细胞因子联合DVH参数预测放射性肺炎的临床研究  

Combination of serum cytokine with lung DVH for prediction of radiation pneumonitis

作　　者：姬巍[1] 王绿化[1] 赵路军[1] 蒋恒[1] 王小震[1] 张莉[1] 欧广飞[1] 杨伟志[1] 冯勤富[1] 周宗玫[1] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤医院肿瘤研究所放疗科,北京100021

出　　处：《中华放射肿瘤学杂志》2007年第6期473-477,共5页Chinese Journal of Radiation Oncology

基　　金：首都医学发展科研基金(2002-1016);首都医学发展科研基金(2002-3009)

摘　　要：目的评价肺癌胸部放疗前及照射40～50 Gy时血浆中TGF-β、IL-6及ACE含量变化、肺受照射剂量体积因素与放射性肺炎发生的关系。方法67例肺癌患者按治疗常规给予放疗或(和)化疗;男60例,女7例,中位年龄58岁(26～81岁)。放疗前、照射40～50 Gy时采血冻存,采用酶联免疫吸附法检测血液中TGF-β、IL-6及ACE含量。放射性肺炎根据CTC AE3.0标准评价,评价终点为≥2级放射性肺炎。结果存活患者中位随访时间22.6个月。2级以上的放射性肺炎发生率25.4%。自放疗开始至发生放射性肺炎的中位时间73天。放疗前、放疗40～50 Gy时血浆中TGF-β、IL-6含量以及其在放疗期间的变化与放射性肺炎无明显相关性。发生放射性肺炎组患者的疗前、疗中血浆ACE含量明显低于未发生肺炎者(P=0.033、0.004)。发生放射性肺炎组的全肺接受10 Gy照射体积(V10)为44%,高于未发生肺炎组的39%(P=0.029)。健肺MLD、V10、V15、V20分别高于未发生肺炎组(1931 cGy:990 cGy、52%:35%、48%:23%、37%:10%,P<0.05)。将生物因素ACE含量和DVH参数联合分析发现疗中血浆ACE含量和全肺V10组合是放射性肺炎最强的预测因素。疗中ACE含量ACE>506 ng/ml且全肺V10≤40%时,放射性肺炎的发生风险最低,13例中无一发生;但如果ACE≤506 ng/ml且全肺V10>40%时,放射性肺炎风险达50%(6/12);其他情况疗中ACE>506 ng/ml且V10>40%或疗中ACE≤506 ng/ml且V10≤40%时,放射性肺炎发生率26.7%(P=0.008)。结论(1)放疗前、放疗中血浆ACE含量低是放射性肺炎发生的高危因素。(2)血浆ACE联合DVH参数V10有望作为预测放射性肺炎发生的指标。Objective To study the relationship between radiation pneumonitis （RP） and plasma transform growth factor beta （TGF-β）, interleukin 6 （ IL-6）, angiotensin-converting enzyme （ACE） and physical parameters（ V10, V15, V20and MLD）. Methods Among all patients with lung cancer treated with radiotherapy （RT） between February 2004 and August 2005, 67 patients were identified who met the follow- ing inclusion criteria： （ 1 ） newly diagnosed lung cancer treated with RT ＋ chemotherapy with curative intent; （2） KPS 〉 70 ; （ 3 ） expected survival 〉 6 months; （4） follow-up time more than 6 months ; （ 5 ） no pneumonectomy. Blood samples were collected and measured with enzyme-linked immunosorbent assay （ELISA）. TGF-13, IL-6 and ACE measurements were applied before RT （Pre-RT） and when RT dose reached 40-50 Gy （during-RT）. Fifty-eight patients were treated with computed tomography based 3-dimensional planning and had dose-volume histogram data available. The endpoint of the study was the development of ≥ grade 2 RP （ NCI [ National Cancer Institute] common toxicity criteria 3.0）. Results The median follow-up time of the living patients was 22.6 months. The incidence of ≥ grade 2 RP for all 67 patients was 25.4%. For both RP and non-RP groups, there was no difference between Pre- and during- RT level of TGF-13 or IL-6. Both pre-RT and during-RT ACE level was lower in RP group than in non-RP group （ P = 0. 033 and P = 0. 004）. Fifty-eight patients received 3-dimensional conformal RT （3 DCRT）. In the RP group, patients had higher all lung V10, contralateral MLD, contra-lateral V10, contra-lateral V15 and contra lateral V20（44% vs 39%, 1931 cGy vs 990 cGy, 52% vs 35%, 48% vs 27% and 37% vs 10% ,P 〈 0.05）. The subgroup of 54 patients, treated with 3DCRT and with ACE data available, were divided into Group Ⅰ （ n = 13, with ACE 〉 506 ng/ml and V10 ≤40% ）, Group Ⅱ （ n = 30, with ACE 〉 506 ng/ml and V10 〉40% ; ACE ≤ 506 ng/ml and V10

关 键 词：肺肿瘤/放疗 放射性肺炎 细胞因子 剂量体积直方图 预测价值 

分 类 号：R818[医药卫生—放射医学] R734.2[医药卫生—临床医学]