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年轻人的第三大常见肿瘤。骨源性肉瘤（OS）（占所有原发性骨肉瘤的35%）和尤文氏肉瘤是最常见和第二常见的骨肿瘤。最准确的预后指标是新辅助化疗后肿瘤坏死百分比，由经验丰富的病理学家在术后估计。术前评估肿瘤坏死和早期或先验的反应标志物是必要的，以进一步推进这些疾病的治疗。该提案的目标是：1A）确定动态对比增强磁共振成像（DCE-MRI）是否可以可靠地预测坏死百分比。1B）评估以下假设：在患有尤文氏病或OS的患者中，先验或早期（18-24天）DCE-MRI研究预测通过在手术时进行的病理分析测量的坏死百分比和无病生存率。2）比较使用“半定量”分析与定量模型的预测值。我们还将比较直接测量输入函数的效果，以确定更复杂的建模方案在预测肿瘤反应方面是否更准确。还将分析2位点交换模型分析的价值和放松平衡跨细胞膜水转运保持在“快速交换极限”的假设并将该概念替换为更严格的2位点交换（2SX）模型的影响，以及其对评价DCE-MRI数据与肿瘤坏死和缓解的关系的影响。这将确定分析方法是否影响预测肿瘤缓解或坏死百分比的准确性。3)确定与当前临床标志物相比，DCE-MRI结果是否是肿瘤缓解的上级和独立标志物。我们将比较DCE-MRI研究与分子和临床预测的预后价值。该项目将确定DCE-MRI预测肿瘤坏死的潜力，并作为肿瘤对新辅助治疗反应的先验或早期标志物。如果成功，它将提供一种预测化疗失败/反应的工具，从而导致患者特异性治疗，这可能会改善结局。

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.