Advanced PET/CT Imaging for Improving Clincail Trials

描述（由申请人提供）：本提案的目标是通过增强肿瘤反应定量PET/CT成像的有效性来改善癌症临床试验。这有三个不同且相互关联的组成部分：（1）测量和减少多中心定量PET/CT成像测量的偏倚和方差，（2）设计适用于临床试验中定量PET/CT成像的最佳PET图像分析方法，以及（3）开发和测试将定量PET/CT成像作为癌症临床试验设计中的生物标志物和反应测量的指南。基本主题包括优化在癌症治疗临床试验中从成像中收集的临床和生物学数据，将成像组件的设计与癌症临床治疗试验的阶段和复杂性相匹配，以及将成像方法与肿瘤类型和治疗剂相匹配。该提案中使用的机制是与包括PET成像在内的现有临床癌症试验相结合的方法的开发和测试。这包括在华盛顿大学当地进行的影像学研究，作为我们癌症中心指导的区域网络的一部分的小型多中心试验，以及作为国家多中心试验的参与者。重点是早期药物试验（I期和II期研究）和成像生物标志物研究;然而，研究的方法和开发的工具同样适用于大型（III期）试验和成像作为替代终点。所有三个目标的综合结果将使临床研究者、合作癌症试验组和制药公司能够优化PET成像在癌症临床试验中的使用，并在选择研究设计和样本量时考虑定量PET成像标记物。

DESCRIPTION (provided by applicant): The goal of this proposal is to improve cancer clinical trials by enhancing the effectiveness of quantitative PET/CT imaging of tumor response. This has three distinct and linked components; (1) measuring and reducing the bias and variance of multi-center quantitative PET/CT imaging measurements, (2) devising optimal PET image analysis methods appropriate for quantitative PET/CT imaging in clinical trials, and (3) developing and testing guidelines for incorporating quantitative PET/CT imaging as a biomarker and measure of response in cancer clinical trial design. Underlying themes include optimizing the clinical and biologic data that can be gleaned from imaging in the setting of cancer therapy clinical trials, matching the design of the imaging components to the phase and complexity of the cancer clinical therapy trial, and matching the imaging approach to the type of tumor and the therapeutic agent. The mechanism used in the proposal is the development and testing of methods in tandem with existing clinical cancer trials that include PET imaging. This includes imaging studies performed locally at the University of Washington, in small multi-center trials as part of a regional network directed by our cancer center, and as a participant in national multi-center trials. The focus is on early drug trials (Phase I and II studies) and imaging biomarker studies; however, the methods investigated and tools developed will be equally applicable to larger (Phase III) trials and imaging as a surrogate endpoint. The combined results from all three aims will enable clinical investigators, cooperative cancer trial groups, and pharma, to optimize the use of PET imaging in cancer clinical trials and to include considerations for quantitative PET imaging markers in choosing a study design and sample size.