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Gut. 2017 Feb;66(2):285-292. doi: 10.1136/gutjnl-2015-309996. Epub 2015 Oct 26.

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

Author information

1
Department of Medicine, Boston University Medical Center, Boston, Massachusetts, USA.
2
Department of Biomedical Engineering, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
3
Department of Preventive Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
4
Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA.
5
Department of Medicine, The University of Chicago Medical Center, Chicago, Illinois, USA.
6
Department of Medicine, NorthShore University Health Systems, Evanston, Illinois, USA.
7
Department of Obstetrics and Gynecology, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
8
Department of Medicine, Robert H. Lurie Cancer Center, Northwestern University, Chicago, Illinois, USA.
9
Department of Pathology, The University of Chicago Medical Center, Chicago, Illinois, USA.

Abstract

OBJECTIVE:

A major impediment to translating chemoprevention to clinical practice has been lack of intermediate biomarkers. We previously reported that rectal interrogation with low-coherence enhanced backscattering spectroscopy (LEBS) detected microarchitectural manifestations of field carcinogenesis. We now wanted to ascertain if reversion of two LEBS markers spectral slope (SPEC) and fractal dimension (FRAC) could serve as a marker for chemopreventive efficacy.

DESIGN:

We conducted a multicentre, prospective, randomised, double-blind placebo-controlled, clinical trial in subjects with a history of colonic neoplasia who manifested altered SPEC/FRAC in histologically normal colonic mucosa. Subjects (n=79) were randomised to 325 mg aspirin or placebo. The primary endpoint changed in FRAC and SPEC spectral markers after 3 months. Mucosal levels of prostaglandin E2 (PGE2) and UDP-glucuronosyltransferase (UGT)1A6 genotypes were planned secondary endpoints.

RESULTS:

At 3 months, the aspirin group manifested alterations in SPEC (48.9%, p=0.055) and FRAC (55.4%, p=0.200) with the direction towards non-neoplastic status. As a measure of aspirin's pharmacological efficacy, we assessed changes in rectal PGE2 levels and noted that it correlated with SPEC and FRAC alterations (R=-0.55, p=0.01 and R=0.57, p=0.009, respectively) whereas there was no significant correlation in placebo specimens. While UGT1A6 subgroup analysis did not achieve statistical significance, the changes in SPEC and FRAC to a less neoplastic direction occurred only in the variant consonant with epidemiological evidence of chemoprevention.

CONCLUSIONS:

We provide the first proof of concept, albeit somewhat underpowered, that spectral markers reversion mirrors antineoplastic efficacy providing a potential modality for titration of agent type/dose to optimise chemopreventive strategies in clinical practice.

TRIAL NUMBER:

NCT00468910.

KEYWORDS:

COLORECTAL NEOPLASIA

PMID:
26503631
PMCID:
PMC5108693
DOI:
10.1136/gutjnl-2015-309996
[Indexed for MEDLINE]
Free PMC Article

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