Prospective Study Of The Relationship Between Low Dose Irradiated Volume And Radiation-induced Lung Injury

Objective:All patients are divided into three groups by V5 from low to high in the non-randomized clinical prospective study. The three groups were compared with the incidence of radiation-induced lung injury, in order to know about V5 for the significance of radiation-induced lung injury. We can determine a reasonable V5 for Chinese reference, on purpose that we can create more, comprehensive treatment plan, and do more safe and reliable radiation therapy.Methods:Forty-six NSCLC patients with stageⅢ-Ⅳfrom the radiotherapy department in Tianjin Cancer Hospital, was recorded from 2008.11.4 to 2009.8.23. all the patients are devided into three group, groupV5<45%, group45%55%. Acquisition NSCLC radiation lung injury risk factors collected form the main content can be divided into three parts:1. General clinical data. Including:1) age, sex, KPS score, smoking or not, history of related diseases affecting lung function, the tumor location, pathology types, clinical staging.2) radiotherapy methods,3D-CRT(Three Dimensional Comformal Radiotherapy), IMRT(Intensity-modulated radiation therapy), SRT(Stereotactic Radiotherapy) 3) history of chemotherapy (?)estment, taxinol using,4) pulmonary funn(?)ti(?)2. Blood sample were collected at the time, before radiation, in radiation at 30-40Gy, and one month after radiation. The cytokines such as IL-1,IL-6,ACE, were detected by ELISA, during in the radiation therapy.3. We get the date, the V5,V10,V15,V20,MLD,PTV, and the total dose and fraction, by the analysis of the radiotherapy program and DVH graph,4. According to the CTC AE 3.0, acute lung pneumonia criteria,Grade 2 or worse lung injury was used as end point. All patients were followed up in the case of acute radiation pneumonitis, and detailed records, grading, and be treated accordingly.Results:1. The occurrence of radiation-induced lung injury The follow-up time was end on March 12,2010. The middle time was 7 months, from 6 month to 13.5 month. There are no case lost.The three groups with different grades of acute radiation pneumonitis were significantly different (χ2=37.510, P=0.000). With the rise of V5,> 2 radiation pneumonitis radiation pneumonitis incidence rates are significantly increased, from 38.9%,64.2% to 57.1%.The level 0-1 radiation pneumonitis from 61.1%,35.7% to 42.9%; The level 2 radiation pneumonitis incidence rates are from 33.3%,21.4% to 21.4%; The level 3 radiation pneumonitis from 5.6%,41.9% to 35.7%. The occurrence of severe radiation pneumonitis (≥3 level) rise with V5 ascension.There is heterogeneity in the clinical data in gender (χ2=10.535, P=0.005), KPS score (χ2=6.895, P=0.032), lung function (χ2=10.471, P=0.005), the tumor location (χ2=6.330, P=0.042), V30 (%) (F=9.693,P=0.000), MLD(Gy) (F= 5.520, P=0.007), the number of radiation field (F=5.539, P=0.007) in three groups. There is significant relationship in gender (χ2=8.863, P=0.003), V30 (χ2=10.501, P =0.001), lung function (χ2=19.942, P=0.000) with radiation pneumonitis except V 20 (χ2=1.565,P=0.211) by hierarchical analysis. The two factors, gender (P=0.229) and V30 (P=0.813), are confounding factors, and pulmonary function (P=0.034) is the risk factor (Exp (B)=3.733) by the further Binary Logistic regression analysis. The decreased lung function can increase the occurrence of acute radiation pneumonitis. The patients with normal lung function are divided into three groups according V5; the occurrence of acute radiation pneumonitis in the three groups were significantly different (χ2=40.299, P=0.000), mainly due to the different V5. The level 1 radiation pneumonitis from 72.7%,50% to 50%; The level 2 radiation pneumonitis incidence rates are from 27.3%,16.7% to 20%; The level 3 radiation pneumonitis from 50%,33.3% to 30%.3. The changes of biological factors in the process of radiotherapySeparate analysis of content of IL-1, IL-6 and ACE in 24 cases with radiation pneumonitis in the time of before radiation, in radiation at 30-40Gy, and one month after radiation. The IL-1 content of the dynamic changes in the 3 groups do not change, but gradually increase. The content of IL-6 increasing with V5 shows a rising trend in the radiation process, and are significantly higher, in the patients with pneumonia in the V5> 55% group (P=0.003). The content of ACE is no significant difference in the process, there is no increasing with the increasing of V5.Conclusions:1. The incidence of acute radiation pneumonitis is different with different V5. The trend of the incidence of severe acute radiation pneumonitis (≥3 level) gradually increases with the increasing of V5.The lower dose distributing to the larger lung mass is unsafe. It is prone to cause acute radiation pneumonitis, and may endange the lives of patients. Therefore, we recommend that should be careful in the use of sIMRT during thoracic radiotherapy.The the volume of the lung tissue in low-dose irradiation may be more important in acute radiation pneumonia.2. The safest way controlling radiation-induced lung injury is to reduce the dose to normal lung tissue, while reducing the volume irradiated.3. IL-6 can predict the incidence of acute radiation pneumonitis as an effective predictor, especially in low-dose irradiated volume larger. Its predictive value is more obvious.4. Poor lung function may increase the occurrence of acute radiation pneumonitis, and we should control the volume of low-dose irradiation in patients with Poor lung function.