结合肺灌注影像参数的等效均匀剂量模型与放射性肺炎的相关性研究

背景与目的:目前,临床上用来预测放射性肺损伤的肺剂量体积参数准确度较低,且阈值不统一.该研究通过肺功能影像,探讨结合肺血流参数的等效均匀剂量(equivalent uniform dose,EUD)在预测放射性肺炎方面的价值.方法:将15例肺癌放疗患者肺灌注影像与定位CT影像形变融合,以肺灌注最高计数为归一点,将肺依功能状态分为四级区域,取每级区域中的平均计数与最高计数的比值作为肺灌注系数代入EUD模型中,获得肺部的功能等效均匀剂量(functional equivalent uniform dose,fEUD)模型.比较单肺及双肺的fEUD与不含肺功能指数的等效均匀剂量(general equivalent uniform dose,gEUD)、V5、V20在预测放射性肺炎方面的统计学差异,并进一步分析上述参数的统计学分布特征及彼此之间的相关性.放射性肺炎的判断标准采用不良事件常用术语评定标准(Common Terminology Criteria for Adverse Events,CTCAE)4.03版肺部症状3级以上,P<0.05为差异有统计学意义.结果:该研究的样本中,当V5、V20等指标显示与放射性肺炎无关时,高剂量侧肺的fEUD值呈现与放射性肺炎显著相关(P=0.007).单侧肺fEUD值与gEUD值呈显著线性关系(t=0.815,P=0.000).结论:单侧肺fEUD较传统剂量-体积指标更好地体现了肺功能不同区域间的放射生物学差异,可以作为放射性肺炎预测指标,建议阈值为21 Gy.     

细胞因子联合DVH参数预测放射性肺炎的临床研究

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。     

剂量体积直方图参数评估放射性肺损伤的作用

一个理想的放射治疗计划 ,要求对肿瘤有最大的控制率和对周围正常组织产生较小并发症 ,因此 ,要在不同的治疗方案中优选出好的计划 ,就必须找到一个可以预测正常组织放疗并发症概率的参数或方法。肺组织对放射线敏感 ,是限制胸部肿瘤 (肺癌、食管癌等 )放疗剂量提高的主要器官之一。如果能找到某些参数或方法预测放射性肺损伤的概率 ,将有利于胸部肿瘤放疗方案的优选。近年来 ,国外许多学者正在努力尝试通过剂量体积直方图 (dosevolumehistograms ,DVH)的有关参数评估放射性肺损伤 ,并在临床实践中得到了推广应用 ,但其中还有很多问题有待…     

用剂量体积直方图评估放射性肺损伤

一个理想的放射治疗计划 ,包括该计划对肿瘤有最大的控制率和对周围正常组织产生较小并发症两方面。要在不同的治疗方案中优选出该计划 ,就必须找到一个可以预测正常组织放射治疗并发症概率的参数或方法。肺组织对放射线敏感 ,是限制胸部肿瘤 (肺癌、食管癌等 )放射治疗剂量提高的主要器官之一。如果能找到一个参数或方法预测放射性肺损伤 (急性放射性肺炎和放射性肺纤维化 )的概率 ,可能有利于胸部肿瘤放射治疗方案的优选。近年来 ,国外较多学者正在努力尝试找到剂量体积直方图 (ｄｏｓｅｖｏｌｕｍｅｈｉｓ ｔｏｇｒａｍｓ,ＤＶＨｓ)的有…     

剂量体积直方图(DVH)预测肺癌放疗后放射性肺炎的价值

根治性放疗是不能手术的非小细胞肺癌(non-small cell lung cancer,NSCLC)和局限期小细胞肺癌(small cell lungcancer,SCLC)的重要治疗手段。三维适形放疗是20世纪90年代发展起来的一种新型放疗技术,已经用于肺癌的放疗。三维治疗计划能较准确地明确肿瘤靶体积,使重要器官如脊髓、心脏、肝脏和正常肺组织少受或免受不必要的照射,减少急性或慢性的毒性反应,从而提高放疗的治疗增益比。放射性肺炎(radiation pneumonitis,RP)是胸部照射最常见的剂量限制性并发症,对患者的生活质量和肺功能有很大影响。接受根治性放疗的肺癌中大约有13%~37…     

肺癌放疗后放射性肺炎剂量学相关预测因素的研究进展

放射性肺炎（radiation pneumonitis,RP）是肺癌放射治疗的主要并发症之一,本文现将近年来通过剂量体积直方图（dose-volume histograms,DVH）有关参数评估放射性肺损伤的研究现状并作系统回顾。     

血浆白细胞介素6、血管紧张素转换酶水平及放射剂量体积直方图参数对放射性肺炎预测的临床价值

 目的　研究血浆中白细胞介素6（IL-6）、血管紧张素转换酶（ACE）水平及剂量体积直方图（DVH）参数与放射性肺炎发生的相关性,并评价其在预测放射性肺炎中的临床价值。方法　常规给予60例不能手术切除或者不愿意手术切除的局部晚期非小细胞肺癌患者三维适形放疗。分别在放疗前、放疗中（放疗第1周至第6周）、放疗后（放疗第8、12周）采用酶联免疫吸附法（ELISA）检测血浆中IL-6及ACE的含量。 依照美国放射肿瘤学协作组（RTOG）放射性肺损伤标准进行放射性肺炎诊断及分级,以出现放射性肺炎组为观察组,未出现放射性肺炎组为对照组,统计两组血浆中IL-6、 ACE、DVH参数V20、V30、平均肺剂量（MLD）及正常组织并发症概率（NTCP）。结果　60例患者中16例发生放射性肺炎,其中5例发生于放疗中,10例发生于放疗结束后1个月内,1例发生于放疗结束后2个月内;包括Ⅱ级11例,Ⅲ级5例。放疗前、中、后血浆IL-6水平变化在观察组与对照组间差异均有统计学意义,ACE在放疗中第3周至第6周两组间差异有统计学意义（均P＜0.05）。V20、V30、MLD及NTCP在观察组与对照组分别为（46.2±4.5）%比（30.5±7.5）%、（37.5±5.6）%比（20.5±5.6）%、（20.4±2.3）Gy比（15.5±3.5）Gy、（25.2±8.2）%比（9.9±4.5）%,两组间差异有统计学意义（均P＜0.05）。结论　血浆中IL-6、ACE水平、V20、V30、MLD及NTCP指标均与放射性肺炎的发生有关。     

非小细胞肺癌同期放化疗后重度急性放射性肺炎的预测因素

目的 评价剂量体积直方图参数及临床因素对非细胞肺癌三维适形放疗同期化疗后急性重度放射性肺炎(SARP)的预测价值。方法 回顾分析2006-2010年行三维适形放疗同期化疗的非小细胞肺癌 147例病例资料。对有无SARP的剂量学参数行成组t检验,对有差异的和临床因素行Logistic法多因素预测分析。用受试者工作特征(ROC)曲线分析各剂量学因素的预测价值,Pearson法分析剂量学数据间相关性并从剂量学参数中提取有代表性因子。结果 全组患者SARP发生率为9.5%。平均肺剂量(MLD)、V₂₀、V₃₀、V₄₀、V₅₀与SARP发生相关(χ²=4.87~6.84,P=0.009~0.025)。控制SARP发生率≤5%时的界值分别为MLD≤16.77 Gy,V₂₀≤34.15%, V₃₀≤23.62%, V₄₀≤18.57%, V₅₀≤13.02%, 其敏感性、特异性、ROC曲线下面积分别为78.0%、48.1%、0.678,42.9%、82.0%、0.661,78.6%、52.9%、0.667,71.4%、61.7%、0.677,57.1%、67.7%、0.651。因子分析显示可考虑选取MLD、V₂₀、V₃₀中的1个或2个,V₄₀、V₅₀中的1个用于预测SARP。肿瘤位于右中下肺者SARP发生率高于其他部位(22.2%∶6.7%,χ²=6.19,P=0.023)。结论 MLD、V₂₀、V₃₀、V₄₀、V₅₀可用于放射性肺炎预测,但单个预测价值不佳,要多种参数联合使用。肿瘤位于右肺中下叶者放疗后发生SARP危险性较肿瘤位于其他部位者高。     

Ⅲ＋Ⅳ期非小细胞肺癌调强放疗剂量学参数预测有症状放射性肺炎的临床研究

目的：探讨接受调强放疗（intensity modulated radiotherapy,IMRT）的Ⅲ、Ⅳ期非小细胞肺癌（non－small－cell lung cancer,NSCLC）患者正常肺组织剂量－体积参数对有症状放射性肺炎（≥2级,radiation pneu-monitis,RP）的预测作用。方法：回顾性分析53例接受调强放疗的Ⅲ、Ⅳ期NSCLC患者临床资料,记录剂量－体积参数V5、V20、平均肺剂量（MLD）及≥2级RP发生率。肺损伤评估根据CTCAE4．0标准。单因素及多因素分析各个剂量学参数与≥2级RP之间的关系,并采用ROC曲线分析各剂量参数的敏感性、特异性对预测≥2级RP的价值。结果：53例患者中2级RP发生率为9．43％（5／53）,3级RP发生率为5．66％（3／53）,4级RP发生率为3．77％（2／53）,≥2级RP总发生率为18．87％（10／53）。经Spearman等级相关分析,V5、V20、MLD均与≥2级RP的发生相关（r＝0．485、0．404、0．404,P＝0．000、0．003、0．003）。单因素分析发现V5、V20、MLD与≥2级RP的发生有相关性（t＝－4．588、－2．433、－2．845,P＝0．000、0．019、0．006）。经单因素分析中有意义的参数,再次进行多因素分析显示：V5是≥2级RP发生的独立影响因素（P＝0．03）。经ROC曲线分析,V5预测≥2级RP有统计学意义（P＜0．05）,其曲线下面积为0．862,敏感性和特异性分别为1．00、0．442。当V5临界值为43．65％时≥2级RP发生率分别为7．14％、32％。结论：剂量－体积参数V5、V20、MLD与≥2级RP相关,其中V5是独立预测因素。     

基于剂量组学预测肺癌患者放射性肺炎发生的研究

目的 探讨剂量组学在预测肺癌根治性放疗患者放射性肺炎发生中的应用潜能。方法 回顾性收集行根治性放疗的314例肺癌患者的临床资料、放疗剂量文件、定位及随访CT图像,根据临床资料及影像学随访资料对放射性肺炎进行分级,提取全肺的剂量组学特征,构建机器学习模型。应用1000次自助抽样法（bootstrap）的最小绝对值收敛和选择算子嵌套逻辑回归（LASSO‐LR）及1000次bootstrap的赤池信息量准则（AIC）向后法筛选与放射性肺炎相关的剂量组学特征,随机按照7∶3划分为训练集及验证集,应用逻辑回归建立预测模型,并应用ROC曲线及校正曲线评价模型的性能。结果 共提取120个剂量组学特征,经LASSO‐LR降维筛选得到12个特征进入“特征池”,再经过AIC向后法筛选,最终筛选出6个剂量组学特征进行模型构建,训练集AUC为0.77（95%CI为0.65~0.87）,独立验证集AUC为0.72（95%CI为0.64~0.81）。结论 利用剂量组学建立的预测模型具有预测放射性肺炎发生的潜力,但仍需继续纳入多中心数据及前瞻性数据进一步挖掘剂量组学的应用潜能。     

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.     

Incidence of radiation pneumonitis after thoracic irradiation: Dose-volume correlates

PURPOSE: To define clinical and dosimetric parameters correlated with the risk of clinically relevant radiation pneumonitis (RP) after thoracic radiotherapy. METHODS AND MATERIALS: Records of consecutive patients treated with definitive thoracic radiotherapy were retrospectively reviewed for the incidence of RP of Grade 2 or greater by the Common Toxicity Criteria. Dose-volume histograms using total lung volume (TL) and TL minus gross tumor volume (TL-G) were created with and without heterogeneity corrections. Mean lung dose (MLD), effective lung volume (V(eff)), and percentage of TL or TL-G receiving greater than or equal to 10, 13, 15, 20, and 30 Gy (V10-V30, respectively) were analyzed by logistic regression. Receiver operating characteristic (ROC) curves were generated to estimate RP predictive values. RESULTS: Twelve cases of RP were identified in 92 eligible patients. Mean lung dose, V10, V13, V15, V20, and V(eff) were significantly correlated to RP. Combinations of MLD, V(eff), V20, and V30 lost significance using TL-G and heterogeneity corrections. Receiver operating characteristic analysis determined V10 and V13 as the best predictors of RP risk, with a decrease in predictive value above those volumes. CONCLUSIONS: Intrathoracic radiotherapy should be planned with caution when using radiotherapy techniques delivering doses of 10 to 15 Gy to large lung volumes.     

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.     

经调强适形放疗治疗的肺癌患者发生放射性肺炎的相关因素分析

 目的　探讨调强适形放疗（IMRT）治疗肺癌发生放射性肺炎（RP）的相关因素,寻找合理的预测性指标,为放疗计划的制定提供参考。方法　对163例经IMRT治疗肺癌患者的临床资料及剂量-体积直方图的相关参数进行量化分析,放疗结束后随访时间≥6个月,应用统计学方法研究其与RP之间的关系。结果　≥2级RP的发生率为28.22 %（46／163）。单因素分析发现下叶肿瘤（P＝0.033）、合并慢性阻塞性肺疾病（COPD）（P＝0.020）、联合化疗（P＝0.020）、未预防性使用糖皮质激素及抗生素（P＝0.025）与RP的发生有关。其中肺基础疾病及联合化疗是影响≥2级RP发生的独立因素。多因素分析表明健侧肺V20、全肺V5及靶区总体积是RP发生的独立影响因素。结论　RP的发生与多种因素相关,放疗计划应根据患者的具体情况合理地制定。     

Dose-volume histogram analysis as predictor of radiation pneumonitis in primary lung cancer patients treated with radiotherapy

PURPOSE: To determine the relationship between various parameters derived from lung dose-volume histogram analysis and the risk of symptomatic radiation pneumonitis (RP) in patients undergoing radical radiotherapy for primary lung cancer. METHODS AND MATERIALS: The records of 156 patients with lung cancer who had been treated with radical radiotherapy (>/=45 Gy) and for whom dose-volume histogram data were available were reviewed. The incidence of symptomatic RP was correlated with a variety of parameters derived from the dose-volume histogram data, including the volume of lung receiving 10 Gy (V(10)) through 50 Gy (V(50)) and the mean lung dose (MLD). RESULTS: The rate of RP at 6 months was 15% (95% confidence interval 9-22%). On univariate analysis, only V(30) (p = 0.036) and MLD (p = 0.043) were statistically significantly related to RP. V(30) correlated highly positively with MLD (r = 0.96, p < 0.001). CONCLUSION: V(30) and MLD can be used to predict the risk of RP in lung cancer patients undergoing radical radiotherapy.     

The impact of heterogeneity correction on dosimetric parameters that predict for radiation pneumonitis

PURPOSE: To determine if heterogeneity correction significantly affects commonly measured dosimetric parameters predicting pulmonary toxicity in patients receiving radiation for lung cancer. METHODS AND MATERIALS: Sixty-eight patients treated for lung cancer were evaluated. The conformal treatment technique mostly employed anteroposterior/posterior-anterior fields and off-cord obliques. The percent total lung volume receiving 20 Gy or higher (V20) and mean lung dose (MLD) were correlated with the incidence of radiation pneumonitis. Parameters from both heterogeneity-corrected and heterogeneity-uncorrected plans were used to assess this risk. RESULTS: Univariate analysis revealed a significant correlation between the development of radiation pneumonitis and both V20 and MLD. A best-fit line to a plot of V20 from the homogeneous plan against the corresponding V20 heterogeneous value produced a slope of 1.00 and zero offset, indicating no difference between the two parameters. For MLD, a similarly significant correlation is seen between the heterogeneous and homogeneous parameters, indicating a 4% difference when correcting for heterogeneity. A significant correlation was also observed between the MLD and V20 parameters (p < 0.0001). CONCLUSIONS: A high degree of correlation exists between heterogeneity-corrected and heterogeneity-uncorrected dosimetric parameters for lung and the risk of developing pneumonitis. Either V20 or MLD predicts the pneumonitis risk with similar effect.     

肺灌注显像检查预测肺癌放射性肺损伤的价值

目的探讨肺癌患者肺灌注显像的特点及其放射治疗过程中的变化,观察其与放射性肺损伤发生的关系。方法31例接受根治性放疗的肺癌患者接受了肺灌注显像检查,其中8例仅在放疗前接受了此项检查。以照射前后计算区域的肺灌注平均计数值占相应全肺平均计数值的百分比,比较照射前后肺灌注的变化。放射性肺损伤的评价按美国肿瘤放射治疗组（RTOG）急性放射性肺炎标准评定。结果31例患者中,中央型22例,周围型9例。病理类型：鳞癌12例,腺癌1例,小细胞肺癌15例,未分型3例。Ⅰ、Ⅱ期8例,Ⅲa期9例,Ⅲb期14例。行适形放疗26例,常规放疗5例;照射剂量32—72Gy,中位剂量58Gy。6例发生2级或3级放射性肺炎,无放射性肺炎死亡病例。全部患者治疗前均有不同程度的灌注受损,中央型肺癌患者灌注受损范围≥2级者占68．2％（15／99）,而周围型仅占22．2％（2／9,P=0．04）。受损范围为1级和2级以上者,分别有40．0％（6／15）和37．5％（6／16）的患者发生2级以上放射性肺损伤。在两次行肺灌注检查的23例中,肺灌注受损有所改善者占70．0％（16／23）,其中2级以上放射性肺炎发生率为31．3％（5／16）;在肺灌注受损加重者中,2级以上放射性肺炎发生率为42．9％（3／7）。结论灌注受损是肺癌患者的常见表现,中央型肺癌灌注受损较重,放射治疗后多数病例肺灌注受损有所改善;放疗前和放疗中,肺灌注受损范围的变化和放射性肺损伤的发生无明显相关性。     

High-dose preoperative chemoradiotherapy in esophageal cancer patients does not increase postoperative pulmonary complications: Correlation with dose-volume histogram parameters

Purpose

To investigate the association of high-dose preoperative chemoradiotherapy (CRT) and dose-volume histogram (DVH) parameters of lungs with incidence of postoperative pulmonary complications and to identify predictive clinical factors of pulmonary complications.

Methods

Data of 65 patients were collected retrospectively. Thirty-five patients underwent transthoracic esophagectomy (TTE) alone and 30 received cisplatin and 5-fluorouracil, concomitant with radiotherapy, median dose 66 Gy, and followed by TTE. From the DVH for each lung alone and for both lungs together as one organ we generated total lung volume, mean radiotherapy dose, relative and absolute volumes receiving more than a threshold dose, and relative and absolute volumes receiving less than a threshold dose. Postoperative pulmonary complications were defined as pneumonia or respiratory failure.

Results

Sixty percent of the patients in the TTE alone group had postoperative pulmonary complications versus 63% in the CRT + TTE group. Postoperative mortality was 8.6% and 16.7% in the respective patient groups (p = NS). None of the DVH parameters was associated with postoperative pulmonary complications. Squamous cell carcinoma was an adverse factor related to increased postoperative pulmonary complications.

Conclusion

High-dose preoperative CRT was not associated with increased postoperative pulmonary complications in this cohort of esophageal cancer patients.