Abstract：
OBJECTIVE: To measure dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarker repeatability in patients with non-small cell lung cancer (NSCLC). To use these statistics to identify which individual target lesions show early biological response.
METHODS: A single-centre, prospective DCE-MRI study was performed between September 2015 and April 2017. Patients with NSCLC were scanned before standard-of-care radiotherapy to evaluate biomarker repeatability and two weeks into therapy to evaluate biological response. Volume transfer constant (Ktrans), extravascular extracellular space volume fraction (ve) and plasma volume fraction (vp) were measured at each timepoint along with tumour volume. Repeatability was assessed using a within-subject coefficient of variation (wCV) and repeatability coefficient (RC). Cohort treatment effects on biomarkers were estimated using mixed-effects models. RC limits of agreement revealed which individual target lesions changed beyond that expected with biomarker daily variation.
RESULTS: Fourteen patients (mean age, 67 years +/- 12, 8 men) had 22 evaluable lesions (12 primary tumours, 8 nodal metastases, 2 distant metastases). The wCV (in 8/14 patients) was between 9.16% to 17.02% for all biomarkers except for vp, which was 42.44%. Cohort-level changes were significant for Ktrans and ve (p < 0.001) and tumour volume (p = 0.002). Ktrans and tumour volume consistently showed the greatest number of individual lesions showing biological response. In distinction, no individual lesions had a real change in ve despite the cohort-level change.
CONCLUSIONS: Identifying individual early biological responders provided additional information to that derived from conventional cohort cohort-level statistics, helping to prioritise which parameters would be best taken forward into future studies.
CONCLUSIONS: Dynamic contrast-enhanced magnetic resonance imaging biomarkers Ktrans and tumour volume are repeatable and detect early treatment-induced changes at both cohort and individual lesion levels, supporting their use in further evaluation of radiotherapy and targeted therapeutics.
CONCLUSIONS: Few literature studies report quantitative imaging biomarker precision, by measuring repeatability or reproducibility. Several DCE-MRI biomarkers of lung cancer tumour microenvironment were highly repeatable. Repeatability coefficient measurements enabled lesion-specific evaluation of early biological response to therapy, improving conventional assessment.
METHODS: A single-centre, prospective DCE-MRI study was performed between September 2015 and April 2017. Patients with NSCLC were scanned before standard-of-care radiotherapy to evaluate biomarker repeatability and two weeks into therapy to evaluate biological response. Volume transfer constant (Ktrans), extravascular extracellular space volume fraction (ve) and plasma volume fraction (vp) were measured at each timepoint along with tumour volume. Repeatability was assessed using a within-subject coefficient of variation (wCV) and repeatability coefficient (RC). Cohort treatment effects on biomarkers were estimated using mixed-effects models. RC limits of agreement revealed which individual target lesions changed beyond that expected with biomarker daily variation.
RESULTS: Fourteen patients (mean age, 67 years +/- 12, 8 men) had 22 evaluable lesions (12 primary tumours, 8 nodal metastases, 2 distant metastases). The wCV (in 8/14 patients) was between 9.16% to 17.02% for all biomarkers except for vp, which was 42.44%. Cohort-level changes were significant for Ktrans and ve (p < 0.001) and tumour volume (p = 0.002). Ktrans and tumour volume consistently showed the greatest number of individual lesions showing biological response. In distinction, no individual lesions had a real change in ve despite the cohort-level change.
CONCLUSIONS: Identifying individual early biological responders provided additional information to that derived from conventional cohort cohort-level statistics, helping to prioritise which parameters would be best taken forward into future studies.
CONCLUSIONS: Dynamic contrast-enhanced magnetic resonance imaging biomarkers Ktrans and tumour volume are repeatable and detect early treatment-induced changes at both cohort and individual lesion levels, supporting their use in further evaluation of radiotherapy and targeted therapeutics.
CONCLUSIONS: Few literature studies report quantitative imaging biomarker precision, by measuring repeatability or reproducibility. Several DCE-MRI biomarkers of lung cancer tumour microenvironment were highly repeatable. Repeatability coefficient measurements enabled lesion-specific evaluation of early biological response to therapy, improving conventional assessment.
摘要：
目的：测量非小细胞肺癌（NSCLC）患者的动态对比增强磁共振成像（DCE-MRI）生物标志物的可重复性。使用这些统计数据来识别哪些个体靶病变显示出早期生物学反应。
方法：单中心，2015年9月至2017年4月进行了前瞻性DCE-MRI研究。NSCLC患者在标准治疗放疗前进行扫描，以评估生物标志物的可重复性，并在治疗后两周进行扫描，以评估生物反应。体积转移常数(Ktrans),在每个时间点测量血管外细胞外空间体积分数（ve）和血浆体积分数（vp）以及肿瘤体积。使用受试者内变异系数(wCV)和重复性系数(RC)评估重复性。使用混合效应模型估计队列治疗对生物标志物的影响。RC一致性极限揭示了哪些个体目标病变的变化超出了生物标志物每日变化的预期。
结果：14名患者(平均年龄，67岁+/-12，8名男性）有22个可评估的病变（12个原发性肿瘤，8个淋巴结转移，2个远处转移）。除vp外，所有生物标志物的wCV（在8/14患者中）在9.16％至17.02％之间，为42.44%。队列水平变化对于Ktrans和ve(p<0.001)和肿瘤体积(p=0.002)是显著的。Ktrans和肿瘤体积始终显示出最大数量的个体病变，显示出生物学反应。在区别上,尽管有队列水平的变化,但没有单个病变的ve发生真正的变化.
结论：识别个体早期生物反应者提供了来自传统队列队列水平统计的额外信息，帮助优先考虑哪些参数最好用于未来的研究。
结论：动态对比增强磁共振成像生物标志物Ktrans和肿瘤体积是可重复的，并在队列和个体病变水平上检测早期治疗引起的变化。支持其在进一步评估放射治疗和靶向治疗中的使用。
结论：很少有文献研究报告定量成像生物标志物的精确性，通过测量重复性或再现性。肺癌肿瘤微环境的几种DCE-MRI生物标志物是高度可重复的。重复性系数测量能够对治疗的早期生物学反应进行病变特异性评估，改进常规评估。
方法：单中心，2015年9月至2017年4月进行了前瞻性DCE-MRI研究。NSCLC患者在标准治疗放疗前进行扫描，以评估生物标志物的可重复性，并在治疗后两周进行扫描，以评估生物反应。体积转移常数(Ktrans),在每个时间点测量血管外细胞外空间体积分数（ve）和血浆体积分数（vp）以及肿瘤体积。使用受试者内变异系数(wCV)和重复性系数(RC)评估重复性。使用混合效应模型估计队列治疗对生物标志物的影响。RC一致性极限揭示了哪些个体目标病变的变化超出了生物标志物每日变化的预期。
结果：14名患者(平均年龄，67岁+/-12，8名男性）有22个可评估的病变（12个原发性肿瘤，8个淋巴结转移，2个远处转移）。除vp外，所有生物标志物的wCV（在8/14患者中）在9.16％至17.02％之间，为42.44%。队列水平变化对于Ktrans和ve(p<0.001)和肿瘤体积(p=0.002)是显著的。Ktrans和肿瘤体积始终显示出最大数量的个体病变，显示出生物学反应。在区别上,尽管有队列水平的变化,但没有单个病变的ve发生真正的变化.
结论：识别个体早期生物反应者提供了来自传统队列队列水平统计的额外信息，帮助优先考虑哪些参数最好用于未来的研究。
结论：动态对比增强磁共振成像生物标志物Ktrans和肿瘤体积是可重复的，并在队列和个体病变水平上检测早期治疗引起的变化。支持其在进一步评估放射治疗和靶向治疗中的使用。
结论：很少有文献研究报告定量成像生物标志物的精确性，通过测量重复性或再现性。肺癌肿瘤微环境的几种DCE-MRI生物标志物是高度可重复的。重复性系数测量能够对治疗的早期生物学反应进行病变特异性评估，改进常规评估。
