非小细胞肺癌放疗前后血清TGF-β1水平测定的临床意义

Clinical study of serum TGF-β1 in non-small cell lung cancer before and after radiotherapy

目的探讨血清转化生长因子β1(transforming growth factor-β1,TGF-β1)在非小细胞肺癌(non-small cell lung cancer,NSCLC)放疗后疗效评价的意义以及与症状性放射性肺炎(radioactive pneumonia,RP)发生的相关性。方法收集经病理学证实为NSCLC并接受3D-CRT的患者264例。放疗前及放疗结束时空腹采肘静脉血检测血清TGF-β1水平。放疗结束后1个月按照WHO统一评价标准评价近期疗效。放疗开始至结束后3个月内每周按美国肿瘤放射治疗协作组织(Radiation Therapy Oncology Group,RTOG)急性放射损伤分级标准评价RP。结果患者放疗前血清TGF-β1水平为442.20~12 840.0ng/L,中位数和四分位数间距分别为677.5ng/L和2 186.7ng/L,放疗后血清TGF-β1水平为280.0~11753.0ng/L,中位数和四分位数间距位为605.0ng/L和1 172.6ng/L,放疗前后差异有统计学意义(Z=-4.617,P=0.000)。男性较女性RP发生率高,吸烟者较不吸烟者RP发生率高,PTV>450cm^3者较≤450cm^3者RP发生率高,放疗时间≤45d者较>45d者RP发生率高,放疗剂量<60Gy者较≥60Gy者RP发生率高,放疗后血清TGF-β1水平升高者较下降者RP发生率高,差异均有统计学意义(P<0.05)。同期化疗者较非同期化疗者总有效率高,放疗剂量≥60Gy者较<60Gy者总有效率高,放疗前血清TGF-β1≤677.5ng/L较>677.5ng/L者总有效率高,差异均有统计学意义(P<0.05)。Logistic回归分析显示,吸烟、PTV>450cm^3、放疗后血清TGF-β1水平升高是RP发生的危险因素;同期化疗、放疗剂量≥60Gy、中央型肺癌、放疗前血清TGF-β1水平≤677.5ng/L者近期疗效更好(P<0.05)。结论放疗后血清TGF-β1水平升高者RP发生风险增大,放疗前TGF-β1低水平者相对高水平者预后好,血清TGF-β1水平测定可作为NSCLC预后的预测因子。

Objective To assess the value of serum transforming growth factor-β1（TGF-β1） in predicting the radioactive pneumonia（RP） and the short-term effect,and to provide a reference for radiotherapy（RT） of non-small cell lung cancer（NSCLC）.Methods An analysis was performed on the medical records of 264 cases with NSCLC.The pathology was confirmed via histology or cytology,using three dimensional conformal radiation therapy.The serum TGF-β1 level was detected before and after RT for all the patients.The TGF-β1 level in serum was detected with enzyme-linked immunosorbent assay.Short-term effect was evaluated according to the WHO unified evaluation criterion after a month of radiotherapy and RP was diagnosed by Radiation Therapy Oncology Group（RTOG） grading standard of acute radiation injury.SPSS 17.0 statistical software was used for statistics.Results The level of serum TGF-β1 pre-radiotherapy was 442.20-12 840.00 ng/L,the median and the quartile values were 677.5 ng/L and 2 186.7 ng/L.The levels of TGF-β1 post-radiotherapy were 280.0-11 753.0 ng/L,median and quartile values were 605.0 ng/L and 1 172.6 ng/L,respectively（Z=-4.617,P=0.000）.There were higher incidence of RP in male than female patients,smokers than non-smokers,PTV〉450 cm3 than≤450 cm3,radiotherapy period≤45 d than〉45 d（P〈0.05）,in patients with radiotherapy dose〈60 Gy,and with increased levels of TGF-β1 after radiotherapy（P〈0.05）.Patients with concurrent chemo-radiotherapy,radiotherapy dose higher than 60 Gy,serum TGF-β1〈677.5 ng/L pre-radiotherapy preferred to have better response rate（P〈0.05）.Multivariate analysis showed that smoking,PTV〉450 cm3,increased serum levels of TGF-β1 after chemotherapy were RP risk factors（P〈0.05）.Patients with concurrent chemotherapy,radiotherapy dose≥60 Gy,central lung cancer,serum TGF-β1 levels≤677.5 ng/L pre-radiotherapy had better efficacy（P〈0.05）.Conclusion Lower level of TGF-β1 before radiotherapy predicted a better prognosis.Patients with increased serum TGF-β1 levels after radiotherapy had more RP risks.Serum TGF-β1 levels could be considered as a predictor of NSCLC prognosis.