Armour E P, White J R, Armin A, Corry P M, Coffey M, DeWitt C, Martinez A
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073, USA.
Int J Radiat Oncol Biol Phys. 1997 Jul 1;38(4):825-34. doi: 10.1016/s0360-3016(97)89478-3.
Clinical protocols utilizing pulsed low dose rate brachytherapy (PDR) to replace traditional continuous low dose rate brachytherapy (CLDR) employ irradiation in individual pulses given at intervals of a few hours. A critical factor in determining whether PDR will produce equivalent or greater late-occurring normal tissue toxicity is the dose per pulse. A rat rectal model was used to determine the role of pulse size in modifying dose effectiveness in producing late-occurring toxicity.
A rat model in which the rectum is irradiated with 192Ir sources was used in conjunction with an intracavitary applicator. A section of rectum 1.3 cm in length was irradiated with either 0.75 Gy/h CLDR or one of five schemes of PDR. The schemes applied 0.375, 0.75, 1.5, 3.0, or 6.0 Gy pulses at 0.5, 1.0, 2.0, 4.0, or 8.0 h intervals, respectively. Rats were observed for up to 300 days after completion of irradiation for rectal obstruction. Rectal specimens were taken at the time of sacrifice for obstruction or at the end of follow-up and analyzed histologically for injury.
Effectiveness of irradiation was analyzed by calculating the ED50 for incidence of obstruction and severe histological injury. The ED50 for obstruction after treatment with CLDR and pulse sizes of 0.375, 0.75, and 1.5 Gy were 70.5, 68.0, 68.6, and 68.8 Gy, respectively. These values were not significantly different. Compared to CLDR, the ED50 for obstruction after pulse sizes of 3.0 and 6.0 Gy were significantly different at 60.9 and 46.3 Gy, respectively. The relative changes in ED50 for the different radiation schemes in producing ulceration, fibrosis, and vascular sclerosis injury were similar to that observed for obstruction. The endpoints of colitis cystica profunda and atypical epithelial regeneration varied less with increasing pulse size.
We have demonstrated that for late rat rectal injury, dose responses to PDR pulse sizes up to 1.5 Gy at 2-h intervals are not distinguishable from that seen with CLDR at a dose rate of 0.75 Gy/h.
利用脉冲低剂量率近距离放射疗法（PDR）取代传统连续低剂量率近距离放射疗法（CLDR）的临床方案采用以数小时为间隔的单个脉冲进行照射。确定PDR是否会产生同等或更大的晚期正常组织毒性的一个关键因素是每个脉冲的剂量。使用大鼠直肠模型来确定脉冲大小在改变产生晚期毒性的剂量有效性方面的作用。
使用一种大鼠模型，其中直肠用192Ir源进行照射，并结合腔内施源器。用0.75 Gy/h的CLDR或五种PDR方案之一对一段1.3 cm长的直肠进行照射。这些方案分别以0.5、1.0、2.0、4.0或8.0小时的间隔施加0.375、0.75、1.5、3.0或6.0 Gy的脉冲。在照射完成后观察大鼠长达300天，以观察直肠梗阻情况。在因梗阻处死时或随访结束时采集直肠标本，并进行组织学分析以评估损伤情况。
通过计算梗阻发生率和严重组织学损伤的半数有效剂量（ED50）来分析照射的有效性。CLDR以及脉冲大小为0.375、0.75和1.5 Gy治疗后梗阻的ED50分别为70.5、68.0、68.6和68.8 Gy。这些值无显著差异。与CLDR相比，脉冲大小为3.0和6.0 Gy治疗后梗阻的ED50分别为60.9和46.3 Gy，有显著差异。不同放射方案在产生溃疡、纤维化和血管硬化损伤方面的ED50相对变化与梗阻情况相似。随着脉冲大小增加，深部囊性结肠炎和非典型上皮再生的终点变化较小。
我们已经证明，对于大鼠晚期直肠损伤，以2小时为间隔、脉冲大小高达1.5 Gy的PDR的剂量反应与以0.75 Gy/h的剂量率进行CLDR时的情况无明显区别。
