术后放疗联合替莫唑胺化疗对高级别脑胶质瘤临床疗效及酪氨酸激酶2和血管内皮细胞生长因子表达的影响
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摘要
目的:探究术后放疗联合替莫唑胺化疗对高级别脑胶质瘤临床疗效及酪氨酸激酶2(DDR2)和血管内皮细胞生长因子(VEGF)表达的影响。方法:抽取2012年10月至2014年4月我院64例高级别脑胶质瘤患者,随机数表法分组,各32例。对照组采用放疗联合静脉注射尼莫司汀化疗治疗,研究组采用放疗联合替莫唑胺,连续服用4～6个周期,1、2年后进行随访。疗程结束时统计两组临床疗效、不良反应发生率及1、2年生存率,分析治疗前后认知功能(MMSE)与日常生活能力(ADL)评分及DDR2与VEGF吸光度值(OD值)变化情况。结果:研究组治疗有效率(65.63%)、疾病控制率(87.50%)高于对照组(40.63%、65.63%),差异有统计学意义(P<0.05);治疗前两组MMSE及ADL评分比较,差异无统计学意义(P>0.05),治疗后两组各指标评分均较治疗前增高,且研究组MMSE及ADL评分高于对照组,差异有统计学意义(P<0.05);治疗前两组DDR2及VEGF OD值比较,差异无统计学意义(P>0.05),治疗后研究组DDR2及VEGF OD值优于对照组,差异有统计学意义(P<0.05);两组均无患者出现Ⅲ及Ⅳ度不良反应,研究组呕吐、恶心、脱发、骨髓抑制发生率与对照组比较,差异均无统计学意义(P>0.05);研究组2年生存率(65.63%)高于对照组(40.63%),差异有统计学意义(P<0.05)。结论:术后放疗联合替莫唑胺化疗治疗高级别脑胶质瘤效果显著,可有效降低酪氨酸激酶2和血管内皮细胞生长因子表达水平,改善患者认知功能及日常生活能力,提高治疗效果及生存率,且安全性较高。
Objective: To investigate the effect of postoperative radiotherapy combined with temozolomide chemotherapy on the clinical ef?cacy of high grade gliomas and the expression of tyrosine kinase 2(DDR2)and vascular endothelial growth factor(VEGF). Methods: 64 patients with high grade glioma were randomly divided into two groups according to the random number table method in the hospital from October 2012 to April 2014, with 32 cases in each group. The control group was treated with radiotherapy combined with intravenous nimustine, the study group was treated with radiotherapy combined with temozolomide for 4 to 6 cycles and followed up for 1 to 2 years. At the end of the course of treatment, the clinical ef?cacy, the incidence of adverse reactions and the survival rate of 1 year and 2 years were analyzed. Mini-mental state examination(MMSE)and activity of daily living scale(ADL)and the optical density(OD)of DDR2 and VEGF were analyzed before and after treatment. Results: The effective rate(65.63%)and disease control rate(87.50%)of the study group were signi?cantly higher than those of the control group(40.63%, 65.63%)(P<0.05); There was no signi?cant difference in MMSE and ADL scores between the two groups before treatment(P>0.05); the scores of MMSE and ADL in the two groups were higher than those in the control group before and after treatment(P<0.05); there was no signi?cant difference in the values of DDR2 and VEGF between the two groups before treatment(P> 0.05); after treatment, the OD values of the two groups were lower than before treatment, and the study group of DDR2 and VEGF OD values was lower than the control group, the difference was statistically signi?cant(P<0.05); no adverse events occurred in patients with III and IV; the incidence of vomiting, nausea, alopecia and myelosuppression in the study group was not signi?cantly different from that in the control group(P> 0.05); the 2-year survival rate(65.63%)in the study group was signi?cantly higher than that in the control group(40.63%)(P<0.05). Conclusion: Postoperative radiotherapy combined with temozolomide chemotherapy in the treatment of high-grade gliomas has signi?cant effect, can effectively reduce the tyrosine kinase 2 and vascular endothelial growth factor expression level, improve cognitive function and daily life ability, and improve the therapeutic effect and survival rate, with high safety.
Objective: To investigate the effect of postoperative radiotherapy combined with temozolomide chemotherapy on the clinical ef?cacy of high grade gliomas and the expression of tyrosine kinase 2(DDR2)and vascular endothelial growth factor(VEGF). Methods: 64 patients with high grade glioma were randomly divided into two groups according to the random number table method in the hospital from October 2012 to April 2014, with 32 cases in each group. The control group was treated with radiotherapy combined with intravenous nimustine, the study group was treated with radiotherapy combined with temozolomide for 4 to 6 cycles and followed up for 1 to 2 years. At the end of the course of treatment, the clinical ef?cacy, the incidence of adverse reactions and the survival rate of 1 year and 2 years were analyzed. Mini-mental state examination(MMSE)and activity of daily living scale(ADL)and the optical density(OD)of DDR2 and VEGF were analyzed before and after treatment. Results: The effective rate(65.63%)and disease control rate(87.50%)of the study group were signi?cantly higher than those of the control group(40.63%, 65.63%)(P<0.05); There was no signi?cant difference in MMSE and ADL scores between the two groups before treatment(P>0.05); the scores of MMSE and ADL in the two groups were higher than those in the control group before and after treatment(P<0.05); there was no signi?cant difference in the values of DDR2 and VEGF between the two groups before treatment(P> 0.05); after treatment, the OD values of the two groups were lower than before treatment, and the study group of DDR2 and VEGF OD values was lower than the control group, the difference was statistically signi?cant(P<0.05); no adverse events occurred in patients with III and IV; the incidence of vomiting, nausea, alopecia and myelosuppression in the study group was not signi?cantly different from that in the control group(P> 0.05); the 2-year survival rate(65.63%)in the study group was signi?cantly higher than that in the control group(40.63%)(P<0.05). Conclusion: Postoperative radiotherapy combined with temozolomide chemotherapy in the treatment of high-grade gliomas has signi?cant effect, can effectively reduce the tyrosine kinase 2 and vascular endothelial growth factor expression level, improve cognitive function and daily life ability, and improve the therapeutic effect and survival rate, with high safety.
引文
[1]陈惠,张建庆,章恒.高级别脑胶质瘤术后调强放射治疗联合替莫唑胺化疗的效果观察[J].中国医药,2013,8(12):1714-1715.
[2]Towner Michael,Ihnat Debra,Saunders Anja,et al.A new anti-glioma therapy,AG119:pre-clinical assessment in a mouse GL261 glioma model[J].BMC cancer,2015,15(1):522.
[3]黄仁华,侯艳丽,徐欣,等.脑胶质瘤术后三维适形放疗联合替莫唑胺疗效分析[J].肿瘤学杂志,2015,21(3):219-222.
[4]Chiang KL,Chang KP,Lee YY,et al.Role of temozolomide in the treatment of newly diagnosed diffuse brainstem glioma in children:experience at a single institution[J].Child's nervous system,2010,26(8):1035-1041.
[5]李俊杰,王博,毕智勇,等.高级别脑胶质瘤术后三维适形放疗联合替莫唑胺化疗的疗效分析[J].湖南中医药大学学报,2013,33(10):11.
[6]赵东利,刘锐,邓怀慈,等.恶性脑胶质瘤术后替莫唑胺同步放化疗与单纯放疗的疗效对比[J].西部医学,2014,26(9):1141-1143
[7]范阳华,吕世刚,吴雷,等.放疗联合替莫唑胺治疗恶性脑胶质瘤疗效及安全性的系统评价[J].重庆医科大学学报,2015,40(5):728-735.
[8]王浩,吴磊,刘秋芳,等.替莫唑胺在高级别脑胶质瘤术后同步放化疗中的临床研究[J].西部医学,2013,25(9):1316-1319.
[9]陈孝平,汪建平.外科学[M].第8版.北京:人民卫生出版社,2013:210-215.
[10]姚晓峰,欧阳翠微.替莫唑胺联合放射治疗治疗恶性脑胶质瘤的疗效观察[J].中国肿瘤临床与康复,2014,21(6):709-712.
[11]郭旗,田野.放疗对低级别脑胶质瘤患者认知功能的影响及防治方法[J].中华放射医学与防护杂志,2015,35(5):397-400.
[12]Macdonald Glenn J,Lesser Stephen W,Coons David G,et al.Phase 2 study of temozolomide-based chemoradiation therapy for high-risk low-grade gliomas:preliminary results of Radiation Therapy Oncology Group 0424[J].International journal of radiation oncology,biology,physics,2015,91(3):497-504.
[13]姚春筱,张树平,陈保民,等.调强适形放疗联合替莫唑胺治疗恶性脑胶质瘤的临床观察[J].中国肿瘤,2013,22(3):238-240.
[14]Bow Lee S,Hwang Noam,Schildhaus Joanna,et al.Local deliver y of angiogenesis-inhibitor minocycline combined with radiotherapy and oral temozolomide chemotherapy in 9L glioma[J].Journal of neurosurgery,2014,120(3):662-669.
[15]毛德强,潘玲,戴勤弼,等.术后放疗联合替莫唑胺治疗高级别胶质瘤的近期临床疗效及安全性观察[J].重庆医学,2013,42(1):21-23.
[16]Christina K,Speirs Joseph R,Simpson Clifford G,et al.Impact of 1p/19q codeletion and histology on outcomes of anaplastic gliomas treated with radiation therapy and temozolomide[J].International journal of radiation oncology,biology,physics,2015,91(2):268-276.
[17]孙文博.酪氨酸激酶2(DDR2)和血管内皮细胞生长因子(V EGF)在脑胶质瘤中的表达及相关性研究[D].河北医科大学,2015:34-37.
[18]Carlos Rodrigo,Hardebeck Bipasha,Mukherjee Nozomi,et al.Inhibition of DNA double-strand break repair by the dual PI3K/mTOR inhibitor NVP-BEZ235 as a strategy for radiosensitization of glioblastoma[J].Clinical cancer research:an official journal of the American Association for Cancer Research,2014,20(5):1235-1248.
[19]Elodie A,Pérès Aurélie N,Gérault Samuel,et al.Silencing erythropoietin receptor on glioma cells reinforces efficacy of temozolomide and X-rays through senescence and mitotic catastrophe[J].Oncotarget,2015,6(4):2101-2119.
[20]李子煌,李先明,杨东,等.替莫唑胺联合放疗治疗高级别脑胶质瘤的临床分析[J].肿瘤防治研究,2015,42(2):185-189.
[21]Grossman Harry,Brastianos Jaishri O,Blakeley Antonella,et al.Combination of anti-VEGF therapy and temozolomide in two experimental human glioma models[J].Journal of neuro-oncology,2014,116(1):59-65.
[22]Jeyapala n Je r rold,Boxe r ma n Joh n,Dona hue Ma rc,et al.Pa cl it a xel poliglumex,temozolomide,and radiation for newly diagnosed high-grade glioma:a Brown University Oncology Group Study[J].American journal of clinical oncology,2014,37(5):444-449.
[2]Towner Michael,Ihnat Debra,Saunders Anja,et al.A new anti-glioma therapy,AG119:pre-clinical assessment in a mouse GL261 glioma model[J].BMC cancer,2015,15(1):522.
[3]黄仁华,侯艳丽,徐欣,等.脑胶质瘤术后三维适形放疗联合替莫唑胺疗效分析[J].肿瘤学杂志,2015,21(3):219-222.
[4]Chiang KL,Chang KP,Lee YY,et al.Role of temozolomide in the treatment of newly diagnosed diffuse brainstem glioma in children:experience at a single institution[J].Child's nervous system,2010,26(8):1035-1041.
[5]李俊杰,王博,毕智勇,等.高级别脑胶质瘤术后三维适形放疗联合替莫唑胺化疗的疗效分析[J].湖南中医药大学学报,2013,33(10):11.
[6]赵东利,刘锐,邓怀慈,等.恶性脑胶质瘤术后替莫唑胺同步放化疗与单纯放疗的疗效对比[J].西部医学,2014,26(9):1141-1143
[7]范阳华,吕世刚,吴雷,等.放疗联合替莫唑胺治疗恶性脑胶质瘤疗效及安全性的系统评价[J].重庆医科大学学报,2015,40(5):728-735.
[8]王浩,吴磊,刘秋芳,等.替莫唑胺在高级别脑胶质瘤术后同步放化疗中的临床研究[J].西部医学,2013,25(9):1316-1319.
[9]陈孝平,汪建平.外科学[M].第8版.北京:人民卫生出版社,2013:210-215.
[10]姚晓峰,欧阳翠微.替莫唑胺联合放射治疗治疗恶性脑胶质瘤的疗效观察[J].中国肿瘤临床与康复,2014,21(6):709-712.
[11]郭旗,田野.放疗对低级别脑胶质瘤患者认知功能的影响及防治方法[J].中华放射医学与防护杂志,2015,35(5):397-400.
[12]Macdonald Glenn J,Lesser Stephen W,Coons David G,et al.Phase 2 study of temozolomide-based chemoradiation therapy for high-risk low-grade gliomas:preliminary results of Radiation Therapy Oncology Group 0424[J].International journal of radiation oncology,biology,physics,2015,91(3):497-504.
[13]姚春筱,张树平,陈保民,等.调强适形放疗联合替莫唑胺治疗恶性脑胶质瘤的临床观察[J].中国肿瘤,2013,22(3):238-240.
[14]Bow Lee S,Hwang Noam,Schildhaus Joanna,et al.Local deliver y of angiogenesis-inhibitor minocycline combined with radiotherapy and oral temozolomide chemotherapy in 9L glioma[J].Journal of neurosurgery,2014,120(3):662-669.
[15]毛德强,潘玲,戴勤弼,等.术后放疗联合替莫唑胺治疗高级别胶质瘤的近期临床疗效及安全性观察[J].重庆医学,2013,42(1):21-23.
[16]Christina K,Speirs Joseph R,Simpson Clifford G,et al.Impact of 1p/19q codeletion and histology on outcomes of anaplastic gliomas treated with radiation therapy and temozolomide[J].International journal of radiation oncology,biology,physics,2015,91(2):268-276.
[17]孙文博.酪氨酸激酶2(DDR2)和血管内皮细胞生长因子(V EGF)在脑胶质瘤中的表达及相关性研究[D].河北医科大学,2015:34-37.
[18]Carlos Rodrigo,Hardebeck Bipasha,Mukherjee Nozomi,et al.Inhibition of DNA double-strand break repair by the dual PI3K/mTOR inhibitor NVP-BEZ235 as a strategy for radiosensitization of glioblastoma[J].Clinical cancer research:an official journal of the American Association for Cancer Research,2014,20(5):1235-1248.
[19]Elodie A,Pérès Aurélie N,Gérault Samuel,et al.Silencing erythropoietin receptor on glioma cells reinforces efficacy of temozolomide and X-rays through senescence and mitotic catastrophe[J].Oncotarget,2015,6(4):2101-2119.
[20]李子煌,李先明,杨东,等.替莫唑胺联合放疗治疗高级别脑胶质瘤的临床分析[J].肿瘤防治研究,2015,42(2):185-189.
[21]Grossman Harry,Brastianos Jaishri O,Blakeley Antonella,et al.Combination of anti-VEGF therapy and temozolomide in two experimental human glioma models[J].Journal of neuro-oncology,2014,116(1):59-65.
[22]Jeyapala n Je r rold,Boxe r ma n Joh n,Dona hue Ma rc,et al.Pa cl it a xel poliglumex,temozolomide,and radiation for newly diagnosed high-grade glioma:a Brown University Oncology Group Study[J].American journal of clinical oncology,2014,37(5):444-449.