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OBJECTIVE To investigate the effects of aucubin （Auc） on the malignant biological behavior of breast cancer cells by regulating cyclin-dependent kinase 1（CDK1）/cyclin B1（CCNB1）/Polo-like kinase 1 （PLK1） signaling pathway. METHODS Human breast cancer cells MCF-7 were divided into control group， Auc low-， medium- and high-concentration groups （AUC-L， AUC-M， AUC-H groups， 20， 40 and 80 μmol/L Auc）， Auc-H+pcDNA-NC group （80 μmol/L Auc+transfected pcDNA- NC plasmid）， and Auc-H+pcDNA-CDK1 group （80 μmol/L Auc+transfected pcDNA-CDK1 plasmid）. Cell proliferation， clonal formation， invasion and migration abilities， apoptosis and cycle distribution， and the expressions of related proteins of apoptosis， epithelial-mesenchymal transformation （EMT） and CDK1/CCNB1/PLK1 signaling pathway were detected in each group. The transplanted tumor model of BALB/c nude mice was established by subcutaneous inoculation of MCF-7 cell suspension， and the mice were divided into control group and Auc group （12 mice in each group）. The tumor volume， mass and the expressions of related proteins of CDK1/CCNB1/PLK1 signaling pathway in tumor tissues were detected. RESULTS Compared with control group， the number of clonal formation， proliferation rate， cell invasion number， scar healing rate， G1/G0 phase and S phase cell proportions， and the expressions of B cell lymphoma-2 （Bcl-2）， N-cadherin， fibronectin， CDK1， CCNB1 and PLK1 were decreased significantly （P＜0.05）. The apoptotic rate， G2/M phase cell proportion and the expressions of Bcl-2 associated X protein and E-cadherin were significantly increased， in a dose-dependent manner （P＜0.05）. Compared with the Auc-H+pcDNA-NC group， there was no statistical significance in the above indexes in the Auc-H group （P＞0.05）， while the above indexes in the Auc-H+ pcDNA-CDK1 group were significantly reversed （P＜0.05）. Compared with the control group， the tumor volume and mass， and the expressions of CDK1， CCNB1 and PLK1 in tumor tissue of Auc group were significantly decreased （P＜0.05）. CONCLUSIONS Auc can inhibit the proliferation， invasion and migration of breast cancer cells， induce cell cycle arrest， and inhibit the progression of EMT， which may be related to inhibiting the activation of the CDK1/CCNB1/PLK1 signaling pathway.
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Advanced esophageal cancer accounts for a large proportion of all esophageal cancer cases, and the treatment modality recommended by the current guidelines is systemic treatment. Radiotherapy is an important treatment option for malignant tumors, which is widely applied in clinical practice. Retrospective analysis and small-sample prospective studies have shown that combination of radiotherapy with chemotherapy, targeted therapy, and immunotherapy has the advantages of improving disease control rate, symptom remission rate and prolonging survival of advanced esophageal cancer patients. Therefore, it is an important clinical topic issue to make better use of the advantages of radiotherapy for esophageal cancer, such as rapid relief of symptoms, durable efficacy, and stimulation of immune neoantigens, etc. To optimize the treatment strategy of advanced esophageal cancer, the radiotherapy strategy for esophageal cancer with oligometastases or multiple metastases, and the screening method for the eligible population for radiotherapy were reviewed, aiming to provide reference for improving the status of radiotherapy in comprehensive treatment of advanced esophageal cancer.
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Objective:To screen the factors influencing overall survival (OS) of patients undergoing radical resection for colorectal cancer (CRC) and to construct a prognostic model for OS of patients after CRC.Methods:The clinical data of 350 patients with stage Ⅰ-Ⅳ CRC who underwent radical resection in the People's Hospital of Wuhan University from March 2017 to December 2019 were collected retrospectively. Patients were divided into subgroups 0 ( n=70), 1 ( n=172), and 2 ( n=108) according to different preoperative systemic inflammation score (SIS). The relationship between different SIS, neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), systemic immune inflammation index (SII) and prognosis of CRC patients undergoing radical surgical resection were analyzed, and Cox regression models were used to perform univariate and multifactorial analyses of factors affecting patient prognosis, and column line graph models were constructed based on the results of multifactorial analyses. Results:By the deadline of follow-up, 80 of 350 CRC patients died, and the 5-year OS rate was 77.14%. The 5-year survival rates of patients in SIS group 0, group 1 and group 2 were 95.71%, 79.65% and 61.11% respectively, with a statistically significant difference ( χ2=30.19, P<0.001). Statistically significant differences in age ( χ2=19.40, P<0.001), tumor site ( χ2=8.18, P=0.017), T stage ( χ2=10.01, P=0.007), TNM stage ( χ2=14.80, P=0.001), tumor diameter ( χ2=13.91, P=0.001) and carcino-embryonic antigen (CEA) level ( χ2=10.12, P=0.006) among patients in SIS group 0, group 1 and group 2. The 5-year OS rates of patients in the low NLR and high NLR groups were 82.67% and 56.16% respectively, with a statistically significant difference ( χ2=24.96, P<0.001) ; the 5-year OS rates of patients in the low LMR and high LMR groups were 66.85% and 88.17% respectively, with a statistically significant difference ( χ2=22.45, P<0.001) ; the 5-year OS rates of patients in the low SII and high SII groups were 86.14% and 69.02% respectively, with a statistically significant difference ( χ2=14.76, P<0.001). Univariate analysis showed that age ( HR=2.58, 95% CI: 1.54-4.32, P<0.001), T stage ( HR=2.41, 95% CI: 1.24-4.68, P=0.009), N stage ( HR=3.03, 95% CI: 1.85-4.94, P<0.001), TNM stage ( HR=3.61, 95% CI: 2.15-6.04, P<0.001), nerve invasion ( HR=1.97, 95% CI: 1.27-3.08, P=0.002), vascular invasion ( HR=2.31, 95% CI: 1.49-3.59, P<0.001), preoperative SIS 1 score ( HR=5.09, 95% CI: 1.57-16.56, P=0.007), SIS 2 score ( HR=11.05, 95% CI: 3.42-35.65, P<0.001), NLR ( HR=2.97, 95% CI: 1.90-4.64, P<0.001), LMR ( HR=0.31, 95% CI: 0.19-0.52, P<0.001), and SII ( HR=2.50, 95% CI: 1.54-4.06, P<0.001) were all independent influence factors affecting the postoperative prognosis of CRC patients undergoing radical surgical resection; multivariate analysis showed that age >60 years ( HR=2.27, 95% CI: 1.31-3.91, P=0.003), TNM stage Ⅲ-Ⅳ ( HR=7.08, 95% CI: 1.89-26.59, P=0.004), and preoperative SIS 2 score ( HR=4.02, 95% CI: 1.09-14.83, P=0.037) were all independent risk factors affecting the postoperative prognosis of CRC patients undergoing radical surgical resection. The nomogram model built based on the screened variables has high prediction accuracy: the C-index of the nomogram was 0.75. Conclusion:Age>60 years old, TNM stage Ⅲ-Ⅳ, SIS 2 score are all independent risk factors for postoperative prognosis of colorectal cancer. The nomograph model constructed by this method has high prediction accuracy.
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In the past decade, rapid breakthroughs have been made in the systemic treat-ment of advanced unresectable hepatocellular carcinoma. Single systemic therapy has little effect on controlling tumor local recurrence and distant metastasis, and the combination modality therapy is the treatment for the majority of patients with advanced hepatocellular carcinoma. The change of tumor microenvironment is the research hotspot of antitumor therapy at present. Targeted therapy, immunotherapy and radiotherapy can lead to a change in the tumor microenvironment of primary hepatic carcinoma. The synergistic effect of combined therapy is particularly important. The authors report the clinical efficacy of programmed death ligand-1 inhibitor plus vascular endothelial growth factor inhibitor in the first-line treatment of a patient with advanced unresectable hepatocellular carci-noma. The results show that partial response being achieved according to the modified response evaluation criteria in solid tumors, and the survival time is more than 20 months with no obvious adverse reactions and high quality of life.
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Objective:To investigate the safety and efficacy of chemoradiotherapy compared with chemotherapy after R0 excision in pN + esophageal squamous cell carcinoma (ESCC) patients. Methods:A retrospective analysis was performed on the pathological data of 99 pN + ESCC patients who underwent radical esophagectomy with R0 resection in Renmin Hospital of Wuhan University from January 2017 to December 2020. According to postoperative adjuvant treatment methods, the patients were divided into chemo-radiotherapy group ( n=41) and chemotherapy group ( n=58). The main outcome measures were disease-free survival (DFS), overall survival (OS) and the incidences of treatment-related adverse events. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to analyze the prognostic factors. Results:The median DFS and OS of 99 patients were 20.0 months and 28.0 months respectively. The 1- and 3-year DFS rates were 60.8% and 34.5% respectively. The 1- and 3-year OS rates were 83.5% and 40.2% respectively. The median DFS was 39.0 months in the chemoradiotherapy group and 10.0 months in the chemotherapy group, and the 1- and 3-year DFS rates were 79.4% vs. 48.3% and 57.3% vs. 24.5% respectively, with a statistically significant difference ( χ2=12.27, P<0.001). The median OS in the chemoradiotherapy group was not reached, and 21.0 months in the chemotherapy group, and the 1- and 3-year OS rates of the chemoradiotherapy group and chemotherapy group were 92.1% vs. 75.9% and 60.8% vs. 27.3%, with a statistically significant difference ( χ2=11.12, P=0.001). Univariate analysis showed that pN stage ( HR=0.58, 95% CI: 0.34-0.97, P=0.038), nerve invasion ( HR=1.88, 95% CI: 1.11-3.20, P=0.020) and adjuvant therapy ( HR=0.37, 95% CI: 0.21-0.67, P<0.001) were independent influencing factors of DFS in pN + ESCC patients. Adjuvant therapy ( HR=0.33, 95% CI: 0.17-0.66, P=0.001) was an independent factor influencing OS in pN + ESCC patients. Multivariate analysis showed that pN stage ( HR=0.54, 95% CI: 0.30-0.97, P=0.038) and adjuvant therapy ( HR=0.38, 95% CI: 0.21-0.69, P=0.001) were independent prognostic factors of DFS. Adjuvant therapy ( HR=0.34, 95% CI: 0.17-0.69, P=0.003) was an independent prognostic factor for OS. During adjuvant therapy, there were statistically significant differences in the incidences of leukopenia [65.85% (27/41) vs. 31.03% (18/58), χ2=11.75, P=0.001], thrombocytopenia [29.27% (12/41) vs. 10.34% (6/58), χ2=5.78, P=0.016], radioactive esophagitis [21.95% (9/41) vs. 0 (0/58), χ2=11.48, P=0.001], and radioactive pneumonia [21.95% (9/41) vs. 0 (0/58), χ2=11.48, P=0.001] between the two groups. Conclusion:Compared with chemotherapy, chemoradiotherapy can significantly improve DFS and OS of pN + ESCC patients with R0 resection after radical surgery, and the adverse reactions can be tolerated. pN stage and adjuvant therapy are independent prognostic factors for DFS, and adjuvant therapy is an independent prognostic factor for OS.
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Objective To explore the effect of apatinib in first-line treatment of advanced liver cancer. Methods Retrospective analysis was performed on 35 patients with advanced liver cancer treated in our department from July 2017 to January 2020. All patients were given apatinib mesylate tablet 250-500 mg orally with QD. The patients with effective disease control (including CR, PR and SD) were given administration until PD or intolerance or death occurred. The primary endpoints were PFS and OS, and the secondary endpoints were DCR and ORR. The side effect was observed. Results There was one case of CR, 17 cases of PR and 11 cases of SD. The ORR and DCR were 51.43% and 82.86%. The median PFS and OS were 9.7 and 11.1 months. The main adverse reactions included hand-foot syndrome, hypertension, proteinuria, etc. Most grade 3-5 adverse reactions were reversible with good safety. Conclusion Apatinib can significantly improve the clinical benefits of liver cancer patients. It is an alternative first-line treatment for advanced liver cancer.
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Objective:To investigate the efficacy of anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKI) in treatment of inflammatory myofibroblastic tumor (IMT).Methods:The clinicopathological data of one recurrent abdominal IMT patient in Renmin Hospital of Wuhan University in 2018 were retrospectively analyzed. The clinicopathological and molecular characteristics, ALK-TKI treatment efficacy and prognosis of 41 patients with IMT reported in the literature from January 2010 to August 2020 were systematically reviewed.Results:This patient with abdominal IMT in Renmin Hospital of Wuhan University was a 27-year-old female who relapsed 2 months after surgery. Chemotherapy combined with bevacizumab was ineffective. After oral administration of crizotinib, the condition resolved after 1 month, and complete remission (CR) was achieved after 29 months. The median age of onset of 41 IMT cases reported in the literature was 22 years old (0-61 years old), of which 32 cases (78.0%) had multiple organ involvement, all of which had recurrence or metastasis. There were 38 cases of ALK mutation and 3 cases of TFG-ROS1 fusion gene-positive. Thirty-four patients treated with crizotinib in the first-line treatment of ALK-TKI, and the median resistance time of crizotinib was 8 months (2-48 months). The total clinical benefit rate of ALK-TKI was 85.3% (29/34), and 20 patients achieved CR. The median time for the first CR was 11 months (4-36 months), and the median duration time of medication for CR patients was 19.5 months (2-60 months). The median progression-free survival (PFS) time of 24 patients who underwent surgery and/or chemotherapy and radiotherapy was 4 months (1-45 months); after progression, ALK-TKI treatment was performed, and the median PFS time was 14 months (3-62 months).Conclusions:IMT is a true neoplasm with characteristics of recurrence and metastasis. Reasonable combination of ALK-TKI with surgery, radiotherapy and chemotherapy can improve the prognosis of IMT patients.
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General education curriculum in Wuhan University has entered "3.0 era", in which general education curriculum of oncology has opened several cycles and been loved by the majority of students, meanwhile some problems have come up. In this article, the background of setting up general education curriculum of oncology in Wuhan University is reviewed. By sorting out teaching concepts and curriculum objectives, teaching content and organizational processes, teaching methods and evaluation methods and preliminary teaching effects, we emphatically discuss the role of clarifying teaching goals, optimizing curriculum designs, compiling basic teaching materials, improving teaching methods and reforming the evaluation system in promoting the setting and development of general education curriculum of oncology in comprehensive universities.
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Objective:To investigate the treatment, safety and prognosis of advanced non-small cell lung cancer patients with leptomeningeal metastasis and performance status score more than 3.Methods:The clinical data of 6 NSCLC patients with leptomeningeal metastasis admitted to the People's Hospital of Wuhan University from November 2016 to September 2018 were analyzed retrospectively. The curative effect and adverse reactions were observed, and the prognosis was analyzed.Results:There were 5 females and 1 male among 6 patients. The median age was 57 years old (46-74 years old). All 6 patients were diagnosed as stage Ⅳ lung adenocarcinoma. There were 3 patients with epidermal growth factor receptor (EGFR) exon 21 mutation, 2 patients with exon 19 mutation and one with anaplastic lymphoma kinase (ALK) fusion mutation. The time window of leptomeningeal metastasis occurred after the progression of adenocarcinoma of lung: 3 cases was more than 12 months, the other 3 cases was less than 12 months, and the average was 20.3 month. Performance status score was more than 3 when leptomeningeal metastasis occurred. The brain magnetic resonance imaging of 6 patients showed linear enhancement of leptomeningeal, cancer cells were found in cerebrospinal fluid in one case, 4 cases were treated with a combination of bevacizumab and EGFR-tyrosine kinase inhibitor (EGFR-TKI), 1 case was treated with oral administration of EGFR-TKI, 1 case was treated with oral administration of EGFR-TKI combined with temozolomide. The median overall survival (mOS) was 9 months (2-13 months), and the median progression free survival was 6 months (2-11 months).Conclusion:Lung adenocarcinoma may be prone to leptomeningeal metastasis; for NSCLC patients with leptomeningeal metastasis and performance status score more than 3, a combination of EGFR-TKI and bevacizumab has good tolerance, high safety and considerable curative effect.
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Objective:To investigate the clinical characteristics and prognosis of patients with cutaneous intravascular large B-cell lymphoma (IVLBCL).Methods:The data of 30 cutaneous IVLBCL published between January 1989 and May 2019 in China were systematically reviewed. The clinical manifestation, biochemical and imaging characteristics and diagnostic features of patients were summarized, and then the survival of different groups was also analyzed.Results:The median onset age was 61.5 years old (25.0-83.0 years old), and there were 22 (73.3%) females. All 30 patients presented with cutaneous lesions. Initial symptoms showed cutaneous lesions in 16 (53.3%) patients; and B symptom, respiratory symptoms or central nervous system (CNS) occurred in 14 (46.7%) patients with late cutaneous lesions. Cutaneous lesions were heterogeneous, and 76.7% (23/30) lesions located in lower abdomen and proximal limbs. And 76.2% (16/21) were positive in image examination, and 78.3% (18/23) had two or more extranodal organs invasion. The median time from onset to visit was 2.5 months (0.4-24.0 months), and clinical misdiagnosis rate was 56.7%(17/30). All IVLBCL patients were confirmed by biopsy, including 6 cases (27.3%, 6/22) of bone marrow involvement, 1 case (3.3%) of hemophagocytic syndrome-associated variant, and 29 cases (96.7%) of classical variant. Finally, 81.8% (18/22) patients received anthracycline-based combined chemotherapy. Compared with non-chemotherapy group, the median OS time of chemotherapy group was prolonged [11.0 months (2.0-60.0 months) vs. 2.0 months (0.7-24.0 months), P = 0.002]. Patients with CNS symptoms had shorter median OS time compared with patients without CNS symptoms [2.0 months (0.7-6.0 months) vs. 11.0 months (1.0-60.0 months), P < 0.01]. The median OS time in the group of cutaneous lesions as initial symptom combined with other symptoms was longer than that in group of late cutaneous lesions and other symptoms as initial symptom [unreached (2.0-60.0 months) vs. 3.0 months (1.5-24.0 months), P = 0.032]. Conclusions:Cutaneous IVLBCL is a rare disease with atypical clinical characteristics in China. Prompt attention and biopsy in time will be helpful for early diagnosis. Accompanied with CNS symptoms suggests poor prognosis; and timely chemotherapy can improve the prognosis of the patients.
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Objective@#To investigate the salvage strategy and efficacy for patients with locally recurrent esophageal squamous cell carcinoma after definitive radiochemotherapy.@*Methods@#A total of 126 patients who met the inclusion criteria were enrolled in this study and divided into the salvage surgery, salvage radiochemotherapy and best supportive care.@*Results@#Fifty-eight of 126 patients received salvage esophagectomy, 52 underwent salvage radiochemotherapy and the remaining 16 patients received best supportive care. The 1-, 3-, 5-year overall survival rates of patients receiving salvage therapy were 51%, 16% and 4% for the three groups, whereas all patients in the best supportive care group died within 12.0 months (P<0.001). The 1-, 3-, 5-year survival rates in the salvage surgery and salvage radiochemotherapy groups were 48%, 20% and 7%, and 51%, 11% and 3%, respectively (P=0.473). Multivariate analysis by Cox proportional hazard model showed that T staging of recurrent tumors and salvage regimen were the independent prognostic factors in patients with locally recurrent esophageal cancer (both P<0.001). Postoperative infection occurred in 16% of the patients in the salvage surgery group, and the incidence of esophagotracheal fistula and mediastinoesophageal fistula was 10% and 6% in the salvage radiochemotherapy group.@*Conclusions@#A survival benefit can be elicited by salvage surgery or salvage radiochemotherapy in patients with locally recurrent esophageal cancer after definitive radiochemotherapy. Nevertheless, extensive attention should be paid to the management of postoperative complications in clinical practice.
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Objective To summarize the outcomes and prognostic factors in esophageal cancer (EC) patients.Methods A total of 307 EC patients of stages Ⅱ-Ⅲ were treated with concurrent chemoradiotherapy in our hospital from September 2006 to July 2014.There were 73 patients with stage Ⅱ and 234 with stage Ⅲ.The radiotherapy dose was 50-70 Gy (median 60 Gy).Concurrent chemoradiotherapy were used with fluorouracil plus platinum (PF,166),paclitaxel plus platinum (TP,82) or platinum only (P,59).The Kaplan-Meier method was used to calculate overall survival (OS) and progression-free survival (PFS) rates,the log-rank test was used for survival difference analysis and univariate prognostic analysis.The Cox regression model was used for multivariate prognostic analysis.Results The 1-,3-5-year OS and PFS rates were85.6％,53.8％,36.9％ and 74.6％,43.7％,33.1％,respectively.The median OS and PFS were 41.6 months and 29.8 months.The univariate analysis indicated that T stage,N stage,clinical stage,lesion location,lesion length and chemotherapy regimen were prognostic factors for OS and PFS (P=0.007 and 0.013,0.000 and 0.000,0.000 and 0.000,0.002 and 0.000,0.141 and 0.005,0.018 and 0.165).Multivariate analysis showed that T stage,N stage,lesion location and chemotherapy regimen were prognostic factors for OS (P =0.024,0.000,0.007 and 0.028),lesion location,lesion length and N stage were prognostic factors for PFS (P=0.004,0.033 and 0.035).The median OS and PFS for EC patients treated by total dose 50-60 Gy,＞60-70 Gy were 47.4 months,37.8 months (P=0.469) and34.1 months,25.1 months (P=0.0.233),therewere no statistic difference.Conclusions The outcome of EC patients treated with concurrent chemoratherapy could obtain a long-term survival,combination chemotherapy is superior to single drug,there are no statistical difference between high-dose and low-dose,and the acute toxic effects can be tolerated.
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Objective: To prepare dexketoprofen trometamol hydrogel patches, optimize the formula and evaluate in vitro transdermal properties.Methods: Dexketoprofen trometamol hydrogel patches were prepared with NP-800 as the hydrogel patch carrier, aluminum hydrochloride as the crosslinking agent, EDTA as the crosslinking modifier and glycerol as the moisturizing agent.The formula was screened by orthogonal design with the initial viscosity, holding force, peel strength and 12 h cumulative transdermal quantity as the evaluation indices to screen out the best formula.The transdermal absorption test was carried out with an improved Franz diffusion cells to compare the enhancement of Aznoe, oleic acid and menthanol on dexketoprofen trometamol hydrogel patches.Results: The best formula was as follows: the mass percentage of NP-800, glycerol, glycerol and EDTA was 5%, 0.3% , 25% and 0.15% , respectively.The transdermal enhancers had transdermal enhancement on dexketoprofen trometamol, and among them, 3% Azone had the most significant enhancement with the enhancing rate of 3.26.Conclusion: The preparation and formula of dextroxyprofen trometamol hydrogel patches are stable, reasonable and feasible.
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Objective To determine the feasibility and toxicity of the addition of cetuximab to paclitaxel,cisplatin,and concurrent intensity modulated radiation therapy (IMRT) for patients with esophageal squamous cell carcinoma (ESCC).Methods Nineteen patients with stage Ⅰ to Ⅲ ESCC,without distant organ metastases,were eligible.All patients received cetuximab,an initial dose of 400 mg/m2 in the first week followed by weekly injection of 250 mg/m2,paclitaxel 45 mg/m2 and cisplatin 20 mg/m2 weekly for 7 weeks with IMRT of 59.4 Gy/33 fractions.Results Two patients discontinued because of severe adverse events.Seventeen patients completed the planned treatment protocol.Of whom,12 patients achieved completeremission.The objective response rate was 100％.A median follow-up time was 29.3 months.The 1-year overall survival and recurrence-free survival rate was 100％ and 82％,respectively.Main toxicities including myelosuppression,esophagitis and skin rash happened in 19 patients.Grade ≥2 neutropenia,esophagitis and skin toxicity noted rates was 89％,84％ and 58％,respectively.Local recurrence was found in two patients.Neck lymph node and lung metastasis found in one patient.Conclusions Cetuximab,when combined with paclitaxel,cisplatin and IMRT,is efficient and safe for esophageal squamous cell carcinoma,Further clinical study is needed.