Dynamic Magnetic Resonance Imaging of Bone Tumors

描述(由申请人提供)： 原发性骨肿瘤是青少年和青壮年的第三大常见肿瘤。骨肉瘤(OS)(占所有原发骨肉瘤的35%)和尤文肉瘤是最常见和次要的骨肿瘤。最准确的预后指标是新辅助化疗后肿瘤坏死率，这是由有经验的术后病理学家估计的。手术前对肿瘤坏死的评估和早期或先验的反应标记对于进一步推进这些疾病的治疗是必要的。这项建议的目标是：1)确定动态增强磁共振成像(DCE-MRI)是否可以可靠地预测坏死率。1b)评估假设，在尤文氏症或OS患者中，先验的或早期(18-24天)DCE-MRI研究通过手术时进行的病理分析来预测坏死率和无病存活率2)比较“半定量”分析与定量模型的预测价值。我们还将比较直接测量输入函数的效果，以确定是否更复杂的建模方案在预测肿瘤反应方面更准确。还将分析双部位交换模型分析的价值，以及放宽平衡跨细胞膜水运输保持在“快速交换极限”的假设，并用更严格的双部位交换(2SX)模型取代这一概念的效果，以及它在评估DCE-MRI数据与肿瘤坏死和疗效关系中的作用。这将决定分析方法是否会影响预测肿瘤反应或坏死率的准确性。3)确定与目前的临床标记物相比，DCE-MRI结果是否是肿瘤反应的更好和独立的标记物。我们将比较DCE-MRI研究与分子和临床预测指标的预后价值。该项目将确定DCE-MRI预测肿瘤坏死的潜力，并将其作为肿瘤对新辅助治疗反应的先验或早期标记。如果成功，它将提供一种工具来预测化疗失败/反应，从而产生针对患者的治疗，这可能会改善结果。

DESCRIPTION (provided by applicant): Primary bone tumors are the third most frequent tumors of adolescents and young adults. Osteogenic sarcomas (OS) (35% of all primary bone sarcomas) and Ewing's sarcoma are the most and second most common bone tumors. The most accurate prognostic indicator is percent tumor necrosis post neoadjuvant chemotherapy, as estimated by an experienced pathologist post surgery. A pre-surgical estimate of tumor necrosis and an early or a priori marker of response are necessary to further advance treatment in these diseases. The goals of this proposal are to: 1A) To determine if dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) can reliably predict percent necrosis. 1B) Evaluate the hypothesis that in patients with Ewing's or OS, the a priori or early (18-24 days) DCE-MRI study predicts percent necrosis measured by pathological analysis performed at surgery and disease free survival 2) Compare the predictive value of using "semi-quantitative" analyses vs. quantitative models. We will also compare the effects of measuring the input function directly in order to determine if more complex modeling schemes are more accurate in predicting tumor response. The value of the 2 site exchange model analysis and the effect of relaxing the assumption that equilibrium transcytolemmal water transport remains in the "fast exchange limit" and replacing this concept with a more rigorous two site exchange (2SX) model, and its effect on evaluating the DCE-MRI data relationship to tumor necrosis and response will also be analyzed. This will determine if the method of analysis impacts accuracy of predicting tumor response or percent necrosis. 3) Determine if the DCE-MRI results are superior and independent markers of tumor response compared to current clinical markers. We will compare the prognostic value of the DCE-MRI studies vs. molecular and clinical prognosticators. This project will determine the potential of DCE-MRI to predict tumor necrosis and as an a priori or early marker of tumor response to neoadjuvant therapy. If successful, it will provide a tool to predict failure/response to chemotherapy, resulting in patient specific treatment which will likely enhance outcome.