Krause Mechthild, Wohlfarth Jana, Georgi Benjamin, Pimentel Nuno, Dorner Daniela, Zips Daniel, Eicheler Wolfgang, Hessel Franziska, Short Susan C, Joiner Michael C, Baumann Michael
Clinic for Radiotherapy and Radiation Oncology, Medical Faculty Carl Gustav Carus, University of Technology, Dresden, Germany.
Int J Radiat Biol. 2005 Oct;81(10):751-8. doi: 10.1080/09553000500491537.
Low dose hyperradiosensitivity (HRS) has been observed in HGL21- and T98G human glioblastoma cells in vitro. The present study investigates whether these effects translate into improved outcome of ultrafractionated irradiation (UF) in vivo.
T98G or HGL21 were transplanted on the hind leg of nude mice. Tumours were irradiated with UF (3 fractions of 0.4 Gy per day, interval 4 h, 7 days per week) or with conventional fractionation (CF; 1 fraction of 1.68 Gy per day, 5 days per week) over 2 or 4 weeks in HGL21 and 2,4 or 6 weeks in T98G. In HGL21, graded top-up doses under clamped hypoxia were applied after 4 weeks of fractionated irradiation. Additional groups of animals were irradiated with single doses under clamp hypoxic conditions with or without whole body irradiation (WBI) before tumour transplantation. Experimental endpoints were growth delay (time to 5-fold starting volume, GD(V5)) and local tumour control.
In T98G tumours median relative GD(V5) was 1.2 [95% C.I. 0.96; 8] in the CF and 0.8 [0.7; 1.02] in the UF arm (p = 0.009) indicating that ultrafractionation is less efficient than conventional fractionation. The TCD50 value of 33.5 Gy [22; 45] after UF was higher than TCD50 of 23.6 Gy [16; 31] after CF (p = 0.15). In HGL21 the median relative GD(V5) was not significantly different between CF and UF. The top-up TCD50 value of 16.1 Gy [95% C.I. 9; 23 Gy] after CF was significantly lower than the corresponding value of 33.2 Gy [23; 44] after UF irradiation (p = 0.007), indicating a higher efficacy of CF compared to UF.
The results on human T98G and HGL21 glioblastoma do not support the hypothesis that HRS in vitro translates into improved outcome of ultrafractionated irradiation in vivo.
在体外培养的HGL21和T98G人胶质母细胞瘤细胞中观察到了低剂量超敏反应（HRS）。本研究旨在探讨这些效应在体内是否能转化为超分割照射（UF）的更好疗效。
将T98G或HGL21细胞接种于裸鼠后腿。在HGL21组中，对肿瘤进行2周或4周的超分割照射（每天3次，每次0.4 Gy，间隔4小时，每周7天）或常规分割照射（CF；每天1次，每次1.68 Gy，每周5天）；在T98G组中，照射2、4或6周。在HGL21组中，分割照射4周后，在钳夹缺氧条件下给予递增剂量照射。另外几组动物在肿瘤移植前，在钳夹缺氧条件下接受单次剂量照射，有无全身照射（WBI）。实验终点为生长延迟（达到起始体积5倍的时间，GD(V5)）和局部肿瘤控制。
在T98G肿瘤中，CF组的中位相对GD(V5)为1.2 [95%置信区间0.96；8]，UF组为0.8 [0.7；1.02]（p = 0.009），表明超分割照射的效率低于常规分割照射。UF照射后的TCD50值为33.5 Gy [22；45]，高于CF照射后的TCD50值23.6 Gy [16；31]（p = 0.15）。在HGL21组中，CF组和UF组的中位相对GD(V5)无显著差异。CF照射后的递增TCD50值为16.1 Gy [95%置信区间9；23 Gy]，显著低于UF照射后的相应值33.2 Gy [23；44]（p = 0.007），表明CF组比UF组疗效更高。
关于人T98G和HGL21胶质母细胞瘤的研究结果不支持体外HRS能转化为体内超分割照射更好疗效这一假说。
