18F-FDG PET/CT在非小细胞肺癌放射治疗中的应用及相关分析
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摘要
目的：淋巴结分期是非小细胞肺癌(non-small-cell lung cancer, NSCLC)的重要预后指标,也是最重要的治疗指导因素。本研究旨在评估PET联合CT(PET-CT)诊断的临床Ⅰ期(T1-2N0)NSCLC的淋巴结阴性预测值(negative predictive value, NPV)并探究与该期病变隐匿淋巴结转移相关的风险因素。
方法：从MEDLINE数据库中收集有关Ⅰ期NSCLC采用PET-CT进行淋巴结分期的研究。根据STARD (The initiative of standards for reporting of diagnostic accuracy)标准来筛选高质量的研究进入荟萃分析。以纵隔镜或者开胸手术获得病理学证实作为淋巴结受累的金标准来评估PET-CT分期的准确性,采用Stata软件进行荟萃分析。
结果：包含共1122名NSCLC病人的10项研究纳入了荟萃分析。T1和T2期NSCLC的纵隔淋巴结NPV分别为0.94和0.89。合并T1期和T2期NSCLC,纵隔淋巴结的NPV为0.93,总体淋巴结的NPV为0.87。病理类型为腺癌(风险比RR=2.72)以及原发灶具有18F-FDG高代谢的NSCLC具有更高的隐匿性淋巴结转移风险。
结论：尽管PET-CT诊断的临床T1-2N0期NSCLC具有一定几率的隐匿淋巴结转移率,但T1NO患者的纵隔NPV相对较低,提示该亚群NSCLC患者也许不必要进行常规的有创纵隔分期检查。
目的：本研究旨在评估未接受任何治疗的非小细胞肺癌(non-small cell lung cancer, NSCLC):1)体积和FDG摄取的自然倍增时间(doubling time, DT);2)治疗前疾病进展情况；3)自然病程及治疗等待时间(time to treatment, TTT)对预后的影响。
方法：在治疗开始前具有至少2次PET/CT扫描的不可手术的Ⅰ-Ⅲ期NSCLC患者纳入本研究。基于PET/CT图像勾画代谢肿瘤体积(PET-MTV)和基于CT勾画的大体肿瘤体积(CT-GTV)。记录PET-MTV内经纵隔血池标化后的最大和平均代谢活性(NSUVmax及NSUVmean)。疗前肿瘤进展定义为PET/CT上发现的任何新发病灶或者基于AJCC第七版TNM分期的升高。采用生存分析方法探究治疗等待时间对总生存时间(OS)及无进展生存时间(PFS)的影响。
结果：34例NSCLC纳入分析,两次疗前PET/CT的中位间隔时间(ISI)和TTT分别为43天和48天。在此间隔内,肿瘤体积显著增大但肿瘤的FDG摄取／代谢活性则相对稳定。基于指数模型,估算的PET-MTV、CT-GTV、NSUVmean及NSUVmax的倍增时间分别为124、139、597及333天。20.6%的病人在PET/CT诊断NSCLC至治疗开始前发生肿瘤进展,且进展风险随着等待时间的延长而增加(OR=1.027,P=0.02)。肿瘤的DT及TTT对OS及PFS无显著影响。
结论：未治疗的NSCLC体积增长迅速,但代谢活性则相对稳定。基于PET的代谢体积和基于CT的大体肿瘤体积倍增时间无差别。治疗前疾病进展风险随治疗等待时间的延长而升高。肿瘤倍增时间和治疗等待时间可能不影响预后。
目的：本研究基于18F FDG PET/CT,应用多种代谢反应评估系统对非小细胞肺癌(non-small cell lung cancer, NSCLC)治疗后的代谢反应进行分别评估,旨在分析：1)比较不同FDG摄取活性测量方法之间的一致性和差异性；2)各种评估系统对治疗后代谢反应评估的一致性和差异性；3)各系统评估的分类代谢反应对治疗后生存的预测价值；4)探索作为连续变量的FDG代谢下降百分比对预后的价值并提出能够区分不同预后人群的最佳界点。
方法：本研究为一系列基于PET/CT的前瞻性研究的二次分析。入组的NSCLC病人在放射治疗开始前2周内、疗中(约40Gy)以及治疗后复查均进行18F FDG PET/CT检查,并通过与疗前基线代谢水平进行比较,应用如下方法进行疗中和疗末代谢反应的评价：1)视觉定性评估方法；2)基于肿瘤SUV变化百分比的半定量评估方法,包括基于肿瘤最大SUV绝对值(ASUV),经纵隔血池(MBP)标化的相对最大SUV (NSUV-A)以及经肝脏标化的相对最大SUV(NSUV-L)的三种计算方法。应用Kappa系数比较各分类评估系统之间的一致性；应用生存分析方法评价各系统对总生存时间(overall survival, OS)的影响。
结果：44例病人纳入分析(36男性vs.8女性,年龄70±10岁)。疗后PET/CT扫描距离放疗结束的间隔为45-176天,中位93天。疗前、中、后进行的PET/CT扫描中,肝脏的平均SUV都显著高于MBP的平均SUV(P<0.001)；但三次扫描中肝脏和MBP的SUV都没有发生显著动态变化。由ASUV、NSUV-A和NSUV-L衍生的疗中和疗后肿瘤代谢变化百分比高度相关,组内相关系数(ICC)分别为0.919和0.943；以相同界值点转化的三套治疗反应分类之间也具有较好一致性(Kappa系数0.535-1.000)。视觉评估分类与基于NSUV-A半定量标准评估的治疗分类之间具有较差的一致性(Kappa系数0.393)。不论采用何种评估标准,分类变量形式的疗后肿瘤代谢反应都与生存时间显著相关(P<0.001),其中两种标准都认可的CMR病人具有尤其明显的生存优势。作为连续变量,疗后肿瘤SUV下降百分比与预后显著相关(HR=0.213)。在现有半定量评估标准判断的PMR(SUV下降≥30%)人群中,肿瘤SUV下降≥70%亚组具有更优的预后(P<0.001)。
结论：在接受根治性放化疗的NSCLC中,基于肿瘤绝对SUV或者经内参器官标化的相对SUV进行半定量评估的代谢反应结果具有较好的一致性,但与经视觉定性评估的代谢反应之间的一致性较差,主要分歧在于对CMR人群的判定。不论采用何种评估标准,分类变量形式的代谢反应都与生存时间显著相关,而联合定性和半定量方法进行的治疗反应分组能够更好地区分具有不同预后的人群。作为连续变量,SUV每下降1%都能够带来生存获益。在现有分类标准评定的PMR人群中,肿瘤SUV下降≥70%的亚组具有相对更佳的预后。
Purpose:Nodal staging of non-small-cell lung cancer (NSCLC) is crucial in evaluation of prognosis and determination of therapeutic strategy. This study aimed to determine the negative predictive value (NPV) of combined positron emission tomography and computed tomography (PET-CT) in patients with stage I (T1-2N0) NSCLC and to investigate the possible risk factors for occult nodal disease.
Methods:Studies investigating the performance of PET in conjunction with CT in the nodal staging of stage I NSCLC were identified in the MEDLINE database. The initiative of standards for reporting of diagnostic accuracy (STARD) was used to ensure study quality. Pathologic assessments through mediastinoscopy or thoracotomy were required as the reference standard for evaluation of PET-CT accuracy. Stata-based meta-analysis was applied to calculate the individual and pooled NPVs.
Results:Ten studies with a total of1122patients with stage Ⅰ(T1-2N0) NSCLC were eligible for analysis. The NPVs of combined PET and CT for mediastinal metastases were0.94in T1disease and0.89in T2disease. Including both T1disease and T2disease, the NPVs were0.93for mediastinal metastases and0.87for overall nodal metastases. Adenocarcinoma histology type (risk ratio [RR],2.72) and high fluorine-18(18F) fluorodeoxyglucose (FDG) uptake in the primary lesion were associated with greater risk of occult nodal metastases.
Conclusions:Although overall occult nodal metastases in clinical stage T1-2N0NSCLC is not infrequent, combined PET and CT provide a favorable NPV for mediastinal metastases in T1N0NSCLC, suggesting a low yield from routine invasive staging procedures for this subgroup of patients.
Purpose:The aims of this study were to:1) estimate the volumetric and metabolic growth rate of non-small cell lung cancer (NSCLC),2) evaluate disease progression prior to treatment, and3) explore the effects of tumor growth rate and time to treatment (TTT) on survival outcome.
Methods:Patients with inoperable Stage Ⅰ-Ⅲ NSCLC with serial pre-treatment PET/CT scans were eligible for this study. PET-derived metabolic tumor volumes (PET-MTV) and CT-derived gross tumor volumes (CT-GTV) were contoured using PET/CT information. Normalized standardized uptake values (NSUV) in tumors including the NSUVmean and NSUVmax were measured. Tumor growth rates expressed as doubling time (DT) were estimated using an exponential model. Pre-treatment disease progression was defined as the development of any new site of disease on PET/CT and change in TNM Stage (AJCC7th Ed.) was recorded. Patient-outcome data was analyzed with respect to overall and progression free survival.
Results:Thirty-four patients with a median inter-scan interval (ISI) of43days and TTT of48days were analyzed. Tumor volumes showed remarkable inter-scan growth while NSUV did not increase significantly. The DT for PET-MTV, CT-GTV, NSUVmean and NSUVmax were124,139,597, and333days, respectively. Pre-treatment disease progression occurred in20.6%patients with longer ISI being a significant risk factor (OR=1.027,p=0.02). The optimal threshold ISI to predict progression was58days (4.8%vs.46.2%, p=0.007). Neither tumor growth rates nor TTT were significantly correlated to overall survival or progression free survival.
Conclusions:NSCLC displays rapid tumor volume growth whereas tumor metabolic activity is relatively stable over the same time period. Longer delays before initiation of treatment are associated with higher risk of pre-treatment disease progression.
Purpose:Based on18F FDG PET-CT in patients with NSCLC, this study aimed to:1) compare multiple methods in quantifying post-treatment FDG uptake reduction in NSCLC;2) compare qualitative and semi-quantitative assessment of categorical metabolic response;3) evaluate the prognostic value of categorical metabolic response and4) investigate the relationship between numerical post-treatment change of metabolic activity and overall survival (OS) and explore an optimal cutoff to distinguish better responders.
Methods:This is a secondary analysis of a series of prospective studies. Enrolled patients with NSCLC underwent18F-fluorodeoxyglucose PET/CT imaging within2weeks prior to, midway through, and following radiation treatment (RT). Metabolic therapeutic response was assessed using following methods;1) visual assessment,2) semi-quantitative assessment based on FDG uptake reduction using three types of calculation including absolute maximum SUV (ASUV), mediastinum blood pool (MBP) normalized maximum SUV (NSUV-A) and liver normalized maximum SUV (NSUV-L). Kappa coefficient was used to evaluate the agreement between various categorical variables and survival analyses were adopted to analyze the effect of multiple response criteria on overall survival (OS).
Results:Forty-four patients (36M:8F, median age70±10) were eligible for present analysis. The interval between end of RT and post-RT PET/CT scan ranged from45to176days, with a median of93days. Mean SUV of liver was significantly higher than that of MBP at all time points of studies (P<0.001). Neither MBP nor liver had significant metabolic change over time. Reduction percentage of ASUV, NSUV-A and NSUV-L were highly correlated with each other, resulting in the during-and post-treatment intraclass coefficients of0.919and0.943, respectively. There was a moderate agreement between ASUV and NSUV derived response distribution (Kappa coefficient=0.535) and a dramatic concordance between categorical response determined by NSUV-A and NSUV-L (Kappa coefficient=1.0), whereas a poor agreement was observed between visual and semi-quantitative responses (Kappa coefficient=0.393). Categorical responses were significantly correlated with OS independent of employed response assessment criteria (P<0.001) and those with complete metabolic response (CMR) obtained the longest OS. As continuous variable, reduction percentage of NSUV-A showed pronounced association with OS (hazard ratio, HR=0.213). Seventy percent of NSUV-A reduction was identified as another optimal cutoff to distinguish patients with most significant difference in OS (P<0.001)
Conclusions:For NSCLC patients acquiring radical chemoradiaotherapy, semi-quantitative metabolic therapeutic response distributions using different interpretation criteria show good correlation between each other, whereas have great discrepancy with that based on visual assessment, most often in the CMR identification. Current categorical responses demonstrate significant association with overall survival and the combination of visual and semi-quantitative assessment can further improve the predictability of long-term survival. As continuous variable, more numerical reduction percentage is correlated with prolonged overall survival. Seventy percent of metabolic reduction may be another optimal threshold to distinguish responders from non-responders.
方法：从MEDLINE数据库中收集有关Ⅰ期NSCLC采用PET-CT进行淋巴结分期的研究。根据STARD (The initiative of standards for reporting of diagnostic accuracy)标准来筛选高质量的研究进入荟萃分析。以纵隔镜或者开胸手术获得病理学证实作为淋巴结受累的金标准来评估PET-CT分期的准确性,采用Stata软件进行荟萃分析。
结果：包含共1122名NSCLC病人的10项研究纳入了荟萃分析。T1和T2期NSCLC的纵隔淋巴结NPV分别为0.94和0.89。合并T1期和T2期NSCLC,纵隔淋巴结的NPV为0.93,总体淋巴结的NPV为0.87。病理类型为腺癌(风险比RR=2.72)以及原发灶具有18F-FDG高代谢的NSCLC具有更高的隐匿性淋巴结转移风险。
结论：尽管PET-CT诊断的临床T1-2N0期NSCLC具有一定几率的隐匿淋巴结转移率,但T1NO患者的纵隔NPV相对较低,提示该亚群NSCLC患者也许不必要进行常规的有创纵隔分期检查。
目的：本研究旨在评估未接受任何治疗的非小细胞肺癌(non-small cell lung cancer, NSCLC):1)体积和FDG摄取的自然倍增时间(doubling time, DT);2)治疗前疾病进展情况；3)自然病程及治疗等待时间(time to treatment, TTT)对预后的影响。
方法：在治疗开始前具有至少2次PET/CT扫描的不可手术的Ⅰ-Ⅲ期NSCLC患者纳入本研究。基于PET/CT图像勾画代谢肿瘤体积(PET-MTV)和基于CT勾画的大体肿瘤体积(CT-GTV)。记录PET-MTV内经纵隔血池标化后的最大和平均代谢活性(NSUVmax及NSUVmean)。疗前肿瘤进展定义为PET/CT上发现的任何新发病灶或者基于AJCC第七版TNM分期的升高。采用生存分析方法探究治疗等待时间对总生存时间(OS)及无进展生存时间(PFS)的影响。
结果：34例NSCLC纳入分析,两次疗前PET/CT的中位间隔时间(ISI)和TTT分别为43天和48天。在此间隔内,肿瘤体积显著增大但肿瘤的FDG摄取／代谢活性则相对稳定。基于指数模型,估算的PET-MTV、CT-GTV、NSUVmean及NSUVmax的倍增时间分别为124、139、597及333天。20.6%的病人在PET/CT诊断NSCLC至治疗开始前发生肿瘤进展,且进展风险随着等待时间的延长而增加(OR=1.027,P=0.02)。肿瘤的DT及TTT对OS及PFS无显著影响。
结论：未治疗的NSCLC体积增长迅速,但代谢活性则相对稳定。基于PET的代谢体积和基于CT的大体肿瘤体积倍增时间无差别。治疗前疾病进展风险随治疗等待时间的延长而升高。肿瘤倍增时间和治疗等待时间可能不影响预后。
目的：本研究基于18F FDG PET/CT,应用多种代谢反应评估系统对非小细胞肺癌(non-small cell lung cancer, NSCLC)治疗后的代谢反应进行分别评估,旨在分析：1)比较不同FDG摄取活性测量方法之间的一致性和差异性；2)各种评估系统对治疗后代谢反应评估的一致性和差异性；3)各系统评估的分类代谢反应对治疗后生存的预测价值；4)探索作为连续变量的FDG代谢下降百分比对预后的价值并提出能够区分不同预后人群的最佳界点。
方法：本研究为一系列基于PET/CT的前瞻性研究的二次分析。入组的NSCLC病人在放射治疗开始前2周内、疗中(约40Gy)以及治疗后复查均进行18F FDG PET/CT检查,并通过与疗前基线代谢水平进行比较,应用如下方法进行疗中和疗末代谢反应的评价：1)视觉定性评估方法；2)基于肿瘤SUV变化百分比的半定量评估方法,包括基于肿瘤最大SUV绝对值(ASUV),经纵隔血池(MBP)标化的相对最大SUV (NSUV-A)以及经肝脏标化的相对最大SUV(NSUV-L)的三种计算方法。应用Kappa系数比较各分类评估系统之间的一致性；应用生存分析方法评价各系统对总生存时间(overall survival, OS)的影响。
结果：44例病人纳入分析(36男性vs.8女性,年龄70±10岁)。疗后PET/CT扫描距离放疗结束的间隔为45-176天,中位93天。疗前、中、后进行的PET/CT扫描中,肝脏的平均SUV都显著高于MBP的平均SUV(P<0.001)；但三次扫描中肝脏和MBP的SUV都没有发生显著动态变化。由ASUV、NSUV-A和NSUV-L衍生的疗中和疗后肿瘤代谢变化百分比高度相关,组内相关系数(ICC)分别为0.919和0.943；以相同界值点转化的三套治疗反应分类之间也具有较好一致性(Kappa系数0.535-1.000)。视觉评估分类与基于NSUV-A半定量标准评估的治疗分类之间具有较差的一致性(Kappa系数0.393)。不论采用何种评估标准,分类变量形式的疗后肿瘤代谢反应都与生存时间显著相关(P<0.001),其中两种标准都认可的CMR病人具有尤其明显的生存优势。作为连续变量,疗后肿瘤SUV下降百分比与预后显著相关(HR=0.213)。在现有半定量评估标准判断的PMR(SUV下降≥30%)人群中,肿瘤SUV下降≥70%亚组具有更优的预后(P<0.001)。
结论：在接受根治性放化疗的NSCLC中,基于肿瘤绝对SUV或者经内参器官标化的相对SUV进行半定量评估的代谢反应结果具有较好的一致性,但与经视觉定性评估的代谢反应之间的一致性较差,主要分歧在于对CMR人群的判定。不论采用何种评估标准,分类变量形式的代谢反应都与生存时间显著相关,而联合定性和半定量方法进行的治疗反应分组能够更好地区分具有不同预后的人群。作为连续变量,SUV每下降1%都能够带来生存获益。在现有分类标准评定的PMR人群中,肿瘤SUV下降≥70%的亚组具有相对更佳的预后。
Purpose:Nodal staging of non-small-cell lung cancer (NSCLC) is crucial in evaluation of prognosis and determination of therapeutic strategy. This study aimed to determine the negative predictive value (NPV) of combined positron emission tomography and computed tomography (PET-CT) in patients with stage I (T1-2N0) NSCLC and to investigate the possible risk factors for occult nodal disease.
Methods:Studies investigating the performance of PET in conjunction with CT in the nodal staging of stage I NSCLC were identified in the MEDLINE database. The initiative of standards for reporting of diagnostic accuracy (STARD) was used to ensure study quality. Pathologic assessments through mediastinoscopy or thoracotomy were required as the reference standard for evaluation of PET-CT accuracy. Stata-based meta-analysis was applied to calculate the individual and pooled NPVs.
Results:Ten studies with a total of1122patients with stage Ⅰ(T1-2N0) NSCLC were eligible for analysis. The NPVs of combined PET and CT for mediastinal metastases were0.94in T1disease and0.89in T2disease. Including both T1disease and T2disease, the NPVs were0.93for mediastinal metastases and0.87for overall nodal metastases. Adenocarcinoma histology type (risk ratio [RR],2.72) and high fluorine-18(18F) fluorodeoxyglucose (FDG) uptake in the primary lesion were associated with greater risk of occult nodal metastases.
Conclusions:Although overall occult nodal metastases in clinical stage T1-2N0NSCLC is not infrequent, combined PET and CT provide a favorable NPV for mediastinal metastases in T1N0NSCLC, suggesting a low yield from routine invasive staging procedures for this subgroup of patients.
Purpose:The aims of this study were to:1) estimate the volumetric and metabolic growth rate of non-small cell lung cancer (NSCLC),2) evaluate disease progression prior to treatment, and3) explore the effects of tumor growth rate and time to treatment (TTT) on survival outcome.
Methods:Patients with inoperable Stage Ⅰ-Ⅲ NSCLC with serial pre-treatment PET/CT scans were eligible for this study. PET-derived metabolic tumor volumes (PET-MTV) and CT-derived gross tumor volumes (CT-GTV) were contoured using PET/CT information. Normalized standardized uptake values (NSUV) in tumors including the NSUVmean and NSUVmax were measured. Tumor growth rates expressed as doubling time (DT) were estimated using an exponential model. Pre-treatment disease progression was defined as the development of any new site of disease on PET/CT and change in TNM Stage (AJCC7th Ed.) was recorded. Patient-outcome data was analyzed with respect to overall and progression free survival.
Results:Thirty-four patients with a median inter-scan interval (ISI) of43days and TTT of48days were analyzed. Tumor volumes showed remarkable inter-scan growth while NSUV did not increase significantly. The DT for PET-MTV, CT-GTV, NSUVmean and NSUVmax were124,139,597, and333days, respectively. Pre-treatment disease progression occurred in20.6%patients with longer ISI being a significant risk factor (OR=1.027,p=0.02). The optimal threshold ISI to predict progression was58days (4.8%vs.46.2%, p=0.007). Neither tumor growth rates nor TTT were significantly correlated to overall survival or progression free survival.
Conclusions:NSCLC displays rapid tumor volume growth whereas tumor metabolic activity is relatively stable over the same time period. Longer delays before initiation of treatment are associated with higher risk of pre-treatment disease progression.
Purpose:Based on18F FDG PET-CT in patients with NSCLC, this study aimed to:1) compare multiple methods in quantifying post-treatment FDG uptake reduction in NSCLC;2) compare qualitative and semi-quantitative assessment of categorical metabolic response;3) evaluate the prognostic value of categorical metabolic response and4) investigate the relationship between numerical post-treatment change of metabolic activity and overall survival (OS) and explore an optimal cutoff to distinguish better responders.
Methods:This is a secondary analysis of a series of prospective studies. Enrolled patients with NSCLC underwent18F-fluorodeoxyglucose PET/CT imaging within2weeks prior to, midway through, and following radiation treatment (RT). Metabolic therapeutic response was assessed using following methods;1) visual assessment,2) semi-quantitative assessment based on FDG uptake reduction using three types of calculation including absolute maximum SUV (ASUV), mediastinum blood pool (MBP) normalized maximum SUV (NSUV-A) and liver normalized maximum SUV (NSUV-L). Kappa coefficient was used to evaluate the agreement between various categorical variables and survival analyses were adopted to analyze the effect of multiple response criteria on overall survival (OS).
Results:Forty-four patients (36M:8F, median age70±10) were eligible for present analysis. The interval between end of RT and post-RT PET/CT scan ranged from45to176days, with a median of93days. Mean SUV of liver was significantly higher than that of MBP at all time points of studies (P<0.001). Neither MBP nor liver had significant metabolic change over time. Reduction percentage of ASUV, NSUV-A and NSUV-L were highly correlated with each other, resulting in the during-and post-treatment intraclass coefficients of0.919and0.943, respectively. There was a moderate agreement between ASUV and NSUV derived response distribution (Kappa coefficient=0.535) and a dramatic concordance between categorical response determined by NSUV-A and NSUV-L (Kappa coefficient=1.0), whereas a poor agreement was observed between visual and semi-quantitative responses (Kappa coefficient=0.393). Categorical responses were significantly correlated with OS independent of employed response assessment criteria (P<0.001) and those with complete metabolic response (CMR) obtained the longest OS. As continuous variable, reduction percentage of NSUV-A showed pronounced association with OS (hazard ratio, HR=0.213). Seventy percent of NSUV-A reduction was identified as another optimal cutoff to distinguish patients with most significant difference in OS (P<0.001)
Conclusions:For NSCLC patients acquiring radical chemoradiaotherapy, semi-quantitative metabolic therapeutic response distributions using different interpretation criteria show good correlation between each other, whereas have great discrepancy with that based on visual assessment, most often in the CMR identification. Current categorical responses demonstrate significant association with overall survival and the combination of visual and semi-quantitative assessment can further improve the predictability of long-term survival. As continuous variable, more numerical reduction percentage is correlated with prolonged overall survival. Seventy percent of metabolic reduction may be another optimal threshold to distinguish responders from non-responders.
引文
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