Objective To prospectively study the dynamic variation of vascular endothelial growth factor (VEGF),the short-term efficiency and the tolerability of the esophageal cancer patients treated by radiotherapy combined with thalidomide.Methods The serum samples of 86 esophageal cancer patients were collected before,during and after the radiotherapy.The VEGF levels were assayed by enzyme-linked immunosorbent assay (ELISA).3 patients interrupted the treatment because of intolerance radiotherapy.Based on the changes of VEGF level,32 esophageal cancer cases whose VEGF levels increased or remained were assigned to the group to which thalidomide was given during the whole course of radiotherapy.The rest 51 patients whose VEGF level decreased received radiotherapy without thalidomide during the whole course.In addition,30 healthy cases were included in control group.Then the efficiency and safety of the introduction of thalidomide in radiotherapy were investigated. Results The VEGF levels of 86 esophageal cancer cases were significantly higher than the 30 healthy control cases ( t =5.07,P ＜ 0.01 ),which were also correlated with the primary tumor size ( t =4.55,P ＜ 0.01 ),lymph node metastasis ( t =7.50,P ＜0.01 ),histological type( F =3.40,P ＜ 0.01 ) and clinical stage ( t =2.52,P ＜ 0.0 l ).However,it was irrelevant to the lesion site,distant metastasis,X-ray pathologic type,gender or age ( P ＞ 0.05).For the thalidomide involved group, the VEGF level after radiotherapy was significantly lower than during radiotherapy (t =2.37,P ＜0.05 ) with an effective rate of 71.88％.For the rest 51 cases without using thalidomide,the effective rate was 78.43％ yet there was no significant difference between the VEGF levels during and after radiotherapy ( t =0.18,P ＞ 0.05 ).62.50％ patients reported symptoms of dizzy and burnout after using thalidomide,while this incidence was 15.69％ for the rest patients (x2 =19.28,P =0.000).For the groups with or without thalidomide combination,the sleepiness incidences were 18.75％and 1.96％,respectively (x2 =5.168,P =0.023 ); the Ⅲ - Ⅳ grade esophagitis incidences were 12.50％ and 11.76％,respectively (x2 =0.061,P =0.806) ; the Ⅱ - Ⅳ grade leukocyte decrease incidences were 6.25％ and 9.80％,respectively (x2 =0.026,P =0.872) ; the Ⅲ - Ⅳ grade platelet descend incidences were 3.13％ and 5.88％,respectively (x2 =0.002,P =0.965 ) ; the Ⅲ - Ⅳ grade nausea and vomiting incidences were 9.38％ and 27.45％,respectively (x2 =2.913,P =0.088 ). No anaphylaxis was observed. Conclusions Thalidomide can decrease the VEGF expression level of esophageal cancer patients.Patients treated with thalidomide show good tolerance and compliance.
Key words:
Esophageal cancer; Radiotherapy; Vascular endothelial growth factor; Thalidomide
Objective
To observe the pathological response in tumor tissues and the vascular endothelial growth factor (VEGF) changes in serum of patients with esophageal carcinoma receiving radiotherapy or concurrent chemoradiotherapy, and to investigate the relationship between these two factors and the prognosis of these patients.
Methods
A total of eighty-nine patients with esophageal carcinoma treating with radiotherapy or concurrent chemo-radiotherapy were prospective included. Gastroscopy and biopsy were performed at 4 week of radiotherapy to assess pathologicalresponse. VEGF serum levels were measured by double antibody sandwich avidin-biotin ELISA prior to, at 4 week of, and 1 week after radiotherapy. The relationship between pathological response in tumor tissues and VEGF serum changes and the prognosis of the patients were analyzed. The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method, and the Log-rank test was used for survival analysis. Multivariate Cox proportional hazard model was used to analyze the prognostic factors.
Results
Pathological responses were classified into two degrees: Non-CR responses (22 cases), and CR responses (67 cases). The 1-, 3- and 5-year OS rates in CR group and non-CR group were 77.6%, 46.3%, 35.2% (median OS: 30.0 months, 95%CI 14.3-45.6 months) and 50.0%, 0.0%, 0.0% (median OS: 11.4 months, 95%CI 4.2-18.6 months), respectively, showing that the OS in CR group were significantly higher than that in non-CR group (P<0.001). Meanwhile, the 1-, 3- and 5-year PFS rates in CR group and non-group were 69.7%, 40.9%, 34.3% (median PFS: 21.7 months, 95%CI 13.1-30.3 months) and 36.4%, 0.0%, 0.0% (median PFS: 7.4 months, 95%CI 2.1-12.4 months), respectively, showing that the PFS in CR group was significantly higher than that in non-CR group (P<0.001). VEGF serum changes were classified into three degrees: increased group (16 cases), stable group (43 cases) and decreased group (30 cases). The 1-, 3- and 5-year OS rates in VEGF increased group were 50.0%, 18.8%, 12.5% (median OS: 9.2 months, 95%CI 2.2-17.9 months), respectively, while the 1-, 3- and 5-year OS rates in VEGF stable group were 67.4%, 30.2%, 19.9% (median OS: 19.9 months, 95%CI 14.9-24.9 months), respectively, and the 1-, 3- and 5-year OS rates in VEGF-decreased group were 86.7%, 50.0%, 42.9% (median OS: 28.7 months, 95%CI 5.4-51.2 months), respectively, showing that the OS in VEGF-decreased group was significantly the highest among the three groups (P<0.05). The 1-, 3- and 5-year PFS rates in VEGF-increased group were 43.8%, 12.5%, 0 (median PFS: 8.0 months, 95%CI 2.5-15.9 months), respectively, while the 1-, 3- and 5-year PFS rates in VEGF stable group were 57.1%, 26.2%, 20.8% (median PFS: 15.5 months, 95%CI 10.7-20.4 months), respectively, and the 1-, 3- and 5-year PFS rates in VEGF decreased group were 76.7%, 46.7%, 39.7% (median PFS: 20.1 months, 95%CI 2.4-40.1 months), respectively, showing that the PFS in VEGF decreased group was significantly the highest among the three groups (P=0.013).
Conclusions
Pathological response and VEGF changing trend during radiotherapy were both closely related to prognosis of patients with esophageal carcinoma.
Trial registration
This clinical trial was registered in the United States Trial, ID: NCT01551641
Key words:
Esophageal carcinoma; Radiotherapy; Pathological response; Vascular endothelial growth factor; Prognosis
We aim to investigate the effects of adipose‐derived stem cells (ASCs) transplantation on irradiation‐induced skeletal muscle fibrosis. Sixty‐four rabbits were randomly divided into ASCs group and PBS group followed by irradiation at unilateral hip with a single dose of 80 Gy. Nonirradiated side with normal skeletal muscle served as normal control. Skeletal muscle tissues were collected from eight rabbits in each group at 1 w, 4 w, 8 w, and 26 w after irradiation. Migration of ASCs was observed in the peripheral tissues along the needle passage in the injured muscle. The proportion of the area of collagen fibers to the total area in sections of ASCs group was lower than those of PBS groups at 4 w, 8 w, and 26 w after irradiation. Significant decrease was noted in the integrated optimal density of the transforming growth factor β 1 (TGF‐ β 1) in the ASCs group compared with those of PBS group at 4 w, 8 w, and 26 w after irradiation. Moreover, the expression of TGF‐ β 1 was lower in the ASCs group compared to those of the PBS group at each time point determined by Western blot analysis. ASCs transplantation could alleviate irradiation fibrosis by suppressing the level of TGF‐ β 1 in the irradiated skeletal muscle.
Objective To establish a rabbit model of radiation-induced skeletal muscle injury in order to study the ultrastructural pathological changes and underlying mechanism.Methods 28 New Zealand rabbits were randomly divided into 2 groups with 16 rabbits in experimental group and 12 rabbits in control group.The experimental rabbits were irradiated on hip with a single dose of 80 Gy of 9 MeV electrons from a linear accelerator.1 month and 6 months after irradiation the pathological changes were respectively observed under light microscope and electron microscope.Results One month after irradiation,the morphologic changes including degeneration,necrosis of muscle cells,and hemorrhage between the muscle cells were observed under light microscope and the swelling of myofibrillae,blurring of light and shade band,vacuolar degeneration of mitochondria and amorphous areas of necrosis were observed under electron microscope.Six months after irradiation,the morphologic changes of nucleolus chips,fibrous connective tissue,thickening of vascular wall and vascular congestion between the muscle cells and the amorphous areas of necrosis in the experimental group were much more serious than those of 1 month after irradiation.In addition,the myofilaments were lost in degeneration areas and the sarcomere became shorten.Observation with electron microscope showed that the mitochondrial size and its morphological changes were varied and the amounts of collagen between myofibrillaes were increased 6 months after irradiation.Conclusions A rabbit model of high-dose irradiated skeleton muscle injury was successfully established with a single dose of 80 Gy of 9 MeV electrons from a linear accelerator.The degeneration and necrosis of muscle cells may be promoted by mitochondrial and vascular injury,degeneration of vessel and nerve fiber.
Key words:
Rabbits; Muscle skeletal; Radiation injury; Electron beam; Ultrastructure
higher level of VEGF compared with the 30 healthy controls before radiotherapy (P < 0.01), and the VEGF level was significantly correlated with primary tumor size, lymph node metastasis, histopathologic type, and clinical stage (P < 0.01).Of 83 evaluable cases, VEGF level was significantly decreased after radiotherapy in 32 patients in the drug group (P < 0.05), with an effective rate of 71.88%.The incidence of dizziness and/or burnout in the drug group and non-drug group was 62.50% and 15.69%, respectively (P = 0.000), and the incidence of somnolence was 12.50% and 0%, respectively (P = 0.019).No significant differences were observed. CONCLUSION:Thalidomide can down-regulate serum VEGF level in EC patients, and combined with radiotherapy may improve treatment outcome.Thalidomide was well tolerated by EC patients.
Background: Locoregional recurrence (LR) is the major cause for poor response after radical resection in patients with esophageal carcinoma (EC). Therefore, early diagnosis and positive treatment is crucial for the extension of overall survival in EC patients. We aim to investigate the feasibility of squamous cell cancer antigen (SCC-Ag), cytokeratin 21-1 fragment (CYFRA21-1), and carcinoembryonic antigen (CEA) in the diagnosis of postoperative LR in patients with EC, and the correlation between their expression and the prognosis of the disease.
Background: To investigate the relationship between pathologic tumor response to concurrent chemoradiotherapy and variation of serum VEGF in patients with esophageal cancer.Materials and Methods: Forty six patients with esophageal cancer who were treated with concurrent chemo-radiotherapy were enrolled.Endoscopic and pathologic examination was conducted before and four weeks afterwards.Serum level of VEGF was documented before, four weeks later and after chemo-radiotherapy.The relationship between pathologic response and the variation of serum level of VEGF and its influence on the prognosis were investigated.Results: Serum level of VEGF decreased remarkably during and after chemo-radiotherapy in patients whose pathologic response was severe (F=5.393,4.587, P(0.05).There were no statistical differences of serum VEGF level before, during and after chemo-radiotherapy for patients whose pathologic response was moderate or mild.There were 18 (85.7%),7 (53.8%)and 6 patients (50.0%) whose serum VEGF level dropped in the severe, moderate and mild group, respectively, with significant differences among these groups (p=0.046).Two year survival rates of patients with severe, moderate and mild pathologic response were 61.9%, 53.8% and 33.3% respectively, and no statistically difference between severe and mild group regarding OS (p=0.245) was tested.Conclusions: Tumor pathologic response during chemo-radiotherapy and the changes of serum VEGF lever could predict curative effects of chemo-radiotherapy in patients with esophageal cancer.
Objective To investigate the changes and clinical value of serum vascular endothelial growth factor (VEGF) level before,during and after radiotherapy in patients with esophageal carcinoma.Methods The sera of 67 esophageal carcinoma patients and 30 healthy control cases were collected.The VEGF level in serum samples were measured with enzyme-linked immunosorbent assay (ELISA) method.The relations among VEGF level changes,clinical stages and radiotherapy effect were analyzed.Results The VEGF levels of patients with esophagus cancer before,during and after radiotherapy were significantly higher than those in control group ( F =11.65,P ＜ 0.01 ).The VEGF level after radiotherapy was significant lower than that before radiotherapy ( F =10.72,P ＜ 0.01 ).The average VEGF level of patients with T3 and T4 was significantly higher than that of control group ( F =14.10,P ＜ 0.01 ).The average VEGF level of patients with N1 and N2 was significantly higher than that of control group( F =8.64,P ＜0.01).In 62 patients,the serum VEGF level increased in 21 cases but decreased in 41 cases after radiotherapy.With difference in radiotherapy efficiency of 61.90％ and 90.24％,respectively(x2 =6.08,P＜ 0.05).The average VEGF level during and after radiotherapy for 50 cases of CR + PR were significantly lower than that before radiotherapy( F =7.98,P ＜ 0.01 ).Conclusions Monitoring the serum VEGF level of patients with esophagus cancer can help evaluate the radiosensitivity,which has a significance in predicting the prognosis of radiotherapy.
Key words:
Esophageal carcinoma; Radiotherapy ; Vascular endothelial growth factor
Background: Many studies have focused on the relationship between dynamic changes in serum vascular endothelial growth factor (VEGF) and the prognosis of esophageal cancer (EC) patients undergoing chemo-radiotherapy (CRT). Few studies have reported the appropriate time-point for the measurement of VEGF during radiotherapy. In this study, we aimed to identify the appropriate time-point for VEGF measurement during radiotherapy among EC patients.
Methods: Serum VEGF in 76 EC patients was determined before, during (per 10 Gy) and after radiotherapy. The levels were categorized into three groups depending on the VEGF changes: increased, stable and decreased.
Results: The 1-year overall survival (OS) and progression-free survival (PFS) rates of the patients were 55.7% and 51.4%, respectively, with median OS of 15.8 months [95% confidence interval (CI): 10.4–21.2 months] and 12.5 months (95% CI: 7.6–17.5 months), respectively. There were 13 cases of recurrence within 2 years post-treatment. The 1-yr OS rates of the patients with increased, stable and decreased VEGF were 31.6%, 60.0% and 71.4%, respectively (P=0.034). Significant differences were noticed in the 1-yr PFS rates among those with increased, stable and decreased VEGF (P=0.039). The 1-yr local control (LC) rates showed no significant differences (P=0.306). Compared to those before radiotherapy, the serum VEGF levels of 19 patients were found to be increased at approximately 20–30 Gy during radiotherapy or post-radiotherapy. VEGF decreases were noticed in 21 cases at 20–30 Gy during radiotherapy. Conclusions: Serum VEGF changes could be used to predict the prognosis of EC patients undergoing CRT. It is appropriate to determine serum VEGF at 20–30 Gy during radiotherapy and post-radiotherapy among EC patients.
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