MRI For Staging DCIS and Assessing Response to Treatment

描述(申请人提供)：导管原位癌(DCIS)是一种早期的、侵袭前的乳腺癌，如果实现局部控制，预后良好。然而，由于通常很难在乳房X光检查和临床检查中判断DCIS的真实范围，DCIS一旦被发现就会得到积极的治疗，使用手术、放射和激素治疗，目的是防止疾病的进展。然而，有证据表明，并不是所有的DCIS病变都会进展为浸润性癌症。人们有兴趣找到更好的方法来评估DCIS，并潜在地识别那些进展缓慢的浸润性癌症或根本没有进展的DCIS病变。这种进展缓慢的DCIS病变可以通过预防或逆转进展为侵袭性疾病的治疗方法进行非手术治疗。这项研究的目的是提高我们使用磁共振成像技术测量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成像特征，如果及早发现，这两者都可以改变患者的治疗。主要目的是改进现有的对比剂增强(CE)MR方法，这些方法已经被测试为浸润性癌，以更好地识别DCIS并确定其范围。我们还将研究两种新的技术来表征DCIS的能力：高光谱空间分辨率成像(HISS)和扩散加权成像(DWI)。HISS和DWI将分别添加与组织细胞密度和体素下脂肪和水光谱成分相关的DCIS信息，这可能是对CE-MRI提供的关于肿瘤血管生成的信息的补充。成像技术的组合将被应用于测量激素和他汀类药物治疗后DCIS与治疗相关的变化。两项旨在研究激素和他汀类药物治疗DCIS可行性的试点临床试验正在我们机构开始，并将招募经活检证实的DCIS患者在手术前接受短期治疗。将使用成像和组织生物标记物对患者进行评估，以评估治疗后的变化(荷尔蒙试验)和测量与剂量相关的影响(他汀类试验)。这两项试验都旨在确定对治疗变化敏感的生物标记物，并可用于随后的更大规模试验，以测试非手术疗法降低DCIS进展为浸润性癌症的风险的能力。试点试验为改进DCIS的MRI方法并提高其指导患者选择和治疗评估的有效性提供了机会。

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.