Molecular Imaging to Identify Tumor Margins

分子成像识别肿瘤边缘

基本信息

批准号：
8787724
负责人：
James Peter Basilion
金额：
$ 20.68万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-01-01 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8787724
关键词：
Address American Biochemistry Breast Cancer Treatment Breast-Conserving Surgery Cancerous Cessation of life Clinical Clinical Protocols Cosmetics Cytology Data Detection Diffusion Disease Distant Drug Formulations Emotional Excision Formalin Frozen Sections Goals Gold Hand Health Health Care Costs Home environment Hospitals Image Imaging Techniques Imaging technology Individual Infiltration Institution Institutional Review Boards Laboratories Malignant Neoplasms Mammaplasty Mammary Gland Parenchyma Mammography Mastectomy Methods Molecular Probes New York Normal tissue morphology Operative Surgical Procedures Paraffin Embedding Pathologist Pathology Patients Penetration Peptide Hydrolases Procedures Protocols documentation Provider Recurrence Repeat Surgery Reporting Research Resected Roentgen Rays Sampling Sampling Errors Solutions Specimen Surface Surgeon Surveys Survival Rate Techniques Technology Testing Time Tissues Topical application Translations Tumor Tissue Validation Vascularization Woman Work base breast lumpectomy cancer cell cancer surgery cellular imaging cost design economic impact human tissue image guided imaging agent imaging probe improved malignant breast neoplasm molecular imaging new technology novel optical imaging overexpression prevent research study screening standard of care statistics success tumor

项目摘要

DESCRIPTION (provided by applicant): More than 230,000 women will undergo surgery for breast cancer in 2012 in the US. Of these, around 75% will be candidates and choose breast conserving surgery (BCS). BCS is cosmetically preferable to the alternative (mastectomy) and long-term survival rates are equivalent. But BCS has the potential to be significantly more expensive. Of the 175,000 women who undergo BCS, 25%-40% will be recalled to the hospital for additional surgery to remove active cancerous tissue that was not detected and removed during the first procedure. Apart from the negative impact on patients, which is the primary concern of clinicians, second surgeries have a significant economic impact on healthcare costs in general as well as on individual provider institutions. The current "gold standard" for the detection of active tumor margins after tumor excision is FFPE (Formalin-Fixed, Paraffin-Embedded) tissue pathology. Tissue removed by the surgeon is evaluated for active tumor margins after the patient is discharged and results may take up to two weeks. Because it is not performed intra-operatively, FFPE virtually guarantees there will be second surgeries when active margins are detected. More importantly, FFPE does not examine the entire excised tumor, but only a number of frozen sections. The inevitable sampling errors may miss active tumor "spikes". Data suggests that approximately 15% of patients that are declared to have "clean" margins have local recurrence within a year indicating that pathology missed disease in the margins, likely due to undersampling. Recently, The New York Times reported on surgical breast cancer treatments in the USA further underscoring that an unmet public need, the reduction in second surgeries due to undetected/unexcised cancer cells in tumor margins, clearly exists ("Breast Cancer Surgery Rules Are Called Unclear", NY Times, page A1, February 1, 2012). A recent survey revealed that only 48% of the 351 American surgeons who responded grossly examine margins intraoperatively with a pathologist and even fewer used any techniques during the surgery to determine if they had removed all the cancer tissue from the breast. Out of all the participating surgeons, 28% would consider a 1-mm margin free of cancer as negative, 50% a 2-mm margin, 12% a 5- mm margin and 3% a 10-mm margin. Clearly, these shortcoming define an unmet clinical need for BCS. Solution to the Unmet Need. Molecular imaging is a relatively new field that tries to identify cells by imaging them based on differences in their biochemistry rather than trying to resolve subtle anatomical differences that are used to identify cancer in typical X-ray or mammography exams. For a number of years our laboratory has been looking into the possibility of using quenched molecular imaging probes and application technologies to rapidly identify cancer cells in the body. Recently, we have developed novel techniques to apply molecular probes topically to tissues and very rapidly differentiate cancer cells from normal tissues. Our idea is to utilize this novel technology pioneered in our laboratories to develop a standardized method to reduce re-excisions and false negatives for BCS patients. Exploiting increased protease expression at the edge of breast cancers this proposal introduces the novel concept of ex vivo topical administration of quenched molecular imaging probes to identify cancer. Minutes after application, limited diffusion of the probe into lumpectomy specimens defines a margin and allows identification of infiltrating cancer cells without a requirement for vascularization. This approach enables rapid and global identification of cancer presence both on the surface and in the margins of resected specimens during surgery, all of which is unique to this technology. If successful this technology could reduce the number of re-excisions by up to 60%. Moreover, if will reduce re-excisions and the false negative rate that results from undersampling during histopathological analysis. The research proposed here will first optimize the probe mixtures for this procedure and then will test the technology in the lumpectomy specimens of 50 women. The results of this study will statistically test this technology. Since all of the procedures happen outside of the body, there are minimal regulatory hurdles to drive this technology rapidly into the hands of surgeons.

描述（由申请人提供）：2012年，超过230,000名女性将在2012年接受乳腺癌手术。其中，约有75％的人将是候选人，并选择乳房保存手术（BCS）。 BC在化妆上比替代性（乳房切除术）更可取，并且长期存活率等效。但是BCS有可能更昂贵。在接受BCS的175,000名妇女中，将召回医院进行其他手术，以去除第一次手术期间未发现和去除的活性癌组织。除了对患者的负面影响（这是临床医生的主要关注点）外，第二次手术对总体以及对医疗保健成本以及个人提供商机构的经济影响有重大影响。肿瘤切除后检测活性肿瘤边缘的当前“金标准”是FFPE（福尔马林固定，石蜡包裹的）组织病理学。在患者出院后，评估外科医生去除的组织的活性肿瘤边缘，结果可能需要长达两周。由于未进行术中进行，因此FFPE实际上确保检测到主动边缘时将进行第二次手术。更重要的是，FFPE不会检查整个切除的肿瘤，而仅检查许多冷冻切片。不可避免的采样错误可能会错过主动肿瘤“尖峰”。数据表明，大约有15％的患者在一年之内有“干净”边缘的局部复发，这表明病理学遗失了边缘的疾病，这可能是由于采样不足所致。最近，《纽约时报》报道了美国的手术乳腺癌治疗，进一步强调了公众的需求未满足，由于肿瘤边缘未被发现/未发现/未发现的癌细胞引起的第二次手术减少，显然存在（“乳腺癌手术规则不清楚”，纽约时报，纽约时报，第A1页，A1，2012年2月1日，2012年）。最近的一项调查显示，在手术期间，只有48％的351名美国外科医生对术中的边缘进行了反应，在手术过程中使用了任何技术来确定他们是否已从乳房中去除所有癌症组织。在所有参与的外科医生中，有28％的人认为没有癌症的1毫米保证金为阴性，50％a 2毫米的保证金，12％A 5毫米保证金和10毫米的保证金。显然，这些缺点定义了对BC的未满足的临床需求。解决未满足的需求的方法。分子成像是一个相对较新的领域，试图通过差异来通过成像来识别细胞在其生物化学中，而不是试图解决用于鉴定典型X射线或乳房X线摄影检查中癌症的细微解剖学差异。多年来，我们的实验室一直在研究使用淬灭的分子成像探针和应用技术来快速鉴定体内的癌细胞。最近，我们开发了新型技术，将分子探针局部应用于组织，并非常快速地将癌细胞与正常组织区分开。我们的想法是利用在我们的实验室中开创的这项新技术来开发一种标准化方法，以减少BCS患者的重新选择和假否定性。利用增加的蛋白酶表达在乳腺癌的边缘，此提案引入了猝灭分子成像探针的新型局部局部给药以鉴定癌症。应用几分钟后，将探针扩散到乳房切除术标本中定义了边缘，并允许鉴定浸润的癌细胞无需血管化。这种方法可以快速而全球地鉴定在手术期间在切除的标本的表面和切除标本的边缘上的存在，所有这些标本都是该技术所独有的。如果成功，该技术可以将重新陈述的数量减少多达60％。此外，如果在组织病理学分析期间采样不足导致的降采样率会减少重新审查和假负率。这里提出的研究将首先优化此过程的探针混合物，然后测试 50名女性乳房切除术标本中的技术。这项研究的结果将在统计上测试这项技术。由于所有程序都发生在身体外，因此有最小的调节障碍将这项技术迅速驱逐到外科医生手中。