Background: The main manifestations of radiation pneumonitis are injury of alveolar epithelial and endothelial cells, abnormal expression of cytokines, abnormal proliferation of fibroblasts and synthesis of fibrous matrix. The occurrence of radiation pneumonitis is associated with multiplecytokine level abnormality. These cytokines can also be used as bio-markers to predict the occurrence of radiation pneumonitis. This study was to evaluate the correlation between the change of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1), intercellular adhesion molecules 1 (ICAM-1) and interleukin-17A (IL-17A) before and after radiotherapy and radiation pneumonitis for local advanced non-small cell lung cancer (NSCLC) patients with concurrent chemoradiotherapy.
Methods: NSCLC patients (68 cases) were treated with concurrent radiotherapy and chemotherapy, every patient's normal tissue were controlled with a same radation dose. 68 local advanced NSCLC patients with concurrent chemoradiotherapy were detected the levels of Ape1/Ref-1, ICAM-1 and IL-17A in serum by ELISA before radiotherapy and in the 14th week after radiotherapy. Acute and advanced radiation pulmonary injury was graded according to Radiation Therapy Oncology Group/European Organization For Research and Treatment (RTOG/EORTC) diagnostic and grading criteria. Grade 2 or more radiation pneumonitis was taken as the main end point.
Results: Eighteen cases out of 68 developed radiation pneumonitis, 50 of 68 cases have no radiation pneumonia development. There was no significant change of Ape1/Ref-1 levels before and after radiotherapy in radiation pneumonitis group (P>0.05). There was no significant change of Ape1/Ref-1 concentration in serum after radiotherapy between radiation pneumonitis group and non-radiation pneumonitis group (P>0.05). Compared with before radiotherapy, upregulation degree of ICAM-1 levels in radiation pneumonitis group was significantly higher than that in non- radiation pneumonitis group (P<0.05). There was no significant change of IL-17A concentration before and after radiotherapy in radiation pneumonitis group, but after radiotherapy IL-17A concentration in serum were remarkably higher than that in non-radiation pneumonitis group (P<0.05). Correlation analysis found that the change of ICAM-1 before and after radiotherapy has no obvious correlation with the incidence of radiation pneumonitis, and IL-17A change has obvious correlation with the incidence of radiation pneumonitis.
Conclusions: On the basis of strictly controlling radiation dose on normal tissue, IL-17A in serum could be the predictive factors of radiation pneumonitis for local advanced NSCLC patients with concurrent chemoradiotherapy.
【中文题目：局部晚期非小细胞肺癌患者血清中Ape1/Ref-1、ICAM-1及IL-17A水平与放射性肺炎发生的相关性研究】 【中文摘要：背景与目的 放射性肺炎主要表现为肺泡上皮及内皮细胞损伤、细胞炎性因子异常表达、纤维母细胞异常增殖及纤维基质合成，其发生与多种细胞因子水平异常相关，这些细胞因子亦可作为预测放射性肺炎发生的生物学指标。本研究评价局部晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）同步放化疗患者放疗前和放疗后血清中脱嘌呤脱嘧啶核酸内切酶1（apurinic/apyrimidinic endonuclease 1/redox factor-1, Ape1/Ref-1）、细胞间粘附分子-1（intercellular adhesion molecules 1, ICAM-1）和白细胞介素-17A（interleukin-17A, IL-17A）水平的变化与放射性肺炎发生的相关性。方法 68例晚期NSCLC患者均行同步放化疗，每位患者正常组织受照剂量相同。在治疗前及治疗后第14周，采用ELISA法检测血清中Ape1/Ref-1、ICAM-1及IL-17A水平。应用美国肿瘤放射治疗协作组和欧洲肿瘤治疗研究协作组（Radiation Therapy Oncology Group/European Organization For Research and Treatment, RTOG/EORTC）诊断分级标准作为急性和晚期肺放射损伤分级标准评价，评价终点≥2级判定为放射性肺炎。结果 18例发生放射性肺炎，50例无放射性肺炎发生。放射性肺炎组放疗前后Ape1/Ref-1水平无显著性变化（P>0.05）；放射性肺炎组与非放射性肺炎组Ape1/Ref-1水平无显著性变化（P>0.05）。与放疗前相比，放疗后放射性肺炎组ICAM-1水平上调幅度比非放射性肺炎组ICAM-1水平上调幅度大（P<0.05）。放射性肺炎组患者的IL-17A水平在放疗后显著上升（P<0.05），而非放射性肺炎组IL-17A水平放疗前后水平无显著性变化（P>0.05）；放疗后，放射性肺炎组IL-17A水平比非放射性肺炎显著性升高（P<0.05）。相关性分析发现放疗前后ICAM-1的变化与放射性肺炎的发生无明显相关性，而IL-17A的变化与放射性肺炎的发生具有明显相关性。结论 晚期NSCLC患者同步放化疗时，在严格限制正常组织受照剂量的同时，血清IL-17A可能是放射性肺炎的预测因子。 】 【中文关键词：放射性肺炎；Ape1/Ref-1; ICAM-1; IL-17A】.
Keywords: Ape1/Ref-1; ICAM-1; IL-17A; Radiation pneumonitis.