Phase I Amount
$1,030,462
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.
Public Health Relevance Statement: Public Health Relevance: Existing colorectal cancer screening techniques do not allow accurate and cost-effective screening of the entire at-risk population - all patients over 50 years age (> 100 million Americans). This SBIR project will lead towards the development of a highly sensitive, minimally invasive, and commercially viable optical technology that would enable risk-stratification of the general population for colorectal cancer by rectal insertion of a minimally invasive optical probe that can be performed by the primary care physician or OBGYN at an annual physical exam.
Project Terms: adenoma; Adenomatous Polyps; Age; Age-Years; Algorithmic Software; Algorithms; American; Animals; Area; base; Biophotonics; blind; Cancer Etiology; cancer risk; Cancerous; carcinogenesis; Cessation of life; Clinical; clinical application; clinically relevant; cohort; Colon; Colon Carcinoma; Colonic Adenoma; Colonoscopy; Colorectal Cancer; colorectal cancer screening; commercialization; cost; cost effective; Data; design; Detection; Development; Diagnostic; Diet; Diffuse; Disinfection; Dysplasia; Engineering; Ensure; Epigenetic Process; Event; Excision; Exhibits; extracellular; FDA approved; Fiber Optics; Future; General Population; Generations; Genetic; Goals; Gold; Grant; Guidelines; Health system; Higher Order Chromatin Structure; Histologic; Hospitals; Human; in vivo; Individual; Injury; instrumentation; Intestines; Lead; Length; Lesion; Licensing; Life; Marketing; Methodology; Microscopy; minimal risk; minimally invasive; Molecular; Mucous Membrane; Multi-Institutional Clinical Trial; nanoscale; Neoplasms; neoplastic; novel; Optics; Organ; Pathway interactions; Patient Schedules; patient subsets; Patients; Pilot Projects; Population; Populations at Risk; Premalignant; Preparation; Primary Care Physician; primary care setting; Primary Health Care; Procedures; Protocols documentation; Provider; public health relevance; Publishing; Reading; rectal; Rectum; Research; Resolution; Risk; Risk Factors; Safety; Science; screening; sensor; Small Business Innovation Research Grant; Smoking; Specificity; Stratification; success; System; Techniques; Technology; Testing; Time; Tissues; Touch sensation; Universities; Update; Validation; Villous
