Multicenter Clinical Trials Using 18F-FDG PET to Measure Early Response to Oncologic Therapy: Effects of Injection-to-Acquisition Time Variability on Required Sample Size.
Multicenter Clinical Trials Using 18F-FDG PET to Measure Early Response to Oncologic Therapy: Effects of Injection-to-Acquisition Time Variability on Required Sample Size.
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DOI：
10.2967/jnumed.115.162289
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
Kinahan PE
中科院分区：
文献类型：
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作者：
Kurland BF;Muzi M;Peterson LM;Doot RK;Wangerin KA;Mankoff DA;Linden HM;Kinahan PE
摄取时间(示踪剂注射和图像采集之间的持续时间)影响18F-脱氧葡萄糖(18F-FDG)正电子发射断层扫描(PET)图像中肿瘤的标准摄取值(SUV)。由于摄取时间不同，肿瘤SUV的变化将被低估或高估。本研究采用虚拟临床试验方法，研究摄取时间对肿瘤反应评估的影响。从乳腺癌患者的18F-FDG PET动态扫描中估计肿瘤动力学参数，并用于模拟注射后45-120分钟的时间-活动曲线(TAC)。五分钟摄取时间框架遵循四种情况：(#1)标准化静态测量时间(所有人60-65分钟)，(#2)从严格遵守标准化规程的学术PET设备采样的摄取时间，(#3)与#2相似但偏离标准更大的分布，(#4)匆忙扫描(开始图像采集45-65分钟)和频繁延迟(58-115分钟摄取时间)的混合。对于场景1、#2、#3和#4，超出范围扫描的比例(<；50或>；70分钟，或成对扫描之间的>；15分钟差)分别为0%、20%、44%和%。已发表的基于摄取时间依赖的局部线性的SUV校正在单独的分析中被应用。摄取时间变化的影响被评估为检测反应的敏感性(在18F-FDG PET SUV中观察到≥变化30%的概率，假设真实下降40%)和特异度(观察绝对变化30%的可能性，假设没有真实变化)。情景1的敏感度为96%，情景4的敏感度为73%(95%可信区间为70%-76%)，情景2的敏感度为92%(90%-93%)。所有情景的特异度为≥91%。与方案1相比，单臂第二阶段试验需要增加8%-115%的样本量。如果摄取时间已知，SUV校正方法可以将灵敏度提高到87%-95%，并将样本量增加减少到<；27%。摄取时间偏离标准化方案的情况经常发生，潜在地降低了18F-FDG PET反应生物标记物的性能。根据摄取时间对SUV进行校正可以提高灵敏度，但需要改进算法。更严格的摄取时间控制和有效的校正算法可以提高使用18F-FDG PET终点进行临床试验的功率和降低成本。
Uptake time (duration between tracer injection and image acquisition) affects the standardized uptake value (SUV) measured for tumors in 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) images. With dissimilar uptake times, changes in tumor SUVs will be under- or overestimated. This study examines the influence of uptake time on tumor response assessment, using a virtual clinical trials approach. Tumor kinetic parameters were estimated from dynamic 18F-FDG PET scans of breast cancer patients and used to simulate time-activity curves (TACs) for 45–120 minutes post-injection. Five-minute uptake time frames followed four scenarios: (#1) standardized static measurement time (60–65 minutes for all), (#2) uptake times sampled from an academic PET facility with strict adherence to standardization protocols, (#3) distribution similar to #2 but with greater deviation from standards, (#4) mixture of hurried scans (45–65 minute start of image acquisition) and frequent delays (58–115 minute uptake time). The proportion of out-of-range scans (<50 or >70 minutes, or >15 minutes difference between paired scans) was 0%, 20%, 44%, and 64% for scenarios #1, #2, #3, and #4. A published SUV correction based on local linearity of uptake time dependence was applied in a separate analysis. Influence of uptake time variation was assessed as sensitivity for detecting response (probability of observing a change of ≥30% decrease in 18F-FDG PET SUV, given a true decrease of 40%) and specificity (probability of observing absolute change of <30%, given no true change). Sensitivity was 96% for scenario #1, and ranged from 73% for scenario #4 (95% confidence interval 70%–76%) to 92% (90%–93%) for scenario #2. Specificity for all scenarios was ≥91%. Single-arm phase II trials required 8%–115% greater sample size for scenarios #2–#4 compared to #1. If uptake time is known, SUV correction methods may raise sensitivity to 87%–95% and reduce the sample size increase to <27%. Uptake time deviations from standardized protocols occur frequently, potentially decreasing performance of 18F-FDG PET response biomarkers. Correcting SUV for uptake time improves sensitivity, but algorithm refinement is needed. Stricter uptake time control and effective correction algorithms could improve power and decrease costs for clinical trials using 18F-FDG PET endpoints.