NOVEL BIOMARKERS OF MALIGNANT PROGRESSION IN RECURRENT LOW GRADE GLIOMA

该研究的目的是评估非侵入性成像参数作为肿瘤生物标志物的作用。 弥漫性低级别胶质瘤的恶变和使用这些参数来选择区域 表征与复发疾病相关的基因突变。这些研究将具有重要的意义 通过提供客观标准来预测病变何时发生，对这些患者的管理产生了影响 转化为更恶性的表型，是否以及在哪里进行手术干预，以及如何选择 下一条线疗法。这是一个重要的问题，因为有肿瘤复发的患者以前的LGG 根据组织学亚型、分级和分子/细胞遗传学特征有不同的结果。这个 恶性转化的机制尚不清楚，治疗策略通常是在没有 复发性肿瘤的组织学证实。在我们之前的孢子项目中，我们应用了磁共振 成像(MRI)和光谱成像(MRS！)在肿瘤切除前对125名患者进行评估 被认为是从之前的LGG复发的。活体磁共振测量的显著差异是 与那些没有恶变的肿瘤相比，发现有恶变的肿瘤。人血清白蛋白体外分析 提供的图像引导组织样本的组织状态、IDHI突变和体外核磁共振谱 导致新假说被研究的新信息1.扩展这一点 通过使用图像引导组织样本的下一代测序来定义突变简档的方法 明确的组织学将增加识别驱动恶性转化的突变的可能性 并首次阐述了与治疗效果和自然因素有关的肿瘤基因组进化 疾病的病史。特定的目标1将体内MR参数与恶性转化和 临床结果和特定目标2将使用来自具有或不具有 恶性转化的特征，以及来自当前和后续的配对样本 手术检查突变图谱的进化。所获得的知识将产生重大影响 取决于病人的护理。 相关性(见说明)； 这一新的项目将把预测恶性转化的非侵入性成像标记与 基因突变变化的空间和时间模式的评估 最初诊断为低级别胶质瘤的复发性疾病。这将使我们了解到 这将有助于制定预防或治疗复发的策略。

The goal of the proposed study is to evaluate the role of noninvasive imaging parameters as biomarkers of malignant transformation in diffuse low grade glioma and to use these parameters to select regions for characterizing the genetic mutations associated with recurrent disease. The studies will have a significant impact on the management of these patients by providing objective criteria to predict when a lesion transforms to a more malignant phenotype, whether and where to intervene surgically and how to select the next line therapy. This is an important problem because patients with tumors that recur from a prior LGG have different outcomes depending on histological subtype, grade, and molecular/cytogenetic features. The mechanisms of malignant transformation are unclear and treatment strategies are often pursued without histological confirmation of recurrent tumor. In our previous SPORE Project, we applied magnetic resonance imaging (MRi) and spectroscopic imaging (MRS!) to evaluate 125 patients prior to resection of tumors that were thought to have recurred from a prior LGG. Significant differences in the in vivo MR measures were seen for tumors with malignant transformation compared to those that did not. Ex vivo analysis of the histological status, IDHI mutations and ex-vivo NMR spectra from the image guided tissue samples provided new information that resulted in novel hypotheses being investigated in Specific Aim 1. Extending this approach by defining the mutation profile using next-generation sequencing of image guided tissue samples with defined histology will increase the probability of identifying mutations that drive malignant transformation and address, for the first time, the tumor genome evolution associated with treatment effects and the natural history of the disease.Specific Aim 1 will relate in-vivo MR parameters to malignant transfomriation and clinical outcome and Specific Aim 2 will use paired samples from lesions that either do or do not have the characteristics of malignant transformation, as well as paired samples from the current and subsequent surgery to examine the evolution of the mutation profile. The knowledge gained will make a major impact upon patient care. RELEVANCE (See instructions); This novel project will integrate non-invasive imaging markers that predict malignant transformation with an evaluation of the spatial and temporal patterns of changes in genetic mutations of patients who present with recurrent disease from an original diagnosis of low grade glioma. This will inform on the mechanisms of malignant transformation and will facilitate the development of strategies to prevent or treat the recurrence.