Radiation pneumonitis as a function of mean lung dose: An analysis of pooled data of 540 patients
Radiation pneumonitis as a function of mean lung dose: An analysis of pooled data of 540 patients
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DOI：
10.1016/s0360-3016(98)00196-5
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发表时间：
1998-08-01
影响因子：
7
通讯作者：
TEN Haken, RK
中科院分区：
文献类型：
--
作者：
Kwa, SLS;Lebesque, JV;TEN Haken, RK
目的：为了确定放射性肺炎的发病率和三维剂量分布在lung.Methods和材料之间的关系：在五个机构，放射性肺炎的发病率进行了评估，在540例患者。将患者分为两组：肺组，包括399例肺癌和1例食管癌患者和1例淋巴结。乳腺组：恶性淋巴瘤78例，乳腺癌59例，其他肿瘤3例。每部分剂量在1.0和2.7戈伊之间变化，处方总剂量在20和92戈伊之间。三维剂量计算进行了组织密度不均匀性校正。通过使用α/β比为2.5和3.0戈伊的线性二次模型，将物理剂量分布转换为以2戈伊为单位的生物等效剂量分布，即归一化总剂量（NTD）分布。将两个肺视为一个器官，计算剂量体积直方图（DVH），并从这些DVH中获得平均（生物）肺剂量; NTDmean。当放射性肺炎等级为2级（需要药物治疗的类固醇）或更高时，将放射性肺炎评分为并发症。常规正常组织并发症概率（NTCP）模型的莱曼（n = 1）的统计分析，vas应用沿着与机构依赖的偏移参数来解释系统的差异，在不同institutions.Results评分患者的平均肺剂量，NTDmean，范围从0到34戈伊和73的540例患者发生肺炎，2级或更高。在所有中心，随着NTD平均值的增加，观察到肺炎发生率增加。数据拟合到莱曼模型，NTD 50 = 31.8戈伊，m = 0.43，假设所有患者可以使用相同的参数值。然而，在平均NTD为4 - 16戈伊的低剂量范围内，肺部组中观察到的肺炎发生率（10%）显著（p = 0.02）高于淋巴。乳腺组（1.4%）。此外，不同机构的肺部组之间也存在显著（p = 0.04）差异：对于中心2、3和4，肺炎发生率约为13%，而中心5仅为3%。通过添加肺部组的中心相关偏移值来明确考虑这些差异，显着改善了数据拟合（p < 10（-5）），NTD 50 = 30.5 +/- 1.4戈伊，m = 0.30 +/- 0.02（+/- 1 SE），肺组的偏移为0- 11%，取决于中心。结论：平均肺部剂量（NTDmean）相对容易计算，并且是放射性肺炎风险的有用预测因子。基于大量临床数据集，观察到的NTD平均值和放射性肺炎发生率之间的剂量效应关系可能在肺癌剂量递增研究中具有价值。关于混杂因素和剂量分布的影响与本研究不同，所获得的剂量效应关系的有效性将在未来的研究中进行检验。(C)1998年爱思唯尔科学公司
Purpose: To determine the relation between the incidence of radiation pneumonitis and the three-dimensional dose distribution in the lung.Methods and Materials: In five institutions, the incidence of radiation pneumonitis was evaluated in 540 patients. The patients were divided into two groups: a Lung group, consisting of 399 patients,vith lung cancer and I esophagus cancer patient and a Lymph./Breast group with 78 patients treated for malignant lymphoma, 59 for breast cancer, and 3 for other tumor types. The dose per fraction varied between 1.0 and 2.7 Gy and the prescribed total dose between 20 and 92 Gy. Three-dimensional dose calculations were performed with tissue density inhomogeneity correction. The physical dose distribution was converted into the biologically equivalent dose distribution given in fractions of 2 Gy, the normalized total dose (NTD) distribution, by using the linear quadratic model with an alpha/beta ratio of 2.5 and 3.0 Gy. Dose-volume histograms (DVHs) were calculated considering both lungs as one organ and from these DVHs the mean (biological) lung dose; NTDmean, was obtained. Radiation pneumonitis was scored as a complication when the pneumonitis grade was grade 2 (steroids needed for medical treatment) or higher. For statistical analysis the conventional normal tissue complication probability (NTCP) model of Lyman (with n = 1),vas applied along with an institutional-dependent offset parameter to account for systematic differences in scoring patients at different institutions.Results: The mean lung dose, NTDmean, ranged from 0 to 34 Gy and 73 of the 540 patients experienced pneumonitis, grade 2 or higher. In all centers, an increasing pneumonitis rate aas observed with increasing NTDmean. The data were fitted to the Lyman model with NTD50 = 31.8 Gy and m = 0.43, assuming that for all patients the same parameter values could be used. However, in the low dose range at an NTDmean between 4 and 16 Gy, the observed pneumonitis incidence in the Lung group (10%) was significantly (p = 0.02) higher than in the Lymph./Breast group (1.4%). Moreover, between the Lung groups of different institutions, also significant (p = 0.04) differences were present: for centers 2, 3, and 4, the pneumonitis incidence was about 13%, whereas for center 5 only 3%. Explicitly accounting for these differences by adding center-dependent offset values for the Lung group, improved the data fit significantly (p < 10(-5)) with NTD50 = 30.5 +/- 1.4 Gy and m = 0.30 +/- 0.02 (+/- 1 SE) for all patients, and an offset of 0-11 % for the Lung group, depending on the center.Conclusions: The mean lung dose, NTDmean, is relatively easy to calculate, and is a useful predictor of the risk of radiation pneumonitis. The observed dose- effect relation between the NTDmean and the incidence of radiation pneumonitis, based on a large clinical data set, might be of value in dose-escalating studies for lung cancer. The validity of the obtained dose-effect relation will have to be tested in future studies, regarding the influence of confounding factors and dose distributions different from the ones in this study. (C) 1998 Elsevier Science Inc.