Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions

Abstract

Purpose Colorectal cancer remains the second leading cause of cancer deaths in the U.S. despite being eminently preventable by colonoscopy via removal of premalignant adenomas. In order to more effectively reduce colorectal cancer mortality, improved screening paradigms are needed. Our group pioneered the use of low coherence enhanced backscattering (LEBS) spectroscopy to detect the presence of adenomas throughout the colon via optical interrogation of the rectal mucosa. In a previous ex-vivo biopsy study of 219 patients, LEBS demonstrated excellent diagnostic potential with 89.5% accuracy for advanced adenomas. The objective of the current cross-sectional study is to assess the viability of rectal LEBS in-vivo. Experimental Design Measurements from 619 patients were taken using a minimally invasive 3.4 mm diameter LEBS probe introduced into the rectum via anoscope or direct insertion, requiring ~1 minute from probe insertion to withdrawal. The diagnostic LEBS marker was formed as a logistic regression of the optical reduced scattering coefficient μs∗ and mass density distribution factor D. Results The rectal LEBS marker was significantly altered in patients harboring advanced adenomas and multiple non-advanced adenomas throughout the colon. Blinded and cross-validated test performance characteristics showed 88% sensitivity to advanced adenomas, 71% sensitivity to multiple non-advanced adenomas, and 72% specificity in the validation set. Conclusions We demonstrate the viability of in-vivo LEBS measurement of histologically normal rectal mucosa to predict the presence of clinically relevant adenomas throughout the colon. The current work represents the next step in the development of rectal LEBS as a tool for colorectal cancer risk stratification.

Spectral biomarkers for chemoprevention of colonic neoplasia: a placebo-controlled double-blinded trial with aspirin

“…18 We have previously demonstrated that rectal spectral markers accurately assessed the risk of concurrent and future neoplasia (advanced adenomas and carcinomas). [25][26][27] With regard to chemoprevention, our preclinical data have shown that spectral parameters are normalised by chemopreventive agents. 30 31 These markers encompass the gamut of submicron architecture.…”

“…While there are a number of caveats in the data, including borderline statistical significance, viewed in toto these data appear very promising and provide the impetus to perform larger scale clinical trials (employing the newly developed fiberoptic LEBS probe). 27 The potential clinical applications of the spectral marker-field carcinogenesis strategy include the following: (1) identifying patients at highest risk who may benefit from chemopreventive strategies, (2) in patients whose chemoprevention is initiated, monitor efficacy in order to titrate dosage/alter agent and (3) provide a platform for rapid clinical trials to provide initial validation of chemopreventive agents that demonstrated promise in animal models. This approach of using spectral markers may potentially be a vehicle to allow the era of personalised medicine to be applied to CRC prevention efforts.…”

“…Previous reports demonstrate that rectal LEBS markers predict advanced adenomas (size ≥10 mm or high-grade dysplasia or ≥25% villous features) elsewhere in the colon with excellent accuracy (sensitivity 88-100%, specificity 72-80%). 26 27 We therefore wanted to assess whether the reversal of the neoplastic LEBS signatures in the rectal mucosa could provide insights into chemoprevention.…”

Biomarkers in Colorectal Cancer Screening

“…Early efforts with low-coherence enhanced backscattering spectroscopy have provided hopeful results that office-based interrogation of the rectal mucosa can predict the presence of neoplasia throughout the colorectum. 61 …”

Fully automated fiber-based optical spectroscopy system for use in a clinical setting

“…In the last three decades, there have been hundreds of in vivo studies using optical spectroscopy for a myriad of applications. [1][2][3][4][5][6][7][8][9] Many of the instruments in those studies have been fiber-optic-based probes, which can be extraordinarily robust, flexible, relatively cheap, and easy to assemble. While there have been many studies showing promising results in a number of different applications, currently there are few FDA-approved fiber-based optical spectroscopy techniques, which have been implemented in a clinical setting for diagnostic applications.…”