of c-Myc expression by USP28.

Comparison of different treatment modalities in node-positive patients after radical resection for squamous cell carcinoma of the thoracic esophagus / 中华放射肿瘤学杂志

Objective To compare the efficacy between different modalities in the treatment of positive lymph nodes after radical resection for squamous cell carcinoma of thoracic esophagus(TESCC),and to explore the best treatment mode. The Kaplan?Meier method was used to calculate survival rates. The log-rank test and Cox model were used for univariate and multivariate prognostic analyses,respectively. Methods A retrospective analysis was performed among 548 patients with TESCC who were admitted to our hospital and had positive lymph nodes after radical resection. The efficacy of different treatment methods was evaluated. Propensity scores(PSM)were used to make 1-to-1 patient matching between different treatment groups to further analyze and figure out the best treatment model for patients. The Kaplan?Meier method was used to calculate the overall survival(OS)and disease-free survival(DFS)rates. The log-rank test was used for survival analysis and univariate prognostic analysis. The Cox regression model was used for multivariate prognostic analysis. Results In all patients,the 1-,3-,and 5-year OS rates were 79.9%, 38.1% and 28.5%,respectively,while the 1-,3-,and 5-year DFS rates were 68.5%,39.8% and 32.5%, respectively. After 1-to-1 matching based on PSM,there were no differences in general clinical pathological data between the four groups. After PSM,there were significant differences in 1-,3-,and 5-year OS and DFS rates between the surgery alone group,the postoperative radiotherapy group,the postoperative chemotherapy group,and the postoperative chemoradiotherapy(POCRT)group(P=0.000,0.000).There were significant differences in OS and DFS rates between patients with stage N1,N2,and N3disease(P=0.000,0.000).The result of the Cox multivariate analysis showed that treatment method and N staging were two independent prognostic factors for OS and DFS(P=0.001,0.000,0.025,0.016). Conclusions Patients with positive lymph nodes after radical resection for TESCC have a poor prognosis. Moreover,the prognosis becomes worse with the increase in metastatic lymph nodes. POCRT may improve the survival in those patients. Prospective studies are needed to further confirm those conclusions.

Abdominal lymph node recurrence after radical surgery in patients with middle thoracic esophageal squamous cell carcinoma:risk factors and guidance for postoperative radiotherapy / 中华放射肿瘤学杂志

Objective To analyze the risk factors for abdominal lymph node recurrence after radical surgery in patients with middle thoracic esophageal squamous cell carcinoma (TE-SCC),and to design the target volume for postoperative radiotherapy based on the results.Methods A retrospective study was performed among 913 patients with middle TE-SCC undergoing radical surgery who were admitted to our hospital from 2007 to 2012.Influencing factors were analyzed for abdominal lymph node recurrence after treatment.The efficacy was compared between different treatment methods in the high-risk population.Comparison of categorical data was made by chi-square test.The overall survival rates (OS) were calculated by the Kaplan-Meier method and analyzed by the univariate log-rank analysis.The influencing factors for abdominal lymph node recurrence were analyzed by the multivariate logistic regression equation.Results After treatment,37 patients had abdominal lymph node recurrence,yielding a recurrence rate of 4.1％.A total of 53 recurrent sites were found.The univariate analysis showed that no/low differentiation,pT3+4 stage,no less than 3 positive postoperative lymph nodes,and positive postoperative abdominal lymph nodes were influencing factors for abdominal lymph node recurrence (P =0.032,0.001,0.009,0.000).The multivariate regression analysis showed that pathological T staging and positive postoperative abdominal lymph nodes were influencing factors for abdominal lymph node recurrence (P=0.011,0.000).For patients with pT3+4 stage disease and positive postoperative abdominal lymph nodes,postoperative radiotherapy improved OS and local control rates but failed to reduce the distant metastasis-free rate.Conclusions T staging and positive postoperative abdominal lymph nodes are important risk factors for abdominal lymph node recurrence after radical surgery in patients with middle TE-SCC.Postoperative adjuvant therapy is recommended for patients with pT3+4 stage disease and positive postoperative abdominal lymph nodes.

Comparison of IPSA and HIPO inverse planning optimization algorithms for cervical cancer intracavitary/interstitial brachytherapy / 中华放射医学与防护杂志

Objective To compare the difference of dose distribution between inverse planning simulated annealing (IPSA) and hybrid inverse treatment planning and optimization (HIPO) in 3D brachytherapy plan of cervical cancer,and to provide evidence for selection of reverse planning optimization method for cervical cancer brachytherapy.Methods From Dec 2016 to May 2017,totally 43 cases of patients with cervical cancer radical surgery were selected.Original IPSA brachytherapy treatment plan optimization was applied to all cases.Based on the information of original image,IPSA and HIPO plans were established according to the same initial conditions.Parameters of Dg0,D100,V100％,Homogeneity Index (HI),and conformal index (CI) of the bladder,rectum and sigmoid D2 cm3 data for High-Risk Clinical Target Volume (HR-CTV) were assessed.Results There was no statistically significant difference in D90,D100 and CI for HR-CTV between the two groups.But the V100％ of HR-CTV in HIPO group was significantly higher than that in IPSA group [(87.72 ±0.49)％ vs.(85.01 ± 0.55)％,t =2.54,P ＜0.05].Furthermore,HI in HIPO group was (0.51 ±0.08),which was higher than that in IPSA group (0.42 ± 0.06),and the difference was statistically significant (t =3.02,P ＜ 0.05).Compared with IPSA,bladder D2 cm3 and rectum D2 cm3 [(3.04 ± 0.37) Gy] for HIPO plan were lower [(3.42 ± 0.17) Gy vs.(3.57 ± 0.28) Gy,(3.04 ± 0.37) Gy vs.(3.57 ± 0.28) Gy],which had reached statistical significance (t =0.27,0.19,P ＜ 0.05).There was no statistical significance in the D2 cm3 dose of sigmoid.Conclusions In the treatment of cervical cancer,better target area HI and less irradiated dose of bladder and rectum can be obtained by HIPO optimization than IPSA optimization.

Efficacy of postoperative chemoradiotherapy after radical resection of squamous cell carcinoma of upper thoracic esophagus / 中华放射医学与防护杂志

Objective To compare the prognosis of patients with squamous cell carcinona of the upper thoracic esophagus after radical resection with and without postoperative chemoradiotherapy (POCRT).Methods From January 2007 to December 2011,168 patients with upper thoracic esophageal carcinoma who were treated in the Fourth Hospital of Hebei Medical University were retrospectively included in this study.According to the different treatment method,they were divided into simple surgery group (86 cases) and POCRT group (82 cases) respectively.Based on SPSS statistical software,the group data composition,prognostic analysis and multivariate prognostic analysis were performed by x2 test,Log-rank method and Cox regression model,respectively.Results The 1,3,5 year-survival rate,recurrence rate and distant metastasis rate were 83.9％,52.4％,43.5％,26.5％,40.8％,43.4％ and 5.3％,11.4％,16.9％,respectively.The result of multivariate analysis showed that gender,T stage,N stage and treatment method were independent prognostic factors of overall survival (P =0.020,0.008,0.005,0.000);N staging and treatment method were the independent prognostic factors of local/regional recurrence (P =0.001,0.003);differentiation and T staging were the independent prognostic factors of distant metastasis (P =0.045,0.020).The intrathoracic regional recurrence rate of operation only group and POCRT group patients were 44.2％ (38/86) and 29.3％ (24/82) respectively,where the difference was statistically significant (x2 =7.110,P ＜ 0.05).The rate of metastasis were 19.8％ (17/86) and 13.4％ (11/82) respectively without significant difference (P ＞0.05).Conclusions The recurrence rate of patients with upper thoracic esophageal squamous cell carcinoma after radical resection was still high.Postoperative chemoradiotherapy can improve the overall survival rate and reduce the recurrence rate,but whether it can reduce the patient's distant metastasis rate needs further study.

Failure patterns of radical surgery in patients with T1-4N0-1M0 thoracic esophageal squamous cell carcinoma: implications for the target area design of postoperative therapy / 中华放射医学与防护杂志

Objective To analyze the failure patterns and prognostic factors of radical surgery in patients with T1-4N0-1M0 thoracic esophageal squamous cell carcinoma (TESCC),and the implications for the target area design of postoperative therapy.Methods We retrospectively analyzed 1 191 patients with TESCC who underwent radical surgery at our institution.The failure patterns,the prognostic factors,as well as the effects of lesion locations and N stage on the failure patterns were analyzed.Results The thoracic-region recurrence rate and the distant metastasis rate was 31.7％ and 16.4％ in all patients.The multivariate analysis showed that the lesion locations,the degree of inflammatory adhesion,T staging,N staging and the rate of lymph nodes metastasis were independent factors affecting the regional recurrence (P ＜ 0.05).Gender,tumor differentiation and the rate of lymph nodes metastasis were independent factors affecting distant metastasis (P ＜ 0.05).The intrathoracic lymph nodes recurrence rate of upper/middle TESCC was significantly higher than that of the lower TESCC (x2 =6.179,P =0.046),while the abdomen lymph nodes recurrence rate of the lower was significantly higher than that of upper/middle TESCC (x2 =15.853,P ＜ 0.05).The recurrence rate and distant metastasis rate of stage N1 patients were significantly higher than that of N0 patients (x2 =7.764-56.495,P ＜ 0.05).The abdomen lymph nodes recurrence rate of stage N1 patients was significantly higher than that of N0 in upper TESCC (x2 =7.905,P ＜0.05).The supraclavicular and intrathoracic lymph nodes recurrence rates of stage N1 patients were significantly higher than that of N0 patients in middle TESCC (x2 =12.506,18.436,P ＜ 0.05).The supraclavicular lymph nodes,anastomosis and abdomen lymph node recurrence rates of stage N1 were significantly higher than that of N0 patients in lower TESCC (x5 =5.272,4.878,18.006,P ＜ 0.05).The anastomotic recurrence rate of stage T3+4 was higher than that of T1+2 in middle/lower TESCC (x2 =4.341,7.154,P ＜ 0.05),and the abdominal lymph nodes recurrence rate of stage T3 +4 was higher than that of T1 +2 in lower TESCC (x2 =5.366,P ＜ 0.05).Conclusions The lymphatic drainage regions for postoperative radiotherapy (PORT) are selective.We suggest that abdominal lymph nodes drainage area should be noted for the stage N1 patients with upper TESCC,and the supraclavicular lymph nodes drainage area should be noted for the N1 patients with lower TESCC.In addition,the anastomosis is suggested to be included in PORT target area for stage T3/T4 middle/lower TESCC patients.

Effect of BMI-1 on radiosensitization of esophageal carcino-ma cells after silencing of BMI-1 gene / 中华放射肿瘤学杂志

Objective To investigate the effects of BMI-1 expression inhibition by RNA interference on the radiosensitivity of esophageal cancer TE-13 cells and its mechanism.Methods The siRNA based on the sequence of BMI-1 mRNA was synthesized to transfect cultured TE-13 cells as BMI-1 siRNA group,a negative one was synthesized to transfect cultured TE-13 cells as negative control group (NC group),and untransfected TE-13 cells were named as control group.The expression of the BMI-1 mRNA and protein in TE-13 cells was measured by quantitative real-time PCR and Western blot,respectively.The cell proliferation and the radiosensitivity of TE-13 cells were measured by MTS and colony-forming assay,respectively.Flow cytometry was used to analyze cell cycle and apoptosis.The expression of BCL-2 and BAX in TE-13 cells was measured by Western blot.Comparison between groups was made by analysis of variance.Results The BMI-1 siRNA group had significantly lower expression of BMI-1 mRNA and protein than the control group and the NC group (P=0.000,0.000).The proliferation of TE-13 cells in the BMI-1 siRNA group decreased significantly after irradiation (P=0.031).The colony-forming assay showed that the BMI-1 siRNA group had a significantly higher radiosensitivity than the control group and the NC group (P=0.000).After irradiation,the BMI-1 siRNA group had a significantly lower percentage of cells in G2/M phase than the control group and the NC group (P=0.000,0.000).The BMI-1 siRNA group had a significantly increased apoptosis rate (P=0.000,0.000),significantly reduced expression of BCL-2(P=0.000,0.000),and significantly increased expression of BAX after irradiation (P=0.000,0.000).Conclusions BMI-1 siRNA can inhibit the expression of BMI-1 gene in esophageal cancer TE-13 cells,eliminate the cell cycle arrest in G2/M phase,induce cell apoptosis after ionizing irradiation in vitro,and increase the radiosensitivity,which may be related to the regulation of the expression of BCL-2 and BAX.

Effect of postoperative adjuvant therapy on the prognosis of patients with stage pT3N0M0 thoracic esophageal squamous cell carcinoma:a preliminary analysis / 中华放射肿瘤学杂志

Objective To determine the prognostic factors in patients with stage pT3N0M0 thoracic esophageal squamous cell carcinoma (TSCC) after esophagectomy, and to compare the effects of different treatment modalities on the prognosis of patients.Methods A retrospective analysis was conducted on 480 patients with stage pT3N0M0 TSCC from 2007 to 2010 to determine the prognostic factors in the patients, and to compare the effects of different treatment modalities on their prognosis.Survival rate was calculated using the Kaplan-Meier estimator, and multivariate analysis of prognostic factors was performed using the Cox model.Results Of the 439, 333, and 278 patients who completed the 1-, 3-, and 5-year follow-up, respectively, the 1-, 3-, and 5-year overall survival (OS) rates were 90.0%, 68.7%, and 57.9%(median 87 months, 95% confidence interval (CI=74.7-99.4), respectively, and the 1-, 3-, and 5-year disease-free survival (DFS) rates were 82.3%, 60.4%, and 52.3%(median 71.3 months, 95%CI=55.1-87.5), respectively.In order to account for the different constituent ratios of some clinical and pathological data between the three groups of patients, 55 patients in each group were matched using propensity score matching (PSM)(all P>0.05).It was found that the post-PSM 1-,3-, and 5-year OS and DFS were significantly different between patients who received surgery only, postoperative chemotherapy (POCT), and postoperative chemoradiotherapy/radiotherapy (POCRT/RT)(P=0.000 and 0.006,respectively).Multivariate Cox analysis showed that age, lesion location, and treatment modality were independent prognostic factors for OS and DFS (P=0.029,0.004,0.000 and P=0.009,0.003,0.002), and the length of lesion was also an independent prognostic factor for DFS (P=0.003).Conclusions Although the rate of post-operative treatment failure is still high among patients with stage pT3N0M0 TSCC, POCRT/PORT can improve the prognosis and the 5-year OS and DFS of these patients.However, further large-sample prospective studies will be required to confirm these findings.

Analysis of postoperative failure in patients with stage pT3N0M0 thoracic esophageal squamous cell carcinoma and consideration of postoperative radiotherapy / 中华放射肿瘤学杂志

Objective To investigate the failure mode in patients with stage pT3N0M0 thoracic esophageal squamous cell carcinoma (TESCC) after surgery,and to discuss the significance and feasibility of postoperative radiotherapy according to the failure mode.Methods A retrospective analysis was performed on 227 patients with stage pT3N0M0 TESCC who met the inclusion criteria from January 2007 to December 2010.Their postoperative failure mode was analyzed,and,with reference to relevant research,the significance of postoperative radiotherapy and its target patients were explored.The Kaplan-Meier method was used to calculate overall survival (OS),local recurrence (LR),and distant metastasis (DM) rates,and the log-rank test was used for survival difference analysis and univariate prognostic analysis.The Cox model was used for multivariate prognostic analysis.Results After surgery,there were 58 patients (25.6％) with LR in the thoracic cavity and 27 patients (11.9％) with DM,and 10 patients had both LR and DM.Twentynine (50％) of the 58 patients had recurrence in the thoracic mediastinal lymph nodes.The results of univariate analysis showed that the 3-and 5-year OS rates of patients with upper thoracic esophageal cancer were significantly lower than those of patients with middle and lower esophageal cancer (P =0.000),and the chest-regional recurrence rate was significantly higher in the former group than in the latter two groups (P=0.047);the 3-and 5-year OS rates of patients with poorly differentiated squamous cell carcinoma were significantly lower than those of patients with moderately and well differentiated squamous cell carcinoma (P =0.005),and the DM rate was significantly higher than in the former group than in the latter two groups (P=0.000).The results of multivariate analysis showed that lesion site and the degree of pathological differentiation were independent prognostic factors for OS (P=0.014 and 0.010);lesion site was the independent prognostic factor for chest-regional recurrence (P=0.046);the degree of pathological differentiation was the independent prognostic factor for DM (P=0.000).Conclusions For patients with stage pT3N0M0 TESCC after two-field esophagectomy,the most common failure mode is chest-regional recurrence,especially in patients with upper thoracic esophageal cancer.Therefore,postoperative radiotherapy is suggested for upper-thoracic TESCC.