Wang Jian Z, Rhee Juong G, Shi Peipei, Stewart Robert D, Allen Li X
Department of Radiation Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Int J Radiat Biol. 2008 Jun;84(6):515-22. doi: 10.1080/09553000802061285.
The prolonged delivery times associated with intensity modulated radiation therapy (IMRT) may reduce treatment effectiveness of radiation therapy for cancers with short repair half-times. In this study, in vitro radiation experiments with DU-145 prostate cancer cells were designed to quantify the half-time of sublethal damage repair.
A series of single-fraction and split-dose clonogenic survival experiments were performed and analyzed using the linear-quadratic (LQ) survival model with mono-/two-component exponential and reciprocal-time repair kinetic models.
Our data indicate that DU-145 cells are very radiosensitive (alpha = 0.44 Gy(-1), standard CI: 0.41-0.49 Gy(-1)) and are relatively insensitive to dose fractionation (alpha/beta = 16 Gy, standard CI: 12-34 Gy). The estimated repair half-time is 23 min (standard CI: 10-97 min) with some evidence that a small portion of the sublethal damage is repaired more slowly.
The reported radiosensitivity parameters (alpha and alpha/beta) are larger than those derived from other in vitro experiments and clinical data. In contrast, the half-time for sublethal damage repair ( approximately 23 min) is close to the one derived from clinical data ( approximately 16 min). For such short repair half-times, the effectiveness of IMRT treatments may be substantially improved by decreasing the fraction delivery time.
与调强放射治疗(IMRT)相关的延长的递送时间可能会降低对修复半衰期短的癌症的放射治疗效果。在本研究中,设计了针对DU-145前列腺癌细胞的体外放射实验,以量化亚致死损伤修复的半衰期。
进行了一系列单次分割和分次剂量克隆形成存活实验,并使用具有单/双组分指数和倒数时间修复动力学模型的线性二次(LQ)存活模型进行分析。
我们的数据表明,DU-145细胞对放射非常敏感(α = 0.44 Gy⁻¹,标准置信区间:0.41 - 0.49 Gy⁻¹),并且对剂量分割相对不敏感(α/β = 16 Gy,标准置信区间:12 - 34 Gy)。估计的修复半衰期为23分钟(标准置信区间:10 - 97分钟),有证据表明一小部分亚致死损伤修复得更慢。
报告的放射敏感性参数(α和α/β)大于从其他体外实验和临床数据得出的参数。相比之下,亚致死损伤修复的半衰期(约23分钟)接近从临床数据得出的半衰期(约16分钟)。对于如此短的修复半衰期,通过减少分次递送时间,IMRT治疗的效果可能会得到显著改善。