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目的研究血清转化生长因子-β1(TGF-β1)、白介素-6(IL-6)、血栓调解蛋白(TM)水平以及剂量体积因素与急性放射性肺炎(ARP)发生的相关性。方法对27例肺癌、16例食管癌、1例胸腺瘤患者按常规给予三维适形放射治疗(3DCRT)和化疗;其中19例采用同步放化疗,25例采用序贯化放疗。放疗前和放疗30Gy时用酶联免疫吸附法(ELISA)检测患者血清IL-6、TGF-β1、TM水平。依照美国国立肿瘤研究所CTCAEv3.0标准,为ARP评级,评价≥2级定为ARP。并分析TGF-β1、IL-6、TM水平、肺功能指标以及剂量体积因素与ARP发生率的关系。剂量体积因素包括平均肺剂量(MLD)和Vx(指照射总剂量高于xGy的肺体积占全肺总体积的百分数)。结果44例患者中有15例发生了ARP,9例2级,6例3级。ARP发生与未发生组照射30Gy时TGF-β1水平(pg/mL)平均值分别为:(866±270 vs 396±338,P=0.000)。ARP发生率在年龄<60和≥60岁组分别是:46.15%(12/26)和16.67%(3/18)(P=0.042);有、无吸烟史组是:45.45%(15/33)和0%(0/11)(P=0.017);在照射30Gy后TM降低与增高组是:45.16%(14/31)和7.69%(1/13)(P=0.041);在MLD(Gy)<10和≥10组是:16.67%(5/25)和55%(10/19)(P=0.024);在V30<13%和≥13%组是22.22%(6/27)和52.94%(9/17)(P=0.036)。V20<25%与≥25%之间,ARP发生率差异无统计学意义。多因素分析提示MLD(P=0.012)和放疗30Gy时TGF-β1水平(P=0.001)与ARP的发生有相关性。结论TGF-β1以及MLD是有意义的预测ARP的早期指标,第1秒用力呼气量(FEV1)实测/预测值%的大小对ARP的严重程度有一定的预测价值。
Objective To investigate the correlation between serum levels of transforming growth factor-β1 (TGF-β1), interleukin-6 (IL-6), thrombomodulin (TM) and dose-volume factors in acute radiation pneumonitis (ARP). Methods Three-dimensional conformal radiotherapy (3DCRT) and chemotherapy were given routinely in 27 patients with lung cancer, 16 patients with esophageal cancer and 1 patient with thymoma. Of them, 19 patients received concurrent chemoradiotherapy and 25 patients received sequential radiotherapy. Serum levels of IL-6, TGF-β1 and TM were detected by enzyme-linked immunosorbent assay (ELISA) before radiotherapy and 30 Gy of radiotherapy. According to the American National Cancer Institute CTCAEv3.0 standards for the ARP rating, rating ≥ 2 set as ARP. The relationship between the levels of TGF-β1, IL-6, TM, pulmonary function, dose-volume and the incidence of ARP was analyzed. Dose volume factors include the mean lung dose (MLD) and Vx (referring to the percentage of lung volume above the total volume of the total lung that the total radiation dose is above xGy). Results Of the 44 patients, 15 had ARP, 9 had 2, and 6 had 3. The mean levels of TGF-β1 (pg / mL) at 30 Gy of ARP-treated and untreated groups were (866 ± 270 vs 396 ± 338, P = 0.000), respectively. The incidence of ARP was 46.15% (12/26) and 16.67% (3/18) respectively in the age group <60 and ≥60 years (P = 0.042); there was 45.45% (15/33 ) And 0% (0/11) respectively (P = 0.017). After 30 Gy irradiation, TM decreased and increased group was 45.16% (14/31) and 7.69% (1/13) Gy was <10 and ≥10 was 16.67% (5/25) and 55% (10/19) (P = 0.024), 22.22% (6/27) at V30 <13% 52.94% (9/17) (P = 0.036). V20 <25% and ≥25%, the incidence of ARP difference was not statistically significant. Multivariate analysis indicated that the levels of TGF-β1 (P = 0.001) in MLD (P = 0.012) and 30 Gy in radiotherapy were correlated with the occurrence of ARP. Conclusion TGF-β1 and MLD are meaningful early predictors of ARP. The measured / predicted percent of forced expiratory volume in one second (FEV1) has some predictive value for the severity of ARP.