Stereotactic ablative radiotherapy should be combined with a hypoxic cell radiosensitizer.
Stereotactic ablative radiotherapy should be combined with a hypoxic cell radiosensitizer.
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立体定向消融放疗应与缺氧细胞放射增敏剂联合使用。
DOI：
10.1016/j.ijrobp.2010.04.070
复制
发表时间：
2010-10-01
影响因子：
7
通讯作者：
Loo, Billy W., Jr.
中科院分区：
文献类型：
--
作者：
Brown, J. Martin;Diehn, Maximilian;Loo, Billy W., Jr.
关键词：
评估肿瘤缺氧对临床使用的立体定向消融放射治疗（SABR）方案预期细胞杀伤的影响，并确定使用临床可用的缺氧细胞放射增敏剂可以在多大程度上预防缺氧的负面影响。我们使用标准LQ模型和通用存活曲线（USC）修正，在假设和不假设20%肿瘤细胞缺氧的情况下，计算了临床使用的SABR方案的预期肿瘤细胞杀伤水平。我们将所得结果与我们自己的不同大小肺肿瘤的临床数据以及其他人的已发表数据进行比较。我们还计算了在临床可达到的药物浓度下加入缺氧细胞增敏剂依他硝唑对细胞存活的预期影响。如果不考虑肿瘤缺氧，用任何目前使用的SABR方案对肿瘤细胞杀伤进行建模产生的结果与大多数临床发现不一致。然而，假设肿瘤缺氧，预期的细胞杀伤水平与临床数据一致。因为只有一些最小的肿瘤的临床数据与无肿瘤缺氧一致，但这些肿瘤的敏感性可能有其他原因。在临床上可达到的肿瘤浓度下添加依他硝唑会使SABR中使用的大辐射剂量的预期肿瘤细胞杀伤大幅增加。肿瘤缺氧的存在是限制SABR在周围正常组织可耐受的辐射剂量下治愈肿瘤的一个主要负面因素。然而，缺氧的这种负面影响可以通过添加临床耐受剂量的缺氧细胞放射增敏剂依他硝唑来克服。
To evaluate the effect of tumor hypoxia on the expected cell killing by clinically used regimens of stereotactic ablative radiotherapy (SABR), and to determine the extent to which the negative effect of hypoxia could be prevented using a clinically available hypoxic cell radiosensitizer. We have calculated the expected level of tumor cell kill from clinically used regimens of SABR both with and without the assumption of 20% of the tumor cells being hypoxic using the standard LQ model and the universal survival curve (USC) modification. We compare the results obtained with our own clinical data on lung tumors of different sizes and with the published data of others. We also have calculated the expected effect on cell survival of adding the hypoxic cell sensitizer etanidazole at clinically achievable drug concentrations. Modeling tumor cell killing with any of the currently used regimens of SABR produces results that are inconsistent with the majority of the clinical findings if tumor hypoxia is not considered. However, with the assumption of tumor hypoxia the expected level of cell killing is consistent with the clinical data. For only some of the smallest tumors are the clinical data consistent with no tumor hypoxia, but there could be other reasons for the sensitivity of these tumors. The addition of etanidazole at clinically achievable tumor concentrations produces a large increase in the expected tumor cell kill from the large radiation doses used in SABR. The presence of tumor hypoxia is a major negative factor in limiting the curability of tumors by SABR at radiation doses that are tolerable to surrounding normal tissues. However, this negative effect of hypoxia could be overcome by the addition of clinically tolerable doses of the hypoxic cell radiosensitizer etanidazole.
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影响因子：
2.6
作者：
BROWN, JM
通讯作者：
BROWN, JM
DOI：
10.1016/j.ijrobp.2009.02.027
发表时间：
2010-03-01
影响因子：
7
作者：
Dunlap, Neal E.;Cai, Jing;Larner, James M.
通讯作者：
Larner, James M.
DOI：
10.1016/s0360-3016(00)01584-4
发表时间：
2001-05-01
影响因子：
7
作者：
Goodman, KA;Sneed, PK;Larson, DA
通讯作者：
Larson, DA
DOI：
10.1016/j.ijrobp.2008.08.036
发表时间：
2008-12-01
影响因子：
7
作者：
Hoppe, Bradford S.;Laser, Benjamin;Rosenzweig, Kenneth E.
通讯作者：
Rosenzweig, Kenneth E.
DOI：
10.1016/0360-3016(86)90080-5
发表时间：
1986-04-01
影响因子：
7
作者：
KALLMAN, RF;DORIE, MJ
通讯作者：
DORIE, MJ