Study On The Relationship Between The Irradiation Dose And Volume In Radiation-induced Lung Injury

Objective:To investigate the relationships between the irradiation dose and volume in radiation-induced lung injury through setting—up the model of graded volume irradiation of the rat lung.Methods:ELEKTA precise 2.03 treatment plan system was applied to calculate the irradiation dose and volume.Functional,biochemical,histopathological and CT changes were compared biweekly after single irradiation of the regional lung.Results:1.Rat model of lung fibrosis:Single dose irradiation(2000cGy and 4610cGy)to two different volume levels(100%and 25%)were applied to set up the model of graded volume irradiation of the rat lung.2.Weight:Delayed growth was observed after irradiation(2^nd-16^thweeks,p＜0.05). The weight was presented as control group＞100%group＞25%group.3.Breathing rates(BR):Functionally,both of the 100%and 25%cohorts observed BR increases after irradiation,especially in the period of 6^th-8^thweeks.100%group was earlier and faster.25%group,although pathology was more severe,hardly any obvious increase in BR was observed.In the period of 6^th-8^thweeks 5 rats died of respiratory failure,1 in 25%group and 4 in 100%group.4.Computed tomography image:Radiographic changes were observed in the early period(4^thw)and it comes to the most obvious changes in the mediated period(8^thw). The extensiveness of high density and the decreased lung permeability was presented in 100%group and ground glass opacity,patchy consolidation was presented in 25% group without pleural effusion,pleural thickening and lung shrinking.5.ELISA:Plasma TGF-β1 levels has a transient decrease during 2^nd-4^thweeks after radiation in 100%group following a returning of a higher level from the end of the 4^th week and then reach peak at the 8^thweek.TGF-β1 has a continuous low level in 25% group after radiation.6.HE stain:Morphologicly,100%group was mainly presented as vascular damage which was signed of vascular wall edema,hypertrophy and sclerosis,25%group was mainly presented as erythrocyte cell exudation,inflammation and parenchymal damage.7.Immunohistochemistry:TGF-β1 was observed increased expression at 4^thweek following a retuming of a low level at the 8^thweek.The overall trend was presented as control group＜25%group＜100%group(p＜0.05).Conclusions:1.Setting up the model of graded volume irradiation of rat lung using ELEKTA precise 2.03 treatment plan system is feasible.2.The mechanism underlying symptomatic radiation-induced lung injury varies depending on time and irradiation volume,with vascular damage at large volume/low doses and parenchymal injury at higher doses and low volume.3.Recoverable vascular damage induced respiratory dysfunction at large volume/low doses and parenchymal injury compensated by normal lung tissue out of irradiation field at higher doses/low volumes.4.Radiographic changes were observed in the early period(4w)which has profit of the early detection of radiation-induced lung injury.5.The level of TGF-β1 was elevated locally at the site of radiation injury,but it did not pass through the vascular endothelium into the general circulation,so increases in plasma levels were not commensurate and homeochronous with the increases in lung tissue,and the predictive power of TGF-β1 needs advanced study.6.Delivery of a small dose of radiation to a large volume is not safe.Low dose smeared out overlarge volumes,albeit reversible,may already give rise to fateful respiratory dysfunction.IMRT delivered low-to-intermediate doses to significant portions of healthy lung and may yield unexpected toxicity,so we therefore recommend caution in the utilization of this technique in lung cancer.7.Damage to the lung may be more dependent on the volume irradiation than on the radiation dose.Clinically,the safest approach is to limit both the volume of normal lung that is irradiated and the amount of radiation that it receives.