Imaging and Tissue Biomarkers in Patients with Newly Diagnosed GBM

描述（由申请人提供）：该项目的目的是将代谢和生理磁共振成像数据整合到新诊断的多形性胶质母细胞瘤（GBM）患者的临床管理中，这些患者正在接受放射、化疗和抗血管生成治疗的联合治疗。我们目前的研究已经提供了强有力的证据，磁共振光谱成像（MRSI），灌注加权成像（PWI）和扩散加权成像（DWI）产生有关这些病变的生物学行为的信息，可能对临床决策有价值。我们建议探讨这些成像方法在量化成像参数变化和评估同时使用Enzastaurin，替莫唑胺和放射治疗（ETRT）的患者的治疗反应方面的影响，ETRT是一种结合细胞毒性和抗血管生成方法的治疗策略。第一个感兴趣的领域是验证选定的影像学变量的生物学解释，这些变量被认为是肿瘤范围、异质性和治疗反应性的代表性替代品，以及与生存有关的预后意义。第二个感兴趣的领域是评估ETRT之前的成像特征以及ETRT导致的短期和长期变化，以便量化和评估治疗反应。以前的研究没有利用最先进的代谢和生理成像方法来选择患者，识别显微镜下的疾病和异质性，或评估对治疗的反应。我们认为确定这种方法是否可行和获得证据将有助于决定如何最好地将这些信息整合到未来的临床试验中是至关重要的。

DESCRIPTION (provided by applicant): The objective of this project is to integrate metabolic and physiologic MR imaging data into the clinical management of patients with newly diagnosed glioblastoma multiforme (GBM) who are being treated with combined radiation, chemo and antiangiogenic therapy. Our current studies have provided strong evidence that Magnetic Resonance Spectroscopic Imaging (MRSI), Perfusion Weighted imaging (PWI) and Diffusion Weighted Imaging (DWI) produce information concerning the biological behavior of such lesions that is likely to be valuable for clinical decision making. We propose to explore the impact of these imaging methods with respect to quantifying changes in imaging parameters and assessing therapeutic response in patients treated with concurrent Enzastaurin, Temozolomide and Radiation Therapy (ETRT), a therapeutic strategy that combines cytotoxic and antiangiogenic approaches. The first area that is of interest is to validate the biological interpretation of selected imaging variables presumed to be representative surrogates for tumor extent, heterogeneity, and therapeutic responsiveness, as well as prognostic significance with respect to survival. The second area of interest is in evaluating imaging characteristics prior to ETRT and their short and longer term changes that occur as a result of ETRT in order to quantify and assess treatment response. Previous studies have not utilized state of the art metabolic and physiologic imaging methods to select patients, to identify microscopic disease and heterogeneity or to evaluate response to therapy. We believe that it is critical to determine whether this approach is feasible and to obtain evidence that would help in deciding how to best integrate such information into future clinical trials. Specific Aim 1 will provide direct correlation between specific in vivo imaging and tissue characteristics by immunohistochemical and ex vivo NMR spectroscopy of image guided surgical samples from patients with newly diagnosed GBM. This will establish the link between in vivo and ex vivo MR parameters and biological behavior as defined by molecular morphology. Specific Aim 2 will analyze the characteristics of GBM in patients who are participating in an institutional Phase II clinical trial of ETRT. It will examine the relationship between pre-ETRT MR parameters and subsequent imaging changes at multiple time points up to 6 months after completion of RT. While the focus of this proposal is on one specific clinical trial, the knowledge that will be gained has broad implications for selecting and designing many other types of antiangiogenic and molecularly targeted therapies and is likely to enhance the non-invasive imaging based interpretation of treatment response, change the definition of tumor burden in patients with GBM as well as improve patient selection for future clinical trials.