DIFFUSION MRI TO ASSESS PANCREATIC TUMOR RESPONSE

描述（由申请人提供）：放化疗已用于胰腺癌的辅助治疗和确定性治疗，但预后仍然很差。最近，新辅助放化疗已被提议用于可切除或边缘可切除的胰腺癌患者，以提高完全切除的机会。不幸的是，非侵入性评估胰腺癌对新辅助治疗的治疗反应的能力有限。虽然计算机断层扫描（CT）通常用于评估放化疗后的胰腺肿瘤缓解，但研究表明CT检测到的缓解并不常见，并且低估了生物学缓解的真实率。我们机构最近的研究集中在用扩散MRI评估脑、乳腺和转移性前列腺癌的治疗反应，这是一种成像工具，利用磁共振脉冲序列测量水的表观扩散系数（ADC），ADC代表细胞水平组织内水的流动性。由于肿瘤细胞死亡导致的细胞膜完整性的丧失降低了水的扩散限制并增加了ADC。因此，弥散MRI有可能测量成功治疗后发生的早期细胞变化。我们的影像学研究小组最近证实，弥散MRI不仅是高级别脑肿瘤患者治疗反应的早期预测因子，而且也是总生存率的早期预测因子。因此，我们假设弥散MRI可以成功地用于评估胰腺癌的治疗反应。本提案的长期目标是在正式的II期试验中测试弥散MRI在接受新辅助放化疗的患者中的效用。在此，我们建议生成此类试验设计所需的数据。这项初步研究的具体目的是表征新辅助放化疗前后的胰腺肿瘤扩散系数，并将胰腺肿瘤ADC治疗诱导的变化与切除肿瘤的组织病理学分析相关联。作为次要目的，我们将扩散成像的变化与CT确定的缓解（根据RECIST标准）以及肿瘤标志物水平的变化相关联。如果弥散MRI被证明是胰腺肿瘤反应的可靠评估，它可能成为一个有价值的工具，不仅可以确定哪些患者可以接受成功的肿瘤切除术，而且还可以在未来的临床试验中评估新的治疗方案的疗效。 项目健康相关性：目前的成像方法往往低估了胰腺癌治疗反应的频率和程度。扩散MRI是一种新型的成像工具，它有可能测量成功治疗（如放化疗）后发生的细胞变化。本研究的目的是评估扩散MRI在评估胰腺癌患者治疗反应中的实用性。一旦我们证明弥散MRI是评估胰腺癌缓解的良好工具，该试验将广泛适用于边缘可切除、不可切除和转移性胰腺癌患者，并将有助于评估任何未来的实验性治疗。

DESCRIPTION (provided by applicant): Chemoradiotherapy has been in use for pancreatic cancer in the adjuvant and definitive settings, but the prognosis remains poor. Recently, neoadjuvant chemoradiation has been proposed for patients with resectable or borderline resectable pancreatic cancer to improve chances for a complete resection. Unfortunately, the ability to non-invasively assess treatment response in pancreatic cancer to neoadjuvant therapy is limited. While computed tomography (CT) is routinely used to assess pancreatic tumor response following chemoradiation, studies suggest that CT-detected responses are infrequent and underestimate the true rate of biologic response. Recent research at our institution has focused on assessing treatment response in brain, breast, and metastatic prostate cancer with diffusion MRI, an imaging tool which utilizes magnetic resonance pulse sequences to measure the apparent diffusion coefficient (ADC) of water, which represents the mobility of water within tissues at the cellular level. Loss of cell membrane integrity due to tumor cell death reduces the diffusion restrictions of water and increases the ADC. Therefore, diffusion MRI has the potential to measure early cellular changes that occur in response to successful therapies. Our imaging group has recently demonstrated that diffusion MRI is an early predictor not only of therapeutic response, but also of overall survival in patients with high grade brain tumors. Therefore, we hypothesize that diffusion MRI can be successfully used to assess treatment response in carcinoma of the pancreas. The long-term goal of this proposal is to test the utility of diffusion MRI in patients undergoing neoadjuvant chemoradiotherapy in a formal phase II trial. Herein, we propose to generate the data needed for the design of such trial. The specific aim of this pilot study is to characterize pancreatic tumor diffusion coefficients before and after neoadjuvant chemoradiation, and to correlate therapy-induced changes in pancreatic tumor ADCs with histopathologic analysis of resected tumors. As a secondary objective, we will correlate changes in diffusion imaging with CT- determined responses (per RECIST criteria) as well as alterations in tumor marker levels. If diffusion MRI is demonstrated to be a reliable assessment of pancreatic tumor response, it could become a valuable tool not only for determining which patients can undergo successful tumor resection, but also for the evaluation of efficacy of new treatment regimens in future clinical trials. PROJECT HEALTH RELEVANCE: Current imaging methods often underestimate the frequency and degree of treatment response in pancreatic cancer. Diffusion MRI is a novel imaging tool which has the potential to measure cellular changes that occur in response to successful therapies, such as chemoradiation. The goal of this study is to assess the utility of diffusion MRI in assessing treatment responses in patients with pancreatic cancer. Once we have shown that diffusion MRI is a good tool for assessing response in pancreatic cancer, this test will have wide applicability in patients with borderline-resectable, unresectable, and metastatic pancreatic cancer, and will assist in evaluating any future experimental treatment.