1.Endothelial progenitor cells: potential therapeutic targets for ischemic stroke
Yidian FU ; Jingbo ZHANG ; Mengyao ZHAO ; Zhenjie TENG ; Peiyuan LYU
International Journal of Cerebrovascular Diseases 2023;31(12):938-943
Endothelial progenitor cells (EPCs) are immature endothelial cells that can proliferate and differentiate into mature endothelial cells. After vascular injury, EPCs migrate from the bone marrow to the ischemic area, participating in damaged endothelial repair and neovascularization, providing a new potential therapeutic approach for vascular diseases including ischemic stroke. This article reviews the feasibility and limitations of EPCs as potential therapeutic targets for ischemic stroke.
2.Characteristics of traditional Chinese medicine pattern distribution of metabolic syndrome based on latent class analysis and latent structure analysis
AXINBAI MALINA ; Yidian YANG ; Huan ZHANG ; Yuqing ZHAO ; Liping ZHANG
Journal of Beijing University of Traditional Chinese Medicine 2024;47(4):532-544
Objective To analyze the distribution of traditional Chinese medicine patterns in metabolic syndrome(MS),with the aim of deriving the attributes and characteristics of patterns in patients with MS more accurately and finely.Methods The data of 695 MS patients admitted to Dongfang Hospital,Beijing University of Chinese Medicine from December 2017 to September 2022 were retrospectively analyzed to derive traditional Chinese medicine patterns using latent class analysis and latent structure analysis,and the above results were used to identify the pattern type of each patient according to differentiation of syndromes,to determine the traditional Chinese medicine pattern types of MS patients.Results A total of 9,044 times of the symptoms and signs were included in this study,and the top 10 high-frequency symptoms and signs were dry mouth and polydipsia(77.70%),fatigue(60.58%),greasy fur(59.14%),blurred vision(54.68%),slippery pulse(53.96%),wiry pulse(52.09%),white fur(48.92%),numbness of the limbs(43.60%),yellow fur(39.71%),and cold limbs(36.40%).Based on the result of the latent class analysis,this study determined the main pattern elements of 695 patients with MS.The pathological pattern elements included qi deficiency,phlegm-dampness,dampness-heat,qi stagnation,yin deficiency,fire-heat,and impairment of body fluids;the pathological pattern elements were mainly located in liver,spleen,lung,and kidney;the 695 patients could be classified into three main groups:predominantly deficiency syndrome,predominantly excess syndrome,and deficiency syndrome accompanied with excess syndrome.Through analyzing the latent structure model of the symptoms and signs of 695 patients with MS,six basic syndromes were established,which were the syndromes of hyperactivity of liver yang,deficiency in the spleen with dampness retention,deficiency of both kidney yin and yang,consumption of body fluids due to intense heat,blood stasis due to qi deficiency,and stagnation of liver qi with stomach heat.Combined with the theory of Chinese medicine,the four-diagnosis information of 695 cases of MS was comprehensively integrated,and on the basis of latent class analysis and latent structure analysis,secondary syndrome differentiation of patients was performed.A total of 20 syndromes with a frequency of occurrence of>1%were finally obtained,with the highest frequency being the syndrome of stagnation of liver qi and spleen deficiency,internal retention of dampness-heat(12.66%).Conclusion The pathogenesis of MS is complex and the pattern types are widely distributed,but in general,the syndrome of stagnation of liver qi and spleen deficiency,and internal retention of dampness-heat is the most common.Therefore,clinically,based on syndrome differentiation and treatment,attention should be paid to combining the application of invigorating the spleen and soothing the liver,and clearing heat to resolve turbidity.
3.Prognostic analysis of fluoroucil combined with cisplatin and paclitaxel combined with cisplatin regimens with concurrent radiotherapy in treatment of esophageal squamous cell carcinoma
Qingshan ZHU ; Tingwei MA ; Nengchao WANG ; Weipeng LIU ; Zhijie HE ; Xiaomin WANG ; Jing SHEN ; Tao WEI ; Shijie ZHAO ; Yidian ZHAO ; Fujun ZHAO ; Lianjie FENG
Cancer Research and Clinic 2020;32(6):381-386
Objective:To compare the prognosis of fluoroucil combined with cisplatin and paclitaxel combined with cisplatin regimens with concurrent radiotherapy in treatment of esophageal squamous cell carcinoma.Methods:A total of 120 patients with esophageal squamous cell carcinoma who were admitted to Anyang Tumor Hospital of Henan Province from December 2012 to November 2018 were randomly divided into group A and group B by using a random number generator. Group A was given cisplatin combined with 5-fluorouracil, and group B was given cisplatin combined with paclitaxel. Both groups had the same radiotherapy regimen, and both used intensity-modulated radiation therapy (IMRT). Completions of 50 Gy radiotherapy and at least one cycle of chemotherapy were considered to be in line with the plan. Survival data was analyzed in the term of intention-to-treat (ITT) and per-protocol (PP) set.Results:Of the 120 patients, 114 patients were treated and the adverse reactions could be evaluated, including 55 cases in group A and 59 cases in group B. The incidence of grade Ⅲ-Ⅳ leukopenia in group B was higher than that in group A [49.2% (29/59) vs. 25.5% (14/55)], and the difference was statistically significant ( χ2 = 6.805, P = 0.012), and there were no statistical differences in the other adverse reactions between the two groups (All P > 0.05). A total of 113 cases can be analyzed for survival. According to ITT analysis, the median progression-free survival (PFS) time in group A and group B was 28.0 months (95% CI 15.5-34.5 months) and 27.0 months (95% CI 17.0-41.0 months), the median overall survival (OS) time was 28.0 months (95% CI 15.8-34.2 months) and not reached, the differences were not statistically significant (both P > 0.05). According to PP analysis, the median PFS time in group A and group B was 28.0 months (95% CI 15.8-34.2 months) and 29.0 months (95% CI 14.9-45.1 months), the median OS time in group A and group B was 28.0 months (95% CI 3.7-52.3 months) and not reached, the differences were not statistically significant (both P > 0.05). Conclusions:The fluorouracil combined with cisplatin regimen and paclitaxel combined with cisplatin regimen with concurrent radiotherapy have similar PFS and OS time in treatment of esophageal squamous cell carcinoma, the adverse reactions are different, but they are all tolerable. In individualized clinical practice, the toxicities and costs of the two regimens can be comprehensively considered.
4.Research progress of glymphatic system and central nervous system diseases
Mengyao ZHAO ; Yidian FU ; Xiaohan LIANG ; Xiaohan LYU ; Peiyuan LYU
Chinese Journal of Nervous and Mental Diseases 2023;49(11):689-694
The glymphatic system is a unique network of the central nervous system that facilitates the removal of metabolic waste from the brain and maintains homeostasis.The glymphatic system is relatively active during sleep,and its physiological function is affected by many factors.The application of non-invasive imaging techniques to evaluate the function of the glymphatic system has promoted the development of clinical studies.More and more studies have demonstrated the association between the function of glymphatic system and the pathogenesis of neurodegenerative diseases,cerebrovascular diseases and other central nervous system diseases.The glymphatic system is expected to become a novel target for predicting prognosis of central nervous system diseases and clinical effects.
5.Comparison of clinical efficacy and prognosis of intensity-modulated radiotherapy and three dimensional conformal radiotherapy in patients with stage Ⅱ/m esophageal cancer: a multi-center retrospective analysis in Beijing, Tianjin and Hebei province (3JECROG R-06)
Yonggang XU ; Xin WANG ; Chen LI ; Lan WANG ; Chun HAN ; Junqiang CHEN ; Wencheng ZHANG ; Xiaomin WANG ; Xiaolin GE ; Wenbin SHEN ; Miaomiao HU ; Qianqian YUAN ; Chongli HAO ; Ling LI ; Zhiguo ZHOU ; Shuai QIE ; Na LU ; Qingsong PANG ; Ping WANG ; Yidian ZHAO ; Xinchen SUN ; Kaixian ZHANG ; Xueying QIAO ; Miaoling LIU ; Yadi WANG ; Shuchai ZHU ; Dazhi CHEN ; Qinhong WU ; Hong GAO ; Xia XIU ; Gaofeng LI ; Zefen XIAO
Chinese Journal of Radiation Oncology 2019;28(6):405-411
Objective To compare the therapeutic effects between three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) in patients with stage Ⅱ/Ⅲ esophageal cancer and investigate the prognostic factors.Methods Medical record of 2 132 patients with stage Ⅱ/Ⅲ esophageal cancer who underwent definitive radiotherapy with/without chemotherapy in 10 hospitals from January 2002 to December 2016 from were retrospectively analyzed.Among these patients,37.9% of them were aged ≥ 70 years,33.9% with neck and upper esophageal tumors and 66.1% with middle and lower esophageal and borderline tumors.The median gross tumor volume (GTV) and lymph node gross tumor volume (GTVnd) was 41.6 cm3.Among them,32% were stage Ⅱ] and 68% were stage Ⅲ.A total of 723 patients received 3DCRT and 1 409 cases received IMRT.Patients received an equivalent dose in 2 Gy (EQD2) ≥ 60 Gy accounted for 86.1%,and 41.1% of them received concurrent chemoradiotherapy.Results The median follow-up time was 60.8 months.The 1-,3-and 5-year overall survival (OS) of all patients was 73.9%,41.7% and 32.6%,and the 1-,3-and 5-year progression-free survival (PFS) was 62.2%,37.3% and 32%,respectively.Multivariate analysis demonstrated that age,primary tumor location,clinical stage,tumor target volume,EQD2 and concurrent chemoradiotherapy were the independent prognostic factors for OS.Age,primary tumor location,clinical stage,tumor target volume and EQD2 were the independent prognostic factors for PFS.The OS and PFS did not significantly differ among the low-risk,low-/moderate-risk,moderate-/high-risk and high-risk groups according to age≥70 years,tumor diameter>5 cm,tumor volume ≥41.6 cm3 and stage Ⅲ (P<0.001).After the propensity score matching (PSM) method,neither 3DCRT nor IMRT yielded significant advantages in OS or PFS (P=0.971;P=0.658).However,IMRT tended to yield survival benefits in low-risk patients (P=0.125).Conclusions Both 3DCRT and IMRT yield relatively high OS rate in patients with stage Ⅱ/Ⅲ esophageal cancer.The prognosis model established in this investigation can properly predict the survival of patients.Low-risk patients tend to obtain survival benefits from IMRT.
6.Effect of tumor length on clinical stage for non-operative esophageal squamous cell carcinoma patients——multicenter retrospective data analysis (3JECROG R-01D)
Zhiguo ZHOU ; Xin WANG ; Lan WANG ; Junqiang CHEN ; Wencheng ZHANG ; Xiaomin WANG ; Xiaolin GE ; Wenbin SHEN ; Miaomiao HU ; Qianqian YUAN ; Yonggang XU ; Chongli HAO ; Shuai QIE ; Na LU ; Qingsong PANG ; Ping WANG ; Yidian ZHAO ; Xinchen SUN ; Kaixian ZHANG ; Gaofeng LI ; Ling LI ; Miaoling LIU ; Yadi WANG ; Chen LI ; Shuchai ZHU ; Zefen XIAO ; Chun HAN ; Xueying QIAO
Chinese Journal of Radiation Oncology 2019;28(7):490-494
Objective To retrospectively analyze the effect of tumor length on the prognosis in stage Ⅱ/Ⅲ esophageal squamous cell carcinoma (ESCC) patients treated with definitive radiotherapy and to evaluate the role of tumor length in clinical stage for non-operative ESCC patients.Methods The data of 2 086 ESCC patients who were treated with definitive radiotherapy from 2002 to 2016 in 10 hospitals (3JECROG) were analyzed.The effect of tumor length on overall survival (OS) was analyzed and stratified analysis of tumor length was done in different stages of ESCC.Results The median OS and median progression-free survival (PFS) time of the whole group were 25.6 months and 18.2 months respectively.The Cox multivariate analysis showed that treatment moda,aga,alinical stage and tumor length were independent prognostic factors.The median,1-,3-,and 5-year OS were 28.9 months,77.3%,45.0%,and 36.3% versus 21.9 months,69.9%,37.9%,and 28.1% for patients with ≤ 5 cm and patients > 5 cm respectively (P<0.05).For stage Ⅱ patienta,abe median OS were 42.1 and 38.9 months respectively in ≤ 5 cm group and>5 cm group (P=0.303).And for stage Ⅲ patienta,abe median OS were 23.9 and 19.3 months respectively in ≤5 cm group and>5 cm group (P<0.001).The median OS with N1was 24.1 and 18.4 montha,aespectively in ≤5 cm group and>5 cm group (P<0.001).Conclusions The tumor length was an independent prognostic factor for stage Ⅱ/Ⅲ patients treated definitive radiotherapy.The tumor length may be helpful in clinical staging of ESCa,aspecially for stage Ⅲ and N1.
7.Efficacy analysis of the radiotherapy and chemotherapy in patients with stage Ⅳ esophageal squamous carcinoma: a multicenter retrospective study of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG R-01F)
Miaomiao HU ; Qianqian YUAN ; Xusheng ZHANG ; Sen YANG ; Xin WANG ; Lan WANG ; Junqiang CHEN ; Wencheng ZHANG ; Xiaomin WANG ; Xiaolin GE ; Wenbin SHEN ; Yonggang XU ; Chongli HAO ; Zhiguo ZHOU ; Shuai QIE ; Na LU ; Qingsong PANG ; Yidian ZHAO ; Xinchen SUN ; Gaofeng LI ; Ling LI ; Xueying QIAO ; Miaoling LIU ; Yadi WANG ; Chen LI ; Shuchai ZHU ; Chun HAN ; Kaixian ZHANG ; Zefen XIAO
Chinese Journal of Oncology 2020;42(8):676-681
Objective:To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation.Methods:The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed.Results:The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups ( P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy ( P<0.05). Multivariate analysis demonstrated that PGTV dose ( OR=0.693, P=0.004), radiation esophagitis ( OR=0.867, P=0.038), and radiation pneumonia ( OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions:For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.
8.Long-term efficacy and safety of simultaneous integrated boost radiotherapy in non-operative esophageal squamous cell carcinoma: a multicenter retrospective data analysis (3JECROG R-05)
Xiaomin WANG ; Lan WANG ; Xin WANG ; Junqiang CHEN ; Chen LI ; Wencheng ZHANG ; Xiaolin GE ; Wenbin SHEN ; Miaomiao HU ; Qianqian YUAN ; Yonggang XU ; Chongli HAO ; Zhiguo ZHOU ; Shuai QIE ; Na LU ; Chun HAN ; Qingsong PANG ; Ping WANG ; Xinchen SUN ; Kaixian ZHANG ; Gaofeng LI ; Ling LI ; Miaoling LIU ; Yadi WANG ; Xueying QIAO ; Shuchai ZHU ; Zongmei ZHOU ; Yidian ZHAO ; Zefen XIAO
Chinese Journal of Oncology 2021;43(8):889-896
Objective:To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients.Methods:The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed.Results:The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively ( P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively ( P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm 3, the median survival time of SIB and No-SIB group was 34.7 and 30.3 months ( P=0.155), respectively. In the patients whose GTV volume>50 cm 3, the median survival time of SIB and No-SIB group was 16.1 and 20.1 months ( P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group ( P<0.001). Conclusions:The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.
9.Efficacy analysis of the radiotherapy and chemotherapy in patients with stage Ⅳ esophageal squamous carcinoma: a multicenter retrospective study of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG R-01F)
Miaomiao HU ; Qianqian YUAN ; Xusheng ZHANG ; Sen YANG ; Xin WANG ; Lan WANG ; Junqiang CHEN ; Wencheng ZHANG ; Xiaomin WANG ; Xiaolin GE ; Wenbin SHEN ; Yonggang XU ; Chongli HAO ; Zhiguo ZHOU ; Shuai QIE ; Na LU ; Qingsong PANG ; Yidian ZHAO ; Xinchen SUN ; Gaofeng LI ; Ling LI ; Xueying QIAO ; Miaoling LIU ; Yadi WANG ; Chen LI ; Shuchai ZHU ; Chun HAN ; Kaixian ZHANG ; Zefen XIAO
Chinese Journal of Oncology 2020;42(8):676-681
Objective:To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation.Methods:The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed.Results:The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups ( P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy ( P<0.05). Multivariate analysis demonstrated that PGTV dose ( OR=0.693, P=0.004), radiation esophagitis ( OR=0.867, P=0.038), and radiation pneumonia ( OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions:For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.
10.Long-term efficacy and safety of simultaneous integrated boost radiotherapy in non-operative esophageal squamous cell carcinoma: a multicenter retrospective data analysis (3JECROG R-05)
Xiaomin WANG ; Lan WANG ; Xin WANG ; Junqiang CHEN ; Chen LI ; Wencheng ZHANG ; Xiaolin GE ; Wenbin SHEN ; Miaomiao HU ; Qianqian YUAN ; Yonggang XU ; Chongli HAO ; Zhiguo ZHOU ; Shuai QIE ; Na LU ; Chun HAN ; Qingsong PANG ; Ping WANG ; Xinchen SUN ; Kaixian ZHANG ; Gaofeng LI ; Ling LI ; Miaoling LIU ; Yadi WANG ; Xueying QIAO ; Shuchai ZHU ; Zongmei ZHOU ; Yidian ZHAO ; Zefen XIAO
Chinese Journal of Oncology 2021;43(8):889-896
Objective:To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients.Methods:The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed.Results:The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively ( P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively ( P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy ( P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm 3, the median survival time of SIB and No-SIB group was 34.7 and 30.3 months ( P=0.155), respectively. In the patients whose GTV volume>50 cm 3, the median survival time of SIB and No-SIB group was 16.1 and 20.1 months ( P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group ( P<0.001). Conclusions:The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.