放射性肺炎临床相关预测因素的研究进展

放射性肺炎(RP)作为胸部放疗最常见的不良反应,通常发生在放疗开始后3个月内。RP不仅直接导致患者肺功能和生活质量的下降,而且限制了处方剂量的给定和放疗计划的实施,影响放疗疗效,严重时甚至导致患者死亡。目前有大量研究致力于探索预测RP的因素,本综述就其中与临床相关的预测因素进行分类阐述,包括剂量学参数、外周血细胞及细胞...     

放射性肺炎易感基因遗传多态性位点的研究进展

肺癌是现今发病率和死亡率均位居第一的恶性肿瘤^[1]。放疗是中晚期肺癌的主要治疗手段,至少60%肺癌患者需要接受放疗^[2]。而肺癌放疗的首要剂量限制因素便是RP。RP是胸部放疗常见并发症,是胸部恶性肿瘤放疗后正常肺组织受到辐射损伤而引起的无菌性炎症反应。RP主要临床表现为发热、咳嗽、胸痛、气紧和呼吸困难等,严重者常常因为呼吸窘迫和高热而死亡,还有一部分患者只有影像学改变而无临床症状。影响RP风险因素有性别、年龄、吸烟、KPS评分、病理类型、剂量学参数、肿瘤部位、合并其他疾病情况和化疗情况等^[3-4]。但是,在充分考虑以上影响因素的情况下,对相同临床分期、肺功能相似的患者给予相同剂量和相似体积的照射,RP的发展快慢与严重程度也不尽相同,有的患者在放疗期间或者放疗后3月内便出现急性RP症状,有的则出现在放疗后 1年多,呈慢性RP表现,有的则没有RP发生。大量临床观察发现RP发病具有个体差异性,提示RP发生还可能与遗传因素有关。     

血浆中TNF-α、IL-6、ACE水平及DVH参数与放射性肺炎发生的相关性研究

背景与目的:随着放射治疗的广泛应用,放射性肺炎(radiation pneumonitis,RP)也日益明显地表现出来,严重时甚至会加速患者的死亡,成为胸部肿瘤放射治疗的剂量限制因素.本研究旨在探讨血浆中TNF-α、IL-6、ACE水平及DVH参数与RP发生的相关性,评价其在预测RP中的价值.方法:123例胸部肿瘤患者按常规给予三维适形放射治疗或调强放射治疗.放射治疗前及照射45～50 Gy时采用酶联免疫吸附法(ELISA)检测血浆中TNF-α、IL-6及ACE的含量.RP的评价依照RTOG急性RP分级标准,观察终点为出现Ⅱ级以及以上RP.DVH参数包括平均肺剂量(MLD)和V10、V20、V30(Vx指照射总剂量高于xGy的肺体积占全肺总体积的百分数).结果:123例接受三维适行或调强放疗的胸部肿瘤患者中有18例患者发生了RP,其中Ⅱ级16例,Ⅲ级2例.血浆中TNF-α、IL-6、ACE水平在放疗前中位数分别为66.3 pg/mL、32.1 pg/mL、19 ng/mL,照射45～50 Gy时中位数分别为125.5 pg/mL、109.3 pg/mL、3.0 ng/mL,差异均有统计学意义(P均为0.000).放疗前后血浆中TNF-α、IL-6、ACE水平变化在未发生RP组与发生RP组间无明显差别.V10、V20、V30、MLD在未发生RP组与发生RP组间差异有统计学意义(P分别为0.011,0.029,0.009,0.006).将上述指标与RP的发生作多因素分析,未发现其中与RP发生有关的独立预测因素.结论:照射45～50 Gy后血浆中TNF-α、IL-6、ACE水平均较放疗前有明显变化,但与RP的发生无明显相关性.V10、V20、V30、MLD、是否合并化疗均与RP的发生有关.上述指标中未发现与RP有关的独立预测因素.     

转化生长因子β1预测放射性肺炎临床初探

目的:前瞻性研究转化生长因子β1(TGF-β1)与放射性肺炎(RP)的关系。方法:2004年1月～2005年12月,121例符合研究条件的食管癌及肺癌患者接受了15MVX线常规胸部照射,DT60～68Gy/30～34f/42～46d。放疗前均行胸部CT扫描,并经三维TPS生成DVH图,得出V20。放疗前、放疗中第20天以及放疗结束时行血清TGF-β1检测。根据增强CT结果结合临床症状诊断RP。结果:121例患者中有32例发生了RP。TGF-β1比率≥1者较易发生RP。结论:生物学因子TGF-β1比率对放射性肺炎的发生有一定预测作用。     

放射性肺炎临床相关因素的研究进展

放疗是肺癌综合治疗的重要组成部分.随着三维适形放疗(3DCRT)和调强放疗(IMRT)的开展,肺癌控制概率明显提高,正常组织并发症也受到越来越多关注.放射性肺炎(radiation pneumonitis,RP)是胸部肿瘤照射最常见的剂量限制性并发症,对患者肺功能和生活质量有很大影响.尽管其存在和危险I生已被认识多年,但RP的发生、发展、预测和预防方面仍存在不解之处.胸部肿瘤接受过根治性放疗者大约13%～37%发生RP[1],发生时间一般在放疗后6周至6个月,发生亚临床功能和影像学改变的比例更高.     

老年食管癌放疗致放射性肺炎相关因素分析

目的探讨老年食管癌患者三维适形放疗后放射性肺炎(RP)发生的相关因素。方法回顾性分析行三维适形放疗的90例老年食管癌患者的临床资料及放疗物理参数。结果 15例患者出现RP;RP相关因素有慢性阻塞性肺病(COPD)、再程放疗、放疗剂量、照射野数、肺V5、V10、V15、V20、V25、V30、V40等;性别、吸烟史、糖尿病、临床分期与RP的发生无关。结论 V10、V15、V20、MLD和COPD是RP的独立危险因素。     

预测放射性肺病发生的早期指标研究

肺是放射敏感性器官，对胸部肿瘤进行放射治疗时，正常肺组织因受到射线照射而产生的损伤，称为放射性肺病（radiation pneumopathy，RP）。早期的RP指放疗后1～3月出现的急性放射性肺炎（acute radiation pneumonitis，ARP），晚期的RP发生于放疗后数月至数年，临床表现为放射性肺纤维化（radiation pulmonary fibrosis，RPF）。[第一段]     

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。     

非小细胞肺癌放疗患者发生放射性肺炎的危险因素分析及血清sCD163对RP的诊断价值

目的 探讨非小细胞肺癌(NSCLC)放疗患者发生放射性肺炎(RP)的危险因素及血清可溶性清道夫受体分化抗原163(sCD163)对RP的早期诊断价值.方法 选取接受放疗的NSCLC患者130例,根据患者有无发生RP将患者分为RP组(n=38)和非RP组(n=92),分析非小细胞肺癌(NSCLC)患者放疗后放射性肺炎(R...     

放射性肺炎预测因素的相关性研究

目的前瞻性研究转化生长因子(TGF-β_1)、V_(20)及肺功能与放射性肺炎(RP)的关系,并建立放射性肺炎预测指数模型。方法121例符合研究条件的食管癌及肺癌患者接受15 MV X线常规胸部照射D_T60～68 Gy分30～34次42～46d完成。放疗前均行胸部CT扫描,并经三维TPS生成DVH图,得出V_(20)。放疗前、放疗第20天以及放疗结束时,均行血清TGF-β_1检测及肺功能(PFTs)测定。根据增强CT结合临床症状诊断RP。结果121例中32例发生了RP。Logistic回归模型分析结果显示,V_(20)和TGF-β_1比率对RP的发生有影响,V_(20)≥30%者较易发生RP,TGF-β_1比率≥1者较易发生RP。肺功能差者与肺功能正常者相比,发生RP的概率无差别(P=0.079)。预测方程为PI= 2.941×TGF-β_1比率 2.141×V_(20)-FEV_1/FVC,121例的PI中位值为2.89(1.7～6.8)。按PI值将其划分为预后好组(55例,PI<2.8)、预后中组(37例,2.8≤PI<4.5)、预后差组(29例,PI≥4.5)。在自身样本中的符合率为79.6%。结论TGF-β_1比率与放射物理因素V_(20)的有机结合对放射性肺炎发生有一定预测作用。PI方程可定量确定发生放射性肺炎的高危人群,并在决定某种放疗方案时前瞻性地预测放射性肺炎发生概率及程度。     

放射性肺炎发生的相关因素

放射性肺炎既降低了患者的生活质量,又是胸部肿瘤放疗的剂量限制因素.放射性肺炎是多因素相互作用的结果.剂量体积直方图参数可以用来评价治疗计划的优劣并有效预测放射性肺炎,但是其预测放射性肺损伤的把握度尚欠佳,因此与其他预测因子,如细胞因子联合预测放射性肺炎成为目前研究的热点.     

放射性肺损伤发生机制研究进展

放射性肺损伤(RILI)是胸部肿瘤放疗过程中常见并发症,可分为早期放射性肺炎和晚期放射性肺纤维化。目前临床上主要使用糖皮质激素控制早期炎症,而放射性肺纤维化尚无有效治疗药物,患者最终会因呼吸功能衰竭而死亡。RILI的发病机制尚未完全阐明,目前报道的相关机制包括遗传异质性、氧化应激、细胞损伤等。本文就RILI的发病机制进行文献综述。     

肺低剂量区体积预测胸中下段食管癌放射性肺炎的价值

目的 明确肺低剂量区体积在预测接受放射治疗的胸中下段食管癌患者出现急性放射性肺炎（radiation pneumonitis, RP）的价值。方法 对205例接受放射治疗并符合入组条件的胸中下段食管癌患者发生RP的情况进行分析,对患者临床资料和治疗计划等指标进行单因素及多因素分析,评价肺低剂量区体积指标的价值。结果 全组患者出现≥2级RP的患者为60例占29.27%（60/205）,其中2级48例（23.41%）,3级10例（4.88%）,4级2例（0.98%）。单因素分析结果显示食管癌病变X 线长度、GTV最大横径、GTV长度、射野数、肺MLD、GTV体积、PTV体积、肺V5、肺V10和肺V15均影响患者≥2级RP的发生。多因素分析结果显示射野数、肺MLD及肺V5为患者≥2级RP发生的独立预测影响因素。ROC曲线分析结果显示本组患者肺V5取值为51.17%为预测放射性肺炎的效能值。结论 肺低剂量区体积V5为接受放疗的胸中下段食管癌患者发生≥2级RP的重要预测因素,建议在以后制定胸中下段食管癌的放射治疗计划时应该予以重视,取值应≤51.17%。     

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.     

Radiation pneumonitis in lung cancer patients: a retrospective study of risk factors and the long-term prognosis

PURPOSE: To retrospectively evaluate the risk factors for acute radiation pneumonitis (RP) and long-term prognosis of patients with lung cancer treated by thoracic radiotherapy. METHODS AND MATERIALS: Of the 256 lung cancer patients who underwent definitive thoracic radiotherapy between June 1988 and May 1998, the 191 patients who were capable of being evaluated were divided into three groups according to the grade of RP. RP was defined as "severe," when it caused severe clinical symptoms, such as intractable cough, dyspnea at rest, and the need for oxygen or steroid therapy. The definition was made by using a modification of the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer acute radiation morbidity scoring criteria. Factors that influenced the incidence of severe RP were assessed by using the Mantel-Haenszel chi(2) test in the univariate analysis and the logistic regression test in the multivariate analysis. Survival rates was calculated by using the Kaplan-Meier method, and the p values indicating the significance of differences between the RP groups were calculated by the log-rank test. RESULTS: Of the 94 patients (49%) who experienced clinical RP in this study, the RP was mild in 69 (36%) and severe in 25 (13%) patients. The 3-year survival rates of the patients who experienced no, mild, and severe RP were 33.4%, 38.2%, and and 0%, respectively, and the survival rate of the patients who experienced severe RP was significantly poorer than the other two groups combined (p = 0.0028). The incidence of severe RP did not correlate with any of the baseline patient characteristics, radiotherapeutic factors, or chemotherapeutic variables. Two clinical risk factors were identified from medical records before radiotherapy: low PaO2 (< 80 torr) and high C-reactive protein (CRP) (> 1.0 ng/mL). Both of them were significantly related to the development of severe RP in the univariate analysis (p = 0.004 and 0.013, respectively), and low PaO2 remained a significant risk factor in the multivariate analysis (p = 0.034). Multivariate analysis also revealed the occurrence of severe RP to be the most important factor determining poor survival (p = 0.0065). There was no significant difference in survival rate according to whether the patients had been treated with corticosteroids. CONCLUSION: Mild and severe RP occurred in 69 (36%) and 25 (13%), respectively, of 191 lung cancer patients who had undergone irradiation of the chest. Only severe RP was an adverse prognostic factor. Low PaO2 (< 80 torr) before radiotherapy was a significant risk factor predictive of severe RP. The role of corticosteroids in RP could not be accurately determined.     

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.     

放疗前HRCT肺组织异常影像学征象与肺癌三维技术放疗后RP的相关性研究

目的 探讨肺癌患者放疗前HRCT肺组织异常影像学征象与RP发生的相关性。方法 回顾分析2009—2011年间行三维技术放疗的 262例肺癌患者放疗前HRCT片和临床资料。异常影像学特征包括网格影、蜂窝改变、磨玻璃影、肺气肿。临床资料包括一般情况、肿瘤因素、治疗因素。Logistic法进行单因素、多因素预测分析。结果 129例 出现网格影,其中轻度 56例 、中度 49例 、重度 24例 ; 37例 合并网格状改变; 22例 合并磨玻璃影。 154例 出现肺气肿中1级 71例 、2级 55例 、3级 20例 、4级 8例 。 58例 发生RP中 1~ 2级 39例、 3~ 5级 19例 。发生RP者中 34例 疗前HRCT表现网格影, 38例 表现肺气肿, 6例 合并蜂窝状改变, 2例 合并磨玻璃影。单因素分析显示合并慢性阻塞性肺病、FEV₁/FCV、 V₂₀、MLD、化疗、HRCT表现为肺气肿和网格影与RP发生相关。多因素分析显示同期+诱导化疗、重度网格影和3级肺气肿是≥3级RP的预测因素。结论 放疗前HRCT肺组织异常影像学征象有助于预测肺癌患者放疗后RP的发生。     

La prise en charge du cancer de la prostate à haut risque: chirurgie ou hormonoradiothérapie

Among the different treatment options recommended for high-risk prostate cancer (HRPC), radical prostatectomy (RP) is recognized along with radiotherapy, but its role is still controversial in monotherapy and difficult to evaluate in combined treatments. The results of clinical trials combining an external radiotherapy with a long-term androgen deprivation in locally advanced tumours sustain the principle of a multidisciplinary management in HRPC. Clinical and histological data associated with the MRI assessment remain essential and enhance the preoperative multidisciplinary decision, especially regarding nodal and distant metastases. An enlarged RP with an extended pelvic lymphadenectomy can be considered a viable alternative to radiotherapy and hormonal therapy. Morbidity of the procedure is similar to RP for organ-confined tumours, despite more erectile dysfunction due to non-sparing RP is observed in most of the cases. Oncological results of recent studies show 10-year and 15-year specific survival rates to be around 85% and 75% respectively, similar to those with hormonoradiotherapy. For high-risk and locally advanced prostate cancers, combined androgen deprivation and radiotherapy improved progression-free survival and overall survival. Local control is always necessary, but some patients will benefit from local aggressive treatment (surgery, postoperative radiotherapy or high dose radiotherapy), some may have a shorter adjuvant treatment, and probably some will need an intensification of general therapy: optimization of these approaches need further randomized trials.     

上下肺叶放射敏感性的差异

目的:探讨上下肺叶的放射敏感性差异,以期指导放疗计划的设计和评估,并预测放射性肺损伤的发生概率。方法:回顾性分析106例接受3D-CRT治疗的胸部肿瘤病人,对比研究全肺、左右肺、上下肺叶的受照剂量与放射性肺损伤（radiation pulmonary injury,RP）发生的关系,用SPSS 17.0进行分析。结果:在RP-、RP+组中全肺、左右肺的受照剂量均无统计学差异（P>0.05）。上下肺叶的受照剂量存在统计学差异（P<0.05）,且在RP-组和RP+组,上肺的受照剂量均较下肺高;HR=1.69。结论:下肺的放射敏感性比上肺高,在放疗计划的设计和评估中应考虑该因素的影响。