Predictive MRI metrics for tumor aggressiveness in micropapillary thyroid cancer

摘要 该提案是一项应用先进磁共振成像（MRI）的早期临床试验 技术，以管理乳头状微小癌（PMC）面临的日益常见的临床困境 患者在过去的25年里，甲状腺癌的发病率在世界范围内增加了6倍。 美国的自20世纪90年代中期以来，发病率的急剧上升导致人们认识到甲状腺癌具有 成为一个主要的公共卫生问题，而且它仍然是一个问题。至少有一半的快速增长， 甲状腺癌的发病率是由于PMC，其复发率高达6%，并且具有疾病特异性。 手术切除后存活率超过99%。需要立即手术治疗， 最近的两项前瞻性临床研究表明，即使没有任何 治疗时，绝大多数PMC的大小保持稳定，并局限于甲状腺， 然后进行长达10年的积极监视。未能准确预测的侵略性， 几乎所有PMC患者术前肿瘤常导致立即手术切除， 巨大数量的惰性恶性肿瘤患者面临手术风险。非侵入性MRI指标 在鉴别良性和恶性甲状腺结节方面显示出希望，但到目前为止，还不能分层 甲状腺肿瘤手术前的侵略性。我们将致力于通过以下方式应对这一临床挑战： 评价弥散加权（DW-）MRI和动态对比增强（DCE-）MRI方法， 定量生物标志物结合了关于肿瘤细胞结构和血管分布的综合信息。的目标 这项试点临床试验是为了奠定基础，批判性地评估和比较MRI生物标志物作为定量 （替代）生物标志物的侵略性在PMC，并提供科学依据，其转化为 病人管理数据建模的结果将准确地量化肿瘤细胞结构、血管分布及其 相关的异质性和改善PMC中肿瘤侵袭性的评估。的长期目标 这项工作将是进行临床试验，使用个性化的生物标志物，以提供个性化的 管理方法，建议立即手术或积极监测PMC患者。 假设是：（i）系统评价可靠和可重复的采集方案， MRI数据的处理将提高DW-MRI和DCE-MRI量化肿瘤细胞性的准确性， 血管分布及其相关的异质性。(ii)MRI生物标志物将识别具有侵袭性的PMC 这些表型应该是立即手术而不是积极监测的候选者。具体目标 具体目标1：评价可重复和可靠的DW-MRI和DCE-MRI方案， PMC。具体目标2：确定可以预测具有侵袭性组织学病变的PMC的定量MRI生物标志物 和分子表型。

Abstract The proposal is an early phase clinical trial with application of advanced magnetic resonance imaging (MRI) techniques to an increasingly common clinical dilemma faced in managing papillary micro carcinoma (PMC) patients. Over the past 25 years, there has been a six-fold increase in the incidence of thyroid cancer in the United States. Since the mid-1990s, a sharp rise in incidence led to the recognition that thyroid cancer had become a major public health problem, and it continues to be one. At least half of the rapid increase in the incidence of thyroid cancer is due to PMC, which has a recurrence rate of up to 6% and a disease-specific survival rate of more than 99% following surgical resection. The need for immediate surgical treatment has been brought into question by two recent prospective clinical studies that demonstrated that even without any treatment, the vast majority of these PMCs remains stable in size and confined to the thyroid gland when followed with active surveillance for up to 10 years. The failure to accurately predict the aggressiveness of tumors pre-operatively often leads to immediate surgical resection in nearly all patients with PMC, exposing a huge number of people with indolent malignancies to the risks of surgery. Non-invasive MRI metrics have shown promise in differentiating benign and malignant thyroid nodules but so far, have not been able to stratify thyroid tumors based on aggressiveness before surgery. We will aim to address this clinical challenge by evaluating diffusion weighted (DW-)MRI and dynamic contrast enhanced (DCE-)MRI methods that provide quantitative biomarkers incorporating integrated information on tumor cellularity and vascularity. The goal of this pilot clinical trial is to lay the groundwork to critically evaluate and compare MRI biomarkers as quantitative (surrogate) biomarkers of aggressiveness in PMCs and to provide the scientific basis for their translation into patient management. Metrics from data modeling will accurately quantify tumor cellularity, vascularity and their associated heterogeneity and improve assessment of tumor aggressiveness in PMC. The long-term goal of this work will be to perform clinical trials using individualized biomarkers to provide a personalized management approach that recommends either immediate surgery or active surveillance for PMC patients. The hypothesis is that (i) systematic evaluation of a reliable and reproducible protocol for the acquisition and processing of MRI data will improve the accuracy of DW-MRI and DCE-MRI to quantify tumor cellularity, vascularity and their associated heterogeneity. (ii) MRI biomarkers will identify PMCs with aggressive phenotypes that should be candidates for immediate surgery rather than active surveillance. The specific aims of the study are: Specific Aim 1: To evaluate a reproducible and reliable DW-MRI and DCE-MRI protocol for PMC. Specific Aim 2: To identify quantitative MRI biomarkers that can predict PMCs with aggressive histologic and molecular phenotypes.