The Experiment About The Biological Effectiveness Of Intense-modulated Radiation Therapy On Rats

Background and Objective: Intensity-modulated radiation therapy (IMRT) is a new irradiation technique developed to improve target dose conformity and normal tissue sparing. It could optimize the physical dose distribution of radiotherapy, there by enhance the tumor local control and lower the radiation-induced acute and late toxicities. The advantages of IMRT make more and more patients with malignant tumor select to receive radiotherapy with this advanced technique. However, the prolonged fraction-delivery-time in IMRT might cause significant change in radiobiological effectiveness in comparison to conventional external beam radiation therapy (EBRT). IMRT delivers dose, either dynamically or statically (e.g. step-and-shoot),many beam apertures (segments) are shaped with multi leaf collimator. It takes much longer time to deliver a single Fractional dose with IMRT than EBRT. Generally, EBRT takes about 2-5 min to deliver a single fractional dose, whereas IMRT with static delivery requires 15-45 min to deliver the same fractional dose. The prolonged fraction-delivery-time in IMRT might have a negative effect on tumor cell killing because of time-dependent sub-lethal damage repair (SLDR). And the fractional numbers and the dose of the subsegments may also affect the radiobiological performance. This study was designed to explore the impact of prolonged fraction-delivery-time, fractional segments and its dose in IMRT on cell killing of small intestine.Material and Methods: The important aspects of quality assure (QA) for the experiments, including dose verification and equivalence verification on radiobiological effectiveness of the sub-fractionation pattern of fraction-delivery-time modeling IMRT used in this study. One hundred and eighty Kunming rats are divided into five groups at random, group A contain 15 rats unirradiated, group B contain 15 rats irradiated in conventional external beam radiation, group C contain 50 rats irradiated in modeling IMRT for 15 minutes, group D contain 50 rats irradiated in modeling IMRT for 30 minutes and group D contain 50 rats irradiated in modeling IMRT for 45 minutes. The group C is divided into five subgroups, C₁,C₂,C₃,C₄ and C₅ in order to be irradiated in modeling IMRT 15 minutes with 5 segments,10 segments, 20 segments, 40 segments, 80 segments. And the same process is taken on the group D and E. All the irradiated groups are given 12Gy fractionated into 3 times interval 4 hours. The rats are irradiated with linear accelerator at the dose rate 300cGy/min. The rats are executed after 72 hours. Take out of 2cm jejunum 3cm far away from pyloric orifice. This section jejunum is colored in hematoxylin eosin stain. Then observing and recording the numbers of the cells of crypt and the height of the villi of small intestine. For the rest of the small intestine is checked by the flow cytometer,(FCM) to detect out the percent of G₂ cells after the epithelial cells are extracted out.Result: The villi of small intestine gradually become higher along with fractional delivery time of the modeling IMRT. There is significant difference between modeling IMRT pattern and conventional radiation therapy pattern (F=12.14,P=0.000). but there is no significant difference between modeling IMRT for 15min pattern and conventional radiation therapy pattern (t=-0.89,P=0.385). The survival crypt cells of small intestine become more and more prolongation of the fractional delivery time of IMRT, the difference between modeling IMRT pattern and conventional radiation therapy pattern is significant(F=40.41,P=0.000). The amount of survival crypt cells of small intestine irradiated modeling IMRT with different fractional delivery time are all significant larger than that irradiated in conventional radiation therapy pattern. The percent of G₂ phase cells checked with flow cytometry gets the same result. We observed when the segments of modeling IMRT with the same fractional delivery time become more the amount of survival crypt cells of small intestine become larger, this difference is no significant modeling IMRT for 15min pattern. In the modeling IMRT in 30min, the amount of survival crypt cells of small intestine of 20 segments is much larger than that of 5 segments.Conclusion: In comparison of conventional radiation therapy the prolonged fraction-delivery-time modeling IMRT significantly decreased the cells killing of small intestine , the fractional segments and dose of the fractional segments also affect the IMRT ability of cells killing , along with the increasing of the fractional segments and its decreasing dose ,the modeling IMRT significantly decreased the cells killing of small intestine. As a special and neoteric radiation therapy, IMRT have its distinct biological effect, if we want to find out the of concrete and full cell killing mechanism of IMRT ,we have to do more and more deep investigations.