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Preliminary clinical characterization of serum, plasma and urine biomarkers for colorectal neoplasms.

Dean E. Brenner, Primary Investigator

In recognition of the fact that novel potential biomarkers are continually being identified and will need to be validated in a rapid, efficient and scientifically rigorous manner, the NCI has made an enormous commitment to the development of a network that will facilitate biomarker development and validation in multiple organ sites. As part of the National Cancer Institute-funded Early Detection Research Network (EDRN), the Great Lakes-New England Clinical Epidemiological Center (GLNE CEC) proposes a research study that validates potential molecular markers (“biomarkers”) for the detection of precancerous and cancerous conditions and cancer risk assessment. Although examples of such biomarkers are currently in clinical use (ie CEA, CA-125), there are limitations to all of them. Our consortium will initially focus on gastrointestinal neoplasia.

The goal of this phase of the proposed research is to determine the reproducibility of a biomarker in a clinical context. Potential sources of biomarker variability might be diurnal variation of secretion, antibody production of a serum biomarker, within day temperature variations, assay variability, variations in biological sample procurement, handling and storage, gender, race, and female cyclic hormonal variation. In addition, it is important to determine how a biomarker varies with different medical conditions. For example, comparisons of the presence of a particular biomarker between inflammatory vs. malignant diseases are essential to determine its potential usefulness in aiding risk assessment or early detection of tumors.

We propose to collect data and obtain biological samples to assess biomarker variability using standard FDA methods for laboratory assay validation as a model. Data collection will consist of serum, plasma, urine, and tumor samples from patients with known diagnoses of cancers, with gastrointestinal polyps, inflammatory lesions and normal control patients. If a given biomarker, or panel of markers, is shown in these studies to be potentially reliable, future phases of this research will focus on validation of the marker in larger patient cohorts as well as longitudinal studies (for example, assessment of the biomarker’s response to chemopreventive agents).

Evaluation of stool based markers for the early detection of colorectal cancers and adenomas.

Dean E. Brenner, Primary Investigator

In recognition of the fact that novel potential biomarkers are continually being identified and will need to be validated in a rapid, efficient and scientifically rigorous manner, the NCI has made an enormous commitment to the development of a network that will facilitate biomarker development and validation in multiple organ sites. As part of the National Cancer Institute-funded Early Detection Research Network (EDRN), the Great Lakes-New England Clinical Epidemiological Center (GLNE CEC) proposes a research study that validates potential molecular markers (“biomarkers”) for the detection of precancerous and cancerous conditions and cancer risk assessment. Although examples of such biomarkers are currently in clinical use (i.e. CEA, CA-125), there are limitations to all of them. Our consortium focuses on gastrointestinal neoplasia.

The goals of this phase of the proposed research are as follows:

1. Preliminary exploration of sensitivity and specificity relative to adenocarcinomas, adenomas and normal tissue of stool-based biomarkers to be considered for a future panel for the early detection of colonic neoplasia.

2. Characterization of the utility of individual markers and prototype panels under a number of assumptions concerning prevalence and cost of misclassification.

3. Preliminary exploration of sensitivity and specificity relative to adenocarcinomas, adenomas and normal tissue of serum-based or urine-based biomarkers to be considered for a future panel for the early detection of colonic neoplasia.

4. Construction of a panel of markers from Objective 1 to classify:
-Participants with normal colons versus participants with adenomas or cancers
-Participants with normal colons or adenomas versus participants with cancers.
-Participants with normal colons versus participants with adenomas versus participants with cancers.

5. Comparison of the markers and panels to the established current standard, FOBT.

6. Assess the usefulness of two different stool collection tools for detection of stool based
biomarkers.

7. Development of a bank of stool samples linked to serum, tissue, urine and clinical data from patients with colorectal cancer, adenomas and normal controls for validation of stool-based markers that may be developed in the future.

To meet our goals we propose to collect stool, serum, plasma and urine samples from 600 patients (200 colorectal cancer, 200 adenomas and 200 controls). The stool samples will be assayed for 5 stool based biomarkers. EDRN Common Data Elements (CDEs) will be completed by the recruiting sites and provided for the laboratories developing the assay. Each biomarker will be analyzed individually and considered as a potential panel marker to be used for future large-scale screening longitudinal trials.

Based upon the outcomes of a subset of these biomarkers, samples will be then sent to the UCLA Biomarker Validation Lab (BVL) for assay validation and preparation for a biomarker panel validation project. This validation project will be the subject of a subsequent protocol.


VIRTUAL COLONGRAPHY

Pilot study to evaluate the feasibility of MR colonography with oral fecal tagging in the detection of colorectal lesions

Principal Investigator: Saroja Adusumilli, MD

Colonoscopy is considered to be the test of choice when screening for colon cancer and polyps. However, patients often avoid screening for colon cancer and polyps for a variety of reasons including the perceived invasiveness of the procedure and the bowel cleansing (Prep).

For this pilot study, we are looking for volunteers who are due for their scheduled follow-up colonoscopy. MR Colonography will be performed within the month before the colonoscopy. The blinded results of both studies will be compared. No laxatives or other bowel cleansing procedures will be performed before the MRI.

MR Colonography is a novel method for detecting colonic lesions that will eliminate the bowel cleansing prep. It requires the patient to drink a small amount of barium with each meal, for 48 hours before the MRI procedure. The barium will coat the stool which will then be "invisible" on the MRI pictures (called "tagging"). At the time of the MRI, intravenous contrast will be given to detect polyps or other masses. In addition, during the MRI the colon will be distended with a water enema; otherwise, polyps can be hidden if the bowel is collapsed on itself.