肺癌患者急性放射性肺损伤发生的相关因素分析

[目的]分析肺癌患者放射治疗后急性放射性肺损伤发生的影响因素。[方法]选取171例肺癌放射治疗的患者,采用Logistic回归分析研究性别、年龄、是否化疗、放疗剂量、V5、V20、平均肺剂量(MLD)等因素与患者3级及以上急性放射性肺损伤发生率的相关性。[结果]171例肺癌放射治疗的患者中,发生3级及以上急性放射性肺损伤50例(29.3%)。单因素分析发现,吸烟、放疗前化疗周期数多、同期放化疗、V5>40%、V20>25%、V20>28%、MLD>10Gy、MLD>13Gy均可导致肺癌患者3级及以上放射性肺损伤发生率的升高。多因素分析显示,吸烟、放疗前化疗周期数多、V20>28%、MLD>13Gy与3级及以上放射性肺损伤发生率有关。[结论]在肺癌放疗计划设计中,应针对中国肺癌患者的特点,设定适合的物理参数;此外,还需考虑患者的吸烟史、化疗史等个体化因素,尽可能降低急性放射性肺损伤的发生率。     

弥漫性恶性胸膜间皮瘤三维适形放疗的近期疗效及其与改良的半胸照射放疗技术比较的研究

ObjectiveTo observe the effects of the new technique of flexible 3D-conformal radiotherapy with combination of photon and electron (3DCRT) in the treatment of the patients with diffuse malignant pleural mesothelioma (MPM),and carry out the comparative study between flexible 3DCRT and hemithoracic conventional radiotherapy (CRT).MethodsFrom January 2004 to October 2007,8 patients with MPM were treated with flexible 3DCRT.5 patients had received cycles of chemotherapy before radiation.New technique of flexible 3DCRT with combination of photon and electron was used in our study,and DT 32.2-64 Gy with conventional split were delivered.CRT technique was mimicked to compare with 3DCRT technique to predict the possibility of lung damage in two methods.ResultsOne patient reached CR and other 7 patients got PR after radiation.Two patients died during the follow-up.The median survival time (MST) was 15.4 months and it was 18.8 months for sequential chemotherapy and radiotherapy group and 9.7 months for radiotherapy alone group.The V20,V30,and ipsilateral and centralateral median lung dosage (MLD) were 20.5%,15.6%,18.8 Gy and 2.2 Gy respectively when the flexible 3DCRT technique was used,whereas they were 36.8%,27.9%,31.1 Gy and 1.2 Gy respectively when the CRT technique was used.They were statistically different for the lung V20,V30 and ipsilateral MLD between the two techniques (P＜0.01),whereas there was no different for the contralateral MLD (P＝0.08).All patients received radiation were found to have lung fibrosis and classified as grades 1-2 radiation pneumonitis.The quality of life was increased from score 2.83 to 3.76 and it was significantly different (P＜0.01).ConclusionMPM is moderately sensitive to radiation.The flexible 3DCRT technique is feasible in the treatment of MPM and lung damage is reduced apparently comparing with the CRT technique.The quality of life of patients with MPM is improved after irradiation.     

三维适形放疗与改良半胸照射放疗治疗弥漫性恶性胸膜间皮瘤的比较研究

目的：弥漫性恶性胸膜间皮瘤治疗以手术和化疗为主,放疗常规采用半胸照射的技术,因肺损伤较大,使得放疗在弥漫性恶性胸膜间皮瘤治疗中的价值不明确。我们采用X射线三维适形放疗（3DCRT）加电子线野灵活布野的模式治疗8例弥漫性恶性胸膜间皮瘤,观察其近期疗效和放射损伤,并模拟改良的常规半胸照射放疗的方法,比较两种技术的肺损伤大小。方法：自2004年1月～2007年11月,我院收治的8例弥漫性恶性胸膜间皮瘤,其中5例为多程化疗失败者,3例为单纯放疗。化疗方案为GP、NP、TP和培美曲塞＋卡铂,放疗采用X射线三维适形放疗和电子线野灵活布野的治疗模式,按常规分割的方式给予总量32．2～64．0Gy照射。同时模拟常规半胸照射放疗的技术,采用TPS系统模拟并计算肺的V20、V30和平均肺受量（MLD）,与三维适形放疗和电子线野灵活布野的治疗模式相比较。结果：8例患者放疗后,1例患者达CR,其余患者均达PR。随访至2008年2月,2例患者死亡,其余6例均存活,平均生存时间为15．4个月。采用化疗＋放疗者平均生存时间为18．8个月,单纯放疗组为9．7个月。采用三维适形放疗加电子线野灵活布野的治疗模式8例患者的平均V20为20．5％,V30为15．6％,患侧肺MLD为18．8Gy,健侧肺MLD2．2Gy。模拟常规半胸照射放疗技术8例患者的平均V20为36．8％,V30为27．9％,患侧肺MLD为31．1Gy,健侧肺MLD1．2Gy。两种技术的肺V20、V30和患侧肺MLD均存在差异,显示三维适形放疗加电子线野灵活布野的治疗模式可能有降低正常肺照射剂量的趋势;健侧肺MLD两者无明显差异。采用三维适形放疗加电子线野灵活布野治疗模式的8例患者均出现1～2度放射性肺炎。根据治疗前和治疗后生活质量评估显示治疗后的生活质量由治疗前的平均2．83上升为3．76,生活质量有所     

Partial irradiation of the lung

Many factors like fractionation, overall treatment time, and patient specific aspects are important when studying and quantifying the effects of partial lung irradiation. The local reactions of lung tissue to irradiation are described with regard to the dose-volume effect. Different models that are used to predict the incidence of radiation pneumonitis and the influence of irradiation on the overall lung function are discussed. The easy-to-calculate mean lung dose (MLD) and the volume irradiated to 20 Gy (V20) can both be used to predict the incidence of radiation pneumonitis. These parameters represent 2 extremes in underlying local dose-effect relations for radiation pneumonitis. However, clinically applied treatment plans show a high correlation between the V20 and the MLD, so that the decision for the "best" underlying local dose-effect relation should be based on the analysis of additional patient data. Dose-escalation studies and multi-center co-operation will create more possibilities to investigate all confounding factors concerning lung irradiation.     

Correlation of dosimetric factors and radiation pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study

PURPOSE: To determine dosimetric factors for lung, lung subregions, and heart that correlate with radiation pneumonitis (Radiation Therapy Oncology Group Grade 3 or more) in the 78 evaluable patients from a Phase I dose escalation study (1991-2003) of three-dimensional conformal radiation therapy (3D-CRT) of non-small-cell lung cancer. METHODS AND MATERIALS: There were 10 > or = Grade 3 pneumonitis cases within 6 months after treatment. Dose-volume factors analyzed for univariate correlation with > or = Grade 3 pneumonitis were mean dose (MD), effective uniform dose (d(eff)), normal tissue complication probability (NTCP), parallel model f(dam) and V(D) for 5 < or = D < or = 60 Gy for whole, ipsilateral, contralateral, upper and lower halves of the lungs and heart D05, and mean and maximum doses. RESULTS: The most significant variables (0.005 < p < 0.006) were ipsilateral lung V(D) for D < 20 Gy. Also significant (p < 0.05) for ipsilateral lung were V(D) for D < 50 Gy, MD, f(dam) and d(eff); for total lung V(D) (D < 50 Gy), MD, f(dam), d(eff) and NTCP; for lower lung V(D) (D < 60 Gy), MD, f(dam) and d(eff). All variables for upper and contralateral lung were insignificant, as were heart variables. CONCLUSIONS: Previously reported correlations between severe pneumonitis and whole lung V13 and with other dose-volume factors of total lung and lower lung are confirmed. The most significant correlations were for (V05-V13) in ipsilateral lung.     

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.     

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.     

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.     

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.     

非小细胞肺癌全肺切除术后胸部放疗致肺损伤的剂量学分析

目的:确定全肺切除术后胸部放疗引起放射性肺炎的预测参数,并设立参考阈值。方法:2007年4月-2010年10月前瞻性、连续纳入44例全肺切除术后的非小细胞肺癌患者。所有患者术后均接受胸部放疗(三维适形放疗或调强放疗)。记录肺平均剂量(mean lung dose,MLD)以及接受5Gy及以上剂量照射的肺体积占总肺体积的百分比V5以及V10、V15、V20和V30。应用受试者工作特征曲线评估这些参数与放射性肺炎之间的关系,找出预测能力较强的参数并确定安全阈值。结果:所有44例患者中,发生2级以上放射性肺炎的有13例(29.5%),其中发生3级的4例,无患者发生4和5级放射性肺炎。所有的放射性肺炎均发生在放疗后9个月内,其中84.6%(11/13)的放射性肺炎发生在放疗后6个月内,中位时间为放疗后2个月。受试者工作特征(receiver operating characteristic,ROC)曲线下面积最大的3个参数分别为V5(0.824)、MLD(0.806)和V10(0.801),参考阈值分别为21.5%、450cGy和8.5%。4例发生3级放射性肺炎的患者,MLD>800(804～887)cGy,V5>28%(28%～42%),V10>20%(20%～36%)。结论:全肺切除术后行胸部放射治疗是安全而可行的,为避免发生2级以上的放射性肺炎,建议余肺剂量限定于V5<21.5%(敏感度为78.6%、特异度为84.6%),MLD<450cGy(敏感度为79.6%、特异度为65.4%),V10<8.5%(敏感度为85.7%、特异度为61.5%)。为避免发生3级以上的放射性肺炎,建议余肺MLD<800cGy。     

Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma

PURPOSE: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women's Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy. METHODS AND MATERIALS: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m(2)). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patients received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test. RESULTS: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 5-57 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.3-22.3%), 15.2 Gy (range, 13.3-17 Gy), and 98.6% (range, 81-100%), respectively, as compared with 10.9% (range, 5.5-24.7%) (p = 0.08), 12.9 Gy (range, 8.7-16.9 Gy) (p = 0.07), and 90% (range, 66-98.3%) (p = 0.20), respectively, for the patients who did not develop pneumonitis. CONCLUSIONS: Intensity-modulated RT treatment for mesothelioma after EPP and adjuvant chemotherapy resulted in a high rate of fatal pneumonitis when standard dose parameters were used. We therefore recommend caution in the utilization of this technique. Our data suggest that with IMRT, metrics such as V5 and MLD should be considered in addition to V20 to determine tolerance levels in future patients.     

Feasibility of using intensity-modulated radiotherapy to improve lung sparing in treatment planning for distal esophageal cancer.

BACKGROUND AND PURPOSE: To evaluate the feasibility whether intensity-modulated radiotherapy (IMRT) can be used to reduce doses to normal lung than three-dimensional conformal radiotherapy (3 DCRT) in treating distal esophageal malignancies. PATIENTS AND METHODS: Ten patient cases with cancer of the distal esophagus were selected for a retrospective treatment-planning study. IMRT plans using four, seven, and nine beams (4B, 7B, and 9B) were developed for each patient and compared with the 3 DCRT plan used clinically. IMRT and 3 DCRT plans were evaluated with respect to PTV coverage and dose-volumes to irradiated normal structures, with statistical comparison made between the two types of plans using the Wilcoxon matched-pair signed-rank test. RESULTS: IMRT plans (4B, 7B, 9B) reduced total lung volume treated above 10 Gy (V(10)), 20 Gy (V(20)), mean lung dose (MLD), biological effective volume (V(eff)), and lung integral dose (P<0.05). The median absolute improvement with IMRT over 3DCRT was approximately 10% for V(10), 5% for V(20), and 2.5 Gy for MLD. IMRT improved the PTV heterogeneity (P<0.05), yet conformity was better with 7B-9B IMRT plans. No clinically meaningful differences were observed with respect to the irradiated volumes of spinal cord, heart, liver, or total body integral doses. CONCLUSIONS: Dose-volume of exposed normal lung can be reduced with IMRT, though clinical investigations are warranted to assess IMRT treatment outcome of esophagus cancers.     

肺癌同期放化治疗中放射性肺损伤的相关因素分析

 目的 观察三维适形放疗联合同期化疗治疗局部晚期非小细胞肺癌中放射性肺损伤情况,对其相关因 素进行分析,寻找合理的预测性 指标。 方法 47例符合入组条件的非小细胞肺癌患者接受三维适形放疗及同期化疗。处方剂量为60Gy常规 放疗,同期化疗方案为NP方案,对三维适形治疗计划及临床资料进行单因素、多因素分析,评 价肺损伤情况。 结果 （1）完全缓解3例, 部分缓解42例,总有效率为95.74%,1年生存率75.78%。全组发生急性放 射性肺炎0级2例,1级20 例,2级17例,3级8例,无4级放射性肺炎发生。（2）与严重放射性肺炎发生呈正相关的剂量 学因素为MLD、肺NTCP,肺V5、 V15、V20。临床资料中仅发现肿瘤GTV与严重放射性肺炎发生相关;多因素分析显示全肺平均 剂量为放射性肺炎的独立影 响因素。 结论 剂量学因素（MLD、肺NTCP,肺V5、V15、V20）可以较好地预测严重放射性肺炎的发生,全肺 平均剂量是放射性肺炎发生的独立影响因素。     

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。     

非小细胞肺癌吉西他滨诱导化疗+放疗后放射性肺炎危险因素及剂量学分析

目的 对非小细胞肺癌(NSCLC)吉西他滨化疗后急性放射性肺炎(ARP)的发生情况进行总结,阐明吉西他滨诱导化疗后发生急性放射性肺炎的高危因素及剂量学限制。方法 回顾性分析2010-2017年间浙江省肿瘤医院放疗科收治的接受吉西他滨化疗+胸部放疗的NSCLC患者191例,收集患者的基本信息、放化疗情况以及ARP情况。Logistic法单因素和多因素分析影响ARP发生的因素。结果 共49例患者发生≥2级ARP,占25.7%。单因素分析显示吉西他滨累积剂量≥9.0g发生ARP概率是<9.0g的3.45倍(P=0.015),放疗剂量≥50Gy与ARP发生有关(P=0.008),放化疗间隔时间在10周内ARP发生风险增加7.69倍(P=0.047);双肺V5Gy、V20Gy、V30Gy和平均肺剂量(MLD)均能有效预测ARP发生(P≤0.001)。多因素分析仅有放疗剂量(P=0.044)和V5Gy(P=0.02)是ARP发生的预测因素。结论 对于接受吉西他滨化疗的NSCLC患者来说,吉西他滨累积剂量、化放疗间隔时间以及放疗剂量均与ARP的发生有关,同时应当限制双肺V5Gy、V20Gy、V30Gy和MLD,以减少ARP的发生。     

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.     

非小细胞肺癌三维适形放疗剂量递增的临床研究

目的通过临床剂量递增获得非小细胞肺癌（NSCLC）三维适形放射治疗的最大耐受剂量并观察其疗效。方法对84例Ⅰ～Ⅲ期NSCLC采用三维适形放射治疗（3D-CRT）,不进行区域淋巴结预防性照射。在CTV照射患者60Gy（2Gy/次,1次/天,5天/周）后,开始对GTV进行剂量递增。2～4Gy/次,递增次数为3～11次。根据肺V20和将患者分为V20〈25%组和V2025%～36%组,两组患者再根据总剂量分剂量亚组,观察放射性损伤发生率和疗效。以≥15%的患者出现3级以上急性放射性肺损伤（RTOG）为限制剂量递增标准。结果全组84例。V20〈25%组45例,剂量亚组分别为70Gy、74Gy、78Gy、82Gy。3级放射性肺炎发生率为4.4%（2/45）。V2025%～36%组39例,剂量亚组分别为66Gy、70Gy、74Gy、78Gy。3级放射性肺炎发生率为5.1%（2/39）。全组中位生存时间14个月,1、2年总生存率分别为69.5%、52.8%,1、2年局部控制率分别为79.7%、53.6%。随着剂量增加,1、2年生存率和局部控制率有所增高,但统计学检验均无统计学差异（P〉0.05）。结论采用3DCRT治疗NSCLC时,提高局部放射剂量应考虑正常肺组织所受照射的剂量和体积。当V20〈25%时,可以安全地递增到82Gy,其放射性损伤可以接受;当V20为25%～36%时,可以递增到76Gy。但当V20〉30%时,增加到更高的放射剂量应谨慎,而提高局部剂量对生存率和局部控制率的意义仍有待进一步研究。     

调强适形放疗致老年食管癌放射性肺损伤的相关因素分析

目的：分析接受调强适形放疗老年食管癌患者中发生放射性肺损伤的相关因素。方法：回顾分析接受调强适形放疗的86例老年食管癌患者的临床资料,包括患者年龄、性别、卡氏评分、T 分期、吸烟史、基础肺疾病、病变部位、肺平均剂量 MLD、双肺 V5、V10、V20及 V30等因素。结果：在86例老年食管癌患者中,有17例发生放射性肺损伤。单因素分析显示,放射性肺损伤与高龄、卡氏评分、基础肺疾病、肺平均剂量 MLD、双肺V5、V10、V20及 V30因素有相关性。结论：老年食管癌患者进行调强放疗时,应充分考虑高龄、卡氏评分、基础肺疾病、肺平均剂量 MLD、双肺 V5、V10、V20及 V30因素,预测和减少发生放射性肺损伤的风险。     

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.     

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.