Radiation pneumonitis: local dose versus [18F]-fluorodeoxyglucose uptake response in irradiated lung

PURPOSE: To quantify the relationship between the local radiation dose received and the posttreatment positron emission tomography/computed tomography (PET/CT) [(18)F]2-fluoro-2-deoxyglucose (FDG) uptake in the lung. METHODS AND MATERIALS: The data from 36 patients treated for esophageal cancer with thoracic radiotherapy who underwent restaging PET/CT imaging between 4 and 12 weeks after radiotherapy completion were evaluated. Their treatment planning CT was registered with the restaging PET/CT. Using histogram analysis, the voxel average FDG-PET uptake vs. radiation dose was obtained for each case. Hierarchical linear regression models for each patient were applied to study the variation in the linear trends between cases. Deviation of the dose-response curve from a linear model was tested. RESULTS: The median time between radiotherapy completion and FDG-PET imaging was 40 days (range, 26-70 days). The median of the mean standard uptake value in the lung that received 0-5 Gy was 0.63 (range, 0.36-1.27), 5-10 Gy was 0.77 (range, 0.40-1.35), 10-20 Gy was 0.80 (range, 0.40-1.72), and >20 Gy was 1.08 (range, 0.44-2.63). A hierarchical linear regression model of the radiation dose and normalized FDG uptake per case found an adequate fit with the linear model, and the addition of quadratic and logarithmic functions did not improve the fit. The 36 cases had a posterior mean of slopes range of 0.0048-0.069. CONCLUSION: The regional dose vs. radiation pneumonitis response was evaluated with FDG-PET/CT imaging. Statistical modeling found a linear relationship. The slope of this relationship varied over an order of magnitude, reflecting the range of the underlying biological response to radiation among the study population.     

Radiation pneumonitis in patients treated for malignant pulmonary lesions with hypofractionated radiation therapy

Purpose

We evaluated the relationship between the mean lung dose (MLD) and the incidence of radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT), and compared this with conventional fractionated radiation therapy (CFRT).

Materials and methods

For both SBRT (n = 128) and CFRT (n = 142) patients, RP grade ?2 was scored. Toxicity models predicting the probability of RP as a function of the MLD were fitted using maximum log likelihood analysis. The MLD was NTD (Normalized Total Dose) corrected using an α/β ratio of 3 Gy.

Results

SBRT patients were treated with 6-12 Gy per fraction with a median MLD of 6.4 Gy (range: 1.5-26.5 Gy). CFRT patients were treated with 2 Gy or 2.25 Gy per fraction, the median MLD was 13.2 Gy (range: 3.0-23.0 Gy). The crude incidence rates of RP were 10.9% and 17.6% for the SBRT and CFRT patients, respectively. A significant dose-response relationship for RP was found after SBRT, which was not significantly different from the dose-response relationship for CFRT (p = 0.18).

Conclusion

We derived a significant dose-response relationship between the risk of RP and the MLD for SBRT from the clinical data. This relation was not significantly different from the dose-response relation for CFRT, although statistical analysis was hampered by the low number of patients in the high dose range.     

肺灌注显像联合剂量体积直方图参数预测放射性肺炎的临床研究

 目的　观察接受三维适形或调强放疗的肺癌患者放疗前后肺灌注显像的变化、肺受照射的剂量体积直方图（DVH）参数等,并结合临床因素,探讨其与放射性肺炎发生的相关性。方法　18例接受三维适形或调强放疗的肺癌患者放疗前后行肺灌注显像检查,比较照射前后肺灌注显像的变化。放射性肺炎的评价按美国肿瘤放疗协作组（RTOG）急性放射性肺炎标准评定。获得的CT与单光子发射CT（SPECT）肺灌注图像融合后,将等剂量曲线投影到SPECT图像,将传统的DVH转换成f-DVH。将f-DVH曲线中每例患者的V5、V10和V20所对应的灵敏度与特异度相加,取其最大值,寻找到曲线的界值。分析放疗前后肺灌注显像变化及肺受照射的DVH与放射性肺炎发生的相关性。结果　18例患者中,33.3 %（6／18）发生了2级以上放射性肺炎。放疗前后肺灌注受损加重者2级以上放射性肺炎发生率为62.5 %（5／8）,肺灌注受损改善者发生率为10.0 %（1／10）。f-DVH图曲线中V5、V10和V20的界值分别为53 %、41 %和27 %,以V5对中重度急性放射性肺炎的预测准确度最高。放疗前后肺灌注显像的变化联合全肺DVH参数V5是放射性肺炎最强的预测因素。结论　肺癌患者放疗前后肺灌注显像能反映患侧肺灌注功能的变化。放疗前后肺灌注显像的变化联合DVH参数V5有望作为预测放射性肺炎发生的指标。     

Stereotactic body radiotherapy for lung tumors in patients with subclinical interstitial lung disease: The potential risk of extensive radiation pneumonitis

Purpose

To evaluate the toxicity and efficacy of thoracic stereotactic body radiotherapy (SBRT) in patients with subclinical interstitial lung disease (ILD).

Methods and materials

One hundred patients with 124 lung tumors were treated with SBRT at our institution according to our own protocols; patients with subclinical (untreated and oxygen-free) ILD were treated with SBRT, while those with clinical ILD (post- or under treatment) were not. The administration of 48 Gy in four fractions was used in 103 (83%) of the 124 tumors. The presence of subclinical ILD in the pre-SBRT CT findings was reviewed by two chest radiologists. The relationships between radiation pneumonitis (RP) and clinical factors were investigated.

Results

Subclinical ILD was recognized in 16 (16%) of 100 patients. Grade 2–5 RP was recognized in 13 (13%) of 100 patients. Grade 2–5 RP was observed in three (19%) of 16 patients with subclinical ILD. Subclinical ILD was not found to be a significant factor influencing Grade 2–5 RP; however, extensive RP beyond the irradiated field, including the contralateral lung, was recognized in only three patients with subclinical ILD, and the rate of extensive RP was significantly high in the patients with subclinical ILD. Grade 4 or 5 extensive RP was recognized in only two patients with subclinical ILD. Dosimetric factors of the lungs (V5, V10, V15, V20, V25, MLD) were significantly associated with Grade 2–5 RP. The three-year overall survival and local control rates of all patients were 53% and 86%, respectively. No significant differences were seen in either overall survival or local control rates between the patients with ILD and those without ILD.

Conclusions

Subclinical ILD was not found to be a significant factor for Grade 2–5 RP or clinical outcomes in the current study; however, uncommon extensive RP can occur in patients with subclinical ILD.     

The effect of contrast material on radiation dose during computed tomography pulmonary angiography

This study evaluated the impact of contrast material (CM) on radiation dose for adults undergoing computed tomography pulmonary angiography (CTPA). A previously developed physiologically based pharmacokinetic (PBPK) model and phantoms representing the average (reference) adult male and female individual were used to evaluate the iodine concentration in tissues as a function of time elapsed since the initiation of iodinated contrast medium administration. In order to estimate the radiation dose more accurately, a detailed model of pulmonary vessels was added to the phantoms. Then, the material composition of phantoms was modified to include the iodine concentration in different organs and tissues at different acquisition times after CM injection. The calculations were performed using Monte Carlo N-Particle extended code (MCNPX) version 2.6.0.The radiation dose estimates during CTPA were provided as a function of scan acquisition time after injection considering the distribution of iodinated CM within ICRP reference phantoms. It was shown that the estimated radiation dose to the lungs could be 31–40% (27–34%) larger when considering the effect of iodinated contrast administration with injection rate of 5 (3) mL/s. Moreover, the effective dose for contrast-enhanced CT (CECT) would be utmost 10–13% larger than that for non-enhanced CT (NECT). The radiation doses to the other organs in-/outside the scanned region would be decreased if the scan performed on time. In case of late scanning, absorbed dose decreases slightly for lungs (∼15–20%) whereas becomes (∼10% or more) higher than its NECT value for some organs such as heart muscle, kidneys, and spleen. To sum up, the late scanning (Δt > 5 s after the end of injection) is not recommended because of higher dose delivered to other organs than the lungs (particularly heart muscle).     

CT图像影像组学特征参数变化与放射性肺炎的相关性研究

目的 应用影像组学技术分析发生放射性肺炎(RP)的肺癌患者定位及复位CT图像特征参数变化,筛选与RP发生密切相关的指标。方法 选取放疗后经过随访发生2级及以上RP的肺癌患者31例,获取其放疗前的定位CT图像和经过40 Gy放疗后的复位CT图像,将患侧肺和健侧肺设置为提取参数的ROI,在完成正常肺组织自动分割后,使用IBEX软件进行radiomics特征参数的提取,比较这些特征参数在定位和复位CT图像中的差异。结果 (1)每个时段的单侧肺分别提取了86个有效参数指标;(2)放疗前患侧肺和健侧肺差异有统计学意义的参数指标有22个;(3)复位CT中健侧肺和患侧肺差异有统计学意义的参数有12个;(4)患侧肺放疗前后差异有统计学意义的参数有28个;(5)健侧肺放疗前后差异有统计学意义的参数有28个。结论 在发生RP的肺癌患者中,部分CT影像组学特征在定位和复位CT间差异显著,对这些指标动态变化的追踪分析具有预测RP发生的潜在优势。     

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.     

Evaluation of fluoride-labeled boronophenylalanine-PET imaging for the study of radiation effects in patients with glioblastomas

Here we demonstrate that differentiation between glioblastoma (GB) tumor progression (TP) and radiation necrosis (RN) can be achieved with fluoride-labeled boronoalanine positron emission tomography (F-BPA-PET). F-BPA-PET images were obtained from histologically verified 38 GB, 8 complete RN, and 5 RN cases with partial residual tumors. The lesion/normal (L/N) ratios for these groups were 4.2 +/- 1.4, 1.5 +/- 0.3, and 2.0 +/- 0.3, respectively. Ten GB patients underwent F-BPA-PET twice (once before and once after radiation treatment) due to enlargement of the original lesion or the development of new lesions post radiation. The L/N ratios of ten original site lesions had decreased by the second PET, and these lesions were revealed to be RN. In contrast, the L/N ratios of two lesions distant from the original site increased, and these lesions were revealed as cases of TP. Repeat PET imaging was found to be useful for evaluating changes in GB-associated tumor activity with respect to the treatment received.     

PET/CT模拟定位系统在放射治疗中的初步应用

目的:评价PET/CT模拟定位系统在放射治疗中的作用。方法:将PET/CT、三维激光定位系统和Focus3.2.1三维计划系统通过网络连接,形成放疗科专用的三维PET/CT模拟定位计划系统,分别对62例肿瘤患者进行PET/CT模拟定位和治疗计划。结果:通过改造组成的PET/CT模拟定位系统,比CT模拟定位提供更丰富和准确的图像信息,指导靶区GTV的勾画和放疗效果的评价。结论:PET/CT模拟定位系统明显提高放疗的定位精度,是未来放疗治疗定位的发展趋势。     

Radiation pneumonitis and fibrosis: mechanisms underlying its pathogenesis and implications for future research

Radiation pneumonitis and subsequent radiation pulmonary fibrosis are the two main dose-limiting factors when irradiating the thorax that can have severe implications for patients' quality of life. In this article, the current concepts about the pathogenetic mechanisms underlying radiation pneumonitis and fibrosis are presented. The clinical course of fibrosis, a postulated acute inflammatory stage, and a late fibrotic and irreversible stage are discussed. The interplay of cells and the wide variety of molecules orchestrating the immunologic response to radiation, their interactions with specific receptors, and the cascade of events they trigger are elucidated. Finally, the implications of this knowledge with respect to the therapeutic interventions are critically presented.     

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。     

A case of metachronous bilateral Breast Cancer with bilateral radiation pneumonitis after breast-conserving therapy

We report a patient with metachronous bilateral breast cancer who has twice developed radiation pneumonitis after breast-conserving therapy for each breast. The patient was a 48-year-old woman, who presented with Stage I right breast cancer. After wide excision of the right breast tumor and dissection of level I axillary lymph nodes, systemic therapy with oral 5-FU and tamoxifen was started. Subsequently, tangential irradiation with a total dose of 50 Gy in 25 fractions was given. Seven months after irradiation, she developed respiratory symptoms and radiation pneumonitis was diagnosed. The symptoms resolved with oral prednisolone. Thirty months after the right breast cancer treatment, Stage I left breast cancer was diagnosed. After wide excision of the left breast tumor and partial removal of the level I axillary lymph nodes, the same oral systemic chemo-hormonal therapy was initiated. Thereafter, tangential irradiation with a total dose of 50 Gy in 25 fractions was given. Four months after irradiation, she developed respiratory symptoms. A chest X-ray showed an area of increased density in the left lung consistent with radiation pneumonitis. The symptoms were mild and they improved spontaneously without medication. Although there is insufficient evidence to justify or withhold whole breast radiation therapy from patients with a history of contralateral breast cancer and radiation pneumonitis, it is essential to discuss the adequacy of whole breast irradiation and the possibility of alternative approaches, such as breast-conserving surgery without irradiation or partial breast irradiation for this rare condition.     

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.     

Modeling radiation pneumonitis risk with clinical, dosimetric, and spatial parameters

PURPOSE: To determine the clinical, dosimetric, and spatial parameters that correlate with radiation pneumonitis. METHODS AND MATERIALS: Patients treated with high-dose radiation for non-small-cell lung cancer with three-dimensional treatment planning were reviewed for clinical information and radiation pneumonitis (RP) events. Three-dimensional treatment plans for 219 eligible patients were recovered. Treatment plan information, including parameters defining tumor position and dose-volume parameters, was extracted from non-heterogeneity-corrected dose distributions. Correlation to RP events was assessed by Spearman's rank correlation coefficient (R). Mathematical models were generated that correlate with RP. RESULTS: Of 219 patients, 52 required treatment for RP (median interval, 142 days). Tumor location was the most highly correlated parameter on univariate analysis (R = 0.24). Multiple dose-volume parameters were correlated with RP. Models most frequently selected by bootstrap resampling included tumor position, maximum dose, and D35 (minimum dose to the 35% volume receiving the highest doses) (R = 0.28). The most frequently selected two- or three-parameter models outperformed commonly used metrics, including V20 (fractional volume of normal lung receiving >20 Gy) and mean lung dose (R = 0.18). CONCLUSIONS: Inferior tumor position was highly correlated with pneumonitis events within our population. Models that account for inferior tumor position and dosimetric information, including both high- and low-dose regions (D(35), International Commission on Radiation Units and Measurements maximum dose), risk-stratify patients more accurately than any single dosimetric or clinical parameter.