IMRT、VMAT模式照射离体人肺癌细胞的生物学效应研究
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摘要
目的观察调强适形放射治疗(IMRT)、容积旋转调强放射治疗(VMAT)模式照射离体人肺癌细胞的生物效应,研究IMRT、VMAT模式放疗照射的作用机制,为制订合理的临床放疗方案提供理论依据。方法选取人肺鳞癌细胞SK-MES-1、人肺小细胞癌细胞NCI-H446,分别进行体外琼脂悬浮克隆培养法建立肿瘤模型。分别使用9个不同的照射剂量点进行急速照射研究,照射3 min后计算细胞存活分数,采用Graph Pad Prism软件处理数据,根据线性二次方程拟合细胞存活曲线,再把呈指数生长期的SK-MES-1、NCI-H446分别分成四个组:1VMAT模式照射组(直线型加速器能量为6 MV 6 min照射);IMRT模式15 min照射组;IMRT模式30 min照射组;IMRT模式45 min照射组。每组照射总量为8 Gy,1次/d,2 Gy/次,4 d内完成。最后,采用克隆分析法计算细胞的存活分数,对比IMRT模式和VMAT模式的放射特点及生物效应。结果①急速照射完成后,分析得到SK-MES-1、NCI-H446细胞的放射生物学参数。SK-MES-1细胞各参数详细数值分别为(D_0、Dq、N值、α值、β值、α/β值):0.87 Gy、0.48 Gy、3.6、0.17 Gy~(-1)、0.091 Gy~(-2)、1.87 Gy;NCI-H446细胞以上各参数数值分别为0.61 Gy、0.35 Gy、4.0、0.98 Gy~(-1)、0.089 Gy~(-2)、11.01 Gy。②总量为8 Gy的4 d照射中,SK-MES-1细胞各照射组(VMAT模式照射组和IMRT模式15、30、45 min照射组)的细胞存活率分别为7.25%、8.95%、9.63%、11.32%,IMRT模式照射下的细胞存活率较VMAT模式明显增加。NCI-H446细胞以上各组照射后的细胞存活率分别为0.192%、0.205%、0.208%、0.209%,差异不明显。结论人肺鳞癌细胞SK-MES-1的细胞放射敏感性(D_0、N值)相对人肺小细胞癌细胞NCI-H446更低,亚致死性损伤修复能力(Dq值和α/β值)相对NCI-H446细胞更强,剂量率改变对其放射生物效应影响明显,IMRT模式单次剂量输出时间延长导致SK-MES-1细胞生存率增加,NCI-H446细胞增加不明显。
Objective To observe the biological effects of intensity-modulated radiotherapy(IMRT) and volumetric modulated arc therapy(VMAT) irradiation for the human lung cancer cells in vitro, and to study the mechanism of IMRT and VMAT irradiation, in order to provide evidence for formulating reasonable clinical radiotherapy plan.Methods The human lung squamous carcinoma cells SK-MES-1 and human lung small cell cancer cells NCI-H446 were selected to establish tumor model by agar suspension culture method in vitro, then the cells were given rapid radiation research at 9 dose levels. After irradiation for 3 min, the survival percentage of cells was calculated,Graph Pad Prism software was used to process data, the cell survival curve was fit with linear-quadratic formula, then the SK-MES-1, NCI-H446 at exponential growth phase were divided into four groups: VMAT irradiation group(the energy of linear accelerator was 6 MV, for 6 min); IMRT irradiation for 15 min group; IMRT irradiation for 30 min group; IMRT irradiation for 45 min group. The total irradiation of each group was 8 Gy, once a day, 2 Gy every time,finished in 4 days. At last, the cloning assay was used to calculate the survival rate of cells, to compare the radiation characteristics and biological effects between IMRT model and VMAT model. Results①After finishing rapid radiation, the radiobiological parameters ofSK-MES-1, NCI-H446 cells were achieved. The detailed numerical value of each parameter of SK-MES-1 cells(D0,Dq, N value, α value, β value, α/β value) was 0.87 Gy, 0.48 Gy, 3.6, 0.17 Gy-1, 0.091 Gy-2, 1.87 Gy respectively;which of NCI-H446 cells was 0.61 Gy, 0.35 Gy, 4.0, 0.98 Gy-1, 0.089 Gy-2, 11.01 Gy respectively.② In the irradiation of 4 d with 8 Gy, the survival rate of SK-MES-1 cells in all groups(VMAT irradiation group and IMRT irradiation for 15, 30, 45 min group) was 7.25%, 8.95%, 9.63%, 11.32% respectively, the survival rate under the IMRT irradiation was higher than that of VMAT irradiation. The survival rate of NCI-H446 cells in the groups above was0.192%, 0.205%, 0.208%, 0.209% respectively, the difference was not obvious. Conclusion The cellular radiosensitivity(D0, N value) of human lung squamous carcinoma cells SK-MES-1 is lower than that of human lung small cell cancer cells NCI-H446, the sublethal damage repair capacity(Dq value and α/β value) is stronger than that of NCI-H446, the changes of dosage rates has significant influence for the radiobiological effect, the prolonged single dose output time of IMRT model lead to the increase the survival rate of SK-MES-1 cells, without obvious increase in NCI-H446 cells.
Objective To observe the biological effects of intensity-modulated radiotherapy(IMRT) and volumetric modulated arc therapy(VMAT) irradiation for the human lung cancer cells in vitro, and to study the mechanism of IMRT and VMAT irradiation, in order to provide evidence for formulating reasonable clinical radiotherapy plan.Methods The human lung squamous carcinoma cells SK-MES-1 and human lung small cell cancer cells NCI-H446 were selected to establish tumor model by agar suspension culture method in vitro, then the cells were given rapid radiation research at 9 dose levels. After irradiation for 3 min, the survival percentage of cells was calculated,Graph Pad Prism software was used to process data, the cell survival curve was fit with linear-quadratic formula, then the SK-MES-1, NCI-H446 at exponential growth phase were divided into four groups: VMAT irradiation group(the energy of linear accelerator was 6 MV, for 6 min); IMRT irradiation for 15 min group; IMRT irradiation for 30 min group; IMRT irradiation for 45 min group. The total irradiation of each group was 8 Gy, once a day, 2 Gy every time,finished in 4 days. At last, the cloning assay was used to calculate the survival rate of cells, to compare the radiation characteristics and biological effects between IMRT model and VMAT model. Results①After finishing rapid radiation, the radiobiological parameters ofSK-MES-1, NCI-H446 cells were achieved. The detailed numerical value of each parameter of SK-MES-1 cells(D0,Dq, N value, α value, β value, α/β value) was 0.87 Gy, 0.48 Gy, 3.6, 0.17 Gy-1, 0.091 Gy-2, 1.87 Gy respectively;which of NCI-H446 cells was 0.61 Gy, 0.35 Gy, 4.0, 0.98 Gy-1, 0.089 Gy-2, 11.01 Gy respectively.② In the irradiation of 4 d with 8 Gy, the survival rate of SK-MES-1 cells in all groups(VMAT irradiation group and IMRT irradiation for 15, 30, 45 min group) was 7.25%, 8.95%, 9.63%, 11.32% respectively, the survival rate under the IMRT irradiation was higher than that of VMAT irradiation. The survival rate of NCI-H446 cells in the groups above was0.192%, 0.205%, 0.208%, 0.209% respectively, the difference was not obvious. Conclusion The cellular radiosensitivity(D0, N value) of human lung squamous carcinoma cells SK-MES-1 is lower than that of human lung small cell cancer cells NCI-H446, the sublethal damage repair capacity(Dq value and α/β value) is stronger than that of NCI-H446, the changes of dosage rates has significant influence for the radiobiological effect, the prolonged single dose output time of IMRT model lead to the increase the survival rate of SK-MES-1 cells, without obvious increase in NCI-H446 cells.
引文
[1]陈万青,张思维,曾红梅,等.中国2010年恶性肿瘤发病与死亡[J].中国肿瘤,2014,23(1):1-10.
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[4]王志,邬蒙,何秀琴,等.鼻咽癌CNE1、CNE2细胞系IMRT模式离体照射生物效应研究[J].实用癌症杂志,2008,23(3):248-251.
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[6]张春,潘建基,张瑜,等.鼻咽癌适形调强放疗对腮腺功能影响的前瞻性研究[J].实用癌症杂志,2007,22(4):380.
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[8]Vieillot S,Azria D,Lemanski C,et al.Plan comparison of volumetric-modulated arc therapy(Rapid Arc)and conventional intensity-modulated radiation therapy(IMRT)in anal canal cancer[J].Radiat Oncol,2010,5(8):1984-1990.
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[11]张矛,金海国,卜明伟,等.脑胶质瘤术后VMAT与IMRT放疗技术间比较[J].中国医学物理学杂志,2011,28(6):2959-2963.
[12]张瑞,习勉,李巧巧,等.胸上段食管癌容积旋转调强和静态调强与三维适形放疗计划的剂量学比较[J].中山大学学报:医学科学版,2012,33(2):260-264.
[13]商海焦,陈利,王学涛,等.鼻咽癌CDR-VMAT与ssIMRT剂量学比较评估[J].中国医学物理学杂志,2014,31(1):4612-4616.
[14]迟锋,温戈,陈利,等.直肠癌术前三维适形和五野及容积弧形调强放疗剂量学比较[J].中华肿瘤防治杂志,2014,21(18):1455-1460.
[15]郭蕊,孙颖,黄劭敏,等.鼻咽癌容积旋转调强放疗与常规静态调强放疗的剂量学对比研究[J].中山大学学报:医学科学版,2012,33(6):835-840,855.
[16]张黎,习勉,孙文钊,等.肝癌三维适形、静态调强与容积旋转调强放射治疗的剂量学研究[J].中山大学学报:医学科学版,2012,33(3):402-406.
[17]张耀文,郑安平,董尚文,等.胸上段食管癌容积旋转调强与静态调强放疗计划的剂量学比较[J].中华肿瘤防治杂志,2014,21(23):1902-1906,1910.
[18]易金玲,金献测,周永强,等.鼻咽癌IMRT与VMAT治疗的计划与剂量验证比较研究[J].中国医学物理学杂志,2013,30(1):3859-3865.
[19]徐莉霞,李夏东,章霓,等.胃癌术后IMRT和VMAT计划的剂量学比较[J].实用肿瘤杂志,2015,30(2):154-156.
[20]蒋军.容积弧形调强放疗、固定野调强放疗与三维适形放疗在局部晚期非小细胞肺癌中的剂量学对比研究[D].苏州:苏州大学,2014.
[2]Siegel R,Naishadham D,Jemal A.Cancer statistics,2013[J].CA:a cancer journal for clinicians,2013,63(1):11-30.
[3]殷蔚伯.肿瘤放射治疗学[M].北京:中国协和医科大学出版社,2008:240-245.
[4]王志,邬蒙,何秀琴,等.鼻咽癌CNE1、CNE2细胞系IMRT模式离体照射生物效应研究[J].实用癌症杂志,2008,23(3):248-251.
[5]姜玲,熊晓鹏,胡超苏,等.照射实施时间延长对肿瘤细胞杀灭效应影响的体外实验研究[J].中国癌症杂志,2009,19(2):112-117.
[6]张春,潘建基,张瑜,等.鼻咽癌适形调强放疗对腮腺功能影响的前瞻性研究[J].实用癌症杂志,2007,22(4):380.
[7]Otto K.Volumetric modulated arc therapy:IMRT in a single gantry arc[J].Medical Physics,2008,35(1):310.
[8]Vieillot S,Azria D,Lemanski C,et al.Plan comparison of volumetric-modulated arc therapy(Rapid Arc)and conventional intensity-modulated radiation therapy(IMRT)in anal canal cancer[J].Radiat Oncol,2010,5(8):1984-1990.
[9]Shang J,Kong W,Wang YY,et al.VMAT planning study in rectal cancer patients[J].Radiat Oncol,2014,9(1):219.
[10]van Gijn W,Marijnen CA,Nagtegaal ID,et al.Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer:12-year follow-up of the multicentre,randomised controlled TME trial[J].Lancet Oncol,2011,12(6):575-582.
[11]张矛,金海国,卜明伟,等.脑胶质瘤术后VMAT与IMRT放疗技术间比较[J].中国医学物理学杂志,2011,28(6):2959-2963.
[12]张瑞,习勉,李巧巧,等.胸上段食管癌容积旋转调强和静态调强与三维适形放疗计划的剂量学比较[J].中山大学学报:医学科学版,2012,33(2):260-264.
[13]商海焦,陈利,王学涛,等.鼻咽癌CDR-VMAT与ssIMRT剂量学比较评估[J].中国医学物理学杂志,2014,31(1):4612-4616.
[14]迟锋,温戈,陈利,等.直肠癌术前三维适形和五野及容积弧形调强放疗剂量学比较[J].中华肿瘤防治杂志,2014,21(18):1455-1460.
[15]郭蕊,孙颖,黄劭敏,等.鼻咽癌容积旋转调强放疗与常规静态调强放疗的剂量学对比研究[J].中山大学学报:医学科学版,2012,33(6):835-840,855.
[16]张黎,习勉,孙文钊,等.肝癌三维适形、静态调强与容积旋转调强放射治疗的剂量学研究[J].中山大学学报:医学科学版,2012,33(3):402-406.
[17]张耀文,郑安平,董尚文,等.胸上段食管癌容积旋转调强与静态调强放疗计划的剂量学比较[J].中华肿瘤防治杂志,2014,21(23):1902-1906,1910.
[18]易金玲,金献测,周永强,等.鼻咽癌IMRT与VMAT治疗的计划与剂量验证比较研究[J].中国医学物理学杂志,2013,30(1):3859-3865.
[19]徐莉霞,李夏东,章霓,等.胃癌术后IMRT和VMAT计划的剂量学比较[J].实用肿瘤杂志,2015,30(2):154-156.
[20]蒋军.容积弧形调强放疗、固定野调强放疗与三维适形放疗在局部晚期非小细胞肺癌中的剂量学对比研究[D].苏州:苏州大学,2014.