不同剂量适形放疗对非小细胞肺癌患者放射性肺损伤及炎症的影响比较

Inflammation and radiation-induced lung damage in non-small cell lung cancer patients subjected to different doses of 3D conformal radiotherapy:Comparative study

目的探讨非小细胞肺癌(NSCLC)患者在不同放疗剂量下放射性肺损伤(RILD)的发生率及炎症改变。方法采用前瞻性研究方法,选择笔者所在医院2017年1月—2017年6月放疗科接受三维适形放疗的NSCLC患者90例,随机分为低剂量组(10~30 Gy)、中剂量组(31~60 Gy)和大剂量组(>60 Gy)。比较每组患者放射性肺损伤的发生率和放射相关参数;采用酶联免疫吸附试验检测放疗前、放疗后1 W和4 W的血清干扰素诱导蛋白-10(IP-10)、金属蛋白酶组织抑制蛋白(TIMP-1)、白介素6(IL-6)和转化生长因子β(TGF-β)的表达。结果低、中和高剂量组患者RILD发生率分别是17.4%(4/23)、56.7%(14/30)和76.0%(19/25)。三组患者的MLD分别是(21.8±5.2)、(40.0±5.6)和(63.0±2.1)Gy。随着放疗剂量的增加,患者的全肺V5≥45%、全肺V10≥45%、全肺V20≥29%、全肺V30≥19%、患肺V5≥71%、患肺V10≥56%、患肺V20≥46%和患肺V30≥42%比例依次升高。与低剂量组比较,中剂量组和高剂量组的全肺MLD≥17.5 Gy及患肺MLD≥23.5 Gy比例明显增加,但中剂量组和高剂量组比较差异无统计学意义。放疗剂量增加导致血清炎症因子IP-10、IL-6和TGF-β升高而TIMP-1降低。结论放疗剂量的增加可提高NSCLC患者RILD的发生率,可能与V5、V10、V20和V30比例增加有关,同时血清炎症因子IP-10、IL-6和TGF-β升高而TIMP-1降低。

Objective To explore the inflammation and incidence of radiation-induced lung damage（RILD） in non-small cell lung cancer（NSCLC） patients with different dose of three-demensional conformal radiotherapy. Methods A total of ninety NSCLC patients received three-demensional conformal radiotherapy in the department of Radiotherapy at our hospital from Januanry 2017 to June 2017 were enrolled via a prospective study. According to the dose of radiotherapy,these patients were randomly divided into low-dose group（10-30 Gy）,moderate-dose group（31-60 Gy） and high-dose group（〉60 Gy）. The general materials,incidence of RILD and radiation related parameters were recored and compared. The level of interferon inducible protein-10（IP-10）,tissue inhibitor of metalloproteinase（TIMP-1）,interleukin-6（IL-6） and transforming growth factor-β（TGF-β） in serum at baseline,1 W and 4 W after radiation were assessed by enzyme linked immunosorbent assay. Results There were seven patients quited the study in low-dose group because of inadequate dosage and unsatisfactory effect of radiation,five cases excluded because of not acceptable high-doase radiation. The incidence of RILD in low-dose group,moderate-dose group and high-dose group were 17.4%（4/23）,56.7%（14/30） and 76.0%（19/25）respectively,and the MLD in these groups were（21.8±5.2）,（40.0±5.6） and（63.0±2.1）Gy respectively. The V5≥45%,V10≥45%,V20≥29% and V30≥19% of total lung and V5≥71%,V10≥56%,V20≥46% and V30≥42%of ipsilateral lung were successively increased in low-dose group,moderate-dose group and high-dose group.Compared with low-dose group,the MLD of total lung ≥17.5 Gy and MLD of ipsilateral lung ≥23.5 Gy in moderate-dose and high-dose group were increased,but these changes in moderate-dose and high-dose group were similar. The increased dose of radiation would trigger the up-regulation of IP-10,IL-6 and TGF-β level but the reduction of TIMP-1 level. Conclusion The increased dose of radiation would be favor to the high incidence of RILD,which is associated with the increased V5,V10,V20 and V30 in total and ipsilateral lung,up-regulation of IP-10,IL-6 and TGF-β level but the reduction of TIMP-1 level.