DIFFUSION MRI TO ASSESS PANCREATIC TUMOR RESPONSE

描述(申请人提供)：化疗和放射治疗已用于胰腺癌的辅助和明确治疗，但预后仍然很差。最近，有人建议对可切除或边缘可切除的胰腺癌患者进行新辅助放化疗，以提高完全切除的机会。不幸的是，非侵入性评估胰腺癌新辅助治疗反应的能力是有限的。虽然计算机断层扫描(CT)通常被用来评估胰腺肿瘤化疗后的反应，但研究表明，CT检测到的反应很少见，而且低估了真实的生物反应速度。我们机构最近的研究集中于使用扩散磁共振成像评估脑、乳腺癌和转移性前列腺癌的治疗反应，扩散磁共振成像是一种成像工具，利用磁共振脉冲序列来测量水的表观扩散系数(ADC)，这代表了水在细胞水平上组织内的流动性。由于肿瘤细胞死亡而导致的细胞膜完整性丧失，减少了水的扩散限制，增加了ADC。因此，弥散磁共振成像有可能测量成功治疗后发生的早期细胞变化。我们的成像小组最近证明，弥散磁共振不仅是治疗反应的早期预测指标，而且是高级别脑瘤患者总体生存的早期预测指标。因此，我们假设扩散磁共振成像可以成功地用于评估胰腺癌的治疗反应。这项建议的长期目标是在正式的II期试验中测试扩散磁共振成像在接受新辅助化疗的患者中的有效性。在此，我们建议生成设计此类试验所需的数据。这项初步研究的具体目的是描述新辅助化疗前后胰腺肿瘤的扩散系数，并将治疗诱导的胰腺肿瘤ADCs的变化与切除肿瘤的组织病理学分析相关联。作为次要目标，我们将把扩散成像的变化与CT确定的反应(根据RECIST标准)以及肿瘤标记物水平的变化联系起来。如果弥散磁共振成像被证明是胰腺肿瘤反应的可靠评估，它不仅可以成为判断哪些患者可以成功切除肿瘤的有价值的工具，而且还可以在未来的临床试验中评估新治疗方案的疗效。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。扩散磁共振成像是一种新的成像工具，它有可能测量在成功的治疗(如化疗和放射治疗)后发生的细胞变化。本研究的目的是评估弥散磁共振成像在评估胰腺癌患者治疗反应中的作用。一旦我们证明扩散磁共振成像是评估胰腺癌疗效的一个很好的工具，这项测试将广泛适用于边界可切除、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.