Colon cancer risk-stratification via optical analysis of rectal ultrastructure

 描述（申请人提供）：这项小型企业创新研究资助的目标是开发和商业化一种高度准确的、微创的结直肠癌（CRC）风险分层技术，该技术简单到可以由初级保健提供者在年度体检中进行。（> 1亿美国人），CRC仍然是癌症死亡的第二大原因。这部分是由于现有CRC筛查技术的局限性，包括结肠镜检查，结肠镜检查被认为是CRC筛查的“金标准”。这是因为由于各种原因（包括费用、患者不情愿、并发症和内窥镜医生数量不足），只有一小部分符合条件的人群接受结肠镜检查。此外，目前对“平均风险”人群进行结肠镜检查的做法是非常低效的，因为只有约6%的筛查人群具有显著的瘤形成（晚期腺瘤）。因此，开发一种微创测试来识别患有和不患有结肠腺瘤的患者对于更好地针对患者进行结肠镜检查至关重要。这将首次实现对CRC的全人群筛查。西北大学和北岸大学卫生系统的工程师，生物学家和临床医生组成的跨学科团队开发了低相干增强后向散射（LEBS），这是一种新型的生物光子技术，能够感测组织病理学正常粘膜中遗传/表观遗传变化的纳米级组织形态学相关性。初步的动物和人体研究表明，LEBS有可能检测到组织学上正常的组织中的细微变化，这是由于器官不同部位存在癌性/癌前病变所致，这是场致癌作用的公认概念的结果。这为通过直肠组织粘膜的实时LEBS分析来检测结肠肿瘤的存在开辟了可能性，在PC或OBGYN环境中盲插微创LEBS探头时，这是很容易获得的。事实上，在对约500名患者（为结肠镜检查进行肠道准备）进行的初步研究中， 注意到，来自内窥镜检查正常直肠粘膜读数的LEBS标志物反映了结肠其他部位肿瘤病变的显著性（晚期腺瘤>腺瘤>无肿瘤）。在直肠LEBS分析的未来确定性临床验证之前，需要几个步骤。在授权期的第1年，将开发必要的仪器，以将LEBS技术从其用于GI医院环境的初始产品配置转换为允许在PC和OBGYN环境中使用的配置，并将对250名随后接受结肠镜检查的患者进行直肠LEBS试验，随后将制定LEBS预测规则。在资助期的第2年，预测规则将通过一个由250名未准备接受结肠镜检查的患者组成的独立队列进行验证，其中先前开发的直肠LEBS预测规则将前瞻性地应用于晚期腺瘤和任何腺瘤。成功的SBIR研究将使美国生物光学公司能够创建一个商业上可行的诊断系统，这对未来的多中心临床试验和FDA批准至关重要。

 DESCRIPTION (provided by applicant): The goal of this small business innovation research grant is to develop and commercialize a highly accurate, minimally invasive risk stratification technique for colorectal cancer (CRC) that is simple enough to be performed by the primary care provider during an annual physical exam. Although existing guidelines recommend CRC screening for all patients over age 50 (>100 million Americans), CRC remains the second leading cause of cancer death. This is in part due to the limitations in the existing CRC screening techniques including colonoscopy which is considered a `gold standard' for CRC screening. This is because only a small fraction of eligible population undergoes colonoscopy due to variety of reasons including expense, patient reluctance, complications, and insufficient number of endoscopists. Furthermore, the current practice of colonoscopy on the "average risk" population is remarkably inefficient as only ~6% of the screening population have significant neoplasia (advanced adenomas). Hence developing a minimally invasive test to identify patients who do and do not harbor colonic adenomas is of crucial importance to better target patients for colonoscopy. This would enable, for the first time, a population wide screening for CRC. An interdisciplinary team of engineers, biologists and clinicians at Northwestern University and Northshore University Health System has developed Low-Coherence Enhanced Backscattering (LEBS), a novel biophotonic technique that enables sensing the nanoscale tissue morphological correlates of the genetic/epigenetic changes in otherwise histopathologically normal mucosa. Preliminary animal and human studies demonstrated the potential of LEBS to detect subtle alterations in histologically normal- appearing tissue that is due to the presence of cancerous/precancerous lesions present in a different part of an organ, a consequence of the well-established concept of field carcinogenesis. This opens a possibility to detect the presence of colonic neoplasia by means of real-time LEBS analysis of rectal tissue mucosa, which is readily available upon blind insertion of the minimally invasive LEBS probe in PC or OBGYN setting. Indeed, in pilot studies on ~500 patients (with bowel preparation for colonoscopy), it was noted that the LEBS marker from endoscopically-normal rectal mucosal readings mirrored the significance of neoplastic lesions elsewhere in the colon (advanced adenomas > adenomas > no neoplasia). There are several steps that are required prior to the future definitive clinical validation of rectal LEBS analysis. In In year 1 of the grant period, instrumentation will be developed necessary to transition the LEBS technology from its initial product configuration intended for use in GI hospital-based setting, to a configuration allowing for use in PC and OBGYN settings, and a rectal LEBS trial will be conducted of 250 patients who will later undergo colonoscopy, and a LEBS prediction rule will be subsequently formulated. In year 2 of the grant period, the prediction rule will be verified via an independent cohort of 250 unprepped patients scheduled for colonoscopy, where the previously developed rectal LEBS prediction rule will be prospectively applied for both advanced adenomas and any adenomas. The successful SBIR research would enable American BioOptics to create a commercially viable diagnostic system that would be critical for future multi-center clinical trials and FDA approval.