A prospective study on radiation pneumonitis following conformal radiation therapy in non-small-cell lung cancer: clinical and dosimetric factors analysis.

BACKGROUND AND PURPOSE: Clinical and dosimetric prognostic factors for radiation pneumonitis (RP) have been reported after three-dimensional conformal radiotherapy (3D-CRT) in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Ninety-six patients who received 3D-CRT for stage IA to IIIB NSCLC were evaluated prospectively. Surgery was performed before radiation in 51% of the patients (n = 49). RP was diagnosed six-eight weeks after 3D-CRT using the Lent-Soma classification. Factors evaluated included treatment factors such as total mean lung dose (MLD), and dose-volume histogram (DVH) thresholds for several radiation dose steps. These thresholds were originally determined from the median of the irradiated lung volume at each step. RESULTS: Six patients could not be evaluated for RP six weeks after 3D-CRT. Of the 90 remaining patients, 40 (44%) had RP (i.e. grade > or =1) at 6 weeks, including 7 patients (7.8%) with severe RP (grade > or =2). Regarding the whole toxicity (grade > or =1), age (> or =60 years), MLD, V20 and V30 were significantly related to RP. DVH thresholds determined for radiation doses from 20 to 40 Gy were also predictive of RP. Considering only severe RP (grade > or =2), only MLD, V20 and V30 remained associated with increased acute pulmonary toxicity. CONCLUSIONS: In this study, dosimetric factors (MLD, V20, V30) and age (> or =60 years) were predictive of RP regarding the whole pulmonary toxicity (grade > or =1). In addition, thresholds from 20 to 40 Gy, based on a stratification according to the median of the percentage of irradiated lung volume, were also predictive factors. They may, therefore, help discriminate patients at high and low risk for RP. However, only MLD, V20 and V30 remained associated with severe RP (grade > or =2), probably due to the small number of severe events in our series.     

Clinical dose-volume histogram analysis in predicting radiation pneumonitis in Hodgkin's lymphoma

PURPOSE: To quantify the incidence of radiation pneumonitis (RP) in a modern Hodgkin's lymphoma (HL) cohort, and to identify any clinically relevant parameters that may influence the risk of RP. METHODS AND MATERIALS: Between January 2003 and February 2005, 64 consecutive HL patients aged 18 years or older receiving radical mediastinal radiation therapy (RT) were retrospectively reviewed. Symptomatic cases of radiation pneumonitis were identified. Dose-volume histogram parameters, including V(13), V(20), V(30), and mean lung dose (MLD), were quantified. RESULTS: At a median follow-up of 2.1 years, the actuarial survival for all patients was 91% at 3 years. There were 2 (2/64) cases of Radiation Therapy Oncology Group (RTOG) Grade 2 RP (incidence 3.1%). Both index cases with corresponding V(20) values of 47.0% and 40.7% were located in the upper quartile (2/16 cases), defined by a V(20) value of > or =36%, an incidence of 12.5% (p = 0.03). Similarly for total MLD, both index cases with values of 17.6 Gy and 16.4 Gy, respectively, were located in the upper quartile defined by MLD > or =14.2 Gy, an incidence of 11.8% (2/17 cases, p = 0.02). CONCLUSIONS: Despite relatively high V(20) values in this study of HL patients, the incidence of RP was only 3%, lower compared with the lung cancer literature. We suggest the following clinically relevant parameters be considered in treatment plan assessment: a V(20) greater than 36% and an MLD greater than 14 Gy, over and above which the risk of RTOG Grade 2 or greater RP would be considered clinically significant.     

Radiation-induced pulmonary toxicity: a dose-volume histogram analysis in 201 patients with lung cancer

PURPOSE: To relate lung dose-volume histogram-based factors to symptomatic radiation pneumonitis (RP) in patients with lung cancer undergoing 3-dimensional (3D) radiotherapy planning. METHODS AND MATERIALS: Between 1991 and 1999, 318 patients with lung cancer received external beam radiotherapy (RT) with 3D planning tools at Duke University Medical Center. One hundred seventeen patients were not evaluated for RP because of <6 months of follow-up, development of progressive intrathoracic disease making scoring of pulmonary symptoms difficult, or unretrievable 3D dosimetry data. Thus, 201 patients were analyzed for RP. Univariate and multivariate analyses were performed to test the association between RP and dosimetric factors (i.e., mean lung dose, volume of lung receiving >or=30 Gy, and normal tissue complication probability derived from the Lyman and Kutcher models) and clinical factors, including tobacco use, age, sex, chemotherapy exposure, tumor site, pre-RT forced expiratory volume in 1 s, weight loss, and performance status. RESULTS: Thirty-nine patients (19%) developed RP. In the univariate analysis, all dosimetric factors (i.e., mean lung dose, volume of lung receiving >or=30 Gy, and normal tissue complication probability) were associated with RP (p range 0.006-0.003). Of the clinical factors, ongoing tobacco use at the time of referral for RT was associated with fewer cases of RP (p = 0.05). These factors were also independently associated with RP according to the multivariate analysis (p = 0.001). Models predictive for RP based on dosimetric factors only, or on a combination with the influence of tobacco use, had a concordance of 64% and 68%, respectively. CONCLUSIONS: Dosimetric factors were the best predictors of symptomatic RP after external beam RT for lung cancer. Multivariate models that also include clinical variables were slightly more predictive.     

肺癌、纵隔肿瘤及食管癌放疗后放射性肺炎发生因素的对比研究

 目的　对肺癌（肺靶区）与纵隔肿瘤及食管癌（纵隔靶区）三维适形放疗中放射性肺炎（RP）发生的影响因素及剂量体积直方图（DVH）参数进行对比研究。方法　回顾性分析接受放射治疗的肺癌、纵隔肿瘤及食管癌患者83例的临床资料,采用χ2 检验对临床因素（性别、年龄、肿瘤部位、分期、化疗）与RP发生的相关性进行分析;分别对两靶区的DVH参数与RP的发生进行相关性分析;用t检验对肺靶区与纵隔靶区DVH参数进行比较。结果　≥2级 RP 发生率为36.5 %（31／81）。各临床因素与≥2级RP发生无关（χ2 值分别为0.377、0.215、0.018、0.717、0.215,均P＞0.05）。两靶区的DVH参数中,V5、V10、V20、V30、全肺平均剂量（MLD）与RP的发生均具有明显相关性。两靶区发生RP的患者V5[（50.9±17.8）%、（69.9±20.4）%]（t＝2.745,P＜0.05）、V10[（38.6±15.2）%、（53.5±18.8）%]（t＝2.434,P＜0.05）差异均有统计学意义,而V20（t＝0.388,P＞0.05）、V30（t＝0.005,P＞0.05）及MLD（t＝0.138,P＞0.05）差异均无统计学意义。两靶区未发生RP患者的DVH参数t检验后得到类似结果。结论　在肺靶区、纵隔靶区的放疗中,RP的发生与DVH参数密切相关,尤其是V20、V30及MLD对RP的发生有重要的影响。     

Ⅲ+Ⅳ期非小细胞肺癌三维适形或调强放疗中复合指标预测放射性肺炎前瞻性临床研究

目的 探讨非小细胞肺癌三维适形或调强放疗正常肺V5和V10联合V20评价放射性肺炎(RP)的意义.方法 采用三维适形或调强后程加速超分割放疗经病理或细胞学证实初治非小细胞肺癌患者90例,其中Ⅲa期6例、Ⅲb期29例、Ⅳ期55例.放疗剂量61～80 Gy,中位数70 Gy.由剂量体积直方图计算全肺V5、V10、V20、V30、平均肺剂量(MLD),对侧肺V5、V10及同侧肺V30.用CTC3.0标准评估肺损伤.结果 90例患者中发生RP为1级29例、2级23例、3级5例、4级1例、5级1例.全肺V5、V10、V20、对侧肺V10、大体肿瘤体积(GTV)、计划靶体积、射野数目与≥1级RP相关(χ2=2.04、2.05、2.01、4.62、6.50、5.61、5.61,P=0.044、0.043、0.047、0.030、0.010、0.020、0.020),全肺V5、V10、V20和V30、MLD与≥2级RP相关(χ2=2.05、2.20、2.96、4.96、5.20,P=0.040、0.030、0.000、0.030、0.020).多因素分析显示GTV与≥1级RP发生相关(χ2=4.06,P=0.044),V20与≥2级RP发生相关(χ2=9.61,P=0.002).全肺V5、V10、V20的中位数分别为66%、48%、31%.V20>31%时≥2级RP概率增加,V20>31%+V10>48%+V5>66%时≥2级RP概率增加,V20>31%+V5>66%时≥2级RP概率增加;V20>31%时V10>48%与<48%比较RP概率相似,V20≤31%时V5>66%与<66%、V10>48%与<48%比较RP概率也相似.性别、年龄、临床分期、病理类型、治疗方式、KPS与≥1、2级RP无关.结论 肺V5、V10联合V20评价放射性肺炎的发生可能提高预测放射性肺炎的能力.     

Analysis of dose-volume histogram parameters for radiation pneumonitis after definitive concurrent chemoradiotherapy for esophageal cancer

Purpose

To evaluate dose-volume histogram (DVH) parameters as predictors of radiation pneumonitis (RP) in esophageal cancer patients treated with definitive concurrent chemoradiotherapy.

Patients and methods

Thirty-seven esophageal cancer patients treated with radiotherapy with concomitant chemotherapy consisting of 5-fluorouracil and cisplatin were reviewed. Radiotherapy was delivered at 2 Gy per fraction to a total of 60 Gy. For most of the patients, two weeks of interruption was scheduled after 30 Gy. The percentage of lung volume receiving more than 5-50 Gy in increments of 5 Gy (V5-V50, respectively), and the mean lung dose (MLD) were analyzed.

Results

Ten (27%) patients developed RP of grade 2; 2 (5%), grade 3; 0 (0%), grade 4; and 1 (3%), grade 5. By univariate analysis, all DVH parameters (i.e., V5-V50 and MLD) were significantly associated with grade ?2 RP (p < 0.01). The incidences of grade ?2 RP were 13%, 33%, and 78% in patients with V20s of ?24%, 25-36%, and ?37%, respectively. The optimal V20 threshold to predict symptomatic RP was 30.5% according to the receiver operating characteristics curve analysis.

Conclusion

DVH parameters were predictors of symptomatic RP and should be considered in the evaluation of treatment planning for esophageal cancer.     

非小细胞肺癌三维适形放疗放射性肺损伤剂量学因素分析

目的 观察非小细胞肺癌三维适形放疗患者急性放射性肺炎的发生情况,并分析其与各剂 量学因素的关系。方法 收集2010年6月—2010年12月间首程行三维适形放疗的非小细胞肺癌患者68 例。从治疗计划系统的剂量体积直方图中获取以下剂量学参数：处方剂量、平均肺剂量(MLD)、正常 肺体积剂量（V5~V50间隔5 Gy）等,分别采用单因素及多因素分析各个剂量学参数与放射性肺炎之 间的关系,并采用受试者工作特征曲线寻找预测界值。结果 V5是放射性肺炎发生的独立预后因素 （χ2=5.15,P=0.023）。患者肺脏的V5超过57%时放射性肺炎的发生率可能会增加。结论 临床医师 在审核治疗计划时,除了要考虑V20、V30、MLD等常用参数外,还应关注V5的大小。     

Dose–volume factors predicting radiation pneumonitis in patients receiving salvage radiotherapy for postlobectomy locoregional recurrent non-small-cell lung cancer

Background The correlation between treatment-related factors and lung toxicity has not been sufficiently evaluated in salvage radiotherapy. Methods Twenty-one patients with recurrent non-small- cell lung cancer (NSCLC) after lobectomy received salvage radiotherapy to a total dose of 46–60 Gy. The effects of radiotherapy parameters on the development of radiation pneumonitis (RP) were examined using dose–volume histograms. Results Grade 1 RP was observed in 4, grade 2 in 2, and grade 3 in 1 patient. Patients who developed RP had a significantly higher value in V dose (V13, V20) parameters and mean lung dose (MLD) than those who did not develop RP. Concerning G2 or higher RP, 3 patients who developed ≥G2 RP had a significantly higher value in V20, V13, and MLD than the remaining patients with P values of 0.01, 0.015, and 0.016, respectively. The mean V20, V13, and MLD in these 3 patients were 27%, 29.3%, and 14.8 Gy, respectively, whereas the mean V20, V13, and MLD in the remaining 18 patients were 15.8%, 18.3%, and 8.8 Gy, respectively. Three of 6 patients with a V20 ≥20% developed ≥G2 RP whereas this did not occur in the remaining patients (P = 0.015). Similarly, 3 of 6 patients with a V13 ≥23% developed ≥G2 RP whereas this did not occur in the remaining patients (P = 0.015). Conclusions These data suggest that a somewhat lower V dose value or MLD, as compared with the setting of definitive radiotherapy, could be a surrogate for RP in patients undergoing salvage radiotherapy for recurrent NSCLC.     

不同肺体积确定方法和剂量分割方法对肺剂量体积参数的影响

目的 分析不同肺体积确定方法和不同剂量分割方法对肺剂量体积参数的影响.方法 随机搜集20例肺癌患者,根据病情以瓦里安Eclipse TPS进行三维适形治疗计划设计.以不同CT值范围确定患者肺体积、靶体积(GTV、CTV、PTV)是否从肺体积中减除及不同分割剂量为影响因素,计算肺剂量体积参数受影响的程度.结果 当CT值在-300～ -980至-500～ -980范围变化时,全肺体积减少的中位数为-9.10%,明显高于V30、V20、V10和MLD的中位变化(为-3.18%、-1.13%、0.82%和-0.79%).CT值-400～ -980确定的全肺体积随减除靶体积的增加V30、V20、V10和MLD的变化也加大,其中V30变化最大,V10变化最小.5例PTV体积＜140 cm3(中位PTV体积为78 cm3)患者设置总物理剂量60 Gy,分割剂量由2 Gy增加至10 Gy时,由物理剂量转换为生物等效剂量的V30、V20、V10和MLD逐渐增加(呈正相关),且三者变化相同(增加幅度约为40%).在＞6Gy分割剂量后,MLD变化更大(36%).结论 不同CT值范围勾画并确定肺体积时,对全肺体积影响最大,V30变化有统计学意义(尚不足以左右放疗计划的取舍),V20、V10和MLD的变化无统计学意义.全肺体积减去与之相重叠的靶体积(GTV、CTV、PTV)后,V30的变化最大,而影响最小的是V10.增加分割剂量也明显增加剂量体积参数,而剂量分割方式在3个因素中似乎影响最大(＞10%).     

Radiation pneumonitis following concurrent accelerated hyperfractionated radiotherapy and chemotherapy for limited-stage small-cell lung cancer: Dose-volume histogram analysis and comparison with conventional chemoradiation

PURPOSE: The aim of this study was twofold: to determine whether the dose-volume metrics are valuable in predicting radiation pneumonitis (RP) in small-cell lung cancer (SCLC) patients treated with accelerated hyperfractionated radiotherapy and chemotherapy (AHFRT + CT); and to clarify how AHFRT influences the risk of RP in comparison to conventional once-daily radiotherapy and chemotherapy (QDRT + CT). METHODS AND MATERIALS: Study subjects were 43 patients with SCLC treated with AHFRT + CT. Radiotherapy was delivered at 1.5 Gy/fraction (fr) twice daily to 45 Gy/30 fr/3 weeks. We analyzed the relation between RP incidence and several dosimetric factors. We also compared this series data with our previously published data from lung cancer patients treated with QDRT + CT. RESULTS: Radiation pneumonitis Grades 1, 2, and 3 were observed in 28 patients, 7 patients, and 1 patient, respectively. Univariate analysis revealed that the percentage of lung volume receiving more than 15 Gy, 20 Gy, and 30 Gy (V15, V20, V30) and normal tissue complication probability were of predictive value for the development of RP. The 12-month cumulative incidences of RP greater than Grade 2 were 0%, 7.1%, 25%, and 42.9% in patients with a V20 of < or =20%, 21-25%, 26-30%, and > or =31%, respectively. These incidences were lower than that of our patients treated with QDRT + CT. CONCLUSIONS: Dosimetric factors are valuable in predicting RP in SCLC patients treated with AHFRT + CT. Regarding the incidence of RP, AHFRT appears to have some advantage over QDRT.     

3DCRT计划中不同肺定义对肺癌放疗的影响

目的 探讨3DCRT计划中双肺－GTV、CTV、PTV三种定义下正常肺DVH参数差异及对RP的预测价值。方法 对2006—2010年间行3DCRT的147例NSCLC患者分别定义双肺－GTV、CTV、PTV正常肺并收集相关DVH剂量学信息,比较参数值差异及其对RP的预测价值。剂量学参数间差异采用成组t检验,用ROC曲线分析各剂量学因素的预测价值。结果 以MLD为例,双肺－GTV定义下与双肺－CTV、PTV的差值分别为(1.16±0.96)、(3.45±1.43) Gy。同一患者不同定义下MLD最大差值为8.73 Gy。双肺－GTV下MLD对≥2、3级RP预测价值优于双肺－CTV、PTV的,表现为ROC曲线下面积较大,分别为0.614和0.678、0.566和0.602、0.551和0.616(P=0.024和0.056、0.269和0.226、0.317和0.167)。对肺V₅—V₅₀的分析也得出类似结论。结论 基于不同定义下所得的剂量学参数存在较大差异,临床不能忽视;基于双肺－GTV所得相关剂量学参数对RP预测价值最佳,建议采用。     

Updated assessment of the six-minute walk test as predictor of acute radiation-induced pneumonitis

PURPOSE: To assess the utility of the 6-minute walk test (6MWT) as a predictor of symptomatic radiation-induced pneumonitis (RP). METHODS: As part of a prospective trial to study radiation-induced lung injury, 53 patients receiving thoracic radiotherapy (RT) underwent a pre-RT 6MWT, pulmonary function tests (PFTs), and had >or=3-month follow-up for prospective assessment of Grade 2 or worse RP (requiring medications or worse). Dosimetric parameters (e.g., the percentage of lung receiving >or=30 Gy) were extracted from the lung dose-volume histogram. The correlations between the 6MWT and PFT results were assessed using Pearson's correlation. The receiver operating characteristic technique was used in patient subgroups to evaluate the predictive capacities for RP of the dosimetric parameters, 6MWT results, and PFT results, or the combination (using discriminant analysis) of all three metrics. ROCKIT software was used to compare the receiver operating characteristic areas between each predictive model. The association of the decline in 6MWT with the development of RP was evaluated using Fisher's exact test. RESULTS: The pre-RT PFT and 6MWT results correlated weakly (r = 0.44-0.57, p or=30 Gy, receiver operating characteristic area 0.73, p = 0.03). Including the PFT or 6MWT results with the percentage of lung receiving >or=30 Gy did not improve the predictions. The predictive abilities of dosimetric-based models improved when the analysis was restricted to those patients whose tumors were not causing regional lung dysfunction. No correlation was found between the decline in the 6MWT result and the RP rate (p = 0.6). CONCLUSION: Although the PFTs and 6MWT are related to each other, the correlation coefficients were weak, suggesting that they could be measuring different physiologic functions. In the present data set, the addition of the PFTs or 6MWT did not increase the ability of the dosimetric parameters to predict for acute symptomatic RP. Additional work is needed to better understand the interaction among the PFT results, exercise tolerance (6MWT), and the risk of RT-induced lung dysfunction.     

Evaluation of the Radiation Pneumonia Development Risk in Lung Cancer Cases

Background: Concurrent chemo-radiotherapy is the recommended standard treatment modality for patients with locally advanced lung cancer. The purpose of three-dimensional conformal radiotherapy (3DCRT) is to minimize normal tissue damage while a high dose can be delivered to the tumor. The most common dose limiting side effect of thoracic RT is radiation pneumonia (RP). In this study we evaluated the relationship between dose-volume histogram parameters and radiation pneumonitis. This study targeted prediction of the possible development of RP and evaluation of the relationship between dose-volume histogram (DVH) parameters and RP in patients undergoing 3DCRT. Materials and Methods: DVHs of 41 lung cancer patients treated with 3DCRT were evaluated with respect to the development of grade ≥ 2 RP by excluding gross tumor volume (GTV) and planned target volume (PTV) from total (TL) and ipsilateral (IPSI) lung volume. Results: Were admitted statistically significant for p<0.05. Conclusions: The cut-off values for V5, V13, V20, V30, V45 and the mean dose of TL-GTV; and V13, V20,V30 and the mean dose of TL-PTV were statistically significant for the development of Grade ≥2 RP. No statistically significant results related to the development of Grade ≥2 RP were observed for the ipsilateral lung and the evaluation of PTV volume. A controlled and careful evaluation of the dose-volumehistograms is important to assess Grade ≥2 RP development of the lung cancer patients treated with concurrent chemo-radiotherapy. In the light of the obtained data it can be said that RP development may be avoided by the proper analysis of the dose volume histograms and the application of optimal treatment plans.     

Radiation pneumonitis: correlation of toxicity with pulmonary metabolic radiation response

PURPOSE: To characterize the relationship between radiation pneumonitis (RP) clinical symptoms and pulmonary metabolic activity on post-treatment [(18)F]-fluorodeoxyglucose positron emission tomography (FDG-PET). PATIENTS AND METHODS: We retrospectively studied 101 esophageal cancer patients who underwent restaging FDG-PET/computed tomography imaging 3-12 weeks after completing thoracic radiotherapy. The National Institutes of Health Common Toxicity Criteria, version 3, was used to score the RP clinical symptoms. Linear regression was applied to the FDG-PET/computed tomography images to determine the normalized FDG uptake vs. radiation dose. The pulmonary metabolic radiation response (PMRR) was quantified as this slope. Modeling was performed to determine the interaction of PMRR, mean lung dose (MLD), and the percentage of lung receiving >20 Gy with RP outcomes. RESULTS: Of the 101 patients, 25 had Grade 0, 10 had Grade 1, 60 had Grade 2, 5 had Grade 3, and 1 had Grade 5 RP symptoms. Logistic regression analysis demonstrated that increased values of both MLD and PMRR were associated with a greater probability of RP clinical symptoms (p = 0.032 and p = 0.033, respectively). Spearman's rank correlation found no association between the PMRR and the dosimetric parameters (planning target volume, MLD, percentage of lung receiving >5-30 Gy). Twofold cross-validation demonstrated that the combination of MLD and PMRR was superior to either alone for assessing the development of clinical RP symptoms. The combined MLD (or percentage of lung receiving >20 Gy) and PMRR had a greater sensitivity and accuracy (53.3% and 62.5%, respectively) than either alone. CONCLUSION: The results of this study have demonstrated a significant correlation between RP clinical symptoms and the PMRR measured by FDG-PET/computed tomography after thoracic radiotherapy.     

非小细胞肺癌三维适形放疗同期化疗后急性放射性肺炎发生因素分析

目的 分析三维适形放疗同期化疗非小细胞肺癌急性放射性肺炎(RP)的发生率及相关因素.方法 搜集2006年1月到2008年10月间首程行三维适形放疗并同期化疗的非小细胞肺癌病例90例,对相关放射剂量体积资料和治疗毒性的临床资料进行统计分析.结果 1级急性RP的发生率为32.2%,2级30.0%,3级5.6%,4级0%,5级1.1%.临床因素单因素分析有统计学差异的是原发肿瘤部位.剂量学方面当平均肺剂量以17 Gy,V_5、V_(10)、V_(20)、V_(30)、V_(40)分别以47%、36%、24%、23%、22%为界分组时组间差异有统计学意义.多因素分析显示平均肺剂量是独立预测因子.结论 RP的发生发展受到多因素综合作用,制定肺癌尤其是中下叶肺癌的三维放疗计划时应将平均肺剂量控制在17 Gy以下.     

Comparing different NTCP models that predict the incidence of radiation pneumonitis. Normal tissue complication probability

PURPOSE: To compare different normal tissue complication probability (NTCP) models to predict the incidence of radiation pneumonitis on the basis of the dose distribution in the lung. METHODS AND MATERIALS: The data from 382 breast cancer, malignant lymphoma, and inoperable non-small-cell lung cancer patients from two centers were studied. Radiation pneumonitis was scored using the Southwestern Oncology Group criteria. Dose-volume histograms of the lungs were calculated from the dose distributions that were corrected for dose per fraction effects. The dose-volume histogram of each patient was reduced to a single parameter using different local dose-effect relationships. Examples of single parameters were the mean lung dose (MLD) and the volume of lung receiving more than a threshold dose (V(Dth)). The parameters for the different NTCP models were fit to patient data using a maximum likelihood analysis. RESULTS: The best fit resulted in a linear local dose-effect relationship, with the MLD as the resulting single parameter. The relationship between the MLD and NTCP could be described with a median toxic dose (TD(50)) of 30.8 Gy and a steepness parameter m of 0.37. The best fit for the relationship between the V(Dth) and the NTCP was obtained with a D(th) of 13 Gy. The MLD model was found to be significantly better than the V(Dth) model (p <0.03). However, for 85% of the studied patients, the difference in NTCP calculated with both models was <10%, because of the high correlation between the two parameters. For dose distributions outside the range of the studied dose-volume histograms, the difference in NTCP, using the two models could be >35%. For arbitrary dose distributions, an estimate of the uncertainty in the NTCP could be determined using the probability distribution of the parameter values of the Lyman-Kutcher-Burman model. CONCLUSION: The maximum likelihood method revealed that the underlying local dose-effect relation for radiation pneumonitis was linear (the MLD model), rather than a step function (the V(Dth) model). Thus, for the studied patient population, the MLD was the most accurate predictor for the incidence of radiation pneumonitis.     

肺低剂量区体积预测急性放射性肺炎价值探讨

目的 观察胸部肿瘤三维适形放疗患者放射性肺炎发生情况,分析其与各临床、剂量学因素关系,探讨低剂量区体积对放射性肺炎的预测价值.方法 2005-2008年本科收治的中晚期非小细胞肺癌(NSCLC)及食管癌患者共161例接受了三维适形放疗,其中局部晚期NSCLC患者53例,处方剂量60 Gy分30～34次,均行长春瑞滨+顺铂同期化疗;食管癌患者108例,处方剂量58～70 Gy分29～35次,单纯放疗46例,余62例接受亚叶酸钙+氟尿嘧啶+顺铂同期化疗.对急性放射性肺炎进行Spearman等级相关分析、Logistic因素分析及受试者工作特征(ROC)曲线分析.结果 随访率100%.全组急性放射性肺炎总发生率为57.8%(93例),其中NSCLC组为94%(50例,4、5级各1例),食管癌组为39.8%(43例,无≥4级病例).等级相关分析结果显示患者性别(r=0.19,P=0.016)、大体肿瘤体积(r=0.52,P=0.000))、平均肺剂量(r=0.33,P=0.000)、肺正常组织并发症概率(r=0.30,P=0.000)、接受5、10、15、20、25、30 Gy照射的肺体积百分比(肺V5～V30,r=0.21～0.29,P=0.000～0.027)均与放射性肺炎发生相关.Logistic因素分析结果显示肺V5(X2=7.07,P=0.008)、大体肿瘤体积(X2=10.21,P=0.001)是预测≥2级放射性肺炎最有价值指标.ROC曲线分析结果显示曲线下面积为0.684,P=0.000;曲线界值为V5=55%.肺V5≥55%组与<55%组≥2级放射性肺炎发生率分别为43%(36/84)和18%(14/77).结论 平均肺剂量、正常组织并发症概率、V5～V30可较好预测放射性肺炎的发生,其中V5可能是最有价值的预测性指标.当V5>55%时≥2级的急性放射性肺炎的发生率可能会明显增加,制定治疗计划时除平均肺剂量、V20、V30外,还应将低剂量区体积限制在适当范围内.     

非小细胞肺癌术后适形放疗肺损伤相关因素研究

目的 分析非小细胞肺癌(NSCLC)术后接受三维适形放疗(3DCRT)肺损伤的相关因素.方法 对2002年11月至2006年3月符合入组条件的90例患者进行回顾性分析,其中Ⅰ～Ⅱ期12例(切缘阳性),ⅢA期53例,ⅢB期25例.术后均接受了中位剂量60 Gy的3DCRT,38例接受了中位3周期术后化疗.观察指标为CTC 3.0 2级以上放射性肺炎(RP).应用ROC曲线分析健侧、患侧和双肺接受x Gy剂量的相对体积(Vx)和绝对体积与RP的关系.结果 全组共9例患者出现有症状的RP,RP发生率为10%.接受全肺切除的20例患者中无RP发生.RP中位发生时间在放疗开始后101 d,其中2级7例,3级2例.双肺V30、V35在RP组明显高于未发生RP组(19%∶14%,U=-2.16,P=0.030;15%:11%,U=-2.65,P=0.007).以患侧肺接受30 Gy照射的绝对体积作为分界点进行ROC曲线分析结果 显示曲线下面积为0.757,对RP预测的敏感性为88%、特异性为70%.患肺接受30 Gy照射的绝对体积>340 cm3的RP发生率明显高于体积<340 cm3的(29%∶3%,x2=9.75,P=0.003).结论 对于肺叶切除的NSCLC患者接受术后放疗,患肺接受30 Gy照射的绝对体积与RP相关.对全肺切除患者,单肺V20限制在10%以下,接受术后放疗是安全可行的.     

Significance of plasma transforming growth factor-β levels in radiotherapy for non–small-cell lung cancer

PURPOSE: In dose-escalation studies of radiotherapy (RT) for non-small-cell lung cancer (NSCLC), radiation pneumonitis (RP) is the most important dose-limiting complication. Transforming growth factor-beta1 (TGF-beta1) has been reported to be associated with the incidence of RP. It has been proposed that serial measurements of plasma TGF-beta1 can be valuable to estimate the risk of RP and to decide whether additional dose-escalation can be safely applied. The aim of this study was to evaluate prospectively the time course of TGF-beta1 levels in patients irradiated for NSCLC in relation to the development of RP and dose-volume parameters. METHODS AND MATERIALS: Plasma samples were obtained in 68 patients irradiated for medically inoperable or locally advanced NSCLC (dose range, 60.8-94.5 Gy) before and 4, 6, and 18 weeks after the start of RT. Plasma TGF-beta1 levels were determined using a bioassay on the basis of TGF-beta1-induced plasminogen activator inhibitor-1 expression in mink lung cells. All patients underwent chest computed tomography scans before RT that were repeated at 18 weeks after RT. The computed tomography data were used to calculate the mean lung dose (MLD) and to score the radiation-induced radiologic changes. RP was defined on the basis of the presence of either radiographic changes or clinical symptoms. Symptomatic RP was scored according to the Common Toxicity Criteria (Grade 1 or worse) and the Southwestern Oncology Group criteria (Grade 2 or worse). Multivariate analyses were performed to investigate which factors (pre- or posttreatment TGF-beta1 level, MLD) were associated with the incidence of RP. To improve our understanding of the time course of TGF-beta1 levels, we performed a multivariate analysis to investigate which factors (pre-RT TGF-beta1 level, MLD, RP) were independently associated with the posttreatment TGF-beta1 levels. RESULTS: The pre-RT TGF-beta1 levels were increased in patients with NSCLC (median 21 ng/mL, range, 5-103 ng/mL) compared with healthy individuals (range, 4-12 ng/mL). On average, the TGF-beta1 levels normalized toward the end of treatment and remained stable until 18 weeks after RT. In 29 patients, however, TGF-beta1 was increased at the end of RT with respect to the pre-RT value. The multivariate analyses revealed that the MLD was the only variable that correlated significantly with the risk of both radiographic RP (p = 0.05) and symptomatic RP, independent of the scoring system used (p = 0.05 and 0.03 for Southwestern Oncology Group and Common Toxicity Criteria systems, respectively). The TGF-beta1 level at the end of RT was significantly associated with the MLD (p <0.001) and pre-RT TGF-beta1 level (p = 0.001). CONCLUSION: The MLD correlated significantly with the incidence of both radiographic and symptomatic RP. The results of our study did not confirm the reports that increased levels of TGF-beta1 at the end of RT are an independent additional risk factor for developing symptomatic RP. However, the TGF-beta1 level at the end of a RT was significantly associated with the MLD and the pre-RT level.     

Intensity-modulated radiotherapy for resected mesothelioma: the Duke experience

PURPOSE: To assess the safety and efficacy of intensity-modulated radiotherapy (IMRT) after extrapleural pneumonectomy for malignant pleural mesothelioma. METHODS AND MATERIALS: Thirteen patients underwent IMRT after extrapleural pneumonectomy between July 2005 and February 2007 at Duke University Medical Center. The clinical target volume was defined as the entire ipsilateral hemithorax, chest wall incisions, including drain sites, and involved nodal stations. The dose prescribed to the planning target volume was 40-55 Gy (median, 45). Toxicity was graded using the modified Common Toxicity Criteria, and the lung dosimetric parameters from the subgroups with and without pneumonitis were compared. Local control and survival were assessed. RESULTS: The median follow-up after IMRT was 9.5 months. Of the 13 patients, 3 (23%) developed Grade 2 or greater acute pulmonary toxicity (during or within 30 days of IMRT). The median dosimetric parameters for those with and without symptomatic pneumonitis were a mean lung dose (MLD) of 7.9 vs. 7.5 Gy (p = 0.40), percentage of lung volume receiving 20 Gy (V(20)) of 0.2% vs. 2.3% (p = 0.51), and percentage of lung volume receiving 5 Gy (V(20)) of 92% vs. 66% (p = 0.36). One patient died of fatal pulmonary toxicity. This patient received a greater MLD (11.4 vs. 7.6 Gy) and had a greater V(20) (6.9% vs. 1.9%), and V(5) (92% vs. 66%) compared with the median of those without fatal pulmonary toxicity. Local and/or distant failure occurred in 6 patients (46%), and 6 patients (46%) were alive without evidence of recurrence at last follow-up. CONCLUSIONS: With limited follow-up, 45-Gy IMRT provides reasonable local control for mesothelioma after extrapleural pneumonectomy. However, treatment-related pulmonary toxicity remains a significant concern. Care should be taken to minimize the dose to the remaining lung to achieve an acceptable therapeutic ratio.