1.Predictive value of enhanced CT radiomics feature model for 5-year overall survival in patients with esophageal squamous cell carcinoma after radiotherapy
Jie KONG ; Liang CHEN ; Zhikun LIU ; Shuchai ZHU ; Fang YANG ; Yuguang SHANG ; Jialiang REN
Chinese Journal of Radiation Oncology 2023;32(11):970-977
Objective:To evaluate the value of enhanced CT radiomics feature model for predicting 5-year overall survival (OS) of esophageal squamous cell carcinoma patients after radiotherapy.Methods:Clinical data of 218 patients with esophageal squamous cell carcinoma treated with radical chemoradiotherapy in the Fourth Hospital of Hebei Medical University from July 2016 to December 2017 were retrospectively analyzed. Patients were randomly divided into the training group ( n=153) or a validation group ( n=65) at a 7 vs. 3 ratio. Enhanced CT radiomics features were extracted. The data in the training group was used to construct the prediction model, and the data in the validation group were utilized to validate the efficiency of this model for predicting the 5-year OS of patients. The predictive performance of this model was assessed by the receiver operating characteristic (ROC) curve, consistency index (C-index), and decision curve analysis (DCA). Results:The 1-, 3-, 5-year OS rates were 67.0%, 33.4%, 24.9%. Five radiomic features were selected from extracted features in the training group to construct the radiomic signature (RS) for predicting 5-year OS. The area under the ROC curve (AUC) was 0.760 in the training group and 0.707 in the validation group, and the C-index was 0.680 and 0.684, respectively. The radiomics nomogram, which incorporated the RS with clinical risk factors, were established to predict the 5-year OS of esophageal squamous cell carcinoma patients after radiotherapy. The AUC was 0.782 in the training group and 0.751 in the validation group, and the C-index was 0.708 and 0.688, respectively. According to the optimal cutoff of the model, all patients were divided into the high risk and low risk groups. The 1-, 3-, 5-year OS rates were 86.5%, 65.4%, 28.9% in the low risk group, and 58.4%, 17.8%, 5.9% in the high risk group, and the differences were statistically significant (all P<0.001). Similar conclusions were obtained in the validation group (all P<0.001). Conclusion:Enhanced CT radiomics features can be utilized to construct the prediction model for 5-year OS of esophageal squamous cell carcinoma patients after radiotherapy, which can be applied in clinical practice.
2.Establishment of HPLC fingerprint of Yi drugs of MaRSDenia tenacissima and evaluation of chemometrics
Zhikun ZHU ; Yuanyuan GUO ; Piao WANG ; Wubing WANG ; Siqi LI ; Lingyun CHEN
International Journal of Traditional Chinese Medicine 2023;45(12):1549-1554
Objective:To establish the HPLC fingerprint of MaRSDenia tenacissima; To evaluate the different origins of MaRSDenia tenacissima by combining chemometric methods.Methods:High performance liquid chromatography (HPLC) method was adopted, with DiKMA C18 column (250 mm× 4.6 mm, 5 μm), acetonitrile-0.05% phosphoric acid aqueous solution as mobile phase gradient elution, flow rate of 1.0 ml/min. The detection wavelength was set at 230 nm, the column temperature was 30 ℃, and sample size was 10 μl. Chromatographic information was imported into the similarity evaluation system for TCM chromatographic fingerprints (2012 version) for similarity analysis. SPSS Statistics 26 was used for system clustering analysis, and SIMCA 14.1 software was used for principal component analysis and partial least squares discriminant analysis (PLS-DA).Results:Totally 12 common peaks were identified. Two chromatographic peaks were identified as tenacissoside G and tenacissoside I. The relative similarity of fingerprints of 15 batches of samples and references ranged from 0.942 to 0.995. When the square Euclidean distance was 20, the samples could be grouped into two categories: S1-S3, S13-S15 were grouped into one category, and S4-S12 were grouped into another category. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) showed that there were significant differences among 15 batches of MaRSDenia tenacissima, and there was a certain correlation with the origin.Conclusion:The results can provide a reference for analyzing the differences of MaRSDenia tenacissima from different producing areas and the quality standards of related formula granules in the later stage.
3.Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with supplemental radiotherapy under different prognostic scores
Dongxing SHEN ; Zhikun LIU ; Zhensheng LI ; Huina HAN ; Yuguang SHANG ; Longyu ZHU ; Deyou KONG ; Andu ZHANG ; Jie KONG ; Jian ZHANG ; Fang YANG ; Fuyin QU ; Jun ZHANG
Chinese Journal of Radiation Oncology 2022;31(2):131-137
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.
4.Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with different doses of whole brain radiotherapy
Dongxing SHEN ; Zhikun LIU ; Zhensheng LI ; Huina HAN ; Yuguang SHANG ; Longyu ZHU ; Deyou KONG ; Jian ZHANG ; Fuyin QU ; Jun ZHANG
Chinese Journal of Radiation Oncology 2022;31(4):340-346
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.
5.Comparison of different local treatment patterns in breast cancer with ipsilateral supraclavicular lymph node metastasis
Zhikun LIU ; Xiaohong LI ; Longyu ZHU ; Huina HAN ; Andu ZHANG ; Xuejuan DUAN ; Yuguang SHANG ; Dongxing SHEN ; Ling PEI ; Sicong JIA ; Li ZHU ; Jun ZHANG
Chinese Journal of Radiation Oncology 2021;30(5):462-467
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.
6.Efficacy of prophylactic irradiation of internal mammary lymph nodes in breast cancer: a Meta-analysis
Sicong JIA ; Zhikun LIU ; Jun ZHANG ; Chenguang ZHAO ; Longyu ZHU ; Jie KONG ; Huina HAN ; Yuguang SHANG ; Dongxing SHEN ; Xuejuan DUAN
Chinese Journal of Radiation Oncology 2021;30(9):903-909
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).
7.Maze Ⅳ in the treatment of heart valve disease with persistent atrial fibrillation in elderly patients: A cohort study
Zhikun FU ; Huijuan YANG ; Xiangli ZHANG ; Shuguang ZHANG ; Heng YANG ; Yongfeng ZHU ; Peng DU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(12):1413-1417
Objective To investigate the clinical effect of Maze Ⅳ in the treatment of elderly patients with valvular heart disease and persistent atrial fibrillation (AF). Methods We retrospectively analyzed the clinical data of 78 elderly patients with cardiac valve disease combined with persistent AF in our hospital from 2017 to 2018. The patients were allocated to two groups including a trial group (n=37) and a control group (n=41). There were 21 males and 16 females aged 61 to 74 (65.2±2.5) years in the trial group. There were 23 males and 18 females aged 62 to 76 (64.8±3.3) years in the control group. The clinical effects of the two groups were compared. Results There was no statistical difference in baseline data between the two groups (P>0.05). The aortic occlusion time, extracorporeal circulation time, and operation time of the trial group were longer than those of the control group with statistical differences (P<0.05). There was no statistical difference in postoperative ventilator assistance time, complication rate, mortality, ICU retention time, perioperative drainage, red blood cell transfusion volume, or length of hospital stay between the two groups (P>0.05). At the time of discharge, postoperaive 1-month, 3-month, 6-month, and 12-month, the maintenance rates of sinus rhythm in the control group were statistically different from those of the trial group (P<0.05). Compared with the control group, left atrial diameter, left ventricular end diastolic diameter and the decrease of pulmonary artery systolic blood pressure were statistically different (P<0.05). Conclusion Maze Ⅳ is safe and effective in the treatment of elderly patients with valvular heart disease and persistent AF, which is conducive to the recovery and maintenance of sinus rhythm, and is beneficial to the remodeling of the left atrium and left ventricle and the reduction of pulmonary systolic blood pressure with improvement of life quality of the patients.
8.The effect of RNF2 knockdown on the radiosensitivity in transplanted tumor of nude mice of esophageal carcinoma in vivo
Xingxiao YANG ; Xueyuan ZHANG ; Qiaofang LI ; Ming MA ; Zhikun LIU ; Shuchai ZHU
Chinese Journal of Radiation Oncology 2019;28(8):612-615
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.
9.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
Wenbin SHEN ; Hongmei GAO ; Shuchai ZHU ; Teng LI ; Shuguang LI ; Youmei LI ; Zhikun LIU ; Juan LI ; Jingwei SU
Chinese Journal of Radiological Medicine and Protection 2018;38(4):265-272
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.
10.Efficacy of postoperative chemoradiotherapy after radical resection of squamous cell carcinoma of upper thoracic esophagus
Wenbin SHEN ; Hongmei GAO ; Shuchai ZHU ; Teng LI ; Shuguang LI ; Youmei LI ; Zhikun LIU ; Juan LI ; Jingwei SU ; Jinrui XU
Chinese Journal of Radiological Medicine and Protection 2018;38(5):355-359
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.

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