Novel Biophotonics Methodology for Colon Cancer Screening

Supported by multiple grans from the NIH, we have developed and performed preliminarily
clinical studies on a suite of biophotonics techniques that promises to have unprecedented
accuracy in risk- stratification of colonic neoplasia. The main goal for this study is to
establish a Bioengineering Research Partnership (BRP) with the objective to refine and
provide comprehensive, definitive multi-center validation of these novel methodologies for
colorectal cancer (CRC) screening, thus providing a quantum leap in population screening.

Colonoscopy has the potential of reducing colorectal cancer (CRC) occurrence by ~90% through
the identification and interdiction of the precursor lesion, the adenomatous polyp. However,
CRC remains the second leading cause of cancer deaths in the United States with an
anticipated 153,760 new cases in 2007. The major reason why existing CRC screening strategy
is not adequate is as follows:

According to existing recommendations, every patient over the age of 50 is considered at
risk for CRC and is a candidate for colonoscopic surveillance to be performed at least every
10 years. However, screening the entire eligible population (>80 million Americans over age
50) through colonoscopy is practically impossible for a variety of reasons including expense
(the financial burden on the health care would be ~$100B a year), patient reluctance,
complication rate, and insufficient number of endoscopists. Indeed, currently only less than
20% of the population undergo colonoscopy. The potential solution to this could be
risk-stratification. The lifetime incidence of colon polyps is ~20-30% and CRC is ~6%. Thus,
instead of performing colonoscopy on the entire population, targeting the group at risk for
developing neoplasia would allow the focusing of this finite endoscopic resource on subjects
who will actually benefit from this invasive test. Current approaches at risk-stratification
(e.g. flexible sigmoidoscopy, fecal occult blood test) are plagued by unacceptably poor
sensitivity and positive predictive value. Thus, more accurate approaches are urgently
needed to triage patients for colonoscopy. This test has to be considerably less expensive
than colonoscopy (a colonoscopy costs ~$1,000-2,000), minimally invasive and performed by a
primary care physician. (The strategy is analogous to the Pap-smear screening for cervical
cancer: 50 years ago, cervical cancer used to be the first major cause of cancer deaths in
women. The incidence was reduced by more than 70%, from number 1 killer in women to number
13, by introduction of the Pap-smear as an initial screening test. Currently, no such
initial screening test is available in case of CRC.)

The proposed program is based on novel spectroscopic techniques developed by our
multidisciplinary team, comprised of biomedical and electrical engineers,
gastroenterologists, cancer biologists, and biostatisticians. Two techniques have been
developed: low-coherence enhanced backscattering (LEBS) spectroscopy and four-dimensional
elastic light scattering fingerprinting (ELF). Many screening techniques (e.g., flexible
sigmoidoscopy) exploit the "field effect" of colon carcinogenesis, the proposition that the
genetic/environmental milieu that results in a neoplastic lesion in one area of the colon
should be detectable in uninvolved (i.e., colonoscopically normal-appearing) mucosa
throughout the colon. Several lines of evidence suggest that nano/micro-architectural
alterations are among the earliest pre-neoplastic markers of colon carcinogenesis.

Our group was the first to explore the concept of the field effect for cancer screening by
means of optical examination of colonoscopcially and histologically normal rectal tissue. A
key capability of ELF and LEBS is that they sense these changes in microscopically normal
tissue at a distance from a precancerous lesion. This opens up a possibility to identifying
patients harboring adenomas in the colon by assessment of histologically and
colonoscopically normal-appearing rectal mucosa without the need for colonoscopy.

We have completed successful animal and human studies showing that ELF and LEBS markers have
superior performance to any existing markers of the field-effect of CRC. We have published
the first demonstration that marked ELF/LEBS aberrations could be detected far earlier than
any currently known markers of CRC including morphological (e.g. aberrant crypt foci,
adenomas) or cellular (apoptosis, proliferation) markers. In our human studies, we
demonstrated that the assessment of ELF/LEBS signatures in the endoscopically normal rectal
mucosa (the most readily accessible colonic mucosa) accurately identified patients harboring
neoplasia elsewhere in the colon. Indeed, the sensitivity of rectal ELF/LEBS was 100% for
identifying the presence of adenomas elsewhere in the colon, far exceeding any previously
described markers. This suggests that ELF/EBS could be exploited for CRC screening by means
of a simple and inexpensive optical test without the need for either colonoscopy or bowel
preparation.

Based on our preliminary data, we hypothesize that ELF/LEBS will be able to identify
subjects who do and do not harbor adenomas in the colon based on optical alterations in the
rectal mucosa that will be assessed without the need for colonoscopy and bowel preparation.

Inclusion Criteria:

- Patients who have appointments in the GI Clinic and are/or will be scheduled for an
colonoscopy as per standard of care.

- Patients must be 18 years of age or older.

Exclusion Criteria:

- Patients who have a history of Inflammatory Bowel Disease.

- Patients who have colitis.

- Patients who are undergoing chemotherapy.