肺癌放射性肺炎危险因素的Meta分析

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段晨阳, 刘梦颖, 吴剑, 张杰, 张吉强. 肺癌放射性肺炎危险因素的Meta分析.循证医学, 2013, 13(2): 106-115
DUAN Chen-yang, LIU Meng-ying, WU Jian, ZHANG Jie, ZHANG Ji-qiang. Risk Factors on Radiation Pneumonitis： A Meta-Analysis. Journal of Evidence-Based Medicine, 2013,13(2): 106-115 复制到剪切板

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肺癌放射性肺炎危险因素的Meta分析

段晨阳^a, 刘梦颖^a, 吴剑^a, 张杰^a, 张吉强^b

解放军第三军医大学 a. 临床医学系，b. 基础部神经生物学教研室, 重庆 400038

通讯作者:张吉强,Tel： 023-68752232; E-mail：zhangjqtmmu@yahoo.com

作者简介:段晨阳与刘梦颖并列第一作者。段晨阳（1991-）,男,石家庄人,在读硕士研究生,主要研究方向为肿瘤医学研究。刘梦颖（1992-）,女,河北沧州人,在读硕士研究生,主要研究方向为肿瘤医学研究。

基金:国家自然科学基金资助项目（81171035）;

摘要

目的探讨影响放射性肺炎发生的因素,为更好地指导临床治疗、减少放射性肺炎的发生提供依据。方法计算机检索PubMed数据库、EMBASE数据库、Cochrane协作网和CNKI数据库,并辅以手工检索等方法,应用RevMan 5.1软件对截止2012年2月发表的预测肺癌放疗后发生放射性肺炎的文献数据进行Meta分析。结果共纳入文献75篇。暴露因素包括患者自身因素（性别、年龄、慢性肺疾病、肺功能、合并糖尿病）、肿瘤部位、治疗方案（放疗前有无手术、是否行联合放化疗及使用放疗增敏剂阿米福汀）。Meta分析结果显示其比值比及其95%可信区间分别为：性别0.97[0.82,1.15],年龄0.90[0.63,1.28],合并慢性肺疾病2.18[1.59,3.00],放疗前肺功能0.27[0.11,0.65],合并糖尿病2.46[1.33,4.58],左下肺部肿瘤0.71[0.57,0.90],放疗前肺部手术0.92[0.67,1.25],放化疗联合1.41[1.17,1.71],使用放疗增敏剂阿米福汀2.38[1.79,3.16]。结论影响放射性肺炎发生的因素有合并慢性肺疾病、放疗前肺功能、糖尿病、左下肺部肿瘤、放化疗联合以及使用放疗增敏剂阿米福汀。本项研究的结果认为肺功能较好且无慢性肺疾病和糖尿病等合并症的上肺肺癌患者,在单纯放疗的基础上加用放疗增敏剂阿米福汀,可以降低患者的放射性肺炎发生率。

关键词: 肺癌; 放射性肺炎; 放射性肺损伤; 危险因素; Meta分析

中图分类号:R734.2 文献标识码:A

Risk Factors on Radiation Pneumonitis： A Meta-Analysis

DUAN Chen-yang^a, LIU Meng-ying^a, WU Jian^a, ZHANG Jie^a, ZHANG Ji-qiang^b

a. Department of Clinical Medicine

b. Department of Neurobiology, Third Military Medical University, Chongqing 400038, China

Abstract

Objective To study the risk factors of radiation pneumonitis in order to find prognostic parameters and provide reference standard for the best clinical treatment plan.Methods The database of PubMed, EMBASE, Cochrane Library and CNKI were searched from the date of their establishments to Februɑry 2012, and other supplied sources were also retrieved. Meta-analysis on literatures predicting radiation pneumonitis after radiotherapy were conducted by using RevMan 5.1 software.Results A total of 75 studies were included. The exposure factors included the patient's own factors （sex, age, chronic lung disease, pulmonary function, diabetes）, tumor site, therapeutic schedule （operation before radiotherapy, combined radiochemotherapy, using radiotherapy sensitization agent Amifostine）. Meta-analysis results showed that the OR and 95%CI of each factors were： 0.97[0.82,1.15], 0.90[0.63,1.28], 2.18[1.59,3.00], 0.27[0.11,0.65], 2.46[1.33,4.58], 0.71[0.57,0.90], 0.92[0.67,1.25], 1.41[1.17,1.71], 2.38[1.79,3.16], respectively.Conclusions The risk factors of radiation pneumonitis are chronic lung disease, pulmonary function, diabetes, tumor located in left lower lung, combined radiochemotherapy and using radiotherapy sensitization agent Amifostine. The study results indicate that upper lung cancer patients with good pulmonary function and without comorbidity such as diabetes or chronic pulmonary disease have less chance getting radiation pneumonitis based on the simple radiotherapy added with Amifostine—a radiotherapy sensitizer.

Key words: lung cancer; radiation pneumonitis; radiation lung injury; risk factors; meta-analysis

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肺癌是世界上死亡率最高的恶性肿瘤,大约2/3的肺癌患者需要接受放射治疗。随着放射治疗技术的飞速发展,伴随的毒副作用,包括放射性肺损伤（radiation lung injury）也成为一个日益突出的问题。据国外资料统计,急性放射性肺损伤的发生率为5%~36%^{[ 1, 2]},由此造成的呼吸衰竭是放射性肺损伤的主要致死原因之一。放射性肺损伤分为早期急性放射性肺炎（radiation pneumonitis, RP）和晚期放射性肺纤维化（radiation pulmonary fiberosis, RPF）,二者是连续的过程,目前临床上尚没有令人满意的治疗措施和有效的预测手段,而放射性肺炎一旦发生,将直接影响到患者的治疗效果和生存质量。因此,对放射性肺损伤的预测已成为医学领域中的一项重要课题。本研究对截止2012年2月发表的预测肺癌放疗后发生放射性肺炎的文献进行Meta分析,以期得到影响放射性肺炎发生的因素,为更好地指导临床治疗、减少放射性肺炎的发生提供依据。

1 资料与方法

1.1 资料来源

以“肺癌（lung cancer）”、“ 放射性肺炎（radiation pneumonitis）”、“ 放射性肺损伤（radiation lung injury）”为关键词在PubMed数据库、EMBASE数据库、Cochrane协作网以及CNKI数据库中进行检索。所有检索均截止至2012年2月,手工检索相关期刊,必要时向有关专家索要相关研究资料。

1.2 文献筛选

纳入标准：①研究对象为经细胞学或病理学确诊为原发性肺癌的首次行肺部放射治疗的患者;②文献中记录了各暴露因素发生放射性肺炎及非放射性肺炎的例数、百分比或均数±标准差（mean±SD）;③对同一研究组观察不同年限的结果,仅取观察年限最长、最新发表的研究。

排除标准：①无法获得全文的会议摘要;②入组患者同时行胸部其他部位的放疗,或曾在治疗前1年内行胸部放疗;③研究结果为放射性肺纤维化;④评分差的文献;⑤重复发表的文献。

1.3 文献筛选及质量评价

由两人各自独立地完成对入选研究进行资料摘录。将发生放射性肺炎的患者视为放射性肺炎组,未发生放射性肺炎的患者视为非放射性肺炎组。

病例对照研究及队列研究使用Newcastle-Ottawa评分标准^{[ 3]},根据病例的选择、设计和分析的可比性、暴露或结局的确定及评估等三方面进行质量评估;随机对照研究采用CONSORT 2010声明进行评分,共计25项,分别从文章题目及摘要、引言、方法（主要包括试验设计、干预措施、结局指标、随机方法、盲法、统计分析等）、结果（主要包括受试者流程、基线资料、结局及危害等）、讨论（局限性、可推广性）及其他信息进行评价^{[ 4]}。

1.4 统计方法

应用Cochrane协作网提供的RevMan 5.1软件。采用Q检验明确有无异质性。经Q检验若无明显统计学差异（ P>0.10,或 P≤0.10且 I²≤50%）,选用固定效应模型进行分析;若有统计学差异（ P≤0.10且 I²>50%）,则选用随机效应模型。整合结果以 P≤0.05为差异有统计学意义。敏感性分析用于判断结果的稳定性和强度。主要包括：改变纳入标准、研究质量的高低、统计模型和效应量,观察两种模型的效应值整合结果和异质性有无变化。发表偏倚的识别常采用绘制漏斗图,漏斗图对称则说明发表偏倚得到有效控制。

2 结果

2.1 文献检索结果

按纳入标准通过浏览目录和摘要初步检索出文献75篇^{[ 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79]},其中Nakayama、Vujaskovic等^{[ 78, 79]}的研究因病例数少,根据Newcastle-Ottawa评分较低而排除。纳入的文献中有6篇^{[ 63, 83, 84, 85, 86, 87]}对放射性肺炎的发生率与使用放疗增敏剂阿米福汀的关系进行分析,均为随机对照试验,其中1篇文献有两组数据^{[ 73]}。其余68篇文献均为病例对照研究。纳入的研究均描述了纳入及排除标准,放射性肺炎的诊断标准、随访时间及失访率等内容。暴露因素包括患者自身因素（性别、年龄、慢性肺疾病、肺功能、合并糖尿病）,肿瘤部位,治疗方案（放疗前有无手术、是否行联合放化疗及使用放疗增敏剂阿米福汀）等。

2.2 资料和数据提取

对入组文献进行全文阅读,提取了以下内容：①文献一般资料（包括作者姓名、发表年份、作者单位等信息）;②研究对象资料（研究例数、是否为原发性肺癌或与其他类型肿瘤同时分析等）;③观察终点（放射性肺炎的诊断及分级、放射性肺炎发生例数等）;④各个暴露因素下放射性肺炎组与非放射性肺炎组的数值或比例;⑤对于等级资料,提取上述参数不同等级情况下两组的病例数或百分比;对于连续性资料,提取两组的例数及上述参数的mean±SD。

2.3统计学结果

2.3.1患者自身因素

2.3.1.1性别18篇文献2 178例样本纳入分析,Q检验无异质性,采用固定效应模型计算比值比（odds ratio,OR）及95%可信区间（confidence interval,CI）为0.97[0.82,1.15], P=0.73,提示差异无统计学意义。

2.3.1.2年龄10篇文献880例以≤60岁vs. >60岁分析,10篇1 396例以≤70岁vs. >70岁分析, 6篇621例分析年龄mean±SD与放射性肺炎发生率的关系。效应值合并后均无异质性,采用固定效应模型得OR及95%CI值分别为0.90[0.63,1.28]、1.13[0.84,1.52]及-0.01[-1.98,1.96], P分别为0.56、0.34及1.00,均与放射性肺炎的发生无相关性。

2.3.1.3合并慢性肺疾病13篇共1 409例进行分析,无异质性,固定效应模型得OR及95%CI值为2.18[1.59,3.00], P<0.000 01,提示合并慢性肺疾病的患者容易发生放射性肺炎;调整模型后OR及95%CI值为2.35[1.57,3.51], P<0.000 1,两种模型结果一致,结果可信,见图1和图2。

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	图1 有无慢性肺疾病与RP的效应值比较及敏感性分析图

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	图2 有无慢性肺疾病与RP的倒漏斗图

2.3.1.4放疗前肺功能放疗前1秒用力呼气量（forced expiratory volume in 1s, FEV1）≥2L vs. <2L与放射性肺炎的分析,无异质性,固定效应模型得OR及95%CI为0.27[0.11,0.65], P=0.004,提示放疗前FEV1<2L的患者发生放射性肺炎的概率较高。调整模型后,OR及95%CI分别为0.27[0.11,0.66], P=0.004,两种模型结果一致,结果可信,见图3。但倒漏斗图未完全显示,考虑存在发表偏倚,见图4。

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	图3 放疗前FEV1≥2或<2L与RP的效应值比较及敏感性分析图

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	图4 放疗前FEV1≥2或<2L与RP的倒漏斗图

2.3.1.5糖尿病3篇365例样本量对此进行分析,无异质性,OR及95%CI为2.46 [1.33, 4.58], P=0.004,表明合并糖尿病的患者易于发生放射性肺炎。调整模型后,OR及95%CI为2.46[1.32,4.60], P=0.005,两模型结果一致,敏感性较低,稳定性结果,结果可信,见图5和图6。

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	图5 有无糖尿病与RP的效应值比较及敏感性分析图

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	图6 有无糖尿病与RP的倒漏斗图

2.3.2肿瘤部位13篇2 211例、9篇1 880例及3篇381例患者分别对上肺vs. 中下肺、右肺vs. 左肺、中央型vs. 周围型进行分析,合并后均无异质性,OR及95%CI分别为0.71[0.57,0.90]、1.18[0.91,1.52]、1.33[0.76,2.35], P为0.005、0.21、0.32,提示肿瘤位于左下肺放疗后易于发生放射性肺炎。调整为随机效应模型,OR及95%CI分别为0.74[0.56,0.99]、 1.17[0.90,1.52]、 1.32[0.74,2.33], P分别为0.04、0.23、0.34,两种结果一致,敏感性较低,稳定性较高,结果可信。

2.3.3治疗因素

2.3.3.1放疗前肺部手术Q检验无异质性,OR及95%CI值为0.92[0.67,1.25], P=0.59,提示无相关性;随机效应模型得OR及95%CI值为0.86[0.53,1.41], P=0.56,两组结果一致,稳定性高,结果可信。

2.3.3.2放化疗联合分别有31篇3 572例和18篇1 760例样本量进行放化疗联合vs.单独放疗、序贯vs. 同步放化疗的分析,均无异质性,OR及95%CI分别为1.41[1.17,1.71]及0.97 [0.76,1.25], P分别为0.000 3及0.83,说明放化疗联合的患者易于发生放射性肺炎;随机效应模型下OR及95%CI分别为1.38[1.10,1.72]及1.02[0.71,1.47], P分别为0.005及0.90,两组结果差别不大,稳定性较高,结果可信,见图7~ 图10。

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	图7 放化疗联合或单独放疗与RP的效应值比较及敏感性分析图

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	图8 序贯或同步放化疗与RP的效应值比较及敏感性分析图

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	图9 放化疗联合或单独放疗与RP的倒漏斗图

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	图10 序贯或同步放化疗与RP的倒漏斗图

2.3.3.3放疗增敏剂阿米福汀7篇703例样本量进行分析,Q检验无异质性,由于纳入文献为随机对照试验,选用相对危险度（relative risk,RR）作为效应值,固定效应模型得RR及95%CI为2.38[1.79,3.16], P<0.000 01,说明该因素与放射性肺炎的发生有关;调整模型后,RR及95%CI为2.32[1.67,3.23], P<0.000 01,两种结果一致,结果可信,见图11和图12。

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	图11 单独放化疗或联合阿米福汀与RP的效应值比较及敏感性分析图

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	图12 单独放化疗或联合阿米福汀与RP的倒漏斗图

3 讨论

放射性肺炎是胸部放疗剂量的主要限制性因素,同时也是影响患者放疗后生存质量的最常见因素之一,使得最大程度提高靶区剂量且尽可能减少放射性肺炎的发生成为肺癌治疗策略必须考虑的因素,也是待解决的热点问题之一。

目前部分研究认为,临床因素方面,性别、年龄身体状况及肺功能、肿瘤及治疗因素与放射性肺炎有关。Dang 等^{[ 11]}的研究认为,男性患者放疗后容易发生放射性肺炎,但较多研究认为女性容易发生^{[ 5, 28]},考虑女性肺体积相对较小,同样的照射野更容易发生放射性肺炎。目前的研究普遍认为放化疗联合治疗^{[ 10, 11, 26, 72]}、合并慢性肺疾病^{[ 7, 16, 26]}和放疗前肺功能较差^{[ 7, 16, 28]}的患者存在化疗对肺组织的毒副作用、有效肺体积较小及低氧等引起放射性肺损伤的病理生理过程,因此容易发生放射性肺炎。对于与吸烟的关系,尚未得到统一的结论。Vogelius等^{[ 80]}的系统评价显示老年患者、肿瘤位于中下肺、存在合并症等是放射性肺炎的危险因素,而当前吸烟和有吸烟史是保护因素,考虑可能是吸烟所致的低氧和免疫抑制作用使吸烟患者的肺的耐受性增加。

本文的结果均经过异质性分析及敏感性检验,结果可信。本文还利用敏感性分析评估了发表偏倚对最后结果的可能影响。基于本项研究的结果,我们认为肺功能较好的且无慢性肺疾病和糖尿病等合并症的上肺肺癌患者,在单纯放疗的基础上加用放疗增敏剂阿米福汀,可以降低患者的放射性肺炎发生率。

The authors have declared that no competing interests exist.

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2012

1.447

0.0

2012

2.107

0.0

Wang

, Sun

, Zhu

, et al. Functional dosimetric metrics for predicting radiation-induced lung injury in non-small cell lung cancer patients treated with chemoradiotherapy[J]. Radiat Oncol, 2012, 7(1): 69.

<li>1.Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, People’s Republic China</li><li>2.Jinan Central Hospital affiliated to Shandong University, Jinan, People’s Republic China</li><li>4.Jinan Central Hospital affiliated to Shandong University, 105 Jiefang Road, Jinan, 250012, People’s Republic China</li><li>3.The First People’s Hospital of Qndao Economic and Technical Development Zone, Qingdao, People’s Republic China</li>

2010

5.118

0.0

Stang

Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrand omized studies in meta-analyses[J]. Eur J Epidemiol, 2010, 25(9): 603-605.

1.Institut für Klinische Epidemiologie, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, Magdeburger Str. 8, 06097, Halle (Saale), Germany

The quality assessment of non-randomized studies is an important component of a thorough meta-analysis of non-randomized studies. Low quality studies can lead to a distortion of the summary effect estimate. Recent guidelines for the reporting of meta-analyses of observational studies recommend the assessment of the study quality (MOOSE) [1]. In principal, three categories of quality assessments tools are available: scales, simple checklists, or checklists with a summary judgment (for details see Sanderson et al. 2007 [2]). The results of the quality assessment can be used in several ways such as forming inclusion criteria for the meta-analysis, informing a sensitivity analysis or meta-regression, weighting studies, or highlighting areas of methodological quality poorly addressed by the included studies [3]. It has been criticized that the use of summary scores involve inherent weighting of component items including items that may not be related to the validity of the study findings [2] ...

1.Institut für Klinische Epidemiologie, Medizinische Fakult?t, Martin-Luther-Universit?t Halle-Wittenberg, Magdeburger Str. 8, 06097 Halle (Saale), Germany

... 病例对照研究及队列研究使用Newcastle-Ottawa评分标准^[3],根据病例的选择、设计和分析的可比性、暴露或结局的确定及评估等三方面进行质量评估 ...

2010

0.0

... 随机对照研究采用CONSORT 2010声明进行评分,共计25项,分别从文章题目及摘要、引言、方法（主要包括试验设计、干预措施、结局指标、随机方法、盲法、统计分析等）、结果（主要包括受试者流程、基线资料、结局及危害等）、讨论（局限性、可推广性）及其他信息进行评价^[4] ...

2006

0.0

... Dang 等^[11]的研究认为,男性患者放疗后容易发生放射性肺炎,但较多研究认为女性容易发生^[5,28],考虑女性肺体积相对较小,同样的照射野更容易发生放射性肺炎 ...

2012

0.0

2010

2.107

0.0

... 目前的研究普遍认为放化疗联合治疗^{[10,11,26,72]}、合并慢性肺疾病^[7,16,26]和放疗前肺功能较差^[7,16,28]的患者存在化疗对肺组织的毒副作用、有效肺体积较小及低氧等引起放射性肺损伤的病理生理过程,因此容易发生放射性肺炎 ...

2004

4.52

0.0

2012

5.201

0.0

Mak

, Alexand er

, Asomaning

, et al. A single-nucleotide polymorphism in the MTHFR (methylene tetrahydrofolate reductase) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy[J]. Cancer, 2012, 118(14): 3654-3665.

1Harvard Radiation Oncology Program, Boston, Massachusetts 2Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts 3Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 4Division of Hematology/Oncology, Massachusetts General Hospital, Boston, Massachusetts 5Institute of Environmental Health, National Taiwan University, Taipei, Taiwan 6Department of Radiation Oncology, Massachusetts General Hospital Boston, Massachusetts *Harvard School of Public Health, 665 Huntington Avenue, Building 1, Room 1402, Boston, MA 02115

BACKGROUND:

This study examined the association between functional single-nucleotide polymorphisms in candidate genes from oxidative stress pathways and risk of radiation pneumonitis (RP) in patients treated with thoracic radiation therapy for locally advanced lung cancer.

2010

0.0

2010

0.0

Dang

, Li

, Lu

, et al. Analysis of related factors associated with radiation pneumonitis in patients with locally advanced non-small-cell lung cancer treated with three-dimensional conformal radiotherapy[J]. J Cancer Res Clin Oncol, 2010, 136(8): 1169-1178.

1.Department of Radiation Oncology, The First Affiliated Hospital of China Medical University, 110001, Shenyang, China

To investigate the correlation among DVH (lung dose–volume histogram) parameters, clinical factors, and grade ≥ 2 radiation pneumonitis (RP) in patients with locally advanced non-small-cell lung cancer (NSCLC) treated with three-dimensional conformal radiotherapy (3D-CRT), and the differences between patients treated with 3D-CRT alone or that combined with chemotherapy on RP.

2010

0.0

Zhang

, Yang

, Bi

, et al. ATM polymorphisms are associated with risk of radiation-induced pneumonitis[J]. Int J Radiat Oncol Biol Phys, 2010, 77(5): 1360-1368.

Purpose

Since the ataxia telangiectasia mutated (ATM) protein plays crucial roles in repair of double-stranded DNA breaks, control of cell cycle checkpoints, and radiosensitivity, we hypothesized that variations in this gene might be associated with radiation-induced pneumonitis (RP).

Methods and Materials

A total of 253 lung cancer patients receiving thoracic irradiation between 2004 and 2006 were included in this study. Common Terminology Criteria for Adverse Events version 3.0 was used to grade RP. Five haplotype-tagging single nucleotide polymorphisms (SNPs) in the ATM gene were genotyped using DNA from blood lymphocytes. Hazard ratios (HRs) and 95% confidence intervals (CIs) of RP for genotypes were computed by the Cox model, adjusted for clinical factors. The function of the ATM SNP associated with RP was examined by biochemical assays.

Results

During the median 22-month follow-up, 44 (17.4%) patients developed grade ≥ 2 RP. In multivariate Cox regression models adjusted for other clinical predictors, we found two ATM variants were independently associated with increased RP risk. They were an 111G > A) polymorphism (HR, 2.49; 95% CI, 1.07–5.80) and an ATM 126713G > A polymorphism (HR, 2.47; 95% CI, 1.16–5.28). Furthermore, genotype-dependent differences in ATM expression were demonstrated both in cell lines (p < 0.001) and in individual lung tissue samples (p = 0.003), which supported the results of the association study.

Conclusions

Genetic polymorphisms of ATM are significantly associated with RP risk. These variants might exert their effect through regulation of ATM expression and serve as independent biomarkers for prediction of RP in patients treated with thoracic radiotherapy.

2000

2.698

0.0

2006

0.0

2011

2.552

0.0

1998

5.201

0.0

Monson

, Stark

, Reilly

, et al. Clinical radiation pneumonitis and radiographic changes after thoracic radiation therapy for lung carcinoma[J]. Cancer, 1998, 82(5): 842-850.

1Joint Center for Radiation Therapy, Harvard Medical School, Boston, Massachusetts 2Division of Diagnostic Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 3Division of Pulmonary Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 4Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 5Division of Medical Oncology, Dana Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts †<div class="para">Division of Radiation Oncology, City of Hope National Medical Center, Duarte, California.</div> ‡<div class="para">Department of Radiology, Palo Alto VA Hospital, Palo Alto, California.</div> *Division of Radiation Oncology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010

BACKGROUND

The authors attempted to determine the incidence of and risk factors for clinical radiation pneumonitis in patients treated for lung carcinoma. They also sought to describe the corresponding posttreatment radiographic changes.

2008

2.911

0.0

2010

4.163

0.0

Roeder

, Friedrich

, Timke

, et al. Correlation of patient-related factors and dose-volume histogram parameters with the onset of radiation pneumonitis in patients with small cell lung cancer[J]. Strahlenther Onkol, 2010, 186(3): 149-156.

Purpose:

To analyze the association of patient- and treatment-related factors with the onset of radiation pneumonitis in a homogeneously treated cohort of patients suffering from small cell lung cancer (SCLC).

1.Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany 2.Clinical Cooperation Unit of Radiation Oncology, DKFZ, Heidelberg, Germany 3.Department of Pulmonary and Respiratory Care Medicine, Thoraxklinik Heidelberg, University of Heidelberg, Heidelberg, Germany 4.Department of Radiation Oncology, Helios Clinic Berlin-Buch, Berlin, Germany 5.Department of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany

2001

6.355

0.0

2006

1.727

0.0

Uno

, Isobe

, Kawakami

, et al. Dose-volume factors predicting radiation pneumonitis in patients receiving salvage radiotherapy for postlobectomy locoregional recurrent non-small-cell lung cancer[J]. Int J Clin Oncol, 2006, 11(1): 55-59.

Background

The correlation between treatment-related factors and lung toxicity has not been sufficiently evaluated in salvage radiotherapy.

1.Chiba University Graduate School of Medicine Department of Radiology 1-8-1 Inohana, Chuo-ku Chiba 260-8670 Japan 1-8-1 Inohana, Chuo-ku Chiba 260-8670 Japan 2.Chiba University, Graduate School of Medicine Department of Thoracic Surgery Chiba Japan Chiba Japan 3.Keio University School of Medicine Department of Radiology Tokyo Japan Tokyo Japan

2005

0.0

2005

6.339

0.0

2007

1.367

0.0

2009

0.0

Song

, Yu

JM.

Effect of diabetes mellitus on the development of radiation pneumonitis in patients with non-small cell lung cancer[J]. Zhonghua Zhong Liu Za Zhi, 2009, 31(1): 45-47.

目的探讨伴有糖尿病的肺癌患者在接受放射治疗后放射性肺炎的发生情况.方法 156例非小细胞肺癌(NSCLC)患者均接受三维适形放射治疗,其中伴有糖尿病者52例,无糖尿病的对照组104例,随访观察1年,比较两组患者放射性肺炎的发生情况,并分析血糖控制水平和糖尿病病史与放射性肺炎的发病相关性.结果糖尿病组和对照组患者放射性肺炎的发病率分别为40.4%和21.2%.(P<0.05),伴有糖尿病的肺癌患者放射性肺炎的发病危险是对照组患者的2.05倍(95%CI为1.17～3.58).糖尿病组和对照组患者放射性肺炎的严重程度无明显差异.血糖控制较好的NSCLC患者放射性肺炎的发病率(30.6%)低于血糖控制欠佳者(62.5%,P<0.05).糖尿病病史较长的NSCLC患者与糖尿病病史较短者比较,放射性肺炎的发病率差异无统计学意义(P0.05).结论糖尿病为NSCLC患者发生放射性肺炎的易感因素,其易感程度与血糖控制水平有关.

Abstract：

Objective The purpose of this study was to investigate whether the associated diabetes mellitus exerts a certain effect on the development of radiation pneumonitis in patients with non-small cell lung cancer. Methods 156 patients with non small cell lung cancer were treated with three-dimensional conformal radiation therapy in this study, including 52 associated with diabetes and 104 non-diabetic patients as a control group. All the patients were followed up for one year and the development of radiation pneumonitis was observed. Radiation pneumonitis was diagnosed according to the criteria of radiation therapy oncology group. The morbidities of radiation pneumonitis in the two groups were compared. The relationships between the morbidity of radiation pneumonitis and blood sugar level as well as diabetic history were analyzed by chi-square test. Results Twenty-one (40.4%) of 52 patients with diabetes had radiation pneumonitis (grade 2 or greater), while in the control group only 22 of 104 patients (21.2%) suffered from radiation pneumonitis. There was a statistically significant difference between the two groups in the morbidity of the radiation pneumonitis (P<0.05), with a relative risk value of 2.05 (95% CI, 1.17, 3.58). The rate of the radiation pneumonitis in the patients with a lower blood sugar level (<7 mmol/L) was significantly lower than that in those with a higher blood sugar level (30.6% vs. 62.5%, P<0.05). However, the rate of radiation pneumonitis in the patients with a longer diabetic history was not significantly different from that in those with a shorter diabetic history (P0.05). Conclusion Non-small cell lung cancer patients with diabetes mellitus are more vulnerable than those without to radiation pneumonitis. Therefore, diabetes mellitus is a newly discovered risk factor to radiation pneumonitis, and the blood sugar level is positively correlated with the morbidity of radiation pneumonitis.

2010

0.0

Xiao

, Ding

, Feng

, et al. Efficacy of Liangxue Jiedu Huoxue decoction in prevention of radiation pneumonitis: A rand omized controlled trial[J]. Zhong Xi Yi Jie He Xue Bao, 2010, 8(7): 624-628.

背景:放射性肺炎是胸部肿瘤放射治疗中最常见的并发症之一,严重影响患者的生存质量,甚至威胁生命.目前尚无有效的中医或西医治疗方案预防放射性肺炎的发生.目的:观察凉血解毒活血汤预防放射性肺炎的临床疗效.设计、场所、对象和干预措施:前瞻性随机对照设计.将解放军总医院放疗科确定需要进行放射治疗的肺癌患者100例,随机分为治疗组和对照组,每组各50例.对照组单纯行放疗,治疗组在进行放疗的同时口服凉血解毒活血汤.治疗过程中治疗组脱落3例,剔除1例;对照组脱落6例,剔除2例.主要结局:比较放射性肺炎发生率,并用美国肿瘤放射治疗协作组(Radiation Therapy Oncology Group,RTOG)急性放射性损伤分级标准、临床影像生理评分系统(clinical-radiographic-physiologic score system,CRP)、身体机能状态量表(Karnofsky Performance Status Scale,KPS)进行评估.结果:放射性肺炎发生率,治疗组为13.04%,对照组为33.33%,两组比较,差异有统计学意义(P＜0.05);按RTOG分级标准,治疗组放射性肺炎患者肺损伤程度明显低于对照组(P＜0.05);治疗组CRP评分显著低于对照组(P＜0.05);治疗组KPS评分显著高于对照组(P＜0.05).结论:凉血解毒活血汤可降低肺癌放疗患者的放射性肺炎发生率,减轻急性放射性肺损害程度,并可减轻患者症状,改善患者生存质量.

2003

4.52

0.0

2005

0.0

Wang

, Wang

, Feng

, et al. Factors predicting radiation toxicity in the treatment of three-dimensional conformal radiotherapy for lung cancer[J]. Zhongguo Fei Ai Za Zhi, 2005, 8(5): 454-458.

背景与目的在胸部肿瘤的放射治疗中,肺、食管等正常组织往往会受到一定剂量的照射,造成不同程度的放射损伤.本研究拟分析肺癌三维适形放射治疗中放射性食管和肺损伤的发生率及其相关因素.方法收集1999年3月至2003年9月首程行三维适形放疗的肺癌病例,总计112例,男87例,女25例,中位年龄64岁(20～87岁).其中非小细胞肺癌97例,小细胞肺癌15例.放疗中位单次剂量2 Gy,每周5次,中位总剂量60 Gy.结果 2级以上急性放射性肺损伤为7.1%(8/112);2级以上晚期放射性肺损伤为1.8%(2/112);2级急性放射性食管损伤8.9%(10/112).单因素和多因素分析均未发现与急性放射性肺损伤相关的临床因素和物理因素.单因素分析显示,疗前体重下降≥5%和行化疗或同时化放疗的病例,急性放射性食管损伤的发生率升高,统计学分析均有显著性差异,其中疗前体重下降≥5%在多因素分析中也有统计学意义(P=0.016).结论此研究未能发现与急性放射性肺损伤相关的临床因素和物理因素,但发现与急性放射性食管损伤相关的因素是疗前体重下降≥5%.

2000

0.0

2004

0.0

2010

3.73

0.0

Hildebrand t

, Komaki

, Liao

, et al. Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer[J]. PLoS One, 2010, 5(8): e12402.

1 Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America 2 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America 3 Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America 4 Hamon Center for Therapeutic Oncology Research, The University of Texas Southwestern Medical Center, Dallas, Texas, United States of America 5 Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America

Treatment of non-small cell lung cancer (NSCLC) with radiotherapy or chemoradiotherapy is often accompanied by the development of esophagitis and pneumonitis. Identifying patients who might be at increased risk for normal tissue toxicity would help in determination of the optimal radiation dose to avoid these events. We profiled 59 single nucleotide polymorphisms (SNPs) from 37 inflammation-related genes in 173 NSCLC patients with stage IIIA/IIIB (dry) disease who were treated with definitive radiation or chemoradiation. For esophagitis risk, nine SNPs were associated with a 1.5- to 4-fold increase in risk, including three PTGS2 (COX2) variants: rs20417 (HR:1.93, 95% CI:1.10–3.39), rs5275 (HR:1.58, 95% CI:1.09–2.27), and rs689470 (HR:3.38, 95% CI:1.09–10.49). Significantly increased risk of pneumonitis was observed for patients with genetic variation in the proinflammatory genes IL1A, IL8, TNF, TNFRSF1B, and MIF. In contrast, NOS3:rs1799983 displayed a protective effect with a 45% reduction in pneumonitis risk (HR:0.55, 95% CI:0.31–0.96). Pneumonitis risk was also modulated by polymorphisms in anti-inflammatory genes, including genetic variation in IL13. rs20541 and rs180925 each resulted in increased risk (HR:2.95, 95% CI:1.14–7.63 and HR:3.23, 95% CI:1.03–10.18, respectively). The cumulative effect of these SNPs on risk was dose-dependent, as evidenced by a significantly increased risk of either toxicity with an increasing number of risk genotypes (P<0.001). These results suggest that genetic variations among inflammation pathway genes may modulate the development of radiation-induced toxicity and, ultimately, help in identifying patients who are at an increased likelihood for such events.

2011

2.867

0.0

2008

0.0

2006

0.0

2012

0.0

2006

0.0

2003

0.0

2011

3.73

0.0

Yin

, Liao

, Huang

, et al. Polymorphisms of homologous recombination genes and clinical outcomes of non-small cell lung cancer patients treated with definitive radiotherapy[J]. PLoS One, 2011, 6(5): e20055.

1 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America 2 Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America 3 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

The repair of DNA double-strand breaks (DSBs) is the major mechanism to maintain genomic stability in response to irradiation. We hypothesized that genetic polymorphisms in DSB repair genes may affect clinical outcomes among non-small cell lung cancer (NSCLC) patients treated with definitive radio(chemo)therapy. We genotyped six potentially functional single nucleotide polymorphisms (SNPs) (i.e., RAD51 −135G>C/rs1801320 and −172G>T/rs1801321, XRCC2 4234G>C/rs3218384 and R188H/rs3218536 G>A, XRCC3 T241M/rs861539 and NBN E185Q/rs1805794) and estimated their associations with overall survival (OS) and radiation pneumonitis (RP) in 228 NSCLC patients. We found a predictive role of RAD51 −135G>C SNP in RP development (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.31–0.86, P = 0.010 for CG/CC vs. GG). We also found that RAD51 −135G>C and XRCC2 R188H SNPs were independent prognostic factors for overall survival (adjusted HR = 1.70, 95% CI, 1.14–2.62, P = 0.009 for CG/CC vs. GG; and adjusted HR = 1.70; 95% CI, 1.02–2.85, P = 0.043 for AG vs. GG, respectively) and that the SNP-survival association was most pronounced in the presence of RP. Our study suggests that HR genetic polymorphisms, particularly RAD51 −135G>C, may influence overall survival and radiation pneumonitis in NSCLC patients treated with definitive radio(chemo)therapy. Large studies are needed to confirm our findings.

2005

1.574

0.0

2009

1.898

0.0

2010

1.898

0.0

2001

0.0

2007

0.0

1997

0.0

1998

5.061

0.0

2005

2.147

0.0

De Petris

, Lax

, Sirzén

, et al. Role of gross tumor volume on outcome and of dose parameters on toxicity of patients undergoing chemoradiotherapy for locally advanced non-small cell lung cancer[J]. Med Oncol, 2005, 22(4): 375-381.

The aim of this retrospective study was to evaluate the prognostic role of gross tumor volume (GTV) on survival of locally advanced NSCLC patients, regardless of TNM stage, and to analyze whether GTV and other radiotherapy (RT) parameters wre important for the development of lung toxicity. Thirty-two patients with locally advanced NSCLC (stage IIIA bulky/IIIB) treated with chemoradiotherapy were retrospectively analyzed. Patients received induction chemotherapy followed by combination treatment (27 patients) or induction chemotherapy followed by RT alone (5 patients). Thoracic RT consisted in 60 Gy, with standard fractionation and was the same for all 32 patients. Dose volume histograms were collected from the 3D treatment plans and GTV, planning target volume, mean lung dose, volume of lung receiving more than 20 Gy or more than 30 Gy were analyzed. Survival was significantly longer in patients with a GTV<100 cm³ compared with patients having GTV>100 cm³ (p=0.03). In a multivariate analysis only N-status and GTV were predictors of survival with a risk ratio of 0.51 and 0.62, respectively. Ten patients (31%) developed radiation pneumonitis grade 2 or higher. None of the RT parameters examined correlated significantly with the development of lung toxicity. In locally advanced NSCLC, GTV and N-status play a prognostic role even in patients at the same clinical stage and receiving a combination of chemo- and radiotherapy. This could imply a reassessment of the current staging system in patients with non-resectable NSCLC to better identify those patients who would benefit more from the combined treatment, despite its higher toxicity.

1.Karolinska University Hospital Department of Hospital Physics 17176 Stockholm Sweden 17176 Stockholm Sweden 2.Karolinska University Hospital Dpt. of Oncology and Pathology, Radiumhemmet 17176 Stockholm Sweden 17176 Stockholm Sweden

1999

1.898

0.0

2006

2.147

0.0

Matsuno

, Satoh

, Ishikawa

, et al. Simultaneous measurements of KL-6 and SP-D in patients undergoing thoracic radiotherapy[J]. Med Oncol, 2006, 23(1): 75-82.

Purpose

Radiation pneumonitis (RP) is a serious complication in patients undergoing thoracic radiotherapy (TRT). Serum KL-6 and SP-D have been shown to increase in several kinds of interstitial pneumonia. To evaluate their clinical usefulness in detecting RP, we serially measured them in patients receiving TRT.

1.University of Tsukuba Division of Respiratory Medicine, Institute of Clinical Medicine 305-8575 Tsukuba-city, Ibaraki Japan 305-8575 Tsukuba-city, Ibaraki Japan

1999

6.355

0.0

2010

0.0

1.393

2006

0.0

2007

0.0

Mao

, Kocak

, Zhou

, et al. The impact of induction chemotherapy and the associated tumor response on subsequent radiation-related changes in lung function and tumor response[J]. Int J Radiat Oncol Biol Phys, 2007, 67(5): 1360-1369.

Purpose: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response.

Methods and Materials: As part of a prospective institutional review board–approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher’s exact test, analysis of variance, and linear or logistic regression.

Results: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p = 0.009–0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy–associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT.

Conclusions: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction.

2005

0.0

Kocak

, Yu

, Zhou

, et al. The impact of pre-radiotherapy surgery on radiation-induced lung injury[J]. Clin Oncol (R Coll Radiol), 2005, 17(4): 210-216.

Abstract

Aims

The use of postoperative radiation therapy (PORT) is predicated by an assessment of the potential benefits and risks, including radiation-induced lung injury. In this study, the risk of radiation-induced lung injury is assessed in patients who received PORT, and compared with a group of patients who received radiation without prior surgery, to determine if surgery increases the risk of radiation pneumonitis.

Materials and methods

From 1991 to 2003, 251 patients with lung cancer were enrolled into a prospective study to assess radiation-induced lung injury. All patients received three-dimensional-planned, external-beam radiotherapy. One hundred and seventy-seven patients with over 6-months follow-up were eligible. For the current analysis, 49 patients (28%) had surgical intervention before radiotherapy. The rates of Grade 2 symptomatic pneumonitis in subgroups, based on the type of pre-radiation surgery, were computed and compared using Fisher's Exact Test. To consider the confounding factor of irradiated lung volume, patient subgroups were further defined on the basis of the mean lung dose.

Results

Surgical procedures included pneumonectomy (n = 9), lobectomy (n = 16), wedge resection (n = 8) and exploration without resection (n = 16). Radiation-induced lung injury occurred in 33 out of 177 (19%) patients, including 18% of the surgical group and 19% of the non-surgical group. Additionally, no statistically significant difference was found in the rate of radiation-induced lung injury based on the extent of resection.

Conclusions

The incidence of pneumonitis is similar in the surgical and non-surgical groups. Thus, PORT may be safely given to selected patients after surgical exploration or resection.

2003

18.038

0.0

2005

0.0

Clenton

, Fisher

, Conway

, et al. The use of lung dose-volume histograms in predicting post-radiation pneumonitis after non-conventionally fractionated radiotherapy for thoracic carcinoma[J]. Clin Oncol (R Coll Radiol), 2005, 17(8): 599-603.

Abstract

Aims

To assess the use of lung dose–volume histogram (DVH) parameters (specifically V_20Gy) in the prediction of radiation pneumonitis for non-conventional fraction sizes used in the treatment of lung cancer.

Materials and methods

Patients requiring computed tomography planning for thoracic radiotherapy between January 1999 and January 2002 were identified. The patients receiving radical or high-dose palliative radiotherapy had DVH produced routinely during planning. These were retrospectively reviewed and the case notes accessed for additional pre-treatment parameters, demographics and evidence of radiation pneumonitis. The severity of the pneumonitis was then scored using Radiation Therapy Oncology Group criteria. Data were analysed using the SPSS computer program.

Results

One hundred and sixty consecutive patients were reviewed. Ninety patients received hypofractionated treatment (fraction size > 2.5 Gy) and 57 continuous hyperfractionated accelerated radiation therapy (CHART) (fraction size 1.5 Gy). Lung V_20Gy values ranged from 3% to 53%, with a median value of 24%. Only six patients reported grade 2, and 16 patients grade 3 pneumonitis. Two patients developed fatal, grade 5 pneumonitis. No correlation between pneumonitis score and V_20Gy or other possible predictive factors was found.

Conclusion

The 15% grade 2–5 pneumonitis rate we document is at the lower end of the spectrum reported in other studies. This suggests that using published data on limiting V_20Gy values to reduce the risk of radiation pneumonitis can be extrapolated to planning treatment with non-conventionally fractionated radiotherapy.

2004

4.52

0.0

2009

0.0

1995

0.0

2006

0.0

2010

0.0

2007

0.0

2007

0.0

2011

0.0

2011

0.0

... 纳入的文献中有6篇^{[63,83,84,85,86,87]}对放射性肺炎的发生率与使用放疗增敏剂阿米福汀的关系进行分析,均为随机对照试验,其中1篇文献有两组数据^[73] ...

2005

0.0

Yorke

, Jackson

, Rosenzweig

, et al. Correlation of dosimetric factors and radiation pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study[J]. Int J Radiat Oncol Biol Phys, 2005, 63(3): 672-682.

2010

0.0

Barriger

, Fakiris

, Hanna

, et al. Dose-volume analysis of radiation pneumonitis in non-small-cell lung cancer patients treated with concurrent Cisplatinum and Etoposide with or without consolidation Docetaxel[J]. Int J Radiat Oncol Biol Phys, 2010, 78(5): 1381-1386.

Purpose

To examine the rates and risk factors for radiation pneumonitis (RP) in non–small-cell lung cancer (NSCLC) patients treated with chemoradiotherapy.

Methods and Materials

We reviewed dosimetry records from Stage III NSCLC patients treated on a prospective randomized trial. Patients received concurrent cisplatinum/etoposide with radiation therapy to 59.4Gy. A total of 243 patients were enrolled; 167 did not experience progression and were randomized to observation (OB) or consolidation docetaxel (CD). Toxicity was coded based on the presence of Grade 0 to 1 vs. Grade 2 to 5 RP using the Common Toxicity Criteria and Adverse Events (CTCAE) v3.0.

Results

Median age and follow-up were 63 years and 16 months, respectively. Overall, Grade 0 to 1 and Grade 2 to 5 RP were reported in 226 patients and 17 patients (7%) respectively. Median mean lung dose (MLD), V5, V20, and V30 for evaluable patients were 18 Gy, 52%, 35%, and 29%. MLD in Grade 0 to 1 and Grade 2 to 5 patients was 1,748 c Gy and 2,013 cGy in respectively (p = 0.12). Grade 2 to 5 RP developed in 2.2% and 19% of patients with MLD < 18 Gy and MLD > 18 Gy, respectively (p = 0.015). Mean V20 was 33.7% and 37.7% for Grade 0 to 1 and Grade 2 to 5 groups, respectively (p = 0.29). Grade 2 to 5 RP developed in 4.8% and 17% of patients with V20 < 35% and V20 > 35%, respectively. The OB and CD groups had similar MLD and V20, and the RP rates were 3.6% and 14.6%, respectively (p = 0.015). Patients who developed Grade 0 to 1 and Grade 2 to 5 RP had similar mean V5, V10, V15, V20, V25, V30, age, smoking history, and tumor characteristics.

Conclusions

The overall rate of Grade 2 to 5 RP was 7% in patients treated with chemoradiotherapy. In this analysis, predictive factors for RP were MLD > 18 Gy and treatment with CD.

2009

2.107

0.0

2009

0.0

Zhang

, Yu

JM.

Application of stand ardized uptake value for FDG PET-CT in predicting radiation pneumonitis[J]. Zhonghua Zhong Liu Za Zhi, 2009, 31(8): 622-625.

目的探讨肺癌患者放射治疗前后FDG PET-CT标准摄取值(SUV)及其变化在预测放射性肺炎发生中的作用.方法 40例未经手术的非小细胞肺癌(NSCLC)患者在放射治疗前后均行PET-CT检查,分别测量出受照≤5 Gy、5.1～15 Gy、15.1～35 Gy、35.1～60 Gy以及>60 Gy肺组织放射治疗前后的平均SUV,比较发生放射性肺炎组与未发生放射性肺炎组SUV的变化情况,以及受照肺组织的SUV与未受照射肺组织SUV值之比(L/B).结果 40例患者中,有8例在治疗后发生放射性肺炎,其中2级6例,3级2例.受照剂量35.1～60 Gy肺组织的SUV与放射性肺炎的发生明显相关,当SUV≥1时,放射性肺炎的发生率为41.7%,明显高于全组放射性肺炎的发生率(20.0%;X2=3.96,P<0.05),SUV预测放射性肺炎的敏感度和特异度分别为62.5%和78.1%.L/B≥2.5时,放射性肺炎的发生率为40.7%,亦明显高于全组放射性肺炎的发生率(20.0%;X2=4.92,P<0.05).以L/B≥2.5为标准预测放射性肺炎的敏感度和特异度分别为72.7%和90.9%.SUV≥1与L/B≥2.5在预测放射性肺炎发生率之间的差异无统计学意义(X2=0.002,P>0.05).结论 SUV和L/B的大小与放射性肺炎的发生呈正相关,临床医生可根据FDG PET-CT提供的SUV和L/B来预测放射性肺炎的发生.

Abstract：

Objective To investigate the correlation of radiation pneumonitis (RP) with standardized uptake value (SUV) for fluoredeoxyglueose (FDG) positron emission tomography and computed tomography (PET-CT) in lung cancer patients treated with radiation therapy. Methods Fourty patients with unresectable non-small cell lung cancer (NSCLC) received FDG PET-CT before and after radiotherapy. The average SUV of the lung tissue irradiated with a dose of≤5 Gy, 5.1 ～ 15 Gy, 15.1 ～ 35 Gy, 35.1～ 60 Gy, > 60 Gy were measured. The correlation between SUV and RP was analyzed by comparing the SUV in the patients with RP and without. The SUV ratio of the irradiated lung tissue to that of the non-irradiated lung tissue (L/B) was also calculated. Results Of the 40 patients, 8 developed RP, including 6 eases of grade 2 and 2 cases of grade 3. The SUV of irradiated lung tissues with a dose of 35.1 ～ 60 Gy was significantly correlated with RP. When SUV ≥ 1, the RP incidence rate was 41.7% versus 20.0% in the whole group, with a statistically significant difference. (X2 = 3.96, P < 0.05 ). The sensitivity and specificity of SUV in predicting RP was 62.5% and 78.1%, respectively. When the value of L/B ≥2.5, the RP incidence rate was 40. 7% in this group versus 20. 0% in the whole group, with a statistical significance (X2 = 4.92, P < 0.05 ). If taking L/B ≥2.5 as a threshold value, the sensitivity and specificity in predicting RP was 72.7% and 90.9%, respectively. No statistically significant difference was found in predicting radiation pneumonitis between SUV≥1 and L/B≥2.5(X2 = 0.002, P>0.05). Conclusion The standardized uptake value ( SUV ) and the SUV ratio of the irradiated lung tissue to that of the non-irradiated lung tissue (L/B) for FDG PET-CT are positively correlated with radiation pneumonitis, and clinicians may use it to predict the occurrence of radiation pneumonitis.

2007

2.518

0.0

Zhao

, Wang

, Ji

, et al. Association between plasma angiotensin-converting enzyme level and radiation pneumonitis[J]. Cytokine, 2007, 37(1): 71-75.

Abstract

Angiotensin-converting enzyme (ACE) plays an important role in pulmonary fibrosis and may be involved in the development of radiation-induced lung damage. The objective of this study was to evaluate the predictive value of plasma ACE in radiation pneumonitis (RP). Patients with stage I–III lung cancer were treated with radiotherapy with or without chemotherapy. ACE levels were measured using enzyme-linked immunosorbent assay before radiotherapy (pre-RT) and when a median dose of 45 Gy (Range: 40–48 Gy) was reached (during-RT). The primary end point was ?grade 2 RP. Statistic significances were evaluated with independent T-test and chi-square. Thirty-nine patients were enrolled in this study, among which 33.3% experienced ?grade 2 RP. ACE levels, either pre-RT or during-RT, were significantly lower in the RP group than in the non-RP group (P = 0.02 and 0.03, respectively). Nine out of the 19 patients (47.4%) with pre-RT ACE levels ?462 ng/mL experienced RP, versus 3 of 19 (15.8%) patients with ACE levels >462 ng/mL (P = 0.04). This study suggested that plasma ACE as a predictive factor for radiation pneumonitis deserves further study.

2006

2.518

0.0

Evans

, Kocak

, Zhou

, et al. Does transforming growth factor-beta1 predict for radiation-induced pneumonitis in patients treated for lung cancer?[J]Cytokine, 2006, 35(3-4): 186-192.

2001

0.0

1998

0.0

2001

0.0

2003

4.327

0.0

2002

3.971

0.0

2002

3.971

0.0

2001

0.0

2004

0.0

Komaki

, Lee

, Milas

, et al. Effects of Amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small cell lung cancer: Report of a rand omized comparative trial[J]. Int J Radiat Oncol Biol Phys, 2004, 58(5): 1369-1377.

Abstract

Purpose

To determine the ability of amifostine to reduce the severity and/or incidence of the acute toxicities of concurrent chemotherapy and radiotherapy (RT) for non–small-cell lung cancer.

Methods and materials

Patients with inoperable, nonmetastatic non–small-cell lung cancer receiving concurrent chemoradiotherapy were randomized to one of two treatment groups. Arm 1 patients received thoracic RT (total dose, 69.6 Gy in 58 fractions of 1.2 Gy b.i.d. 5 d/wk), plus oral etoposide (50 mg b.i.d. 30 min before thoracic RT for 10 days, repeated on Day 29) and cisplatin (50 mg/m² i.v. on Days 1, 8, 29, and 36). Arm 2 patients received the same treatment plus amifostine (500 mg i.v. 20–30 min before any treatment the first 2 days of each week). Acute effects were assessed using the National Cancer Institute Common Toxicity Criteria.

Results

Sixty-two patients were enrolled between November 1998 and January 2001. The minimal follow-up was 24 months, and the median follow-up of living patients was 31 months. The patient and tumor characteristics were equally distributed between the patients in the two arms. The median survival time was 20 months in Arm 1 patients and 19 months in Arm 2 patients. The maximal esophageal toxicity was mild (Grade 1) in 23%, moderate (Grade 2) in 42%, and severe (Grade 3-4) in 35% of patients in Arm 1; the corresponding rates for the Arm 2 patients were 48%, 35%, and 16% (p = 0.021). Severe pneumonitis occurred in 16% of the Arm 1 and none of the Arm 2 patients (p = 0.020, chi-square test). Neutropenic fever occurred in 39% of Arm 1 and 16% of Arm 2 patients (p = 0.046, chi-square test). Mild hypotension, dysgeusia, and sneezing were significantly more frequent among the patients in Arm 2.

Conclusion

Amifostine reduced the severity and incidence of acute esophageal, pulmonary, and hematologic toxicity resulting from concurrent cisplatin-based chemotherapy and RT. Amifostine had no apparent effect on survival in these patients with unresectable non–small-cell lung cancer, suggesting that it does not have a tumor-protective effect.

1996

0.0

2000

1.895

0.0

2010

4.52

0.0

... Vogelius等^[80]的系统评价显示老年患者、肿瘤位于中下肺、存在合并症等是放射性肺炎的危险因素,而当前吸烟和有吸烟史是保护因素,考虑可能是吸烟所致的低氧和免疫抑制作用使吸烟患者的肺的耐受性增加 ...