Clinical trial of thalidomide combined with radiotherapy in patients with esophageal cancer

AIM:To investigate the short-term efficacy and tolerability of radiotherapy plus thalidomide in patients with esophageal cancer(EC).METHODS:Serum samples from 86 EC patients were collected before,during,and after radiotherapy,and the vascular endothelial growth factor(VEGF)level was examined by ELISA.According to the change in serum VEGF level during radiotherapy,the patients were divided into two groups:in the drug group,VEGF level was increased or remained unchanged,and thalidomide was administered up to the end of radiotherapy;in the non-drug group,VEGF level was decreased and radiotherapy was given alone.Thirty healthy volunteers served as controls.The efficacy and safety of radiotherapy plus thalidomide therapy were investigated.RESULTS:The 86 EC patients had a significantly 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 in32 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 was62.50%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.

Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines

AIM:To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics.METHODS:A serum-free medium(SFM)suspension was used to culture esophageal cancer stem cell lines and enrich the esophageal stem-like spheres.A reverse transcription polymerase chain reaction assay was used to detect stem cell gene expression in the spheroid cells.Radiosensitivity of stem-like spheres and parental cells were evaluated by clonogenic assays.Furthermore,different cells after different doses of irradiation were tested to evaluate the change in sphere formation,cell cycle and CD44+CD271+expression of tumor stem-like spheroid cells using flow cytometry beforeand after irradiation.RESULTS:The cells were observed to generate an increased number of spheres in SFM with increasing cell passage.Radiation increased the rate of generation of stem-like spheres in both types of cells.The average survival fraction(SF2)of the cultured KYSE-150compared with TE-1 stem-like spheres after 2 Gy of radiation was 0.81±0.03 vs 0.87±0.01(P<0.05),while the average SF2 of KYSE-150 compared with TE-1 parental cells was 0.69±0.04 vs 0.80±0.03,P<0.05.In the esophageal parental cells,irradiation dose-dependently induced G2 arrest.Stem-like esophageal spheres were resistant to irradiation-induced G2arrest without significant changes in the percentage population of irradiated stem-like cells.Under irradiation at 0,4,and 8 Gy,the CD44+CD271+cell percentage for KYSE150 parental cells was 1.08%±0.03%vs1.29%±0.07%vs 1.11%±0.09%,respectively;the CD44+CD271+cell percentage for TE1 parental cells was 1.16%±0.11%vs 0.97%±0.08%vs 1.45%±0.35%,respectively.The differences were not statistically significant.Under irradiation at 0,4,and 8 Gy,the CD44+CD271+cell percentage for KYSE-150 stemlike spheres was 35.83%±1.23%vs 44.9%±1.67%vs 57.77%±1.88%,respectively;the CD44+CD271+cell percentage for TE1 stem-like spheres was 16.07%±0.91%vs 22.67%±1.12%,16.07%±0.91%vs33.27%±1.07%,respectively.The 4 and 8 Gy irradiated KYSE-150 and TE-1 stem-like spheres were compared with the 0 Gy irradiated group,and the differences were statistically significant(P<0.05).CONCLUSION:The KYSE-150 and TE-1 stem-like spheres are more radioresistant than their parental cells which may suggest that cancer stem cells are related to radioresistance.

Serum transforming growth factor-β1 level reflects disease status in patients with esophageal carcinoma after radiotherapy

AIM: To evaluate the relationship between changes in serum transforming growth factor β1 (TGFβ1) level and curative effect of radiotherapy (RT) in patients with esophageal carcinoma. METHODS: Ninety patients with histologically confi rmed esophageal carcinoma were enrolled. Serum samples for TGFβ1 analysis were obtained before and at the end of RT. An enzyme-linked immunosorbent assay was used to measure serum TGFβ1 level. Multivariate analysis was performed to investigate the relationship between disease status and changes in serum TGFβ1 level. RESULTS: Serum TGFβ1 level in patients with esophageal carcinoma before RT was signifi cantly higher than that in healthy controls (P < 0.001). At the end of RT, serum TGFβ1 level was decreased in 67.82% (59/87) of the patients. The overall survival rate at 1, 3 and 5 years was 48.28% (42/87), 19.54% (17/87) and 12.64% (11/87), respectively. Main causes of death were local failure and regional lymph node metastasis. In patients whose serum TGFβ1 level decreased after RT, the survival rate at 1, 3 and 5 years was 61.02% (36/59), 28.81% (17/59) and 18.64% (11/59), respectively. The survival rate at 1 year was 17.86% (5/28) in patients whose serum TGFβ1 level increased after RT, and all died within 18 mo (P < 0.01). CONCLUSION: Serum TGFβ1 level may be a useful marker for monitoring disease status after RT in patients with esophageal carcinoma.

Theory of mind deficits in patients with esophageal cancer combined with depression

AIM:To characterize the two components of theory of mind(ToM) in patients with esophageal cancer combined with depression.METHODS:Sixty-five patients with esophageal cancer combined with depression(depressed group) and 62 normal controls(control group) were assessed using reading the mind in the eyes test,faux pas task,verbal fluency test,digit span test and WAIS IQ test.The depressed group was divided into two subgroups including psychotic depressed(PD) group(32 cases) and nonpsychotic depressed(NPD) group(33 cases).The clinical symptoms of patients were assessed using Beck depression inventory version Ⅱ and brief psychiatric reacting scale(BPRS).RESULTS:There was a significant difference between the depressed group and the control group on tasks involving ToM social perceptual components(mind reading:t = 7.39,P < 0.01) and tests involving ToM social cognitive components(faux pas questions:t = 13.75,P < 0.01),respectively.A significant difference was also found among the PD group,the NPD group and the control group on mind reading(F = 32.98,P < 0.01) and faux pas questions(χ 2 = 78.15,P < 0.01),respectively.The PD group and NPD group performed worse than normal group controls both on mind reading and faux pas questions(P < 0.05).The PD group performed significantly worse than the NPD group on tasks involving ToM(mind reading:F = 18.99,P < 0.01;faux pas questions:F = 36.01,P < 0.01).In the depressed group,there was a negative correlation between ToM performances and BPRS total score(mind reading:r =-0.35,P < 0.01;faux pas questions:r =-0.51,P < 0.01),and between ToM performances and hostile suspiciousness factor score(mind reading:r =-0.75,P < 0.01;faux pas questions:r =-0.73,P < 0.01),respectively.CONCLUSION:The two components of ToM are both impaired in patients with esophageal cancer combined with depression.This indicates that there may be an association between ToM deficits and psychotic symptoms in clinical depression.

Randomized clinical trial on seven-day-per-week continuous accelerated irradiation for patients with esophageal carcinoma: Preliminary report on tumor response and acute toxicity

AIM: Tumor response and normal tissue toxicity of seven-day-per-week continuous accelerated irradiation (CAIR) for patients with esophageal carcinoma were evaluated and compared to conventional irradiation (CR). METHODS: Sixty patients with squamous cell carcinoma of the esophagus were randomized into two groups: the CAIR group (30 patients) and the CR group (30 pa- tients). Patients in the CAIR group received radiotherapy (RT) with 2 Gy/fraction per day at 7 d/wk with a total dose of 50-70 Gy (average dose 64.2 Gy). The overall time of irradiation was 3.6-5.0 wk (average 4.6 wk). RT in the CR group was 2 Gy/fraction per day at 5 d/wk with a total dose of 40-70 Gy (average dose 61.7 Gy). The overall time of irradiation was 4.0-7.0 wk (average 6.4 wk). RESULTS: The data showed that the immediate tumor response to RT was better in the CAIR group than in the CR group. Efficiency rates (CR plus PR) were 82.8% (24/29) and 58.6% (17/29), respectively (P = 0.047). In both groups the incidences of esophagitis and tracheitis were insignificant (P = 0.376, 0.959), and no patient re- ceived toxicity that could not be tolerated. CONCLUSION: CAIR shortens overall treatment time and is well tolerated by patients. It may be superior to CR in enhancing the local response of tumor, but its remote effect for esophageal carcinoma awaits further follow-up.