MRI For Staging DCIS and Assessing Response to Treatment

描述（由申请人提供）：导管原位癌（DCIS）是一种早期、侵袭前的乳腺癌，如果局部控制得到了很好的预后。然而，由于乳腺x线摄影和临床检查往往难以了解DCIS的真实程度，因此一旦发现DCIS，就会积极治疗，采用手术、放疗和激素治疗，以防止疾病进展。然而，有证据表明并非所有DCIS病变都会发展为浸润性癌。人们对寻找更好的方法来评估DCIS，并潜在地识别那些进展缓慢的DCIS病变，或者根本没有进展。这种进展缓慢的DCIS病变可能可以通过非手术治疗来预防或逆转进展为侵袭性疾病。本研究的目的是提高我们使用MR成像技术测量DCIS的能力，并通过组织病理学相关性确定与隐匿性侵袭性疾病和多中心性相关的影像学特征，如果早期发现，这两种特征都可以改变患者的治疗方法。主要目的是改进现有的已经用于浸润性癌的对比增强（CE） MR方法，以更好地识别DCIS并确定其范围。我们还将研究两种表征DCIS的新技术：高光谱空间分辨率成像（HiSS）和扩散加权成像（DWI）。HiSS和DWI将分别增加与组织细胞和亚体脂肪和水光谱成分相关的DCIS信息，这可能是对CE-MRI提供的肿瘤血管生成信息的补充。影像技术的结合将用于测量DCIS在激素和他汀类药物治疗后的治疗相关变化。两项试点临床试验旨在研究激素和他汀类药物治疗DCIS的可行性，并将招募活检证实的DCIS患者在手术前接受短期治疗。将使用成像和组织生物标志物对患者进行评估，以评估治疗后的变化（激素试验）和测量剂量相关效应（他汀类药物试验）。这两项试验旨在确定对治疗变化敏感的生物标志物，并可用于后续更大规模的试验，以测试非手术治疗降低DCIS进展为侵袭性癌症风险的能力。试点试验为改进DCIS的MRI方法提供了机会，并提高了其在指导患者选择和治疗评估方面的有效性。

DESCRIPTION (provided by applicant): Ductal carcinoma in situ (DCIS) is an early, pre-invasive form of breast cancer that conveys an excellent prognosis if local control is achieved. However, because it is often difficult to appreciate the true extent of DCIS on mammography and clinical exam, DCIS is treated aggressively once detected, using surgery, radiation and hormonal treatment, with the goahof preventing disease progression. Yet, there is evidence that not all DCIS lesions will progress to invasive cancer. There is interest in finding better ways to assess DCIS and potentially identify those DCIS lesions that progress slowly to invasive cancer, or not at all. It is possible that such slowly progressing DCIS lesions could be treated non-surgically with therapies that prevent or reverse progression to invasive disease. The goal of this study is to improve our ability to measure DCIS using MR imaging techniques and to determine through histopathologic correlation the imaging characteristics associated with occult invasive disease and multi-centricity, both of which can change patient management if identified early. The primary aim is to refine existing contrast-enhanced (CE) MR methods that have already been tested for invasive carcinoma, to better identify DCIS and define its extent. We will also investigate two new techniques for their ability to characterize DCIS: high spectral spatial resolution imaging (HiSS) and diffusion-weighted imaging (DWI). HiSS and DWI will add information about DCIS related to tissue cellularity and subvoxelar fat and water spectral components, respectively, that may be complementary to the information about tumor angiogenesis provided by CE-MRI. The combination of imaging techniques will be applied to measure treatment- related changes in DCIS in response to hormonal and statin therapy. Two pilot clinical trials designed to investigate the feasibility of hormonal and statin treatment for DCIS are beginning at our institution and will enroll patients with biopsy-proven DCIS to receive short-term treatments prior to surgery. Patients will be evaluated using both imaging and tissue biomarkers to assess change with treatment (hormonal trial) and measure dose-related effects (statin trial). Both trials are intended to identify biomarkers that are sensitive to treatment change and can be used in subsequent larger trials to test non-surgical therapies for their ability to reduce the risk of DCIS progression to invasive cancer. The pilot trials afford an opportunity to refine MRI methods for DCIS and to improve their effectiveness for guiding patient selection and treatment assessment.